Sim, Jae Kyeom; Oh, Jee Youn; Lee, Eun Joo; Hur, Gyu Young; Lee, Seung Heon; Lee, Sung Yong; Lee, Sang Yeub; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Min, Kyung Hoon
2016-05-01
Acute exacerbation and bacterial pneumonia are major life-threatening conditions in patients with interstitial lung disease (ILD). The rapid recognition of these 2 different conditions is important for their proper treatment. An elevated procalcitonin (PCT) level is commonly detected in patients with bacterial infections. This study assessed the usefulness of the serum PCT level as a biomarker for the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD. In this prospective observational study, we enrolled patients with ILD who had experienced recently progressive dyspnea and exhibited new infiltrations on chest radiographs. We classified these patients into an acute exacerbation group and a bacterial pneumonia group and compared their baseline characteristics and laboratory parameters, including the PCT level. Of 21 patients with ILD, 9 patients had bacterial pneumonia. Both the groups showed similar baseline characteristics. The bacterial pneumonia group demonstrated a high PCT level. The PCT level in the acute exacerbation group was significantly lower than that in the bacterial pneumonia group (0.05 versus 0.91ng/mL, respectively; P < 0.001). Other parameters, such as the C-reactive protein level, leukocyte count and body temperature, were also lower in the acute exacerbation group. At a cutoff value of 0.1ng/mL, the sensitivity, specificity and negative predictive values of the serum PCT level were 88.9%, 100.0% and 92.3%, respectively. These findings suggest that the serum PCT level is useful in the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
[Comparative diagnosis of bacterial pneumonia and pulmonary tuberculosis in HIV positive patients].
Horo, K; Koné, A; Koffi, M-O; Ahui, J M B; Brou-Godé, C V; Kouassi, A B; N'Gom, A; Koffi, N G; Aka-Danguy, E
2016-01-01
Immunodepression induced by the human immunodeficiency virus (HIV) modifies the clinical, radiological and microbiological manifestations of pulmonary tuberculosis; leading to similarities between pulmonary tuberculosis and acute community-acquired bacterial pneumonia. A consequence is the high proportion of discordant pre- and post-mortem diagnoses of pneumonia. The aim of our study was to contribute to the improvement in the diagnosis of acute bacterial pneumonia in HIV positive patients in areas where tuberculosis is endemic. This retrospective study in HIV positive patients has compared 94 cases of positive smear cases pulmonary tuberculosis and 78 cases of acute community-acquired bacterial pneumonia. Using logistic regression, the following features were positively associated with bacterial pneumonia: the sudden onset of signs (OR=8.48 [CI 95% 2.50-28.74]), a delay in the evolution of symptoms of less than 15 days (OR=3.70 [CI 95% 1.11-12.35]), chest pain (OR=2.81 [CI 95% 1.10-7.18]), radiological alveolar shadowing (OR=12.98 [CI 95% 4.66-36.12) and high leukocytosis (OR=3.52 [CI 95% 1.19-10.44]). These five variables allowed us to establish a diagnostic score for bacterial pneumonia ranging from 0 to 5. The area under the ROC curve was 0.886 [CI 95% 0.84-0.94, P<0.001]). Its specificity was >96.8% for a score of greater than or equal to 4. The diagnostic score for acute community-acquired pneumonia may improve the management of bacterial pneumonia in areas where tuberculosis is endemic. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Cortes, Margarida Barreto; Fernandes, Samuel Raimundo; Aranha, Patricia; Avô, Luís Brito; Falcão, Luís Menezes
2017-05-31
Acute bacterial pneumonia is a common and potentially fatal disease where early recognition and treatment are crucial. Increasing medical literature suggests worse outcomes in patients admitted for medical and surgical conditions during the weekend. Little is known about this effect in patients with acute bacterial pneumonia. Obective: The aim of this study was to evaluate the impact of weekend and holiday hospital admission on the outcomes of acute bacterial pneumonia. Retrospective analysis of adult patients (> 18 years) with acute bacterial pneumonia collected from a tertiary referral center database. Length of stay, total cost, admission to intensive care unit, development of sepsis and organ failure, and mortality were compared between patients admitted on a weekday and patients admitted during a weekend or holiday. We analyzed 53 854 hospital admissions from 42 512 patients (median age 84.0 years, range 18 - 118 years), corresponding to 30 554 admissions during weekdays, 21 222 at weekends and 2078 during public holidays. Weekend and holiday admission was not associated with increased costs, length of stay, intensive care unit admission, development of sepsis, organ failure, and mortality. A weekend/holiday effect in acute bacterial pneumonia was not evident in our series.
Cunha, Burke A; Syed, Uzma; Mickail, Nardeen
2010-01-01
The swine influenza (H1N1) pandemic began in Mexico and rapidly spread worldwide. As is the case with pandemic influenza A, the majority of early deaths have been in young healthy adults. The complications of pandemic H1N1 have been reported from several centers. Noteworthy has been the relative rarity of bacterial coinfection in bacterial pneumonia in hospitalized adults with H1N1 pneumonia. Simultaneous bacterial community-acquired pneumonia due to methicillin-sensitive Staphylococcus aureus or community-acquired methicillin resistant S. aureus and subsequent bacterial community-acquired pneumonia due to S. pneumoniae or Haemophilus influenzae have been reportedly rare (0.4%-4% of well-documented cases). Cardiac complications of H1N1 infection have been uncommon. Young healthy adults without a cardiac history who have H1N1 and chest pain usually have either acute myocardial infarction or acute myocarditis. Cardiac symptomatology with H1N1 often overshadows pulmonary manifestations, that is, influenza pneumonia. With H1N1 pneumonia, clinicians should be alert for otherwise unexplained tachycardia or chest pain that may represent acute myocardial infarction or myocarditis. We present a case of rapidly fatal H1N1 in a young adult treated with oseltamivir and peramivir. He was initially tachycardic, thought to represent myocarditis. He subsequently became hypotensive and expired. At autopsy there was cardiomegaly present but there were no signs of acute myocardial infarction or myocarditis. Pathologically, he died of severe H1N1 pneumonia and not bacterial pneumonia. Copyright © 2010 Elsevier Inc. All rights reserved.
[Etiological diagnosis of acute pneumopathies. Evaluative study. 100 cases in a pneumologic center].
Denjean, A; Geslin, P; Hirsch, A; Lemoine, J L
1977-05-14
This study involved 100 patients with acute pneumonia and hospitalised in a specialised service: 12 bacterial pneumonia, 40 viral pneumonia (i.e. 52% of the total). Only precise viral and bactérial studies could improve these results. Given the poor results obtained using the microbiological techniques available here, the authors suggest the inclusion in all subsequent studies of aetiological diagnosis of a quantitative examination of sputum bacterial flora and examination for the detection of bacterial exoantigens.
Acute appendicitis presenting with Klebsiella pneumoniae septicemia due to bacterial translocation.
Salemis, Nikolaos S
2009-10-01
Bacterial translocation (BT) is defined as the passage of viable bacteria from the gastrointestinal tract, across the intestinal wall, to the mesenteric lymph nodes or other extranodal sites and bloodstream. It has been shown in both animal and human studies and has been implicated as a source of sepsis in susceptible patients. Herein, a rare case of acute appendicitis in a nonimmunocompromised patient who presented with manifestations of Klebsiella pneumoniae septicemia, is described. Translocation of Klebsiella pneumoniae through the compromised appendix mucosa leading in dissemination of the infection into the bloodstream was likely the main causative factor for the atypical and toxic presentation of acute appendicitis. Thorough clinical investigation ruled out other sources of infection. Emergency physicians should be aware that septicemia may be the dominant presentation of acute appendicitis, due to dissemination of the infection into the bloodstream, secondary to bacterial translocation.
2016-10-03
Bloodstream Infections (BSI) Due to CRE; Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE; Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE; Complicated Urinary Tract Infection (cUTI) Due to CRE; Acute Pyelonephritis (AP) Due to CRE
Lee, Chi-Tsung; Hsiao, Kuang-Ming; Chen, Jin-Cherng; Su, Cheng-Chuan
2015-11-01
Acute bacterial meningitis causes high morbidity and mortality; the associated clinical symptoms often are insensitive or non-specific; and the pathogenic bacteria are geographically diverse. Clinical diagnosis requires a rapid and accurate methodology. This study aimed to develop a new multiplex polymerase chain reaction (mPCR) assay to detect simultaneously six major bacteria that cause adult bacterial meningitis in Taiwan: Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii. Species-specific primers for the six bacteria were developed using reference strains. The specificities of the mPCRs for these bacteria were validated, and the sensitivities were evaluated via serial dilutions. The mPCR assay specifically detected all of the six pathogens, particularly with sensitivities of 12 colony forming units (CFU)/mL, 90 CFU/mL, and 390 CFU/mL for E. coli, S. pneumoniae, and K. pneumoniae, respectively. This mPCR assay is a rapid and specific tool to detect the six major bacterial pathogens that cause acute adult meningitis in Taiwan, particularly sensitive for detecting E. coli, S. pneumoniae, and K. pneumoniae. The assay may facilitate early diagnosis and guidance for antimicrobial therapy for adult patients with this deadly disease in Taiwan. © 2015 APMIS. Published by John Wiley & Sons Ltd.
Romero-Espinoza, Jose A; Moreno-Valencia, Yazmin; Coronel-Tellez, Rodrigo H; Castillejos-Lopez, Manuel; Hernandez, Andres; Dominguez, Aaron; Miliar-Garcia, Angel; Barbachano-Guerrero, Arturo; Perez-Padilla, Rogelio; Alejandre-Garcia, Alejandro; Vazquez-Perez, Joel A
2018-01-01
Acute asthma exacerbations and pneumonia are important causes of morbidity and mortality in children and may coexist in the same children, although symptom overlap may lead to difficulties in diagnosis. Microbial and viral diversity and differential abundance of either may play an important role in infection susceptibility and the development of acute and chronic respiratory diseases. To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. During the winter seasons of 2013-2014 and 2014-2015, 134 nasopharyngeal swabs samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were selected based on clinical diagnosis of asthma or pneumonia. The virome and bacteriome were characterized using Whole Genome Sequencing (WGS) and in-house bioinformatics analysis pipeline. The Asthma group was represented mainly by RV-C, BoV-1 and RSV-B and the pneumonia group by Bacteriophage EJ-1 and TTMV. TTV was found in both groups with a similar amount of reads. About bacterial composition Moraxella catarrhalis, Propionibacterium acnes and Acinetobacter were present in asthma and Veillonella parvula and Mycoplasma pneumoniae in pneumonia. Streptococcus pneumoniae and Haemophilus influenzae were mostly found with both asthma and pneumonia. Our results show a complex viral and bacterial composition in asthma and pneumonia groups with a strong association of RV-C presence in asthmatic children. We observed Streptococcus pneumoniae and Haemophilus influenzae concurrently in both groups.
Serikov, Vladimir B; Mikhaylov, Viatcheslav M; Krasnodembskay, Anna D; Matthay, Michael A
2008-01-01
Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD(50) intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP(+) leukocytes. Postinflammatory foci of lung fibrosis were evident after 1-2 months. The fibrotic foci in lung stroma contained clusters of GFP(+) CD45(+) cells, GFP(+) vimentin-positive cells, and GFP(+) collagen I-positive fibroblasts. GFP(+) endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.
Anon, Jack B
2004-08-02
Acute bacterial rhinosinusitis (ABRS) is a secondary bacterial infection of the nose and paranasal sinuses, usually preceded by a viral upper respiratory infection or allergy, with symptoms that have not improved after 10 days or that have worsened after 5 to 7 days. Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of ABRS in adults. Increasing rates of antimicrobial resistance among S. pneumoniae and beta-lactamase production among H. influenzae are formidable challenges to the successful treatment of infections caused by these organisms. To this end, various formulations of amoxicillin-clavulanate have been developed, the most recent of which is pharmacokinetically enhanced and provides a total daily dose of 4,000 mg of amoxicillin and 250 mg of clavulanate. This formulation has been shown to be safe and effective in the treatment of infections caused by penicillin-resistant S. pneumoniae (minimum inhibitory concentration 2 microg/mL); the clavulanate component provides adequate coverage of beta-lactamase-producing pathogens.
Shih, Chia-Jen; Tarng, Der-Cherng; Yang, Wu-Chang; Yang, Chih-Yu
2014-07-01
Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life‑threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01-3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature.
Romero-Espinoza, Jose A.; Moreno-Valencia, Yazmin; Coronel-Tellez, Rodrigo H.; Castillejos-Lopez, Manuel; Hernandez, Andres; Dominguez, Aaron; Miliar-Garcia, Angel; Barbachano-Guerrero, Arturo; Perez-Padilla, Rogelio; Alejandre-Garcia, Alejandro
2018-01-01
Background Acute asthma exacerbations and pneumonia are important causes of morbidity and mortality in children and may coexist in the same children, although symptom overlap may lead to difficulties in diagnosis. Microbial and viral diversity and differential abundance of either may play an important role in infection susceptibility and the development of acute and chronic respiratory diseases. Objectives To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. Methods During the winter seasons of 2013–2014 and 2014–2015, 134 nasopharyngeal swabs samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were selected based on clinical diagnosis of asthma or pneumonia. The virome and bacteriome were characterized using Whole Genome Sequencing (WGS) and in-house bioinformatics analysis pipeline. Results The Asthma group was represented mainly by RV-C, BoV-1 and RSV-B and the pneumonia group by Bacteriophage EJ-1 and TTMV. TTV was found in both groups with a similar amount of reads. About bacterial composition Moraxella catarrhalis, Propionibacterium acnes and Acinetobacter were present in asthma and Veillonella parvula and Mycoplasma pneumoniae in pneumonia. Streptococcus pneumoniae and Haemophilus influenzae were mostly found with both asthma and pneumonia. Conclusions Our results show a complex viral and bacterial composition in asthma and pneumonia groups with a strong association of RV-C presence in asthmatic children. We observed Streptococcus pneumoniae and Haemophilus influenzae concurrently in both groups. PMID:29447223
Hoshina, Takayuki; Nanishi, Etsuro; Kanno, Shunsuke; Nishio, Hisanori; Kusuhara, Koichi; Hara, Toshiro
2014-10-01
The aim of this study is to investigate the utility of several biomarkers in differentiating bacterial community-acquired lower respiratory tract infection (CA-LRTI) from non-bacterial CA-LRTI in children and the difference of their diagnostic performance between pneumonia and bronchitis. A retrospective cohort study composed of 108 pediatric patients hospitalized for CA-LRTI was performed during 2010-2013. Based on the findings of chest X-ray and sputum samples, patients were divided into 4 categories, group of bacterial pneumonia or bronchitis, and non-bacterial (viral or etiology-unknown) pneumonia or bronchitis. Peripheral white blood cell and neutrophil counts, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels were compared among the 4 groups. Finally, 54 patients were the subject of this study. In the patients with pneumonia, serum CRP and PCT levels were significantly elevated in the group of bacterial pneumonia (CRP: p = 0.02, PCT: p = 0.0008). The area under the receiver operating characteristic curve for PCT for distinguishing between bacterial and non-bacterial pneumonia was the largest, and sensitivity, specificity, positive predictive value and negative predictive value of PCT were best among 4 markers. On the other hand, in the patients with bronchitis, neutrophil count was significantly decreased in non-bacterial bronchitis whereas no significant differences of WBC count, CRP level or PCT level were seen. In conclusion, PCT was the most useful marker to differentiate bacterial pneumonia whereas neutrophil count contributed most to the discrimination of bacterial bronchitis. The diagnostic performance of biomarkers may be different between pneumonia and bronchitis. Copyright © 2014. Published by Elsevier Ltd.
Management update of acute bacterial rhinosinusitis and the use of cefdinir.
Gwaltney, Jack M
2002-12-01
The pathogenesis, bacteriology, diagnosis, and antimicrobial treatment of acute bacterial rhinosinusitis (ABRS) is reviewed. Most cases of ABRS arise as complications of the rhinosinusitis of colds and other acute viral respiratory infections. Nose blowing during colds may be a risk factor for ABRS by propelling bacteria-laden nasal fluid into the sinus cavity. The bacterial causes of ABRS continue to be S pneumoniae. H influenzae, other streptococcal species, M catarrhalis, anaerobes, and S aureus. Clinical diagnosis of ABRS is based on obtaining a history of a cold or influenza-like illness that is no better or worse after >/=7 days. A 10-day course of treatment with an antimicrobial effective against resistant S pneumoniae and H influenzae is recommended. A clinical trial was reviewed in which cefdinir was effective in treating ABRS.
Clark, Tristan W; Medina, Marie-jo; Batham, Sally; Curran, Martin D; Parmar, Surendra; Nicholson, Karl G
2014-11-01
Many adult patients hospitalised with acute respiratory illness have viruses detected but the overall importance of viral infection compared to bacterial infection is unclear. Patients were recruited from two acute hospital sites in Leicester (UK) over 3 successive winters. Samples were taken for viral and bacterial testing. Of the 780 patients hospitalised with acute respiratory illness 345 (44%) had a respiratory virus detected. Picornaviruses were the most commonly isolated viruses (detected in 23% of all patients). Virus detection rates exceeded 50% in patients with exacerbation of asthma (58%), acute bronchitis and Influenza-like-illness (64%), and ranged from 30 to 50% in patients with an exacerbation of COPD (38%), community acquired pneumonia (36%) and congestive cardiac failure (31%). Bacterial detection was relatively frequent in patients with exacerbation of COPD and pneumonia (25% and 33% respectively) but was uncommon in all other groups. Antibiotic use was high across all clinical groups (76% overall) and only 21% of all antibiotic use occurred in patients with detectable bacteria. Respiratory viruses are the predominant detectable aetiological agents in most hospitalised adults with acute respiratory illness. Antibiotic usage in hospital remains excessive including in clinical conditions associated with low rates of bacterial detection. Efforts at reducing excess antibiotic use should focus on these groups as a priority. Registered International Standard Controlled Trial Number: 21521552. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
21 CFR 520.2261b - Sulfamethazine powder.
Code of Federal Regulations, 2011 CFR
2011-04-01
... (bacterial scours) (E. coli), and bacterial pneumonia (Pasteurella spp.). (iii) Limitations. Add the required... (bacterial scours) (E. coli), necrotic pododermatitis (foot rot) (Fusobacterium necrophorum), calf diphtheria... coryza (Haemophilus gallinarum), coccidiosis (Eimeria tenella, E. necatrix), acute fowl cholera...
21 CFR 522.2260 - Sulfamethazine.
Code of Federal Regulations, 2010 CFR
2010-04-01
..., thereafter. (2) Indications for use. For cattle for treatment of bacterial pneumonia and bovine respiratory... (Fusobacterium necrophorum), acute mastitis and acute metritis (Streptococcus spp.) when caused by one or more...
Benninger, Michael S
2003-10-01
Community-acquired bacterial respiratory tract infections are among the most common health disorders requiring medical care and are associated with substantial morbidity, mortality, and direct and indirect costs. Recent increases in the prevalence of antimicrobial resistance have resulted in reduced susceptibility of the most common respiratory tract bacterial pathogens to a number of antimicrobials. Amoxicillin/clavulanate potassium extended release (ER) tablets (Augmentin XR, GlaxoSmithKline) is a new formulation of amoxicillin/clavulanate that retains activity against betalactamase-producing organisms whilst increasing the activity against Streptococcus pneumoniae through elevated and sustained plasma amoxicillin concentrations. The bilayer tablet provides immediate release of clavulanate and both immediate and sustained release of amoxicillin to maintain therapeutic concentrations of amoxicillin over longer periods of the dosing interval. In clinical trials of acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP), amoxicillin/clavulanate ER was shown to have excellent bacteriological and clinical success rates, even in patients infected with antimicrobial-resistant pathogens, and was found to be generally well tolerated. Amoxicillin/clavulanate ER is approved in the US for the treatment of patients with ABS or CAP caused by beta-lactamase-producing pathogens (ie, Haemophilus influenzae, Moraxella catarrhalis, Haemophilus parainfluenzae, Klebsiella pneumoniae, or methicillin-susceptible Staphylococcus aureus) and S. pneumoniae with reduced susceptibility to penicillin (penicillin minimum inhibitory concentration = 2.0 microg/ml).
Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco
2008-05-30
Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4-8 weeks. Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 +/- 104 L/min vs 276 +/- 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 +/- 24.54 vs FEV1% 92.91 +/- 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38-13.32). Our data suggest an association between acute atypical infection and a more severe AEBA.
Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco
2008-01-01
Background Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. Methods We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4–8 weeks. Results Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 ± 104 L/min vs 276 ± 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 ± 24.54 vs FEV1% 92.91 ± 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38–13.32). Conclusion Our data suggest an association between acute atypical infection and a more severe AEBA. PMID:18513407
Etiology of Acute Bacterial Meningitis in Iran: a Systematic Review.
Ghotaslou, Reza; Yeganeh-Sefidan, Fatemeh; Salahi-Eshlaqi, Behnaz; Ebrahimzadeh-Leylabadlo, Hamed
2015-08-01
Acute bacterial meningitis (ABM) is one of the most severe infectious diseases, causing neurologic sequel, and a case fatality rate of 20-30%. The aim of this paper was to summarize the main causes of ABM in Iran. We searched the data for relevant articles using meningitis, etiology, and Iran as search terms. We found 23 papers for inclusion in the review that focused specifically on the ABM, addressing etiology and acute meningitis. Finally, during the 23 years, a total of 18163 cases were recorded, and 1074 cases of which met the criteria for bacterial meningitis. The most common agent associated with bacterial meningitis was S. pneumoniae, followed by H. influenzae, Enterobacter spp., N. meningitidis, and group B streptococcus. The total incidence of ABM during 1991 to 2002 was higher than during 2003-2013. S. pneumoniae still remains a main cause of bacterial meningitis. For improved outcomes, studies are needed to further clarify the etiology of meningitis in Iran, explore simple, accurate, and practical diagnostic tools as PCR, and investigate the most appropriate specific and supportive interventions to manage and prevent meningitis as vaccination.
González-DelCastillo, J; Núñez-Orantos, M J; Candel, F J; Martín-Sánchez, F J
2016-09-01
Antibiotic treatment inadequacy is common in these sites of infection and may have implications for the patient's prognosis. In acute bacterial skin and skin structure infections, the document states that for the establishment of an adequate treatment it must be assessed the severity, the patient comorbidity and the risk factors for multidrug-resistant microorganism. The concept of health care-associated pneumonia is discussed and leads to errors in the etiologic diagnosis and therefore in the selection of antibiotic treatment. This paper discusses how to perform this approach to the possible etiology to guide empirical treatment.
Bansal, Shruti; Chhibber, Sanjay
2010-04-01
Acute lung injuries due to acute lung infections remain a major cause of mortality. Thus a combination of an antibiotic and a compound with immunomodulatory and anti-inflammatory activities can help to overcome acute lung infection-induced injuries. Curcumin derived from the rhizome of turmeric has been used for decades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatory properties by downregulation of various inflammatory mediators. Keeping these properties in mind, we investigated the anti-inflammatory properties of curcumin in a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillation of bacteria in this mouse model of acute pneumonia-induced inflammation resulted in a significant increase in neutrophil infiltration in the lungs along with increased production of various inflammatory mediators [i.e. malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), tumour necrosis factor (TNF)-alpha] in the lung tissue. The animals that received curcumin alone orally or in combination with augmentin, 15 days prior to bacterial instillation into the lungs via the intranasal route, showed a significant (P <0.05) decrease in neutrophil influx into the lungs and a significant (P <0.05) decrease in the production of MDA, NO, MPO activity and TNF-alpha levels. Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-alpha levels significantly (P >0.05) as compared to the control group. We therefore conclude that curcumin ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, curcumin can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in the case of acute lung infection.
Kumar, Vijay; Chhibber, Sanjay
2008-09-11
Thalidomide (alpha-naphtylimidoglutarimide), a psychoactive drug that readily crosses blood-brain barrier, has been shown to exhibit anti-inflammatory, anti-angiogenic, immunomodulatory properties through a mechanism that is not fully established. Keeping these properties in mind, we tried to find out the anti-inflammatory properties of thalidomide in mouse model of acute inflammation by introducing K. pneumoniae B5055 in BALB/c mice via intranasal route. The intranasal instillation of bacteria in this mouse model of acute pneumonia induced inflammation accompanied with significant increase in neutrophil infiltration in the lungs and also increased production of mediators of inflammation (i.e. malondialdehyde, myeloperoxidase and nitric oxide) in the lung tissue. The animals, which received thalidomide alone orally or in combination with augmentin, 30 min prior to bacterial instillation into the lungs via intranasal route, showed significant (P<0.05) decrease in neutrophil influx into the lungs and there was significant (P<0.05) decrease in the production of malondialdehyde, nitric oxide and myeloperoxidase activity. But the augmentin treatment alone did not decrease the malondialdehyde, myeloperoxidase and nitric oxide significantly (P>0.05) as compared to the control group. We therefore conclude that thalidomide ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P<0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, it can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in case of acute lung infection.
Ouédraogo, S M; Toloba, Y; Badoum, G; Ouédraogo, G; Boncoungou, K; Bambara, M; Ouédraogo, E W M; Zigani, A; Sangaré, L; Ouédraogo, M
2010-01-01
Bacterial Pneumopathies are low respiratory infections due to parenchyma pulmonary attack, which etiologic agent is a bacteria different from tubercular bacillus. Factually, the treatment is based on a probalistic antibiotherapy. This requires awareness of the epidemiology of the germs which are responsible in a given region, at a given period. In order to better grasp mainly the bacteriological and therapeutic aspects of adult bacterial Pneumopathies in Burkina Faso, we have come up with a two year journal/documentary. The reported most frequent germs are respectively: Streptococcus pneumoniae (32,6%), Klebsiella pneumoniae (21%) et Staphylococcus aureus (13,9%). Negative Gram bacteries represented 53.5% of isolated germ and Acinetobacter was found only with HIV positive patients. The streptococcus was sensitive to association amoxicilline + clavulanic in 91.7% of the cases, to ceftriaxone in 83.3% of cases, to ampicilline and to amoxicilline in 66.7% of cases The clinical evolution of our patients was favorable in 74.5% of the cases with 21.8% deaths. The evolution was more significant within alcoholic patients (p = 0.001) as well as tobacco addicted patients (p = 0.02). The high morbi-morbidity due to acute pneumopathy could be improved through a better awareness and regular updating of local bacterial ecology.
Liao, Chen-Yi; Yang, Ya-Sung; Yeh, Yen-Cheng; Ben, Ren-Jy; Lee, Ching-Chang; Tsai, Chi-Chang; Wang, Chien-Yao; Kuo, Wu-Hsien; Wang, Chih-Chiang
2016-08-09
Prostate abscess is usually a complication of acute urinary tract infection. Invasive liver abscess syndrome is characterized with Klebsiella pneumoniae related multiple organ metastasis. Concomitant pyogenic liver abscess and prostate abscess have rarely been reported. Recurrent episode of liver abscess is even rarer. We report a 71-year-old male with acute bacterial prostate abscess and urinary tract infection caused by K. pneumoniae associated with multiple liver abscess, psoas muscle abscess and osteomyelitis. Blood culture and urine culture yielded K. pneumoniae, which confirmed the diagnosis of invasive liver abscess syndrome caused by K. pneumoniae. The patient was successfully treated with empirical antibiotics for 6 weeks. This case emphasizes the importance of timely and accurate diagnosis followed by appropriate treatment in disseminated K. pneumoniae infection to prevent significant morbidity and mortality.
Sharma-Chawla, Niharika; Sender, Vicky; Kershaw, Olivia; Gruber, Achim D; Volckmar, Julia; Henriques-Normark, Birgitta; Stegemann-Koniszewski, Sabine; Bruder, Dunja
2016-12-01
Influenza A virus (IAV) and Streptococcus pneumoniae are major causes of respiratory tract infections, particularly during coinfection. The synergism between these two pathogens is characterized by a complex network of dysregulated immune responses, some of which last until recovery following IAV infection. Despite the high serotype diversity of S. pneumoniae and the serotype replacement observed since the introduction of conjugate vaccines, little is known about pneumococcal strain dependency in the enhanced susceptibility to severe secondary S. pneumoniae infection following IAV infection. Thus, we studied how preinfection with IAV alters host susceptibility to different S. pneumoniae strains with various degrees of invasiveness using a highly invasive serotype 4 strain, an invasive serotype 7F strain, and a carrier serotype 19F strain. A murine model of pneumococcal coinfection during the acute phase of IAV infection showed a significantly increased degree of pneumonia and mortality for all tested pneumococcal strains at otherwise sublethal doses. The incidence and kinetics of systemic dissemination, however, remained bacterial strain dependent. Furthermore, we observed strain-specific alterations in the pulmonary levels of alveolar macrophages, neutrophils, and inflammatory mediators ultimately affecting immunopathology. During the recovery phase following IAV infection, bacterial growth in the lungs and systemic dissemination were enhanced in a strain-dependent manner. Altogether, this study shows that acute IAV infection predisposes the host to lethal S. pneumoniae infection irrespective of the pneumococcal serotype, while the long-lasting synergism between IAV and S. pneumoniae is bacterial strain dependent. These results hold implications for developing tailored therapeutic treatment regimens for dual infections during future IAV outbreaks. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
What's new in the treatment of serious MRSA infection?
Holmes, Natasha E; Howden, Benjamin P
2014-12-01
Vancomycin has been the cornerstone of treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections. This review describes new MRSA-active antibiotics that have recently been introduced and highlights emerging resistance. Elevations in the vancomycin minimum inhibitory concentration within the susceptible range are associated with treatment failure and mortality in the treatment of MRSA infections. Ceftaroline and ceftobiprole are anti-MRSA cephalosporins and are noninferior to comparator agents in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and pneumonia. Tedizolid is more potent than linezolid, has improved pharmacokinetics and reduced toxicity and is active against cfr-containing S. aureus. Telavancin now has approval for treatment of hospital-acquired pneumonia, and recent phase 2 trial data showed similar cure rates in S. aureus bacteremia. Dalbavancin and oritavancin are administered once weekly and are noninferior to comparators for acute bacterial skin and skin structure infections. Resistance has emerged against many new anti-MRSA antimicrobials including ceftaroline. Combination therapy of β-lactams with vancomycin or daptomycin is increasing. Several new MRSA-active agents are now approved for use, although much of the data is derived from treatment of acute bacterial skin and skin structure infections or pneumonia. Further studies are required for more invasive infections, such as bacteremia and endocarditis.
File, Thomas M; Benninger, Michael S; Jacobs, Michael R
2004-06-01
Current treatment guidelines for community-acquired respiratory tract infections no longer depend solely on the characteristics of the patient and the clinical syndrome, but on those of the offending pathogen, including presence and level of antimicrobial resistance. The most common respiratory tract pathogens known to cause acute bacterial rhinosinusitis (ABRS) and community-acquired pneumonia (CAP) include Streptococcus pneumoniae and Haemophilus influenzae. The prevalence of antimicrobial resistance, especially b-lactum and macrolide resistance, among S pneumoniae and H influenzae has increased dramatically during the past 2 decades, diminishing the activity of many older antimicrobials against resistant organisms. A pharmacokinetically enhanced formulation of amoxicillin/clavulanate has been developed to fulfill the need for an oral b-lactam antimicrobial that achieves a greater time that the serum drug concentration exceeds the minimum inhibitory concentration (T > MIC) of antimicrobials against pathogens than conventional formulations to improve activity against S pneumoniae with reduced susceptibility to penicillin. The b-lactamase inhibitor clavulanate allows for coverage of b-lactamase-producing pathogens, such as H influenzae and M catarrhalis. This article reviews the rationale for, and evolution of, oral amoxicillin clavulanate for ABRS and CAP
Yaguchi, Daizo; Ichikawa, Motoshi; Shizu, Masato; Inoue, Noriko; Kobayashi, Daisuke; Imai, Naoyuki; Ito, Masao
2018-05-01
Sometimes, pleural effusion accompanying an acute Mycoplasma pneumoniae infection or tuberculous pleurisy has similar analysis results. We report a case of tuberculous pleurisy which was initially diagnosed as acute M pneumoniae infection, which is of special interest because anti-Mycoplasma antibody results were positive, which served as a red herring. A 20-year-old woman visited the outpatient emergency romm of our hospital for chief complaints of high fever, dry cough, and pleuralgia persiting for 2 days. Since anti-mycoplasma antibody test results were positive, we treated acute M pneumoniae infection and drained her pleural effusion. The condition tended to improve, but on day 16 postadmission, the acid-fast bacterial culture of the pleural effusion was positive for Mycobacterium tuberculosis. Tuberculous pleurisy. After the diagnosis, the patient received antituberculous drugs. She completed treatment with no noticeable adverse events, and the right pleural effusion disappered and diffuse right pleural thickening improved. Exudative pleural effusion with lymphocyte dominance and a high adenosine deaminase level in M pneumoniae infection have been reported. Even though the condition suggests acute M pneumoniae infection, clinicians should be aware that tuberculous pleurisy and M pneumoniae infection can share similar clinical features, and should understand the usefulness and limitations of the anit-Mycoplasma antibody test.
Mina, Michael J.; Klugman, Keith P.; Rosch, Jason W.; McCullers, Jonathan A.
2015-01-01
Background. Infection with influenza A virus (IAV) increases susceptibility to respiratory bacterial infections, resulting in increased bacterial carriage and complications such acute otitis media, pneumonia, bacteremia, and meningitis. Recently, vaccination with live attenuated influenza virus (LAIV) was reported to enhance subclinical bacterial colonization within the nasopharynx, similar to IAV. Although LAIV does not predispose to bacterial pneumonia, whether it may alter bacterial transmigration toward the middle ear, where it could have clinically relevant implications, has not been investigated. Methods. BALB/c mice received LAIV or phosphate-buffered saline 1 or 7 days before or during pneumococcal colonization with either of 2 clinical isolates, 19F or 7F. Middle ear bacterial titers were monitored daily via in vivo imaging. Results. LAIV increased bacterial transmigration to and persistence within the middle ear. When colonization followed LAIV inoculation, a minimum LAIV incubation period of 4 days was required before bacterial transmigration commenced. Conclusions. While LAIV vaccination is safe and effective at reducing IAV and coinfection with influenza virus and bacteria, LAIV may increase bacterial transmigration to the middle ear and could thus increase the risk of clinically relevant acute otitis media. These data warrant further investigations into interactions between live attenuated viruses and naturally colonizing bacterial pathogens. PMID:25505300
Stoma, Igor; Karpov, Igor; Krivenko, Svetlana; Iskrov, Igor; Milanovich, Natalia; Koritko, Alla; Uss, Anatoly
2018-05-01
The role of MSCs in infection prevention and treatment is still discussed in transplant and hematological patients. The spectrum and risk factors for infections after MSCs transplantation in patients with acute GVHD have not been studied before. To determine the risk factors and spectrum of infectious complications in patients received mesenchymal stem cell transplantation as a treatment for acute GVHD. A prospective observational study was performed to evaluate the risk factors and characteristics of infectious complications after MSCs transplantation in adult patients having acute GVHD. Thirty-four episodes of MSCs transplantation in patients with acute GVHD after allogeneic HSCT were enrolled in the study. MSCs were given at a median dose of 1.32 (interquartile range 0.87-2.16) mln cells/kg per infusion at 91 days (interquartile range 31-131 days) after HSCT. Data relating to age, gender, date, and type of transplantation, characteristics of MSCs, infectious agents, and antimicrobial therapy and prevention regimens were prospectively collected in all of the enrolled patients. The episode of proven infectious complication was set as a primary outcome. There were totally 68 patients with acute GVHD in the study; among them there were 34 cases of MSCs transplantation performed. Among the registered infectious episodes were viral infections (CMV-associated disease, EBV-associated disease), invasive pulmonary aspergillosis, bacterial bloodstream infections, and pneumonia. MSCs transplantation has shown no statistically significant association with risk of infectious complications in patients with acute GVHD in a performed multivariate analysis. Among the most frequent infections in acute GVHD, we have described CMV, invasive aspergillosis, and bacterial infections (bloodstream infections or pneumonia). Among risk factors for infectious complications in patients with acute GVHD with/without MSCs transplantation are progression of main disease and neutropenia below 500 cells/mm 3 (for aspergillosis) and unrelated HSCT in the past history and progression of main disease (for bacterial bloodstream infections and pneumonia).
Searching for Helicobacter pylori and Chlamydia pneumoniae in primary endodontic infections.
Rôças, Isabela N; Siqueira, José F
2012-04-01
The purpose of this study was to search samples from primary endodontic infections for the presence of two common human bacterial pathogens - Helicobacter pylori and Chlamydia pneumoniae. Genomic DNA isolated from samples taken from 25 root canals of teeth with asymptomatic (chronic) apical periodontitis and 25 aspirates from acute apical abscess was initially amplified by the multiple displacement amplification approach and then used as template in species-specific polymerase chain reaction (PCR) for detection of H. pylori and C. pneumoniae. All clinical samples were positive for the presence of bacterial DNA. However, no clinical sample was positive for either H. pylori or C. pneumoniae. Neither H. pylori nor C. pneumoniae were found in samples from primary endodontic infections. These findings suggest that these species are not candidate endodontic pathogens and that the necrotic root canal does not serve as a reservoir for these human pathogens in healthy patients.
Rosenblut, Andres; Napolitano, Carla; Pereira, Angelica; Moreno, Camilo; Kolhe, Devayani; Lepetic, Alejandro; Ortega-Barria, Eduardo
2017-01-01
Abstract The impact of bacterial conjugate vaccines on acute otitis media (AOM) is affected by several factors including population characteristics, bacterial etiology and vaccine conjugation method, carrier, and coverage. This study estimated the baseline etiology, distribution, and antibiotic susceptibility of bacterial serotypes that causes AOM in children aged <5 years in a public setting in Santiago, Chile. Children aged ≥3 months and <5 years referred to the physician for treatment of AOM episodes (with an onset of symptoms <72 h) were enrolled between September 2009 and September 2010. Middle ear fluid (MEF) was collected by tympanocentesis or by otorrhea for identification and serotyping of bacteria. Antibacterial susceptibility was tested using E-test (etrack: 112671). Of 160 children (mean age 27.10 ± 15.83 months) with AOM episodes, 164 MEF samples (1 episode each from 156 children; 2 episodes each from 4 children) were collected. Nearly 30% of AOM episodes occurred in children aged 12 to 23 months. Streptococcus pneumoniae (41.7% [58/139]) and Haemophilus influenzae (40.3% [56/139]) were predominant among the cultures that showed bacterial growth (85% [139/164]). All Streptococcus pneumoniae positive episodes were serotyped, 19F (21%) and 14 (17%) were the predominant serotypes; all Haemophilus influenzae strains were nontypeable. Streptococcus pneumoniae were resistant to penicillin (5%) and erythromycin (33%); Haemophilus influenzae were resistant to ampicillin (14%) and cefuroxime and cefotaxime (2% each). AOM in Chilean children is predominantly caused by Streptococcus pneumoniae and nontypeable Haemophilus influenzae. Use of a broad spectrum vaccine against these pathogens might aid the reduction of AOM in Chile. PMID:28178138
Damron, F. Heath; Oglesby-Sherrouse, Amanda G.; Wilks, Angela; Barbier, Mariette
2016-01-01
Determining bacterial gene expression during infection is fundamental to understand pathogenesis. In this study, we used dual RNA-seq to simultaneously measure P. aeruginosa and the murine host’s gene expression and response to respiratory infection. Bacterial genes encoding products involved in metabolism and virulence were differentially expressed during infection and the type III and VI secretion systems were highly expressed in vivo. Strikingly, heme acquisition, ferric-enterobactin transport, and pyoverdine biosynthesis genes were found to be significantly up-regulated during infection. In the mouse, we profiled the acute immune response to P. aeruginosa and identified the pro-inflammatory cytokines involved in acute response to the bacterium in the lung. Additionally, we also identified numerous host iron sequestration systems upregulated during infection. Overall, this work sheds light on how P. aeruginosa triggers a pro-inflammatory response and competes for iron with the host during infection, as iron is one of the central elements for which both pathogen and host fight during acute pneumonia. PMID:27982111
Empyema necessitans in a six-month-old girl.
Goussard, P; Gie, Robert; Janson, Jacques; Andronikou, Savvas
2018-05-23
Empyema necessitans is a rare complication of acute bacterial pneumonia, especially in children. It is a complication of empyema characterised by the extension of pus from the pleural cavity into the thoracic wall to form a mass of purulent fluid in the adjacent soft tissue. An inflammatory chest wall mass following pneumonia caused by Streptococcus pneumonia in a six-month-old infant is reported. The case emphasises that children presenting with persistent fever and a painful chest wall mass following pneumonia should be investigated immediately as there might be an urgent need for surgery.
21 CFR 520.2260a - Sulfamethazine oblet, tablet, and bolus.
Code of Federal Regulations, 2010 CFR
2010-04-01
... and nonlactating dairy cattle. Treatment of bacterial pneumonia and bovine respiratory disease complex... mastitis (Streptococcus spp.), acute metritis (Streptococcus spp.), coccidiosis (Eimeria bovis and Eimeria...
Participation of necroptosis in the host response to acute bacterial pneumonia
Ahn, Danielle; Prince, Alice
2017-01-01
Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus as well as the host-adapted pathogens responsible for health care associated pneumonias such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcesens are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages and in doing so contribute to host pathology through loss of their critical immunoregulatory functions. However, in other settings of infection, necroptosis promotes pathogen removal and eradication of infected cells to control excessive proinflammatory signaling. Bacterial production of pore forming toxins provides a common mechanism to activate necroptosis by diverse bacterial species, with variable consequences depending upon the specific pathogen. Included in this brief review are data demonstrating the ability of the carbapenem-resistant ST258 K. pneumoniae to activate necroptosis in the setting of pneumonia, which is counterbalanced by their suppression of CYLD expression. Exactly how necroptosis and other mechanisms of cell death are co-regulated in the response to specific pulmonary pathogens remains a topic of active investigation and may provide potential therapeutic targets in the future. PMID:28125817
Participation of Necroptosis in the Host Response to Acute Bacterial Pneumonia.
Ahn, Danielle; Prince, Alice
2017-01-01
Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus, as well as the host-adapted pathogens responsible for health care-associated pneumonias, such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcecsens, are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages, and, in so doing, contribute to host pathology through the loss of their critical immunoregulatory functions. However, in other settings of infection, necroptosis promotes pathogen removal and the eradication of infected cells to control excessive proinflammatory signaling. Bacterial production of pore-forming toxins provides a common mechanism to activate necroptosis by diverse bacterial species, with variable consequences depending upon the specific pathogen. Included in this brief review are data demonstrating the ability of the carbapenem-resistant ST258 K. pneumoniae to activate necroptosis in the setting of pneumonia, which is counterbalanced by their suppression of CYLD expression. Exactly how necroptosis and other mechanisms of cell death are coregulated in the response to specific pulmonary pathogens remains a topic of active investigation, and it may provide potential therapeutic targets in the future. © 2017 S. Karger AG, Basel.
[Infection and sickle cell anemia].
Bégué, P
1999-01-01
Sickle cell disease is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumococcal bacteremia and meningitis are so severe as to warrant prophylactic penicillin therapy, which has provided a dramatic decrease in early mortality. Bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia. Osteomyelitis is generally due to a salmonella, most often S. enteritidis; multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Parvovirus B 19 infection causes acute bone marrow failure. Malaria does not result in cerebral malaria but can lead to severe anemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (septicemia, meningitis, osteomyelitis), and mycoplasmas (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at four months of age and on closely-spaced immunizations, most notably against pneumococci, the hepatitis B virus, S. typhi, and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. Conjugated pneumococcal vaccines are effective in protecting infants and should therefore be used in sickle cell patients.
21 CFR 520.2261a - Sulfamethazine sodium drinking water solution.
Code of Federal Regulations, 2010 CFR
2010-04-01
... nonlactating dairy cattle. Treatment of bacterial pneumonia and bovine respiratory disease complex (shipping... mastitis (Streptococcus spp.), and acute metritis (Streptococcus spp.). (ii) Swine. Treatment of porcine...
Pesavento, P A; Hurley, K F; Bannasch, M J; Artiushin, S; Timoney, J F
2008-01-01
An outbreak of acute, fatal, hemorrhagic pneumonia was observed in more than 1,000 mixed breed dogs in a single animal shelter. The Department of Anatomic Pathology at the University of California at Davis School of Veterinary Medicine performed necropsies on dogs that were found moribund in acute respiratory distress or found dead with evidence of nasal bleeding. All dogs had hemothorax and an acute, fibrinosuppurative pneumonia. Large numbers of gram-positive cocci were observed within the lungs of all dogs and within septic thromboemboli of remote organs in about 50% of cases. Bacterial cultures from the dogs and their environment revealed widespread beta-hemolytic Streptococus equi subspecies zooepidemicus (Lancefield Group C). Extensive diagnostic testing failed to reveal the consistent presence of copathogens in individual cases. The clinical, epidemiologic, molecular biologic, and pathologic data indicate that a single clone of S. zooepidemicus was the cause of an acutely fatal respiratory infection in these dogs.
2001-10-01
infection, (2) pneumonia, and (3) cellulitis or folliculitis acute respiratory infection viral and bacterial etiology studies, requiring systemic...acute respiratory infection 6.5 12.9 0.50 (0.28-0.92) Pneumonia 3.2 5.2 0.62 (0.25-1.52) Cellulitis or folliculitis 10.6 13.7 0.78 (0.47-1.28) Attrition...477 (93%) of 511 trainees were enrolled. The 2 study 57 were treated with antibiotics for cellulitis or folliculitis . All groups had very similar
[Severe infections in children with sickle cell disease: clinical aspects and prevention].
Bégué, P; Castello-Herbreteau, B
2001-09-01
Sickle-cell disease (SCD) is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumonococcal bacteremia and meningitis due to S. pneumoniae are often lethal and justify the penicillin prophylaxis, which has provided a dramatic decrease in early mortality bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia, because they are often intricated. Osteomyelitis is generally due to Salmonella, most often S. enteritidis. Multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Osteomyelitis is less frequent in developed countries and must been differentiated with bone infarction by use of bone scintigraphy. Parvovirus B19 infection causes acute erythroblastopenias. Malaria does not result in cerebral malaria, but can lead to severe anaemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (osteomyelitis, meningitis), and M. pneumoniae (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at three months of age and no closely-spaced immunizations, most notably against peumococci, hepatitis B virus, S. typhi and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. New conjugated pneumococcal vaccines are effective in protecting very young infants and should therefore be used in sickle cell patients.
Mina, Michael J; Klugman, Keith P; Rosch, Jason W; McCullers, Jonathan A
2015-07-15
Infection with influenza A virus (IAV) increases susceptibility to respiratory bacterial infections, resulting in increased bacterial carriage and complications such acute otitis media, pneumonia, bacteremia, and meningitis. Recently, vaccination with live attenuated influenza virus (LAIV) was reported to enhance subclinical bacterial colonization within the nasopharynx, similar to IAV. Although LAIV does not predispose to bacterial pneumonia, whether it may alter bacterial transmigration toward the middle ear, where it could have clinically relevant implications, has not been investigated. BALB/c mice received LAIV or phosphate-buffered saline 1 or 7 days before or during pneumococcal colonization with either of 2 clinical isolates, 19F or 7F. Middle ear bacterial titers were monitored daily via in vivo imaging. LAIV increased bacterial transmigration to and persistence within the middle ear. When colonization followed LAIV inoculation, a minimum LAIV incubation period of 4 days was required before bacterial transmigration commenced. While LAIV vaccination is safe and effective at reducing IAV and coinfection with influenza virus and bacteria, LAIV may increase bacterial transmigration to the middle ear and could thus increase the risk of clinically relevant acute otitis media. These data warrant further investigations into interactions between live attenuated viruses and naturally colonizing bacterial pathogens. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Mofredj, A; Baraka, D
1997-01-01
Although utility of beta-lactams in the treatment of legionnaire's disease could not be demonstrated, clinical cures of human legionellosis with imipenem have been reported. We report the case of a 45-year-old man who presented clinical and radiological features of 'typical' bacterial pneumonia. He was successfully treated with imipenem. Serologic studies showed seroconversion for Legionella pneumophila.
CSF lactate level: a useful diagnostic tool to differentiate acute bacterial and viral meningitis.
Abro, Ali Hassan; Abdou, Ahmed Saheh; Ustadi, Abdulla M; Saleh, Ahmed Alhaj; Younis, Nadeem Javeed; Doleh, Wafa F
2009-08-01
To evaluate the potential role of CSF lactate level in the diagnosis of acute bacterial meningitis and in the differentiation between viral and bacterial meningitis. This was a hospital based observational study, conducted at Infectious Diseases Unit, Rashid Hospital Dubai, United Arab Emirates, from July 2004 to June 2007. The patients with clinical diagnosis of acute bacterial meningitis and who had CSF Gram stain/culture positive, CSF analysis suggestive of bacterial meningitis with negative Gram stain and culture but blood culture positive for bacteria and patients with clinical diagnosis suggestive of viral meningitis supported by CSF chemical analysis with negative Gram stain and culture as well as negative blood culture for bacteria were included in the study. CT scan brain was done for all patients before lumber puncture and CSF and blood samples were collected immediately after admission. CSF chemical analysis including lactate level was done on first spinal tap. The CSF lactate level was tested by Enzymatic Colorimetric method. A total 95 adult patients of acute meningitis (53 bacterial and 42 viral) fulfilled the inclusion criteria. Among 53 bacterial meningitis patients, Neisseria meningitides were isolated in 29 (54.7%), Strept. Pneumoniae in 18 (33.96%), Staph. Aureus in 2 (3.77%), Klebsiell Pneumoniae in 2 (3.77%), Strept. Agalactiae in 1 (1.8%) and E. Coli in 1 (1.8%). All the patients with bacterial meningitis had CSF lactate > 3.8 mmol/l except one, whereas none of the patients with viral meningitis had lactate level > 3.8 mmol/l. The mean CSF lactate level in bacterial meningitis cases amounted to 16.51 +/- 6.14 mmol/l, whereas it was significantly lower in viral group 2.36 +/- 0.6 mmol/l, p < .0001. CSF lactate level was significantly high in bacterial than viral meningitis and it can provide pertinent, rapid and reliable diagnostic information. Furthermore, CSF lactate level can also differentiate bacterial meningitis from viral one in a quick and better way.
Noreddin, Ayman M; Elkhatib, Walid F; Cunnion, Kenji M; Zhanel, George G
2011-01-01
Levofloxacin is the synthetic L-isomer of the racemic fluoroquinolone, ofloxacin. It interferes with critical processes in the bacterial cell such as DNA replication, transcription, repair, and recombination by inhibiting bacterial topoisomerases. Levofloxacin has broad spectrum activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation such that patients can be conveniently transitioned between these formulations when moving from the inpatient to the outpatient setting. Furthermore, levofloxacin demonstrates excellent safety, and has good tissue penetration maintaining adequate concentrations at the site of infection. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP are well established. Furthermore, a high-dose (750 mg) and short-course (5 days) of once-daily levofloxacin has been approved for use in the US in the treatment of CAP, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infections. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent antibacterial activity, decreases the potential for drug resistance, and has better patient compliance.
The Most Common Detected Bacteria in Sputum of Patients with the Acute Exacerbation of COPD
Cukic, Vesna
2013-01-01
Introduction: Acute exacerbation of COPD (AECOPD) may be triggered by infection with bacteria or viruses or by environmental pollutants; the cause of about one-third of exacerbations cannot be identified. Objective: To determine the most common bacteria in sputum culture of patients with AECOPD hospitalized in Intensive care unit of Clinic for pulmonary disease and TB “Podhrastovi” in the 2012. Material and methods: This is a retrospective analysis of sputum bacterial cultures of patients with AECOPD treated in the Intensive care unit of Clinic for pulmonary disease and TB “Podhrastovi” during 2012 .year. Each patient was required to give two sputum for bacterial examination. Each patient was treated with antibiotics prior to admission in Clinic “Podhrastovi”. The results of sputum bacterial culture findings are expressed in absolute number and percentage of examined patients. Results: In 2012, 75 patients with AECOPD were treated in Intensive care unit of Clinic for pulmonary disease and TB“Podhrastovi”. 44 (58.66%) of patients had normal –nonpathogenic – usual bacterial flora isolated in sputum cultures, 31 (41.34%) had a pathogen bacteria in sputum culture as follows: 7 had Streptoccocus pneumoniae, 8 had Klebsiella pneumoniae (2 with Streptococcus pneumoniae, one with Acinetobacter baumani) ,4 Escherichia colli, others are one or two cases with other bacteria. Conclusion: Bacterial airway infections play a great role in many, but not in all, of cases of AECOPD. So there is the need to do a sputum bacterial culture examination in each patient with AECOPD and with appropriate antibiotics to contribute to curing of them. PMID:24511262
Giuffrida, M J; Valero, N; Mosquera, J; Duran, A; Arocha, F; Chacín, B; Espina, L M; Gotera, J; Bermudez, J; Mavarez, A; Alvarez-Mon, M
2017-04-01
This study was aimed to determine the profiles of serum cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non-asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and non-asthmatic patients was observed. However, higher concentrations of chemokines (MCP-1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non-asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non-asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status. © 2017 The Foundation for the Scandinavian Journal of Immunology.
Comparison of culture and PCR methods in the diagnosis of bacterial meningitis.
Başpınar, Emel Ödemiş; Dayan, Saim; Bekçibaşı, Muhammed; Tekin, Recep; Ayaz, Celal; Deveci, Özcan; Hoşoğlu, Salih
Our aim in this study is to compare the standard culture method with the multiplex PCR and the Speed-Oligo ® Bacterial Meningitis Test (SO-BMT) - a hybridization-based molecular test method - during the CSF examination of the patients with the pre-diagnosis of acute bacterial meningitis. For the purposes of this study, patients with acute bacterial meningitis treated at the Dicle University Medical Faculty Hospital, Infectious Diseases and Clinical Microbiology Clinic between December 2009 and April 2012 were retrospectively evaluated. The diagnosis of bacterial meningitis was made based on the clinical findings, laboratory test anomalies, CSF analysis results, and the radiological images. Growth was observed in the CSF cultures of 10 out of the 57 patients included in the study (17.5%) and Streptococcus pneumoniae was isolated in all of them. The CSF samples of 34 patients (59.6%) were positive according to the SO-BMT and S. pneumoniae was detected in 33 of the samples (97.05%), while Neisseria meningitidis was found in 1 sample (2.95%). In a total of 10 patients, S. pneumoniae was both isolated in the CSF culture and detected in the SO-BMT. The culture and the SO-BMT were negative in 23 of the CSF samples. There was no sample in which the CSF culture was positive although the SO-BMT was negative. While SO-BMT seems to be a more efficient method than bacterial culturing to determine the pathogens that most commonly cause bacterial meningitis in adults, further studies conducted on larger populations are needed in order to assess its efficiency and uses. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.
Back to the Basics: Community-Acquired Pneumonia in Children.
Boyd, Kathleen
2017-07-01
Community-acquired pneumonia (CAP) is a common childhood infection and often a reason for inpatient admission, especially when a child is hypoxic or in respiratory distress. Despite advances in technology and diagnostics, it remains difficult to accurately differentiate bacterial CAP from a viral process. Most of the laboratory tests routinely done in inpatient medicine, such as complete blood counts and acute phase reactants, do little to differentiate a viral pneumonia from a bacterial pneumonia. Clinicians must rely heavily on the clinical presentation and decide whether to treat empirically with antibiotics. Guidelines published by the Infectious Disease Society of America in 2011 have helped clinicians standardize the diagnosis and treatment of CAP. The guidelines recommend relatively narrow-spectrum antibiotics, such as ampicillin or penicillin, as empiric coverage for the fully immunized child older than age 3 months who requires hospitalization for CAP. [Pediatr Ann. 2017;46(7):e257-e261.]. Copyright 2017, SLACK Incorporated.
2011-01-01
Background Acute otitis media (AOM) is one of the most frequently encountered bacterial infections in children aged < 5 years; Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are historically identified as primary AOM causes. Nevertheless, recent data on bacterial pathogens causing AOM in Latin America are limited. This prospective study aimed to identify and characterize bacterial etiology and serotypes of AOM cases including antimicrobial susceptibility in < 5 year old Colombian children. Methods From February 2008 to January 2009, children ≥3 months and < 5 years of age presenting with AOM and for whom a middle ear fluid (MEF) sample was available were enrolled in two medical centers in Cali, Colombia. MEF samples were collected either by tympanocentesis procedure or spontaneous otorrhea swab sampling. Bacteria were identified using standard laboratory methods, and antimicrobial resistance testing was performed based on the 2009 Clinical and Laboratory Standards Institute (CLSI) criteria. Most of the cases included in the study were sporadic in nature. Results Of the 106 enrolled children, 99 were included in the analysis. Bacteria were cultured from 62/99 (63%) of samples with S. pneumoniae, H. influenzae, or S. pyogenes. The most commonly isolated bacteria were H. influenzae in 31/99 (31%) and S. pneumoniae in 30/99 (30%) of samples. The majority of H. influenzae episodes were NTHi (27/31; 87%). 19F was the most frequently isolated pneumococcal serotype (10/30; 33%). Of the 30 S. pneumoniae positive samples, 8/30 (27%) were resistant to tetracycline, 5/30 (17%) to erythromycin and 8/30 (27%) had intermediate resistance to penicillin. All H. influenzae isolates tested were negative to beta-lactamase. Conclusions NTHi and S. pneumoniae are the leading causes of AOM in Colombian children. A pneumococcal conjugate vaccine that prevents both pathogens could be useful in maximizing protection against AOM. PMID:21208431
[Clinical evaluation of cefdinir 5% fine granules in pediatrics].
Iwai, N; Nakamura, H; Taneda, Y; Miyazu, M; Kasai, K; Watanabe, Y
1991-10-01
Clinical evaluation in pediatrics on cefdinir (CFDN, FK482) (5% fine granules), a new oral cephem, was performed. 1. CFDN was administered to 112 pediatric patients with ages between 1 month to 13 years with various infections. Dose levels used were 3.0-8.9 mg/kg (mean 5.1 mg/kg) t.i.d. for 3-14 days (mean 6.7 days). The studied patients included 2 patients with scarlet fever, 6 with acute pharyngitis, 6 with acute rhinopharyngitis, 52 with acute purulent tonsillitis, 8 with acute bronchitis, 24 with acute pneumonia, 7 with acute urinary tract infections, 1 with acute vaginitis, and 6 with impetigo. Total doses ranged from 0.6 to 4.05 g. One hundred eleven of the 112 patients were evaluated for clinical efficacy and all the patients were evaluated for safety. 2. Clinical effects were excellent in 51 cases, good in 57, and fair in 3 with an extremely high efficacy rate of 97.3%. Efficacy rates were 100% in scarlet fever, acute pharyngitis, acute purulent tonsillitis, acute bronchitis, acute vaginitis and impetigo, and 83.3%, 95.7%, 85.7% in acute rhinopharyngitis, acute pneumonia, and acute urinary tract infections, respectively. Good clinical effects were observed regardless of diseases. 3. Causative organisms were identified in 79 cases, of which 71 were found to be monobacterial infections and 8 were found to be multi-bacterial infections. In mono-bacterial infections, clinical efficacies were 100% for those caused by Staphylococcus aureus/Streptococcus pyogenes/Streptococcus pneumoniae/beta-Streptococcus except those in A and B groups with an overall efficacy of 100% against Gram-positive cocci (GPC) and they were 89.5%, 100%, 100% for those caused by Haemophilus influenzae, Haemophilus parainfluenzae, and Escherichia coli, respectively, with an overall efficacy of 90.3% in Gram-negative rods (GNR). In multi-bacterial infections also, a clinical efficacy of 100% was obtained. 4. Bacteriological effects were studied for 89 strains in the 79 cases. The eradication rate for a few strains of S. pneumoniae was low, 25%, but it was 100% for S. aureus, with the same results for S. pyogenes, and beta-Streptococcus. The eradication rate on GPC was high 94.1%. Among GNR, 66.7% of E. coli, 50.0% of H. influenzae, and 71.4% of H. parainfluenzae was eradicated. The overall eradication rate for GNR was 55.3%, lower than that for GPC. Microbial substitutions were observed in 13 cases, with Haemophilus sp. replacing other bacteria. 5. Diarrhea and soft stools were noted in 4 and 2 patients, respectively. The severity of these side effects, however, was slight and it was possible to continue the CFDN treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Application of thin-section low-dose chest CT (TSCT) in the management of pediatric AIDS.
Ambrosino, M M; Roche, K J; Genieser, N B; Kaul, A; Lawrence, R M
1995-01-01
The aim of this study was to evaluate the usefulness of thin-section low-dose computed tomography (TSCT) in the management of children with AIDS, as chest radiographs (CXR) often fail to adequately explain the patients' clinical status. We performed 54 noncontrast TSCTs on 32 children. The patients aged from 3 months to 14.6 years, were diagnosed as having bacterial pneumonia, lumphocytic interstitial pneumonitis (LIP), Pneumocystis carinii pneumonia (PCP), or Mycobacterium avium-intracellulare infection (MAI). The scans were correlated with the clinical diagnosis, T-lymphocyte-subset percentages, and p24-antigen levels. Subsegmental consolidations were seen in patients with LIP, PCP, and MAI, and as an isolated finding in those with only bacterial pneumonia. Ground-glass haziness was seen exclusively with acute PCP. Reticulonodular thickening was identified only in patients with LIP. Mosaic perfusion was seen with MAI, LIP, and pneumonia. The presence of adenopathy correlated with CD4+ T-cell subset percentages. The greatest value of CT in this study was in detecting new disease when chest films failed to correlate with a patient's clinical state, and in demonstrating acute/subacute disease in patients with severe baseline chest-film changes. Recurrent pneumonias may represent progression of "smoldering" disease, rather than true recurrent disease following complete clearing. Adenopathy with low CD4+ levels should suggest lymphoma or infection with MAI.
A definite case of (L)-carbocisteine-induced pneumonia with CATCH22 syndrome.
Kudo, Kenichiro; Ichihara, Eiki; Hisamoto, Akiko; Hotta, Katsuyuki; Miyahara, Nobuaki; Tanimoto, Yasushi; Akagi, Sadaharu; Kato, Katsuya; Tanimoto, Mitsune; Kiura, Katsuyuki
2013-01-01
A 32-year-old male with CATCH22 syndrome presented with a high fever and productive cough after taking drugs for acute bronchitis, including (L)-carbocisteine. Chest radiography revealed ground-glass opacities in the bilateral lung fields. He had a history of similar pneumonia. Under the assumption of drug-induced pneumonia, or bacterial or viral pneumonia, all drugs including (L)-carbocisteine were discontinued, and antibiotics were started. A drug-induced lymphocyte stimulation test was positive only for (L)-carbocisteine. The only drug in common between this and the previous episode of pneumonia was (L)-carbocisteine. We thus concluded that this was a definite case of (L)-carbocisteine-induced pneumonia in a patient with CATCH22 syndrome.
Poe, Stephanie L.; Arora, Meenakshi; Oriss, Timothy B.; Yarlagadda, Manohar; Isse, Kumiko; Khare, Anupriya; Levy, David E.; Lee, Janet S.; Mallampalli, Rama; Ray, Anuradha; Ray, Prabir
2012-01-01
Bacterial pneumonia remains a significant burden worldwide. Although an inflammatory response in the lung is required to fight the causative agent, persistent tissue-resident neutrophils in non-resolving pneumonia can induce collateral tissue damage and precipitate acute lung injury. However, little is known about mechanisms orchestrated in the lung tissue that remove apoptotic neutrophils to restore tissue homeostasis. In mice infected with Klebsiella pneumoniae, a bacterium commonly associated with hospital-acquired pneumonia, we show that interleukin-10 is essential for resolution of lung inflammation and recovery of mice after infection. Although IL-10−/− mice cleared bacteria, they displayed increased morbidity with progressive weight loss and persistent lung inflammation in the later phase after infection. A source of tissue IL-10 was found to be resident CD11b+Gr1intF4/80+ cells resembling myeloid-derived suppressor cells that appeared with a delayed kinetics after infection. These cells efficiently efferocytosed apoptotic neutrophils, which was aided by IL-10. The lung neutrophil burden was attenuated in infected STAT1−/− mice with concomitant increase in the frequency of the MDSC-like cells and lung IL-10 levels. Thus, inhibiting STAT1 in combination with antibiotics may be a novel therapeutic strategy to address inefficient resolution of bacterial pneumonia. PMID:22785228
Animal models of hospital-acquired pneumonia: current practices and future perspectives
Bielen, Kenny; ’S Jongers, Bart; Malhotra-Kumar, Surbhi; Jorens, Philippe G.; Goossens, Herman
2017-01-01
Lower respiratory tract infections are amongst the leading causes of mortality and morbidity worldwide. Especially in hospital settings and more particularly in critically ill ventilated patients, nosocomial pneumonia is one of the most serious infectious complications frequently caused by opportunistic pathogens. Pseudomonas aeruginosa is one of the most important causes of ventilator-associated pneumonia as well as the major cause of chronic pneumonia in cystic fibrosis patients. Animal models of pneumonia allow us to investigate distinct types of pneumonia at various disease stages, studies that are not possible in patients. Different animal models of pneumonia such as one-hit acute pneumonia models, ventilator-associated pneumonia models and biofilm pneumonia models associated with cystic fibrosis have been extensively studied and have considerably aided our understanding of disease pathogenesis and testing and developing new treatment strategies. The present review aims to guide investigators in choosing appropriate animal pneumonia models by describing and comparing the relevant characteristics of each model using P. aeruginosa as a model etiology for hospital-acquired pneumonia. Key to establishing and studying these animal models of infection are well-defined end-points that allow precise monitoring and characterization of disease development that could ultimately aid in translating these findings to patient populations in order to guide therapy. In this respect, and discussed here, is the development of humanized animal models of bacterial pneumonia that could offer unique advantages to study bacterial virulence factor expression and host cytokine production for translational purposes. PMID:28462212
Noreddin, Ayman M; Elkhatib, Walid F; Cunnion, Kenji M; Zhanel, George G
2011-01-01
Levofloxacin is the synthetic L-isomer of the racemic fluoroquinolone, ofloxacin. It interferes with critical processes in the bacterial cell such as DNA replication, transcription, repair, and recombination by inhibiting bacterial topoisomerases. Levofloxacin has broad spectrum activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation such that patients can be conveniently transitioned between these formulations when moving from the inpatient to the outpatient setting. Furthermore, levofloxacin demonstrates excellent safety, and has good tissue penetration maintaining adequate concentrations at the site of infection. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP are well established. Furthermore, a high-dose (750 mg) and short-course (5 days) of once-daily levofloxacin has been approved for use in the US in the treatment of CAP, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infections. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent antibacterial activity, decreases the potential for drug resistance, and has better patient compliance. PMID:22046107
Farajzadah Sheikh, Ahmad; Saki, Nader; Roointan, Mitra; Ranjbar, Reza; Yadyad, Mohammad Jaafar; Kaydani, Abbas; Aslani, Sajad; Babaei, Mansoor; Goodarzi, Hamed
2015-01-01
Background: Based on many studies, otitis media with effusion (OME) is one of the major causes of childhood hearing loss, social malformation and medical costs. The pathogenesis still remains unclear, though it is known that this complication is closely related to bacterial infections. Alloiococcus otitidis, Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis are the most common bacterial pathogens isolated from middle ear effusions (MEEs). Objectives: Due to the prevalence of OME in children, we decided to investigate bacterial agents that cause diseases such as A. otitidis, H. influenzae, S. pneumonia and M. catarrhalis in these subjects. Patients and Methods: Forty-five children between one and 15 years of age were selected for this study. Seventy specimens were collected from MEE by myringotomy and inoculated in PBS buffer. Conventional culture and PCR methods were used for identification of bacterial agents. Results: The bacterial cultures in 8.6% of samples were positive by conventional culture, with A. otitidis, M. catarrhalis and S. pneumoniae present in 1.4%, 2.9% and 4.3% of samples, respectively. No H. influenzae was isolated. By the PCR method, A. otitidis was the most frequently isolated bacterium, found in 25.7% of samples, followed by S. pneumoniae, M. catarrhalis and H. influenzae, which were identified in 20%, 12% and 20% of samples, respectively. Overall, 55 out of 70 samples were positive by both the PCR and culture method. Conclusions: It can be concluded that A. otitidis was the major causative agent of MEE in children with OME. Therefore clinicians should be aware that bacterial infection plays an important role in the progression of acute otitis media to OME in children of our region. PMID:25861433
Bucior, Iwona; Abbott, Jason; Song, Yuanlin; Matthay, Michael A.
2013-01-01
Treatment of acute and chronic pulmonary infections caused by opportunistic pathogen Pseudomonas aeruginosa is limited by the increasing frequency of multidrug bacterial resistance. Here, we describe a novel adjunctive therapy in which administration of a mix of simple sugars—mannose, fucose, and galactose—inhibits bacterial attachment, limits lung damage, and potentiates conventional antibiotic therapy. The sugar mixture inhibits adhesion of nonmucoid and mucoid P. aeruginosa strains to bronchial epithelial cells in vitro. In a murine model of acute pneumonia, treatment with the sugar mixture alone diminishes lung damage, bacterial dissemination to the subpleural alveoli, and neutrophil- and IL-8-driven inflammatory responses. Remarkably, the sugars act synergistically with anti-Pseudomonas antibiotics, including β-lactams and quinolones, to further reduce bacterial lung colonization and damage. To probe the mechanism, we examined the effects of sugars in the presence or absence of antibiotics during growth in liquid culture and in an ex vivo infection model utilizing freshly dissected mouse tracheas and lungs. We demonstrate that the sugar mixture induces rapid but reversible formation of bacterial clusters that exhibited enhanced susceptibility to antibiotics compared with individual bacteria. Our findings reveal that sugar inhalation, an inexpensive and safe therapeutic, could be used in combination with conventional antibiotic therapy to more effectively treat P. aeruginosa lung infections. PMID:23792737
The Role of Viral, Host, and Secondary Bacterial Factors in Influenza Pathogenesis
Kash, John C.; Taubenberger, Jeffery K.
2016-01-01
Influenza A virus infections in humans generally cause self-limited infections, but can result in severe disease, secondary bacterial pneumonias, and death. Influenza viruses can replicate in epithelial cells throughout the respiratory tree and can cause tracheitis, bronchitis, bronchiolitis, diffuse alveolar damage with pulmonary edema and hemorrhage, and interstitial and airspace inflammation. The mechanisms by which influenza infections result in enhanced disease, including development of pneumonia and acute respiratory distress, are multifactorial, involving host, viral, and bacterial factors. Host factors that enhance risk of severe influenza disease include underlying comorbidities, such as cardiac and respiratory disease, immunosuppression, and pregnancy. Viral parameters enhancing disease risk include polymerase mutations associated with host switch and adaptation, viral proteins that modulate immune and antiviral responses, and virulence factors that increase disease severity, which can be especially prominent in pandemic viruses and some zoonotic influenza viruses causing human infections. Influenza viral infections result in damage to the respiratory epithelium that facilitates secondary infection with common bacterial pneumopathogens and can lead to secondary bacterial pneumonias that greatly contribute to respiratory distress, enhanced morbidity, and death. Understanding the molecular mechanisms by which influenza and secondary bacterial infections, coupled with the role of host risk factors, contribute to enhanced morbidity and mortality is essential to develop better therapeutic strategies to treat severe influenza. PMID:25747532
Respiratory infections and acute lung injury in systemic illness.
Skerrett, S J; Niederman, M S; Fein, A M
1989-12-01
We have discussed the relationship between systemic illness, infection, and lung disease. As we have seen, patients with a wide variety of disease states, including advanced age, diabetes mellitus, alcoholism, collagen vascular disease, cancer, heart failure, and organ transplantation are potentially at increased risk for pneumonia because of disease-related impairments in host defenses. In addition, two virtually ubiquitous conditions in hospitalized patients, malnutrition and therapeutic interventions (especially with common medications), frequently add to the risk of airway invasion by bacterial pathogens. Systemic illness not only makes lung infection more common, but may adversely affect outcome and resolution, as well as determine the clinical presentation of pneumonia. In one particular population, the intubated and mechanically ventilated patient, the risk of infection is particularly high, and nosocomial pneumonia is a major cause of mortality. To the extent that the host response itself leads to the symptoms and signs of infection, systemically ill individuals may have subtle clinical features when serious bacterial invasion is present. Many components of the host defense system can become abnormal with serious illness, but a common mechanism that ties many systemic diseases to pneumonia is an alteration in airway epithelial cell receptivity for bacteria, namely, bacterial adherence, a process that mediates airway colonization, the first pathogenetic step on the road to pneumonia. The impetus for understanding how serious illness promotes lung infection is that once these mechanisms are identified, potential preventative strategies to minimize infection risk in the individual with systemic disease may be developed. The relationship among systemic illness, the lung, and infection also exists in a different direction: infection of a systemic nature (the septic syndrome) can lead to disease in the lung (ARDS). We have described the features of the septic syndrome and identified how it may lead to lung injury, usually by indirect means, through activation of inflammatory mediators that are carried to the lung via the vasculature. Although it is frequently impossible to predict which specific patient with systemic sepsis will develop acute lung injury, the current state of knowledge does permit us to identify high-risk individuals. Surprisingly, clinical assessment rather than biochemical testing is the best predictor of the development of acute lung injury. Patients with severe injury, profound shock and multiple systemic insults are most prone to acute lung injury in the presence of systemic sepsis.(ABSTRACT TRUNCATED AT 400 WORDS)
A trial of high-dose, short-course levofloxacin for the treatment of acute bacterial sinusitis.
Poole, Michael; Anon, Jack; Paglia, Margaret; Xiang, Jim; Khashab, Mohammed; Kahn, James
2006-01-01
Compare two dosage strengths of levofloxacin in the treatment of acute bacterial sinusitis. Multicenter clinical trial comparing levofloxacin 750 mg for 5 days vs levofloxacin 500 mg for 10 days. Sinus fluid samples were obtained by antral puncture (59.2%) or by sinus endoscopy (40.8%). Among microbiologically evaluable patients, 91.4% (139/152) of patients receiving levofloxacin 750 mg achieved clinical success vs 88.6% (132/149) of patients receiving levofloxacin 500 mg (95% CI -10.0, 4.2). Clinical success rates by pathogen were above 90% in both treatment groups for the 3 typical pathogens of acute sinusitis: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The safety profile of the 2 dosage strengths was similar. Levofloxacin 750 mg for 5 days is noninferior to levofloxacin 500 mg for 10 days. Levofloxacin 750 mg for 5 days represents a safe and effective treatment regimen for acute bacterial sinusitis. A-1b.
Jiang, Hongchao; Su, Min; Kui, Liyue; Huang, Hailin; Qiu, Lijuan; Li, Li; Ma, Jing; Du, Tingyi; Fan, Mao; Liu, Xiaomei
2017-01-01
Acute bacterial meningitis is still considered one of the most dangerous infectious diseases in children. To investigate the prevalence and antibiotic resistance profiles of cerebrospinal fluid (CSF) pathogens in children with acute bacterial meningitis in Southwest China, CSF samples from 179 meningitis patients (3 days to 12 years old) with positive culture results were collected from 2012 to 2015. Isolated pathogens were identified using the Vitek-32 system. Gram stain results were used to guide subcultures and susceptibility testing. The antimicrobial susceptibility of isolates was determined using the disc diffusion method. Of the isolates, 50.8% were Gram-positive bacteria, and 49.2% were Gram-negative bacteria. The most prevalent pathogens were E. coli (28.5%), Streptococcus pneumoniae (17.8%), Staphylococcus epidermidis (10.0%), Haemophilus influenzae type b (9.5%), and group B streptococcus (7.2%). In young infants aged ≤3 months, E. coli was the organism most frequently isolated from CSF (39/76; 51.3%), followed by group B streptococcus (13/76; 17.1%) and Streptococcus pneumoniae (8/76; 10.5%). However, in young infants aged >3 months, the most frequently isolated organism was Streptococcus pneumoniae (24/103; 23.3%), followed by Staphylococcus epidermidis (18/103; 17.5%) and Haemophilus influenzae type b (16/103; 15.5%). Antimicrobial susceptibility tests indicated that for E. coli isolates, the susceptibility rates to aminoglycosides ranged from 56.8% to 100.0%, among them, amikacin was identified as the most effective against E. coli. As for cephalosporins, the susceptibility rates ranged from 29.4% to 78.4%, and cefoxitin was identified as the most effective cephalosporin. In addition, the susceptibility rates of piperacillin/tazobactam and imipenem against E. coli were 86.3% and 100%. Meanwhile, the susceptibility rates of Streptococcus pneumoniae isolates to penicillin G, erythromycin, chloramphenicol, ceftriaxone and tetracycline were 68.8%, 0.0%, 87.5%, 81.3% and 0.0%, respectively. Gentamycin, ofloxacin, linezolid and vancomycin were identified as the most effective antibiotics for Streptococcus pneumoniae, each with susceptibility rates of 100%. It was notable that other emerging pathogens, such as Listeria monocytogenes and group D streptococcus, cannot be underestimated in meningitis. PMID:28662145
Jiang, Hongchao; Su, Min; Kui, Liyue; Huang, Hailin; Qiu, Lijuan; Li, Li; Ma, Jing; Du, Tingyi; Fan, Mao; Sun, Qiangming; Liu, Xiaomei
2017-01-01
Acute bacterial meningitis is still considered one of the most dangerous infectious diseases in children. To investigate the prevalence and antibiotic resistance profiles of cerebrospinal fluid (CSF) pathogens in children with acute bacterial meningitis in Southwest China, CSF samples from 179 meningitis patients (3 days to 12 years old) with positive culture results were collected from 2012 to 2015. Isolated pathogens were identified using the Vitek-32 system. Gram stain results were used to guide subcultures and susceptibility testing. The antimicrobial susceptibility of isolates was determined using the disc diffusion method. Of the isolates, 50.8% were Gram-positive bacteria, and 49.2% were Gram-negative bacteria. The most prevalent pathogens were E. coli (28.5%), Streptococcus pneumoniae (17.8%), Staphylococcus epidermidis (10.0%), Haemophilus influenzae type b (9.5%), and group B streptococcus (7.2%). In young infants aged ≤3 months, E. coli was the organism most frequently isolated from CSF (39/76; 51.3%), followed by group B streptococcus (13/76; 17.1%) and Streptococcus pneumoniae (8/76; 10.5%). However, in young infants aged >3 months, the most frequently isolated organism was Streptococcus pneumoniae (24/103; 23.3%), followed by Staphylococcus epidermidis (18/103; 17.5%) and Haemophilus influenzae type b (16/103; 15.5%). Antimicrobial susceptibility tests indicated that for E. coli isolates, the susceptibility rates to aminoglycosides ranged from 56.8% to 100.0%, among them, amikacin was identified as the most effective against E. coli. As for cephalosporins, the susceptibility rates ranged from 29.4% to 78.4%, and cefoxitin was identified as the most effective cephalosporin. In addition, the susceptibility rates of piperacillin/tazobactam and imipenem against E. coli were 86.3% and 100%. Meanwhile, the susceptibility rates of Streptococcus pneumoniae isolates to penicillin G, erythromycin, chloramphenicol, ceftriaxone and tetracycline were 68.8%, 0.0%, 87.5%, 81.3% and 0.0%, respectively. Gentamycin, ofloxacin, linezolid and vancomycin were identified as the most effective antibiotics for Streptococcus pneumoniae, each with susceptibility rates of 100%. It was notable that other emerging pathogens, such as Listeria monocytogenes and group D streptococcus, cannot be underestimated in meningitis.
Ishiguro, Takashi; Kagiyama, Naho; Uozumi, Ryuji; Odashima, Kyuto; Takaku, Yotaro; Kurashima, Kazuyoshi; Morita, Satoshi; Takayanagi, Noboru
2017-06-01
Background : Pneumonia is a major complication of influenza that contributes to mortality. Clinical characteristics and factors of influenza virus contributing to the severity and mortality of pneumonia have not been fully elucidated. Objective : The objective was to clarify clinical characteristics and factors contributing to the severity and mortality of influenza-associated pneumonia ( flu-p ). Methods : We retrospectively analyzed patients with flu-p . Results : From December 1999 to March 2016, 210 patients with a median age of 69 (range, 17 to 92) years with flu-p based on positive rapid antigen tests, increased antibody titers of paired sera, or positive results of reverse transcription polymerase chain reaction were admitted to our institution. A multivariate analysis found that advanced age (≥ 65 years), pneumonia subtypes (unclassified), diabetes mellitus, and acute kidney injury complicated with flu-p were independent factors associated with disease severity, whereas pneumonia subtypes (mixed viral and bacterial pneumonia and unclassified), healthcare-associated pneumonia, acute kidney injury complicated with flu-p , and severity on admission (severe) were independent factors associated with non-survival. Conclusion : The clinical characteristics of flu-p are varied, and the contribution of several factors to the severity and mortality of flu-p suggest their importance in either preventing flu-p or managing flu-p after it develops.
Ishiguro, Takashi; Kagiyama, Naho; Uozumi, Ryuji; Odashima, Kyuto; Takaku, Yotaro; Kurashima, Kazuyoshi; Morita, Satoshi; Takayanagi, Noboru
2017-01-01
Background: Pneumonia is a major complication of influenza that contributes to mortality. Clinical characteristics and factors of influenza virus contributing to the severity and mortality of pneumonia have not been fully elucidated. Objective: The objective was to clarify clinical characteristics and factors contributing to the severity and mortality of influenza-associated pneumonia (flu-p). Methods: We retrospectively analyzed patients with flu-p. Results: From December 1999 to March 2016, 210 patients with a median age of 69 (range, 17 to 92) years with flu-p based on positive rapid antigen tests, increased antibody titers of paired sera, or positive results of reverse transcription polymerase chain reaction were admitted to our institution. A multivariate analysis found that advanced age (≥ 65 years), pneumonia subtypes (unclassified), diabetes mellitus, and acute kidney injury complicated with flu-p were independent factors associated with disease severity, whereas pneumonia subtypes (mixed viral and bacterial pneumonia and unclassified), healthcare-associated pneumonia, acute kidney injury complicated with flu-p, and severity on admission (severe) were independent factors associated with non-survival. Conclusion: The clinical characteristics of flu-p are varied, and the contribution of several factors to the severity and mortality of flu-p suggest their importance in either preventing flu-p or managing flu-p after it develops. PMID:28656006
Puumalainen, Taneli; Quiambao, Beatriz; Abucejo-Ladesma, Erma; Lupisan, Socorro; Heiskanen-Kosma, Tarja; Ruutu, Petri; Lucero, Marilla G; Nohynek, Hanna; Simoes, Eric A F; Riley, Ian
2008-07-21
The World Health Organization's (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies. A group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population. Among the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO-defined severe pneumonia (with chest indrawing) had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation. The WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings. ISRCTN62323832.
Gauchan, E; Adhikari, S
2016-09-01
Pneumonia is a leading cause of childhood mortality in a low resource country. Simple laboratory markers can help differentiate between bacterial and non-bacterial pneumonias for appropriate management. In children aged one to 60 months with features of lower respiratory infection, C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were used to differentiate between bacterial and non-bacterial pneumonias. The cutoff values for detecting bacterial pneumonias were evaluated by statistical tools. Bacterial pneumonia was diagnosed in 285 (43.6%) children out of 654 studied. At a cut-off value of 36 mg/L CRP was predictive of bacterial pneumonias with sensitivity and specificity of 61.8% and 91.3% respectively while the sensitivity and specificity for predicting bacterial pneumonia using NLR was 45.6% and 64% respectively with 1.28 used as a cut-off. Our study shows that CRP is superior to NLR in differentiating bacterial from non-bacterial pneumonias in children.
Phenotypic Characterization and Antibiogram of CSF Isolates in Acute Bacterial Meningitis.
Modi, Syamal; Anand, Amit Kumar
2013-12-01
Acute bacterial meningitis (ABM) is a medical emergency, which warrants an early diagnosis and an aggressive therapy. Despite the availability of potent newer antibiotics, the mortality rate caused by acute bacterial meningitis remains significantly high in India and in other developing countries, which ranges from 16 - 32%. There is a need of a periodic review of bacterial meningitis worldwide, since the pathogens which are responsible for the infection may vary with time, geography and the age of the patient. Our aim was to study the bacterial profiles and antimicrobial susceptibility patterns of the CSF isolates which were obtained from patients of acute bacterial meningitis in our area. Two hundred and fifty two clinically diagnosed cases of acute bacterial meningitis, who were admitted to the wards of a tertiary medical centre in Patna, during the period from August 2011 to December 2012, were included in this study. Two hundred and fifty two CSF samples from as many patients of ABM were processed for cell counts, biochemical analysis, gram staining, culture, antigen detection by latex agglutination test (LAT) and antibiotic susceptibility tests, as per the standard techniques. In this study, 62.3% patients were males and 37.7% were females The most common age group of presentation was 12-60 years (80.2%). Gram stained smears were positive in 162 (64.3%) samples, while culture yielded positive growth in 200 (79.4%) patients. Streptococcus pneumoniae was the most common pathogen which was isolated in 120 (60%) culture positive cases. Cell counts showed the predominance of neutrophils in all cases with ABM. High protein and low sugar levels correlated well with the features of ABM. All gram positive isolates were sensitive to vancomycin. All the gram negative isolates were sensitive to imipenem. Twenty two (8.7%) patients expired during the course of study. Deaths were caused by N.meningitidis in 9 (40.9%) cases, by S.pneumoniae in 3 (13.6%) cases and by H.influenzea in 1 (4.5%) case. In the remaining 9 (40.9%) mortality cases, the organism could not be identified. Simple, rapid, inexpensive tests like gram staining remain significant means for diagnosis of ABM in developing countries. LAT for pneumococcal antigen should be performed first, since Streptococcus pneumoniae remains the major aetiological agent of ABM, both in adults and children. The final diagnosis of ABM depends upon a comprehensive analysis of CSF smears, cultures, LAT, cytological, biochemical and clinical findings of the cases, and a single test or parameter cannot be used to decide the course of management in the patients. However, empirical therapy is advocated, considering the potentially high rate of mortality in these patients.
Hoberman, Alejandro; Dagan, Ron; Leibovitz, Eugene; Rosenblut, Andres; Johnson, Candice E; Huff, Anne; Bandekar, Rajesh; Wynne, Brian
2005-06-01
A large dosage pediatric formulation of amoxicillin/clavulanate with an improved pharmacokinetic/pharmacodynamic profile was developed to eradicate many penicillin-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae (including beta-lactamase-producing strains). This randomized, investigator-blinded, multicenter trial examined treatment of bacterial acute otitis media (AOM) in children 6-30 months of age with amoxicillin/clavulanate (90/6.4 mg/kg/d in 2 divided doses for 10 days) versus azithromycin (10 mg/kg for 1 day followed by 5 mg/kg/d for 4 days). Tympanocentesis was performed at entry for bacteriologic assessment, at the on-therapy visit (day 4-6) to determine bacterial eradication and at any time before the end-of-therapy visit (day 12-14) if the child was categorized as experiencing clinical failure. Clinical assessments were performed at the on-therapy, end-of-therapy and follow-up (day 21-25) visits. We enrolled 730 children; AOM pathogens were isolated at baseline for 249 of the amoxicillin/clavulanate group and 245 of the azithromycin group. For children with AOM pathogens at baseline, clinical success rates at the end-of-therapy visit were 90.5% for amoxicillin/clavulanate versus 80.9% for azithromycin (P < 0.01), and those at the on-therapy and follow-up visits were 94.9% versus 88.0% and 80.3% versus 71.1%, respectively (all P < 0.05). At the on-therapy visit, pretherapy pathogens were eradicated for 94.2% of children receiving amoxicillin/clavulanate versus 70.3% of those receiving azithromycin (P < 0.001). Amoxicillin/clavulanate eradicated 96.0% of S. pneumoniae (92.0% of fully penicillin-resistant S. pneumoniae) and 89.7% of H. influenzae (85.7% [6 of 7 cases] of beta-lactamase-positive H. influenzae). Corresponding rates for azithromycin were 80.4% (54.5%) for S. pneumoniae and 49.1% (100% [1 of 1 case]) for H. influenzae (all P < 0.01 for between-drug comparisons). Amoxicillin/clavulanate was clinically and bacteriologically more effective than azithromycin among children with bacterial AOM, including cases caused by penicillin-resistant S. pneumoniae and beta-lactamase-positive H. influenzae.
Naranjo, Laura; Suarez, Jose Antonio; DeAntonio, Rodrigo; Sanchez, Francis; Calvo, Alberto; Spadola, Enza; Rodríguez, Nicolás; Andrade, Omaira; Bertuglia, Francisca; Márquez, Nelly; Castrejon, Maria Mercedes; Ortega-Barria, Eduardo; Colindres, Romulo E
2012-02-15
Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age. Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes). Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (S. pneumoniae, H. influenzae, S. pyogenes or M. catarrhalis) was cultured from 65.9% (60/91) of episodes. H. influenzae (55.5%; 35/63 episodes) and S. pneumoniae (34.9%; 22/63 episodes) were the most frequently reported bacteria. Among H. influenzae isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for H. influenzae was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six H. influenzae positive samples (66.7%) from recurrent episodes. We found H. influenzae and S. pneumoniae to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.
Davido, B; Badr, C; Lagrange, A; Makhloufi, S; De Truchis, P; Perronne, C; Salomon, J; Dinh, A
2016-06-01
29-69 % of pneumonias are microbiologically documented because it can be considered as an invasive procedure with variable test sensitivity. However, it drastically impacts therapeutic strategy in particular the use of antibiotics. Serum protein electrophoresis (SPEP) is a routine and non-invasive test commonly used to identify serum protein disorders. As virus and bacteria may induce different globulins production, we hypothesize that SPEP can be used as an etiological diagnosis test. Retrospective study conducted from 1/1/13 until 5/1/15 among patient hospitalized for an acute community-acquired pneumonia based on fever, crackles and radiological abnormalities. α/β, α/γ, β/γ globulins and albumin/globulin (A/G) ratio were calculated from SPEP. Data were analyzed in 3 groups: documented viral (DVP) or bacterial pneumonia (DBP) and supposedly bacterial pneumonia (SBP). We used ANOVA statistic test with multiple comparisons using CI95 and ROC curve to compare them. 109 patients included divided into DBP (n = 16), DVP (n = 26) and SBP (n = 67). Mean age was 62 ± 18 year-old with a sex ratio M/F of 1.3. Underlying conditions (e.g. COPD, diabetes) were comparable between groups in multivariate analysis. Means of A/G ratio were 0.80 [0.76-0.84], 0.96 [0.91-1.01], 1.08 [0.99-1.16] respectively for DBP, SBP and DVP (p = 0.0002). A/G ratio cut-off value of 0.845 has a sensitivity of 87.5 % and a specificity of 73.1 %. A/G ratio seems to be an easy diagnostic tool to differentiate bacterial from viral pneumonia. A/G ratio cut-off value below 0.845 seems to be predictable of a bacterial origin and support the use of antibiotics.
2014-01-01
Background Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) are considered major causes of bacterial acute otitis media (AOM) worldwide, but data from Asia on primary causes of AOM are limited. This tympanocentesis-based, multi-center, cross-sectional study assessed bacterial etiology and antimicrobial susceptibility of AOM in Thailand. Methods Children 3 to 59 months presenting with AOM (< 72 hours of onset) who had not received prescribed antibiotics, or subjects who received prescribed antibiotics but remained symptomatic after 48–72 hours (treatment failures), were eligible. Study visits were conducted from April 2008 to August 2009. Bacteria were identified from middle ear fluid collected by tympanocentesis or spontaneous otorrhea swab sampling (< 20% of cases). S. pneumoniae and H. influenzae serotypes were determined and antimicrobial resistance was also assessed. Results Of the 123 enrolled children, 112 were included in analysis and 48% of the 118 samples were positive for S. pneumoniae (23% (27/118)), H. influenzae (18% (21/118)), Moraxella catarrhalis (6% (7/118)) or Streptococcus pyogenes (3% (4/118)). The most common pneumococcal serotypes were 19F (26%) and 14 (22%). The majority of H. influenzae isolates were encapsulated (18/21), with 13 type b (Hib) representing 62% of all H. influenzae isolate or 11% of all samples (13/118), and there were only 3 non-typeable isolates. Despite high antibiotic resistance, amoxicillin/clavulanate susceptibility was high. No pneumococcal vaccine use was reported. Conclusions S. pneumoniae and H. influenzae, both frequently antibiotic resistant, were leading causes of bacterial AOM and there was an unexpectedly high burden of Hib in this population unvaccinated by any Hib conjugate vaccine. Conjugate vaccines effective against pneumococcus and H. influenzae could potentially reduce the burden of AOM in this population. PMID:24947736
Jacobs, Michael R
2005-06-01
Acute bacterial respiratory tract infections cause a great deal of human morbidity and mortality. Treatment guidelines for these infections include macrolides, doxycycline, beta-lactams and beta-lactam/beta-lactamase inhibitor combinations such as amoxicillin/clavulanic acid to provide coverage for the common respiratory pathogens, including penicillin and macrolide nonsusceptible Streptococcus pneumoniae, as well as beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis. In response to recent guidelines recommending higher dose amoxicillin to extend coverage to a higher percentage of S. pneumoniae, a new formulation of amoxicillin/clavulanic acid was developed. This formulation includes a higher amoxicillin dose, with part of the amoxicillin dose being in an extended release formulation, without increasing the clavulanate dose, for twice-daily oral treatment of these infections. Clinical studies of community-acquired pneumonia and acute rhinosinusitis have shown that the new formulation is well tolerated and highly efficacious, with clinical outcomes equivalent to comparators.
Histopathology of ventilator-associated pneumonia (VAP) and its clinical implications.
Torres, A; Fábregas, N; Arce, Y; López-Boado, M A
1999-01-01
Ventilator-associated pneumonia (VAP) is a diffuse polymicrobial and dynamic process, with heterogeneous distribution of lesions, showing different degrees of histological evolution predominating in the dependent lung zones, in which microbiology and histology can be dissociated. This might explain why blind endobronchial techniques to collect respiratory secretions have similar accuracy compared to visually guided samples, explaining the difficulties in validating any methods for its diagnosis. In the clinical setting the association of acute lung injury (ALI) and pneumonia is controversial. However, it is rare to detect diffuse alveolar damage (DAD) in absence of histological signs of pneumonia, probably evidencing that ALI favors the development of pneumonia. Histopathologically, it is difficult to distinguish initial and resolution phases of DAD from pneumonia and vice versa. On the other hand, there is a clear relationship between antimicrobial treatment and the decreased lung bacterial burden which strengthens the importance of distal airway sampling before starting antibiotic therapy.
The role of respiratory viruses in the etiology of bacterial pneumonia
Lee, Kyu Han; Gordon, Aubree; Foxman, Betsy
2016-01-01
Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established. PMID:26884414
Steroids in bacterial meningitis: yes.
Benninger, Felix; Steiner, Israel
2013-02-01
Bacterial meningitis is an infectious condition associated with severe morbidity and mortality, even with rapid diagnosis and appropriate antibiotic therapy. Despite decrease in the rate of bacterial meningitis brought about by vaccination programs against Haemophilus influenzae type-B and Streptococcus pneumonia, the incidence of meningitis is still unacceptably high and acute treatment remains the mainstay of therapy. The infection is accompanied by intense inflammatory response, which may carry deleterious effects upon the tissue. This led to the possibility of adjuvant corticosteroid therapy, as an anti-inflammatory agent, in bacterial meningitis. The debate focuses on the rational and evidence supporting and refuting such an approach.
Bacterial Co-infection in Hospitalized Children with Mycoplasma pneumoniae Pneumonia.
Song, Qing; Xu, Bao-Ping; Shen, Kun-Ling
2016-10-08
To describe the frequency and impact of bacterial co-infections in children hospitalized with Mycoplasma pneumoniae pneumonia. Retrospective, descriptive study. Tertiary-care hospital in Beijing, China. 8612 children admitted to Beijing Childrens Hospital from June 2006 to June 2014. According to the testing results of etiology we divided the cases into pure M. pneumoniae infection group and mixed bacterial infection group. We analyzed clinical features, hospital expenses and differences between these two groups. 173 (2%) of included children had bacterial coinfection. 56.2% of bacterial pathogens were identified as Streptococcus pneumoniae. The most common bacterium causing co-infection in children with M. pneumoniae pneumonia was S. pneumoniae.
Vildagliptin-induced acute lung injury: a case report.
Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Maruyama, Ryoko; Furukawa, Tomoyasu; Tanaka, Junta; Kaneko, Kenzo; Kamoi, Kyuzi
2016-08-12
Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.
Acute bacterial meningitis in Iran: Systematic review and meta-analysis.
Houri, Hamidreza; Pormohammad, Ali; Riahi, Seyed Mohammad; Nasiri, Mohammad Javad; Fallah, Fatemeh; Dabiri, Hossein; Pouriran, Ramin
2017-01-01
Bacterial meningitis persists in being a substantial cause of high mortality and severe neurological morbidity, despite the advances in antimicrobial therapy. Accurate data has not been available regarding the epidemiology of bacterial meningitis particularly in developing countries, yet. Indeed, the present systematic review provides a comprehensive data analysis on the prevalence and epidemiology of bacterial meningitis in Iran. We systematically reviewed articles from 1994 to 2015. The reports which contained the prevalence and etiology of acute bacterial meningitis by valid clinical and laboratory diagnosis were comprised in the present study. Our analysis indicated that Streptococcus pneumoniae (30% [I2 = 56% p < 0.01]), Haemophilus influenza type b (15% [I2 = 82.75% p < 0.001]), coagulase negative staphylococci (CoNS) (14% [I2 = 60.5% p < 0.06]), and Neisseria meningitidis (13% [I2 = 74.16% p < 0.001]) were the most common cause of acute bacterial meningitis among meningitis cases in Iran. Notably, high frequency rates of nosocomial meningitis pathogens were detected in the present analysis. It was magnificently attained that the majority of cases for bacterial meningitis in Iran could be avertable by public immunization schemes and by preventive care to inhibit the broadening of hospital acquired pathogens.
Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia
Cohen, Taylor S.; Prince, Alice S.
2013-01-01
The respiratory tract is exceptionally well defended against infection from inhaled bacteria, with multiple proinflammatory signaling cascades recruiting phagocytes to clear airway pathogens. However, organisms that efficiently activate damaging innate immune responses, such as those mediated by the inflammasome and caspase-1, may cause pulmonary damage and interfere with bacterial clearance. The extracellular, opportunistic pathogen Pseudomonas aeruginosa expresses not only pathogen-associated molecular patterns that activate NF-κB signaling in epithelial and immune cells, but also flagella that activate the NLRC4 inflammasome. We demonstrate that induction of inflammasome signaling, ascribed primarily to the alveolar macrophage, impaired P. aeruginosa clearance and was associated with increased apoptosis/pyroptosis and mortality in a murine model of acute pneumonia. Strategies that limited inflammasome activation, including infection by fliC mutants, depletion of macrophages, deletion of NLRC4, reduction of IL-1β and IL-18 production, inhibition of caspase-1, and inhibition of downstream signaling in IL-1R– or IL-18R–null mice, all resulted in enhanced bacterial clearance and diminished pathology. These results demonstrate that the inflammasome provides a potential target to limit the pathological consequences of acute P. aeruginosa pulmonary infection. PMID:23478406
Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection
Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Martinón-Sánchez, José María; Justicia-Grande, Antonio; Rivero-Calle, Irene; Pinnock, Elli; Salas, Antonio; Fink, Colin
2016-01-01
Background The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. Methods A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. Results 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases. PMID:26872131
Holden, Victoria I; Breen, Paul; Houle, Sébastien; Dozois, Charles M; Bachman, Michael A
2016-09-13
Klebsiella pneumoniae is a Gram-negative pathogen responsible for a wide range of infections, including pneumonia and bacteremia, and is rapidly acquiring antibiotic resistance. K. pneumoniae requires secretion of siderophores, low-molecular-weight, high-affinity iron chelators, for bacterial replication and full virulence. The specific combination of siderophores secreted by K. pneumoniae during infection can impact tissue localization, systemic dissemination, and host survival. However, the effect of these potent iron chelators on the host during infection is unknown. In vitro, siderophores deplete epithelial cell iron, induce cytokine secretion, and activate the master transcription factor hypoxia inducible factor-1α (HIF-1α) protein that controls vascular permeability and inflammatory gene expression. Therefore, we hypothesized that siderophore secretion by K. pneumoniae directly contributes to inflammation and bacterial dissemination during pneumonia. To examine the effects of siderophore secretion independently of bacterial growth, we performed infections with tonB mutants that persist in vivo but are deficient in siderophore import. Using a murine model of pneumonia, we found that siderophore secretion by K. pneumoniae induces the secretion of interleukin-6 (IL-6), CXCL1, and CXCL2, as well as bacterial dissemination to the spleen, compared to siderophore-negative mutants at an equivalent bacterial number. Furthermore, we determined that siderophore-secreting K. pneumoniae stabilized HIF-1α in vivo and that bacterial dissemination to the spleen required alveolar epithelial HIF-1α. Our results indicate that siderophores act directly on the host to induce inflammatory cytokines and bacterial dissemination and that HIF-1α is a susceptibility factor for bacterial invasion during pneumonia. Klebsiella pneumoniae causes a wide range of bacterial diseases, including pneumonia, urinary tract infections, and sepsis. To cause infection, K. pneumoniae steals iron from its host by secreting siderophores, small iron-chelating molecules. Classically, siderophores are thought to worsen infections by promoting bacterial growth. In this study, we determined that siderophore-secreting K. pneumoniae causes lung inflammation and bacterial dissemination to the bloodstream independently of bacterial growth. Furthermore, we determined that siderophore-secreting K. pneumoniae activates a host protein, hypoxia inducible factor (HIF)-1α, and requires it for siderophore-dependent bacterial dissemination. Although HIF-1α can protect against some infections, it appears to worsen infection with K. pneumoniae Together, these results indicate that bacterial siderophores directly alter the host response to pneumonia in addition to providing iron for bacterial growth. Therapies that disrupt production of siderophores could provide a two-pronged attack against K. pneumoniae infection by preventing bacterial growth and preventing bacterial dissemination to the blood. Copyright © 2016 Holden et al.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-29
...] Draft Guidance for Industry on Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing Drugs for Treatment; Availability AGENCY: Food and Drug Administration, HHS. ACTION... guidance for industry entitled ``Hospital- Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial...
Le, Tham; O’Brien, Katherine L.; Murdoch, David R.; Prosperi, Christine; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Scott, J. Anthony G.; Thea, Donald M.; Awori, Juliet O.; Baillie, Vicky L.; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Endtz, Hubert P.; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A.; Moore, David P.; Park, Daniel E.; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D.; Zeger, Scott L.; Deloria Knoll, Maria; Madhi, Shabir A.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fancourt, Nicholas; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Kagucia, E. Wangeci; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Brooks, W. Abdullah; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Ominde, Micah Silaba; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Mahomed, Nasreen; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; Wa Somwe, Somwe; Kwenda, Geoffrey; Anderson, Trevor P.; Mitchell, Joanne
2017-01-01
Abstract Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization–defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for “confirmed” bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to “RSV pneumonia” (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)–negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study. PMID:28575375
Ma, Xiuqing; Cui, Junchang; Wang, Jing; Chang, Yan; Fang, Qiuhong; Bai, Changqing; Zhou, Xiumei; Zhou, Hong; Feng, Huasong; Wang, Ying; Zhao, Weiguo; Wen, Zhongguang; Wang, Ping; Liu, Yi; Yu, Ling; Li, Chunsun; Chen, Liangan
2015-10-01
A prospective observational study to investigate the distribution and antimicrobial resistance of pathogenic bacteria in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing, China. Patients with AECOPD were recruited from 11 general hospitals. Sputum specimens were cultured and bacteria identified. Antibiotic susceptibility was determined for each isolate, and presence of antibiotic resistance genes was evaluated using polymerase chain reaction. Pathogenic bacteria were isolated from 109/318 patients (34.28%); 124 isolates of 22 pathogenic bacterial species were identified, including Klebsiella pneumoniae (16.94%), Pseudomonas aeruginosa (16.94%), Acinetobacter baumannii (11.29%), Streptococcus pneumoniae (8.87%), and Staphylococcus aureus (7.26%). S. aureus was sensitive to tigecycline, teicoplanin, vancomycin and linezolid but resistant to penicillin and levofloxacin. K.pneumoniae, P. aeruginosa, A. baumannii and E. coli were susceptible to amikacin and cefoperazone. K. pneumoniae and P. aeruginosa are the most common pathogenic bacteria in AECOPD cases in Beijing, China. Our antibiotic resistance findings may be helpful in selecting antibiotic therapy. © The Author(s) 2015.
Acute Respiratory Failure in Renal Transplant Recipients: A Single Intensive Care Unit Experience.
Ulas, Aydin; Kaplan, Serife; Zeyneloglu, Pinar; Torgay, Adnan; Pirat, Arash; Haberal, Mehmet
2015-11-01
Frequency of pulmonary complications after renal transplant has been reported to range from 3% to 17%. The objective of this study was to evaluate renal transplant recipients admitted to an intensive care unit to identify incidence and cause of acute respiratory failure in the postoperative period and compare clinical features and outcomes between those with and without acute respiratory failure. We retrospectively screened the data of 540 consecutive adult renal transplant recipients who received their grafts at a single transplant center and included those patients admitted to an intensive care unit during this period for this study. Acute respiratory failure was defined as severe dyspnea, respiratory distress, decreased oxygen saturation, hypoxemia or hypercapnia on room air, or requirement of noninvasive or invasive mechanical ventilation. Among the 540 adult renal transplant recipients, 55 (10.7%) were admitted to an intensive care unit, including 26 (47.3%) admitted for acute respiratory failure. Median time from transplant to intensive care unit admission was 10 months (range, 0-67 mo). The leading causes of acute respiratory failure were bacterial pneumonia (56%) and cardiogenic pulmonary edema (44%). Mean partial pressure of arterial oxygen to fractional inspired oxygen ratio was 174 ± 59, invasive mechanical ventilation was used in 13 patients (50%), and noninvasive mechanical ventilation was used in 8 patients (31%). The overall mortality was 16.4%. Acute respiratory failure was the reason for intensive care unit admission in almost half of our renal transplant recipients. Main causes of acute respiratory failure were bacterial pneumonia and cardiogenic pulmonary edema. Mortality of patients admitted for acute respiratory failure was similar to those without acute respiratory failure.
76 FR 59405 - Anti-Infective Drugs Advisory Committee; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-26
... development of antibacterials for the treatment of hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia, and the draft document entitled ``Guidance for Industry: Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Developing Drugs for Treatment...
The role of respiratory viruses in the etiology of bacterial pneumonia: An ecological perspective.
Lee, Kyu Han; Gordon, Aubree; Foxman, Betsy
2016-02-15
Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.
Higdon, Melissa M; Le, Tham; O'Brien, Katherine L; Murdoch, David R; Prosperi, Christine; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Scott, J Anthony G; Thea, Donald M; Awori, Juliet O; Baillie, Vicky L; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N; Driscoll, Amanda J; Ebruke, Bernard E; Endtz, Hubert P; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A; Moore, David P; Park, Daniel E; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D; Zeger, Scott L; Deloria Knoll, Maria; Madhi, Shabir A
2017-06-15
Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Legionnaire's disease during pregnancy: a case presentation and review of the literature.
Eisenberg, V H; Eidelman, L A; Arbel, R; Ezra, Y
1997-03-01
Acute pneumonia complicating pregnancy can have serious consequences for both the mother and the fetus. Streptococcus pneumoniae remains the most common bacterial pathogen, but Legionella pneumophila must be considered as well, especially in severe multisystem disease. With severe disease, premature delivery may occur as has been described in the only previous report of Legionnaire's disease during pregnancy. We present here the first report of Legionnaire's disease in pregnancy, resulting in the term delivery of a healthy infant. Also presented is an extensive review of the literature.
Nantanda, Rebecca; Tumwine, James K.; Ndeezi, Grace; Ostergaard, Marianne S.
2013-01-01
Background Pneumonia is considered the major cause of mortality among children with acute respiratory disease in low-income countries but may be over-diagnosed at the cost of under-diagnosing asthma. We report the magnitude of asthma and pneumonia among “under-fives” with cough and difficulty breathing, based on stringent clinical criteria. We also describe the treatment for children with acute respiratory symptoms in Mulago Hospital. Methods We enrolled 614 children aged 2–59 months with cough and difficulty breathing. Interviews, physical examination, blood and radiological investigations were done. We defined asthma according to Global Initiative for Asthma guidelines. Pneumonia was defined according to World Health Organization guidelines, which were modified by including fever and white cell count, C-reactive protein, blood culture and chest x-ray. Children with asthma or bronchiolitis were collectively referred to as “asthma syndrome” due to challenges of differentiating the two conditions in young children. Three pediatricians reviewed each participant’s case report post hoc and made a diagnosis according to the study criteria. Results Of the 614 children, 41.2% (95% CI: 37.3–45.2) had asthma syndrome, 27.2% (95% CI: 23.7–30.9) had bacterial pneumonia, 26.5% (95% CI: 23.1–30.2) had viral pneumonia, while 5.1% (95% CI: 3.5–7.1) had other diagnoses including tuberculosis. Only 9.5% of the children with asthma syndrome had been previously diagnosed as asthma. Of the 253 children with asthma syndrome, 95.3% (95% CI: 91.9–97.5) had a prescription for antibiotics, 87.7% (95% CI: 83.1–91.5) for bronchodilators and 43.1% (95% CI: 36.9–49.4) for steroids. Conclusion Although reports indicate that acute respiratory symptoms in children are predominantly due to pneumonia, asthma syndrome contributes a significant proportion. Antibiotics are used irrationally due to misdiagnosis of asthma as pneumonia. There is need for better diagnostic tools for childhood asthma and pneumonia in Uganda. PMID:24312321
Detection of pathogens in Boidae and Pythonidae with and without respiratory disease.
Schmidt, V; Marschang, R E; Abbas, M D; Ball, I; Szabo, I; Helmuth, R; Plenz, B; Spergser, J; Pees, M
2013-03-02
Respiratory diseases in boid snakes are common in captivity, but little information is available on their aetiology. This study was carried out to determine the occurrence of lung associated pathogens in boid snakes with and without respiratory signs and/or pneumonia. In total, 80 boid snakes of the families Boidae (n = 30) and Pythonidae (n = 50) from 48 private and zoo collections were included in this survey. Husbandry conditions were evaluated using a detailed questionnaire. All snakes were examined clinically and grouped into snakes with or without respiratory signs. Tracheal wash samples from all snakes were examined bacteriologically as well as virologically. All snakes were euthanased, and a complete pathological examination was performed. Respiratory signs and pneumonia were detected more often in pythons than in boas. An acute catarrhal pneumonia was diagnosed more often in snakes without respiratory signs than in snakes with respiratory signs, which revealed fibrinous and fibrous pneumonia. Poor husbandry conditions are an important trigger for the development of respiratory signs and pneumonia. Different bacterial pathogens were isolated in almost all snakes with pneumonia, with Salmonella species being the most common. Ferlavirus (formerly known as ophidian paramyxovirus)-RNA was detected only in pythons. Inclusion body disease was rarely seen in pythons but often in boas. Adenovirus and Mycoplasma were other pathogens that were diagnosed in single snakes with pneumonia. In living boid snakes with respiratory signs, tracheal wash samples were found to be a useful diagnostic tool for the detection of viral and bacterial pathogens.
Papavasileiou, Konstantina; Papavasileiou, Eleni; Tzanakaki, Georgina; Voyatzi, Aliki; Kremastinou, Jenny; Chatzipanagiotou, Stylianos
2011-04-01
Acute bacterial meningitis is one of the most severe infectious diseases, affecting mainly infants and, secondarily, older children and adolescents. Diagnosis in the early stages is often difficult and despite treatment with appropriate antibiotic therapy, the case fatality rate remains high. In the present study, the incidence of bacterial meningitis was registered in a general pediatric hospital in Athens, Greece, during a 9-year period (2000-2008), and the use of molecular methods in the diagnosis of bacterial meningitis versus the conventional cultural methods was evaluated. The impact of vaccination against meningitis-causing bacteria on the incidence of bacterial meningitis was also assessed. From a total of 1833 children hospitalized with suspected clinical symptoms and signs of meningitis, all cerebrospinal fluid (CSF) and blood samples were analyzed by white blood cell (WBC) count, measurement of glucose, protein, and C-reactive protein (CRP) levels, as well as by conventional bacteriologic culture methods. If samples showed altered CSF markers that were consistent with meningitis in general, they were further investigated by PCR for bacterial pathogens. Of the 1833 patients, 289 (15.76%) were found to be positive for meningitis after CSF examination, based on white blood cell count and differentiation, glucose, protein, and CRP. Fifty-six of the 289 (19.37%) had confirmed bacterial meningitis, as diagnosed by either culture and/or PCR. Of these 56 cases, 44 (78.6%) were detected only by PCR, and 12 cases (21.4%) were confirmed by PCR and culture. The predominant microorganism was Neisseria meningitidis serogroup B (n = 40; 71.4%), followed by Streptococcus pneumoniae not typed [NT] (n = 7; 12.5%), Streptococcus spp. (n =4; 7.1%), Haemophilus influenzae NT (n = 2; 3.6%), and S. pneumoniae serotype 3, Streptococcus group B, and S. pneumoniae serotype 18C (each n = 1; 1.8%). In Greece, according to data from the National Meningitis Reference Laboratory, vaccination against N. meningitidis serogroup C since 2001 led to a 10-fold decrease in the incidence of meningitis cases, vaccination against S. pneumoniae serotypes included in the heptavalent conjugate vaccine since 2005 led to a 3.4-fold incidence decrease, and vaccination against H. influenzae type b since 1992 led almost to an absence of cases. In the population of the present study, none of the cases were caused by the above-mentioned vaccine pathogens, except for one S. pneumoniae serotype 18C case with no history of past vaccination. The introduction of vaccination against meningitis-causing bacteria has drastically decreased the emergence of the infection. The improved molecular amplification assays proved to be superior to conventional bacteriologic methods and should be introduced into routine diagnosis, as well as the epidemiologic surveillance of bacterial meningitis.
Levofloxacin in the treatment of community-acquired pneumonia.
Noreddin, Ayman M; Elkhatib, Walid F
2010-05-01
Levofloxacin is a fluoroquinolone that has a broad spectrum of activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP are well established. Furthermore, a high-dose (750 mg), short-course (5 days) of once-daily levofloxacin has been approved for use in the USA in the treatment of CAP, acute bacterial sinusitis, acute pyelonephritis and complicated urinary tract infections. Levofloxacin can be used as a monotherapy in patients with CAP, however, levofloxacin combination therapy with anti-pseudomonal beta-lactam (or aminoglycoside) should be considered if Pseudomonas aeruginosa is the causative pathogen of the respiratory infection. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent antibacterial activity, decreases the potential for drug resistance and has better patient compliance. Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation and the patients can switch between these formulations, which results in more options with respect to the therapeutic regimens. Furthermore, levofloxacin is generally well tolerated, has good tissue penetration and adequate concentrations can be maintained at the site of infections.
Nhantumbo, Aquino Albino; Gudo, Eduardo Samo; Caierão, Juliana; Munguambe, Alcides Moniz; Comé, Charlotte Elizabeth; Zimba, Tomás Francisco; Moraes, Milton Ozório; Dias, Cícero; Cantarelli, Vlademir Vicente
2016-06-29
S. pneumoniae is the leading cause of acute bacterial meningitis (ABM) in children. Vaccination using the 10-valent conjugate vaccine (PCV-10) was recently introduced into the National Immunization Program in Mozambique, but data on serotype coverage of this vaccine formulation are scarce. In this study, we investigated the serotype distribution and antimicrobial resistance of isolates of S. pneumoniae causing ABM in children < 5 years at the two largest hospitals in Mozambique. Between March 2013 and March 2014, a total of 352 cerebrospinal fluid (CSF) samples were collected from eligible children, of which 119 (33.8 %) were positive for S. pneumoniae. Of these, only 50 samples met the criteria for serotyping and were subsequently serotyped using sequential multiplex PCR (SM-PCR), but 15 samples were non-typable. The most common serotypes of S. pneumoniae were 1 (18.2 %), 5 (15.2 %), 14 (12.1 %), 9 V (12.1 %), 23 F (9.1 %), 6A (9.1 %), 4 (9.1 %) and 6B (6.1 %). Serotypes 1, 5, 9 V, 6A and 12 were mostly prevalent in Northern Mozambique, while serotypes 23 F, 4, 6B, 3 and 15B were predominant in Southern. Serotype coverage of PCV-10 and PCV-13 vaccine formulations were 81.8 % and 93.9 %, respectively. Serotypes 1, 3, 4, 6B, 14, 23 F were resistant to penicillin and sensitive to ceftriaxone. Our findings shows that changing the current in use PCV-10 vaccine formulation to PCV-13 formulation might increase substantially the protection against invasive strains of S. pneumoniae as the PCV-10 vaccine formulation does not cover the serotypes 3 and 6A, which are prevalent in Mozambique.
Acute bacterial meningitis in Iran: Systematic review and meta-analysis
Riahi, Seyed Mohammad; Nasiri, Mohammad Javad; Fallah, Fatemeh; Dabiri, Hossein; Pouriran, Ramin
2017-01-01
Introduction Bacterial meningitis persists in being a substantial cause of high mortality and severe neurological morbidity, despite the advances in antimicrobial therapy. Accurate data has not been available regarding the epidemiology of bacterial meningitis particularly in developing countries, yet. Indeed, the present systematic review provides a comprehensive data analysis on the prevalence and epidemiology of bacterial meningitis in Iran. Methods We systematically reviewed articles from 1994 to 2015. The reports which contained the prevalence and etiology of acute bacterial meningitis by valid clinical and laboratory diagnosis were comprised in the present study. Results Our analysis indicated that Streptococcus pneumoniae (30% [I2 = 56% p < 0.01]), Haemophilus influenza type b (15% [I2 = 82.75% p < 0.001]), coagulase negative staphylococci (CoNS) (14% [I2 = 60.5% p < 0.06]), and Neisseria meningitidis (13% [I2 = 74.16% p < 0.001]) were the most common cause of acute bacterial meningitis among meningitis cases in Iran. Notably, high frequency rates of nosocomial meningitis pathogens were detected in the present analysis. Conclusions It was magnificently attained that the majority of cases for bacterial meningitis in Iran could be avertable by public immunization schemes and by preventive care to inhibit the broadening of hospital acquired pathogens. PMID:28170400
[Diagnostic values of plasma CD64 and sTREM-1 for pediatric pneumonia].
Zhong, Mei-Feng; Zhao, Jian-Mei
2016-07-01
To determine the diagnostic values of plasma CD64 and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in children with pneumonia. Sixty children with pneumonia between August 2014 and October 2015 were classified into bacterial pneumonia group (25 cases), viral pneumonia group (17 cases), and Mycoplasma pneumonia group (18 cases) according to their clinical manifestations, pathogen cultures, and X-ray findings. Another 30 healthy children who underwent physical examination during the same period were selected as the control group. The concentrations of CD64 and sTREM-1 in blood samples were determined using ELISA. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic sensitivity and specificity of plasma CD64 and/or sTREM-1 for bacterial pneumonia. The expression of CD64 and sTREM-1 in the bacterial pneumonia group was significantly higher than that in the viral pneumonia, Mycoplasma pneumonia, and control groups (P<0.05). The areas under the ROC curves of CD64, sTREM-1, and a combination of the two markers for diagnosing bacterial pneumonia were 0.878, 0.805, and 0.956, respectively. The sensitivity and specificity of CD64 for diagnosing bacterial pneumonia were 81.30% and 92.32%, respectively, when the cut-off value was 641 pg/mL. The sensitivity and specificity of sTREM-1 for diagnosing bacterial pneumonia were 78.65% and 84.67%, respectively, when the cut-off value was 1 479 pg/mL. The sensitivity and specificity of a combination of the two markers for diagnosing bacterial pneumonia were 93.15% and 91.54%, respectively. Plasma CD64 and sTREM-1 can be used as markers for diagnosing pediatric bacterial pneumonia, and a combination of the two markers results in better diagnosis.
Contribution of Progranulin to Protective Lung Immunity During Bacterial Pneumonia.
Zou, Shan; Luo, Qin; Song, Zhixin; Zhang, Liping; Xia, Yun; Xu, Huajian; Xiang, Yu; Yin, Yibing; Cao, Ju
2017-06-01
Progranulin (PGRN) is an important immunomodulatory factor in a variety of inflammatory diseases. However, its role in pulmonary immunity against bacterial infection remains unknown. Pneumonia was induced in PGRN-deficient and normal wild-type mice using Pseudomonas aeruginosa or Staphylococcus aureus, and we assessed the effects of PGRN on survival, bacterial burden, cytokine and chemokine production, and pulmonary leukocyte recruitment after bacterial pneumonia. Patients with community-acquired pneumonia displayed elevated PGRN levels. Likewise, mice with Gram-negative and Gram-positive pneumonia had increased PGRN production in the lung and circulation. Progranulin deficiency led to increased bacterial growth and dissemination accompanied by enhanced lung injury and mortality in bacterial pneumonia, which was associated with impaired recruitment of macrophages and neutrophils in the lung. The reduced number of pulmonary macrophages and neutrophils observed in PGRN-deficient mice was related to a reduction of CCL2 and CXCL1 in the lungs after bacterial pneumonia. Importantly, therapeutic administration of PGRN improved mortality in severe bacterial pneumonia. This study supports a novel role for PGRN in pulmonary immunity and suggests that treatment with PGRN may be a viable therapy for bacterial pneumonia. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Lin, Jr-Shiuan; Szaba, Frank M; Kummer, Lawrence W; Chromy, Brett A; Smiley, Stephen T
2011-07-15
Septic bacterial pneumonias are a major cause of death worldwide. Several of the highest priority bioterror concerns, including anthrax, tularemia, and plague, are caused by bacteria that acutely infect the lung. Bacterial resistance to multiple antibiotics is increasingly common. Although vaccines may be our best defense against antibiotic-resistant bacteria, there has been little progress in the development of safe and effective vaccines for pulmonary bacterial pathogens. The Gram-negative bacterium Yersinia pestis causes pneumonic plague, an acutely lethal septic pneumonia. Historic pandemics of plague caused millions of deaths, and the plague bacilli's potential for weaponization sustains an ongoing quest for effective countermeasures. Subunit vaccines have failed, to date, to fully protect nonhuman primates. In mice, they induce the production of Abs that act in concert with type 1 cytokines to deliver high-level protection; however, the Y. pestis Ags recognized by cytokine-producing T cells have yet to be defined. In this study, we report that Y. pestis YopE is a dominant Ag recognized by CD8 T cells in C57BL/6 mice. After vaccinating with live attenuated Y. pestis and challenging intranasally with virulent plague, nearly 20% of pulmonary CD8 T cells recognize this single, highly conserved Ag. Moreover, immunizing mice with a single peptide, YopE(69-77), suffices to confer significant protection from lethal pulmonary challenge. These findings suggest YopE could be a valuable addition to subunit plague vaccines and provide a new animal model in which sensitive, pathogen-specific assays can be used to study CD8 T cell-mediated defense against acutely lethal bacterial infections of the lung.
Farahani, Hamidreza; Ghaznavi-Rad, Ehsanollah; Mondanizadeh, Mahdieh; MirabSamiee, Siamak; Khansarinejad, Behzad
2016-08-01
Accurate and timely diagnosis of acute bacterial meningitis is critical for antimicrobial treatment of patients. Although PCR-based methods have been widely used for the diagnosis of acute meningitis caused by bacterial pathogens, the main disadvantage of these methods is their high cost. This disadvantage has hampered the widespread use of molecular assays in many developing countries. The application of multiplex assays and "in-house" protocols are two main approaches that can reduce the overall cost of a molecular test. In the present study, an internally controlled tetraplex-PCR was developed and validated for the specific detection of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in cerebrospinal fluid (CSF) samples. The analysis of a panel of other human pathogens showed no cross-reactivity in the assay. The analytical sensitivity of the in-house assay was 792.3 copies/ml, when all three bacteria were presentin the specimens. This value was calculated as 444.5, 283.7, 127.8 copies/ml when only S. pneumoniae, N. meningitidis and H. influenzae, respectively, were present. To demonstrate the diagnostic performance of the assay, a total of 150 archival CSF samples were tested and compared with a commercial multiplex real-time PCR kit. A diagnostic sensitivity of 92.8% and a specificity of 95.1% were determined for the present tetraplex-PCR assay. The results indicate that the established method is sensitive, specific and cost-effective, and can be used particularly in situations where the high cost of commercial kits prevents the use of molecular methods for the diagnosis of bacterial meningitis. Copyright © 2016 Elsevier Ltd. All rights reserved.
2012-01-01
Background Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age. Methods Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes). Results Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (S. pneumoniae, H. influenzae, S. pyogenes or M. catarrhalis) was cultured from 65.9% (60/91) of episodes. H. influenzae (55.5%; 35/63 episodes) and S. pneumoniae (34.9%; 22/63 episodes) were the most frequently reported bacteria. Among H. influenzae isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for H. influenzae was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six H. influenzae positive samples (66.7%) from recurrent episodes. Conclusions We found H. influenzae and S. pneumoniae to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM. PMID:22335965
Jayaraman, Yuvaraj; Veeraraghavan, Balaji; Chethrapilly Purushothaman, Girish Kumar; Sukumar, Bharathy; Kangusamy, Boopathi; Nair Kapoor, Ambujam; Gupta, Nivedita; Mehendale, Sanjay Madhav
2018-01-01
Worldwide, acute bacterial meningitis is a major cause of high morbidity and mortality among under five children, particularly in settings where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is yet to be introduced in the national immunization programs. Estimation of disease burden of bacterial meningitis associated with these pathogens can guide the policy makers to consider inclusion of these newer vaccines in the immunization programs. A network of hospital based sentinel surveillance was established to generate baseline data on the burden of bacterial meningitis among children aged less than 5 years in India and to provide a platform for impact assessment following introduction of the Pentavalent and Pneumococcal Conjugate Vaccines (PCV). During surveillance carried out in select hospitals across India in 2012-2013, information regarding demographics, immunization history, clinical history, treatment details and laboratory investigations viz. CSF biochemistry, culture, latex agglutination and PCR was collected from children aged 1 to 59 months admitted with suspected bacterial meningitis. A total of 3104 suspected meningitis cases were enrolled from 19,670 children admitted with fever at the surveillance hospitals. Of these, 257 cases were confirmed as cases of meningitis. They were due to S. pneumoniae (82.9%), H. influenzae type b (14.4%) and N. meningitidis (2.7%). Highest prevalence (55.3%) was observed among children 1 to 11 months. Antimicrobial susceptibility testing revealed considerable resistance among S. pneumoniae isolates against commonly used antibiotics such as cotrimoxazole, erythromycin, penicillin, and cefotaxime. More commonly prevalent serotypes of S. pneumoniae in circulation included 6B, 14, 6A and 19F. More than 90% of serotypes identified were covered by Pneumococcal Conjugate Vaccine 13. We observed that S. pneumoniae was the commonest cause of bacterial meningitis in hospitalized children under five years of age in India. Continued surveillance is expected to provide valuable information and trends in future, to take an informed decision on introduction of pneumococcal vaccination in Universal Immunization Programme in India and will also eventually help in post-vaccination impact evaluation.
Jayaraman, Yuvaraj; Veeraraghavan, Balaji; Chethrapilly Purushothaman, Girish Kumar; Sukumar, Bharathy; Kangusamy, Boopathi; Nair Kapoor, Ambujam; Gupta, Nivedita
2018-01-01
Background Worldwide, acute bacterial meningitis is a major cause of high morbidity and mortality among under five children, particularly in settings where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is yet to be introduced in the national immunization programs. Estimation of disease burden of bacterial meningitis associated with these pathogens can guide the policy makers to consider inclusion of these newer vaccines in the immunization programs. A network of hospital based sentinel surveillance was established to generate baseline data on the burden of bacterial meningitis among children aged less than 5 years in India and to provide a platform for impact assessment following introduction of the Pentavalent and Pneumococcal Conjugate Vaccines (PCV). Methods During surveillance carried out in select hospitals across India in 2012–2013, information regarding demographics, immunization history, clinical history, treatment details and laboratory investigations viz. CSF biochemistry, culture, latex agglutination and PCR was collected from children aged 1 to 59 months admitted with suspected bacterial meningitis. Results A total of 3104 suspected meningitis cases were enrolled from 19,670 children admitted with fever at the surveillance hospitals. Of these, 257 cases were confirmed as cases of meningitis. They were due to S. pneumoniae (82.9%), H. influenzae type b (14.4%) and N. meningitidis (2.7%). Highest prevalence (55.3%) was observed among children 1 to 11 months. Antimicrobial susceptibility testing revealed considerable resistance among S. pneumoniae isolates against commonly used antibiotics such as cotrimoxazole, erythromycin, penicillin, and cefotaxime. More commonly prevalent serotypes of S. pneumoniae in circulation included 6B, 14, 6A and 19F. More than 90% of serotypes identified were covered by Pneumococcal Conjugate Vaccine 13. Conclusions We observed that S. pneumoniae was the commonest cause of bacterial meningitis in hospitalized children under five years of age in India. Continued surveillance is expected to provide valuable information and trends in future, to take an informed decision on introduction of pneumococcal vaccination in Universal Immunization Programme in India and will also eventually help in post-vaccination impact evaluation. PMID:29768458
[Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].
Sinopalnikov, A I; Zaitsev, A A
2015-04-01
In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.
Hong, Eva; Barraud, Olivier; Bidet, Philippe; Bingen, Edouard; Blondiaux, Nicolas; Bonacorsi, Stéphane; Burucoa, Christophe; Carrer, Amélie; Fortineau, Nicolas; Couetdic, Gérard; Courcol, René; Garnier, Fabien; Hery-Arnaud, Geneviève; Lanotte, Philippe; Le Bars, Hervé; Legrand-Quillien, Marie-Christine; Lemée, Ludovic; Mereghetti, Laurent; Millardet, Chantal; Minet, Jacques; Plouzeau-Jayle, Chloé; Pons, Jean-Louis; Schneider, Jacqueline; Taha, Muhamed-Kheir
2012-01-01
Meningococcal meningitis requires rapid diagnosis and immediate management which is enhanced by the use of PCR for the ascertainment of these infections. However, its use is still restricted to reference laboratories. We conducted an inter-laboratory study to assess the implementation and the performance of PCR in ten French hospital settings in 2010. Our data are in favour of this implementation. Although good performance was obtained in identifying Neisseria meningitidis positive samples, the main issue was reported in identifying other species (Streptococcus pneumoniae and Haemophilus influenzae) which are also involved in bacterial meningitis cases. Several recommendations are required and, mainly, PCR should target the major etiological agents (N. meningitidis, S. pneumonia, and H. influenzae) of acute bacterial meningitis. Moreover, PCR should predict the most frequent serogroups of Neisseria meningitidis according to local epidemiology.
Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin
2014-04-14
Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut). MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.
Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.
Roux, Damien; Gaudry, Stéphane; Khoy-Ear, Linda; Aloulou, Meryem; Phillips-Houlbracq, Mathilde; Bex, Julie; Skurnik, David; Denamur, Erick; Monteiro, Renato C; Dreyfuss, Didier; Ricard, Jean-Damien
2013-09-01
To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. Experimental animal investigation. University research laboratory. Pathogen-free male Wistar rats weighing 250-275 g. Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.
Riccobene, Todd A; Khariton, Tatiana; Knebel, William; Das, Shampa; Li, James; Jandourek, Alena; Carrothers, Timothy J; Bradley, John S
2017-03-01
Ceftaroline, the active form of the prodrug ceftaroline fosamil, is approved for use in adults with community-acquired bacterial pneumonia (CABP) or acute bacterial skin and skin structure infections (ABSSSI) in the United States and for similar indications in Europe. Pharmacokinetic (PK) data from 5 pediatric (birth to <18 years) studies of ceftaroline fosamil were combined with PK data from adults to update a population PK model for ceftaroline and ceftaroline fosamil. This model, based on a data set including 305 children, was used to conduct simulations to estimate ceftaroline exposures and percentage of time that free drug concentrations were above the minimum inhibitory concentration (%fT>MIC) for pediatric dose regimens. With dose regimens of 8 mg/kg every 8 hours (q8h) in children aged 2 months to <2 years and 12 mg/kg (up to a maximum of 400 mg) q8h in children aged 2 years to <18 years or 600 mg q12h in children aged 12 to <18 years, >90% of children were predicted to achieve a target of 36% fT>MIC at an MIC of 2 mg/L, and >97% were predicted to achieve 44% fT>MIC at an MIC of 1 mg/L. Thus, high PK/pharmacodynamic target attainment would be maintained in children for targets associated with 1-log kill of Staphylococcus aureus and Streptococcus pneumoniae. The predicted ceftaroline exposures for these dose regimens were similar to those in adults given 600 mg q12h ceftaroline fosamil. This work contributed to the approval of dose regimens for children aged 2 months to <18 years by the FDA and EMA, which are presented. © 2016, The American College of Clinical Pharmacology.
Childhood Acute Bacterial Meningitis: Clinical Spectrum, Bacteriological Profile and Outcome.
Bari, Attia; Zeeshan, Fatima; Zafar, Aiza; Ejaz, Hassan; Iftikhar, Aisha; Rathore, Ahsan Waheed
2016-10-01
To determine the disease pattern, etiological agents and outcome of childhood acute bacterial meningitis. Adescriptive study. Department of Paediatric Medicine, The Children's Hospital, Lahore, from January to December 2012. Atotal of 199 children between the ages of 1 month and 5 years, admitted with the diagnosis of meningitis on the basis of clinical findings and positive cerebrospinal fluid (CSF), were included. In all patients, complete blood count (CBC), CSF culture sensitivity, and blood culture sensitivity were performed. Data was analysed using SPSS version 20. Out of 199 children, 127 (63.8%) were males with M:F ratio of 1.7:1. Mean age was 11.33 ±12 months. Maximum numbers of children were < 1 year of age, 136 (68.3%). Only 90 (45.2%) children were fully vaccinated according to Expanded Program of Immunisation (EPI) schedule. Presentations with refusal to take feed (p=0.008) and with impaired conscious state were independent predictors of death (p=0.002). Complications were noted in 34 (17%) and were significantly associated with severe malnutrition (p=0.006) and altered conscious level at presentation (p < 0.001). The common pathogens identified on CSF culture were coagulase negative staphylococci (CoNS) in 11 (5.5%) and streptococcus pneumoniaein 5 (2.5%). Overall mortality was 10.1%. The commonest pathogen isolated from children who died was streptococcus pneumoniae(p=0.039). Acute bacterial meningitis mostly affected children under the age of 1 year. CSF culture revealed both Grampositive and Gram-negative bacteria. The most common pathogen in children who died was streptococcus pneumoniae.
Kolar, Milan; Sauer, Pavel; Faber, Edgar; Kohoutova, Jarmila; Stosová, Tatana; Sedlackova, Michaela; Chroma, Magdalena; Koukalova, Dagmar; Indrak, Karel
2009-01-01
The aim of the study was to determine the prevalence of Pseudomonas aeruginosa and Klebsiella pneumoniae strains in patients with acute leukemias, to assess their clinical significance, and to define the sources and ways of their spread using genetic analysis. Thirty-four patients were investigated during the observed period. Twenty-one strains of Pseudomonas aeruginosa and 35 strains of Klebsiella pneumoniae were isolated from patient samples. In the case of Pseudomonas aeruginosa, 47.6% of strains were identified as pathogens and caused infection. By contrast, only 4 isolates (11.4%) of Klebsiella pneumoniae could be regarded as etiological agents of bacterial infection. Based on the obtained results, Klebsiella pneumoniae strains are assumed to be of mostly endogenous origin. In the case of Pseudomonas aeruginosa strains, the proportion of identical strains detected in various patients was higher and exogenous sources were more significant. In addition, our results confirmed the ability of Pseudomonas aeruginosa strains to survive on a particular site in the hospital for a longer time.
Ngo, Chinh C; Massa, Helen M; Thornton, Ruth B; Cripps, Allan W
2016-01-01
Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention. A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases. This review confirmed that Streptococcus pneumoniae and Haemophilus influenzae, remain the predominant bacterial pathogens, with S. pneumoniae the predominant bacterium in the majority reports from AOM patients. In contrast, H. influenzae was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of S. pneumoniae and H. influenzae 3.2 fold compared to culture, whilst Moraxella catarrhalis was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine. Globally, S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations.
Ngo, Chinh C.; Massa, Helen M.; Thornton, Ruth B.; Cripps, Allan W.
2016-01-01
Background Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention. Methods A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases. Results This review confirmed that Streptococcus pneumoniae and Haemophilus influenzae, remain the predominant bacterial pathogens, with S. pneumoniae the predominant bacterium in the majority reports from AOM patients. In contrast, H. influenzae was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of S. pneumoniae and H. influenzae 3.2 fold compared to culture, whilst Moraxella catarrhalis was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine. Conclusions Globally, S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations. PMID:26953891
Johansson Kostenniemi, Urban; Norman, David; Borgström, Malin; Silfverdal, Sven Arne
2015-11-01
This Swedish study reviewed differences in clinical presentation and laboratory findings of acute bacterial meningitis in children aged one month to 17 years in Västerbotten County, Sweden. A register-based study was performed for the period 1986 to 2013 using the Västerbotten County Council's patient registration and laboratory records at the Department of Laboratory Medicine at Umeå University Hospital. The medical records were reviewed to extract data and confirm the diagnosis. We found 103 cases of acute bacterial meningitis, and Haemophilus influenzae was the most common pathogen, causing 40.8% of all cases, followed by Streptococcus pneumoniae at 30.1% and Neisseria meningitidis at 9.7%. Significant differences in clinical presentation and laboratory findings were found. Younger children were more unwell than older ones and had more diffuse symptoms on admission. In addition, important sex-related differences were found that might explain the higher case fatality rates for boys than girls. For example, boys tended to have a higher disturbance in the blood-brain barrier, which is known to be a negative prognostic factor. This study showed that clinical presentation for acute bacterial meningitis varied with age and sex and, to a lesser extent, on the duration of the illness. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A.; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J.; Finkenstaedt, Felix W.; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas
2016-01-01
Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient’s environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS (‘immune paralysis’), sufficient to propagate clinically relevant infection in an injury level dependent manner. PMID:26754788
Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia.
González-Juarbe, Norberto; Gilley, Ryan Paul; Hinojosa, Cecilia Anahí; Bradley, Kelley Margaret; Kamei, Akinobu; Gao, Geli; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier
2015-12-01
Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL. We report that diverse bacterial pathogens that produce a pore-forming toxin (PFT) induce necroptosis of macrophages and this can be blocked for protection against Serratia marcescens hemorrhagic pneumonia. Following challenge with S. marcescens, Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, uropathogenic Escherichia coli (UPEC), and purified recombinant pneumolysin, macrophages pretreated with inhibitors of RIP1, RIP3, and MLKL were protected against death. Alveolar macrophages in MLKL KO mice were also protected during S. marcescens pneumonia. Inhibition of caspases had no impact on macrophage death and caspase-1 and -3/7 were determined to be inactive following challenge despite the detection of IL-1β in supernatants. Bone marrow-derived macrophages from RIP3 KO, but not caspase-1/11 KO or caspase-3 KO mice, were resistant to PFT-induced death. We explored the mechanisms for PFT-induced necroptosis and determined that loss of ion homeostasis at the plasma membrane, mitochondrial damage, ATP depletion, and the generation of reactive oxygen species were together responsible. Treatment of mice with necrostatin-5, an inhibitor of RIP1; GW806742X, an inhibitor of MLKL; and necrostatin-5 along with co-enzyme Q10 (N5/C10), which enhances ATP production; reduced the severity of S. marcescens pneumonia in a mouse intratracheal challenge model. N5/C10 protected alveolar macrophages, reduced bacterial burden, and lessened hemorrhage in the lungs. We conclude that necroptosis is the major cell death pathway evoked by PFTs in macrophages and the necroptosis pathway can be targeted for disease intervention.
Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia
González-Juarbe, Norberto; Gilley, Ryan Paul; Hinojosa, Cecilia Anahí; Bradley, Kelley Margaret; Kamei, Akinobu; Gao, Geli; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier
2015-01-01
Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL. We report that diverse bacterial pathogens that produce a pore-forming toxin (PFT) induce necroptosis of macrophages and this can be blocked for protection against Serratia marcescens hemorrhagic pneumonia. Following challenge with S. marcescens, Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, uropathogenic Escherichia coli (UPEC), and purified recombinant pneumolysin, macrophages pretreated with inhibitors of RIP1, RIP3, and MLKL were protected against death. Alveolar macrophages in MLKL KO mice were also protected during S. marcescens pneumonia. Inhibition of caspases had no impact on macrophage death and caspase-1 and -3/7 were determined to be inactive following challenge despite the detection of IL-1β in supernatants. Bone marrow-derived macrophages from RIP3 KO, but not caspase-1/11 KO or caspase-3 KO mice, were resistant to PFT-induced death. We explored the mechanisms for PFT-induced necroptosis and determined that loss of ion homeostasis at the plasma membrane, mitochondrial damage, ATP depletion, and the generation of reactive oxygen species were together responsible. Treatment of mice with necrostatin-5, an inhibitor of RIP1; GW806742X, an inhibitor of MLKL; and necrostatin-5 along with co-enzyme Q10 (N5/C10), which enhances ATP production; reduced the severity of S. marcescens pneumonia in a mouse intratracheal challenge model. N5/C10 protected alveolar macrophages, reduced bacterial burden, and lessened hemorrhage in the lungs. We conclude that necroptosis is the major cell death pathway evoked by PFTs in macrophages and the necroptosis pathway can be targeted for disease intervention. PMID:26659062
21 CFR 522.820 - Erythromycin.
Code of Federal Regulations, 2011 CFR
2011-04-01
...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...
21 CFR 522.820 - Erythromycin.
Code of Federal Regulations, 2010 CFR
2010-04-01
...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...
21 CFR 522.820 - Erythromycin.
Code of Federal Regulations, 2012 CFR
2012-04-01
...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...
21 CFR 522.820 - Erythromycin.
Code of Federal Regulations, 2014 CFR
2014-04-01
...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...
21 CFR 522.820 - Erythromycin.
Code of Federal Regulations, 2013 CFR
2013-04-01
...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...
Evaluation of posttraumatic recurrent bacterial meningitis in adults.
Deveci, Özcan; Uysal, Cem; Varol, Sefer; Tekin, Recep; Bozkurt, Fatma; Bekçibaşı, Muhammed; Hoşoğlu, Salih
2015-07-01
Acute bacterial meningitis may develop as a complication after head trauma. The aim of this study was to present the demographic, clinical, microbiological and radiological characteristics of adult patients who presented with recurrent bacterial meningitis attacks after trauma. Using a retrospective approach, the medical records of patients with acute recurrent bacterial meningitis (RBM) were reviewed, and those who had a history of trauma were included into the study. RBM was diagnosed based on clinical, bacteriologic and laboratory results. Demographic characteristics, clinical course, laboratory test results including cerebrospinal fluid analysis (CSF), radiological images, and the applied treatments were evaluated. A total of two hundred and twelve patients with acute bacterial meningitis were included into the study. RBM was diagnosed in twenty-five patients (11.8%), and in 18 of these patients (8.5%), the attacks had occurred subsequent to a trauma. In the CSF cultures of four patients, S. pneumoniae growth was observed. CT cisternography indicated CSF leaks in eleven patients. Moreover, bone fractures were observed in the CT images of ten patients. Ceftriaxone therapy was prescribed to 83% of the patients. Eight patients had a history of a fall in childhood, and five were involved in traffic accidents before acute bacterial meningitis. Four of the patients developed epilepsy and one developed deafness as sequelae. Since RBM attacks are frequently observed following trauma, in patients with a history of trauma who present with meningitis, the risk of recurrence should be considered.
Ariza, Horacio; Rojas, Ramon; Johnson, Peter; Gower, Richard; Benson, Alice; Herrington, Janet; Perroncel, Renee; Pertel, Peter
2006-01-01
Background Acute bacterial sinusitis (ABS) is a common infection in clinical practice. Data on time to bacteriologic eradication after antimicrobial therapy are lacking for most agents, but are necessary in order to optimize therapy. This was a prospective, single-arm, open-label, multicenter study to determine the time to bacteriologic eradication in ABS patients (maxillary sinusitis) treated with moxifloxacin. Methods Adult patients with radiologically and clinically confirmed ABS received once-daily moxifloxacin 400 mg for 10 days. Middle meatus secretion sampling was performed using nasal endoscopy pre-therapy, and repeated on 3 consecutive days during treatment. Target enrollment was 30 bacteriologically evaluable patients (pre-therapy culture positive for Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and evaluable cultures for at least Day 2 and Day 3 during therapy visits), including at least 10 each with S. pneumoniae or H. influenzae. Results Of 192 patients enrolled, 42 were bacteriologically evaluable, with 48 pathogens isolated. Moxifloxacin was started on Day 1. Baseline bacteria were eradicated in 35/42 (83.3%) patients by day 2, 42/42 (100%) patients by day 3, and 41/42 (97.6%) patients by day 4. In terms of individual pathogens, 12/18 S. pneumoniae, 22/23 H. influenzae and 7/7 M. catarrhalis were eradicated by day 2 (total 41/48; 85.4%), and 18/18 S. pneumoniae and 23/23 H. influenzae were eradicated by day 3. On Day 4, S. pneumoniae was isolated from a patient who had negative cultures on Days 2 and 3. Thus, the Day 4 eradication rate was 47/48 (97.9%). Clinical success was achieved in 36/38 (94.7%) patients at the test of cure visit. Conclusion In patients with ABS (maxillary sinusitis), moxifloxacin 400 mg once daily for 10 days resulted in eradication of baseline bacteria in 83.3% of patients by Day 2, 100% by Day 3 and 97.6% by Day 4. PMID:16646958
McCormack, Paul L; Keating, Gillian M
2005-01-01
Amoxicillin/clavulanic acid 2000 mg/125 mg extended release (Augmentin XR), referred to herein as amoxicillin/clavulanic acid XR, is a pharmacokinetically enhanced formulation designed to provide more effective therapy in adults and adolescents than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin.Amoxicillin/clavulanic acid XR maintains plasma amoxicillin concentrations >4 microg/mL for a mean of 49% of the dosing interval indicating that it would be highly effective against S. pneumoniae strains with minimum inhibitory concentrations (MICs) above the National Committee for Clinical Laboratory Standard's amoxicillin +/- clavulanic acid susceptibility breakpoint of < or = 2 microg/mL. Amoxicillin/clavulanic acid XR is at least as effective as conventional amoxicillin/clavulanic acid formulations, levofloxacin, and clarithromycin in treating community-acquired pneumonia, acute bacterial sinusitis, or acute exacerbations of chronic bronchitis, and has a tolerability profile comparable to that of conventional amoxicillin/clavulanic acid formulations. While the incidence of amoxicillin- or multidrug-resistant S. pneumoniae is not currently sufficient in most regions to warrant the routine empiric use of amoxicillin/clavulanic acid XR, the drug would be extremely useful in those regions with a high incidence of resistant pathogens or in selected patients (i.e. those with S. pneumoniae isolates having amoxicillin MICs > or = 2 microg/mL but < or = 4 microg/mL).
McCormack, Paul L; Keating, Gillian M
2005-01-01
Amoxicillin/clavulanic acid 2000mg/125mg extended release (Augmentin XR), referred to herein as amoxicillin/clavulanic acid XR, is a pharmacokinetically enhanced formulation designed to provide more effective therapy in adults and adolescents than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin. Amoxicillin/clavulanic acid XR maintains plasma amoxicillin concentrations above 4 microg/mL for a mean of 49% of the dosing interval indicating that it would be highly effective against S. pneumoniae strains with minimum inhibitory concentrations (MICs) above the National Committee for Clinical Laboratory Standard's amoxicillin +/- clavulanic acid susceptibility breakpoint of < or =2 microg/mL. Amoxicillin/clavulanic acid XR is at least as effective as conventional amoxicillin/clavulanic acid formulations, levofloxacin and clarithromycin in treating community-acquired pneumonia, acute bacterial sinusitis or acute exacerbations of chronic bronchitis, and has a tolerability profile comparable to that of conventional amoxicillin/clavulanic acid formulations. While the incidence of amoxicillin- or multidrug-resistant S. pneumoniae is not currently sufficient in most regions to warrant the routine empirical use of amoxicillin/clavulanic acid XR, the drug would be extremely useful in those regions with a high incidence of resistant pathogens or in selected patients (i.e. those with S. pneumoniae isolates having amoxicillin MICs > or =2 microg/mL but < or =4 microg/mL).
Bhuyan, Golam Sarower; Hossain, Mohammad Amir; Sarker, Suprovath Kumar; Rahat, Asifuzzaman; Islam, Md Tarikul; Haque, Tanjina Noor; Begum, Noorjahan; Qadri, Syeda Kashfi; Muraduzzaman, A. K. M.; Islam, Nafisa Nawal; Islam, Mohammad Sazzadul; Sultana, Nusrat; Jony, Manjur Hossain Khan; Khanam, Farhana; Mowla, Golam; Matin, Abdul; Begum, Firoza; Shirin, Tahmina; Ahmed, Dilruba; Saha, Narayan; Qadri, Firdausi
2017-01-01
The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1–5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality. PMID:28346512
Bacterial Pathogens Associated with Community-acquired Pneumonia in Children Aged Below Five Years.
Das, Anusmita; Patgiri, Saurav J; Saikia, Lahari; Dowerah, Pritikar; Nath, Reema
2016-03-01
To determine the spectrum of bacterial pathogens causing community-acquired pneumonia in children below 5 years of age. Children aged below 5 years satisfying the WHO criteria for pneumonia, severe pneumonia or very severe pneumonia, and with the presence of lung infiltrates on chest X-ray were enrolled. Two respiratory samples, one for culture and the other for PCR analysis, and a blood sample for culture were collected from every child. Of the 180 samples processed, bacterial pathogens were detected in 64.4%. Streptococcus pneumoniae and Hemophilus influenzae were most frequently detected. The performance of PCR analysis and culture were identical for the typical bacterial pathogens; atypical pathogens were detected by PCR analysis only. S. pneumoniae and H. influenza were the most commonly detected organisms from respiratory secretions of children with community acquired pneumonia.
Yang, Chang; Hu, Dong-Hui; Feng, Yan
2015-04-01
Inhalation therapy using essential oils has been used to treat acute and chronic sinusitis and bronchitis. The aim of the present study was to determine the chemical composition of the essential oil of Artemisia capillaris, and evaluate the antibacterial effects of the essential oil and its main components, against common clinically relevant respiratory bacterial pathogens. Gas chromatography and gas chromatography‑mass spectrometry revealed the presence of 25 chemical constituents, the main constituents being: α‑pinene, β‑pinene, limonene, 1,8‑cineole, piperitone, β‑caryophyllene and capillin. The antibacterial activities of the essential oil, and its major constituents, were evaluated against Streptococcus pyogenes, methicillin‑resistant Staphylococcus aureus (MRSA), MRSA (clinical strain), methicillin‑gentamicin resistant Staphylococcus aureus (MGRSA), Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae and Escherichia coli. The essential oil and its constituents exhibited a broad spectrum and variable degree of antibacterial activity against the various strains. The essential oil was observed to be much more potent, as compared with any of its major chemical constituents, exhibiting low minimum inhibitory and bacteriocidal concentration values against all of the bacterial strains. The essential oil was most active against S. pyogenes, MRSA (clinical strain), S. pneumoniae, K. pneumoniae, H. influenzae and E. coli. Piperitone and capillin were the most potent growth inhibitors, among the major chemical constituents. Furthermore, the essential oil of A. capillaris induced significant and dose‑dependent morphological changes in the S. aureus bacterial strain, killing >90% of the bacteria when administered at a higher dose; as determined by scanning electron microscopy. In addition, the essential oil induced a significant leakage of potassium and phosphate ions from the S. aureus bacterial cultures. These results indicate that the antibacterial action of A. capillaris essential oil may be mediated through the leakage of these two important ions. In conclusion, A. capillaris essential oil exhibits potent antibacterial activity by inducing morphological changes and leakage of ions in S. aureus bacterial cultures.
21 CFR 520.2260a - Sulfamethazine oblet, tablet, and bolus.
Code of Federal Regulations, 2013 CFR
2013-04-01
... and nonlactating dairy cattle. Treatment of bacterial pneumonia and bovine respiratory disease complex... zurnii). (B) Horses. Treatment of bacterial pneumonia (secondary infections associated with Pasteurella... diphtheria caused by F. necrophorum; bacterial pneumonia associated with Pasteurella spp.; and coccidiosis...
21 CFR 520.2260a - Sulfamethazine oblet, tablet, and bolus.
Code of Federal Regulations, 2014 CFR
2014-04-01
... and nonlactating dairy cattle. Treatment of bacterial pneumonia and bovine respiratory disease complex... zurnii). (B) Horses. Treatment of bacterial pneumonia (secondary infections associated with Pasteurella... diphtheria caused by F. necrophorum; bacterial pneumonia associated with Pasteurella spp.; and coccidiosis...
21 CFR 520.2260a - Sulfamethazine oblet, tablet, and bolus.
Code of Federal Regulations, 2012 CFR
2012-04-01
... and nonlactating dairy cattle. Treatment of bacterial pneumonia and bovine respiratory disease complex... zurnii). (B) Horses. Treatment of bacterial pneumonia (secondary infections associated with Pasteurella... diphtheria caused by F. necrophorum; bacterial pneumonia associated with Pasteurella spp.; and coccidiosis...
Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed
2015-01-01
Background Appropriate intervention is critical in reducing deaths among under-five, severe acutely malnourished (SAM) children with danger signs of severe pneumonia; however, there is paucity of data on outcome of World Health Organisation (WHO) recommended interventions of SAM children with severe pneumonia. We sought to evaluate outcome of the interventions in such children. Methods We prospectively enrolled SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) or Acute Respiratory Infection (ARI) ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), between April 2011 and June 2012 with cough or respiratory difficulty and radiological pneumonia. All the enrolled children were treated with ampicillin and gentamicin, and micronutrients as recommended by the WHO. Comparison was made among pneumonic children with (n = 111) and without WHO defined danger signs of severe pneumonia (n = 296). The outcomes of interest were treatment failure (if a child required changing of antibiotics) and deaths during hospitalization. Further comparison was also made among those who developed treatment failure and who did not and among the survivors and deaths. Results SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%; p<0.001) and fatal outcome (21% vs. 4%; p<0.001) compared to those without danger signs. Only 6/111 (5.4%) SAM children with danger signs of severe pneumonia and 12/296 (4.0%) without danger signs had bacterial isolates from blood. In log-linear binomial regression analysis, after adjusting for potential confounders, danger signs of severe pneumonia, dehydration, hypocalcaemia, and bacteraemia were independently associated both with treatment failure and deaths in SAM children presenting with cough or respiratory difficulty and radiological pneumonia (p<0.01). Conclusion and Significance The result suggests that SAM children with cough or respiratory difficulty and radiologic pneumonia who had WHO-defined danger signs of severe pneumonia more often had treatment failure and fatal outcome compared to those without the danger signs. In addition to danger signs of severe pneumonia, other common causes of both treatment failure and deaths were dehydration, hypocalcaemia, and bacteraemia on admission. The result underscores the importance for further research especially a randomized, controlled clinical trial to validate standard WHO therapy in SAM children with pneumonia especially with danger signs of severe pneumonia to reduce treatment failures and deaths. PMID:26451603
Lascarrou, Jean Baptiste; Lissonde, Floriane; Le Thuaut, Aurélie; Bachoumas, Konstantinos; Colin, Gwenhael; Henry Lagarrigue, Matthieu; Vinatier, Isabelle; Fiancette, Maud; Lacherade, Jean Claude; Yehia, Aihem; Joret, Aurélie; Lebert, Christine; Bourdon, Sandra; Martin Lefèvre, Laurent; Reignier, Jean
2017-08-01
To determine the proportion of patients with documented bacterial aspiration pneumonia among comatose ICU patients with symptoms suggesting either bacterial aspiration pneumonia or non-bacterial aspiration pneumonitis. Prospective observational study. University-affiliated 30-bed ICU. Prospective cohort of 250 patients admitted to the ICU with coma (Glasgow Coma Scale score ≤ 8) and treated with invasive mechanical ventilation. None. The primary outcome was the proportion of patients with microbiologically documented bacterial aspiration pneumonia. Patients meeting predefined criteria for aspiration syndrome routinely underwent telescopic plugged catheter sampling during bronchoscopy before starting probabilistic antibiotic treatment. When cultures were negative, the antibiotic treatment was stopped. Of 250 included patients, 98 (39.2%) had aspiration syndrome, including 92 before mechanical ventilation discontinuation. Telescopic plugged catheter in these 92 patients showed bacterial aspiration pneumonia in 43 patients (46.7%). Among the remaining 49 patients, 16 continued to receive antibiotics, usually for infections other than pneumonia; of the 33 patients whose antibiotics were discontinued, only two subsequently showed signs of lung infection. In the six patients with aspiration syndrome after mechanical ventilation, and therefore without telescopic plugged catheter, antibiotic treatment was continued for 7 days. Mechanical ventilation duration, ICU length of stay, and mortality did not differ between the 43 patients with bacterial aspiration pneumonia and the 49 patients with non-bacterial aspiration pneumonitis. The 152 patients without aspiration syndrome did not receive antibiotics. Among comatose patients receiving mechanical ventilation, those without clinical, laboratory, or radiologic evidence of bacterial aspiration pneumonia did not require antibiotics. In those with suspected bacterial aspiration pneumonia, stopping empirical antibiotic therapy when routine telescopic plugged catheter sampling recovered no microorganisms was nearly always effective. This strategy may be a valid alternative to routine full-course antibiotic therapy. Only half the patients with suspected bacterial aspiration pneumonia had this diagnosis confirmed by telescopic plugged catheter sampling.
Tan, L; Wang, H; Li, C; Pan, Y
2014-12-01
Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are leading causes of mortality in hospital intensive care units. We sought to determine whether dental plaque biofilms might harbor pathogenic bacteria that can eventually cause lung infections in patients with severe AE-COPD. Paired samples of subgingival plaque biofilm and tracheal aspirate were collected from 53 patients with severe AE-COPD. Total bacterial DNA was extracted from each sample individually for polymerase chain reaction amplification and/or generation of bacterial 16S rDNA sequences and cDNA libraries. We used a metagenomic approach, based on bacterial 16S rDNA sequences, to compare the distribution of species present in dental plaque and lung. Analysis of 1060 sequences (20 clones per patient) revealed a wide range of aerobic, anaerobic, pathogenic, opportunistic, novel and uncultivable bacterial species. Species indistinguishable between the paired subgingival plaque and tracheal aspirate samples (97-100% similarity in 16S rDNA sequence) were dental plaque pathogens (Aggregatibacter actinomycetemcomitans, Capnocytophaga sputigena, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and lung pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus pneumoniae). Real-time polymerase chain reaction of 16S rDNA indicated lower levels of Pseudomonas aeruginosa and Porphyromonas gingivalis colonizing the dental plaques compared with the paired tracheal aspirate samples. These results support the hypothesis that dental bacteria may contribute to the pathology of severe AE-COPD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Elucidation of Bacterial Pneumonia-Causing Pathogens in Patients with Respiratory Viral Infection
Jung, Hwa Sik; Kang, Byung Ju; Ra, Seung Won; Seo, Kwang Won; Jegal, Yangjin; Jun, Jae-Bum; Jung, Jiwon; Jeong, Joseph; Jeon, Hee-Jeong; Ahn, Jae-Sung
2017-01-01
Background Bacterial pneumonia occurring after respiratory viral infection is common. However, the predominant bacterial species causing pneumonia secondary to respiratory viral infections other than influenza remain unknown. The purpose of this study was to know whether the pathogens causing post-viral bacterial pneumonia vary according to the type of respiratory virus. Methods Study subjects were 5,298 patients, who underwent multiplex real-time polymerase chain reaction for simultaneous detection of respiratory viruses, among who visited the emergency department or outpatient clinic with respiratory symptoms at Ulsan University Hospital between April 2013 and March 2016. The patients' medical records were retrospectively reviewed. Results A total of 251 clinically significant bacteria were identified in 233 patients with post-viral bacterial pneumonia. Mycoplasma pneumoniae was the most frequent bacterium in patients aged <16 years, regardless of the preceding virus type (p=0.630). In patients aged ≥16 years, the isolated bacteria varied according to the preceding virus type. The major results were as follows (p<0.001): pneumonia in patients with influenza virus (type A/B), rhinovirus, and human metapneumovirus infections was caused by similar bacteria, and the findings indicated that Staphylococcus aureus pneumonia was very common in these patients. In contrast, coronavirus, parainfluenza virus, and respiratory syncytial virus infections were associated with pneumonia caused by gram-negative bacteria. Conclusion The pathogens causing post-viral bacterial pneumonia vary according to the type of preceding respiratory virus. This information could help in selecting empirical antibiotics in patients with post-viral pneumonia. PMID:28905531
Wang, Hao; Anthony, Desiree; Yatmaz, Selcuk; Wijburg, Odilia; Satzke, Catherine; Levy, Bruce; Vlahos, Ross; Bozinovski, Steven
2017-09-15
Formyl peptide receptor 2/lipoxin A 4 (LXA 4 ) receptor (Fpr2/ALX) co-ordinates the transition from inflammation to resolution during acute infection by binding to distinct ligands including serum amyloid A (SAA) and Resolvin D1 (RvD1). Here, we evaluated the proresolving actions of aspirin-triggered RvD1 (AT-RvD1) in an acute coinfection pneumonia model. Coinfection with Streptococcus pneumoniae and influenza A virus (IAV) markedly increased pneumococcal lung load and neutrophilic inflammation during the resolution phase. Fpr2/ALX transcript levels were increased in the lungs of coinfected mice, and immunohistochemistry identified prominent Fpr2/ALX immunoreactivity in bronchial epithelial cells and macrophages. Levels of circulating and lung SAA were also highly increased in coinfected mice. Therapeutic treatment with exogenous AT-RvD1 during the acute phase of infection (day 4-6 post-pneumococcal inoculation) significantly reduced the pneumococcal load. AT-RvD1 also significantly reduced neutrophil elastase (NE) activity and restored total antimicrobial activity in bronchoalveolar lavage (BAL) fluid (BALF) of coinfected mice. Pneumonia severity, as measured by quantitating parenchymal inflammation or alveolitis was significantly reduced with AT-RvD1 treatment, which also reduced the number of infiltrating lung neutrophils and monocytes/macrophages as assessed by flow cytometry. The reduction in distal lung inflammation in AT-RvD1-treated mice was not associated with a significant reduction in inflammatory and chemokine mediators. In summary, we demonstrate that in the coinfection setting, SAA levels were persistently increased and exogenous AT-RvD1 facilitated more rapid clearance of pneumococci in the lungs, while concurrently reducing the severity of pneumonia by limiting excessive leukocyte chemotaxis from the infected bronchioles to distal areas of the lungs. © 2017 The Author(s).
Akhvlediani, Tamar; Bautista, Christian T.; Shakarishvili, Roman; Tsertsvadze, Tengiz; Imnadze, Paata; Tatishvili, Nana; Davitashvili, Tamar; Samkharadze, Tamar; Chlikadze, Rusudan; Dvali, Natia; Dzigua, Lela; Karchava, Mariam; Gatserelia, Lana; Macharashvili, Nino; Kvirkvelia, Nana; Habashy, Engy Emil; Farrell, Margaret; Rowlinson, Emily; Sejvar, James; Hepburn, Matthew; Pimentel, Guillermo; Dueger, Erica; House, Brent; Rivard, Robert
2014-01-01
Objectives There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS) infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis. Methods Children and adults patients clinically diagnosed with meningitis or encephalitis were enrolled at four reference health centers. Cerebrospinal fluid (CSF) was collected for bacterial culture, and in-house and multiplex RT-PCR testing was conducted for herpes simplex virus (HSV) types 1 and 2, mumps virus, enterovirus, varicella zoster virus (VZV), Streptococcus pneumoniae, HiB and Neisseria meningitidis. Results Out of 140 enrolled patients, the mean age was 23.9 years, and 58% were children. Bacterial or viral etiologies were determined in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae, 6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified infections with enterovirus (n = 26), VZV (n = 4), and HSV-1 (n = 2). No patient was positive for mumps or HSV-2. Conclusions Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve health outcomes of CNS infection cases in Georgia. PMID:25369023
Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia.
Kumagai, S; Ishida, T; Tachibana, H; Ito, Y; Ito, A; Hashimoto, T
2015-09-01
The aim of this study was to investigate the influence of bacterial coinfection on patients with pneumococcal pneumonia. We retrospectively analyzed the incidence, clinical features, microbial distributions, and outcomes of patients with bacterial coinfection in a cohort of 433 hospitalized patients with pneumococcal pneumonia. Eighty-five patients (19.6 %) were diagnosed with bacterial coinfection; the most frequent pathogens were Haemophilus influenzae (25 patients, 33.3 %), methicillin-susceptible Staphylococcus aureus (MSSA) (15 patients, 20.0 %), and Moraxella catarrhalis (13 patients, 17.3 %). The CURB-65 score and pneumonia severity index (PSI) were significantly higher in patients with bacterial coinfection (both P < 0.001). In addition, the proportion of patients with bacterial coinfection who met the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria was significantly higher (P < 0.001). Multivariate logistic regression analysis identified three risk factors for bacterial coinfection in patients with pneumococcal pneumonia: alcoholism (odds ratio [OR], 5.12; 95 % confidence interval (95 % CI), 1.60-16.4; P = 0.006), hospitalization for 2 days or more within 90 days preceding admission (OR, 2.02; 95 % CI, 1.03-3.98; P = 0.041), and residence in a nursing home or extended care facility (OR, 3.22; 95 % CI, 1.48-6.97; P = 0.003). Multivariate analysis for 30-day mortality showed that bacterial coinfection was a significant adverse prognostic factor (OR, 2.50; 95 % CI, 1.13-5.53; P = 0.023), independent of IDSA/ATS severe pneumonia, PSI, or healthcare-associated pneumonia. In conclusion, bacterial coinfection may have an adverse impact on severity and outcomes of pneumococcal pneumonia.
21 CFR 520.2345d - Tetracycline powder.
Code of Federal Regulations, 2013 CFR
2013-04-01
.... Control and treatment of bacterial enteritis (scours) caused by Escherichia coli and bacterial pneumonia... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia associated with Pasteurella spp., A...
21 CFR 520.2345d - Tetracycline powder.
Code of Federal Regulations, 2014 CFR
2014-04-01
.... Control and treatment of bacterial enteritis (scours) caused by Escherichia coli and bacterial pneumonia... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia associated with Pasteurella spp., A...
21 CFR 520.2345d - Tetracycline powder.
Code of Federal Regulations, 2012 CFR
2012-04-01
.... Control and treatment of bacterial enteritis (scours) caused by Escherichia coli and bacterial pneumonia... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia associated with Pasteurella spp., A...
Outbreak of pasteurellosis in captive Bolivian squirrel monkeys (Saimiri boliviensis)
YOSHINO, Mizuki; SASAKI, Jun; KURAMOCHI, Konomi; IKEZAWA, Mitsutaka; MUKAIZAWA, Natsuko; GORYO, Masanobu
2017-01-01
In September 2012, five Bolivian squirrel monkeys housed in a zoological park died within sequential several days without obvious clinical signs. In a necrospy, one monkey presented swelling of the kidney with multifocal white nodules in the parenchyma, and other two had pulmonary congestion. Histopathologically, multifocal bacterial colonies of gram-negative coccobacillus were found in the sinusoid of the liver in all monkeys examined (Nos.1−4). Additionally, purulent pyelonephritis, pneumonia and disseminated small bacterial colonies in blood vessels were observed. Immunohistochemically, the bacterial colonies from two monkeys were positive for P. multocida capsular serotype D. Based on these findings, these monkeys were diagnosed as septicemia caused by acute P. multocida infection. PMID:28190821
Outbreak of pasteurellosis in captive Bolivian squirrel monkeys (Saimiri boliviensis).
Yoshino, Mizuki; Sasaki, Jun; Kuramochi, Konomi; Ikezawa, Mitsutaka; Mukaizawa, Natsuko; Goryo, Masanobu
2017-03-23
In September 2012, five Bolivian squirrel monkeys housed in a zoological park died within sequential several days without obvious clinical signs. In a necrospy, one monkey presented swelling of the kidney with multifocal white nodules in the parenchyma, and other two had pulmonary congestion. Histopathologically, multifocal bacterial colonies of gram-negative coccobacillus were found in the sinusoid of the liver in all monkeys examined (Nos.1-4). Additionally, purulent pyelonephritis, pneumonia and disseminated small bacterial colonies in blood vessels were observed. Immunohistochemically, the bacterial colonies from two monkeys were positive for P. multocida capsular serotype D. Based on these findings, these monkeys were diagnosed as septicemia caused by acute P. multocida infection.
Song, Joon Y.; Cheong, Hee J.; Heo, Jung Y.; Noh, Ji Y.; Yong, Hwan S.; Kim, Yoon K.; Kang, Eun Y.; Choi, Won S.; Jo, Yu M.; Kim, Woo J.
2011-01-01
Please cite this paper as: Song et al. (2011). Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia. Influenza and Other Respiratory Viruses 5(6), e535–e543. Background Although influenza virus usually involves the upper respiratory tract, pneumonia was seen more frequently with the 2009 pandemic influenza A/H1N1 than with seasonal influenza. Methods From September 1, 2009, to January 31, 2010, a specialized clinic for patients (aged ≥15 years) with ILI was operated in Korea University Guro Hospital. RT‐PCR assay was performed to diagnose 2009 pandemic influenza A/H1N1. A retrospective case–case–control study was performed to determine the predictive factors for influenza pneumonia and to discriminate concomitant/secondary bacterial pneumonia from primary influenza pneumonia during the 2009–2010 pandemic. Results During the study period, the proportions of fatal cases and pneumonia development were 0·12% and 1·59%, respectively. Patients with pneumonic influenza were less likely to have nasal symptoms and extra‐pulmonary symptoms (myalgia, headache, and diarrhea) compared to patients with non‐pneumonic influenza. Crackle was audible in just about half of the patients with pneumonic influenza (38·5% of patients with primary influenza pneumonia and 53·3% of patients with concomitant/secondary bacterial pneumonia). Procalcitonin, C‐reactive protein (CRP), and lactate dehydrogenase were markedly increased in patients with influenza pneumonia. Furthermore, procalcitonin (cutoff value 0·35 ng/ml, sensitivity 81·8%, and specificity 66·7%) and CRP (cutoff value 86·5 mg/IU, sensitivity 81·8%, and specificity 59·3%) were discriminative between patients with concomitant/secondary bacterial pneumonia and patients with primary influenza pneumonia. Conclusions Considering the subtle manifestations of 2009 pandemic influenza A/H1N1 pneumonia in the early stage, high clinical suspicion is required to detect this condition. Both procalcitonin and CRP would be helpful to differentiate primary influenza pneumonia from concomitant/secondary bacterial pneumonia. PMID:21682848
Aspiration pneumonia. Pathophysiological aspects, prevention and management. A review.
Petroianni, A; Ceccarelli, D; Conti, V; Terzano, C
2006-12-01
Aspiration pneumonias occur more frequently than reported and, in many cases, the disease is not recognised. In hospitalised and institutionalised patients with predisposing diseases prompt diagnosis of this complication and correct preventive measures can drastically reduce the worsening of clinical conditions and the deaths due to aspiration pneumonia. Normal airway structure, effective defence mechanisms, and preventive measures are decisive in reducing aspiration episodes. An increased aspiration risk for food, fluids, medications, or secretions may lead to the development of pneumonia. Pneumonia is the most common respiratory complication in all stroke deaths and in mechanical ventilation patients. In addition, the increased incidence of aspiration pneumonia with aging may be a consequence of impairment of swallowing and the cough reflex. Dysphagia, compromised consciousness, invasive procedures, anaesthesia, insufficient oral care, sleep disorders, and vomiting are all risk factors. Aspiration pneumonia includes different characteristic syndromes based on the amount (massive, acute, chronic) and physical character of the aspirated material (acid, infected, lipoid), needing a different therapeutic approach. Chronic patients education and correct health care practices are the keys for preventing the events of aspiration. In patients at risk a clinical and instrumental assessment of dysphagia should be evaluated. Management includes the removal of etiologic factors (drugs, tubes, mobilisation, oral hygiene), supportive care, and in bacterial pneumonias a specific antibiotic therapy for community-acquired or nosocomial events.
21 CFR 522.90a - Ampicillin trihydrate sterile suspension.
Code of Federal Regulations, 2012 CFR
2012-04-01
... daily, for up to 3 days. For pneumonia: 3 milligrams per pound of body weight, intramuscularly, twice... coli and bacterial pneumonia caused by Pasteurella spp. susceptible to ampicillin. (C) Limitations. Not.... Treatment of bacterial enteritis (colibacillosis) caused by E. coli and bacterial pneumonia caused by...
21 CFR 522.90a - Ampicillin trihydrate sterile suspension.
Code of Federal Regulations, 2013 CFR
2013-04-01
... daily, for up to 3 days. For pneumonia: 3 milligrams per pound of body weight, intramuscularly, twice... coli and bacterial pneumonia caused by Pasteurella spp. susceptible to ampicillin. (C) Limitations. Not.... Treatment of bacterial enteritis (colibacillosis) caused by E. coli and bacterial pneumonia caused by...
Code of Federal Regulations, 2011 CFR
2011-04-01
... of bacterial enteritis caused by E. coli and bacterial pneumonia caused by P. multocida organisms... improved feed efficiency; and for treatment of bacterial enteritis caused by E. coli and bacterial... treatment of bacterial enteritis caused by E. coli and bacterial pneumonia caused by P. multocida organisms...
Elucidation of Bacterial Pneumonia-Causing Pathogens in Patients with Respiratory Viral Infection.
Jung, Hwa Sik; Kang, Byung Ju; Ra, Seung Won; Seo, Kwang Won; Jegal, Yangjin; Jun, Jae Bum; Jung, Jiwon; Jeong, Joseph; Jeon, Hee Jeong; Ahn, Jae Sung; Lee, Taehoon; Ahn, Jong Joon
2017-10-01
Bacterial pneumonia occurring after respiratory viral infection is common. However, the predominant bacterial species causing pneumonia secondary to respiratory viral infections other than influenza remain unknown. The purpose of this study was to know whether the pathogens causing post-viral bacterial pneumonia vary according to the type of respiratory virus. Study subjects were 5,298 patients, who underwent multiplex real-time polymerase chain reaction for simultaneous detection of respiratory viruses, among who visited the emergency department or outpatient clinic with respiratory symptoms at Ulsan University Hospital between April 2013 and March 2016. The patients' medical records were retrospectively reviewed. A total of 251 clinically significant bacteria were identified in 233 patients with post-viral bacterial pneumonia. Mycoplasma pneumoniae was the most frequent bacterium in patients aged <16 years, regardless of the preceding virus type (p=0.630). In patients aged ≥16 years, the isolated bacteria varied according to the preceding virus type. The major results were as follows (p<0.001): pneumonia in patients with influenza virus (type A/B), rhinovirus, and human metapneumovirus infections was caused by similar bacteria, and the findings indicated that Staphylococcus aureus pneumonia was very common in these patients. In contrast, coronavirus, parainfluenza virus, and respiratory syncytial virus infections were associated with pneumonia caused by gram-negative bacteria. The pathogens causing post-viral bacterial pneumonia vary according to the type of preceding respiratory virus. This information could help in selecting empirical antibiotics in patients with post-viral pneumonia. Copyright©2017. The Korean Academy of Tuberculosis and Respiratory Diseases
Achieving bacterial eradication using pharmacokinetic/pharmacodynamic principles.
Dagan, Ron
2003-03-01
Evidence from studies in otitis media indicates that antimicrobials and dosing regimens that have equivalent bacteriologic efficacy against susceptible pathogens can have significantly different bacteriologic success rates against resistant strains of the same species. Unlike macrolide and fluoroquinolone resistance, penicillin resistance can be overcome in Streptococcus pneumoniae by increasing the dose, and hence increasing the time for which the serum concentrations are above the MIC. The new clinical formulation of extra-strength amoxicillin-clavulanate provides 90 mg/kg per day amoxicillin plus 6.4 mg/kg per day clavulanate (14:1) divided every 12 h, compared with 45/6.4 mg/kg per day b.i.d. with conventional dosing. The pharmacokinetic/pharmacodynamic (PK/PD) profiles of extra-strength amoxicillin-clavulanate predict that the new formulation will be more effective than the conventional formulation against S. pneumoniae with elevated amoxicillin MICs and against Haemophilus influenzae. In an open-label, non-comparative study in children with acute otitis media, the extra-strength formulation had high bacteriologic success rates against the major respiratory pathogens, including penicillin-resistant S. pneumoniae. The development of new antimicrobial agents and formulations should be aimed at meeting PK/PD parameters predictive of bacterial eradication of both susceptible and resistant strains.
Song, Meng; Lu, Gejin; Li, Meng; Deng, Xuming; Wang, Jianfeng
2017-08-01
Streptococcus pneumoniae (the pneumococcus) is an opportunistic pathogen responsible for several human diseases, including acute otitis media, pneumonia, sepsis and bacterial meningitis, and possesses numerous virulence factors associated with pneumococcal infection and pathogenesis. With the capacity to form pores in cholesterol-rich membranes, pneumolysin (PLY) is a key virulence factor of S. pneumoniae and causes severe tissue damage during pneumococcal infection. Juglone (JG), a natural 1,4-naphthoquinone widely found in the roots, leaves, woods and fruits of Juglandaceae walnut trees, inhibits PLY-induced hemolysis via inhibition of the oligomerization of PLY and exhibits minimal anti-S. pneumoniae activity. In addition, when human alveolar epithelial (A549) cells were co-cultured with PLY and JG, PLY-mediated cell injury was significantly alleviated. These results indicate that JG directly interacts with PLY to reduce the cytotoxicity of the toxin in human alveolar epithelial cells. Hence, JG is an effective inhibitor of PLY and protects lung cells from PLY-mediated cell injury. This study also provides the basis for the development of anti-virulence drugs for the treatment of S. pneumoniae infections.
Role of fluoroquinolones in lower respiratory tract infections.
Vellend, H
1989-02-01
Oral quinolones such as ciprofloxacin are promising agents in the treatment of serious bronchopulmonary infections due to susceptible gram-negative micro-organisms such as Haemophilus influenzae, Branhamella catarrhalis, Klebsiella pneumoniae and even Pseudomonas aeruginosa. Their moderative activity against Streptococcus pneumoniae may limit the use of these agents in the treatment of acute exacerbations of chronic bronchitis and in the empiric management of community-acquired bacterial pneumonia. Further prospectively designed studies are needed to address this issue. The ability of quinolones to effectively penetrate bronchial mucosa and to be concentrated within macrophages may afford additional advantage to these agents. They should not be used as a sole agent in the treatment of aspiration pneumonia nor anaerobic pleuropulmonary disease. Quinolones are very active in experimental models of Legionnaire's disease and deserve further clinical study. Ciprofloxacin is a promising alternative to standard parenteral drugs in the management of Pseudomonas aeruginosa infections in adults with cystic fibrosis. The potential for drug interactions with theophylline must be kept in mind for patients on both of these drugs.
Efficacy/safety of amoxicillin/clavulanate in adults with bacterial rhinosinusitis.
Anon, Jack B; Berkowitz, Elchonon; Breton, John; Twynholm, Monique
2006-01-01
Acute bacterial rhinosinusitis (ABRS) is a common and uncomfortable condition, frequently caused by Streptococcus pneumoniae or Haemophilus influenzae. Antibacterial resistance among these and other common respiratory pathogens is now widespread and of concern. Pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg was developed to be effective against the common respiratory pathogens, including many resistant strains. This open-label, noncomparative study assessed the bacteriologic and clinical efficacy of amoxicillin/clavulanate 2000/125 mg in adult patients with ABRS. Requirements for study entry included a clinical diagnosis of ABRS supported by radiologic findings. In addition, sinus puncture for bacteriologic assessment was required at study entry. Overall, bacteriologic success (eradication or clinical evidence of eradication) at the follow-up visit (days 17-28) was achieved in 87.8% (722/822) of patients with 1 or more pathogen isolated at screening, in 93.2% (246/264) of patients with S pneumoniae, in 96.7% (29/30) of those with penicillin-resistant S pneumoniae (penicillin minimum inhibitory concentrations >or=2 microg/mL), and in 88.7% (110/124) of patients with beta-lactamase-positive pathogens. Bacteriologic success was achieved against 6 of 7 S pneumoniae isolates with amoxicillin/clavulanic acid minimum inhibitory concentrations of 4/2 microg/mL or higher. Amoxicillin/clavulanate 2000/125 mg was generally well tolerated. This new amoxicillin/clavulanate formulation provides a suitable option for empiric therapy for ABRS in adults.
Dickson, Robert P.; Erb-Downward, John R.; Prescott, Hallie C.; Martinez, Fernando J.; Curtis, Jeffrey L.; Lama, Vibha N.
2014-01-01
The diagnosis and management of pneumonia are limited by the use of culture-based techniques of microbial identification, which may fail to identify unculturable, fastidious, and metabolically active viable but unculturable bacteria. Novel high-throughput culture-independent techniques hold promise but have not been systematically compared to conventional culture. We analyzed 46 clinically obtained bronchoalveolar lavage (BAL) fluid specimens from symptomatic and asymptomatic lung transplant recipients both by culture (using a clinical microbiology laboratory protocol) and by bacterial 16S rRNA gene pyrosequencing. Bacteria were identified in 44 of 46 (95.7%) BAL fluid specimens by culture-independent sequencing, significantly more than the number of specimens in which bacteria were detected (37 of 46, 80.4%, P ≤ 0.05) or “pathogen” species reported (18 of 46, 39.1%, P ≤ 0.0001) via culture. Identification of bacteria by culture was positively associated with culture-independent indices of infection (total bacterial DNA burden and low bacterial community diversity) (P ≤ 0.01). In BAL fluid specimens with no culture growth, the amount of bacterial DNA was greater than that in reagent and rinse controls, and communities were markedly dominated by select Gammaproteobacteria, notably Escherichia species and Pseudomonas fluorescens. Culture growth above the threshold of 104 CFU/ml was correlated with increased bacterial DNA burden (P < 0.01), decreased community diversity (P < 0.05), and increased relative abundance of Pseudomonas aeruginosa (P < 0.001). We present two case studies in which culture-independent techniques identified a respiratory pathogen missed by culture and clarified whether a cultured “oral flora” species represented a state of acute infection. In summary, we found that bacterial culture of BAL fluid is largely effective in discriminating acute infection from its absence and identified some specific limitations of BAL fluid culture in the diagnosis of pneumonia. We report the first correlation of quantitative BAL fluid culture results with culture-independent evidence of infection. PMID:25078910
Moxifloxacin in respiratory tract infections.
Miravitlles, Marc
2005-02-01
Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including Gram-positive (Streptococcus pneumoniae), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis), and atypical strains (Chlamydia pneumoniae, Mycoplasma pneumoniae), as well as multi-drug resistant S. pneumoniae, including strains resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. Moxifloxacin is highly concentrated in lung tissue, and has demonstrated rapid eradication rates. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400mg/day. The ratio of the area under the concentration-time curve to MIC of moxifloxacin is the highest among the fluoroquinolones against S. pneumoniae. The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia (CAP), exacerbations of chronic bronchitis (CB) and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in CAP and exacerbations of CB patients compared with first-line therapy. It has also demonstrated better eradication in exacerbations of CB compared with standard therapy, in particular the macrolides. Treatment guidelines should take into account the results of clinical trials with moxifloxacin in order to establish the role of this antimicrobial in the therapeutic arsenal against respiratory tract infections.
Identification of bacteria causing acute otitis media using Raman microspectroscopy
NASA Astrophysics Data System (ADS)
Ayala, Oscar D.; Wakeman, Catherine A.; Skaar, Eric P.; Mahadevan-Jansen, Anita
2016-03-01
Otitis media (OM) is the leading cause of acute physician visits and prescription of antibiotics for children. Current standard techniques to diagnose acute otitis media (AOM) are limited by their ability to probe only changes in symptoms of the bacterial infection that cause AOM. Furthermore, they are not able to detect the presence of or identify bacteria causing AOM, which is important for diagnosis and proper antibiotic treatment. Our goal is to detect the presence of and identify the pathogens involved in causing AOM based on their biochemical profile using Raman spectroscopy (RS). An inVia confocal Raman microscope (Renishaw) at 785 nm was used to detect bacteria causing AOM in vitro. The three main bacteria that cause AOM, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae were cultured in chocolate agar and Mueller-Hinton agar to determine which agar type would minimize Raman signal from the growth agar. Preliminary results identified specific Raman spectral features characteristic of S. pneumoniae. RS has the potential to accurately diagnose AOM, which will help in identifying the antibiotic that will be most beneficial for the patient and ultimately decrease the course of infection.
... allergic or chemical reactions and certain infections. Eosinophilic Pneumonia Eosinophilic pneumonia describes a category of pneumonias that ... low oxygen in the bloodstream. Acute Idiopathic Eosinophilic Pneumonia Acute idiopathic eosinophilic pneumonia is a more sudden ...
Izumikawa, Koichi; Watanabe, Akira; Miyashita, Naoyuki; Ishida, Tadashi; Hosono, Hiroaki; Kushimoto, Satoru; Kohno, Shigeru
2014-09-01
We performed a postmarketing surveillance study to determine the efficacy and safety of the oral quinolone antibacterial agent, garenoxacin (Geninax(®) Tablets 200 mg), against bacterial pneumonia. Between October 2009 and March 2011, patients with community-acquired pneumonia visited 174 facilities in Japan; we collected survey forms from 739 patients of these patients who were suspected with bacterial pneumonia on the basis of factors, e.g., the presence of purulent sputum or suspected presence of bacterial pathogens in clinical specimens. We examined the safety in 730 patients and the efficacy in 535 patients. The efficacy rate of garenoxacin for bacterial pneumonia was 92.8% (479/516 patients). The eradication rates for Streptococcus pneumoniae and Haemophilus influenzae, the major pathogens of bacterial pneumonia, were 98.5% (65/66 strains) and 100% (65/65 strains), respectively. The incidence of adverse drug reactions (including abnormal laboratory tests) was 7.9% (58/730 patients). Among the main adverse drug reactions, abnormal laboratory tests were observed in 2.1% patients (15/730), hepatobiliary disorders were observed in 1.8% patients (13/730), and skin and subcutaneous tissue disorders were observed in 1.6% patients (12/730). In conclusion, garenoxacin showed an efficacy rate of greater than 90% for bacterial pneumonia and is considered to be useful in daily practice. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Bacterial Infections in Acute-on-Chronic Liver Failure.
Yang, Lingling; Wu, Tianzhou; Li, Jiang; Li, Jun
2018-05-01
Acute-on-chronic liver failure (ACLF) is a newly recognized clinical syndrome characterized by preexisting chronic liver disease or cirrhosis with organ failure and high 28-day mortality (50-90%). Bacterial infections (BIs) play pivotal roles in the development and progression of ACLF either as a main precipitating event or a specific complication. The main organisms isolated as triggering ACLF are Gram-positive bacteria, followed by Gram-negative bacteria. Spontaneous bacterial peritonitis, pneumonia, urinary tract infections, and skin infections are prevalent infections that trigger and complicate ACLF. Despite appropriate antibiotic treatment, BIs account for poor ACLF outcomes and lead to a worse clinical course and higher intensive care unit admission and short-term mortality. Early diagnosis and novel nonantibiotic methods are highly important for managing BIs. Thus, this review focuses on the epidemiology, prognosis, and diagnosis of and management strategies for BIs in ACLF patients as well as the relationship between BIs and ACLF. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Pneumonia after kidney transplant: incidence, risk factors, and mortality.
Dizdar, Oguzhan Sitki; Ersoy, Alparslan; Akalin, Halis
2014-06-01
Pneumonia is an important cause of morbidity and mortality in recipients of solid-organ transplant. We aimed to determine risk factors for development of pneumonia and associated deaths in kidney transplant recipients. A retrospective review of medical records was performed for all kidney transplant recipients from December 1988, to April 2011. The diagnosis of community-acquired pneumonia was made from symptoms, clinical findings, and chest radiography. The diagnosis of nosocomial pneumonia was made according to published criteria. Laboratory and serologic tests, radiographic findings, cultures of respiratory specimens, and tissue biopsies were reviewed. In 406 kidney transplant recipients, there were 82 patients (20%) who had 111 episodes of pneumonia, including 49 nosocomial episodes of pneumonia (44%). Bacterial infections were the most common cause (34 episodes [31%]). In multivariate analysis, significant risk factors associated with pneumonia episodes were older age, hypertension, cardiac disease, history of acute graft rejection, and not using everolimus/mycophenolate mofetil/prednisolone protocol. There were 28 episodes that resulted in death (25%), including 20 nosocomial episodes (71%). In multivariate analysis, significant risk factors associated with death from pneumonia episodes were antibiotic use in the previous 3 months, high C-reactive protein, and low albumin. Cutoff values for increased risk of death from pneumonia included C-reactive protein > 10 mg/dL and procalcitonin > 8.8 ng/mL. Recipients of kidney transplant may be at risk for pneumonia and associated death. Nosocomial pulmonary infections may be associated with marked morbidity and mortality in kidney transplant recipients.
Kohli, Rakhi; Lo, Yungtai; Homel, Peter; Flanigan, Timothy P; Gardner, Lytt I; Howard, Andrea A; Rompalo, Anne M; Moskaleva, Galina; Schuman, Paula; Schoenbaum, Ellie E
2006-07-01
To determine the rate and predictors of community-acquired bacterial pneumonia and its effect on human immunodeficiency virus (HIV) disease progression in HIV-infected women, we performed a multiple-site, prospective study of HIV-infected women in 4 cities in the United States. During the period of 1993-2000, we observed 885 HIV-infected and 425 HIV-uninfected women with a history of injection drug use or high-risk sexual behavior. Participants underwent semiannual interviews, and CD4+ lymphocyte count and viral load were assessed in HIV-infected subjects. Data regarding episodes of bacterial pneumonia were ascertained from medical record reviews. The rate of bacterial pneumonia among 885 HIV-infected women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years in 425 HIV-uninfected women (P < .001). In analyses limited to follow-up after 1 January 1996, highly active antiretroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) use were associated with a decreased risk of bacterial pneumonia. Among women who had used TMP-SMX for 12 months, each month of HAART decreased bacterial pneumonia risk by 8% (adjusted hazard ratio [HR(adj)], 0.92; 95% confidence interval [CI], 0.89-0.95). Increments of 50 CD4+ cells/mm3 decreased the risk (HR(adj), 0.88; 95% CI, 0.84-0.93), and smoking doubled the risk (HR(adj), 2.12; 95% CI, 1.26-3.55). Bacterial pneumonia increased mortality risk (HR(adj), 5.02; 95% CI, 2.12-11.87), with adjustment for CD4+ lymphocyte count and duration of HAART and TMP-SMX use. High rates of bacterial pneumonia persist among HIV-infected women. Although HAART and TMP-SMX treatment decreased the risk, bacterial pneumonia was associated with an accelerated progression to death. Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted.
21 CFR 520.2345c - Tetracycline boluses.
Code of Federal Regulations, 2012 CFR
2012-04-01
... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia caused by Pasteurella spp... doses. (i) Indications for use. Treatment of bacterial pneumonia caused by organisms susceptible to...
21 CFR 520.2345c - Tetracycline boluses.
Code of Federal Regulations, 2013 CFR
2013-04-01
... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia caused by Pasteurella spp... doses. (i) Indications for use. Treatment of bacterial pneumonia caused by organisms susceptible to...
21 CFR 520.2345c - Tetracycline boluses.
Code of Federal Regulations, 2014 CFR
2014-04-01
... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia caused by Pasteurella spp... doses. (i) Indications for use. Treatment of bacterial pneumonia caused by organisms susceptible to...
Detection of acute childhood meningitis by PCR, culture and agglutination tests in Tabriz, Iran.
Ghotaslou, Reza; Farajnia, Safar; Yeganeh, Fatemeh; Abdoli-Oskouei, Shahram; Ahangarzadeh Rezaee, Mohammad; Barzegar, Mohammad
2012-01-01
Meningitis is one of the hazardous and life threatening infections and is associated with mortality and morbidity. The aim of this study was to determine etiological agents of childhood bacterial meningitis. The culture, Gram staining, agglutination and PCR assays were used to examine CSF specimens from 277 patients with presumed bacterial meningitis for the occurrence of 4 most common infectious agents consist of N. meningitis, H. influnsae, S. pneumoniae and S. agalactiae between 2008 and 2009 at different wards of the Children Hospital of Tabriz. The mean age of patients was 35 ± 2 (Mean ± SEM) month, (minimum 11 days maximum 14 years), of all cases 59.6% male and 40.4% female. Overall the diagnosis was confirmed with a CSF culture in 11/277 (3.97%), by agglutination test in 14/277 (5.05%). The isolated bacteria included S. pneumoniae 5 cases, H. influnsae 2 cases, N. meningitis 3 cases and P. aeroginusae 1 case. A positive PCR assay allowed us to diagnose bacterial meningitis in 19 patients (6.8%). In the present study, we found PCR to be a useful and sensitive method for the detection of bacterial DNA in the CSF samples from suspected meningitis patients. Furthermore, to maximize management of meningitis cases, a combination of culture and PCR is necessary.
Dashtdar, Mehrab; Dashtdar, Mohammad Reza; Dashtdar, Babak; shirazi, Mohammad khabaz; Khan, Saeed Ahmad
2013-01-01
Objective: Evaluations of the in-vitro anti-bacterial activities of aqueous extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and Shilajita mumiyo against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) and gram-negative bacteria (Escherichia coli, klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa) are reasonable since these ethnomedicinal plants have been used in Persian folk medicine for treating skin diseases, venereal diseases, respiratory problems and nervous disorders for ages. Methods: The well diffusion method (KB testing) with a concentration of 250 μg/disc was used for evaluating the minimal inhibitory concentrations (MIC). Maximum synergistic effects of different combinations of components were also observed. Results: A particular combination of Acacia catechu (L.F.) Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo extracts possesses an outstanding anti-bacterial activity. It's inhibiting effect on microorganisms is significant when compared to the control group (P< 0.05). Staphylococcus aureus was the most sensitive microorganism. The highest antibacterial activity against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) or gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis and Pseudomonas aeruginosa) was exerted by formula number 2 (Table1). Conclusion: The results reveal the presence of antibacterial activities of Acacia catechu, Castanea sativa husk, Ephedra sp. and Mumiyo against gram-positive and gram-negative bacteria. Synergistic effects in a combined formula, especially in formula number 2 (ASLANⓇ) can lead to potential sources of new antiseptic agents for treatment of acute or chronic skin ulcers. These results considering the significant antibacterial effect of the present formulation, support ethno-pharmacological uses against diarrheal and venereal diseases and demonstrate use of these plants to treat infectious diseases. PMID:25780663
Sperber, Jesper; Nyberg, Axel; Lipcsey, Miklos; Melhus, Åsa; Larsson, Anders; Sjölin, Jan; Castegren, Markus
2017-08-31
Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury. A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H 2 O and a tidal volume of 6 ml x kg -1 . The control group (n = 10) had an end expiratory pressure of 5 cm H 2 O and a tidal volume of 10 ml x kg -1 . 10 11 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements. The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01). In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.
Proulx, Alexandre; Hume, Daniel Z; Drobatz, Kenneth J; Reineke, Erica L
2014-01-01
To determine the proportion of airway bacterial isolates resistant to both empirically selected and recently administered antimicrobials, and to assess the impact of inappropriate initial empiric antimicrobials selection on length of hospital stay and survival to discharge in dogs with bacterial pneumonia. Retrospective study. University veterinary teaching hospital. One hundred and eleven dogs with a clinical diagnosis of bacterial pneumonia that had aerobic bacterial culture and susceptibility testing performed from a tracheal wash sample. None. Overall, 26% (29/111) of the dogs had at least 1 bacterial isolate that was resistant to empirically selected antimicrobials. In dogs with a history of antimicrobial administration within the preceding 4 weeks, a high incidence (57.4%, 31/54) of in vitro bacterial resistance to those antimicrobials was found: 64.7% (11/17) in the community-acquired pneumonia group, 55.2% (16/29) in the aspiration pneumonia group, and 50.0% (4/8) in the other causes of bacterial pneumonia group. No statistically significant association was found between bacterial isolate resistance to empirically selected antimicrobials and length of hospital stay or mortality. The high proportion of in vitro airway bacterial resistance to empiric antimicrobials would suggest that airway sampling for bacterial culture and susceptibility testing may be helpful in guiding antimicrobial therapy and recently administered antimicrobials should be avoided when empirically selecting antimicrobials. Although no relationship was found between inappropriate initial empiric antimicrobial selection and length of hospital stay or mortality, future prospective studies using standardized airway-sampling techniques, treatment modalities, and stratification of disease severity based on objective values, such as arterial blood gas analysis in all dogs with pneumonia, would be needed to determine if a clinical effect of in vitro bacterial resistance to empirically administered antimicrobials truly exists or not. © Veterinary Emergency and Critical Care Society 2013.
Bacterial Pneumonia in Patients with Cancer: Novel Risk Factors and Management.
Wong, Justin L; Evans, Scott E
2017-06-01
Bacterial pneumonias exact unacceptable morbidity on patients with cancer. Although the risk is often most pronounced among patients with treatment-induced cytopenias, the numerous contributors to life-threatening pneumonias in cancer populations range from derangements of lung architecture and swallow function to complex immune defects associated with cytotoxic therapies and graft-versus-host disease. These structural and immunologic abnormalities often make the diagnosis of pneumonia challenging in patients with cancer and impact the composition and duration of therapy. This article addresses host factors that contribute to pneumonia susceptibility, summarizes diagnostic recommendations, and reviews current guidelines for management of bacterial pneumonia in patients with cancer. Copyright © 2016 Elsevier Inc. All rights reserved.
Pneumonia in the surgical intensive care unit: is every one preventable?
Wahl, Wendy L; Zalewski, Christy; Hemmila, Mark R
2011-10-01
Pneumonia is a major complication for hospitalized patients and has come under the scrutiny of health care regulating bodies, which propose that hospital-acquired pneumonia should not be reimbursed and potentially be a "never event." We hypothesized that many of our acutely injured patients develop pneumonia at the time of their initial traumatic event despite aggressive measures to prevent pneumonia during hospitalization. This retrospective review included all mechanically ventilated patients admitted to a mixed surgical intensive care units (ICU; trauma, general surgery, and burns) who developed pneumonia from 2006 to 2008. All pneumonia diagnosed by culture were obtained from bronchoalveolar lavage (BAL) specimens with ≥ 10(4) colony forming united (CFU)/mL considered a positive result. Criteria for ventilator-associated pneumonia (VAP) applied only to those patients ventilated mechanically for >48 hours at the time of a positive BAL culture. Aspiration organisms included Streptococcus species, methicillin-sensitive Staphylococcus aureus, Haemophilus influenzae, and oral flora. This was an institutional review board-approved study. There were 208 mechanically ventilated who patients underwent BAL, half of which were performed in the first 48 hours after admission for fever, infiltrate on chest radiograph, or increasing white blood cell count (early BAL group). Of these patients, 58% had positive BAL cultures (pneumonia) but did not have VAP. Only 10% of patients studied with early BAL had no growth on culture. Although the predominant organisms in the early BAL group were aspiration-type organisms, 17% had resistant pathogens, and 16% had other Gram-negative rods (GNR). This percentage was compared with the VAP group in whom 33% of patients had resistant organisms (P = .04) and 8% other GNR (P = NS). Twenty-five patients with ≤ 10(4) CFU/mL on early BAL underwent repeat BAL, and 16 (64%) were later diagnosed with VAP. Many intubated patients in the surgical ICU had evidence of early pneumonia or bacterial growth within 48 hours after arrival, suggesting early infection or colonization occurred before ICU admission. In addition, 33% with early bacterial growth on early BAL had resistant organisms or GNR on BAL culture, which suggests a patient-derived rather than environmentally acquired source. Copyright © 2011 Mosby, Inc. All rights reserved.
Hong, Hyo-Lim; Kim, Sung-Han; Huh, Jin Won; Sung, Heungsup; Lee, Sang-Oh; Kim, Mi-Na; Jeong, Jin-Yong; Lim, Chae-Man; Kim, Yang Soo; Woo, Jun Hee; Koh, Younsuck
2014-01-01
Background The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. Methods BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis. Results Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960). BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis. Conclusions Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients. PMID:24824328
Chochua, Sopio; D'Acremont, Valérie; Hanke, Christiane; Alfa, David; Shak, Joshua; Kilowoko, Mary; Kyungu, Esther; Kaiser, Laurent; Genton, Blaise; Klugman, Keith P; Vidal, Jorge E
2016-01-01
We assessed nasopharyngeal (NP) carriage of five pathogens in febrile children with and without acute respiratory infection (ARI) of the upper (URTI) or lower tract, attending health facilities in Tanzania. NP swabs collected from children (N = 960) aged 2 months to 10 years, and with a temperature ≥38°C, were utilized to quantify bacterial density of S. pneumoniae (Sp), H. influenzae (Hi), M. catarrhalis (Mc), S. aureus (Sa), and N. meningitidis (Nm). We determined associations between presence of individual species, densities, or concurrent carriage of all species combination with respiratory diseases including clinical pneumonia, pneumonia with normal chest radiography (CXR) and endpoint pneumonia. Individual carriage, and NP density, of Sp, Hi, or Mc, but not Sa, or Nm, was significantly associated with febrile ARI and clinical pneumonia when compared to febrile non-ARI episodes. Density was also significantly increased in severe pneumonia when compared to mild URTI (Sp, p<0.002; Hi p<0.001; Mc, p = 0.014). Accordingly, concurrent carriage of Sp+, Hi+, and Mc+, in the absence of Sa- and Nm-, was significantly more prevalent in children with ARI (p = 0.03), or clinical pneumonia (p<0.001) than non-ARI, and in children with clinical pneumonia (p = 0.0007) than URTI. Furthermore, Sp+, Hi+, and Mc+ differentiated children with pneumonia with normal CXR, or endpoint pneumonia, from those with URTI, and non-ARI cases. Concurrent NP carriage of Sp, Hi, and Mc was a predictor of clinical pneumonia and identified children with pneumonia with normal CXR and endpoint pneumonia from those with febrile URTI, or non-ARI episodes.
2016-01-01
Background We assessed nasopharyngeal (NP) carriage of five pathogens in febrile children with and without acute respiratory infection (ARI) of the upper (URTI) or lower tract, attending health facilities in Tanzania. Methods NP swabs collected from children (N = 960) aged 2 months to 10 years, and with a temperature ≥38°C, were utilized to quantify bacterial density of S. pneumoniae (Sp), H. influenzae (Hi), M. catarrhalis (Mc), S. aureus (Sa), and N. meningitidis (Nm). We determined associations between presence of individual species, densities, or concurrent carriage of all species combination with respiratory diseases including clinical pneumonia, pneumonia with normal chest radiography (CXR) and endpoint pneumonia. Results Individual carriage, and NP density, of Sp, Hi, or Mc, but not Sa, or Nm, was significantly associated with febrile ARI and clinical pneumonia when compared to febrile non-ARI episodes. Density was also significantly increased in severe pneumonia when compared to mild URTI (Sp, p<0.002; Hi p<0.001; Mc, p = 0.014). Accordingly, concurrent carriage of Sp+, Hi+, and Mc+, in the absence of Sa- and Nm-, was significantly more prevalent in children with ARI (p = 0.03), or clinical pneumonia (p<0.001) than non-ARI, and in children with clinical pneumonia (p = 0.0007) than URTI. Furthermore, Sp+, Hi+, and Mc+ differentiated children with pneumonia with normal CXR, or endpoint pneumonia, from those with URTI, and non-ARI cases. Conclusions Concurrent NP carriage of Sp, Hi, and Mc was a predictor of clinical pneumonia and identified children with pneumonia with normal CXR and endpoint pneumonia from those with febrile URTI, or non-ARI episodes. PMID:27907156
Influenza-associated bacterial pneumonia; managing and controlling infection on two fronts.
Campigotto, Aaron; Mubareka, Samira
2015-01-01
Bacterial pneumonia complicating influenza is well-recognized as a severe manifestation of influenza, accounting for a substantial number of deaths from the 1918 influenza pandemic. Influenza-associated bacterial pneumonia remains a major contributor to the burden of influenza, and poses new challenges as antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus spread. We provide an overview of the current state of knowledge of the epidemiology and co-pathogenesis of influenza-associated bacterial pneumonia, and outline management approaches and their limitations. We review preventative measures and discuss implications for pandemic planning. Knowledge gaps are underscored and future research directions are proposed.
21 CFR 520.2345d - Tetracycline powder.
Code of Federal Regulations, 2010 CFR
2010-04-01
... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia associated with Pasteurella spp., A... Mycoplasma gallisepticum and E. coli; control of infectious synovitis caused by M. synoviae susceptible to... of bacterial enteritis (scours) caused by Escherichia coli and bacterial pneumonia (shipping fever...
21 CFR 520.2345d - Tetracycline powder.
Code of Federal Regulations, 2011 CFR
2011-04-01
... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia associated with Pasteurella spp., A... gallisepticum and E. coli; control of infectious synovitis caused by M. synoviae susceptible to tetracycline.... Control and treatment of bacterial enteritis (scours) caused by Escherichia coli and bacterial pneumonia...
21 CFR 520.443 - Chlortetracycline tablets and boluses.
Code of Federal Regulations, 2013 CFR
2013-04-01
... enteritis (scours) caused by Escherichia coli and bacterial pneumonia associated with Pasteurella spp.... coli and Salmonella spp. and bacterial pneumonia associated with Pasteurella spp., Hemophilus spp., and... pneumonia associated with Pasteurella spp., Hemophilus spp., and Klebsiella spp., susceptible to...
21 CFR 520.443 - Chlortetracycline tablets and boluses.
Code of Federal Regulations, 2014 CFR
2014-04-01
... enteritis (scours) caused by Escherichia coli and bacterial pneumonia associated with Pasteurella spp.... coli and Salmonella spp. and bacterial pneumonia associated with Pasteurella spp., Hemophilus spp., and... pneumonia associated with Pasteurella spp., Hemophilus spp., and Klebsiella spp., susceptible to...
Code of Federal Regulations, 2013 CFR
2013-04-01
... Echerichia coli and bacterial pneumonia caused by Pasteurella multocida organisms susceptible to... improved feed efficiency and increased rate of weight gain; and for control of bacterial pneumonia... pneumonia caused by P. multocida organisms susceptible to chlortetracycline. Feed continuously at a rate of...
21 CFR 558.630 - Tylosin and sulfamethazine.
Code of Federal Regulations, 2013 CFR
2013-04-01
... dysentery (vibrionic); control of swine pneumonias caused by bacterial pathogens (Pasteurella multocida and... dysentery (vibrionic); control of swine pneumonias caused by bacterial pathogens (Pasteurella multocida and...; prevention of swine dysentery associated with Brachyspira hyodysenteriae; and control of swine pneumonias...
Code of Federal Regulations, 2014 CFR
2014-04-01
... Echerichia coli and bacterial pneumonia caused by Pasteurella multocida organisms susceptible to... improved feed efficiency and increased rate of weight gain; and for control of bacterial pneumonia... pneumonia caused by P. multocida organisms susceptible to chlortetracycline. Feed continuously at a rate of...
21 CFR 520.443 - Chlortetracycline tablets and boluses.
Code of Federal Regulations, 2012 CFR
2012-04-01
... enteritis (scours) caused by Escherichia coli and bacterial pneumonia associated with Pasteurella spp.... coli and Salmonella spp. and bacterial pneumonia associated with Pasteurella spp., Hemophilus spp., and... pneumonia associated with Pasteurella spp., Hemophilus spp., and Klebsiella spp., susceptible to...
21 CFR 558.630 - Tylosin and sulfamethazine.
Code of Federal Regulations, 2014 CFR
2014-04-01
... dysentery (vibrionic); control of swine pneumonias caused by bacterial pathogens (Pasteurella multocida and... dysentery (vibrionic); control of swine pneumonias caused by bacterial pathogens (Pasteurella multocida and...; prevention of swine dysentery associated with Brachyspira hyodysenteriae; and control of swine pneumonias...
Code of Federal Regulations, 2012 CFR
2012-04-01
... Echerichia coli and bacterial pneumonia caused by Pasteurella multocida organisms susceptible to... improved feed efficiency and increased rate of weight gain; and for control of bacterial pneumonia... pneumonia caused by P. multocida organisms susceptible to chlortetracycline. Feed continuously at a rate of...
[Community acquired bacterial pneumonia and comorbidity in elderly patients].
Fatenkov, O V; Kuzmina, T M; Rubanenko, O A; Svetlova, G N; Djubailo, A V
2017-01-01
We analyzed the clinical course of pneumonia in 67 elderly patients (39 females and 28 males, mean age 74,4±5,2 years) with chronic heart failure and chronic obstructive pulmonary disease (COPD). Patients were divided into 2 groups: 1st group - patients with COPD, 2nd group - patients without COPD. Pharmacological treatment was performed according to temperature, oxygen saturation, acute phase proteins and included ampicillin and sulbactam. The normalization of temperature and oxygen saturation was observed on 3-4 day in patients of the 1st group and on 2 day in patients of the 2nd group, normalization of leukocyte count and erythrocyte sedimentation rate - on 12-13 and 7-8 days, acute phase indicators (C-reactive protein, fibrinogen) on 7 and 5 days, correspondingly. Positive dynamics of chest X-ray was observed on 13 day in patients of the 1st group (the second control and the replacement of antibiotic for levofloxacin) and on 8 day in patients of the 2nd group (the first control).
2014-01-01
Background Acute interstitial pneumonia is a rare interstitial lung disease that rapidly progresses to respiratory failure or death. Several studies showed that myofibroblast plays an important role in the evolution of diffuse alveolar damage, which is the typical feature of acute interstitial pneumonia. However, no evidence exists whether alveolar epithelial cells are an additional source of myofibroblasts via epithelial-mesenchymal transition in acute interstitial pneumonia. Case presentation In this report, we present a case of acute interstitial pneumonia in a previously healthy 28-year-old non-smoking woman. Chest high-resolution computed tomography scan showed bilateral and diffusely ground-glass opacification. The biopsy was performed on the fifth day of her hospitalization, and results showed manifestation of acute exudative phase of diffuse alveolar damage characterized by hyaline membrane formation. On the basis of the preliminary diagnosis of acute interstitial pneumonia, high-dose glucocorticoid was used. However, this drug showed poor clinical response and could improve the patient’s symptoms only during the early phase. The patient eventually died of respiratory dysfunction. Histological findings in autopsy were consistent with the late form of acute interstitial pneumonia. Conclusions The results in this study revealed that alveolar epithelial cells underwent epithelial-mesenchymal transition and may be an important origin of myofibroblasts in the progression of acute interstitial pneumonia. Conducting research on the transformation of alveolar epithelial cells into myofibroblasts in the lung tissue of patients with acute interstitial pneumonia may be beneficial for the treatment of this disease. However, to our knowledge, no research has been conducted on this topic. PMID:24755111
Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H
2016-09-07
Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged <1year, as well as weekly rates for pneumonia and AOM recorded in RENACE were estimated. After PCV introduction, we observed significant vaccine impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9-34.4) for AOM visits, 35% (95% CI 8.6-53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6-29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru. Copyright © 2016. Published by Elsevier Ltd.
Pfaller, Michael A; Jones, Ronald N
2002-09-01
Recently FDA-approved fluoroquinolones like gatifloxacin possess enhanced activity against Gram-positive pathogens such as Streptococcus pneumoniae. However, experience with adverse events among previously used fluoroquinolones has led to expanded post-marketing investigations of clinical efficacy and safety. An open-label gatifloxacin trial was initiated in early 2000, using 2795 (>15000 enrolled cases) primary care providers for treatment of community-acquired respiratory tract infections (CARTI) such as community-acquired pneumonia (CAP), acute bacterial exacerbation of chronic bronchitis (ABECB), acute sinusitis. Microbiology specimens and sputum slides were referred to a reference laboratory, pathogens identified and reference antimicrobial susceptibility tests performed. Results were classified by infection site, geographic census region and patient profile/demographics. The most frequent pathogens were: for CAP (n = 384)-S. pneumoniae (37%) > Hemophilus influenzae (31%) > Moraxella catarrhalis (13%); for ABECB (528)-H. influenzae (37%) > M. catarrhalis (26%) > S. pneumoniae (17%); and for sinusitis (2691)-M. catarrhalis (29%) > H. influenzae (24%) > S. pneumoniae (17%). H. parainfluenzae (ABECB) and S. aureus (sinusitis) were also commonly isolated. CAP S. pneumoniae isolates had significantly less high-level resistance (5% at > or =2 micro g/ml) than those isolates from ABECB or sinusitis (13-15%). United States census zone differences in S. pneumoniae resistance were identified (greatest in West or East South Central, South Atlantic). S. pneumoniae macrolide resistance was high (23-33%) and H. influenzae clarithromycin susceptibility was only 56-62%. beta-lactamase rates in H. influenzae and M. catarrhalis were 21-29% and 88-92%, respectively. Only one S. pneumoniae was not susceptible to gatifloxacin, and this new fluoroquinolone was fourfold more potent than levofloxacin (MIC(50,) 0.25 vs. 1 micro g/ml). This Phase IV surveillance trial (TeqCES) confirmed the clinical importance of S. pneumoniae, H. influenzae and M. catarrhalis in CARTI, and high fluoroquinolone potency/spectrum (>97% susceptible). beta-lactams and macrolides continue to be compromised by increasing resistances in pathogens isolated in these monitored primary care settings.
Akata, Kentaro; Yatera, Kazuhiro; Yamasaki, Kei; Kawanami, Toshinori; Naito, Keisuke; Noguchi, Shingo; Fukuda, Kazumasa; Ishimoto, Hiroshi; Taniguchi, Hatsumi; Mukae, Hiroshi
2016-05-11
Aspiration pneumonia has been a growing interest in an aging population. Anaerobes are important pathogens, however, the etiology of aspiration pneumonia is not fully understood. In addition, the relationship between the patient clinical characteristics and the causative pathogens in pneumonia patients with aspiration risk factors are unclear. To evaluate the relationship between the patient clinical characteristics with risk factors for aspiration and bacterial flora in bronchoalveolar lavage fluid (BALF) in pneumonia patients, the bacterial floral analysis of 16S ribosomal RNA gene was applied in addition to cultivation methods in BALF samples. From April 2010 to February 2014, BALF samples were obtained from the affected lesions of pneumonia via bronchoscopy, and were evaluated by the bacterial floral analysis of 16S rRNA gene in addition to cultivation methods in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). Factors associated with aspiration risks in these patients were analyzed. A total of 177 (CAP 83, HCAP 94) patients were enrolled. According to the results of the bacterial floral analysis, detection rate of oral streptococci as the most detected bacterial phylotypes in BALF was significantly higher in patients with aspiration risks (31.0 %) than in patients without aspiration risks (14.7 %) (P = 0.009). In addition, the percentages of oral streptococci in each BALF sample were significantly higher in patients with aspiration risks (26.6 ± 32.0 %) than in patients without aspiration risks (13.8 ± 25.3 %) (P = 0.002). A multiple linear regression analysis showed that an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≥3, the presence of comorbidities, and a history of pneumonia within a previous year were significantly associated with a detection of oral streptococci in BALF. The bacterial floral analysis of 16S rRNA gene revealed that oral streptococci were mostly detected as the most detected bacterial phylotypes in BALF samples in CAP and HCAP patients with aspiration risks, especially in those with a poor ECOG-PS or a history of pneumonia.
Wagner, Karoline; Springer, Burkard; Pires, Valeria P.
2017-01-01
ABSTRACT Acute bacterial meningitis is a medical emergency, and delays in initiating effective antimicrobial therapy result in increased morbidity and mortality. Culture-based methods, thus far considered the “gold standard” for identifying bacterial microorganisms, require 24 to 48 h to provide a diagnosis. In addition, antimicrobial therapy is often started prior to clinical sample collection, thereby decreasing the probability of confirming the bacterial pathogen by culture-based methods. To enable a fast and accurate detection of the most important bacterial pathogens causing meningitis, namely, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Streptococcus agalactiae, and Listeria monocytogenes, we evaluated a commercially available multiplex LightMix real-time PCR (RT-PCR) in 220 cerebrospinal fluid (CSF) specimens. The majority of CSF samples were collected by lumbar puncture, but we also included some CSF samples from patients with symptoms of meningitis from the neurology department that were recovered from shunts. CSF samples were analyzed by multiplex RT-PCR enabling a first diagnosis within a few hours after sample arrival at our institute. In contrast, bacterial identification took between 24 and 48 h by culture. Overall, a high agreement of bacterial identification between culture and multiplex RT-PCR was observed (99%). Moreover, multiplex RT-PCR enabled the detection of pathogens, S. pneumoniae (n = 2), S. agalactiae (n = 1), and N. meningitidis (n = 1), in four culture-negative samples. As a complement to classical bacteriological CSF culture, the LightMix RT-PCR assay proved to be valuable by improving the rapidity and accuracy of the diagnosis of bacterial meningitis. PMID:29237781
Bettina, Alexandra; Zhang, Zhimin; Michels, Kathryn; Cagnina, R Elaine; Vincent, Isaah S; Burdick, Marie D; Kadl, Alexandra; Mehrad, Borna
2016-06-15
Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells, and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. M-CSF has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden, and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, proliferation of precursors, or recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and antimicrobial functions of both lung and liver mononuclear phagocytes during pneumonia, and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and antimicrobial functions of mononuclear phagocytes in the lungs and liver. Copyright © 2016 by The American Association of Immunologists, Inc.
Bettina, Alexandra; Zhang, Zhimin; Michels, Kathryn; Cagnina, R. Elaine; Vincent, Isaah S.; Burdick, Marie D.; Kadl, Alexandra; Mehrad, Borna
2016-01-01
Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. Macrophage-colony stimulating factor (M-CSF) has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, the proliferation of precursors or the recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and anti-microbial functions of both lung and liver mononuclear phagocytes during pneumonia and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and anti-microbial functions of mononuclear phagocytes in the lungs and liver. PMID:27183631
Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Kuo, Li-Li; Lin, Hsi-Hsun; Chen, Yen-Hsu
2013-01-01
Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia.
Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Kuo, Li-Li; Lin, Hsi-Hsun; Chen, Yen-Hsu
2013-01-01
Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia. PMID:24147043
Should nursing home-acquired pneumonia be treated as nosocomial pneumonia?
Ma, Hon Ming; Wah, Jenny Lee Shun; Woo, Jean
2012-10-01
It is contentious whether nursing home-acquired pneumonia (NHAP) should be treated as community-acquired pneumonia (CAP) or health care-associated pneumonia. This study aimed to compare NHAP with CAP, and to examine whether multidrug-resistant (MDR) bacteria were significantly more common in NHAP than CAP. A prospective, observational cohort study The medical unit of a tertiary teaching hospital Patients 65 years and older, hospitalized for CAP and NHAP confirmed by radiographs from October 2009 to September 2010 Demographic characteristics, Katz score, Charlson comorbidity index (CCI), pneumonia severity (CURB score), microbiology, and clinical outcomes were measured. A total of 488 patients were recruited and 116 (23.8%) patients were nursing home residents. Compared with patients with CAP, patients with NHAP were older and had more comorbidities and higher functional dependence level. A larger proportion of patients with NHAP had severe pneumonia (CURB ≥2) than patients with CAP (30.2% vs 20.7%, P = .034). Similar percentages of patients had identified infective causes in the CAP and NHAP groups (27.7% vs 29.3%, P = .734). Viral infection accounted for more than half (55.9%) of NHAP, whereas bacterial infection was the most frequent (69.9%) cause of CAP. MDR bacteria were found in 6 patients of all study subjects. Nursing home residence and history of MDR bacterial infection were risk factors for MDR bacterial pneumonia, which had more severe pneumonia (CURB ≥2). Logistic regression analysis was limited by the small number of patients with MDR bacterial pneumonia. In both CAP and NHAP, MDR bacterial infections were uncommon. Most cases of NHAP were caused by unknown etiology or viral pathogens. We suggest that NHAP should not be treated as nosocomial infection. The empirical treatment of broad-spectrum antibiotics in NHAP should be reserved for patients with severe pneumonia or at high risk of MDR bacterial infection. Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.
Draft Genome Sequence of a Virulent Strain of Pasteurella Multocida Isolated From Alpaca
Hurtado, Raquel Enma; Aburjaile, Flavia; Mariano, Diego; Canário, Marcus Vinicius; Benevides, Leandro; Fernandez, Daniel Antonio; Allasi, Nataly Olivia; Rimac, Rocio; Juscamayta, Julio Eduardo; Maximiliano, Jorge Enrique; Rosadio, Raul Hector; Azevedo, Vasco; Maturrano, Lenin
2017-01-01
Pasteurella multocida is one of the most frequently isolated bacteria in acute pneumonia cases, being responsible for high mortality rates in Peruvian young alpacas, with consequent social and economic costs. Here we report the genome sequence of P. multocida strain UNMSM, isolated from the lung of an alpaca diagnosed with pneumonia, in Peru. The genome consists of 2,439,814 base pairs assembled into 82 contigs and 2,252 protein encoding genes, revealing the presence of known virulence-associated genes (ompH, ompA, tonB, tbpA, nanA, nanB, nanH, sodA, sodC, plpB and toxA). Further analysis could provide insights about bacterial pathogenesis and control strategies of this disease in Peruvian alpacas. PMID:28698737
Epizootic pneumonia of bighorn sheep following experimental exposure to Mycoplasma ovipneumoniae.
Besser, Thomas E; Cassirer, E Frances; Potter, Kathleen A; Lahmers, Kevin; Oaks, J Lindsay; Shanthalingam, Sudarvili; Srikumaran, Subramaniam; Foreyt, William J
2014-01-01
Bronchopneumonia is a population limiting disease of bighorn sheep (Ovis canadensis). The cause of this disease has been a subject of debate. Leukotoxin expressing Mannheimia haemolytica and Bibersteinia trehalosi produce acute pneumonia after experimental challenge but are infrequently isolated from animals in natural outbreaks. Mycoplasma ovipneumoniae, epidemiologically implicated in naturally occurring outbreaks, has received little experimental evaluation as a primary agent of bighorn sheep pneumonia. In two experiments, bighorn sheep housed in multiple pens 7.6 to 12 m apart were exposed to M. ovipneumoniae by introduction of a single infected or challenged animal to a single pen. Respiratory disease was monitored by observation of clinical signs and confirmed by necropsy. Bacterial involvement in the pneumonic lungs was evaluated by conventional aerobic bacteriology and by culture-independent methods. In both experiments the challenge strain of M. ovipneumoniae was transmitted to all animals both within and between pens and all infected bighorn sheep developed bronchopneumonia. In six bighorn sheep in which the disease was allowed to run its course, three died with bronchopneumonia 34, 65, and 109 days after M. ovipneumoniae introduction. Diverse bacterial populations, predominantly including multiple obligate anaerobic species, were present in pneumonic lung tissues at necropsy. Exposure to a single M. ovipneumoniae infected animal resulted in transmission of infection to all bighorn sheep both within the pen and in adjacent pens, and all infected sheep developed bronchopneumonia. The epidemiologic, pathologic and microbiologic findings in these experimental animals resembled those seen in naturally occurring pneumonia outbreaks in free ranging bighorn sheep.
Han, Seung Beom; Lee, Sung Chul; Lee, Soo Young; Jeong, Dae Chul; Kang, Jin Han
2015-10-13
The rate of urinary tract infections (UTIs) due to extended-spectrum β-lactamase (ESBL)-producing bacterial strains requiring carbapenem therapy has been increasing in children. This study was conducted to evaluate the effect of non-carbapenem antibiotic therapy on childhood UTIs caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae. Medical records of children diagnosed with febrile UTIs due to E. coli or K. pneumoniae between 2010 and 2014 were retrospectively reviewed. The enrolled children were divided into two groups: the ESBL group and the non-ESBL group. Clinical characteristics and therapeutic responses were compared between the two groups. A total of 211 episodes of UTI (204 caused by E. coli; seven caused by K. pneumoniae) were identified in 205 children. Twenty-two (10.4 %) episodes were categorized into the ESBL group. There was no significant difference in the type of antibiotic administered between the two groups. No carbapenems were administered; however, aminoglycosides were administered for 79.1 % of the total episodes. Although empirical antibiotics were appropriate for more episodes in the non-ESBL group compared with the ESBL group (100.0 % vs. 90.9 %, p = 0.011), there were no significant differences in the frequency of defervescence, bacterial eradication from the urine, acute pyelonephritis and vesicoureteral reflux or fever duration between the two groups. Non-carbapenem antibiotics showed favourable therapeutic effects on childhood UTIs caused by ESBL-producing strains. Aminoglycosides can be an alternative to carbapenems in such cases.
Wei, Lan; Liu, Wei; Zhang, Xiao-Ai; Liu, En-Mei; Wo, Yin; Cowling, Benjamin J.; Cao, Wu-Chun
2015-01-01
Abstract Acute respiratory infections (ARIs) cause large disease burden each year. The codetection of viral and bacterial pathogens is quite common; however, the significance for clinical severity remains controversial. We aimed to identify viruses and bacteria in hospitalized children with ARI and the impact of mixed detections. Hospitalized children with ARI aged ≤16 were recruited from 2009 to 2013 at the Children's Hospital of Chongqing Medical University, Chongqing, China. Nasopharyngeal aspirates (NPAs) were collected for detection of common respiratory viruses by reverse transcription polymerase chain reaction (RT-PCR) or PCR. Bacteria were isolated from NPAs by routine culture methods. Detection and codetection frequencies and clinical features and severity were compared. Of the 3181 hospitalized children, 2375 (74.7%) were detected with ≥1 virus and 707 (22.2%) with ≥1 bacteria, 901 (28.3%) with ≥2 viruses, 57 (1.8%) with ≥2 bacteria, and 542 (17.0%) with both virus and bacteria. The most frequently detected were Streptococcus pneumoniae, respiratory syncytial virus, parainfluenza virus, and influenza virus. Clinical characteristics were similar among different pathogen infections for older group (≥6 years old), with some significant difference for the younger. Cases with any codetection were more likely to present with fever; those with ≥2 virus detections had higher prevalence of cough; cases with virus and bacteria codetection were more likely to have cough and sputum. No significant difference in the risk of pneumonia, severe pneumonia, and intensive care unit admission were found for any codetection than monodetection. There was a high codetection rate of common respiratory pathogens among hospitalized pediatric ARI cases, with fever as a significant predictor. Cases with codetection showed no significant difference in severity than those with single pathogens. PMID:25906103
Szaba, Frank M; Kummer, Lawrence W; Duso, Debra K; Koroleva, Ekaterina P; Tumanov, Alexei V; Cooper, Andrea M; Bliska, James B; Smiley, Stephen T; Lin, Jr-Shiuan
2014-05-01
Septic pneumonias resulting from bacterial infections of the lung are a leading cause of human death worldwide. Little is known about the capacity of CD8 T cell-mediated immunity to combat these infections and the types of effector functions that may be most effective. Pneumonic plague is an acutely lethal septic pneumonia caused by the Gram-negative bacterium Yersinia pestis. We recently identified a dominant and protective Y. pestis antigen, YopE69-77, recognized by CD8 T cells in C57BL/6 mice. Here, we use gene-deficient mice, Ab-mediated depletion, cell transfers, and bone marrow chimeric mice to investigate the effector functions of YopE69-77-specific CD8 T cells and their relative contributions during pulmonary Y. pestis infection. We demonstrate that YopE69-77-specific CD8 T cells exhibit perforin-dependent cytotoxicity in vivo; however, perforin is dispensable for YopE69-77-mediated protection. In contrast, YopE69-77-mediated protection is severely impaired when production of TNFα and IFNγ by CD8 T cells is simultaneously ablated. Interestingly, TNFα is absolutely required at the time of challenge infection and can be provided by either T cells or non-T cells, whereas IFNγ provided by T cells prior to challenge appears to facilitate the differentiation of optimally protective CD8 T cells. We conclude that cytokine production, not cytotoxicity, is essential for CD8 T cell-mediated control of pulmonary Y. pestis infection and we suggest that assays detecting Ag-specific TNFα production in addition to antibody titers may be useful correlates of vaccine efficacy against plague and other acutely lethal septic bacterial pneumonias.
CD8+ T cells and Risk for Bacterial Pneumonia and All-Cause Mortality Among HIV-infected Women
Gohil, Shruti; Heo, Moonseong; Schoenbaum, Ellie; Celentano, David; Pirofski, Liise-anne
2012-01-01
Background Bacterial pneumonia risk is disproportionately high among those infected with Human Immunodeficiency Virus (HIV). This risk is present across all CD4+ T cell levels (TCL), suggesting additional factors govern susceptibility. This study examines CD8+ TCL and risk for HIV-associated bacterial pneumonia and all-cause mortality. Methods Demographic, clinical, and laboratory data were obtained for 885 HIV-infected (HIV+) women enrolled in the HIV Epidemiologic Research Study (HERS). Bacterial pneumonia cases were identified using clinical, microbiologic, and radiographic criteria. CD8+ TCLs were assessed at 6-month intervals. Statistical methods included Cox proportional hazards regression modeling and covariate-adjusted survival estimates. Results Relative to a referent CD8+ TCL 401–800 cells/mm3, risk for bacterial pneumonia was significantly higher when CD8+ TCLs were ≤ 400 (hazard ratio 1.65, p=0.017, 95% CI 1.10–2.49), after adjusting for age, CD4+ TCL, viral load, and antiretroviral use. There was also a significantly higher risk of death when CD8+ TCLs were ≤ 400 cells/mm3 (hazard ratio 1.45, p=0.04, 95% CI 1.02–2.06). Covariate-adjusted survival estimates revealed shorter time to pneumonia and death in this CD8+ TCL category and the overall association of the categorized CD8+TCL with bacterial pneumonia and all-cause mortality were each statistically significant (p=0.017 and p<0.0001, respectively). Conclusions CD8+ TCL ≤ 400 cells/mm3 was associated with increased risk for pneumonia and all-cause mortality in HIV-infected women in the HERS Cohort, suggesting that CD8+ TCL could serve as an adjunctive biomarker of pneumonia risk and mortality in HIV-infected individuals. PMID:22334070
Cuomo, Gianluca; Brancaccio, Giuseppina; Stornaiuolo, Gianfranca; Manno, Daniela; Gaeta, Giuseppe L; Mussini, Cristina; Puoti, Massimo; Gaeta, Giovanni B
2018-02-01
Introducion: Bacterial infections frequently complicate liver cirrhosis. The aim of this study was to identify risk factors and clinical impact of bacterial pneumonia in patients with cirrhosis. Bacterial infection prevalence study: consecutive patients with cirrhosis were enroled over a six-month period in 13 Italian centres. Pneumonia and other infections were diagnosed by standard methods. Pneumonia study: cirrhotic patients with pneumonia were enroled for an additional six-month period and HIV-positive patients were included. Pneumonia was the fourth most frequent infection. In the two parts of the study, 79 cases of pneumonia were recorded and 441 patients with cirrhosis without infections served as controls. Seventy-eight patients had extra-pulmonary infections. There were no clinical differences between HIV-negative and -positive cases with pneumonia. Previous gastro-intestinal bleeding (p = .02) and long-term prophylactic antibiotic use (p < .0001) were associated with pneumonia. Hospital stay was longer and renal failure more frequent than in patients without infections. Pneumonia was hospital acquired (HAP) in 6 cases, healthcare associated (HCAP) in 24 and community acquired (CAP) in 28. A new category of antibiotic prophylaxis associated pneumonia (APAP) was proposed for 21 cases. Cultures were positive in 21/79 patients (26.6%) with Gram-positive isolates in 57%. Unfavourable outcomes were recorded in 11.4% of the cases (3.6% of CAP, 33% of HAP, 12.5% of HCAP and 14.3% of APAP). Receiving antibiotic prophylaxis was associated with pneumonia and the study identified a new sub-group of patients, who require broad spectrum initial antibiotic therapy.
21 CFR 522.313b - Ceftiofur hydrochloride.
Code of Federal Regulations, 2010 CFR
2010-04-01
... bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae... treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia...
Tyk2 as a target for immune regulation in human viral/bacterial pneumonia.
Berg, Johanna; Zscheppang, Katja; Fatykhova, Diana; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Eggeling, Stephan; Schimek, Maria; Gruber, Achim D; Suttorp, Norbert; Hippenstiel, Stefan; Hocke, Andreas C
2017-07-01
The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory options are lacking.We established a human lung ex vivo co-infection model to investigate innate immune related mechanisms contributing to the susceptibility of secondary pneumococcal pneumonia.We revealed that type I and III interferon (IFN) inhibits Streptococcus pneumoniae -induced interleukin (IL)-1β release. The lack of IL-1β resulted in the repression of bacterially induced granulocyte-macrophage colony-stimulating factor (GM-CSF) liberation. Specific inhibition of IFN receptor I and III-associated tyrosine kinase 2 (Tyk2) completely restored the S. pneumoniae -induced IL-1β-GM-CSF axis, leading to a reduction of bacterial growth. A preceding IAV infection of the human alveolus leads to a type I and III IFN-dependent blockade of the early cytokines IL-1β and GM-CSF, which are key for orchestrating an adequate innate immune response against bacteria. Their virally induced suppression may result in impaired bacterial clearance and alveolar repair.Pharmacological inhibition of Tyk2 might be a new treatment option to sustain beneficial endogenous GM-CSF levels in IAV-associated secondary bacterial pneumonia. Copyright ©ERS 2017.
Population-based surveillance for bacterial meningitis in China, September 2006-December 2009.
Li, Yixing; Yin, Zundong; Shao, Zhujun; Li, Manshi; Liang, Xiaofeng; Sandhu, Hardeep S; Hadler, Stephen C; Li, Junhong; Sun, Yinqi; Li, Jing; Zou, Wenjing; Lin, Mei; Zuo, Shuyan; Mayer, Leonard W; Novak, Ryan T; Zhu, Bingqing; Xu, Li; Luo, Huiming
2014-01-01
During September 2006-December 2009, we conducted active population and sentinel laboratory-based surveillance for bacterial meningitis pathogens, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b, in 4 China prefectures. We identified 7,876 acute meningitis and encephalitis syndrome cases, including 6,388 among prefecture residents. A total of 833 resident cases from sentinel hospitals met the World Health Organization case definition for probable bacterial meningitis; 339 of these cases were among children <5 years of age. Laboratory testing confirmed bacterial meningitis in 74 of 3,391 tested cases. The estimated annual incidence (per 100,000 population) of probable bacterial meningitis ranged from 1.84 to 2.93 for the entire population and from 6.95 to 22.30 for children <5 years old. Active surveillance with laboratory confirmation has provided a population-based estimate of the number of probable bacterial meningitis cases in China, but more complete laboratory testing is needed to better define the epidemiology of the disease in this country.
Population-based Surveillance for Bacterial Meningitis in China, September 2006–December 2009
Li, Yixing; Yin, Zundong; Shao, Zhujun; Li, Manshi; Liang, Xiaofeng; Sandhu, Hardeep S.; Hadler, Stephen C.; Li, Junhong; Sun, Yinqi; Li, Jing; Zou, Wenjing; Lin, Mei; Zuo, Shuyan; Mayer, Leonard W.; Novak, Ryan T.; Zhu, Bingqing; Xu, Li
2014-01-01
During September 2006–December 2009, we conducted active population and sentinel laboratory–based surveillance for bacterial meningitis pathogens, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b, in 4 China prefectures. We identified 7,876 acute meningitis and encephalitis syndrome cases, including 6,388 among prefecture residents. A total of 833 resident cases from sentinel hospitals met the World Health Organization case definition for probable bacterial meningitis; 339 of these cases were among children <5 years of age. Laboratory testing confirmed bacterial meningitis in 74 of 3,391 tested cases. The estimated annual incidence (per 100,000 population) of probable bacterial meningitis ranged from 1.84 to 2.93 for the entire population and from 6.95 to 22.30 for children <5 years old. Active surveillance with laboratory confirmation has provided a population-based estimate of the number of probable bacterial meningitis cases in China, but more complete laboratory testing is needed to better define the epidemiology of the disease in this country. PMID:24377388
Jin, Xingnan; Zou, Yingxue; Zhai, Jia; Liu, Jie; Huang, Bing
2018-03-01
Mycoplasma pneumoniae pneumonia, a common cause of community-acquired pneumonia in children, is rarely complicated with acute cerebral infarction. We present a 7-year-old boy with severe M pneumoniae pneumonia who developed impaired consciousness, aphasia, and reduced limb muscle power 7 days postadmission. Mycoplasma pneumoniae pneumonia with concomitant acute cerebral infarction. The patient recovered with aggressive antibiotic therapy, antiinflammation therapy with methylprednisolone, and gamma immunoglobulin and anticoagulation therapy with aspirin and low molecular weight heparin along with rehabilitation training. At 8 days postadmission, his consciousness was improved and at the 6-month follow-up visit, his muscle power of bilateral upper and lower limbs was normal except still poor right handgrip power. Stroke or cerebral infarction should be considered and promptly managed in rare cases of M pneumoniae pneumonia with neurologic manifestations.
21 CFR 522.90a - Ampicillin trihydrate suspension.
Code of Federal Regulations, 2014 CFR
2014-04-01
... days. For pneumonia: 3 mg per pound of body weight, intramuscularly, twice daily, for up to 3 days. (ii... pneumonia caused by Pasteurella spp. susceptible to ampicillin. (iii) Limitations. Treated animals must not... for use. Treatment of bacterial enteritis (colibacillosis) caused by E. coli and bacterial pneumonia...
Elsayh, Khalid I; Sayed, Douaa M; Zahran, Asmaa M; Saad, Khaled; Badr, Gamal
2013-01-01
The aim of this study was to evaluate the effects of bacterial pneumonia and malnutrition on the frequency of micronuclei (MN) in peripheral blood of pediatric patients through flow cytometric analysis. The study was an analytical case-control study carried out on 35 malnourished children with bacterial pneumonia and 20 well-nourished children with bacterial pneumonia, in addition to 20 healthy children as controls. Complete physical examination including; anthropometric measurement, Chest roentgenograms were done for all cases. Assessment of MN was done by FACSCalibur flow cytometry. The frequency of micronucleated reticulocytes (MN-RETs) was higher both in the malnourished children with pneumonia and well-nourished children with pneumonia than the controls. Within the malnourished children with pneumonia, patients with kwashiorkor had more micronucleated mature erythrocytes (MN-RBCs) and MN-RETs than patients with marasmus. In conclusion: Pneumonia is associated with an increased frequency of MN and this increment is more pronounced in children with severe malnutrition especially kwashiorkor group. PMID:24260601
Rai, Prashant; Parrish, Marcus; Tay, Ian Jun Jie; Li, Na; Ackerman, Shelley; He, Fang; Kwang, Jimmy; Chow, Vincent T; Engelward, Bevin P
2015-06-30
Streptococcus pneumoniae is a leading cause of pneumonia and one of the most common causes of death globally. The impact of S. pneumoniae on host molecular processes that lead to detrimental pulmonary consequences is not fully understood. Here, we show that S. pneumoniae induces toxic DNA double-strand breaks (DSBs) in human alveolar epithelial cells, as indicated by ataxia telangiectasia mutated kinase (ATM)-dependent phosphorylation of histone H2AX and colocalization with p53-binding protein (53BP1). Furthermore, results show that DNA damage occurs in a bacterial contact-independent fashion and that Streptococcus pyruvate oxidase (SpxB), which enables synthesis of H2O2, plays a critical role in inducing DSBs. The extent of DNA damage correlates with the extent of apoptosis, and DNA damage precedes apoptosis, which is consistent with the time required for execution of apoptosis. Furthermore, addition of catalase, which neutralizes H2O2, greatly suppresses S. pneumoniae-induced DNA damage and apoptosis. Importantly, S. pneumoniae induces DSBs in the lungs of animals with acute pneumonia, and H2O2 production by S. pneumoniae in vivo contributes to its genotoxicity and virulence. One of the major DSBs repair pathways is nonhomologous end joining for which Ku70/80 is essential for repair. We find that deficiency of Ku80 causes an increase in the levels of DSBs and apoptosis, underscoring the importance of DNA repair in preventing S. pneumoniae-induced genotoxicity. Taken together, this study shows that S. pneumoniae-induced damage to the host cell genome exacerbates its toxicity and pathogenesis, making DNA repair a potentially important susceptibility factor in people who suffer from pneumonia.
Anderson, Ronald; Nel, Jan G; Feldman, Charles
2018-04-11
Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.
Detection of Bacterial Meningitis Pathogens by PCR-Mass Spectrometry in Cerebrospinal Fluid.
Jing-Zi, Piao; Zheng-Xin, He; Wei-Jun, Chen; Yong-Qiang, Jiang
2018-06-01
Acute bacterial meningitis remains a life-threatening infectious disease with considerable morbidity and mortality. DNA-based detection methods are an urgent requisite for meningitis-causing bacterial pathogens for the prevention of outbreaks and control of infections. We proposed a novel PCR-mass spectrometry (PCR-Mass) assay for the simultaneous detection of four meningitis-causing agents, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis in the present study. A total of 138 cerebrospinal fluid (CSF) samples (including 56 CSF culture positive, 44 CSF culture negative, and 38 CSF control) were enrolled and analyzed by PCR/Mass. Results were compared to real-time PCR detection. These four targeting pathogens could be discriminated without cross-reaction by the accurate detection of the corresponding extension products with different masses. The limits of detection were 102 copies/reaction for S. pneumoniae, H. influenzae, and N. meningitidis and 103 for M. tuberculosis. The evaluation of the culture-positive CSF specimens from the meningitis patients provided an overall agreement rate of 85.7% with PCR-Mass and real-time PCR. The PCR-Mass was also able to detect the targeting pathogens from culture-negative CSF specimens from meningitis patients receiving early antibiotic treatment. PCR-Mass could be used for the molecular detection of bacterial meningitis and tuberculosis, especially when early antibiotic treatment has been administered to the suspected patients.
del Valle-Mendoza, Juana; Orellana-Peralta, Fiorella; Marcelo-Rodríguez, Alvaro; Verne, Eduardo; Esquivel-Vizcarra, Mónica; Silva-Caso, Wilmer; Aguilar-Luis, Miguel Angel; Weilg, Pablo; Casabona-Oré, Verónica; Ugarte, Claudia; del Valle, Luis J.
2017-01-01
Background Mycoplasma pneumoniae and Chlamydia pneumoniae are atypical pathogens responsible for pneumonia and a leading cause of morbidity and mortality in low income countries. The study objective is to determine the prevalence of this pathogens in Peruvian children with acute respiratory infections. Methods A consecutive cross-sectional study was conducted in Lima, Peru from May 2009 to September 2010. A total of 675 children admitted with clinical diagnoses of acute respiratory infections were tested for Mycoplasma pneumoniae and Chlamydia pneumoniae detection by polymerase chain reaction (PCR), and clinical symptoms were registered by the attending physician. Results Mycoplasma pneumonia was detected in 25.19% (170/675) of nasopharyngeal samples and Chlamydia pneumonia in 10.52% (71/675). The most common symptoms in patients with these atypical pathogens were rhinorrhea, cough and fever. A higher prevalence of Mycoplasma pneumoniae cases were registered in summer, between December 2009 and March 2010. Conclusions Mycoplasma pneumoniae and Chlamydia pneumonia are a significant cause of morbidity in Peruvian children with acute respiratory infections (ARI). Further studies should evaluate the use of reliable techniques such as PCR in Peru in order to avoid underdiagnoses of these atypical pathogens. PMID:28129377
21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.
Code of Federal Regulations, 2014 CFR
2014-04-01
... enteritis caused by Salmonella typhimurium and Escherichia coli (colibacillosis) and bacterial pneumonia... Escherichia coli (colibacillosis) and bacterial pneumonia (shipping fever complex, pasteurellosis) caused by...
21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.
Code of Federal Regulations, 2012 CFR
2012-04-01
... enteritis caused by Salmonella typhimurium and Escherichia coli (colibacillosis) and bacterial pneumonia... Escherichia coli (colibacillosis) and bacterial pneumonia (shipping fever complex, pasteurellosis) caused by...
21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.
Code of Federal Regulations, 2013 CFR
2013-04-01
... enteritis caused by Salmonella typhimurium and Escherichia coli (colibacillosis) and bacterial pneumonia... Escherichia coli (colibacillosis) and bacterial pneumonia (shipping fever complex, pasteurellosis) caused by...
21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.
Code of Federal Regulations, 2011 CFR
2011-04-01
... enteritis caused by Salmonella typhimurium and Escherichia coli (colibacillosis) and bacterial pneumonia... Escherichia coli (colibacillosis) and bacterial pneumonia (shipping fever complex, pasteurellosis) caused by...
Marriott, Helen M; Daigneault, Marc; Thompson, Alfred A R; Walmsley, Sarah R; Gill, Sharonjit K; Witcher, Derrick R; Wroblewski, Victor J; Hellewell, Paul G; Whyte, Moira K B; Dockrell, David H
2012-11-01
Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection.
21 CFR 522.313b - Ceftiofur hydrochloride.
Code of Federal Regulations, 2013 CFR
2013-04-01
... treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with...) Indications for use. For treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated...
21 CFR 522.313b - Ceftiofur hydrochloride.
Code of Federal Regulations, 2012 CFR
2012-04-01
... treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with...) Indications for use. For treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated...
21 CFR 522.313b - Ceftiofur hydrochloride.
Code of Federal Regulations, 2011 CFR
2011-04-01
... treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with...) Indications for use. For treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated...
Dickson, Robert P; Erb-Downward, John R; Prescott, Hallie C; Martinez, Fernando J; Curtis, Jeffrey L; Lama, Vibha N; Huffnagle, Gary B
2014-10-01
The diagnosis and management of pneumonia are limited by the use of culture-based techniques of microbial identification, which may fail to identify unculturable, fastidious, and metabolically active viable but unculturable bacteria. Novel high-throughput culture-independent techniques hold promise but have not been systematically compared to conventional culture. We analyzed 46 clinically obtained bronchoalveolar lavage (BAL) fluid specimens from symptomatic and asymptomatic lung transplant recipients both by culture (using a clinical microbiology laboratory protocol) and by bacterial 16S rRNA gene pyrosequencing. Bacteria were identified in 44 of 46 (95.7%) BAL fluid specimens by culture-independent sequencing, significantly more than the number of specimens in which bacteria were detected (37 of 46, 80.4%, P ≤ 0.05) or "pathogen" species reported (18 of 46, 39.1%, P ≤ 0.0001) via culture. Identification of bacteria by culture was positively associated with culture-independent indices of infection (total bacterial DNA burden and low bacterial community diversity) (P ≤ 0.01). In BAL fluid specimens with no culture growth, the amount of bacterial DNA was greater than that in reagent and rinse controls, and communities were markedly dominated by select Gammaproteobacteria, notably Escherichia species and Pseudomonas fluorescens. Culture growth above the threshold of 10(4) CFU/ml was correlated with increased bacterial DNA burden (P < 0.01), decreased community diversity (P < 0.05), and increased relative abundance of Pseudomonas aeruginosa (P < 0.001). We present two case studies in which culture-independent techniques identified a respiratory pathogen missed by culture and clarified whether a cultured "oral flora" species represented a state of acute infection. In summary, we found that bacterial culture of BAL fluid is largely effective in discriminating acute infection from its absence and identified some specific limitations of BAL fluid culture in the diagnosis of pneumonia. We report the first correlation of quantitative BAL fluid culture results with culture-independent evidence of infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
In-vitro bacterial identification using fluorescence spectroscopy with an optical fiber system
NASA Astrophysics Data System (ADS)
Spector, Brian C.; Werkhaven, Jay A.; Smith, Dana; Reinisch, Lou
2000-05-01
Acute otitis media (AOM) remains a source of significant morbidity in children. With the emergence of antibiotic resistant strains of bacteria, tympanocentesis has become an important method of bacterial identification in the setting of treatment failures. Previous studies described a prototype system for the non-invasive fluorescence identification of bacteria in vitro. We demonstrate the addition of an optical fiber to allow for the identification of a specimen distant to the spectrofluorometer. Emission spectra from three bacteria, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were successfully obtained in vitro. This represents a necessary step prior to the study of in vivo identification of bacteria in AOM using fluorescence spectroscopy.
Oka, Hiroaki; Komiya, Kosaku; Ohama, Minoru; Kawano, Yoshiyuki; Uchida, Masahiro; Miyajima, Hajime; Iwashita, Tomohiko; Okabe, Eiji; Kawamura, Tadao; Yasuda, Kazuhiro; Matsumoto, Taisuke; Kadota, Jun-Ichi
2017-07-01
The number of elderly patients with pneumonia is significantly increasing as the populations in many countries age. Although elderly patients with pneumonia are at risk of developing urinary tract infections, no studies have examined the prevalence or the prognostic impact of this complication. The aim of the present study was to investigate the prevalence of comorbid bacterial pyuria and the impact on the prognosis of elderly patients with pneumonia. We retrospectively evaluated 132 patients aged >65 years who were hospitalized for pneumonia and who underwent a urinary sediment test on admission. The background characteristics, laboratory results and treatment regimens were documented, and the risk factors for the complication of bacterial pyuria and its association with 90-day mortality in pneumonia patients were elucidated. A total of 37 (28%) of 132 patients were complicated by bacterial pyuria. The patients with bacterial pyuria were more often women, showed a poorer performance status, were more frequently fed by percutaneous endoscopic gastrostomy, and more frequently used diapers and/or a bladder catheter. Regarding first-line drugs, 82.6% of the patients received beta-lactamase inhibitors and extended-spectrum penicillins. The use of a bladder catheter and a poor performance status were associated with bacterial pyuria. A multivariate analysis showed that a poor performance status was the only factor associated with 90-day mortality. Bacterial pyuria did not affect the prognosis of patients who were treated with penicillin-based regimens. Thus, broad-spectrum antibiotics are not necessarily required for elderly patients with pneumonia complicated by urinary tract infection. Geriatr Gerontol Int 2017; 17: 1076-1080. © 2016 Japan Geriatrics Society.
Bjerk, Sonja M; Baker, Jason V; Emery, Sean; Neuhaus, Jacqueline; Angus, Brian; Gordin, Fred M; Pett, Sarah L; Stephan, Christoph; Kunisaki, Ken M
2013-01-01
Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist. We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm(3). Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.
Seth, Rajeev; Murthy, Peela Sree Ramchandra; Sistla, Sujatha; Subramanian, Mahadevan; Tamilarasu, Kadhiravan
2017-09-01
Acute bacterial meningitis is one of the major causes of morbidity and mortality in children and geriatric population, especially in developing countries. Methods of identification are standard culture and other phenotypic tests in many resource poor settings. To use molecular methods for the improvement of aetiological diagnosis of acute pyogenic meningitis in patients. CSF samples of 125 patients were included for the study. Gram staining and culture were performed according to standard procedures. Antigen was detected using commercial latex agglutination test kit. Multiplex PCR was performed using previously published primers and protocols. Fischer's exact test was used for finding association between presence of the disease and clinical/biochemical parameters, considering two tailed p<0.05 as statistically significant. Sensitivity, specificity, positive and negative predictive values were calculated using Graphpad QuicCalc software. A total of 39 cases (31.2%) were confirmed to be of acute pyogenic meningitis based on biochemical methods. Only 10/39 was positive for the three organisms tested. Multiplex PCR was able to detect one additional isolate each of Streptococcus pneumoniae and Haemophilus influenzae type b. When compared with multiplex PCR as the gold standard, culture and latex agglutination tests had same sensitivity (80%), specificity (100%), PPV (100%) and NPV (97.8%), whereas Gram stain had poor sensitivity (40%) and good specificity (95.6%). Detection rates were higher in multiplex PCR for the two organisms Streptococcus pneumoniae and Haemophilus influenzae type b. Multiplex PCR was more sensitive than culture or antigen detection, and employing this assay can significantly increase the speed and accuracy of identification of the pathogen.
Tea tree oil nanoemulsions for inhalation therapies of bacterial and fungal pneumonia.
Li, Miao; Zhu, Lifei; Liu, Boming; Du, Lina; Jia, Xiaodong; Han, Li; Jin, Yiguang
2016-05-01
Tea tree oil (TTO) is a natural essential oil with strong antimicrobial efficacy and little drug resistance. However, the biomedical applications of TTO are limited due to its hydrophobicity and formulation problems. Here, we prepared an inhalable TTO nanoemulsion (nanoTTO) for local therapies of bacterial and fungal pneumonia. The optimal formulation of nanoTTOs consisted of TTO/Cremophor EL/water with a mean size of 12.5nm. The nanoTTOs showed strong in vitro antimicrobial activities on Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Candida albicans. After inhalation to the lung, the nanoTTOs had higher anti-fungal effect than fluconazole on the fungal pneumonia rat models with reduced lung injury, highly microbial clearance, blocking of leukocyte recruitment, and decrease of pro-inflammatory mediators. In the case of rat bacterial pneumonia, the nanoTTOs showed slightly lower therapeutic efficacy than penicillin though at a much lower dose. Taken together, our results show that the inhalable nanoTTOs are promising nanomedicines for local therapies of fungal and bacterial pneumonia with no obvious adverse events. Copyright © 2016 Elsevier B.V. All rights reserved.
Postviral Complications: Bacterial Pneumonia.
Prasso, Jason E; Deng, Jane C
2017-03-01
Secondary bacterial pneumonia after viral respiratory infection remains a significant source of morbidity and mortality. Susceptibility is mediated by a variety of viral and bacterial factors, and complex interactions with the host immune system. Prevention and treatment strategies are limited to influenza vaccination and antibiotics/antivirals respectively. Novel approaches to identifying the individuals with influenza who are at increased risk for secondary bacterial pneumonias are urgently needed. Given the threat of further pandemics and the heightened prevalence of these viruses, more research into the immunologic mechanisms of this disease is warranted with the hope of discovering new potential therapies. Published by Elsevier Inc.
Wagner, Karoline; Springer, Burkard; Imkamp, Frank; Opota, Onya; Greub, Gilbert; Keller, Peter M
2018-04-01
Pneumonia is a severe infectious disease. In addition to common viruses and bacterial pathogens (e.g. Streptococcus pneumoniae), fastidious respiratory pathogens like Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp. can cause severe atypical pneumonia. They do not respond to penicillin derivatives, which may cause failure of antibiotic empirical therapy. The same applies for infections with B. pertussis and B. parapertussis, the cause of pertussis disease, that may present atypically and need to be treated with macrolides. Moreover, these fastidious bacteria are difficult to identify by culture or serology, and therefore often remain undetected. Thus, rapid and accurate identification of bacterial pathogens causing atypical pneumonia is crucial. We performed a retrospective method evaluation study to evaluate the diagnostic performance of the new, commercially available Lightmix ® multiplex RT-PCR assay that detects these fastidious bacterial pathogens causing atypical pneumonia. In this retrospective study, 368 clinical respiratory specimens, obtained from patients suffering from atypical pneumonia that have been tested negative for the presence of common agents of pneumonia by culture and viral PCR, were investigated. These clinical specimens have been previously characterized by singleplex RT-PCR assays in our diagnostic laboratory and were used to evaluate the diagnostic performance of the respiratory multiplex Lightmix ® RT-PCR. The multiplex RT-PCR displayed a limit of detection between 5 and 10 DNA copies for different in-panel organisms and showed identical performance characteristics with respect to specificity and sensitivity as in-house singleplex RT-PCRs for pathogen detection. The Lightmix ® multiplex RT-PCR assay represents a low-cost, time-saving and accurate diagnostic tool with high throughput potential. The time-to-result using an automated DNA extraction device for respiratory specimens followed by multiplex RT-PCR detection was below 4 h, which is expected to significantly improve diagnostics for atypical pneumonia-associated bacterial pathogens. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.
Klebsiella pneumoniae inoculants for enhancing plant growth
Triplett, Eric W [Middleton, WI; Kaeppler, Shawn M [Oregon, WI; Chelius, Marisa K [Greeley, CO
2008-07-01
A biological inoculant for enhancing the growth of plants is disclosed. The inoculant includes the bacterial strains Herbaspirillum seropedicae 2A, Pantoea agglomerans P101, Pantoea agglomerans P102, Klebsiella pneumoniae 342, Klebsiella pneumoniae zmvsy, Herbaspirillum seropedicae Z152, Gluconacetobacter diazotrophicus PA15, with or without a carrier. The inoculant also includes strains of the bacterium Pantoea agglomerans and K. pneumoniae which are able to enhance the growth of cereal grasses. Also disclosed are the novel bacterial strains Herbaspirillum seropedicae 2A, Pantoea agglomerans P101 and P102, and Klebsiella pneumoniae 342 and zmvsy.
76 FR 59406 - Anti-Infective Drugs Advisory Committee; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-26
... development of antibacterials for the treatment of community-acquired bacterial pneumonia and the draft document entitled ``Guidance for Industry: Community-Acquired Bacterial Pneumonia: Developing Drugs for...
21 CFR 520.2220b - Sulfadimethoxine tablets and boluses.
Code of Federal Regulations, 2011 CFR
2011-04-01
.... (ii) Indications for use. For the treatment of shipping fever complex and bacterial pneumonia.... (ii) Indications for use. Treatment of shipping fever complex and bacterial pneumonia associated with...
21 CFR 520.2220b - Sulfadimethoxine tablets and boluses.
Code of Federal Regulations, 2012 CFR
2012-04-01
.... (ii) Indications for use. For the treatment of shipping fever complex and bacterial pneumonia.... (ii) Indications for use. Treatment of shipping fever complex and bacterial pneumonia associated with...
21 CFR 520.2220b - Sulfadimethoxine tablets and boluses.
Code of Federal Regulations, 2014 CFR
2014-04-01
.... (ii) Indications for use. For the treatment of shipping fever complex and bacterial pneumonia.... (ii) Indications for use. Treatment of shipping fever complex and bacterial pneumonia associated with...
21 CFR 520.2220b - Sulfadimethoxine tablets and boluses.
Code of Federal Regulations, 2013 CFR
2013-04-01
.... (ii) Indications for use. For the treatment of shipping fever complex and bacterial pneumonia.... (ii) Indications for use. Treatment of shipping fever complex and bacterial pneumonia associated with...
A prospective study of the diagnostic utility of sputum Gram stain in pneumonia.
Anevlavis, Stavros; Petroglou, Niki; Tzavaras, Athanasios; Maltezos, Efstratios; Pneumatikos, Ioannis; Froudarakis, Marios; Anevlavis, Eleftherios; Bouros, Demosthenes
2009-08-01
Sputum Gram stain and culture have been said to be unreliable indicators of the microbiological diagnosis of bacterial pneumonia. The etiological diagnosis of pneumonia is surrounded by great degree of uncertainty. This uncertainty should be and can be calculated and incorporated in the diagnosis and treatment. To determine the diagnostic accuracy and diagnostic value of sputum Gram stain in etiological diagnosis and initial selection of antimicrobial therapy of bacterial community acquired pneumonia (CAP). DESIGN-METHOD: Prospective study of 1390 patients with CAP admitted January 2002-June 2008, to our institutions. Of the 1390 patients, 178 (12.8%) fulfilled the criteria for inclusion into this study (good-quality sputa and presence of the same microorganism in blood and sputum cultures which was used as gold standard for assessing the diagnostic accuracy and diagnostic value of sputum Gram stain). The sensitivity of sputum Gram stain was 0.82 for Pneumococcal pneumonia, 0.76 for Staphylococcal pneumonia, 0.79 for Haemophilus influenzae pneumonia and 0.78 for Gram-negative bacilli pneumonia. The specificity of sputum Gram stain was 0.93 for Pneumococcal pneumonia, 0.96 for Staphylococcal pneumonia, 0.96 for H. influenzae pneumonia and 0.95 for Gram-negative bacilli pneumonia. The positive likelihood ratio (LR+) was 11.58 for Pneumococcal pneumonia, 19.38 for Staphylococcal pneumonia, 16.84 for H. influenzae pneumonia, 14.26 for Gram-negative bacilli pneumonia. The negative likelihood ratio (LR-) was 0.20 for Pneumococcal pneumonia, 0.25 for Staphylococcal pneumonia, 0.22 for H. influenzae pneumonia, and 0.23 for Gram-negative bacilli pneumonia. Sputum Gram stain is a dependable diagnostic test for the early etiological diagnosis of bacterial CAP that helps in choosing orthological and appropriate initial antimicrobial therapy.
Chien, Yu-Wen; Klugman, Keith P; Morens, David M
2010-12-01
Most deaths in the 1918 influenza pandemic were caused by secondary bacterial pneumonia. We performed a systematic review and reanalysis of studies of bacterial vaccine efficacy (VE) in preventing pneumonia and mortality among patients with influenza during the 1918 pandemic. A meta-analysis of 6 civilian studies of mixed killed bacterial vaccines containing pneumococci identified significant heterogeneity among studies and estimated VE at 34% (95% confidence interval [CI], 19%-47%) in preventing pneumonia and 42% (95% CI, 18%-59%) in reducing case fatality rates among patients with influenza, using random-effects models. Using fixed-effect models, the pooled VE from 3 military studies was 59% (95% CI, 43%-70%) for pneumonia and 70% (95% CI, 50%-82%) for case fatality. Military studies showed less heterogeneity and may provide more accurate results than civilian studies, given the potential biases in the included studies. Findings of 1 military study using hemolytic streptococci also suggested that there was significant protection. Despite significant methodological problems, the systematic biases in these studies do not exclude the possibilities that whole-cell inactivated pneumococcal vaccines may confer cross-protection to multiple pneumococcal serotypes and that bacterial vaccines may play a role in preventing influenza-associated pneumonia.
Pett, S L; Carey, C; Lin, E; Wentworth, D; Lazovski, J; Miró, J M; Gordin, F; Angus, B; Rodriguez-Barradas, M; Rubio, R; Tambussi, G; Cooper, D A; Emery, S
2011-04-01
Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/μL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections. Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected. IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/μL (IL-2 arm) and 463cells/μL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/μL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively. Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration. © 2010 British HIV Association.
The relationship between pneumonia and Glasgow coma scale assessment on acute stroke patients
NASA Astrophysics Data System (ADS)
Ritarwan, K.; Batubara, C. A.; Dhanu, R.
2018-03-01
Pneumonia is one of the most frequent medical complications of a stroke. Despite the well-documented association of a stroke associated infections with increased mortality and worse long-term outcome, on the other hand, the limited data available on independent predictors of pneumonia in acute stroke patients in an emergency unit. To determine the independentrelationship between pneumonia and Glasgow Coma Scale assessment on acute stroke patients. The cohort retrospective study observed 55 acute stroke patients who stayed in intensive care unit Adam Malik General Hospital from January until August 2017. Pneumonia was more frequent in patients with Ischemic stroke (OR 5.40; 95% CI: 1.28 – 6.40, p=0.003), higher National Institute of Health Stroke Scale (NIHSS) (p=0.014) and lower Glasgow Coma Scale (p=0.0001). Analysis multivariate logistic regression identified NIHSS as an independent of predictors of pneumonia (95% CI : 1.047 – 1.326, p=0.001). Pneumonia was associated with severity and type of stroke and length of hospital stay. The severity of the deficits evaluated by the NIHSS was shown to be the only independent risk factor for pneumonia in acute stroke patients.
Epizootic Pneumonia of Bighorn Sheep following Experimental Exposure to Mycoplasma ovipneumoniae
Besser, Thomas E.; Cassirer, E. Frances; Potter, Kathleen A.; Lahmers, Kevin; Oaks, J. Lindsay; Shanthalingam, Sudarvili; Srikumaran, Subramaniam; Foreyt, William J.
2014-01-01
Background Bronchopneumonia is a population limiting disease of bighorn sheep (Ovis canadensis). The cause of this disease has been a subject of debate. Leukotoxin expressing Mannheimia haemolytica and Bibersteinia trehalosi produce acute pneumonia after experimental challenge but are infrequently isolated from animals in natural outbreaks. Mycoplasma ovipneumoniae, epidemiologically implicated in naturally occurring outbreaks, has received little experimental evaluation as a primary agent of bighorn sheep pneumonia. Methodology/Principal Findings In two experiments, bighorn sheep housed in multiple pens 7.6 to 12 m apart were exposed to M. ovipneumoniae by introduction of a single infected or challenged animal to a single pen. Respiratory disease was monitored by observation of clinical signs and confirmed by necropsy. Bacterial involvement in the pneumonic lungs was evaluated by conventional aerobic bacteriology and by culture-independent methods. In both experiments the challenge strain of M. ovipneumoniae was transmitted to all animals both within and between pens and all infected bighorn sheep developed bronchopneumonia. In six bighorn sheep in which the disease was allowed to run its course, three died with bronchopneumonia 34, 65, and 109 days after M. ovipneumoniae introduction. Diverse bacterial populations, predominantly including multiple obligate anaerobic species, were present in pneumonic lung tissues at necropsy. Conclusions/Significance Exposure to a single M. ovipneumoniae infected animal resulted in transmission of infection to all bighorn sheep both within the pen and in adjacent pens, and all infected sheep developed bronchopneumonia. The epidemiologic, pathologic and microbiologic findings in these experimental animals resembled those seen in naturally occurring pneumonia outbreaks in free ranging bighorn sheep. PMID:25302992
Pfaller, M. A.; Sader, H. S.; Rhomberg, P. R.
2017-01-01
ABSTRACT The in vitro activities of delafloxacin and comparator antimicrobial agents against 6,485 bacterial isolates collected from medical centers in Europe and the United States in 2014 were tested. Delafloxacin was the most potent agent tested against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus, Streptococcus pneumoniae, viridans group streptococci, and beta-hemolytic streptococci and had activity similar to that of ciprofloxacin and levofloxacin against certain members of the Enterobacteriaceae. Overall, the broadest coverage of the tested pathogens (Gram-positive cocci and Gram-negative bacilli) was observed with meropenem and tigecycline in both Europe and the United States. Delafloxacin was shown to be active against organisms that may be encountered in acute bacterial skin and skin structure infections, respiratory infections, and urinary tract infections. PMID:28167542
Pfaller, M A; Sader, H S; Rhomberg, P R; Flamm, R K
2017-04-01
The in vitro activities of delafloxacin and comparator antimicrobial agents against 6,485 bacterial isolates collected from medical centers in Europe and the United States in 2014 were tested. Delafloxacin was the most potent agent tested against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus , Streptococcus pneumoniae , viridans group streptococci, and beta-hemolytic streptococci and had activity similar to that of ciprofloxacin and levofloxacin against certain members of the Enterobacteriaceae Overall, the broadest coverage of the tested pathogens (Gram-positive cocci and Gram-negative bacilli) was observed with meropenem and tigecycline in both Europe and the United States. Delafloxacin was shown to be active against organisms that may be encountered in acute bacterial skin and skin structure infections, respiratory infections, and urinary tract infections. Copyright © 2017 Pfaller et al.
21 CFR 520.2220b - Sulfadimethoxine tablets and boluses.
Code of Federal Regulations, 2010 CFR
2010-04-01
... body weight. (ii) Indications for use. Treatment of foot rot, bacterial pneumonia, shipping fever, and...) Indications for use. Treatment of shipping fever complex and bacterial pneumonia associated with organisms...
Bacterial pneumonia as an influenza complication.
Martin-Loeches, Ignacio; van Someren Gréve, Frank; Schultz, Marcus J
2017-04-01
The pathogenesis and impact of coinfection, in particular bacterial coinfection, in influenza are incompletely understood. This review summarizes results from studies on bacterial coinfection in the recent pandemic influenza outbreak. Systemic immune mechanisms play a key role in the development of coinfection based on the complexity of the interaction of the host and the viral and bacterial pathogens. Several studies were performed to determine the point prevalence of bacterial coinfection in influenza. Coinfection in influenza is frequent in critically ill patients with Streptococcus pneumoniae being the most frequent bacterial pathogen and higher rates of potentially resistant pathogens over the years. Bacterial pneumonia is certainly an influenza complication. The recent epidemiology findings have helped to partially resolve the contribution of different pathogens. Immunosuppression is a risk factor for bacterial coinfection in influenza, and the epidemiology of coinfection has changed over the years during the last influenza pandemic, and these recent findings should be taken into account during present outbreaks.
Early Bacterial Pneumonia After Hepatic Transplantation: Epidemiologic Profile.
Prieto Amorin, J; Lopez, M; Rando, K; Castelli, J; Medina Presentado, J
2018-03-01
Postoperative pulmonary complications are major cause of morbidity and mortality in patients receiving liver transplantation (LT), particularly bacterial pneumonia occurring within the first 100 days after transplantation. Our aim in this study was to determine the incidence, microorganisms involved, associated factors, and morbidity of bacterial pneumonia presenting in the first 100 days posttransplant. We performed a cohort study in which patients receiving liver transplantation were included prospectively in our national database (Database of Infections in Transplantation of Solid Organs). The study period was from July 14, 2009 to July 24, 2015. One hundred six patients were transplanted during the 6-year period. We documented 9 bacterial pneumonia cases with an incidence of 8.5 per 100 patients; 2 patients had hospital-acquired pneumonia (HAP) and 7 had ventilator-associated pneumonia (VAP). In 4 of the 9 bacterial pneumonia cases, patients presented with bacteremia. Eleven microorganisms were isolated these 9 patients. Microbiologic diagnosis methods included 5 cases of alveolar bronchoalveolar lavage (BAL), 1 case of BAL and pleural fluid puncture, 1 case of pleural fluid puncture, and 1 case through sputum study. Of the 11 isolated organisms, 9 corresponded to Gram-negative bacilli (GNB): Klebsiella spp, n = 3; Acinetobacter baumannii, n = 4; Morganella morganii, n = 1; and Pseudomonas aeruginosa, n = 1. Regarding the resistance profile, 7 presented with a multiresistance profile (MDR) and extreme resistance (XDR). Univariate analysis identified the Model for End-Stage Liver Disease (MELD) pretransplant score as a factor associated with developing pneumonia (P < .001, 95% confidence interval [CI] 2.872-10.167), and early extubation, before 8 hours posttransplant, as a protective factor (P = .008; relative risk [RR] 0.124; 95% CI 0 .041-0.377). Hospital stay was longer in patients with pneumonia compared to those without pneumonia (P < .0001, 95% CI 17.79-43.11 days). There was also an increased risk of death in patients with pneumonia (RR 17.963; 95% CI 5106-63,195). Early bacterial pneumonia after hepatic transplantation is associated with higher morbidity and mortality. At our center, 4 of 9 patients had bacteremia. GNB cases with MDR and XDR profiles are predominant. Early extubation is a protective factor. Copyright © 2017 Elsevier Inc. All rights reserved.
Cuquemelle, E; Soulis, F; Villers, D; Roche-Campo, F; Ara Somohano, C; Fartoukh, M; Kouatchet, A; Mourvillier, B; Dellamonica, J; Picard, W; Schmidt, M; Boulain, T; Brun-Buisson, C
2011-05-01
To determine whether procalcitonin (PCT) levels could help discriminate isolated viral from mixed (bacterial and viral) pneumonia in patients admitted to the intensive care unit (ICU) during the A/H1N1v2009 influenza pandemic. A retrospective observational study was performed in 23 French ICUs during the 2009 H1N1 pandemic. Levels of PCT at admission were compared between patients with confirmed influenzae A pneumonia associated or not associated with a bacterial co-infection. Of 103 patients with confirmed A/H1N1 infection and not having received prior antibiotics, 48 (46.6%; 95% CI 37-56%) had a documented bacterial co-infection, mostly caused by Streptococcus pneumoniae (54%) or Staphylococcus aureus (31%). Fifty-two patients had PCT measured on admission, including 19 (37%) having bacterial co-infection. Median (range 25-75%) values of PCT were significantly higher in patients with bacterial co-infection: 29.5 (3.9-45.3) versus 0.5 (0.12-2) μg/l (P < 0.01). For a cut-off of 0.8 μg/l or more, the sensitivity and specificity of PCT for distinguishing isolated viral from mixed pneumonia were 91 and 68%, respectively. Alveolar condensation combined with a PCT level of 0.8 μg/l or more was strongly associated with bacterial co-infection (OR 12.9, 95% CI 3.2-51.5; P < 0.001). PCT may help discriminate viral from mixed pneumonia during the influenza season. Levels of PCT less than 0.8 μg/l combined with clinical judgment suggest that bacterial infection is unlikely.
Time course of lung function changes in atypical pneumonia.
Benusiglio, L N; Stalder, H; Junod, A F
1980-01-01
We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae. PMID:7444825
Harris, Greg; Kuo Lee, Rhonda; Lam, Christopher K.; Kanzaki, Gregory; Patel, Girishchandra B.; Xu, H. Howard
2013-01-01
Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 108 CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. baumannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans. PMID:23689726
Ceyhan, Mehmet; Ozsurekci, Yasemin; Gürler, Nezahat; Karadag Oncel, Eda; Camcioglu, Yıldız; Salman, Nuran; Celik, Melda; Emiroglu, Melike Keser; Akin, Fatih; Tezer, Hasan; Parlakay, Aslinur Ozkaya; Tuygun, Nilden; Tamburaci, Diyar; Dinleyici, Ener Cagri; Karbuz, Adem; Uluca, Ünal; Alhan, Emre; Çay, Ümmühan; Kurugol, Zafer; Hatipoğlu, Nevin; Şiraneci, Rengin; İnce, Tolga; Sensoy, Gülnar; Belet, Nursen; Coskun, Enes; Yilmaz, Fatih; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Celik, Ümit; Ozen, Metehan; Akaslan, Aybüke; Devrim, İlker; Kuyucu, Necdet; Öz, Fatmanur; Bozdemir, Sefika Elmas; Kara, Ahu
2016-11-01
This is an observational epidemiological study to describe causes of bacterial meningitis among persons between 1 month and 18 y of age who are hospitalized with suspected bacterial meningitis in 7 Turkish regions. covering 32% of the entire population of Turkey. We present here the results from 2013 and 2014. A clinical case with meningitis was defined according to followings: any sign of meningitis including fever, vomiting, headache, and meningeal irritation in children above one year of age and fever without any documented source, impaired consciousness, prostration and seizures in those < 1 y of age. Single tube multiplex PCR assay was performed for the simultaneous identification of bacterial agents. The specific gene targets were ctrA, bex, and ply for N. meningitidis, Hib, and S. pneumoniae, respectively. PCR positive samples were recorded as laboratory-confirmed acute bacterial meningitis. A total of 665 children were hospitalized for suspected acute meningitis. The annual incidences of acute laboratory-confirmed bacterial meningitis were 0.3 cases / 100,000 population in 2013 and 0.9 cases/100,000 in 2014. Of the 94 diagnosed cases of bacterial meningitis by PCR, 85 (90.4%) were meningococcal and 9 (9.6%) were pneumococcal. Hib was not detected in any of the patients. Among meningococcal meningitis, cases of serogroup Y, A, B and W-135 were 2.4% (n = 2), 3.5% (n = 3), 32.9% (n = 28), and 42.4% (n = 36). No serogroup C was detected among meningococcal cases. Successful vaccination policies for protection from bacterial meningitis are dependent on accurate determination of the etiology of bacterial meningitis. Additionally, the epidemiology of meningococcal disease is dynamic and close monitoring of serogroup distribution is comprehensively needed to assess the benefit of adding meningococcal vaccines to the routine immunization program.
Bacterial pneumonia in dogs and cats.
Dear, Jonathan D
2014-01-01
Bacterial pneumonia is a common clinical diagnosis in dogs but seems to occur less commonly in cats. Underlying causes include viral infection, aspiration injury, and foreign body inhalation. Identification of the organisms involved in disease, appropriate use of antibiotics and adjunct therapy, and control of risk factors for pneumonia improve management. Copyright © 2014 Elsevier Inc. All rights reserved.
The rational clinical examination. Does this infant have pneumonia?
Margolis, P; Gadomski, A
1998-01-28
Acute lower respiratory tract illness is common among children seen in primary care. We reviewed the accuracy and precision of the clinical examination in detecting pneumonia in children. Although most cases are viral, it is important to identify bacterial pneumonia to provide appropriate therapy. Studies were identified by searching MEDLINE from 1982 to 1995, reviewing reference lists, reviewing a published compendium of studies of the clinical examination, and consulting experts. Observer agreement is good for most signs on the clinical examination. Each study was reviewed by 2 observers and graded for methodologic quality. There is better agreement about signs that can be observed (eg, use of accessory muscles, color, attentiveness; kappa, 0.48-0.66) than signs that require auscultation of the chest (eg, adventitious sounds; kappa, 0.3). Measurements of the respiratory rate are enhanced by counting for 60 seconds. The best individual finding for ruling out pneumonia is the absence of tachypnea. Chest indrawing, and other signs of increased work of breathing, increases the likelihood of pneumonia. If all clinical signs (respiratory rate, auscultation, and work of breathing) are negative, the chest x-ray findings are unlikely to be positive. Studies are needed to assess the value of clinical findings when they are used together.
21 CFR 522.1664 - Oxytetracycline and flunixin.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 0.9 mg flunixin per lb BW) where retreatment of calves and yearlings for bacterial pneumonia is... inadvisable. (2) Indications for use. For the treatment of bacterial pneumonia associated with Pasteurella spp...
21 CFR 522.1664 - Oxytetracycline and flunixin.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 0.9 mg flunixin per lb BW) where retreatment of calves and yearlings for bacterial pneumonia is... inadvisable. (2) Indications for use. For the treatment of bacterial pneumonia associated with Pasteurella spp...
21 CFR 522.1664 - Oxytetracycline and flunixin.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 0.9 mg flunixin per lb BW) where retreatment of calves and yearlings for bacterial pneumonia is... inadvisable. (2) Indications for use. For the treatment of bacterial pneumonia associated with Pasteurella spp...
21 CFR 522.1664 - Oxytetracycline and flunixin.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 0.9 mg flunixin per lb BW) where retreatment of calves and yearlings for bacterial pneumonia is... inadvisable. (2) Indications for use. For the treatment of bacterial pneumonia associated with Pasteurella spp...
Kim, Ho-Cheol; Choi, Sang-Ho; Huh, Jin-Won; Sung, Heungsup; Hong, Sang Bum; Lim, Chae-Man; Koh, Younsuck
2016-12-01
Respiratory viruses are well-known causes of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and also important pathogens for concomitant pneumonia in COPD (CP-COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated. The clinical and microbiological data from COPD patients admitted with AE-COPD (n = 281) or CP-COPD (n = 284) between January 2010 and December 2012 were reviewed. After excluding 88 patients (40 with AE-COPD and 48 with CP-COPD) who did not undergo a multiplex RT-PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE-COPD and CP-COPD groups were compared. Respiratory viruses were identified in 41.9% of AE-COPD group and 33.5% of the CP-COPD groups. The most common virus was influenza virus in the AE-COPD group (33.7%) versus human coronavirus (24.1%) in the CP-COPD group. Influenza virus was significantly more common in the AE-ACOPD group than in the CP-COPD group (P < 0.01). In-hospital mortality of AE-COPD and CP-COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP-COPD patients, in-hospital mortality of patients with only viral infection group, only bacterial infection group, and viral-bacterial co-infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01). Respiratory viruses were commonly identified in both AE-COPD and CP-COPD, influenza virus and human coronavirus were the most common viruses identified in AE-COPD and CP-COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral-bacterial co-infection group in CP-COPD patients. J. Med. Virol. 88:2092-2099, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Adenosine A2B Receptor Deficiency Promotes Host Defenses against Gram-Negative Bacterial Pneumonia
Barletta, Kathryn E.; Cagnina, R. Elaine; Burdick, Marie D.; Linden, Joel
2012-01-01
Rationale: Activation of the adenosine A2B receptor (A2BR) promotes antiinflammatory effects in diverse biological settings, but the role of this receptor in antimicrobial host defense in the lung has not been established. Gram-negative bacillary pneumonia is a common and serious illness associated with high morbidity and mortality, the treatment of which is complicated by increasing rates of antibiotic resistance. Objectives: To test the hypothesis that absence of adenosine A2B receptor signaling promotes host defense against bacterial pneumonia. Methods: We used a model of Klebsiella pneumoniae pneumonia in wild-type mice and mice with targeted deletion of the A2BR. Host responses were compared in vivo and leukocyte responses to the bacteria were examined in vitro. Measurements and Main Results: A2BR–/– mice demonstrated enhanced bacterial clearance from the lung and improved survival after infection with K. pneumoniae compared with wild-type controls, an effect that was mediated by bone marrow–derived cells. Leukocyte recruitment to the lungs and expression of inflammatory cytokines did not differ between A2BR–/– and wild-type mice, but A2BR–/– neutrophils exhibited sixfold greater bactericidal activity and enhanced production of neutrophil extracellular traps compared with wild-type neutrophils when incubated with K. pneumoniae. Consistent with this finding, bronchoalveolar lavage fluid from A2BR–/– mice with Klebsiella pneumonia contained more extracellular DNA compared with wild-type mice with pneumonia. Conclusions: These data suggest that the absence of A2BR signaling enhances antimicrobial activity in gram-negative bacterial pneumonia. PMID:22997203
RAPID DIAGNOSIS OF PNEUMOCOCCAL PNEUMONIA AMONG HIV-INFECTED ADULTS WITH URINE ANTIGEN DETECTION
Boulware, David R; Daley, Charles L.; Merrifield, Cynthia; Hopewell, Philip C.; Janoff, Edward N.
2007-01-01
Objectives Streptococcus pneumoniae is the leading cause of bacterial pneumonia and associated bacteremia during HIV infection. Rapid diagnostic assays may limit inappropriate therapy. Methods Clinical signs and symptoms and sera and urine were collected prospectively from 70 adults with pneumococcal pneumonia, including 47 with HIV co-infection. Pneumococcal C-polysaccharide antigen was detected in urine using the Binax® immunochromatographic test (ICT). A systematic review of 24 published studies was conducted. Results Clinical symptoms, signs, and laboratory parameters except leukocytosis, were similar in HIV-infected and HIV-seronegative pneumonia. The performance of the urine antigen ICT was independent of HIV-status (sensitivity 81%, specificity 98%, positive (PPV) and negative predictive values (NPV) 98%, and 82%, respectively). The sensitivity of sputum Gram’s stain was 58% [34/59] with sputum unable to be provided by 16%. The CRP response was identical in HIV-infected (mean ± SD) 133 ± 88 vs. seronegative 135 ± 104 mg/L (p=0.9). In the systematic review, the ICT performance revealed 74% sensitivity (95% CI: 72% to 77%) and 94% specificity (95% CI: 93% to 95%). Urine antigen testing increases etiologic diagnosis by 23% (Range: 10% –59%) when testing adults with community acquired pneumonia of unknown etiology. Conclusions Urinary antigen detection provides a credible rapid diagnostic test for pneumococcal pneumonia regardless of HIV-status. CRP response to acute infection is similar in HIV co-infection and increases diagnostic certainty. PMID:17692384
Imipenem/cilastatin-induced acute eosinophilic pneumonia.
Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei
2016-03-04
Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. 2016 BMJ Publishing Group Ltd.
Hart, Samantha K; Waddell, Lori
2016-11-01
To describe a case of suspected drug-induced infiltrative lung disease (ILD) and acute respiratory failure associated with the administration of cytarabine and prednisone in a dog requiring mechanical ventilation. A 4.5-year-old, female spayed Yorkshire Terrier presented to the ICU with acute onset of respiratory distress following a 24-hour cytarabine infusion. The patient was previously diagnosed with meningoencephalitis of unknown etiology (MUO), caudal occipital malformation, and syringohydromyelia, and was being treated with oral prednisone and levetiracetam, and cytarabine infusions. The patient developed tachypnea and dyspnea, and had diffuse crackles on auscultation of all lung fields, and hypoxemia 6 hours following completion of the fourth cytarabine infusion (300 mg/m 2 ). Thoracic radiographs revealed diffuse, bilateral infiltrates consistent with noncardiogenic pulmonary edema or acute respiratory distress syndrome. Respiratory distress and hypoxemia persisted despite oxygen supplementation and furosemide therapy and led to initiation of mechanical ventilation. Approximately 12 hours later, the dog became progressively hypoxemic with worsening pulmonary edema. The owners elected euthanasia. Postmortem examination revealed pulmonary edema and diffuse interstitial pneumonia. Histopathologic evaluation revealed pulmonary edema, severe acute neutrophilic and histiocytic pneumonia, and multifocal interstitial fibrosis. Bacterial culture yielded no growth. Drug-induced ILD is rarely reported in the veterinary literature, and has not previously been reported in dogs receiving cytarabine. As with administration of any medication, adverse events may occur. While ILD is unlikely to be commonly recognized, it may be considered in veterinary patients receiving chemotherapy that acutely become dyspneic. © Veterinary Emergency and Critical Care Society 2016.
[The use of chest X-rays for surveillance of bacterial pneumonias in children in Latin America].
Lagos, Rosanna; di Fabio, José Luis; Moënne, Karla; Muñoz M, Alma; Wasserman, Steven; de Quadros, Ciro
2003-05-01
The Division of Vaccines and Immunization of the Pan American Health Organization (PAHO) is promoting epidemiological surveillance of bacterial pneumonias in children in Latin America in order to generate scientific evidence to support future decisions concerning using vaccines to control such pneumonias in the countries of the Region of the Americas. The diagnosis of these diseases rarely includes bacteriological documentation of the causative agent. Therefore, studies of this type that are carried out around the world accept radiological images of alveolar consolidation as a confirmatory criterion for a presumptively bacterial pneumonia. This piece examines the theoretical rationale and requirements for using thorax radiology as an instrument for epidemiological surveillance of bacterial pneumonias. The piece also summarizes the activities carried out during 2 years of joint efforts between the Center for Vaccine Development (Centro para Vacunas en Desarrollo) of Chile and PAHO's Division of Vaccines and Immunization. During those 2 years, the two groups encouraged the epidemiological study of bacterial pneumonias in Latin American children, using internationally accepted criteria and definitions as well as tools and practical solutions adapted to the reality of the Region of the America. The activities carried out so far show both the need for and the feasibility of standardizing the interpretation of chest radiographs so that they can be used in epidemiological studies.
Biomarkers and Bacterial Pneumonia Risk in Patients with Treated HIV Infection: A Case-Control Study
Bjerk, Sonja M.; Baker, Jason V.; Emery, Sean; Neuhaus, Jacqueline; Angus, Brian; Gordin, Fred M.; Pett, Sarah L.; Stephan, Christoph; Kunisaki, Ken M.
2013-01-01
Background Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist. Methods We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Results Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). Conclusions In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk. PMID:23457535
Atieh, Thérèse; Audoly, Gilles; Hraiech, Sami; Lepidi, Hubert; Roch, Antoine; Rolain, Jean-Marc; Raoult, Didier; Papazian, Laurent; Brégeon, Fabienne
2013-08-01
In severe nosocomial pneumonia, the pathogenic responsibility of bacteria isolated from airways is far from certain, and a lung biopsy is sometimes performed. However, detection and identification of pathogens are frequently unachieved. Here, we developed a protocol for direct visualization of bacteria within the lung tissue using fluorescent in situ hybridization (FISH) in a rat model of Acinetobacter baumannii pneumonia. The reference positive diagnosis of bacterial pneumonia was the presence of pathological signs of pneumonia associated with the proof of bacteria or bacterial PCR products into the parenchyma. By analysis of 122 sets of slices from 26 rats and using the eubacterial probe EUB-338, our results show that FISH reached a sensitivity and a diagnostic accuracy higher than that of optic microscopy (sensitivity: 96% versus 55.4% and diagnostic accuracy: 96.7% versus 66.4%), whereas both approaches had 100% specificity. FISH could be useful especially on negative biopsies from patients with suspected infectious pneumonia. Copyright © 2013 Elsevier Inc. All rights reserved.
Akter, Sonia; Shamsuzzaman, S M; Jahan, Ferdush
2014-08-01
This cross sectional study was conducted to identify the common bacterial causes of community acquired pneumonia (CAP) from sputum and blood by culture and polymerase chain reaction (PCR) and to evaluate the effectiveness of these tests. A total of 105 sputum and blood samples were collected from patients with pneumonia on clinical suspicion. Common causative bacterial agents of pneumonia were detected by Gram staining, cultures, biochemical tests and PCR. Among 55 sputum culture positive cases, a majority (61.82%) of the patients were in the age group between 21-50 years and the ratio between male and female was 2.5:1. Most (61.90%) of the cases were from the lower socio-economic group. Out of 105 samples, 23 (37.12%) were positive by Gram stain, 29 (27.62%) yielded growth in culture media and 37 (35.24%) were positive by PCR for Streptococcus pneumoniae and Haemophilus influenzae. Streptococcus pneumoniae was the most common aetiological agent (19.05%) followed by Klebsiella pneumoniae (13.33%), Haemophilus influenzae (8.57%) and Pseudomonas aeruginosa (5.71%). Multiplex PCR is a useful technique for rapid diagnosis of bacterial causes of pneumonia directly from sputum and blood. Considering culture as a gold standard, the sensitivity of PCR was 96.55% and specificity was 88.15%. More than 80% of Streptococcus pneumoniae isolates were found to be sensitive to ampicillin, amoxycillinclavulanate, and ceftriaxone. Susceptibilities to other antimicrobials ranged from 65% for azithromycin to 70% for levofloxacin. On the other hand, the Gram negative organisms were more sensitive to meropenem, ceftriaxone, amoxycillin-clavulanate and amikacin.
Ma, Hon Ming; Ip, Margaret; Woo, Jean; Hui, David S C
2014-05-01
Health care-associated pneumonia (HCAP) and drug-resistant bacterial pneumonia may not share identical risk factors. We have shown that bronchiectasis, recent hospitalization and severe pneumonia (confusion, blood urea level, respiratory rate, low blood pressure and 65 year old (CURB-65) score ≥ 3) were independent predictors of pneumonia caused by potentially drug-resistant (PDR) pathogens. This study aimed to develop and validate a clinical risk score for predicting drug-resistant bacterial pneumonia in older patients. We derived a risk score by assigning a weighting to each of these risk factors as follows: 14, bronchiectasis; 5, recent hospitalization; 2, severe pneumonia. A 0.5 point was defined for the presence of other risk factors for HCAP. We compared the areas under the receiver-operating characteristics curve (AUROC) of our risk score and the HCAP definition in predicting PDR pathogens in two cohorts of older patients hospitalized with non-nosocomial pneumonia. The derivation and validation cohorts consisted of 354 and 96 patients with bacterial pneumonia, respectively. PDR pathogens were isolated in 48 and 21 patients in the derivation and validation cohorts, respectively. The AUROCs of our risk score and the HCAP definition were 0.751 and 0.650, respectively, in the derivation cohort, and were 0.782 and 0.671, respectively, in the validation cohort. The differences between our risk score and the HCAP definition reached statistical significance. A score ≥ 2.5 had the best balance between sensitivity and specificity. Our risk score outperformed the HCAP definition to predict pneumonia caused by PDR pathogens. A history of bronchiectasis or recent hospitalization is the major indication of starting empirical broad-spectrum antibiotics. © 2014 Asian Pacific Society of Respirology.
Dietert, Kristina; Reppe, Katrin; Mundhenk, Lars; Witzenrath, Martin; Gruber, Achim D.
2014-01-01
The human hCLCA1 and its murine ortholog mCLCA3 (calcium-activated chloride channel regulators) are exclusively expressed in mucus cells and linked to inflammatory airway diseases with increased mucus production, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Both proteins have a known impact on the mucus cell metaplasia trait in these diseases. However, growing evidence points towards an additional role in innate immune responses. In the current study, we analyzed Staphylococcus aureus pneumonia, an established model to study pulmonary innate immunity, in mCLCA3-deficient and wild-type mice, focusing on the cellular and cytokine-driven innate inflammatory response. We compared clinical signs, bacterial clearance, leukocyte immigration and cytokine responses in the bronchoalveolar compartment, as well as pulmonary vascular permeability, histopathology, mucus cell number and mRNA expression levels of selected genes (mClca1 to 7, Muc5ac, Muc5b, Muc2, Cxcl-1, Cxcl-2, Il-17). Deficiency of mCLCA3 resulted in decreased neutrophilic infiltration into the bronchoalveolar space during bacterial infection. Only the cytokines IL-17 and the murine CXCL-8 homolog CXCL-1 were decreased on mRNA and protein levels during bacterial infection in mCLCA3-deficient mice compared to wild-type controls. However, no differences in clinical outcome, histopathology or mucus cell metaplasia were observed. We did not find evidence for regulation of any other CLCA homolog that would putatively compensate for the lack of mCLCA3. In conclusion, mCLCA3 appears to modulate leukocyte response via IL-17 and murine CXCL-8 homologs in acute Staphylococcus aureus pneumonia which is well in line with the proposed function of hCLCA1 as a signaling molecule acting on alveolar macrophages. PMID:25033194
Misawa, Shigeki
2002-07-01
The features and limitations of microbiology processes for the diagnosis of bacterial meningitis were summarized. Requests for physicians were also emphasized. The microbiology laboratory should be responsible for providing highly reliable and concordant data with a variety of clinical settings. Technologists in a microbiology laboratory should perform following subjects: i) Direct smear examination: Presumptive identification by the observers with abundant experience and sufficient training. ii) Rapid bacterial antigen detection tests: Active utilize alone in combination with the direct microscopy. iii) Culture: Cost effective utilize for appropriate media and culture condition based on the bacteriological statistics. Report with bacteriological interpretations and with additional proper comments, if necessary. iv) Antimicrobial susceptibility tests: Determination of penicillin resistance among the strains of penicillin-resistant or-intermediate Streptococcus pneumoniae (PI or PRSP) should be confirmed by MIC procedures; Detection of beta-lactamase producing Haemophilus influenzae (BLP) could detect by beta-lactamase tests, but not clearly identify for beta-lactamase-negative ampicillin-resistant isolates (BLNAR). In addition, a laboratory should provide appropriate information by using the accumulated routine clinical microbiology data, which may help to physicians in selecting an empiric therapy and to the microbiology technologists in processing the routine microbiology. In recent status, the most common organisms isolated from patients with bacterial meningitis continue to be S. pneumoniae and H. influenzae. Among S. pneumoniae strains, penicillin-intermediate(PISP) and--resistant(PRSP) strains had exceeded 50%, and the strains of beta-lactamase producing H. influenzae (BLP) had decreased with less than 10% and beta-lactamase negative ampicillin-resistant strains (BLNAR) have increasing. To providing rapid and accurate results, a laboratory should require the clinical information, including patient's age, major presenting symptoms, and receive antimicrobials prior to specimen collection.
The Multidisciplinary Swallowing Team Approach Decreases Pneumonia Onset in Acute Stroke Patients.
Aoki, Shiro; Hosomi, Naohisa; Hirayama, Junko; Nakamori, Masahiro; Yoshikawa, Mineka; Nezu, Tomohisa; Kubo, Satoshi; Nagano, Yuka; Nagao, Akiko; Yamane, Naoya; Nishikawa, Yuichi; Takamoto, Megumi; Ueno, Hiroki; Ochi, Kazuhide; Maruyama, Hirofumi; Yamamoto, Hiromi; Matsumoto, Masayasu
2016-01-01
Dysphagia occurs in acute stroke patients at high rates, and many of them develop aspiration pneumonia. Team approaches with the cooperation of various professionals have the power to improve the quality of medical care, utilizing the specialized knowledge and skills of each professional. In our hospital, a multidisciplinary participatory swallowing team was organized. The aim of this study was to clarify the influence of a team approach on dysphagia by comparing the rates of pneumonia in acute stroke patients prior to and post team organization. All consecutive acute stroke patients who were admitted to our hospital between April 2009 and March 2014 were registered. We analyzed the difference in the rate of pneumonia onset between the periods before team organization (prior period) and after team organization (post period). Univariate and multivariate analyses were performed using a Cox proportional hazards model to determine the predictors of pneumonia. We recruited 132 acute stroke patients from the prior period and 173 patients from the post period. Pneumonia onset was less frequent in the post period compared with the prior period (6.9% vs. 15.9%, respectively; p = 0.01). Based on a multivariate analysis using a Cox proportional hazards model, it was determined that a swallowing team approach was related to pneumonia onset independent from the National Institutes of Health Stroke Scale score on admission (adjusted hazard ratio 0.41, 95% confidence interval 0.19-0.84, p = 0.02). The multidisciplinary participatory swallowing team effectively decreased the pneumonia onset in acute stroke patients.
Influence of bacterial interactions on pneumococcal colonization of the nasopharynx
Shak, Joshua R.; Vidal, Jorge E.; Klugman, Keith P.
2013-01-01
Streptococcus pneumoniae (the pneumococcus) is a common commensal inhabitant of the nasopharynx and a frequent etiologic agent in serious diseases such as pneumonia, otitis media, bacteremia, and meningitis. Multiple pneumococcal strains can colonize the nasopharynx, which is also home to many other bacterial species. Intraspecies and interspecies interactions influence pneumococcal carriage in important ways. Co-colonization by two or more pneumococcal strains has implications for vaccine serotype replacement, carriage detection, and pneumonia diagnostics. Interactions between the pneumococcus and other bacterial species alter carriage prevalence, modulate virulence, and affect biofilm formation. By examining these interactions, this review highlights how the bacterial ecosystem of the nasopharynx changes the nature and course of pneumococcal carriage. PMID:23273566
Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?
Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M
2015-09-01
This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome. © 2015 Wiley Periodicals, Inc.
Shankar, J; Nguyen, M H; Crespo, M M; Kwak, E J; Lucas, S K; McHugh, K J; Mounaud, S; Alcorn, J F; Pilewski, J M; Shigemura, N; Kolls, J K; Nierman, W C; Clancy, C J
2016-06-01
Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.
White, Anthony R; Kaye, Clive; Poupard, James; Pypstra, Rienk; Woodnutt, Gary; Wynne, Brian
2004-01-01
Amoxicillin/clavulanate (Augmentin) is a broad-spectrum antibacterial that has been available for clinical use in a wide range of indications for over 20 years and is now used primarily in the treatment of community-acquired respiratory tract infections. Amoxicillin/clavulanate was developed to provide a potent broad spectrum of antibacterial activity, coverage of beta-lactamase-producing pathogens and a favourable pharmacokinetic/pharmacodynamic (PK/PD) profile. These factors have contributed to the high bacteriological and clinical efficacy of amoxicillin/clavulanate in respiratory tract infection over more than 20 years. This is against a background of increasing prevalence of antimicrobial resistance, notably the continued spread of beta-lactamase-mediated resistance in Haemophilus influenzae and Moraxella catarrhalis, and penicillin, macrolide and quinolone resistance in Streptococcus pneumoniae. The low propensity of amoxicillin/clavulanate to select resistance mutations as well as a favourable PK/PD profile predictive of high bacteriological efficacy may account for the longevity of this combination in clinical use. However, in certain defined geographical areas, the emergence of S. pneumoniae strains with elevated penicillin MICs has been observed. In order to meet the need to treat drug-resistant S. pneumoniae, two new high-dose amoxicillin/clavulanate formulations have been developed. A pharmacokinetically enhanced tablet dosage form of amoxicillin/clavulanate 2000/125 mg twice daily (available as Augmentin XR in the USA), has been developed for use in adult respiratory tract infection due to drug-resistant pathogens, such as S. pneumoniae with reduced susceptibility to penicillin, as well as beta-lactamase-producing H. influenzae and M. catarrhalis. Amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses (Augmentin ES-600) is for paediatric use in persistent or recurrent acute otitis media where there are risk factors for the involvement of beta-lactamase-producing strains or S. pneumoniae with reduced penicillin susceptibility. In addition to high efficacy, amoxicillin/clavulanate has a well known safety and tolerance profile of the two new high-dose formulations are not significantly different from those of conventional formulations. Amoxicillin/clavulanate is included in guidelines and recommendations for the treatment of bacterial sinusitis, acute otitis media, community-acquired pneumonia and acute exacerbations of chronic bronchitis. Amoxicillin/clavulanate continues to be an important agent in the treatment of community-acquired respiratory tract infections, both now and in the future.
Approach to common bacterial infections: community-acquired pneumonia.
Iroh Tam, Pui-Ying
2013-04-01
Community-acquired pneumonia (CAP) occurs more often in early childhood than at almost any other age. Many microorganisms are associated with pneumonia, but individual pathogens are difficult to identify, which poses problems in antibiotic management. This article reviews the common as well as new, emerging pathogens, as well as the guidelines for management of pediatric CAP. Current guidelines for pediatric CAP continue to recommend the use of high-dose amoxicillin for bacterial CAP and azithromycin for suspected atypical CAP (usually caused by Mycoplasma pneumoniae) in children. Copyright © 2013 Elsevier Inc. All rights reserved.
Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia.
Banoei, Mohammad M; Vogel, Hans J; Weljie, Aalim M; Kumar, Anand; Yende, Sachin; Angus, Derek C; Winston, Brent W
2017-04-19
Metabolomics is a tool that has been used for the diagnosis and prognosis of specific diseases. The purpose of this study was to examine if metabolomics could be used as a potential diagnostic and prognostic tool for H1N1 pneumonia. Our hypothesis was that metabolomics can potentially be used early for the diagnosis and prognosis of H1N1 influenza pneumonia. 1 H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry were used to profile the metabolome in 42 patients with H1N1 pneumonia, 31 ventilated control subjects in the intensive care unit (ICU), and 30 culture-positive plasma samples from patients with bacterial community-acquired pneumonia drawn within the first 24 h of hospital admission for diagnosis and prognosis of disease. We found that plasma-based metabolomics from samples taken within 24 h of hospital admission can be used to discriminate H1N1 pneumonia from bacterial pneumonia and nonsurvivors from survivors of H1N1 pneumonia. Moreover, metabolomics is a highly sensitive and specific tool for the 90-day prognosis of mortality in H1N1 pneumonia. This study demonstrates that H1N1 pneumonia can create a quite different plasma metabolic profile from bacterial culture-positive pneumonia and ventilated control subjects in the ICU on the basis of plasma samples taken within 24 h of hospital/ICU admission, early in the course of disease.
Pfister, Roman; Kochanek, Matthias; Leygeber, Timo; Brun-Buisson, Christian; Cuquemelle, Elise; Machado, Mariana Benevides; Piacentini, Enrique; Hammond, Naomi E; Ingram, Paul R; Michels, Guido
2014-03-10
Procalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza. Clinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search. PCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 μg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 μg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 μg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder. In critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment.
2014-01-01
Introduction Procalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza. Methods Clinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search. Results PCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 μg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 μg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 μg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder. Conclusions In critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment. PMID:24612487
Bacterial Pneumonia in Elderly Japanese Populations
Miyashita, Naoya; Yamauchi, Yasuhiro
2018-01-01
Bacterial pneumonia is one of the most important infectious diseases in terms of incidence, effect on quality of life, mortality, and impact on society. Pneumonia was the third leading cause of death in Japan in 2011. In 2016, 119 650 Japanese people died of pneumonia, 96% of whom were aged 65 years and above. The symptoms of pneumonia in elderly people are often atypical. Aspiration pneumonia is seen more frequently than in young people because of swallowing dysfunction in the elderly. The mortality rate is also higher in the elderly than in young people. In Japan, the population is aging at an unprecedented rate, and pneumonia in the elderly will be increasingly important in medicine and medical economics in the future. To manage pneumonia in the elderly, it is important to accurately evaluate its severity, administer appropriate antibiotic treatment, and implement effective preventive measures. PMID:29434484
Acute pneumonia and the cardiovascular system.
Corrales-Medina, Vicente F; Musher, Daniel M; Shachkina, Svetlana; Chirinos, Julio A
2013-02-09
Although traditionally regarded as a disease confined to the lungs, acute pneumonia has important effects on the cardiovascular system at all severities of infection. Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality. These findings suggest that outcomes of patients with pneumonia can be improved by prevention of the development and progression of associated cardiac complications. Before this hypothesis can be tested, however, an adequate mechanistic understanding of the cardiovascular changes that occur during pneumonia, and their role in the trigger of various cardiac complications, is needed. In this Review, we summarise knowledge about the burden of cardiac complications in adults with acute pneumonia, the cardiovascular response to this infection, the potential effects of commonly used cardiovascular and anti-infective drugs on these associations, and possible directions for future research. Copyright © 2013 Elsevier Ltd. All rights reserved.
Krishnan, Shilpa; Karg, Patricia E; Boninger, Michael L; Brienza, David M
2017-07-01
To determine if the presence of pneumonia and pressure ulcers are associated in individuals with an acute spinal cord injury during acute care and rehabilitation hospitalizations. Retrospective, secondary analyses of data obtained from the Spinal Cord Injury Model Systems enrolled from 1993 until 2006 Setting: Acute care hospitalization and inpatient rehabilitation facilities Participants: A cohort of individuals hospitalized in acute care (n = 3,098) and inpatient rehabilitation (n = 1,768) was included in the analysis. Frequencies of pressure ulcer formation and episodes of pneumonia were noted in both settings. Not applicable. Pressure ulcer formation and diagnosis of pneumonia Results: The development of pressure ulcers, including stage I, was 20.3% acute care and 21.1% during in inpatient rehabilitation. Multivariate logistic regression analyses revealed a significant association of pneumonia with occurrence of pressure ulcers (P ≤ 0.001, OR = 2.3 and 2.2 respectively), the American Spinal Injury Association Impairment Scale grades (P < 0.001), and utilization of mechanical ventilation (P < 0.01) in both settings. A higher presence of pressure ulcers was found in individuals with pneumonia, after adjusting for injury severity, age, sex, and utilization of mechanical ventilation. Impaired inflammatory response and decreased mobility in individuals with pneumonia may predispose these individuals to develop pressure ulcers. Surveillance and preventive measures for pressure ulcers should be rigorous in individuals with SCI and pneumonia.
Schachern, Patricia A; Kwon, Geeyoun; Briles, David E; Ferrieri, Patricia; Juhn, Steven; Cureoglu, Sebahattin; Paparella, Michael M; Tsuprun, Vladimir
2017-10-01
Bacterial resistance in acute otitis can result in bacterial persistence and biofilm formation, triggering chronic and recurrent infections. To investigate the middle ear inflammatory response to bacterial infection in human and chinchilla temporal bones. Six chinchillas underwent intrabullar inoculations with 0.5 mL of 106 colony-forming units (CFUs) of Streptococcus pneumoniae, serotype 2. Two days later, we counted bacteria in middle ear effusions postmortem. One ear from each chinchilla was processed in paraffin and sectioned at 5 µm. The opposite ear was embedded in epoxy resin, sectioned at a thickness of 1 µm, and stained with toluidine blue. In addition, we examined human temporal bones from 2 deceased donors with clinical histories of otitis media (1 with acute onset otitis media, 1 with recurrent infection). Temporal bones had been previously removed at autopsy, processed, embedded in celloidin, and cut at a thickness of 20 µm. Sections of temporal bones from both chinchillas and humans were stained with hematoxylin-eosin and immunolabeled with antifibrin and antihistone H4 antibodies. Histopatological and imminohistochemical changes owing to otitis media. Bacterial counts in chinchilla middle ear effusions 2 days after inoculation were approximately 2 logs above initial inoculum counts. Both human and chinchilla middle ear effusions contained bacteria embedded in a fibrous matrix. Some fibers in the matrix showed positive staining with antifibrin antibody, others with antihistone H4 antibody. In acute and recurrent otitis media, fibrin and neutrophil extracellular traps (NETs) are part of the host inflammatory response to bacterial infection. In the early stages of otitis media the host defense system uses fibrin to entrap bacteria, and NETs function to eliminate bacteria. In chronic otitis media, fibrin and NETs appear to persist.
Kim, Sang Hoon; Jeon, Eun Ju; Hong, Seok Min; Bae, Chang Hoon; Lee, Ho Yun; Park, Moo Kyun; Byun, Jae Yong; Kim, Myung Gu; Yeo, Seung Geun
2017-04-01
Changes over time in pathogens and their antibiotic sensitivity resulting from the recent overuse and misuse of antibiotics in otitis media (OM) have complicated treatment. This study evaluated changes over 5 years in principal pathogens and their antibiotic sensitivity in patients in Korea diagnosed with acute OM (AOM) and OM with effusion (OME). The study population consisted of 683 patients who visited the outpatient department of otorhinolaryngology in 7 tertiary hospitals in Korea between January 2010 and May 2015 and were diagnosed with acute AOM or OME. Aural discharge or middle ear fluid were collected from patients in the operating room or outpatient department and subjected to tests of bacterial identification and antibiotic sensitivity. The overall bacteria detection rate of AOM was 62.3% and OME was 40.9%. The most frequently isolated Gram-positive bacterial species was coagulase negative Staphylococcus aureus (CNS) followed by methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Streptococcus pneumonia (SP), whereas the most frequently isolated Gram-negative bacterium was Pseudomonas aeruginosa (PA). Regardless of OM subtype, ≥ 80% of CNS and MRSA strains were resistant to penicillin (PC) and tetracycline (TC); isolated MRSA strains showed low sensitivity to other antibiotics, with 100% resistant to PC, TC, cefoxitin (CFT), and erythromycin (EM); and isolated PA showed low sensitivity to quinolone antibiotics, including ciprofloxacin (CIP) and levofloxacin (LFX), and to aminoglycosides. Bacterial species and antibiotic sensitivity did not change significantly over 5 years. The rate of detection of MRSA was higher in OME than in previous studies. As bacterial predominance and antibiotic sensitivity could change over time, continuous and periodic surveillance is necessary in guiding appropriate antibacterial therapy. © 2017 The Korean Academy of Medical Sciences.
Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia.
Wu, Muzo; Gibbons, John G; DeLoid, Glen M; Bedugnis, Alice S; Thimmulappa, Rajesh K; Biswal, Shyam; Kobzik, Lester
2017-07-01
Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFNγ to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNγ-treated cells and improved survival in mice with postinfluenza pneumococcal pneumonia. Transcription factor analysis also indicated a role for transcription factor E-box (TFEB) in MARCO recovery. Overexpression of TFEB in THP-1 cells led to marked increases in MARCO. The ability of Akt activation to increase MARCO expression in IFNγ-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in postinfluenza bacterial pneumonia. Copyright © 2017 the American Physiological Society.
Wortham, Jonathan M; Gray, Jennifer; Verani, Jennifer; Contreras, Carmen Lucia; Bernart, Chris; Moscoso, Fabiola; Moir, Juan Carlos; Reyes Marroquin, Emma Lissette; Castellan, Rigoberto; Arvelo, Wences; Lindblade, Kim; McCracken, John P
2015-01-01
Bacterial pneumonia is a leading cause of illness and death worldwide, but quantifying its burden is difficult due to insensitive diagnostics. Although World Health Organization (WHO) protocol standardizes pediatric chest radiograph (CXR) interpretation for epidemiologic studies of bacterial pneumonia, its validity in adults is unknown. Patients (age ≥ 15 years) admitted with respiratory infections to two Guatemalan hospitals between November 2007 and March 2012 had urine and nasopharyngeal/oropharyngeal (NP/OP) swabs collected; blood cultures and CXR were also performed at physician clinical discretion. 'Any bacterial infection' was defined as a positive urine pneumococcal antigen test, isolation of a bacterial pneumonia pathogen from blood culture, or detection of an atypical bacterial pathogen by polymerase chain reaction (PCR) of nasopharyngeal/oropharyngeal (NP/OP) specimens. 'Viral infection' was defined as detection of viral pathogens by PCR of NP/OP specimens. CXRs were interpreted according to the WHO protocol as having 'endpoint consolidation', 'other infiltrate', or 'normal' findings. We examined associations between bacterial and viral infections and endpoint consolidation. Urine antigen and/or blood culture results were available for 721 patients with CXR interpretations; of these, 385 (53%) had endpoint consolidation and 253 (35%) had other infiltrate. Any bacterial infection was detected in 119 (17%) patients, including 106 (89%) pneumococcal infections. Any bacterial infection (Diagnostic Odds Ratio [DOR] = 2.9; 95% confidence Interval (CI): 1.3-7.9) and pneumococcal infection (DOR = 3.4; 95% CI: 1.5-10.0) were associated with 'endpoint consolidation', but not 'other infiltrate' (DOR = 1.7; 95% CI: 0.7-4.9, and 1.7; 95% CI: 0.7-4.9 respectively). Viral infection was not significantly associated with 'endpoint consolidation', 'other infiltrate,' or 'normal' findings. 'Endpoint consolidation' was associated with 'any bacterial infection,' specifically pneumococcal infection. Therefore, endpoint consolidation may be a useful surrogate for studies measuring the impact of interventions, such as conjugate vaccines, against bacterial pneumonia.
Gotanda, Hiroshi; Kameyama, Yumi; Yamaguchi, Yasuhiro; Ishii, Masaki; Hanaoka, Yoko; Yamamoto, Hiroshi; Ogawa, Sumito; Iijima, Katsuya; Akishita, Masahiro; Ouchi, Yasuyoshi
2013-01-01
Acute exogenous lipoid pneumonia is an uncommon condition caused by aspiration of oil-based substances, occurring mainly in children. Here, we report the case of an 83-year-old patient with Alzheimer's disease who presented with coughing and hypoxia. The diagnosis of acute exogenous lipoid pneumonia caused by accidental kerosene ingestion was made on the basis of the patient's clinical history, and typical radiological and cytological findings. The patient's cognitive impairment and an unsafe environment, in which the patient's 91-year-old husband stored kerosene in an old shochu bottle, were responsible for the accidental ingestion. Acute exogenous lipoid pneumonia should be considered in the differential diagnosis for acute respiratory disorders in the rapidly aging population. © 2013 Japan Geriatrics Society.
Wang, Tao; Zhang, Jiahai; Zhang, Xuecheng; Xu, Chao; Tu, Xiaoming
2013-01-01
Streptococcus pneumoniae is a pathogen causing acute respiratory infection, otitis media and some other severe diseases in human. In this study, the solution structure of a bacterial immunoglobulin-like (Big) domain from a putative S. pneumoniae surface protein SP0498 was determined by NMR spectroscopy. SP0498 Big domain adopts an eight-β-strand barrel-like fold, which is different in some aspects from the two-sheet sandwich-like fold of the canonical Ig-like domains. Intriguingly, we identified that the SP0498 Big domain was a Ca2+ binding domain. The structure of the Big domain is different from those of the well known Ca2+ binding domains, therefore revealing a novel Ca2+-binding module. Furthermore, we identified the critical residues responsible for the binding to Ca2+. We are the first to report the interactions between the Big domain and Ca2+ in terms of structure, suggesting an important role of the Big domain in many essential calcium-dependent cellular processes such as pathogenesis. PMID:23326635
The role of pneumolysin in pneumococcal pneumonia and meningitis.
Hirst, R A; Kadioglu, A; O'callaghan, C; Andrew, P W
2004-11-01
Diseases caused by Streptococcus pneumoniae include pneumonia, septicaemia and meningitis. All these are associated with high morbidity and mortality. The pneumococcus can colonize the nasopharynx, and this can be a prelude to bronchopneumonia and invasion of the vasculature space. Proliferation in the blood can result in a breach of the blood-brain barrier and entry into the cerebrospinal fluid (CSF) where the bacteria cause inflammation of the meningeal membranes resulting in meningitis. The infected host may develop septicaemia and/or meningitis secondary to bronchopneumonia. Also septicaemia is a common precursor of meningitis. The mechanisms surrounding the sequence of infection are unknown, but will be dependent on the properties of both the host and bacterium. Treatment of these diseases with antibiotics leads to clearance of the bacteria from the infected tissues, but the bacteriolytic nature of antibiotics leads to an acute release of bacterial toxins and thus after antibiotic therapy the patients can be left with organ-specific deficits. One of the main toxins released from pneumococci is the membrane pore forming toxin pneumolysin. Here we review the extensive studies on the role of pneumolysin in the pathogenesis of pneumococcal diseases.
The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia
Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom
2016-01-01
Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections. PMID:26511795
Influence of bacterial interactions on pneumococcal colonization of the nasopharynx.
Shak, Joshua R; Vidal, Jorge E; Klugman, Keith P
2013-03-01
Streptococcus pneumoniae (the pneumococcus) is a common commensal inhabitant of the nasopharynx and a frequent etiologic agent in serious diseases such as pneumonia, otitis media, bacteremia, and meningitis. Multiple pneumococcal strains can colonize the nasopharynx, which is also home to many other bacterial species. Intraspecies and interspecies interactions influence pneumococcal carriage in important ways. Co-colonization by two or more pneumococcal strains has implications for vaccine serotype replacement, carriage detection, and pneumonia diagnostics. Interactions between the pneumococcus and other bacterial species alter carriage prevalence, modulate virulence, and affect biofilm formation. By examining these interactions, this review highlights how the bacterial ecosystem of the nasopharynx changes the nature and course of pneumococcal carriage. Copyright © 2012 Elsevier Ltd. All rights reserved.
Castinel, Aurélie; Grinberg, Alex; Pattison, Rebecca; Duignan, Pádraig; Pomroy, Bill; Rogers, Lynn; Wilkinson, Ian
2007-05-16
The 2001/2002 and 2002/2003 breeding seasons of New Zealand sea lions (NZSLs) on the Auckland Islands were marked by a high pup mortality caused by acute bacterial infections. As part of a health survey from 1998/1999 to 2004/2005, tissues and swabs of lesions had been collected at necropsy to identify the bacteria associated with pup mortality. Klebsiella pneumoniae was grown in pure culture from 83% of various organs and lesions in 2001/2002 and 76% in 2002/2003, and less frequently in the following seasons (56% in 2003/2004 and 49% in 2004/2005). Pup isolates of K. pneumoniae showed identical minimal inhibitory concentrations (MIC) of cefuroxime, neomycin, cephalotin, cephalexin and dihydrostreptomycin, suggesting clonal aetiology of the pathogen. Isolates also tested negative for production of extended-spectrum beta-lactamases (ESBLs), which was not in favour of an anthropogenetic origin of the epidemic strain. Pulsed-field gel electrophoresis (PFGE) of XbaI DNA macrorestriction fragments was performed on isolates of K. pneumoniae and Klebsiella oxytoca from 35 pups, thee NZSL adult females, and from three human patients for comparison. PFGE showed that pup isolates of K. pneumoniae were genetically indistinguishable but were neither related to K. pneumoniae from humans and from NZSL adults, nor to K. oxytoca from NZSLs. It is concluded that the 2001/2002 and 2002/2003 epidemics at Sandy Bay rookery were caused by a single K. pneumoniae clonal lineage, genetically different from the strain carried by adult NZSLs. An anthropogenic origin of the K. pneumoniae clone could not be confirmed, but further investigations are required to rule-out such occurrence.
Hou, Fei; Wang, Likui; Wang, Hong; Gu, Junchao; Li, Meiling; Zhang, Jingkai; Ling, Xiao; Gao, Xiaofang; Luo, Cheng
2015-06-01
Inflammation is the predominant characteristic of pneumonia. The present study aimed to to identify a faster and more reliable novel inflammatory marker for the diagnosis of pneumonia. The expression of the S100A12 gene was analyzed by reverse transcription quantitative polymerase chain reaction in samples obtained from 46 patients with bacterial pneumonia and other infections, compared with samples from 20 healthy individuals, using the 2‑ΔΔCt method. The expression levels of S100A12 were increased in 12 patients with bacterial pneumonia. Compared with clinical inflammatory data, a positive correlation was observed between the expression of the S100A12 gene and levels of white blood cells, C‑reactive protein (CRP), thrombocytocrit, neutrophils, erythrocyte sedimentation and soterocytes, and an inverse correlation was observed with the width of red blood cell volume distribution and platelet distribution, monocytes and hemoglobin, using Pearson's product‑moment correlation method. The P‑value of CRP and erythrocyte sedimentation were revealed to be statistically significant (P<0.05). A sporadic distribution of S100A12 was observed in a heatmap among the patients with different infections and bacterial pneumonia. Furthermore, the expression of S100A12 occurred in parallel to the number of clumps of inflamed tissue observed in chest computed tomography and X‑ray. The value of gene expression of S100A12 (>1.0) determined using the 2‑ΔΔCt method was associated with more severe respiratory diseases in the patients compromised by bacterial pneumonia, sepsis and pancreatitis. These findings suggested that S100A12 is an effective marker for inflammatory diseases.
21 CFR 522.90b - Ampicillin trihydrate for suspension.
Code of Federal Regulations, 2010 CFR
2010-04-01
.... Treatment of respiratory tract infections caused by organisms susceptible to ampicillin, bacterial pneumonia (shipping fever, calf pneumonia, and bovine pneumonia) caused by Aerobacter spp., Klebsiella spp...
Brady, Jacob S.; Romano-Keeler, Joann; Drake, Wonder P.; Norris, Patrick R.; Jenkins, Judith M.; Isaacs, Richard J.; Boczko, Erik M.
2015-01-01
BACKGROUND: Ventilator-associated pneumonia (VAP) remains a common complication in critically ill surgical patients, and its diagnosis remains problematic. Exhaled breath contains aerosolized droplets that reflect the lung microbiota. We hypothesized that exhaled breath condensate fluid (EBCF) in hygroscopic condenser humidifier/heat and moisture exchanger (HCH/HME) filters would contain bacterial DNA that qualitatively and quantitatively correlate with pathogens isolated from quantitative BAL samples obtained for clinical suspicion of pneumonia. METHODS: Forty-eight adult patients who were mechanically ventilated and undergoing quantitative BAL (n = 51) for suspected pneumonia in the surgical ICU were enrolled. Per protocol, patients fulfilling VAP clinical criteria undergo quantitative BAL bacterial culture. Immediately prior to BAL, time-matched HCH/HME filters were collected for study of EBCF by real-time polymerase chain reaction. Additionally, convenience samples of serially collected filters in patients with BAL-diagnosed VAP were analyzed. RESULTS: Forty-nine of 51 time-matched EBCF/BAL fluid samples were fully concordant (concordance > 95% by κ statistic) relative to identified pathogens and strongly correlated with clinical cultures. Regression analysis of quantitative bacterial DNA in paired samples revealed a statistically significant positive correlation (r = 0.85). In a convenience sample, qualitative and quantitative polymerase chain reaction analysis of serial HCH/HME samples for bacterial DNA demonstrated an increase in load that preceded the suspicion of pneumonia. CONCLUSIONS: Bacterial DNA within EBCF demonstrates a high correlation with BAL fluid and clinical cultures. Bacterial DNA within EBCF increases prior to the suspicion of pneumonia. Further study of this novel approach may allow development of a noninvasive tool for the early diagnosis of VAP. PMID:25474571
Solithromycin for the treatment of community-acquired bacterial pneumonia.
Viasus, Diego; Ramos, Oscar; Ramos, Leidy; Simonetti, Antonella F; Carratalà, Jordi
2017-01-01
Community-acquired pneumonia is a major public health problem worldwide. In recent years, there has been an increase in the frequency of resistance to the antimicrobials such as β-lactams or macrolides which have habitually been used against the causative pathogens. Solithromycin, a next-generation macrolide, is the first fluoroketolide with activity against most of the frequently isolated bacteria in community-acquired pneumonia, including typical and atypical bacteria as well as macrolide-resistant Streptococcus pneumoniae. Areas covered: A detailed assessment of the literature relating to the antimicrobial activity, pharmacokinetic/pharmacodynamic properties, efficacy, tolerability and safety of solithromycin for the treatment of community-acquired bacterial pneumonia Expert commentary: Recent randomized controlled phase II/III trials have demonstrated the equivalent efficacy of oral and intravenous solithromycin compared with fluoroquinolones in patients with lower mild-to-moderate respiratory infections, and have shown that systemic adverse events are comparable between solithromycin and alternative treatments. However, studies of larger populations which are able to identify infrequent adverse events are now needed to confirm these findings. On balance, current data supports solithromycin as a promising therapy for empirical treatment in adults with community-acquired bacterial pneumonia.
González-Juarbe, Norberto; Bradley, Kelley Margaret; Shenoy, Anukul Taranath; Gilley, Ryan Paul; Reyes, Luis Felipe; Hinojosa, Cecilia Anahí; Restrepo, Marcos Ignacio; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier
2017-01-01
We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling. PMID:28387756
González-Juarbe, Norberto; Bradley, Kelley Margaret; Shenoy, Anukul Taranath; Gilley, Ryan Paul; Reyes, Luis Felipe; Hinojosa, Cecilia Anahí; Restrepo, Marcos Ignacio; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier
2017-05-01
We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling.
Zhu, Luchang; Lin, Jingjun; Kuang, Zhizhou; Vidal, Jorge E.; Lau, Gee W.
2015-01-01
Summary The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 “late” competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes. Graphical abstract During genetic transformation of pneumococcus, the alternative sigma factor ComX regulates expression of 14 late competence genes important for virulence. The constitutive baseline expression of some of these genes is important for bacteremia and acute pneumonia infections. In contrast, elevated expression of DprA, CbpD, CibAB, and Cinbox are dependent on competence development, enhancing the release of pneumolysin. These results distinguish the role of basal expression versus competence induction in virulence determinants regulated by ComX. PMID:25846124
Risks and Benefits Associated With Antibiotic Use for Acute Respiratory Infections: A Cohort Study
Meropol, Sharon B.; Localio, A. Russell; Metlay, Joshua P.
2013-01-01
PURPOSE Antibiotics are frequently prescribed for acute nonspecific respiratory infections (ARIs), presumably to avoid small risks of progression to serious bacterial illness. However, even low risks of associated adverse drug events could result in many such events at the population level. Our objective was to assess the risks and benefits of antibiotic use in a cohort of patients with ARIs, comparing outcomes of patients who were prescribed antibiotics with outcomes of patients not receiving antibiotics. METHODS We used a June 1986 to August 2006 cohort of adult patients with ARI visits from a UK primary care database. Exposure was an antibiotic prescribed with the visit. Primary outcomes were hospitalization within 15 days for (1) severe adverse drug events (hypersensitivity, diarrhea, seizure, arrhythmia, hepatic or renal failure), and (2) community-acquired pneumonia. RESULTS The cohort included 1,531,019 visits with an ARI diagnosis; prescriptions for antibiotics were given in 65% of cases. The adjusted risk difference for treated vs untreated patients per 100,000 visits was 1.07 fewer adverse events (95% CI, −4.52 to 2.38; P = .54) and 8.16 fewer pneumonia hospitalizations (95% CI, −13.24 to −3.08; P = .002). The number needed to treat to prevent 1 hospitalization for pneumonia was 12,255. CONCLUSIONS Compared with patients with ARI who were not treated with antibiotics, patients who were treated with antibiotics were not at increased risk of severe adverse drug events and had a small decreased risk of pneumonia hospitalization. This small benefit from antibiotics for a common ambulatory diagnosis creates persistent tension; at the societal level, physicians are compelled to reduce antibiotic prescribing, thus minimizing future resistance, whereas at the encounter level, they are compelled to optimize the benefit-risk balance for that patient. PMID:23508604
Risks and benefits associated with antibiotic use for acute respiratory infections: a cohort study.
Meropol, Sharon B; Localio, A Russell; Metlay, Joshua P
2013-01-01
Antibiotics are frequently prescribed for acute nonspecific respiratory infections (ARIs), presumably to avoid small risks of progression to serious bacterial illness. However, even low risks of associated adverse drug events could result in many such events at the population level. Our objective was to assess the risks and benefits of antibiotic use in a cohort of patients with ARIs, comparing outcomes of patients who were prescribed antibiotics with outcomes of patients not receiving antibiotics. We used a June 1986 to August 2006 cohort of adult patients with ARI visits from a UK primary care database. Exposure was an antibiotic prescribed with the visit. Primary outcomes were hospitalization within 15 days for (1) severe adverse drug events (hypersensitivity, diarrhea, seizure, arrhythmia, hepatic or renal failure), and (2) community-acquired pneumonia. The cohort included 1,531,019 visits with an ARI diagnosis; prescriptions for antibiotics were given in 65% of cases. The adjusted risk difference for treated vs untreated patients per 100,000 visits was 1.07 fewer adverse events (95% CI, -4.52 to 2.38; P = .54) and 8.16 fewer pneumonia hospitalizations (95% CI, -13.24 to -3.08; P = .002). The number needed to treat to prevent 1 hospitalization for pneumonia was 12,255. Compared with patients with ARI who were not treated with antibiotics, patients who were treated with antibiotics were not at increased risk of severe adverse drug events and had a small decreased risk of pneumonia hospitalization. This small benefit from antibiotics for a common ambulatory diagnosis creates persistent tension; at the societal level, physicians are compelled to reduce antibiotic prescribing, thus minimizing future resistance, whereas at the encounter level, they are compelled to optimize the benefit-risk balance for that patient.
Tong, Hua Hua; Li, Yong Xing; Stahl, Gregory L; Thurman, Joshua M
2010-03-01
To define the roles of specific complement activation pathways in host defense against Streptococcus pneumoniae in acute otitis media (AOM), we investigated the susceptibility to AOM in mice deficient in complement factor B and C2 (Bf/C2(-/)(-)), C1qa (C1qa(-/)(-)), and factor B (Bf(-)(/)(-)). Bacterial titers of both S. pneumoniae serotype 6A and 14 in the middle ear lavage fluid samples from Bf/C2(-/)(-), Bf(-)(/)(-), and C1qa(-/)(-) mice were significantly higher than in samples from wild-type mice 24 h after transtympanical infection (P < 0.05) and remained persistently higher in samples from Bf/C2(-/)(-) mice than in samples from wild-type mice. Bacteremia occurred in Bf/C2(-/)(-), Bf(-)(/)(-), and C1qa(-/)(-) mice infected with both strains, but not in wild-type mice. Recruitment of inflammatory cells was paralleled by enhanced production of inflammatory mediators in the middle ear lavage samples from Bf/C2(-/)(-) mice. C3b deposition on both strains was greatest for sera obtained from wild-type mice, followed by C1qa(-)(/)(-) and Bf(-)(/)(-) mice, and least for Bf/C2(-)(/)(-) mice. Opsonophagocytosis and whole-blood killing capacity of both strains were significantly decreased in the presence of sera or whole blood from complement-deficient mice compared to wild-type mice. These findings indicate that both the classical and alternative complement pathways are critical for middle ear immune defense against S. pneumoniae. The reduced capacity of complement-mediated opsonization and phagocytosis in the complement-deficient mice appears to be responsible for the impaired clearance of S. pneumoniae from the middle ear and dissemination to the bloodstream during AOM.
File, Thomas M; Jacobs, Michael R; Poole, Michael D; Wynne, Brian
2002-10-01
The efficacy of a new pharmacokinetically enhanced formulation of amoxycillin/clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of amoxycillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP) with amoxycillin (+/-clavulanic acid) MICs of =4 mg/l, was evaluated in patients with respiratory infections caused by S. pneumoniae, including PRSP (penicillin MICs 2-16 mg/l). Data from nine clinical studies were combined (total intent-to-treat N=5531). Six randomized, double-blind studies used levofloxacin 500 mg od in acute bacterial sinusitis (ABS), levofloxacin 500 mg od in acute exacerbations of chronic bronchitis (AECB), clarithromycin 500 mg bid in AECB, AMX/CA 875/125 mg bid and tid in community-acquired pneumonia (CAP) and AMX/CA 1000/125 mg tid in CAP as comparators. The three remaining studies (two in ABS and one in CAP) were non-comparative. In the AMX/CA 2000/125 mg bid-treated patients evaluable at follow-up (Day 14-39), outcome was successful in 60/64 (93.7%) patients with S. pneumoniae infections in the comparative studies and 348/363 (95.9%) in the non-comparative studies, including 95.6% of all patients and 95.2% of patients whose isolates had AMX/CA MICs of >/=4 mg/l. In the pooled comparator group, the success rate at follow-up was 86.5% (45/52). For PRSP (AMX/CA MICs of 0.5-8 mg/l), the overall success rate was 98.2% (55/56) at follow-up for AMX/CA 2000/125 mg and 50.0% (2/4) for comparators. AMX/CA 2000/125 mg shows efficacy comparable to that of the comparators evaluated against S. pneumoniae infections. Due to its favorable pharmacokinetic/pharmacodynamic profile and promising clinical success, the new AMX/CA 2000/125 mg formulation should be considered for the empirical treatment of respiratory tract infections in regions with a high prevalence of antimicrobial-resistant S. pneumoniae and in patients at high risk of antimicrobial-resistant S. pneumoniae infection as this formulation covers many PRSP that are non-susceptible to amoxycillin (+/-clavulanic acid) (MICs of >/=4 mg/l) as well as common beta-lactamase-producing respiratory pathogens.
Ma, H M; Ip, Margaret; Woo, Jean; Hui, David S C; Lui, Grace C Y; Lee, Nelson L S; Chan, Paul K S; Rainer, T H
2013-09-01
The relationship between healthcare-associated pneumonia (HCAP) and resistant bacteria is unclear. The aim of this study was to identify the risk factors for pneumonia caused by drug-resistant bacteria (DRB). A prospective cohort study was conducted at a tertiary teaching hospital in Hong Kong. Consecutive older patients (aged ≥65 years) were hospitalized with pneumonia from January 2004 to June 2005. DRB comprised methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae and Acinetobacter baumannii. The entire cohort consisted of 1176 older patients. Of 472 (40.1%) patients with etiological diagnosis established, bacterial pneumonia was found in 354 (30.1%) cases. DRB were isolated in 48 patients: P. aeruginosa (41), MRSA (5) and ESBL producing enteric bacilli (3). Co-infection with P. aeruginosa and MRSA was found in one patient. The prevalence of DRB in culture-positive pneumonia was 20.1% (48/239). Patients with DRB were more likely to have limitation in activities of daily living, bronchiectasis, dementia, severe pneumonia, recent hospitalization and recent antibiotic use. Logistic regression revealed that bronchiectasis [relative risk (RR) 14.12, P = 0.002], recent hospitalization (RR 4.89, P < 0.001) and severe pneumonia (RR 2.42, P = 0.010) were independent predictors of drug-resistant bacterial pneumonia. Recent hospitalization is the only risk factor for HCAP which is shown to be associated with DRB. Nursing home residence is not a risk factor. The concept of HCAP may not be totally applicable in Hong Kong where the prevalence of drug-resistant pathogens in pneumonia is low.
Xu, Qingfu; Wischmeyer, Jareth; Gonzalez, Eduardo; Pichichero, Michael E
2017-07-01
We sought to understand how polymicrobial colonization varies during health, viral upper respiratory infection (URI) and acute upper respiratory bacterial infection to understand differences in infection-prone vs. non-prone patients. Nasopharyngeal (NP) samples were collected from 74 acute otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (Mcat) were identified by culture. NP colonization rates of multiple otopathogens during health were significantly lower than during viral URI, and during URI they were lower than at onset of upper respiratory bacterial infection in both AOM infection-prone and non-prone children. AOM infection-prone children had higher polymicrobial colonization rates than non-prone children during health, viral URI and AOM. Polymicrobial colonization rates of AOM infection-prone children during health were equivalent to that of non-prone children during viral URI, and during viral URI were equivalent to that of non-prone during AOM infection. Spn colonization was positively associated with NTHi and Mcat colonization during health, but negatively during AOM infection. The infection-prone patients more frequently have multiple potential bacterial pathogens in the NP than the non-prone patients. Polymicrobial interaction in the NP differs during health and at onset of infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release.
Bryant, Joseph C; Dabbs, Ridge C; Oswalt, Katie L; Brown, Lindsey R; Rosch, Jason W; Seo, Keun S; Donaldson, Janet R; McDaniel, Larry S; Thornton, Justin A
2016-11-09
Streptococcus pneumoniae is one of the leading causes of community acquired pneumonia and acute otitis media. Certain aspects of S. pneumoniae's virulence are dependent upon expression and release of the protein toxin pneumolysin (PLY) and upon the activity of the peroxide-producing enzyme, pyruvate oxidase (SpxB). We investigated the possible synergy of these two proteins and identified that release of PLY is enhanced by expression of SpxB prior to stationary phase growth. Mutants lacking the spxB gene were defective in PLY release and complementation of spxB restored PLY release. This was demonstrated by cytotoxic effects of sterile filtered supernatants upon epithelial cells and red blood cells. Additionally, peroxide production appeared to contribute to the mechanism of PLY release since a significant correlation was found between peroxide production and PLY release among a panel of clinical isolates. Exogenous addition of H 2 O 2 failed to induce PLY release and catalase supplementation prevented PLY release in some strains, indicating peroxide may exert its effect intracellularly or in a strain-dependent manner. SpxB expression did not trigger bacterial cell death or LytA-dependent autolysis, but did predispose cells to deoxycholate lysis. Here we demonstrate a novel link between spxB expression and PLY release. These findings link liberation of PLY toxin to oxygen availability and pneumococcal metabolism.
Pneumococcal vaccination and chronic respiratory diseases.
Froes, Filipe; Roche, Nicolas; Blasi, Francesco
2017-01-01
Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases.
Filioussis, George; Petridou, Evanthia; Karavanis, Emmanouel
2014-01-01
A yet-undescribed bacterial species, tentatively named “Porphyromonas katsikii,” was isolated from individuals of a small goat herd with pyogranulomatous pneumonia during an outbreak of acute respiratory disease. The isolated bacteria grew in the form of black-pigmented colonies after 14 days of incubation under anaerobic conditions at 37°C on a tryptic soy blood agar medium. The bacteria were identified as a yet-undescribed Porphyromonas species by determination of the nucleotide sequence of the rrs 16S rRNA gene, and this species was tentatively named Porphyromonas katsikii. PCR amplification with specific primers for this yet-undescribed species revealed the presence of P. katsikii in the lung tissue of all affected animals, while no PCR signals were evidenced from the lungs of healthy goats or from goats with pasteurellosis caused by Mannheimia haemolytica. These data indicate P. katsikii as the causative agent of acute respiratory distress. P. katsikii is phylogenetically related to Porphyromonas somerae and Porphyromonas levii, which cause pathologies in humans and animals, respectively. P. katsikii was not detected by PCR from samples of the gingival pockets or of the faces of healthy goats. PMID:25540395
Vissing, Nadja H; Chawes, Bo L K; Bisgaard, Hans
2013-11-15
The frequency of pneumonia and bronchiolitis exhibits considerable variation in otherwise healthy children, and suspected risk factors explain only a minor proportion of the variation. We hypothesized that alterations in the airway microbiome in early life may be associated with susceptibility to pneumonia and bronchiolitis in young children. To investigate the relation between neonatal airway colonization and pneumonia and bronchiolitis during the first 3 years of life. Participants comprised children of the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort, a prospective birth cohort study of 411 children born to mothers with asthma. Aspirates from the hypopharynx at age 4 weeks were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Clinical information on pneumonia and bronchiolitis within the first 3 years of life was prospectively collected by the research physicians at the center. Analyses were adjusted for covariates associated with pneumonia and bronchiolitis and bacterial airway colonization. Hypopharyngeal aspirates and full clinical follow-up until 3 years of age were available for 265 children. Of these, 56 (21%) neonates were colonized with S. pneumoniae, H. influenzae, and/or M. catarrhalis at 4 weeks of age. Colonization with at least one of these microorganisms (but not S. aureus) was significantly associated with increased incidence of pneumonia and bronchiolitis (adjusted incidence rate ratio, 1.79 [1.29-2.48]; P < 0.005) independently of concurrent or later asthma. Neonatal airway colonization with S. pneumoniae, H. influenzae, or M. catarrhalis is associated with increased risk of pneumonia and bronchiolitis in early life independently of asthma. This suggests a role of pathogenic bacterial colonization of the airways in neonates for subsequent susceptibly to pneumonia and bronchiolitis.
The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia.
Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost
2016-04-01
Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Makokha, Caroline; Mott, Joshua; Njuguna, Henry N; Khagayi, Sammy; Verani, Jennifer R; Nyawanda, Bryan; Otieno, Nancy; Katz, Mark A
2016-07-01
Although the severe acute respiratory illness (SARI) case definition is increasingly used for inpatient influenza surveillance, pneumonia is a more familiar term to clinicians and policymakers. We evaluated WHO case definitions for severe acute respiratory illness (SARI) and pneumonia (Integrated Management of Childhood Illnesses (IMCI) for children aged <5 years and Integrated Management of Adolescent and Adult Illnesses (IMAI) for patients aged ≥13 years) for detecting laboratory-confirmed influenza among hospitalized ARI patients. Sensitivities were 84% for SARI and 69% for IMCI pneumonia in children aged <5 years and 60% for SARI and 57% for IMAI pneumonia in patients aged ≥13 years. Clinical pneumonia case definitions may be a useful complement to SARI for inpatient influenza surveillance. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
Group A beta-haemolytic streptococcal acute chest event in a child with sickle cell anaemia.
Suara, R O
2001-06-01
Acute chest syndrome is a major cause of death and hospitalisation in children with sickle cell anaemia. It is often initiated by an infection, particularly pneumonia. Microbial agents previously not associated with acute chest syndrome are becoming increasingly important. Group A beta-haemolytic Streptococcus (GABHS) is thought to be an uncommon cause of pneumonia in children with sickle cell anaemia. We report a 15-year-old African-American girl who presented with an acute chest event characterised by fever, cough, chest pain, shortness of breath, right upper abdominal quadrant pain, jaundice and otitis media. Chest radiograph showed multi-lobar pneumonia with left pleural effusion. Group A beta-haemolytic Streptococcus was isolated from culture of pleural and middle ear fluids. She responded to therapy that included antibiotics, exchange blood transfusion, oxygen, thoracotomy chest tube drainage and decortication. In a child with sickle cell anaemia presenting with fever and an acute chest event, pneumonia should be considered and GABHS recognised as a possible aetiological agent. In addition, a chest X-ray should be obtained and antibiotics against agents causing community-acquired pneumonia instituted.
Discovery and Validation of Biomarkers to Guide Clinical Management of Pneumonia in African Children
Huang, Honglei; Ideh, Readon C.; Gitau, Evelyn; Thézénas, Marie L.; Jallow, Muminatou; Ebruke, Bernard; Chimah, Osaretin; Oluwalana, Claire; Karanja, Henri; Mackenzie, Grant; Adegbola, Richard A.; Kwiatkowski, Dominic; Kessler, Benedikt M.; Berkley, James A.; Howie, Stephen R. C.; Casals-Pascual, Climent
2014-01-01
Background. Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management. Methods. We conducted a mass spectrometry–based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC). Results. Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 [95% confidence interval, .64–.79]) and highly predictive of bacteremia (78% [64%–92%]), pneumococcal bacteremia (84% [71%–98%]), and “probable bacterial etiology” (91% [84%–98%]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% [95% confidence interval, 99%–100%]) and Kenyan children (82% [74%–91%]). Conclusions. Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies. PMID:24696240
Pulmonary tuberculosis in severely-malnourished or HIV-infected children with pneumonia: a review.
Chisti, Mohammod Jobayer; Ahmed, Tahmeed; Pietroni, Mark A C; Faruque, Abu S G; Ashraf, Hasan; Bardhan, Pradip K; Hossain, Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus
2013-09-01
Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/ very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies from South Africa and 137 SAM children from other studies, 64 (10%) and 29 (21%) isolates of M. tuberculosis were identified respectively. Children from South Africa were infected with HIV without specification of their nutritional status whereas children from other countries had SAM but without indication of their HIV status. Our review of the existing data suggests that pulmonary tuberculosis may be more common than it is generally suspected in children with acute pneumonia and SAM, or HIV infection. Because of the scarcity of data, there is an urgent need to investigate PTB as one of the potential aetiologies of acute pneumonia in these children in a carefully-conducted larger study, especially outside Africa.
Pulmonary Tuberculosis in Severely-malnourished or HIV-infected Children with Pneumonia: A Review
Ahmed, Tahmeed; Pietroni, Mark A.C.; Faruque, Abu S.G.; Ashraf, Hasan; Bardhan, Pradip K.; Hossain, Md. Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus
2013-01-01
Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies from South Africa and 137 SAM children from other studies, 64 (10%) and 29 (21%) isolates of M. tuberculosis were identified respectively. Children from South Africa were infected with HIV without specification of their nutritional status whereas children from other countries had SAM but without indication of their HIV status. Our review of the existing data suggests that pulmonary tuberculosis may be more common than it is generally suspected in children with acute pneumonia and SAM, or HIV infection. Because of the scarcity of data, there is an urgent need to investigate PTB as one of the potential aetiologies of acute pneumonia in these children in a carefully-conducted larger study, especially outside Africa. PMID:24288943
Yadhav Ml, Kala
2014-04-01
Bacterial meningitis is one of the most serious infections seen in infants and children, which is associated with acute complications and chronic morbidity. Infections of Central Nervous System (CNS) still dominate the scene of childhood neurological disorders in most of the developing tropical countries. To isolate, identify and determine the antibiotic susceptibility patterns of pathogens associated with bacterial meningitis. We also aimed to comparatively evaluate of Gram staining, culture and bacterial antigen detection in cerebrospinal fluid samples. Present comparative study included 100 CSF samples of children below the age of 5 years, who were clinically suspected meningitis cases. The samples were subjected to Gram staining, culture and Latex agglutination test (LAT). The organisms isolated in the study were characterized and antibiotic susceptibility test was done according to standard guidelines. It was done by using Gaussian test. Of the 100 cases, 24 were diagnosed as Acute bacterial meningitis (ABM) cases by. Gram staining, culture and latex agglutination test. 21 (87.5%) cases were culture positive, with 2 cases being positive for polymicrobial isolates. Gram staining was positive in 17 (70.53%) cases and LAT was positive in 18 (33.33%) cases. Streptococcus pneumoniae was the predominant organism which was isolated and it was sensitive to antibiotics. In the present study, male to female ratio was 1.27:1, which showed a male preponderance. With the combination of Gram staining, culture, and LAT, 100% sensitivity and specificity can be achieved (p < 0.001). Gram staining and LAT can detect 85% of cases of ABM. Bacterial meningitis is a medical emergency and making an early diagnosis and providing treatment early are life saving and they reduce chronic morbidity.
[Clinical efficacy of flomoxef in the field of pediatrics].
Ogura, H; Kubota, H; Murakami, N; Tomoda, T; Hamada, F; Matsumoto, K; Araki, K; Ogura, Y; Kurashige, T; Kitamura, I
1987-08-01
A new oxacephem antibiotic, flomoxef sodium (FMOX, 6315-S), was studied for its clinical efficacy in the field of pediatrics. The treated patients were infants and children ranging from 6 months to 14 years old suffering from bacterial pneumonia in 3 cases, acute tonsillitis in 2 cases, acute enterocolitis in 2 cases, and cellulitis and urinary tract infection in 1 case each, a total of 9 cases. FMOX was administered at (levels of) 57-150 mg/kg in daily dose with durations of treatment ranging from 5 to 18 days. Clinical efficacies of good or excellent results were obtained in all cases (excellent in 4, good in 5). As an adverse reaction, eosinophilia was observed in 1 patient. This elevation is, however, normalized with the cessation of the treatment.
Kramna, Lenka; Oikarinen, Sami; Sipilä, Markku; Rautiainen, Markus; Aittoniemi, Janne; Laranne, Jussi; Hyöty, Heikki; Cinek, Ondrej
2017-01-01
ABSTRACT The aim of the study was to analyze the bacteriome of acute otitis media with a novel modification of next-generation sequencing techniques. Outpatient children with acute otitis media were enrolled in the study, and middle ear fluids were collected during 90 episodes from 79 subjects aged 5 to 42 months (median age, 19 months). The bacteriome profiles of middle ear fluid samples were determined by a nested-PCR amplification of the 16S rRNA gene (V4 region), followed by mass sequencing. The profiling results were compared to the results of specific PCR assays targeting selected prevalent pathogens. Bacteriome profiling using nested amplification of low-volume samples was aided by a bioinformatic subtraction of signal contaminants from the recombinant polymerase, achieving a sensitivity slightly lower than that of specific PCR detection. Streptococcus pneumoniae was detected in 28 (31%) samples, Haemophilus influenzae in 24 (27%), Moraxella catarrhalis in 18 (20%), Staphylococcus spp. in 21 (23%), Turicella otitidis in 5 (5.6%), Alloiococcus otitidis in 3 (3.3%), and other bacteria in 14 (16%) using bacteriome profiling. S. pneumoniae was the dominant pathogen in 14 (16%) samples, H. influenzae in 15 (17%), M. catarrhalis in 5 (5.6%), T. otitidis in 2, and Staphylococcus auricularis in 2. Weaker signals of Prevotella melaninogenica, Veillonella dispar, and Veillonella montpellierensis were noted in several samples. Fourteen samples (16%) were not explainable by bacterial pathogens; novel causative agents were not detected. In conclusion, unbiased bacteriome profiling helped in depicting the true mutual quantitative ratios of ear bacteria, but at present, its complicated protocol impedes its routine clinical use. IMPORTANCE Although S. pneumoniae, H. influenzae, and M. catarrhalis have been long established as the most important pathogens in acute otitis media using culture and specific PCR assays, the knowledge of their mutual quantitative relations and possible roles of other bacteria is incomplete. The advent of unbiased bacteriome 16S rRNA gene profiling has allowed the detection of nearly all bacteria present in the sample, and it helps in depicting their mutual quantitative ratios. Due to the difficulties in performing mass sequencing in low-volume samples, only a few bacteriome-profiling studies of otitis media have been published, all limited to cases of chronic otitis media. Here, we present a study on samples obtained from young children with acute otitis media, successfully using a strategy of nested PCR coupled with mass sequencing, and demonstrate that the method can confer quantitative information hardly obtainable by other methods. PMID:28357413
Abdulnour, R E; Sham, H P; Douda, D N; Colas, R A; Dalli, J; Bai, Y; Ai, X; Serhan, C N; Levy, B D
2016-09-01
Bacterial pneumonia is a leading cause of morbidity and mortality worldwide. Host responses to contain infection and mitigate pathogen-mediated lung inflammation are critical for pneumonia resolution. Aspirin-triggered resolvin D1 (AT-RvD1; 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) is a lipid mediator (LM) that displays organ-protective actions in sterile lung inflammation, and regulates pathogen-initiated cellular responses. Here, in a self-resolving murine model of Escherichia coli pneumonia, LM metabololipidomics performed on lungs obtained at baseline, 24, and 72 h after infection uncovered temporal regulation of endogenous AT-RvD1 production. Early treatment with exogenous AT-RvD1 (1 h post infection) enhanced clearance of E. coli and Pseudomonas aeruginosa in vivo, and lung macrophage phagocytosis of fluorescent bacterial particles ex vivo. Characterization of macrophage subsets in the alveolar compartment during pneumonia identified efferocytosis by infiltrating macrophages (CD11b(Hi) CD11c(Low)) and exudative macrophages (CD11b(Hi) CD11c(Hi)). AT-RvD1 increased efferocytosis by these cells ex vivo, and accelerated neutrophil clearance during pneumonia in vivo. These anti-bacterial and pro-resolving actions of AT-RvD1 were additive to antibiotic therapy. Taken together, these findings suggest that the pro-resolving actions of AT-RvD1 during pneumonia represent a novel host-directed therapeutic strategy to complement the current antibiotic-centered approach for combatting infections.
Association between bacterial infection and radiologically confirmed pneumonia among children.
Nascimento-Carvalho, Cristiana M; Araújo-Neto, César A; Ruuskanen, Olli
2015-05-01
The role of chest radiograph (CXR) among children with community-acquired pneumonia is controversial. We aimed to assess if there is association between a specific etiology and radiologically confirmed pneumonia. This was a prospective cross-sectional study. Based on report of respiratory complaints and fever/difficulty breathing plus the detection of pulmonary infiltrate/pleural effusion on the CXR taken upon admission read by the pediatrician on duty, children <5-year-old hospitalized with community-acquired pneumonia were enrolled. On admission, clinical data and biological samples were collected to investigate 19 etiological agents (11 viruses and 8 bacteria). CXR taken upon admission was independently read by a pediatric radiologist blinded to clinical data. The study group comprised 209 cases with evaluated CXR and establishment of a probable etiology. Radiologically confirmed pneumonia, normal CXR and other radiographic diagnoses were described for 165 (79.0%), 36 (17.2%) and 8 (3.8%) patients, respectively. Viral infection was significantly more common among patients without radiologically confirmed pneumonia (68.2% vs. 47.9%; P = 0.02), particularly among those with normal CXR (66.7% vs. 47.9%; P = 0.04) when compared with patients with radiologically confirmed pneumonia. Bacterial infection was more frequent among cases with radiologically confirmed pneumonia (52.1% vs. 31.8%; P = 0.02). Likewise, pneumococcal infection was more frequently detected among children with radiologically confirmed pneumonia in regard to children with normal CXR (24.2% vs. 8.3%; P = 0.04). Sensitivity (95% confidence interval) of radiologically confirmed pneumonia for pneumococcal infection was 93% (80-98%), and negative predictive value (95% confidence interval) of normal CXR for pneumococcal infection was 92% (77-98%). Bacterial infection, especially pneumococcal one, is associated with radiologically confirmed pneumonia.
Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients.
de Steenhuijsen Piters, Wouter A A; Huijskens, Elisabeth G W; Wyllie, Anne L; Biesbroek, Giske; van den Bergh, Menno R; Veenhoven, Reinier H; Wang, Xinhui; Trzciński, Krzysztof; Bonten, Marc J; Rossen, John W A; Sanders, Elisabeth A M; Bogaert, Debby
2016-01-01
Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.
[Imaging origins and characteristics analysis of acute and chronic aspiration pneumonia].
Wang, Kang; Li, Ming; Wang, Xiongbiao; Qin, Jianmin; Wang, Zhi; Zhao, Zehua; Qin, Le; Hua, Yanqing
2014-11-11
To discuss about the pathologic and imaging origins and characteristics of CT scaning and X-ray radiography for acute and chronic aspiration pneumonia. Imaging data from 30 patients with aspiration pneumonia were retrospectively analyzed, CT scaning was performed in 27 patients, which PMVR reconstruction was performed in 21 cases;3 exammed by X-ray with 2 used by esophagography. Opaque bodies were detected in trachea by CT scaning in 12 patients.7 patients in acute phase rapidly developed into acute respiratory distress syndrome(ARDS). CT signs of 30 patients with acute and chronic aspiration pneumonia included: centrilobular nodules were detected in 2 cases with acute phase, 4 cases with subacute phase and 4 cases with chronic phase; the imaging of ground glass opacity were detected in 9 cases with acute phase, 2 cases with subacute phase and 3 cases with chronic phase; the imaging of bronchiectasis was detected in 8 cases with chronic phase, which mucilage embolism was detected in 3 of 8 cases; the imaging of atelectasis was detected in 6 cases with chronic phase; the imaging of sheeted consolidation was detected in 5 cases with chronic phase, 8 case with acute phase; the imaging of interstitial fibrosis was detected in 3 cases with chronic phase. Lesions of inferior lobe of right lung were detected in 9 cases with chronic phase, 4 cases with subacute phase, 11 case with acute phase;lesions of inferior lobe of left lung were detected in 6 cases with chronic phase and 3 cases with subacute group, 11 case with acute phase. The imaging features of acute and chronic aspiration pneumonia overlap with GGO and centrilobular nodules in every group. While the imaging features of atelectasis, bronchiectasis or mucilage embolism are found in chronic phase. The chest CT scaning may accurately evaluate the dynamic change of aspiration pneumonia.
Ichikado, Kazuya
2014-02-01
Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. © 2013 Published by Elsevier Inc.
USDA-ARS?s Scientific Manuscript database
Klebsiella pneumoniae (associated with bacterial pneumonia) was previously isolated from Nezara viridula, a significant vector of cotton boll-rot pathogens. We provide the first annotated genome sequence of the cotton opportunistic strain K. pneumoniae 5-1. This data provides guidance to study the...
Todisco, T; de Benedictis, F M; Dottorini, M
1989-01-01
We studied the evolution of respiratory function during and for 3 years after the acute onset of viral and Mycoplasma pneumoniae pneumonias in 13 school-age children. A mixed type transient ventilatory defect (restrictive and obstructive, but mainly restrictive) with large and small airway involvement was observed during the acute phase of the pneumonias. Residual small airway involvement was found over the next 12 months, but no pulmonary function abnormalities were present after 3 years. At that time, one of the 13 subjects displayed bronchial hyperreactivity to distilled water mist challenge. The authors concluded that viral and Mycoplasma pneumoniae pneumonia in previously healthy school-age children does not cause impaired lung function in later childhood.
Garza-Ramos, Ulises; Moreno-Dominguez, Stephania; Hernández-Castro, Rigoberto; Silva-Sanchez, Jesús; Barrios, Humberto; Reyna-Flores, Fernando; Sanchez-Perez, Alejandro; Carrillo-Casas, Erika M; Sanchez-León, María Carmen; Moncada-Barron, David
2016-04-01
Klebsiella variicola, a bacterium closely genetically related to Klebsiella pneumoniae, is commonly misidentified as K. pneumoniae by biochemical tests. To distinguish between the two bacteria, phylogenetic analysis of the rpoB gene and the identification of unique genes in both bacterial species by multiplex-polymerase chain reaction (PCR) provide the means to reliably identify and genotype K. variicola. In recent years, K. variicola has been described both as the cause of an intrahospital outbreak in a pediatric hospital, which resulted in sepsis in inpatients, and as a frequent cause of bloodstream infections. In the present study, K. pneumoniae and K. variicola were isolated from a unique patient displaying different antimicrobial susceptibility phenotypes and different genotypes of virulence determinants. Eight clinical isolates were obtained at different time intervals; all during a 5-month period. The isolates were identified as K. pneumoniae by an automated identification system. The clinical (biochemical test) and molecular (multiplex-PCR and rpoB gene) characterization identified imipenem resistance in the first six K. pneumoniae ST258 isolates, which encode the SHV-12 cephalosporinase and KPC-3 carbapenemase genes. The two last remaining isolates corresponded to susceptible K. variicola. The bacterial species showed a specific profile of virulence-associated determinants, specifically the fimA, fimH, and ecpRAB fimbrial-encoding genes identified only in K. pneumoniae isolates. However, the entb (enterobactin), mrkD (fimbrial adhesin), uge (epimerase), ureA (urease), and wabG (transferase) genes were shared between both bacterial species. Recent studies attribute a higher mortality rate to K. variicola than to K. pneumonia. This work highlights the identification of K. pneumoniae and the closely related K. variicola isolated from the same patient. The value of distinguishing between these two bacterial species is in their clinical significance, their different phenotypes and genotypes, and the fact that they can be isolated from the same patient.
Nervous System Abnormalities and Legionnaire's Disease.
Halperin, John J
2017-03-01
Although patients with Legionnaire's disease frequently develop alterations of consciousness, this is no more frequent than in patients hospitalized with other, equally severe forms of bacterial pneumonia. Legionella meningitis occurs rarely, if ever. Patients with Legionnaire's are susceptible to critical illness polyneuropathy/myopathy, as are other critically ill patients. Legionnaire's patients may develop MRI hyperdensities in the splenium of the corpus callosum, as may other patients with severe infections. Patients with Legionnaire's may be at increased risk of, and rarely develop, immune-mediated multifocal brain (acute disseminated encephalomyelitis) or peripheral nerve disease (Guillain-Barré syndrome). Copyright © 2016 Elsevier Inc. All rights reserved.
Prevalence of Mycoplasma pneumoniae infection in pediatric patients with acute asthma exacerbation.
Kassisse, Elías; García, Hecmary; Prada, Linair; Salazar, Ixora; Kassisse, Jorge
2018-06-01
Mycoplasma pneumoniae may be involved in refractory asthma exacerbation. To determine the prevalence of Mycoplasma pneumoniae infection in patients with acute asthma exacerbation. Material and method. A prospective, crosssectional, observational, case-control study was carried out in patients older than 2 years old and younger than 12. Immunoglobulin M (IgM) antibodies were serologically determined for M. pneumoniae, using the NovaLisa® NovaTec kit for enzyme-linked immunosorbent assay (ELISA). Test results ≥ 11 NTU (NovaTec units) were regarded as positive. The statistical analysis was performed by means of the analysis of variance (ANOVA) and the χ² test, with a significance level of p < 0.05. One hundred and eighty children were studied, of which 130 had asthma and 50 comprised the control group. Specific IgM was positive for 60 patients, that is 46.15% of the asthmatic children (p < 0.001). The severity of the exacerbation was directly related to IgM levels (p < 0.001). Hospitalization rate was 75%, and it was significantly associated to specific IgM levels (p < 0.001). Our data suggest that children with acute asthma show a high prevalence (46%) of Mycoplasma pneumoniae infection and that there is a close relation between severe acute asthma exacerbation and the presence of Mycoplasma pneumoniae infection. These findings might result in therapeutic implications centered in the use of specific antibiotics to fight this atypical organism. Key words: acute asthma, exacerbation, Mycoplasma pneumoniae. Sociedad Argentina de Pediatría.
Seo, Jin
2013-01-01
Proteases play important roles in the virulence of Pseudomonas aeruginosa. Some are exported to act on host targets and facilitate tissue destruction and bacterial dissemination. Others work within the bacterial cell to process virulence factors and regulate virulence gene expression. Relatively little is known about the role of one class of bacterial serine proteases known as the carboxyl-terminal processing proteases (CTPs). The P. aeruginosa genome encodes two CTPs annotated as PA3257/Prc and PA5134/CtpA in strain PAO1. Prc degrades mutant forms of the anti-sigma factor MucA to promote mucoidy in some cystic fibrosis lung isolates. However, nothing is known about the role or importance of CtpA. We have now found that endogenous CtpA is a soluble periplasmic protein and that a ctpA null mutant has specific phenotypes consistent with an altered cell envelope. Although a ctpA null mutation has no major effect on bacterial growth in the laboratory, CtpA is essential for the normal function of the type 3 secretion system (T3SS), for cytotoxicity toward host cells, and for virulence in a mouse model of acute pneumonia. Conversely, increasing the amount of CtpA above its endogenous level induces an uncharacterized extracytoplasmic function sigma factor regulon, an event that has been reported to attenuate P. aeruginosa in a rat model of chronic lung infection. Therefore, a normal level of CtpA activity is critical for T3SS function and acute virulence, whereas too much activity can trigger an apparent stress response that is detrimental to chronic virulence. PMID:24082078
Fosfomycin i.v. for Treatment of Severely Infected Patients
2018-05-08
Bacterial Infections; Bone Diseases, Infectious; Osteomyelitis; Central Nervous System Bacterial Infections; Meningitis, Bacterial; Encephalitis; Brain Abscess; Urinary Tract Infections; Respiratory Tract Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Intraabdominal Infections; Sepsis; Bacteremia; Endocarditis, Bacterial
Community-acquired pneumonia in children.
Stuckey-Schrock, Kimberly; Hayes, Burton L; George, Christa M
2012-10-01
Community-acquired pneumonia is a potentially serious infection in children and often results in hospitalization. The diagnosis can be based on the history and physical examination results in children with fever plus respiratory signs and symptoms. Chest radiography and rapid viral testing may be helpful when the diagnosis is unclear. The most likely etiology depends on the age of the child. Viral and Streptococcus pneumoniae infections are most common in preschool-aged children, whereas Mycoplasma pneumoniae is common in older children. The decision to treat with antibiotics is challenging, especially with the increasing prevalence of viral and bacterial coinfections. Preschool-aged children with uncomplicated bacterial pneumonia should be treated with amoxicillin. Macrolides are first-line agents in older children. Immunization with the 13-valent pneumococcal conjugate vaccine is important in reducing the severity of childhood pneumococcal infections.
Cukic, Vesna; Hadzic, Armin
2016-01-01
Introduction: Community acquired pneumonia (CAP) is the most common infective pulmonary disease. Objective: To show the most common detected bacteria in bacterial culture of sputum in patients with CAP hospitalized in Clinic for Pulmonary Diseases and TB “Podhrastovi” in four-year period: from 2012 to 2015. Material and methods: This is the retrospective analysis. Each patient gave sputum 3 days in a row when admitted to hospital. Sputum has been examined: bacterial culture with antibiotics sensitivity, Gram stain, Mycobacterium tuberculosis; in cases with high temperature blood cultures were done; when we were suspicious about bronchial carcinoma bronchoscopy with BAL (bronchoalveolar lavage) was done. We show analyzed patients according to age, sex, whether they had pneumonia or bronchopneumonia, bacteria isolated in sputum and in BAL. Results: 360 patients with CAP were treated in four-year period (247 males and 113 females). 167 or 43, 39 % had pneumonia (119 males and 48 females). Number of males was significantly bigger (χ2 = 30,186; p<0,001). 193 or 53, 61 % had bronchopneumonia (128 males and 65 females). Number of males was significantly bigger (χ2 = 20,556; p<0,001). Number of patients with negative bacterial culture of sputum (131–78, 44%) was significantly bigger than number of patients with positive culture (36–21, 56%) (χ2 = 50,042; p<0,001) in pneumonia. Number of patients with negative bacterial culture of sputum (154- 79, 79%) was significantly bigger than number of patients with positive culture (39- 20, 21%) (χ2 = 68,523; p<0,001) in bronchopneumonia. Streptococcus pneumoniae was significantly most common detected bacterium compared with the number of other isolated bacteria; in pneumonia (χ2 =33,222; p<0,001) and in bronchopneumonia (χ2 =51,231; p<0,001). Conclusion: It is very important to detect the bacterial cause of CAP to administrate the targeted antibiotic therapy. PMID:27994296
Soysal, Ahmet; Toprak, Demet Gedikbasi; Türkoğlu, Salih; Bakir, Mustafa
2017-01-11
The aim of this study is to compare the diagnostic performance of the line probe assay (LPA) with conventional multiplex polymerase chain reaction (PCR) for Streptococcus pneumoniae as well as real-time PCR for Neisseria meningitidis and Haemophilus influenzae type b (Hib) in cerebrospinal fluid (CSF) samples from children during the multicenter national surveillance of bacterial meningitis between the years 2006 and 2009 in Turkey. During the study period 1460 subjects were enrolled and among them 841 (57%) met the criteria for probable bacterial meningitis. The mean age of subjects was 51 ± 47 months (range, 1-212 months). We performed the line probe assay in 751 (89%) CSF samples of 841 probable bacterial meningitis cases, of whom 431 (57%) were negative, 127 (17%) were positive for S. pneumoniae, 53 (7%) were positive for H. influenzae type b, and 41 (5%) were positive for N. meningitidis. The LPA was positive in 19 of 23 (82%) S. pneumoniae samples, 4 of 6 (67%) N. meningitidis samples and 2 of 2 (100%) Hib samples in CSF culture-positive cases. The specificity of the LPA for all of S. pneumoniae, H. influenzae type b, and N. meningitidis was 88% (95% CI: 85-91%), when using the standard PCR as a reference. The specificity of LPA for each of S. pneumoniae, H. influenzae type b, and N. meningitidis was 93% (95% CI: 89-95%), 96% (95% CI: 94-98%), and 99% (95% CI: 97-99%), respectively. For all of S. pneumoniae, H. influenzae type b and N. meningitidis the sensitivity of the LPA was 76% (95% CI: 70-82%) and for each of S. pneumoniae, H. influenzae type b and N. meningitidis was 72% (95% CI:63-79%), 88% (95% CI: 73-95%), and 81% (95% CI:67-92%), respectively. The LPA assay can be used to detect common bacterial meningitis pathogens in CSF samples, but the assay requires further improvement.
Galván, E M; Mateyca, C; Ielpi, L
2016-10-01
Most catheter-associated urinary tract infections are polymicrobial. Here, uropathogen interactions in dual-species biofilms were studied. The dual-species associations selected based on their prevalence in clinical settings were Klebsiella pneumoniae-Escherichia coli, E. coli-Enterococcus faecalis, K. pneumoniae-E. faecalis, and K. pneumoniae-Proteus mirabilis. All species developed single-species biofilms in artificial urine. The ability of K. pneumoniae to form biofilms was not affected by E. coli or E. faecalis co-inoculation, but was impaired by P. mirabilis. Conversely, P. mirabilis established a biofilm when co-inoculated with K. pneumoniae. Additionally, E. coli persistence in biofilms was hampered by K. pneumoniae but not by E. faecalis. Interestingly, E. coli, but not K. pneumoniae, partially inhibited E. faecalis attachment to the surface and retarded biofilm development. The findings reveal bacterial interactions between uropathogens in dual-species biofilms ranged from affecting initial adhesion to outcompeting one bacterial species, depending on the identity of the partners involved.
[Mycoplasma pneumoniae meningoencephalitis].
Cambonie, G; Sarran, N; Leboucq, N; Luc, F; Bongrand, A F; Slim, G; Lassus, P; Fournier-Favre, S; Montoya, F; Astruc, J; Rieu, D
1999-03-01
Severe central nervous system diseases, such as encephalitis, have been reported in association with Mycoplasma pneumoniae infections. After an ENT infection, a 9-year-old boy with Down's syndrome developed encephalitis revealed by an acute alteration in consciousness. Head computed tomography showed, after 2 weeks, an infiltration in the basal ganglia region. The diagnosis of Mycoplasma pneumoniae encephalitis was made; recovery was complete in a few weeks. Mycoplasma pneumoniae infection should be considered in all cases of acute encephalopathy; yet the pathogenesis of the disorder is unknown and the treatment uncertain.
Responses to Bacteria, Virus, and Malaria Distinguish the Etiology of Pediatric Clinical Pneumonia.
Valim, Clarissa; Ahmad, Rushdy; Lanaspa, Miguel; Tan, Yan; Acácio, Sozinho; Gillette, Michael A; Almendinger, Katherine D; Milner, Danny A; Madrid, Lola; Pellé, Karell; Harezlak, Jaroslaw; Silterra, Jacob; Alonso, Pedro L; Carr, Steven A; Mesirov, Jill P; Wirth, Dyann F; Wiegand, Roger C; Bassat, Quique
2016-02-15
Plasma-detectable biomarkers that rapidly and accurately diagnose bacterial infections in children with suspected pneumonia could reduce the morbidity of respiratory disease and decrease the unnecessary use of antibiotic therapy. Using 56 markers measured in a multiplexed immunoassay, we sought to identify proteins and protein combinations that could discriminate bacterial from viral or malarial diagnoses. We selected 80 patients with clinically diagnosed pneumonia (as defined by the World Health Organization) who also met criteria for bacterial, viral, or malarial infection based on clinical, radiographic, and laboratory results. Ten healthy community control subjects were enrolled to assess marker reliability. Patients were subdivided into two sets: one for identifying potential markers and another for validating them. Three proteins (haptoglobin, tumor necrosis factor receptor 2 or IL-10, and tissue inhibitor of metalloproteinases 1) were identified that, when combined through a classification tree signature, accurately classified patients into bacterial, malarial, and viral etiologies and misclassified only one patient with bacterial pneumonia from the validation set. The overall sensitivity and specificity of this signature for the bacterial diagnosis were 96 and 86%, respectively. Alternative combinations of markers with comparable accuracy were selected by support vector machine and regression models and included haptoglobin, IL-10, and creatine kinase-MB. Combinations of plasma proteins accurately identified children with a respiratory syndrome who were likely to have bacterial infections and who would benefit from antibiotic therapy. When used in conjunction with malaria diagnostic tests, they may improve diagnostic specificity and simplify treatment decisions for clinicians.
Li, Qiuling; Weng, Kaizhi; Zhu, Ling; Mei, Xuqiao; Xu, Liping; Lin, Jiehua
2014-10-01
To detect the percentage of total natural killer (NK) cells and its different populations in the peripheral blood from neonates with bacterial pneumonia and discuss the clinical significance of NK cells in the pathogenesis of bacterial pneumonia. Flow cytometry was performed to detect the percentages of NK cells and its subsets in peripheral blood lymphocytes from 38 cases of neonatal bacterial pneumonias and 18 cases of normal neonates. Patients recruited were divided into two groups according to hospitalization days and numbers of peripheral leukocytes: hospitalization days within 10 days (including 10 days) as group A, and more than 10 days as group B; the number of peripheral blood leukocytes <5.0×10(9)/L or >20.0×10(9)/L as severe infection group, and 5.0×10(9)/L< number of peripheral blood leukocytes <20.0×10(9)/L as mild infection group. The percentages of peripheral blood NK cells and CD3(-)CD56(neg)CD16(bright) subset in the neonates with bacterial pneumonia were significantly lower than those of the normal newborns (P<0.01), but there were no statistically significant differences in CD3(-)CD56(bright)CD16(neg/dim) and CD3(-)CD56(dim)CD16(bright) subsets. The percentage of CD3(-)CD56(neg)CD16(bright) subset in group A was significantly lower than that of the normal newborns (P<0.01), while the percentages of the total NK cells and other subsets had no statistical significance. The neonates with bacterial pneumonia had significantly lower percentages of the total NK cells and CD3(-)CD56(neg)CD16(bright) subset in group B as compared with the normal neonates (P<0.01). And the percentages of the total NK cells and its subsets in group B were also lower than those in group A (P<0.05). The percentages of NK cells and each subset in severe infection group were significantly lower than those in mild infection group (P<0.05). To the neonates who suffer from bacterial pneumonia, the more serious and the longer hospital stay, the lower the percentages of NK cells and its subsets are.
Van Bambeke, Françoise
2015-01-01
Delafloxacin is a fluoroquinolone lacking a basic substituent in position 7. It shows MICs remarkably low against Gram-positive organisms and anaerobes and similar to those of ciprofloxacin against Gram-negative bacteria. It remains active against most fluoroquinolone-resistant strains, except enterococci. Its potency is further increased in acidic environments (found in many infection sites). Delafloxacin is active on staphylococci growing intracellularly or in biofilms. It is currently evaluated as an intravenous and intravenous/oral stepdown therapy in Phase III trials for the treatment of complicated skin/skin structure infections. It was also granted as Qualified Infectious Disease Product for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, due to its high activity on pneumococci and atypical pathogens.
USDA-ARS?s Scientific Manuscript database
Klebsiella pneumoniae has been known historically as a causal agent of bacterial pneumonia. More recently, K. pneumoniaerepresentatives have been shown to have a broad ecological distribution and are recognized nitrogen-fixers. Previously, we demonstrated the capacity of K. pneumoniae strain Kp 5-1R...
Thompson, Mitchell G; Truong-Le, Vu; Alamneh, Yonas A; Black, Chad C; Anderl, Jeff; Honnold, Cary L; Pavlicek, Rebecca L; Abu-Taleb, Rania; Wise, Matthew C; Hall, Eric R; Wagar, Eric J; Patzer, Eric; Zurawski, Daniel V
2015-10-01
Skin and soft tissue infections (SSTIs) are a common occurrence in health care facilities with a heightened risk for immunocompromised patients. Klebsiella pneumoniae has been increasingly implicated as the bacterial agent responsible for SSTIs, and treatment can be challenging as more strains become multidrug resistant (MDR). Therefore, new treatments are needed to counter this bacterial pathogen. Gallium complexes exhibit antimicrobial activity and are currently being evaluated as potential treatment for bacterial infections. In this study, we tested a topical formulation containing gallium citrate (GaCi) for the treatment of wounds infected with K. pneumoniae. First, the MIC against K. pneumoniae ranged from 0.125 to 2.0 μg/ml GaCi. After this in vitro efficacy was established, two topical formulations with GaCi (0.1% [wt/vol] and 0.3% [wt/vol]) were tested in a murine wound model of MDR K. pneumoniae infection. Gross pathology and histopathology revealed K. pneumoniae-infected wounds appeared to close faster with GaCi treatment and were accompanied by reduced inflammation compared to those of untreated controls. Similarly, quantitative indications of infection remediation, such as reduced weight loss and wound area, suggested that treatment improved outcomes compared to those of untreated controls. Bacterial burdens were measured 1 and 3 days following inoculation, and a 0.5 to 1.5 log reduction of CFU was observed. Lastly, upon scanning electron microscopy analysis, GaCi treatment appeared to prevent biofilm formation on dressings compared to those of untreated controls. These results suggest that with more preclinical testing, a topical application of GaCi may be a promising alternative treatment strategy for K. pneumoniae SSTI. Copyright © 2015 Thompson et al.
Thompson, Mitchell G.; Truong-Le, Vu; Alamneh, Yonas A.; Black, Chad C.; Anderl, Jeff; Honnold, Cary L.; Pavlicek, Rebecca L.; Abu-Taleb, Rania; Wise, Matthew C.; Hall, Eric R.; Wagar, Eric J.; Patzer, Eric
2015-01-01
Skin and soft tissue infections (SSTIs) are a common occurrence in health care facilities with a heightened risk for immunocompromised patients. Klebsiella pneumoniae has been increasingly implicated as the bacterial agent responsible for SSTIs, and treatment can be challenging as more strains become multidrug resistant (MDR). Therefore, new treatments are needed to counter this bacterial pathogen. Gallium complexes exhibit antimicrobial activity and are currently being evaluated as potential treatment for bacterial infections. In this study, we tested a topical formulation containing gallium citrate (GaCi) for the treatment of wounds infected with K. pneumoniae. First, the MIC against K. pneumoniae ranged from 0.125 to 2.0 μg/ml GaCi. After this in vitro efficacy was established, two topical formulations with GaCi (0.1% [wt/vol] and 0.3% [wt/vol]) were tested in a murine wound model of MDR K. pneumoniae infection. Gross pathology and histopathology revealed K. pneumoniae-infected wounds appeared to close faster with GaCi treatment and were accompanied by reduced inflammation compared to those of untreated controls. Similarly, quantitative indications of infection remediation, such as reduced weight loss and wound area, suggested that treatment improved outcomes compared to those of untreated controls. Bacterial burdens were measured 1 and 3 days following inoculation, and a 0.5 to 1.5 log reduction of CFU was observed. Lastly, upon scanning electron microscopy analysis, GaCi treatment appeared to prevent biofilm formation on dressings compared to those of untreated controls. These results suggest that with more preclinical testing, a topical application of GaCi may be a promising alternative treatment strategy for K. pneumoniae SSTI. PMID:26239978
21 CFR 522.313b - Ceftiofur hydrochloride.
Code of Federal Regulations, 2014 CFR
2014-04-01
... bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella... treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Becker, Argentina; Kannan, T. R.; Taylor, Alexander B.
Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and “walking” pneumonia, and are linked to asthma and other reactive airway diseases. As part of the infectious process, the bacterium expresses a 591-aa virulence factor with both mono-ADP ribosyltransferase (mART) and vacuolating activities known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. In this paper, we present the structure of CARDS TX, a triangular molecule in which N-terminal mART and C-terminal tandem β-trefoil domains associate to form anmore » overall architecture distinct from other well-recognized ADP-ribosylating bacterial toxins. We demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin specifically over other membrane lipids, and that cell surface binding and internalization activities are housed within the C-terminal β-trefoil domain. Finally, the results enhance our understanding of Mp pathogenicity and suggest a novel avenue for the development of therapies to treat Mp-associated asthma and other acute and chronic airway diseases.« less
Becker, Argentina; Kannan, T. R.; Taylor, Alexander B.; ...
2015-04-06
Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and “walking” pneumonia, and are linked to asthma and other reactive airway diseases. As part of the infectious process, the bacterium expresses a 591-aa virulence factor with both mono-ADP ribosyltransferase (mART) and vacuolating activities known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. In this paper, we present the structure of CARDS TX, a triangular molecule in which N-terminal mART and C-terminal tandem β-trefoil domains associate to form anmore » overall architecture distinct from other well-recognized ADP-ribosylating bacterial toxins. We demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin specifically over other membrane lipids, and that cell surface binding and internalization activities are housed within the C-terminal β-trefoil domain. Finally, the results enhance our understanding of Mp pathogenicity and suggest a novel avenue for the development of therapies to treat Mp-associated asthma and other acute and chronic airway diseases.« less
Baral, Pankaj; Umans, Benjamin D; Li, Lu; Wallrapp, Antonia; Bist, Meghna; Kirschbaum, Talia; Wei, Yibing; Zhou, Yan; Kuchroo, Vijay K; Burkett, Patrick R; Yipp, Bryan G; Liberles, Stephen D; Chiu, Isaac M
2018-05-01
Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1 + nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1 + -neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity. Vagal ganglia TRPV1 + afferents mediated immunosuppression through release of the neuropeptide calcitonin gene-related peptide (CGRP). Targeting neuroimmunological signaling may be an effective approach to treat lung infections and bacterial pneumonia.
Update on bacterial pneumonia in the foal and weanling.
Reuss, Sarah M; Cohen, Noah D
2015-04-01
Bacterial pneumonia is a common cause of disease in both neonatal and weanling foals. The causal organism or organisms differ with the age of the foal, should be identified via microbiologic culture, and will ultimately dictate appropriate treatment. Initial treatment in neonates should be broad spectrum and bactericidal, whereas weanling age foals may receive more targeted treatment. The combination of a macrolide antibiotic and rifampin remains the gold standard for treatment of Rhodococcus equi pneumonia; however, resistance to these antimicrobials is a concern. Copyright © 2015 Elsevier Inc. All rights reserved.
Onakpoya, Igho J; Walker, A Sarah; Tan, Pui S; Spencer, Elizabeth A; Gbinigie, Oghenekome A; Cook, Johanna; Llewelyn, Martin J; Butler, Christopher C
2018-01-01
Our objective was to assess the clinical effectiveness of shorter versus longer duration antibiotics for treatment of bacterial infections in adults and children in secondary care settings, using the evidence from published systematic reviews. We conducted electronic searches in MEDLINE, Embase, Cochrane, and Cinahl. Our primary outcome was clinical resolution. The quality of included reviews was assessed using the AMSTAR criteria, and the quality of the evidence was rated using the GRADE criteria. We included 6 systematic reviews (n = 3,162). Four reviews were rated high quality, and two of moderate quality. In adults, there was no difference between shorter versus longer duration in clinical resolution rates for peritonitis (RR 1.03, 95% CI 0.98 to 1.09, I2 = 0%), ventilator-associated pneumonia (RR 0.93; 95% CI 0.81 to 1.08, I2 = 24%), or acute pyelonephritis and septic UTI (clinical failure: RR 1.00, 95% CI 0.46 to 2.18). The quality of the evidence was very low to moderate. In children, there was no difference in clinical resolution rates for pneumonia (RR 0.98, 95% CI 0.91 to 1.04, I2 = 48%), pyelonephritis (RR 0.95, 95% CI 0.88 to 1.04) and confirmed bacterial meningitis (RR 1.02, 95% CI 0.93 to 1.11, I2 = 0%). The quality of the evidence was low to moderate. In conclusion, there is currently a limited body of evidence to clearly assess the clinical benefits of shorter versus longer duration antibiotics in secondary care. High quality trials assessing strategies to shorten antibiotic treatment duration for bacterial infections in secondary care settings should now be a priority.
Walker, A. Sarah; Tan, Pui S.; Spencer, Elizabeth A.; Gbinigie, Oghenekome A.; Cook, Johanna; Llewelyn, Martin J.; Butler, Christopher C.
2018-01-01
Our objective was to assess the clinical effectiveness of shorter versus longer duration antibiotics for treatment of bacterial infections in adults and children in secondary care settings, using the evidence from published systematic reviews. We conducted electronic searches in MEDLINE, Embase, Cochrane, and Cinahl. Our primary outcome was clinical resolution. The quality of included reviews was assessed using the AMSTAR criteria, and the quality of the evidence was rated using the GRADE criteria. We included 6 systematic reviews (n = 3,162). Four reviews were rated high quality, and two of moderate quality. In adults, there was no difference between shorter versus longer duration in clinical resolution rates for peritonitis (RR 1.03, 95% CI 0.98 to 1.09, I2 = 0%), ventilator-associated pneumonia (RR 0.93; 95% CI 0.81 to 1.08, I2 = 24%), or acute pyelonephritis and septic UTI (clinical failure: RR 1.00, 95% CI 0.46 to 2.18). The quality of the evidence was very low to moderate. In children, there was no difference in clinical resolution rates for pneumonia (RR 0.98, 95% CI 0.91 to 1.04, I2 = 48%), pyelonephritis (RR 0.95, 95% CI 0.88 to 1.04) and confirmed bacterial meningitis (RR 1.02, 95% CI 0.93 to 1.11, I2 = 0%). The quality of the evidence was low to moderate. In conclusion, there is currently a limited body of evidence to clearly assess the clinical benefits of shorter versus longer duration antibiotics in secondary care. High quality trials assessing strategies to shorten antibiotic treatment duration for bacterial infections in secondary care settings should now be a priority. PMID:29590188
Alternative approaches to ventilator-associated pneumonia prevention.
Berra, L; Sampson, J; Fumagalli, J; Panigada, M; Kolobow, T
2011-03-01
Ventilator-associated pneumonia (VAP), which develops in patients receiving mechanical ventilation, is the most common nosocomial infection in patients with acute respiratory failure. The major mechanism of lower respiratory tract colonization is aspiration of bacteria-colonized secretions from the oropharynx into the lower airways. The hydrostatic pressure of the secretions that collect in the subglottic space, which is the area above the endotracheal tube (ETT) cuff, or aerosolization of bacteria from the secretions collected within the respiratory tubing may facilitate the leakage into the lower airways. Ideally, the elimination of the mechanisms responsible for aspiration would decrease the incidence of VAP. Several preventive measures have been tested in clinical trials with little success.Here we present the results of our efforts to develop novel approaches for the prevention of VAP. Specifically, we found that keeping ventilated patients in a lateral position, which eliminates gravitational forces, is feasible and possibly advantageous. Additionally, several novel medical devices have been recently developed to prevent bacterial biofilm formation from the ETT and breathing tubing. These devices include coated ETTs, mucus shavers and mucus slurpers. Prevention of ETT bacterial colonization showed decreased bacterial colonization of the respiratory circuit and of the lower respiratory tract in laboratory studies and clinical trials. Future large studies should be designed to test the hypothesis that VAP can be prevented with these novel strategies. While there is a current focus on the use of respiratory devices to prevent biofilm formation and microaspiration, it is important to remember that lower respiratory tract colonization is multifactorial. Prevention of VAP cannot be achieved solely by eliminating bacterial biofilm on respiratory devices, and more comprehensive care of the intubated patient needs to be implemented.
21 CFR 558.579 - Sulfaethoxypyridazine.
Code of Federal Regulations, 2010 CFR
2010-04-01
... treatment of bacterial scours, pneumonia, enteritis, bronchitis, septicemia accompanying Salmonella... body weight per day. (ii) Indications for use. For treatment of respiratory infections (pneumonia...
Corticosteroids for acute bacterial meningitis.
Brouwer, Matthijs C; McIntyre, Peter; Prasad, Kameshwar; van de Beek, Diederik
2013-06-04
In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response. To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis. We searched CENTRAL 2012, Issue 12, MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), Web of Science (2010 to January 2013), CINAHL (2010 to January 2013) and LILACS (2010 to January 2013). Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis. We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality. Twenty-five studies involving 4121 participants were included. Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events. Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.
Horsfall, Frank L.; McCarty, Maclyn
1947-01-01
Evidence is presented which indicates that certain polysaccharide preparations derived from various bacterial species, as well as similar materials not of bacterial origin, are capable of lessening the severity of infection with pneumonia virus of mice (PVM) and inhibiting multiplication of the virus in mouse lungs infected with this agent. It seems probable that modification with respect to the virus is mediated by a substance which may be polysaccharide in nature. PMID:19871640
Lodise, Thomas P; Low, Donald E
2012-07-30
Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. Because of its unique spectrum of activity, the Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline as a member of a new subclass of β-lactam antimicrobials, cephalosporins with anti-MRSA activity. The activity of ceftaroline against S. aureus extends to heteroresistant vancomycin-intermediate, vancomycin-intermediate, vancomycin-resistant and daptomycin-nonsusceptible isolates. Ceftaroline has low minimum inhibitory concentrations (MICs) for all tested species of streptococci, and has potent activity against S. pneumoniae isolates with varying degrees of penicillin resistance. The activity of ceftaroline is limited against Enterococcus faecalis and Enterococcus faecium and against anaerobes such as Bacteroides fragilis. The in vitro activity of ceftaroline includes many Gram-negative pathogens, but does not extend to bacteria that produce extended-spectrum β-lactamases, class B metallo-β-lactamases or AmpC cephalosporinases, or to most nonfermentative Gram-negative bacilli. Ceftaroline fosamil has been studied for the treatment of complicated skin and skin structure infections (cSSSI) and community-acquired pneumonia (CAP) in phase III randomized, double-blind, international, multicentre noninferiority clinical trials. Two identical trials (CANVAS 1 and CANVAS 2) compared the efficacy of ceftaroline fosamil with that of vancomycin plus aztreonam in 1378 adults with cSSSI. Results demonstrated that ceftaroline was noninferior to vancomycin plus aztreonam, with 91.6% in the ceftaroline fosamil group (pooled analysis) achieving clinical response compared with 92.7% in the vancomycin plus aztreonam group (difference -1.1%, 95% CI -4.2, 2.0). An additional analysis evaluated clinical cure in a subgroup of patients who met the FDA guidance definition of ABSSSI at treatment day 3. Clinical response, defined as cessation of lesion spread and absence of fever, was 74.0% in the ceftaroline fosamil group compared with 66.2% in the vancomycin plus aztreonam group (treatment difference 7.8%, 95% CI 1.3, 14.0). Clinical efficacy of ceftaroline fosamil in 1240 hospitalized adults with CAP was compared with that of ceftriaxone in two additional phase III trials (FOCUS 1 and FOCUS 2). Of note, because ceftriaxone does not have activity against MRSA, patients with confirmed or suspected MRSA CAP were excluded from the FOCUS trials. Results demonstrated that ceftaroline was noninferior to ceftriaxone, with 84.3% in the ceftaroline fosamil group achieving clinical cure compared with 77.7% in the ceftriaxone group (difference 6.7%, 95% CI 1.6, 11.8). An additional analysis of the trials was conducted in patients with moderate to severe CAP and at least one proven typical bacterial pathogen at baseline (i.e. CABP). Day 4 clinical response rates were 69.5% for ceftaroline and 59.4% for ceftriaxone (difference 10.1%, 95% CI -0.6, 20.6). In the phase III trials, adverse event rates were similar between groups. Overall, ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline fosamil is a broad-spectrum parenteral cephalosporin with excellent in vitro activity against resistant Gram-positive pathogens, including MRSA, as well as many common Gram-negative organisms. It is a welcome treatment option for ABSSSI and CABP.
Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type of bacteria is the most common cause of bacterial meningitis in adults. ...
Bhuiyan, Mejbah Uddin; Snelling, Thomas L; West, Rachel; Lang, Jurissa; Rahman, Tasmina; Borland, Meredith L; Thornton, Ruth; Kirkham, Lea-Ann; Sikazwe, Chisha; Martin, Andrew C; Richmond, Peter C; Smith, David W; Jaffe, Adam; Blyth, Christopher C
2018-01-01
Introduction Pneumonia is the leading cause of childhood morbidity and mortality globally. Introduction of the conjugate Haemophilus influenzae B and multivalent pneumococcal vaccines in developed countries including Australia has significantly reduced the overall burden of bacterial pneumonia. With the availability of molecular diagnostics, viruses are frequently detected in children with pneumonia either as primary pathogens or predispose to secondary bacterial infection. Many respiratory pathogens that are known to cause pneumonia are also identified in asymptomatic children, so the true contribution of these pathogens to childhood community-acquired pneumonia (CAP) remains unclear. Since the introduction of pneumococcal vaccines, very few comprehensive studies from developed countries have attempted to determine the bacterial and viral aetiology of pneumonia. We aim to determine the contribution of bacteria and viruses to childhood CAP to inform further development of effective diagnosis, treatment and preventive strategies. Methods and analysis We are conducting a prospective case–control study (PneumoWA) where cases are children with radiologically confirmed pneumonia admitted to Princess Margaret Hospital for Children (PMH) and controls are healthy children identified from PMH outpatient clinics and from local community immunisation clinics. The case–control ratio is 1:1 with 250 children to be recruited in each arm. Nasopharyngeal swabs are collected from both cases and controls to detect the presence of viruses and bacteria by PCR; pathogen load will be assessed by quantitative PCR. The prevalence of pathogens detected in cases and controls will be compared, the OR of detection and population attributable fraction to CAP for each pathogen will be determined; relationships between pathogen load and disease status and severity will be explored. Ethics and dissemination This study has been approved by the human research ethics committees of PMH, Perth, Australia (PMH HREC REF 2014117EP). Findings will be disseminated at research conferences and in peer-reviewed journals. PMID:29549211
ON THE RELATION OF BACTERIA TO SO-CALLED "CHEMICAL PNEUMONIA"
Koontz, A. R.; Allen, M. S.
1929-01-01
The question of a causal relation of the bacteria in gassed lungs to the pneumonia present cannot be regarded as decided. It may be said that: 1. The appearance of gassed lungs with pneumonia is very similar to the pneumonia of known bacterial origin. 2. In a few cases the type of pneumonia found coincides with the reported cases of so-called "chemical pneumonia," which is characterized by a preponderance of epithelial cells in the exudate. 3. Gassed lungs are not sterile but show highly varying numbers of bacteria. 4. The bacteria are not intracellular and are not present in large numbers in the majority of cases. The arguments for and against a causal relationship between the bacteria and the pneumonia may be summed up as follows: 1. Against a Causal Relationship a. The early appearance of pneumonia after gassing. b. The occurrence of pneumonia with very small numbers of bacteria present. c. The fact that very few bacteria are engulfed by leucocytes in gassed lungs, whereas large numbers are present in the non-gassed pneumonias and are conspicuously intracellular. 2. In Favor of a Causal Relationship a. The presence of bacteria in any numbers. b. The picture of broncho-pneumonia presented is similar to broncho-pneumonia of known bacterial origin. c. Pneumonias characterized by large numbers of epithelial cells in the exudate (so-called "chemical pneumonia") occur in animals that were never gassed or subjected to other irritating substances in any way. PMID:19869606
Inflammatory response in mixed viral-bacterial community-acquired pneumonia.
Bello, Salvador; Mincholé, Elisa; Fandos, Sergio; Lasierra, Ana B; Ruiz, María A; Simon, Ana L; Panadero, Carolina; Lapresta, Carlos; Menendez, Rosario; Torres, Antoni
2014-07-29
The role of mixed pneumonia (virus+bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.
Harada, Tatsuhiko; Ishimatsu, Yuji; Hara, Atsuko; Morita, Towako; Nakashima, Shota; Kakugawa, Tomoyuki; Sakamoto, Noriho; Kosai, Kosuke; Izumikawa, Koichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru
2016-09-01
Secondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A/PR8/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation. Premedication with CAM improved pathologic responses and bacterial load 2 days after S. pneumoniae inoculation. Survival rates were higher in emphysema mice than control mice. While CAM premedication did not affect viral titers or exert antibacterial activity against S. pneumoniae in the lungs, it enhanced host defense and reduced inflammation, as evidenced by the significant reductions in total cell and neutrophil counts and interferon (IFN)-γ levels in bronchoalveolar lavage fluid and lung homogenates. These results suggest that CAM protects against SBP during influenza in elastase-induced emphysema mice by reducing IFN-γ production, thus enhancing immunity to SBP, and by decreasing neutrophil infiltration into the lung to prevent injury. Accordingly, CAM may be an effective strategy to prevent secondary bacterial pneumonia in COPD patients in areas in which vaccines are inaccessible or limited. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT
2018-06-08
Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis
[A clinical study of PC-904 in pediatrics (author's transl)].
Hori, M; Kono, S; Hashimoto, F
1978-07-01
A clinical study of PC-904 was performed in children. The results were as follows; 1) Serum levels of PC-904 after single administration of 20 mg/kg were studied in patients by one-shot intravenous injection or drip infusion for 1 hour or 2 hours. The results obtained in this fundamental study led to the suggestion that the proper dosage in bacterial infections would be 50 approximately 100 mg/kg intravenously in 3 approximately 4 divided doses daily. 2) A clinical study of PC-904 was performed in 16 patients including acute pharyngitis and bronchitis (3 cases), acute bronchopneumonia (3 cases), pertussis pneumonia (1 case), lymphadenitis purulenta (2 cases), acute bronchopneumonia (3 cases), pertussis pneumonia (1 case), lymphadenitis purulenta (2 cases), abscess with chronic granuloma (2 cases) and urinary tract infection (5 cases). About 50 approximately 100 mg/kg of PC-904 were administered in 3 approximately 4 divided doses daily by one-shot intravenous injection. The clinical effects of 2 cases out of 16 were impossible to be evaluated, and thses cases were excluded from the clinical evaluation. Ten cases out of 14 showed excellent or good responses (efficacy rate: 71.4%). 3) The bacteriological examinations were performed and the causative or isolated organisms were determined in 11 cases. The responses were "disappeared" in 6 cases, "decreased" in 2 cases and "not disappeared" in 3 cases. 4) No side effects were observed. Abnormalities of laboratory findings were not also noticed.
CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.
Giulieri, S; Chapuis-Taillard, C; Jaton, K; Cometta, A; Chuard, C; Hugli, O; Du Pasquier, R; Bille, J; Meylan, P; Manuel, O; Marchetti, O
2015-10-01
CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.
Szeredi, Levente; Jánosi, Szilárd; Pálfi, Vilmos
2010-09-01
The infectious origin of fatal cases of calf pneumonia was studied in 48 calves from 27 different herds on postmortem examination. Lung tissue samples were examined by pathological, histological, bacterial culture, virus isolation and immunohistochemical methods for the detection of viral and bacterial infections. Pneumonia was diagnosed in 47/48 cases and infectious agents were found in 40/47 (85%) of those cases. The presence of multiple respiratory pathogens in 23/40 (57.5%) cases indicated the complex origin of fatal calf pneumonia. The most important respiratory pathogens were Mannheimia-Pasteurella in 36/40 (90%) cases, followed by Arcanobacterium pyogenes in 16/40 (40%) cases, Mycoplasma bovis in 12/40 (30%) cases, and bovine respiratory syncytial virus in 4/40 (10%) cases. Histophilus somni was detected in 2/40 (5%) cases, while bovine herpesvirus-1, bovine viral diarrhoea virus and parainfluenza virus-3 were each found in 1/40 (2.5%) case. Mastadenovirus, bovine coronavirus, influenza A virus or Chlamydiaceae were not detected.
Dual role of infections as risk factors for coronary heart disease.
Pesonen, Erkki; Andsberg, Eva; Ohlin, Hans; Puolakkainen, Mirja; Rautelin, Hilpi; Sarna, Seppo; Persson, Kenneth
2007-06-01
The aim of the study was to explore whether exposure to microbial agents determines the prevalence of acute coronary events. Patients with unstable angina pectoris and myocardial infarction (N=335) and their paired controls were investigated. The subjects answered a questionnaire about their childhood contagious diseases: varicella, scarlet fever, measles, rubella, mononucleosis and mumps. Blood samples were taken for bacterial and viral serology. The odds ratio for CHD was highest in the upper quartile of the enterovirus (EV), herpes simplex virus (HSV) and Chlamydia pneumoniae HSP60 IgG antibody titers (1.86, p=0.001, 1.57, p<0.048 and 1.70, p=0.016, respectively). The antibody titers increased cumulatively the risk for CHD (odds ratios 1.89, 2.24, 3.92 and p-values <0.001, 0.001 and 0.047). Childhood contagious diseases (n=6) had a protecting effect against CHD (odds ratio 0.86, p=0.013). The risk for acute coronary events decreased significantly with increasing number of childhood contagious diseases (p=0.007). Infections have a dual role in the genesis of CHD. EV, HSV and C. pneumoniae heat shock protein 60 IgG antibodies are associated with increased risk for CHD. Protection from infections usually suffered during the childhood before the era of MMR vaccination may predispose the individual to CHD.
Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Wei, Yu-Feng; Chiu, Chien-Tung; Wu, Jiun-Ting; Hsu, Chi-Kuei; Chen, Jung-Yueh; Lee, Ho-Sheng; Lin, Hsi-Hsun; Chen, Yen-Hsu
2014-01-01
Background The clinical characteristics of Q fever are poorly identified in the tropics. Fever with pneumonia or hepatitis are the dominant presentations of acute Q fever, which exhibits geographic variability. In southern Taiwan, which is located in a tropical region, the role of Q fever in community-acquired pneumonia (CAP) has never been investigated. Methodology/Principal Findings During the study period, May 2012 to April 2013, 166 cases of adult CAP and 15 cases of acute Q fever were prospectively investigated. Cultures of clinical specimens, urine antigen tests for Streptococcus pneumoniae and Legionella pneumophila, and paired serologic assessments for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Q fever (Coxiella burnetii) were used for identifying pathogens associated with CAP. From April 2004 to April 2013 (the pre-study period), 122 cases of acute Q fever were also included retrospectively for analysis. The geographic distribution of Q fever and CAP cases was similar. Q fever cases were identified in warmer seasons and younger ages than CAP. Based on multivariate analysis, male gender, chills, thrombocytopenia, and elevated liver enzymes were independent characteristics associated with Q fever. In patients with Q fever, 95% and 13.5% of cases presented with hepatitis and pneumonia, respectively. Twelve (7.2%) cases of CAP were seropositive for C. burnetii antibodies, but none of them had acute Q fever. Among CAP cases, 22.9% had a CURB-65 score ≧2, and 45.8% had identifiable pathogens. Haemophilus parainfluenzae (14.5%), S. pneumoniae (6.6%), Pseudomonas aeruginosa (4.8%), and Klebsiella pneumoniae (3.0%) were the most common pathogens identified by cultures or urine antigen tests. Moreover, M. pneumoniae, C. pneumoniae, and co-infection with 2 pathogens accounted for 9.0%, 7.8%, and 1.8%, respectively. Conclusions In southern Taiwan, Q fever is an endemic disease with hepatitis as the major presentation and is not a common etiology of CAP. PMID:25033402
Responses to Bacteria, Virus, and Malaria Distinguish the Etiology of Pediatric Clinical Pneumonia
Valim, Clarissa; Ahmad, Rushdy; Lanaspa, Miguel; Tan, Yan; Acácio, Sozinho; Gillette, Michael A.; Almendinger, Katherine D.; Milner, Danny A.; Madrid, Lola; Pellé, Karell; Harezlak, Jaroslaw; Silterra, Jacob; Alonso, Pedro L.; Carr, Steven A.; Mesirov, Jill P.; Wiegand, Roger C.; Bassat, Quique
2016-01-01
Rationale: Plasma-detectable biomarkers that rapidly and accurately diagnose bacterial infections in children with suspected pneumonia could reduce the morbidity of respiratory disease and decrease the unnecessary use of antibiotic therapy. Objectives: Using 56 markers measured in a multiplexed immunoassay, we sought to identify proteins and protein combinations that could discriminate bacterial from viral or malarial diagnoses. Methods: We selected 80 patients with clinically diagnosed pneumonia (as defined by the World Health Organization) who also met criteria for bacterial, viral, or malarial infection based on clinical, radiographic, and laboratory results. Ten healthy community control subjects were enrolled to assess marker reliability. Patients were subdivided into two sets: one for identifying potential markers and another for validating them. Measurements and Main Results: Three proteins (haptoglobin, tumor necrosis factor receptor 2 or IL-10, and tissue inhibitor of metalloproteinases 1) were identified that, when combined through a classification tree signature, accurately classified patients into bacterial, malarial, and viral etiologies and misclassified only one patient with bacterial pneumonia from the validation set. The overall sensitivity and specificity of this signature for the bacterial diagnosis were 96 and 86%, respectively. Alternative combinations of markers with comparable accuracy were selected by support vector machine and regression models and included haptoglobin, IL-10, and creatine kinase–MB. Conclusions: Combinations of plasma proteins accurately identified children with a respiratory syndrome who were likely to have bacterial infections and who would benefit from antibiotic therapy. When used in conjunction with malaria diagnostic tests, they may improve diagnostic specificity and simplify treatment decisions for clinicians. PMID:26469764
Community-Acquired Bacterial Meningitis in Alcoholic Patients
Weisfelt, Martijn; de Gans, Jan; van der Ende, Arie; van de Beek, Diederik
2010-01-01
Background Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis. Methods/Principal Findings This was a prospective nationwide observational cohort study including patients aged >16 years who had bacterial meningitis confirmed by culture of cerebrospinal fluid (696 episodes of bacterial meningitis occurring in 671 patients). Alcoholism was present in 27 of 686 recorded episodes of bacterial meningitis (4%) and alcoholics were more often male than non-alcoholics (82% vs 48%, P = 0.001). A higher proportion of alcoholics had underlying pneumonia (41% vs 11% P<0.001). Alcoholics were more likely to have meningitis due to infection with Streptococcus pneumoniae (70% vs 50%, P = 0.01) and Listeria monocytogenes (19% vs 4%, P = 0.005), whereas Neisseria meningitidis was more common in non-alcoholic patients (39% vs 4%, P = 0.01). A large proportion of alcoholics developed complications during clinical course (82% vs 62%, as compared with non-alcoholics; P = 0.04), often cardiorespiratory failure (52% vs 28%, as compared with non-alcoholics; P = 0.01). Alcoholic patients were at risk for unfavourable outcome (67% vs 33%, as compared with non-alcoholics; P<0.001). Conclusions/Significance Alcoholic patients are at high risk for complications resulting in high morbidity and mortality. They are especially at risk for cardiorespiratory failure due to underlying pneumonia, and therefore, aggressive supportive care may be crucial in the treatment of these patients. PMID:20161709
Falynskova, I N; Leonova, E I; Fedyakina, I T; Makhmudova, N R; Lepekha, L N; Mikhailova, N A; Rasnetsov, L D; Zverev, V V; Leneva, I A
2015-01-01
Study the effectiveness of the substance and various drug formulations of fullerene-(tris-aminocapronic acid) hydrate (FTAAH onwards) in the model of experimental viral-bacterial pneumonia of mice. BALB/c mice were infected with influenza virus A/California/04/2009 and subsequently infected with Staphylococcus aureus. The animals were treated after viral infection with the substance and various drug forms of FTAAH, as well as comparative preparations--oseltamivir and arbidol. Therapy effectiveness was evaluated by clinical indicators (survival, lifespan, animal mass decrease reduction), virological (virus titer), microbiological (density of bacteria in lungs) parameters, confirmed by pathomorphological characteristics of lungs. FTAAH therapy in injectable form was effective in the model of a combined viral-bacterial pneumonia of mice by all the studied criteria: treatment increased mice survival, reduced the decrease of their body weight, resulted in a reduction of virus titers and density of bacteria in lungs, that correlated with the data from morphological study and signs of bronchopneumonia resolution in mice. FTAAH therapy in rectal form depended on animal infection schemes, as well as preparation dose, increasing with its increase. FTAAH substance is effective in the model of experimental viral-bacterial pneumonia of mice.
Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Karadag Oncel, Eda; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz
2014-01-01
Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.
Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Oncel, Eda Karadag; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz
2014-01-01
Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey. PMID:25483487
Podsiad, Amy; Standiford, Theodore J; Ballinger, Megan N; Eakin, Richard; Park, Pauline; Kunkel, Steven L; Moore, Bethany B; Bhan, Urvashi
2016-03-01
Postinfluenza bacterial pneumonia is associated with significant mortality and morbidity. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. miR-155 has recently emerged as a crucial regulator of innate immunity and inflammatory responses and is induced in macrophages during infection. We hypothesized upregulation of miR-155 inhibits IL-17 and increases susceptibility to secondary bacterial pneumonia. Mice were challenged with 100 plaque-forming units H1N1 intranasally and were infected with 10(7) colony-forming units of MRSA intratracheally at day 5 postviral challenge. Lungs were harvested 24 h later, and expression of miR-155, IL-17, and IL-23 was measured by real-time RT-PCR. Induction of miR-155 was 3.6-fold higher in dual-infected lungs compared with single infection. miR-155(-/-) mice were protected with significantly lower (4-fold) bacterial burden and no differences in viral load, associated with robust induction of IL-23 and IL-17 (2.2- and 4.8-fold, respectively) postsequential challenge with virus and bacteria, compared with WT mice. Treatment with miR-155 antagomir improved lung bacterial clearance by 4.2-fold compared with control antagomir postsequential infection with virus and bacteria. Moreover, lung macrophages collected from patients with postviral bacterial pneumonia also had upregulation of miR-155 expression compared with healthy controls, consistent with observations in our murine model. This is the first demonstration that cellular miRNAs regulate postinfluenza immune response to subsequent bacterial challenge by suppressing the IL-17 pathway in the lung. Our findings suggest that antagonizing certain microRNA might serve as a potential therapeutic strategy against secondary bacterial infection. Copyright © 2016 the American Physiological Society.
Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients
de Steenhuijsen Piters, Wouter A A; Huijskens, Elisabeth G W; Wyllie, Anne L; Biesbroek, Giske; van den Bergh, Menno R; Veenhoven, Reinier H; Wang, Xinhui; Trzciński, Krzysztof; Bonten, Marc J; Rossen, John W A; Sanders, Elisabeth A M; Bogaert, Debby
2016-01-01
Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research. PMID:26151645
21 CFR 522.1660a - Oxytetracycline solution, 200 milligrams/milliliter.
Code of Federal Regulations, 2014 CFR
2014-04-01
..., or intravenously for treatment of pneumonia and shipping fever complex associated with Pasteurella... retreatment of calves and yearlings for bacterial pneumonia is impractical, for treatment of infectious bovine.... coli, pneumonia caused by Pasteurella multocida, and leptospirosis caused by Leptospira pomona. (C) 9...
21 CFR 522.1660a - Oxytetracycline solution, 200 milligrams/milliliter.
Code of Federal Regulations, 2013 CFR
2013-04-01
..., or intravenously for treatment of pneumonia and shipping fever complex associated with Pasteurella... retreatment of calves and yearlings for bacterial pneumonia is impractical, for treatment of infectious bovine..., colibacillosis) caused by E. coli, pneumonia caused by Pasteurella multocida, and leptospirosis caused by...
21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.
Code of Federal Regulations, 2012 CFR
2012-04-01
... treatment of pneumonia and shipping fever complex associated with Pasteurella spp. and Histophilus spp... dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical or for treatment... pneumonia is impractical or for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by...
21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.
Code of Federal Regulations, 2013 CFR
2013-04-01
... treatment of pneumonia and shipping fever complex associated with Pasteurella spp. and Histophilus spp... dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical or for treatment... pneumonia is impractical or for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by...
21 CFR 522.1660a - Oxytetracycline solution, 200 milligrams/milliliter.
Code of Federal Regulations, 2012 CFR
2012-04-01
..., or intravenously for treatment of pneumonia and shipping fever complex associated with Pasteurella... retreatment of calves and yearlings for bacterial pneumonia is impractical, for treatment of infectious bovine..., colibacillosis) caused by E. coli, pneumonia caused by Pasteurella multocida, and leptospirosis caused by...
21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.
Code of Federal Regulations, 2014 CFR
2014-04-01
... treatment of pneumonia and shipping fever complex associated with Pasteurella spp. and Histophilus spp... dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical or for treatment... pneumonia is impractical or for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by...
Mukhopadhyay, Sanjay; Parambil, Joseph G
2012-10-01
Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Walenna, Nirwana Fitriani; Kurihara, Yusuke; Chou, Bin; Ishii, Kazunari; Soejima, Toshinori; Itoh, Ryota; Shimizu, Akinori; Ichinohe, Takeshi; Hiromatsu, Kenji
2018-01-01
Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via β-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway. Copyright © 2017 Elsevier Inc. All rights reserved.
21 CFR 520.2345c - Tetracycline boluses.
Code of Federal Regulations, 2010 CFR
2010-04-01
... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia caused by Pasteurella spp... tetracycline, bacterial enteritis caused by E. coli, and salmonella organisms susceptible to tetracycline. (ii...
21 CFR 520.2345c - Tetracycline boluses.
Code of Federal Regulations, 2011 CFR
2011-04-01
... bacterial enteritis (scours) caused by E. coli and bacterial pneumonia caused by Pasteurella spp... tetracycline, bacterial enteritis caused by E. coli, and salmonella organisms susceptible to tetracycline. (ii...
Case of a lung mass due to melioidosis in Mexico.
Truong, Kimberly K; Moghaddam, Samer; Al Saghbini, Samer; Saatian, Bahman
2015-05-06
Melioidosis, an infection caused by the gram-negative bacterium Burkholderia pseudomallei, is an important cause of pneumonia, skin infection, sepsis, and death in Southeast Asia and Australia, but is exceedingly rare in North America. Pulmonary melioidosis typically presents as acute bacterial pneumonia or cavitary lung lesions resembling tuberculosis. We report melioidosis in a 70-year-old active smoker from Mexico with no history of travel to disease-endemic areas. The patient presented with a left supraclavicular abscess and a non-cavitary, left lung mass encasing a pulmonary vein. Incision and drainage of the patient's subcutaneous abscess isolated B. pseudomallei, and fine-needle aspiration of enlarged mediastinal lymph nodes revealed the presence of intracellular gram-negative bacilli with no evidence of malignancy. Biochemical tests determined that the strain the patient acquired from Mexico is identical to only 1 other isolate from Thailand. This report highlights the blurring epidemiological borders of this organism, its rare presentation mimicking lung malignancy, and an aggressive antimicrobial treatment that resulted in resolution of the patient's symptoms.
Antonova, L P; Romanov, V V; Averbakh, M M
2008-01-01
The paper presents the results of treatment in 30 patients aged 16-59 years who have bronchial asthma and chronic obstructive pulmonary disease, by using a bacterial vaccine (bronchomunal) containing antigens of opportunistic bacteria: Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus viridans, Streptococcus piogenes, Moraxella catarrhalis. Immunotherapy with the vaccine had good and excellent effects in 73.33 of cases; the mean duration of acute respiratory viral infection decreased from 16 to 9 days after vaccination and a need for antibiotics. In the comparison group, a good effect was noted in 40% of the patients during one-year follow-up; the difference was statistically significant. The vaccine's tolerance was good; only 3 (9.9%) patients were observed to have vaccination-induced complications: exacerbations of chronic maxillary sinusitis and chronic bronchitis in 2 and 1 patients, respectively. The positive effect of bronchomunal was associated with the better values of cellular immunity, stabilized phagocytosis, and lower IgE levels.
[Management of Rhinosinusitis in Primary Care].
Gabaldón, N Gómez; Arnaiz, C Manzanares; Cánovas, L Noguero; Armas, J Juan
2018-02-13
Acute rhinosinusitis is an important health problem. Even though its frequency is not well documented in our country?, the economic burden it bears is not insignificant as it notably alters the quality of life of affected patients. Its diagnosis is generally clinical in nature, with further studies reserved only for the differential diagnoses of complications or tumour-like processes. The most frequent causes are viral infections, although Streptococcus pneumoniae and Haemophilus influenzae are the most commonly isolated bacterial agents. Although complications are uncommon nowadays, they can be serious when they occur, and commonly include orbital infections, closely followed in frequency by intracranial and bone infections. Treatment should consist of symptomatic measures, like saline rinses and antibiotics in cases of bacterial origin. Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Prevalence and antimicrobial resistance pattern of bacterial meningitis in Egypt
Shaban, Lamyaa; Siam, Rania
2009-01-01
Infectious diseases are the leading cause of morbidity and mortality in the developing world. In Egypt bacterial diseases constitute a great burden, with several particular bacteria sustaining the leading role of multiple serious infections. This article addresses profound bacterial agents causing a wide array of infections including but not limited to pneumonia and meningitis. The epidemiology of such infectious diseases and the prevalence of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are reviewed in the context of bacterial meningitis. We address prevalent serotypes in Egypt, antimicrobial resistance patterns and efficacy of vaccines to emphasize the importance of periodic surveillance for appropriate preventive and treatment strategies. PMID:19778428
File, Thomas M
2007-12-01
Rising levels of resistance amongst the major respiratory pathogens have compromised empiric antimicrobial therapy. This, coupled with a recent lack in availability of novel classes of antibacterials, has led to a need for new approaches to combat community respiratory tract infections. Bacteriological and clinical efficacy in two trials involving patients with acute bacterial sinusitis and six trials of patients with community-acquired pneumonia has shown that the development of a pharmacokinetically enhanced formulation of amoxicillin/clavulanate (Augmentin SR, available as Augmentin XR in the USA) has allowed amoxicillin/clavulanate to retain its place in the treatment of respiratory tract infections today.
Sui, Zhihai; Zhou, Wenqing; Yao, Kaihu; Liu, Li; Zhang, Gang; Yang, Yonghong
2013-01-01
Streptococcus pneumoniae is a primary cause of bacterial infection in humans. Here, we present the complete genome sequence of S. pneumoniae strain A026, which is a multidrug-resistant strain isolated from cerebrospinal fluid. PMID:24336372
Non-invasive ventilation in acute respiratory failure in children
Abadesso, Clara; Nunes, Pedro; Silvestre, Catarina; Matias, Ester; Loureiro, Helena; Almeida, Helena
2012-01-01
The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO2 at 2, 6, 12 and 24 hours after NIV onset (P<0.05) in both groups. Improvement in pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) was verified at 2, 4, 6, 12 and 24 hours after NIV onset in the success group (P<0.001). In the failure group, significant SpO2/FiO2 improvement was only observed in the first 4 hours. NIV failure occurred in 34 patients (22.5%). Risk factors for NIV failure were apnea, prematurity, pneumonia, and bacterial co-infection (P<0.05). Independent risk factors for NIV failure were apneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42–71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33–111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection. PMID:22802994
Non-invasive ventilation in acute respiratory failure in children.
Abadesso, Clara; Nunes, Pedro; Silvestre, Catarina; Matias, Ester; Loureiro, Helena; Almeida, Helena
2012-04-02
The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO(2) at 2, 6, 12 and 24 hours after NIV onset (P<0.05) in both groups. Improvement in pulse oximetric saturation/fraction of inspired oxygen (SpO(2)/FiO(2)) was verified at 2, 4, 6, 12 and 24 hours after NIV onset in the success group (P<0.001). In the failure group, significant SpO(2)/FiO(2) improvement was only observed in the first 4 hours. NIV failure occurred in 34 patients (22.5%). Risk factors for NIV failure were apnea, prematurity, pneumonia, and bacterial co-infection (P<0.05). Independent risk factors for NIV failure were apneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42-71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33-111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection.
Brouwer, M C; van de Beek, D
2012-05-01
Bacterial meningitis is a severe disease which affects 35.000 Europeans each year and has a mortality rate of about 20%. During the past 25 years the epidemiology of bacterial meningitis has changed significantly due to the implementation of vaccination against Haemophilus influenzae, Neisseria meningtidis group C and Streptococcus pneumoniae. Due to these vaccines, meningitis is now predominantly a disease occurring in adults, caused especially by Streptococcus pneumoniae, while it was formerly a child disease which was largely caused by Haemophilus influenzae. Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients. The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis. The treatment consists of the prescription of antibiotics and dexamethasone.
Congestive heart failure in children with pneumonia and respiratory failure.
Nimdet, Kachaporn; Techakehakij, Win
2017-03-01
Congestive heart failure (CHF) is one of the most common cardiac complications of pneumonia in adulthood leading to increased risk of morbidity and mortality. Little is known, however, of CHF and pneumonia in children. The aim of this study was therefore to investigate the characteristics and factors associated with CHF in under-5 children with pneumonia and respiratory failure. A retrospective cohort was conducted in hospitalized patients aged 2-59 months with community-acquired pneumonia and respiratory failure from June 2011 to June 2014 at Suratthani Hospital, Thailand. The characteristics, therapeutic strategy, and clinical outcomes of CHF were reviewed. Baseline characteristics and basic laboratory investigations on admission were compared between the CHF and non-CHF groups. Of 135 patients, 14 (10%) had CHF. Compared with patients without CHF, the CHF group had prolonged intubation and hospital stay and high rates of associated complications such as ventilator-associated pneumonia, sepsis, shock, and 30 day mortality. CHF was significantly associated with certain characteristics, including male sex and bacterial pneumonia. Pneumonia with respiratory failure is associated with CHF even in healthy children without cardiac risks. The awareness and early recognition of CHF, particularly in male, and bacterial pneumonia, is important in order to provide immediate treatment to reduce complications. © 2016 Japan Pediatric Society.
Grimprel, E; Cohen, R
2010-09-01
Levofloxacin (levogyre form of ofloxacin) has been approved for the treatment of acute and chronic sinusitis, pneumonia, and exacerbation of bronchopulmonary diseases, urinary, digestive and biliary infections in adults. Its pharmacokinetic properties and microbiological spectrum, including penicillin non-susceptible Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Mycoplasma pneumoniae, suggest a potential interest in drug-resistant acute otitis media and community-acquired pneumonia. Only few studies have been performed in the paediatric population but they provided encouraging efficacy and safety data. Complementary data are needed before considering its use in Europe in the setting of a paediatric investigation plan. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Microbiological Characteristics of Acute Prostatitis After Transrectal Prostate Biopsy
Bang, Jun-Ho; Choe, Hyun-Sop; Lee, Dong-Sup; Lee, Seung-Ju
2013-01-01
Purpose We aimed to identify microbiological characteristics in patients with acute prostatitis after transrectal prostate biopsy to provide guidance in the review of prevention and treatment protocols. Materials and Methods A retrospective analysis of medical records was performed in 1,814 cases who underwent prostate biopsy at Seoul St. Mary's Hospital and St. Vincent's Hospital over a 5 year period from 2006 to 2011. Cases in which acute prostatitis occurred within 7 days after the biopsy were investigated. Before starting treatment with antibiotics, sample collections were done for culture of urine and blood. Culture and drug susceptibility was identified by use of a method established by the Clinical and Laboratory Standards Institute. Results A total of 1,814 biopsy procedures were performed in 1,541 patients. For 1,246 patients, the procedure was the first biopsy, whereas for 295 patients it was a repeat biopsy. Twenty-one patients (1.36%) were identified as having acute bacterial prostatitis after the biopsy. Fifteen patients (1.2%) had acute prostatitis after the first biopsy, and 6 patients (2.03%) experienced acute prostatitis after a repeat biopsy. Even though the incidence of acute bacterial prostatitis was higher after repeat biopsy than that after the first biopsy, there was no statistically significant intergroup difference in terms of incidence (χ2=1.223, p=0.269). When the collected urine and blood samples were cultured, Escherichia coli was found in samples from 15 patients (71.4%), Klebsiella pneumoniae in 3 patients (14.3%), Enterobacter intermedius in 1 patient (4.8%), E. aerogenes in 1 patient (4.8%), and Pseudomonas aeruginosa in 1 patient (4.8%). A fluoroquinolone-resistant strain was confirmed in 5 cases (23.8%) in total. Three cases of E. coli and 1 case of Klebsiella had extended-spectrum β-lactamase activity. Conclusions Empirical treatment of acute prostatitis should be done with consideration of geographical prevalence and drug resistance. This study will provide meaningful information for the management of acute prostatitis after transrectal prostate biopsy. PMID:23550205
Naito, Keisuke; Yamasaki, Kei; Yatera, Kazuhiro; Akata, Kentaro; Noguchi, Shingo; Kawanami, Toshinori; Fukuda, Kazumasa; Kido, Takashi; Ishimoto, Hiroshi; Mukae, Hiroshi
2017-01-01
Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, Moraxella catarrhalis was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of Haemophilus influenzae and Pseudomonas aeruginosa were unrelated to the severity of pulmonary emphysematous changes, and Streptococcus species - except for the S. anginosus group and S. pneumoniae - were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that M. catarrhalis is more frequently detected in pneumonia patients with moderate or severe emphysema than in those with no or mild emphysematous changes on chest CT. M. catarrhalis may play a major role in patients with pneumonia complicating severe pulmonary emphysema.
Drug-, toxin-, and radiation therapy-induced eosinophilic pneumonia.
Solomon, Joshua; Schwarz, Marvin
2006-04-01
A significant number of drugs and toxins have been associated with eosinophilic pneumonia. Antibiotics and NSAID, are the most commonly reported drugs. Toxins suspected to cause eosinophilic pneumonia include cigarette smoke and illicit drugs. Drug- or toxin-induced eosinophilic pneumonia is indistinguishable from idiopathic acute or chronic eosinophilic pneumonia by clinical, radiographic, and histopathologic criteria. The diagnosis is supported by a temporal relationship to a drug or toxin. The condition usually resolves with removal from the agent and recurs with rechallenge. Treatment involves discontinuation of the offending drug or toxin and treatment with corticosteroids in severe respiratory failure. There are also mass outbreaks of eosinophilic pneumonia reported, such as the toxic-oil syndrome in 1981 and the eosinophilia-myalgia syndrome related to the ingestion of L-tryptophan in 1989. A recent report has described an outbreak of acute eosinophilic pneumonia found in soldiers in Iraq. Radiation therapy has also been associated with the development of eosinophilic pneumonia in patients receiving this treatment for breast cancer.
Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a murine pneumonia model.
Thomsen, K; Christophersen, L; Bjarnsholt, T; Jensen, P Ø; Moser, C; Høiby, N
2016-03-01
Oral prophylactic therapy by gargling with pathogen-specific egg yolk immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive immunization and we investigated the effects of anti-P. aeruginosa IgY antibodies on bacterial eradication in a murine pneumonia model. P. aeruginosa pneumonia was established in Balb/c mice and the effects of prophylactic IgY administration on lung bacteriology, clinical parameters and subsequent inflammation were compared to controls. Prophylactic administration of IgY antibodies targeting P. aeruginosa significantly reduced the bacterial burden by 2-log 24h post-infection compared to controls and was accompanied by significantly reduced clinical symptom scores and successive inflammatory cytokine profile indicative of diminished lung inflammation. Passive immunization by anti-P. aeruginosa IgY therapy facilitates promptly bacterial clearance and moderates inflammation in P. aeruginosa lung infection and may serve as an adjunct to antibiotics in reducing early colonization. Copyright © 2015. Published by Elsevier B.V.
Wong, Irene O L; Cowling, Benjamin J; Leung, Gabriel M; Schooling, C Mary
2012-01-01
Hong Kong population has experienced drastic changes in its economic development in the 1940s. Taking advantage of Hong Kong's unique demographic and socioeconomic history, characterized by massive, punctuated migration waves from Southern China, and recent, rapid transition from a pre-industrialized society to the first ethnic Chinese community reaching "first world" status over the last 60 years (i.e., in two or three generations), we examined the longitudinal trends in infection related mortality including septicemia compared to trends in non-bacterial pneumonia to generate hypotheses for further testing in other recently transitioned economies and to provide generalized aetiological insights on how economic transition affects infection-related mortality. We used deaths from septicemia and pneumonia not specified as bacterial, and population figures in Hong Kong from 1976-2005. We fitted age-period-cohort models to decompose septicemia and non-bacterial pneumonia mortality rates into age, period and cohort effects. Septicaemia-related deaths increased exponentially with age, with a downturn by period. The birth cohort curves had downward inflections in both sexes in the 1940s, with a steeper deceleration for women. Non-bacterial pneumonia-related deaths also increased exponentially with age, but the birth cohort patterns showed no downturns for those born in the 1940s. The observed changes appeared to suggest that better early life conditions may enable better development of adaptive immunity, thus enhancing immunity against bacterial infections, with greater benefits for women than men. Given the interaction between the immune system and the gonadotropic axis, these observations are compatible with the hypothesis that upregulation of the gonadotropic axis underlies some of the changes in disease patterns with economic development.
Chien, Yu-Wen; Vidal, Jorge E.; Grijalva, Carlos G.; Bozio, Catherine; Edwards, Kathryn M.; Williams, John V.; Griffin, Marie R.; Verastegui, Hector; Hartinger, Stella M.; Gil, Ana I.; Lanata, Claudio F.; Klugman, Keith P.
2012-01-01
Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are commonly carried in the nasopharynx (NP) of young children, and have been speculated to interact with each other. Although earlier studies used cultures alone to assess these interactions, the addition of real-time quantitative polymerase chain reaction (qPCR) provides further insight into these interactions. We compared results of culture and qPCR for the detection of these three bacteria in 446 NP samples collected from 360 healthy young children in a prospective cohort study in the Peruvian Andes. Patterns of concurrent bacterial colonization were studied using repeated measures logistic regression models with generalized estimating equations. Spearman correlation coefficients were employed to assess correlations among bacterial densities. At a bacterial density <105 colony forming units (CFU)/ml measured by qPCR, culture detected significantly less carriers (P<0.0001) for all three pathogens, than at a bacterial density >105 CFU/ml. In addition, there was a positive association between S. pneumoniae and H. influenzae colonization measured by both culture (OR 3.11 – 3.17, p < 0.001) and qPCR (OR 1.95 – 1.97, p < 0.01). The densities of S. pneumoniae and H. influenzae, measured by qPCR, were positively correlated (correlation coefficient 0.32, p < 0.001). A negative association was found between the presence of S. pneumoniae and S. aureus in carriage with both culture (OR 0.45, p = 0.024) and qPCR (OR 0.61, p < 0.05). The impact of density on detection by culture and the observed density-related interactions support use of qPCR in additional studies to examine vaccine effects on diverse bacterial species. PMID:22935873
Chien, Yu-Wen; Vidal, Jorge E; Grijalva, Carlos G; Bozio, Catherine; Edwards, Kathryn M; Williams, John V; Griffin, Marie R; Verastegui, Hector; Hartinger, Stella M; Gil, Ana I; Lanata, Claudio F; Klugman, Keith P
2013-01-01
Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are commonly carried in the nasopharynx of young children, and have been speculated to interact with each other. Although earlier studies used cultures alone to assess these interactions, the addition of real-time quantitative polymerase chain reaction (qPCR) provides further insight into these interactions. We compared results of culture and qPCR for the detection of these 3 bacteria in 446 nasopharynx samples collected from 360 healthy young children in a prospective cohort study in the Peruvian Andes. Patterns of concurrent bacterial colonization were studied using repeated measures logistic regression models with generalized estimating equations. Spearman correlation coefficients were used to assess correlations among bacterial densities. At a bacterial density <10 colony forming units/mL measured by qPCR, culture detected significantly less carriers (P < 0.0001) for all 3 pathogens, than at a bacterial density >10 colony forming units/mL. In addition, there was a positive association between S. pneumoniae and H. influenzae colonization measured by both culture (odds ratio [OR] 3.11-3.17, P < 0.001) and qPCR (OR 1.95-1.97, P < 0.01). The densities of S. pneumoniae and H. influenzae, measured by qPCR, were positively correlated (correlation coefficient 0.32, P < 0.001). A negative association was found between the presence of S. pneumoniae and Staphylococcus aureus in carriage with both culture (OR 0.45, P = 0.024) and qPCR (OR 0.61, P < 0.05). The impact of density on detection by culture and the observed density-related interactions support use of qPCR in additional studies to examine vaccine effects on diverse bacterial species.
Zhang, Tongtong; Zhu, Lifei; Li, Miao; Hu, Yuzhen; Zhang, Erfeng; Jiang, Qingcheng; Han, Guang; Jin, Yiguang
2017-05-01
Bacterial pneumonia is a serious disease with high mortality if no appropriate and immediate therapy is available. Andrographolide (AG) is an anti-inflammatory agent extracted from a traditional Chinese herb andrographis paniculata. Oral AG tablets and pills are clinically applied for treatment of upper respiratory tract infections. However, the low solubility and bioavailability of AG lead to high doses and long-term therapy. Here we developed an andrographolide-β-cyclodextrin inclusion complex (AG-β-CD) for inhalation therapy of Staphylococcus aureus pneumonia. AG-β-CD was identified with X-ray diffraction and FT-IR. Surprisingly, both AG-β-CD and AG showed little in vitro anti-S. aureus activity. However, pulmonary delivery of AG, AG-β-CD, or penicillin had significant anti-S. aureus pneumonia effects. Leukocytes, neutrophils, white blood cells, total proteins, TNF-α, IL-6, NF-κB p65 expression, and bacterial colonies in the bronchoalveolar lavage fluids were detected. Pulmonary delivery of AG and AG-β-CD led to bacterial inhibition and inflammation alleviation by regulating immune responses, while penicillin only killed bacteria without significant immune regulation. Moreover, the antipneumonia activity of AG-β-CD was much higher than that of AG, probably resulting from locally accelerated AG dissolution due to β-CD inclusion. The aerodynamic diameter of AG-β-CD powders was 2.03 μm, suitable for pulmonary delivery. Inhalable AG-β-CD is a promising antibacterial and anti-inflammatory medicine for the treatment of S. aureus pneumonia by regulating immune responses, and the effect is enhanced by β-CD inclusion. AG and its formulations might be potent weapons against the resistant bacterial pneumonia due to their specific mechanism in the future.
Oda, Keishi; Yatera, Kazuhiro; Fujino, Yoshihisa; Kido, Takashi; Hanaka, Tetsuya; Sennari, Konomi; Fushimi, Kiyohide; Matsuda, Shinya; Mukae, Hiroshi
2018-01-01
Respiratory comorbidities are frequently associated with idiopathic pulmonary fibrosis (IPF). However, little is known about their prognostic impact in hospitalized patients with IPF. We examined the impact of respiratory comorbidities on the mortality rates of hospitalized patients with IPF using a Japanese nationwide database. We identified 5665 hospitalized patients diagnosed with IPF between April 2010 and March 2013. The primary outcome was defined as the in-hospital mortality at 30 days after admission. The impact of respiratory comorbidities was assessed using a Cox proportional hazards model that incorporated clinically relevant factors. In hospitalized patients with IPF, the prevalence of bacterial pneumonia, pulmonary hypertension, and lung cancer were 9.5%, 4.6%, and 3.7%, respectively. Among patients with bacterial pneumonia, the four most common pathogens were Streptococcus pneumoniae (31.6%), methicillin-resistant Streptococcus aureus (18.4%), Klebsiella pneumoniae (9.2%), and Pseudomonas aeruginosa (9.2%). Lung cancer was more commonly found in the lower lobes (60.1%) than in other lobes. The survival at 30 days from admission was 78.4% in all patients and significantly lower in IPF patients with bacterial pneumonia (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.63; p < 0.023) and patients with lung cancer (adjusted HR, 1.99; 95% CI, 1.47-2.69; p < 0.001) than in others. Pulmonary hypertension was not associated with mortality. IPF patients with one or more of these three respiratory comorbidities had a poorer survival than others (p < 0.05). Respiratory comorbidities, especially bacterial pneumonia and lung cancer, influence mortality in hospitalized patients with IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Will, M E; Sylvia, D M
1990-07-01
Plants must be established quickly on replenished beaches in order to stabilize the sand and begin the dune-building process. The objective of this research was to determine whether inoculation of sea oats (Uniola paniculata L.) with bacteria (indigenous rhizosphere bacteria and N(2) fixers) alone or in combination with vesicular-arbuscular mycorrhizal fungi would enhance plant growth in beach sand. At two fertilizer-N levels, Klebsiella pneumoniae and two Azospirillum spp. did not provide the plants with fixed atmospheric N; however, K. pneumoniae increased root and shoot growth. When a sparingly soluble P source (CaHPO(4)) was added to two sands, K. pneumoniae increased plant growth in sand with a high P content. The phosphorus content of shoots was not affected by bacterial inoculation, indicating that a mechanism other than bacterially enhanced P availability to plants was responsible for the growth increases. When sea oats were inoculated with either K. pneumoniae or Acaligenes denitrificans and a mixed Glomus inoculum, there was no consistent evidence of a synergistic effect on plant growth. Nonetheless, bacterial inoculation increased root colonization by vesicular-arbuscular mycorrhizal fungi when the fungal inoculum consisted of colonized roots but had no effect on colonization when the inoculum consisted of spores alone. K. pneumoniae was found to increase spore germination and hyphal growth of Glomus deserticola compared with the control. The use of bacterial inoculants to enhance establishment of pioneer dune plants warrants further study.
Sachdev, Anil; Chugh, Krishan; Raghunathan, Veena; Gupta, Dhiren; Wattal, Chand; Menon, Geetha R
2013-01-01
To evaluate the reproducibility of blind bronchial sampling in patients with suspected diagnosis of bacterial ventilator-associated pneumonia. Prospective study. Pediatric intensive care unit of a tertiary care, multidisciplinary, teaching hospital in Northern India. All consecutive patients on mechanical ventilation for >48 hrs were evaluated clinically for ventilator-associated pneumonia. Children with clinical ventilator-associated pneumonia were subjected to blind bronchial sampling twice. Sixty-eight blind bronchial sampling samples from 34 patients were analyzed for polymorphonuclear cells, the presence, type, and number of bacteria. Acinetobacter baumannii was the most common organism grown from distal respiratory secretions. For polymorphonuclear cells, the concordance between two blind bronchial samples was 85.3% and kappa coefficient was 0.65. The concordance for the presence and type of bacteria in Gram staining in two samples was 85.3% and kappa coefficient was 0.68. The intraclass coefficients for bacterial index and predominant species index were 0.82 (95% confidence interval 0.65-0.91) and 0.89 (95% confidence interval 0.78-0.94), respectively. The use of prior antibiotics did not adversely affect the reproducibility of blind bronchial sampling. No major complications were recorded during the procedure. Blind bronchial sampling of lower respiratory tract secretions in mechanically ventilated patients generates reproducible results of quantitative and qualitative cultures. We suggest that blind bronchial sampling may provide valuable clue to the bacterial etiology in ventilated child with suspected clinical ventilator-associated pneumonia.
Maruschke, Matthias; Riebold, Diana; Holtfreter, Martha Charlotte; Sombetzki, Martina; Mitzner, Steffen; Loebermann, Micha; Reisinger, Emil Christian; Hakenberg, Oliver W
2014-12-01
The Pneumocystis pneumonia is an increasing problem in transplanted patients: up to 25% suffer from Pneumocystis pneumonia, occurring during the first 6 months after transplantation. From 2001 to 2009, we investigated 21 patients with pneumonia after renal transplantation for the presence of Pneumocystis jirovecii. The laboratory diagnosis was established by Grocott and Giemsa staining methods and Pneumocystis-specific mitochondrial transcribed large subunit nested polymerase chain reaction (PCR). The PCR was also used for the differentiation of Pneumocystis pneumonia from Pneumocystis carriage. Of 21 patients, 7 had a Pneumocystis pneumonia, 6 were Pneumocystis carriers and 8 patients were negative. Four out of seven Pneumocystis pneumonia patients and two out of six patients with Pneumocystis carriage had a delayed graft function. An acute cytomegalovirus infection after transplantation was not detectable in the patients with Pneumocystis pneumonia, but in three patients with Pneumocystis carriage. Pneumocystis pneumonia was present in 33.3% of transplanted patients with suspected pneumonia. An association between acute rejection or co-infections and Pneumocystis pneumonia or carriage in patients after renal transplantation cannot be excluded. In three out of seven Pneumocystis pneumonia patients, an overlapping of hospitalisation times and an onset of Pneumocystis pneumonia 6 months after transplantation was found. Thus, person-to-person transmission seems probable in these cases.
Alves Galvão, Márcia G; Rocha Crispino Santos, Marilene Augusta; Alves da Cunha, Antonio J L
2016-02-29
Undifferentiated acute respiratory infections (ARIs) are a large and heterogeneous group of infections not clearly restricted to one specific part of the upper respiratory tract, which last for up to seven days. They are more common in pre-school children in low-income countries and are responsible for 75% of the total amount of prescribed antibiotics in high-income countries. One possible rationale for prescribing antibiotics is the wish to prevent bacterial complications. To assess the effectiveness and safety of antibiotics in preventing bacterial complications in children aged two months to 59 months with undifferentiated ARIs. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August week 1, 2015) and EMBASE (1974 to August 2015). Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotic prescriptions with placebo or no treatment in children aged two months to 59 months with an undifferentiated ARI for up to seven days. Two review authors independently assessed trial quality and extracted and analysed data using the standard Cochrane methodological procedures. We identified four trials involving 1314 children. Three trials investigated the use of amoxicillin/clavulanic acid to prevent otitis and one investigated ampicillin to prevent pneumonia.The use of amoxicillin/clavulanic acid compared to placebo to prevent otitis showed a risk ratio (RR) of 0.70 (95% confidence interval (CI) 0.45 to 1.11, three trials, 414 selected children, moderate-quality evidence). Methods of random sequence generation and allocation concealment were not clearly stated in two trials. Performance, detection and reporting bias could not be ruled out in three trials.Ampicillin compared to supportive care (continuation of breastfeeding, clearing of the nose and paracetamol for fever control) to prevent pneumonia showed a RR of 1.05 (95% CI 0.74 to 1.49, one trial, 889 selected children, moderate-quality evidence). The trial was non-blinded. Random sequence generation and allocation concealment methods were not clearly stated, so the possibility of reporting bias could not be ruled out.Harm outcomes could not be analysed as they were expressed only in percentages.We found no studies assessing mastoiditis, quinsy, abscess, meningitis, hospital admission or death. There is insufficient evidence for antibiotic use as a means of reducing the risk of otitis or pneumonia in children up to five years of age with undifferentiated ARIs. Further high-quality research is needed to provide more definitive evidence of the effectiveness of antibiotics in this population.
Repertoire of Intensive Care Unit Pneumonia Microbiota
Bousbia, Sabri; Papazian, Laurent; Saux, Pierre; Forel, Jean Marie; Auffray, Jean-Pierre; Martin, Claude; Raoult, Didier; La Scola, Bernard
2012-01-01
Despite the considerable number of studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively applied modern and traditional laboratory diagnostic techniques to identify microbiota in patients who were admitted to or developed pneumonia in intensive care units (ICUs). During a three-year period, we tested the bronchoalveolar lavage (BAL) of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared the results with those from patients without pneumonia (controls). Samples were tested by amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 have not been previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rDNA gene divergence ≥98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients can present up to 16 different microorganisms in a single BAL (mean ± SD; 3.77±2.93). Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species can be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented. PMID:22389704
Aydemir, Yusuf; Aydemir, Özlem; Pekcan, Sevgi; Özdemir, Mehmet
2017-02-01
Conventional methods for the aetiological diagnosis of community-acquired pneumonia (CAP) are often insufficient owing to low sensitivity and the long wait for the results of culture and particularly serology, and it often these methods establish a diagnosis in only half of cases. To evaluate the most common bacterial and viral agents in CAP using a fast responsive PCR method and investigate the relationship between clinical/laboratory features and aetiology, thereby contributing to empirical antibiotic selection and reduction of treatment failure. In children aged 4-15 years consecutively admitted with a diagnosis of CAP, the 10 most commonly detected bacterial and 12 most commonly detected viral agents were investigated by induced sputum using bacterial culture and multiplex PCR methods. Clinical and laboratory features were compared between bacterial and viral pneumonia. In 78 patients, at least one virus was detected in 38 (48.7%) and at least one bacterium in 32 (41%). In addition, both bacteria and viruses were detected in 16 (20.5%) patients. Overall, the agent detection rate was 69.2%. The most common viruses were respiratory syncytial virus and influenza and the most frequently detected bacteria were S. pneumoniae and H. influenzae. PCR was superior to culture for bacterial isolation (41% vs 13%, respectively). Fever, wheezing and radiological features were not helpful in differentiating between bacterial and viral CAP. White blood cell count, CRP and ESR values were significantly higher in the bacterial/mixed aetiology group than in the viral aetiology group. In CAP, multiplex PCR is highly reliable, superior in detecting multiple pathogens and rapidly identifies aetiological agents. Clinical features are poor for differentiation between bacterial and viral infections. The use of PCR methods allow physicians to provide more appropriate antimicrobial therapy, resulting in a better response to treatment, and it may be possible for use as a routine service if costs can be reduced.
Acute eosinophilic pneumonia secondary to heroin inhalation.
Eyüpoğlu, Damla; Ortaç Ersoy, Ebru; Rollas, Kazım; Topeli, Arzu
2017-06-01
Smoking heroin (chasing the dragon), is a method of inhaling heroin via heating the drug on a tin-foil above a flame. It also has been associated both with the indirect effects of heroin overdose and with direct pulmonary toxicity. We describe a case of acute eosinophilic pneumonia secondary to heroin inhalation in our medical intensive care unit. She presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed bilateral infiltrations. Examination of bronchoalveolar lavage fluid revealed significant eosinophilia. She was diagnosed with acute eosinophilic pneumonia. After heroin abstinence and corticosteroid therapy, remission was achieved rapidly and the patient was discharge on the fourth day of her hospital stay.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nakagawa, Motoo, E-mail: lmloltlolol@gmail.com; Ogino, Hiroyuki; Shimohira, Masashi
2009-05-15
A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.
Sonnappa, Samatha; Martin, Richard; Israel, Elliot; Postma, Dirkje; van Aalderen, Wim; Burden, Annie; Usmani, Omar S; Price, David B
2017-01-01
Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD. The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used. Historical cohort, UK database study of 23,013 patients with obstructive lung disease aged 12-80 years prescribed extra-fine or fine-particle ICS. The endpoints assessed during the outcome year were diagnosis of pneumonia, acute exacerbations and acute respiratory events in relation to ICS dose. To determine the association between ICS particle size, dose and risk of pneumonia in unmatched and matched treatment groups, logistic and conditional logistic regression models were used. 14788 patients were stepped-up to fine-particle ICS and 8225 to extra-fine ICS. On unmatched analysis, patients stepping-up to extra-fine ICS were significantly less likely to be coded for pneumonia (adjusted odds ratio [aOR] 0.60; 95% CI 0.37, 0.97]); experience acute exacerbations (adjusted risk ratio [aRR] 0.91; 95%CI 0.85, 0.97); and acute respiratory events (aRR 0.90; 95%CI 0.86, 0.94) compared with patients stepping-up to fine-particle ICS. Patients prescribed daily ICS doses in excess of 700 mcg (fluticasone propionate equivalent) had a significantly higher risk of pneumonia (OR [95%CI] 2.38 [1.17, 4.83]) compared with patients prescribed lower doses, irrespective of particle size. These findings suggest that patients with obstructive lung disease on extra-fine particle ICS have a lower risk of pneumonia than those on fine-particle ICS, with those receiving higher ICS doses being at a greater risk.
Severe Varicella Pneumonia in Adults: Seven Years’ Single-center Experience from India
Singh, Akashdeep; Parkash, Siddharth; Gupta, Sunil K; Soni, R. K.
2018-01-01
Context: Varicella pneumonia is a rare but a serious complication of chickenpox in adults. There is paucity of data on varicella pneumonia from India. Aims: The aim of this study is to describe the clinical manifestations, hospital course, treatment, and outcome of adult patients with severe varicella pneumonia. Settings and Design: This was a retrospective, observational study of patients with severe varicella pneumonia attending a tertiary care teaching hospital. Subjects and Methods: The cases of varicella were identified by a computerized search of the medical record for the period between January 2010 and December 2016. During this period, 137 patients got admitted with varicella of which 22 had severe varicella pneumonia. Statistical Analysis: Mean and standard deviation were computed. Fisher's Z-test of proportions and analysis of variance were applied. Results: There were 17 (77.3%) men and 5 (22.7%) women. The mean age of the patients was 33.4 ± 10.8 years. History of contact with an infected person followed by high-grade fever and typical rash was present in all patients. Forty-five percent (10/22) of patients were immunosuppressed. All the patients received intravenous acyclovir. Forty-five percent (10/22) of patients received invasive mechanical ventilation. The various factors associated with the need for mechanical ventilation were partial pressure of oxygen:fraction of inspired oxygen ratio <150, quick sequential (sepsis-related) organ failure assessment (qSOFA) >2, and early bacterial coinfection. The mean Intensive Care Unit and hospital stay were 7 days (range; 1–16) and 9 days (range; 4–21), respectively. The overall mortality was 22.7% and reached 50% in those requiring invasive ventilation. The mortality was higher among patients with qSOFA >3, mean arterial blood pressure <60 mmHg, and severe acute respiratory distress syndrome at presentation. Conclusions: Patients with severe varicella pneumonia are at an increased risk of respiratory failure and death. PMID:29657373
Severe Varicella Pneumonia in Adults: Seven Years' Single-center Experience from India.
Singh, Akashdeep; Parkash, Siddharth; Gupta, Sunil K; Soni, R K
2018-03-01
Varicella pneumonia is a rare but a serious complication of chickenpox in adults. There is paucity of data on varicella pneumonia from India. The aim of this study is to describe the clinical manifestations, hospital course, treatment, and outcome of adult patients with severe varicella pneumonia. This was a retrospective, observational study of patients with severe varicella pneumonia attending a tertiary care teaching hospital. The cases of varicella were identified by a computerized search of the medical record for the period between January 2010 and December 2016. During this period, 137 patients got admitted with varicella of which 22 had severe varicella pneumonia. Mean and standard deviation were computed. Fisher's Z-test of proportions and analysis of variance were applied. There were 17 (77.3%) men and 5 (22.7%) women. The mean age of the patients was 33.4 ± 10.8 years. History of contact with an infected person followed by high-grade fever and typical rash was present in all patients. Forty-five percent (10/22) of patients were immunosuppressed. All the patients received intravenous acyclovir. Forty-five percent (10/22) of patients received invasive mechanical ventilation. The various factors associated with the need for mechanical ventilation were partial pressure of oxygen:fraction of inspired oxygen ratio <150, quick sequential (sepsis-related) organ failure assessment (qSOFA) >2, and early bacterial coinfection. The mean Intensive Care Unit and hospital stay were 7 days (range; 1-16) and 9 days (range; 4-21), respectively. The overall mortality was 22.7% and reached 50% in those requiring invasive ventilation. The mortality was higher among patients with qSOFA >3, mean arterial blood pressure <60 mmHg, and severe acute respiratory distress syndrome at presentation. Patients with severe varicella pneumonia are at an increased risk of respiratory failure and death.
Kawanami, Toshinori; Yatera, Kazuhiro; Yamasaki, Kei; Noguchi, Shingo; Fukuda, Kazumasa; Akata, Kentarou; Naito, Keisuke; Kido, Takashi; Ishimoto, Hiroshi; Taniguchi, Hatsumi; Mukae, Hiroshi
2016-04-16
Determining whether methicillin-resistant Staphylococcus aureus (MRSA) is a true causative pathogen or reflective of colonization when MRSA is cultured from the respiratory tract remains important in treating patients with pneumonia. We evaluated the bacterial microbiota in bronchoalveolar lavage fluid (BALF) using the clone library method with a 16S ribosomal RNA (rRNA) gene analysis in 42 patients from a pneumonia registry who had MRSA cultured from their sputum or BALF samples. Patients were divided into two groups: those treated with (Group A) or without (Group B) anti-MRSA agents, and their clinical features were compared. Among 248 patients with pneumonia, 42 patients who had MRSA cultured from the respiratory tract were analyzed (Group A: 13 patients, Group B: 29 patients). No clones of S. aureus were detected in the BALF of 20 out of 42 patients. Twenty-eight of 29 patients in Group B showed favorable clinical outcomes, indicating that these patients had non-MRSA pneumonia. Using a microflora analysis of the BALF, the S. aureus phylotype was predominant in 5 of 28 (17.9%) patients among the detected bacterial phylotypes, but a minor population (the percentage of clones ≤ 10%) in 19 (67.9%) of 28 patients. A statistical analysis revealed no positive relationship between the percentage of clones of the S. aureus phylotype and risk factors of MRSA pneumonia. The molecular method using BALF specimens suggests that conventional cultivation method results may mislead true causative pathogens, especially in patients with MRSA pneumonia. Further studies are necessary to elucidate these clinically important issues.
Sopena, N; Sabrià-Leal, M; Pedro-Botet, M L; Padilla, E; Dominguez, J; Morera, J; Tudela, P
1998-05-01
The aim of this study was to compare the clinical, biological, and radiologic features of presentation in the emergency ward of community-acquired pneumonia (CAP) by Legionella pneumophila (LP) and other community-acquired bacterial pneumonias to help in early diagnosis of CAP by LP. Three hundred ninety-two patients with CAP were studied prospectively in the emergency department of a 600-bed university hospital. Univariate and multivariate analyses were performed to compare epidemiologic and demographic data and clinical, analytical, and radiologic features of presentation in 48 patients with CAP by LP and 125 patients with CAP by other bacterial etiology (68 by Streptococcus pneumoniae, 41 by Chlamydia pneumoniae, 5 by Mycoplasma pneumoniae, 4 by Coxiella burnetii, 3 by Pseudomonas aeruginosa, 2 by Haemophilus influenzae, and 2 by Nocardia species. Univariate analysis showed that CAP by LP was more frequent in middle-aged, male healthy (but alcohol drinking) patients than CAP by other etiology. Moreover, the lack of response to previous beta-lactamic drugs, headache, diarrhea, severe hyponatremia, and elevation in serum creatine kinase (CK) levels on presentation were more frequent in CAP by LP, while cough, expectoration, and thoracic pain were more frequent in CAP by other bacterial etiology. However, multivariate analysis only confirmed these differences with respect to lack of underlying disease, diarrhea, and elevation in the CK level. We conclude that detailed analysis of features of presentation of CAP allows suspicion of Legionnaire's disease in the emergency department. The initiation of antibiotic treatment, including a macrolide, and the performance of rapid diagnostic techniques are mandatory in these cases.
2012-01-01
Introduction Ventilator-associated pneumonia (VAP) may contribute to the mortality associated with acute respiratory distress syndrome (ARDS). We aimed to determine the incidence, outcome, and risk factors of bacterial VAP complicating severe ARDS in patients ventilated by using a strictly standardized lung-protective strategy. Methods This prospective epidemiologic study was done in all the 339 patients with severe ARDS included in a multicenter randomized, placebo-controlled double-blind trial of cisatracurium besylate in severe ARDS patients. Patients with suspected VAP underwent bronchoalveolar lavage to confirm the diagnosis. Results Ninety-eight (28.9%) patients had at least one episode of microbiologically documented bacterial VAP, including 41 (41.8%) who died in the ICU, compared with 74 (30.7%) of the 241 patients without VAP (P = 0.05). After adjustment, age and severity at baseline, but not VAP, were associated with ICU death. Cisatracurium besylate therapy within 2 days of ARDS onset decreased the risk of ICU death. Factors independently associated with an increased risk to develop a VAP were male sex and worse admission Glasgow Coma Scale score. Tracheostomy, enteral nutrition, and the use of a subglottic secretion-drainage device were protective. Conclusions In patients with severe ARDS receiving lung-protective ventilation, VAP was associated with an increased crude ICU mortality which did not remain significant after adjustment. PMID:22524447
El Mdaghri, N; Jilali, N; Belabbes, H; Jouhadi, Z; Lahssoune, M; Zaid, S
2012-11-01
The aim of this prospective study in Morocco was to investigate the causes of invasive bacterial diseases in children in order to inform antibiotic therapy and vaccine choices. Of 238 children aged < or = 5 years admitted to the Children's Hospital of Casablanca for invasive diseases over a 12-month period, 185 were diagnosed with bacterial infection: 76 had chest-X-ray-confirmed pneumonia, 59 had meningitis and 50 had sepsis. Streptococcus pneumoniae was the most common pathogen identified (n = 24), followed by Neisseria meningitidis (n = 18, all group B) and Haemophilus influenzae (n = 11). The rate of penicillin non-susceptibility was 62.5% among Str. pneumoniae isolates and 11.1% among N. meningitidis and all isolates were ceftriaxone-susceptible. Of the 11 H. influenzae isolates, only 1 produced a beta-lactamase. The 5 predominant Str. pneumoniae serotypes were 19F, 14, 23F, 6B and 19A and the theoretical coverage of the 7, 10 and 13-valent pneumococcal conjugate vaccines was 60%, 78% and 91% respectively.
Acute bacterial meningitis in infants and children: epidemiology and management.
Agrawal, Shruti; Nadel, Simon
2011-12-01
Acute bacterial meningitis (ABM) continues to be associated with high mortality and morbidity, despite advances in antimicrobial therapy. The causative organism varies with age, immune function, immunization status, and geographic region, and empiric therapy for meningitis is based on these factors. Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis cause the majority of cases of ABM. Disease epidemiology is changing rapidly due to immunization practices and changing bacterial resistance patterns. Hib was the leading cause of meningitis in children prior to the introduction of an effective vaccination. In those countries where Hib vaccine is a part of the routine infant immunization schedule, Hib has now been virtually eradicated as a cause of childhood meningitis. Vaccines have also been introduced for pneumococcal and meningococcal diseases, which have significantly changed the disease profile. Where routine pneumococcal immunization has been introduced there has been a reported increase in invasive pneumococcal disease due to non-vaccine serotypes. In those parts of the world that have introduced conjugate meningococcal vaccines, there has been a significant change in the epidemiology of meningococcal meningitis. As a part of the United Nations Millennium Development Goal 4, the WHO has introduced a new vaccine policy to improve vaccine availability in resource poor countries. In addition, antibiotic resistance is an increasing problem, especially with pneumococcal infection. Effective treatment focuses on early recognition and use of effective antibiotics. This review will attempt to focus on the changing epidemiology of ABM in pediatric patients due to vaccination, the changing patterns of infecting bacterial serotypes due to vaccination, and on antibiotic resistance and its impact on current management strategies.
[Community acquired bacterial meningitis in patients over 60].
Mora Mora, Luis A; Arco Espinosa, Micke E de; Plumet, Javier; Micheli, Federico
2015-01-01
Acute bacterial meningitis has a global mortality rate of 135000 cases per year. In Argentina over the last 12 years, the annual incidence rate has been 5.5/100 000. About 20% of patients present neurological sequelae, which are more common in patients aged 60 or older. Our objective here is to determine the clinical characteristics, the most common causes and to measure evolution in patients over 60 years old diagnosed with meningitis and treated at the Hospital de Clinicas José de San Martín. This is a retrospective study based on a review of medical records from 2003 to 2013 that takes into account patients older than 60 who were diagnosed with acute bacterial meningitis acquired in the community by a microbiological diagnosis of CSF or those included due to a high suspicion of bacterial meningitis (pleocitosis > 2000 cells/mm3, proteins > 220 mg/dl, glycorrhachia < 34 mg/dl, glycorrhachia/glucose index < 0.23). Cases of TB meningitis, nosocomial, postoperative and other nonbacterial meningitis were excluded. Sixty nine patients were included, 45 (65%) were women with an average age of 78 ± 10.6 years. Only 40% had the triad of classical meningitis symptoms (stiff neck, fever and altered mental status). In 52% of the patients germs developed in the CSF, the most frequent being Streptococcus pneumoniae present in 47% of cases. Lethality rate was 41%, all of them by methicillin-sensitive Staphylococcus aureus. Only 24 (35%) cases were admitted into intensive care. The main sequelae present were motor disorders (12%) and hearing loss (5%).
CYTOKINES AS THE PREDICTORS OF SEVERE MYCOPLASMA PNEUMONIAE PNEUMONIA IN CHILDREN (REVIEW).
Chkhaidze, I; Kapanadze, N
2017-06-01
In spite of many attempts to differentiate bacterial from viral disease and predict severity and outcome, the etiologic diagnosis of paediatric community acquired pneumonia and the estimation of potential outcomes remain unsolved problems in most cases. Mycoplasma pneumoniae is one of the major pathogens causing CAP in children. Although MP infection was traditionally thought to be a self-limited process, more and more severe cases even fatal cases of MP infections were reported in recent years. So it is essential for pediatricians to recognize severe or refractory or severe MP early, treat it promptly and prevent the progress of the disease. In recent years, several new biomarkers have been tested in children with CAP. Some of the biomarkers used for etiologic diagnosis in children with CAP and they also have been used the MP infection severity. Among traditional biomarkers, several cytokines appears to be effective both in selection of bacterial cases and in evaluation of severity. However, a precise cut-off level able to separate bacterial from viral cases and mild from severe cases has not been defined. Further studies enrolled with a large number of children with Mycoplasma pneumoniae is needed to be carried out to identify the potential utility of different cytokines as the good predictors.
Van Bambeke, Françoise
2014-11-01
Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).
USDA-ARS?s Scientific Manuscript database
Klebsiella pneumoniae is an opportunistic pathogen that commonly causes hospital and community acquired bacterial infections in humans. The emergence and rapid spread of multi- drug resistant (MDR) K. pneumoniae is causing drug therapy failure amid patients leading to poor antibiotic management glob...
Boccalini, Sara; Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bonanni, Paolo; Bechini, Angela
2017-02-01
Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002-2007) and vaccination period (VP, 2009-2014). We analyzed hospital discharge records (HDRs) of all hospitals in Tuscany from 2002 to 2014. Hospitalizations potentially due to pneumococcal diseases were 347, 221. The general hospitalization rate was 716/100,000 inhabitants during PVP and 753/100,000 in VP, with a decrease of 29.1% in the age-group 0-9 y ("target" of the vaccination program) and an increase of 75.7% in subjects >64 y of age. During VP, admission days and hospitalization costs increased (6.2% and 24.2%, respectively), especially in patients >64 y (12.9% and 33.8%, respectively); in children <10 y decreased by 21.2% and 12.8%, respectively. The pneumococcal pediatric vaccination resulted in the decrease of hospitalizations in younger but the expected indirect effect in the elderly was not reported, justifying the Tuscan recommendation to extend the vaccination to subjects > 64 y.
Kuroda, Takeshi; Takeuchi, Hiroyuki; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Moriyama, Hiroshi; Nakano, Masaaki; Narita, Ichiei
2016-04-26
Pneumocystis jirovecii pneumonia (PCP) is potentially fatal infectious complication in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. Hospital survival due to human immunodeficiency virus-unrelated PCP reaches to 60%. The high mortality rate results from difficulties in establishing an early diagnosis, concurrent use of prophylactic drugs, possible bacterial coinfection. We herein report a case of PCP in RA patients who developed the architectural distortions of lung in spite of combined modality therapy. A 73-year-old Japanese woman with RA was admitted with shortness of breath. Five weeks previously, she had been started on etanercept in addition to methotrexate (MTX). Chest computed tomography (CT) demonstrated diffuse ground glass opacities distributed throughout the bilateral middle to lower lung fields, and serum β-D-glucan was elevated. Bronchoalveolar lavage fluid revealed no P. jirovecii, but the organism was detected by polymerase chain reaction method. Trimethoprim/sulfamethoxazole was administered with methylprednisolone pulse therapy. However, the follow-up chest X-ray and chest CT demonstrated aggravation of the pneumonia with architectural distortions. Additional direct hemoperfusion with polymyxin B-immobilized fibers and intravenous cyclophosphamide therapy were insufficiently effective, and the patient died on day 25. The architectural distortions of lung should be considered as a cause of death of PCP. For this reason, a high suspicion of this infectious complication must be kept in mind in order to establish an early diagnosis and treatment in patients with RA managed with MTX and biologics.
Dupont, Aline; Mohamed, Fatima; Salehen, Nur'Ain; Glenn, Sarah; Francescut, Lorenza; Adib, Rozita; Byrne, Simon; Brewin, Hannah; Elliott, Irina; Richards, Luke; Dimitrova, Petya; Schwaeble, Wilhelm; Ivanovska, Nina; Kadioglu, Aras; Machado, Lee R; Andrew, Peter W; Stover, Cordula
2014-08-01
Streptococcus pneumoniae and Listeria monocytogenes, pathogens which can cause severe infectious disease in human, were used to infect properdin-deficient and wildtype mice. The aim was to deduce a role for properdin, positive regulator of the alternative pathway of complement activation, by comparing and contrasting the immune response of the two genotypes in vivo. We show that properdin-deficient and wildtype mice mounted antipneumococcal serotype-specific IgM antibodies, which were protective. Properdin-deficient mice, however, had increased survival in the model of streptococcal pneumonia and sepsis. Low activity of the classical pathway of complement and modulation of FcγR2b expression appear to be pathogenically involved. In listeriosis, however, properdin-deficient mice had reduced survival and a dendritic cell population that was impaired in maturation and activity. In vitro analyses of splenocytes and bone marrow-derived myeloid cells support the view that the opposing outcomes of properdin-deficient and wildtype mice in these two infection models is likely to be due to a skewing of macrophage activity to an M2 phenotype in the properdin-deficient mice. The phenotypes observed thus appear to reflect the extent to which M2- or M1-polarised macrophages are involved in the immune responses to S. pneumoniae and L. monocytogenes. We conclude that properdin controls the strength of immune responses by affecting humoral as well as cellular phenotypes during acute bacterial infection and ensuing inflammation.
The obesity paradox in community-acquired bacterial pneumonia.
Corrales-Medina, Vicente F; Valayam, Josemon; Serpa, Jose A; Rueda, Adriana M; Musher, Daniel M
2011-01-01
The impact of obesity on the outcome of pneumonia is uncertain. We retrospectively identified 266 hospitalized patients with proven pneumococcal or Haemophilus community-acquired pneumonia who had at least one body mass index (BMI, kg/m²) value documented in the 3 months before admission. Patients were classified as underweight (BMI <18.5), normal weight (BMI 18.5 to <25), overweight (BMI 25 to <30), or obese (BMI ≥30). The association of absolute BMI values and BMI categories with the mortality at 30 days after admission for pneumonia was investigated. Increasing BMI values were associated with reduced 30-day mortality, even after adjustment for significant covariates (odds ratio 0.88, confidence interval 0.81-0.96; p<0.01). There was a significant trend towards lower mortality in the overweight and obese (non-parametric trend, p=0.02). Our data suggest that obesity may exert a protective effect against 30-day mortality from community-acquired bacterial pneumonia. Copyright © 2010 International Society for Infectious Diseases. All rights reserved.
How Radiotherapy Was Historically Used To Treat Pneumonia: Could It Be Useful Today?
Calabrese, Edward J.; Dhawan, Gaurav
2013-01-01
X-ray therapy was used to treat pneumonia during the first half of the 20th century. Fifteen studies report that approximately 700 cases of bacterial (lobar and bronchopneumonia), sulfanilamide non-responsive, interstitial, and atypical pneumonia were effectively treated by low doses of X-rays, leading to disease resolution, based on clinical symptoms, objective disease biomarkers, and mortality incidence. The capacity of the X-ray treatment to reduce mortality was similar to serum therapy and sulfonamide treatment during the same time period. Studies with four experimental animal models (i.e., mice, guinea pig, cat, and dog) with bacterial and viral pneumonia supported the clinical findings. The mechanism by which the X-ray treatment acts upon pneumonia involves the induction of an anti-inflammatory phenotype that leads to a rapid reversal of clinical symptoms, facilitating disease resolution. The capacity of low doses of X-rays to suppress inflammatory responses is a significant new concept with widespread biomedical and therapeutic applications. PMID:24348219
Systematic Search for Primary Immunodeficiency in Adults With Infections
2018-05-15
Complement Deficiency; Antibody Deficiency; Chronic Sinus Infection; Meningitis, Bacterial; Pneumonia, Bacterial; Otitis Media; Streptococcal Infection; Neisseria Infections; Haemophilus Influenza; Pneumococcal Infections
Epidemiology and antibiotic resistance of bacterial meningitis in Dapaong, northern Togo.
Karou, Simplice D; Balaka, Abago; Bamoké, Mitiname; Tchelougou, Daméhan; Assih, Maléki; Anani, Kokou; Agbonoko, Kodjo; Simpore, Jacques; de Souza, Comlan
2012-11-01
To assess the seasonality of the bacterial meningitis and the antibiotic resistance of incriminated bacteria over the last three years in the northern Togo. From January 2007 to January 2010, 533 cerebrospinal fluids (CSF) samples were collected from patients suspected of meningitis in the Regional Hospital of Dapaong (northern Togo). After microscopic examination, samples were cultured for bacterial identification and antibiotic susceptibility. The study included 533 patients (306 male and 227 female) aged from 1 day to 55 years [average age (13.00±2.07) years]. Bacterial isolation and identification were attempted for 254/533 (47.65%) samples. The bacterial species identified were: Neisseria meningitidis A (N. meningitidis A) (58.27%), Neisseria meningitidis W135 (N. meningitidis W135) (7.09%), Streptococcus pneumoniae (S. pneumoniae) (26.77%), Haemophilus influenza B (H. influenza B) (6.30%) and Enterobacteriaceae (1.57%). The results indicated that bacterial meningitis occur from November to May with a peak in February for H. influenzae and S. pneumoniae and March for Neisseriaceae. The distribution of positive CSF with regards to the age showed that subjects between 6 and 12 years followed by subjects of 0 to 5 years were most affected with respective frequencies of 67.82% and 56.52% (P<0.001). Susceptibility tests revealed that bacteria have developed resistance to several antibiotics including aminosides (resistance rate >20% for both bacterial strains), macrolides (resistance rate > 30% for H. influenzae) quinolones (resistance rate >15% for H. influenzae and N. meningitidis W135). Over three years, the prevalence of S. pneumoniae significantly increased from 8.48% to 73.33% (P<0.001), while the changes in the prevalence of H. influenzae B were not statistically significant: 4.24%, vs. 8.89%, (P = 0.233). Our results indicate that data in African countries differ depending on geographical location in relation to the African meningitis belt. This underlines the importance of epidemiological surveillance of bacterial meningitis. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Johri, Ansh; Schimel, Daniel; Noguchi, Audrey; Hsu, Lewis L.
2010-03-01
Imaging is a crucial clinical tool for diagnosis and assessment of pneumonia, but quantitative methods are lacking. Micro-computed tomography (micro CT), designed for lab animals, provides opportunities for non-invasive radiographic endpoints for pneumonia studies. HYPOTHESIS: In vivo micro CT scans of mice with early bacterial pneumonia can be scored quantitatively by semiautomated imaging methods, with good reproducibility and correlation with bacterial dose inoculated, pneumonia survival outcome, and radiologists' scores. METHODS: Healthy mice had intratracheal inoculation of E. coli bacteria (n=24) or saline control (n=11). In vivo micro CT scans were performed 24 hours later with microCAT II (Siemens). Two independent radiologists scored the extent of airspace abnormality, on a scale of 0 (normal) to 24 (completely abnormal). Using the Amira 5.2 software (Mercury Computer Systems), a histogram distribution of voxel counts between the Hounsfield range of -510 to 0 was created and analyzed, and a segmentation procedure was devised. RESULTS: A t-test was performed to determine whether there was a significant difference in the mean voxel value of each mouse in the three experimental groups: Saline Survivors, Pneumonia Survivors, and Pneumonia Non-survivors. It was found that the voxel count method was able to statistically tell apart the Saline Survivors from the Pneumonia Survivors, the Saline Survivors from the Pneumonia Non-survivors, but not the Pneumonia Survivors vs. Pneumonia Non-survivors. The segmentation method, however, was successfully able to distinguish the two Pneumonia groups. CONCLUSION: We have pilot-tested an evaluation of early pneumonia in mice using micro CT and a semi-automated method for lung segmentation and scoring system. Statistical analysis indicates that the system is reliable and merits further evaluation.
Naucler, Pontus; Darenberg, Jessica; Morfeldt, Eva; Ortqvist, Ake; Henriques Normark, Birgitta
2013-06-01
Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia. To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia. A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden. Data on host factors and initial antibiotic treatment were collected from patient records. Antibiotic resistance and serotype were determined for bacterial isolates. Logistic regression analyses were performed to assess risk factors for 30-day mortality. Smoking, alcohol abuse, solid tumour, liver disease and renal disease attributed to 14.9%, 13.1%, 13.1%, 8.0% and 7.4% of the mortality, respectively. Age was the strongest predictor, and mortality increased exponentially from 1.3% in patients <45 years of age to 26.1% in patients aged ≥85 years. There was considerable confounding by host factors on the association between serotype and mortality. Increasing age, liver disease and serotype were associated with mortality in patients admitted to the ICU. Combined treatment with β-lactam antibiotics and macrolide/quinolone was associated with reduced mortality in patients in the ICU, although confounding could not be ruled out. Host factors appear to be more important than the specific serotype as determinants of mortality in patients with bacteraemic pneumococcal pneumonia. Several host factors were identified that contribute to mortality, which is important for prognosis and to guide targeted prevention strategies.
Vu, Huong Thi Thu; Yoshida, Lay Myint; Suzuki, Motoi; Nguyen, Hien Anh Thi; Nguyen, Cat Dinh Lien; Nguyen, Ai Thi Thuy; Oishi, Kengo; Yamamoto, Takeshi; Watanabe, Kiwao; Vu, Thiem Dinh
2011-01-01
The interplay between nasopharyngeal bacterial carriage, viral coinfection, and lower respiratory tract infections (LRTIs) is poorly understood. We explored this association in Vietnamese children aged less than 5 years. A hospital-based case-control study of pediatric LRTIs was conducted in Nha Trang, Vietnam. A total of 550 hospitalized children (274 radiologically confirmed pneumonia [RCP] and 276 other LRTIs) were enrolled and 350 healthy controls were randomly selected from the community. Polymerase chain reaction-based methods were used to measure bacterial loads of Streptococcus pneumoniae (SP), Haemophilus influenzae, and Moraxella catarrhalis and to detect 13 respiratory viruses and bacterial serotypes in nasopharyngeal samples of study participants. The median nasopharyngeal bacterial load of SP was substantially higher in children with RCP compared with healthy controls or children with other LRTIs (P < 0.001). SP load was 15-fold higher in pneumonia children with viral coinfection compared with those children without viral coinfection (1.4 x 10⁷/mL vs. 9.1 x 10⁵/mL; P 0.0001). SP load was over 200-fold higher in serotypeable SP compared with nontypeable SP (2.5 x 10⁶/mL vs. 1 x 10⁴/mL; P < 0.0001). These associations were independent of potential confounders in multiple regression models. No clear association was found between nasopharyngeal load of Haemophilus influenzae or Moraxella catarrhalis and viral coinfection in either RCP or other LRTIs groups. An increased load of SP in the nasopharynx was associated with RCP, viral coinfection, and presence of pneumococcal capsule.
Nunes, Sheila Elke Araujo; Minamisava, Ruth; Vieira, Maria Aparecida da Silva; Itria, Alexander; Pessoa, Vicente Porfirio; de Andrade, Ana Lúcia Sampaio Sgambatti; Toscano, Cristiana Maria
2017-01-01
ABSTRACT Objective To determine and compare hospitalization costs of bacterial community-acquired pneumonia cases via different costing methods under the Brazilian Public Unified Health System perspective. Methods Cost-of-illness study based on primary data collected from a sample of 59 children aged between 28 days and 35 months and hospitalized due to bacterial pneumonia. Direct medical and non-medical costs were considered and three costing methods employed: micro-costing based on medical record review, micro-costing based on therapeutic guidelines and gross-costing based on the Brazilian Public Unified Health System reimbursement rates. Costs estimates obtained via different methods were compared using the Friedman test. Results Cost estimates of inpatient cases of severe pneumonia amounted to R$ 780,70/$Int. 858.7 (medical record review), R$ 641,90/$Int. 706.90 (therapeutic guidelines) and R$ 594,80/$Int. 654.28 (Brazilian Public Unified Health System reimbursement rates). Costs estimated via micro-costing (medical record review or therapeutic guidelines) did not differ significantly (p=0.405), while estimates based on reimbursement rates were significantly lower compared to estimates based on therapeutic guidelines (p<0.001) or record review (p=0.006). Conclusion Brazilian Public Unified Health System costs estimated via different costing methods differ significantly, with gross-costing yielding lower cost estimates. Given costs estimated by different micro-costing methods are similar and costing methods based on therapeutic guidelines are easier to apply and less expensive, this method may be a valuable alternative for estimation of hospitalization costs of bacterial community-acquired pneumonia in children. PMID:28767921
Mycoplasma pneumoniae: an aetiological agent of acute haemorrhagic oedema of infancy.
Di Lernia, Vito
2014-11-01
Acute haemorrhagic oedema of infancy (AHEI) is considered a separate clinical entity among cutaneous small vessel vasculitis of childhood. It usually occurs in children younger than 2 years of age, with spontaneous recovery occurring within a few weeks. A history of recent upper respiratory or urinary tract infections or immunisation is found in most patients. Although Mycoplasma pneumoniae has been linked to a wide array of skin eruptions or diseases, it is not recognised as a possible cause of acute haemorrhagic oedema of infancy. The authors report a child with AHEI and a concurrent M. pneumoniae infection. © 2013 The Author. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.
Wu, Zegang; Li, Yan; Gu, Jian; Zheng, Hongyun; Tong, Yongqing; Wu, Qing
2014-02-01
Acute respiratory infection is the major cause of disease and death in children, particularly in developing countries. However, the spectrum of pathogenic viruses and atypical bacteria that exist in many of these countries remains incompletely characterized. The aim of this study was to examine the spectrum of pathogenic viruses and atypical bacteria associated with acute respiratory infection in children under the age of 16. A total of 10 435 serum sera specimens were collected from hospitalized children presenting with acute respiratory infection symptoms. Indirect immunofluorescence assays were performed to detect immunoglobulin M antibodies against nine common pathogens: mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila, coxiella burnetii and chamydophila pneumonia. Of the 10 435 specimens examined, 7046 tested positive for at least one pathogen. Among all of the tested pathogens, mycoplasma pneumonia had the highest detection rate (56.9%). Influenza virus A and influenza virus B epidemics occurred during both winter and summer. The detection rate of respiratory syncytial virus and adenovirus was higher in spring. Cases of mixed infection were more complex: 4136 specimens (39.6%) tested positive for ≥2 pathogens. There were statistically significant difference in detection rates of mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila and chamydophila pneumonia among different age groups (P < 0.05). The most common pathogens causing acute respiratory infection among children in Hubei of China were mycoplasma pneumonia, influenza virus B and respiratory syncytial virus. The detection rates for each pathogen displayed specific seasonal and age group variations. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.
Qu, Yanyan; Olonisakin, Tolani; Bain, William; Zupetic, Jill; Brown, Rebecca; Hulver, Mei; Xiong, Zeyu; Shanks, Robert M.Q.; Bomberger, Jennifer M.; Cooper, Vaughn S.; Zegans, Michael E.; Han, Jongyoon; Pilewski, Joseph; Ray, Anuradha; Ray, Prabir; Lee, Janet S.
2018-01-01
Acute lung injury is characterized by excessive extracellular matrix proteolysis and neutrophilic inflammation. A major risk factor for lung injury is bacterial pneumonia. However, host factors that protect against pathogen-induced and host-sustained proteolytic injury following infection are poorly understood. Pseudomonas aeruginosa (PA) is a major cause of nosocomial pneumonia and secretes proteases to amplify tissue injury. We show that thrombospondin-1 (TSP-1), a matricellular glycoprotein released during inflammation, dose-dependently inhibits PA metalloendoprotease LasB, a virulence factor. TSP-1–deficient (Thbs1–/–) mice show reduced survival, impaired host defense, and increased lung permeability with exaggerated neutrophil activation following acute intrapulmonary PA infection. Administration of TSP-1 from platelets corrects the impaired host defense and aberrant injury in Thbs1–/– mice. Although TSP-1 is cleaved into 2 fragments by PA, TSP-1 substantially inhibits Pseudomonas elastolytic activity. Administration of LasB inhibitor, genetic disabling of the PA type II secretion system, or functional deletion of LasB improves host defense and neutrophilic inflammation in mice. Moreover, TSP-1 provides an additional line of defense by directly subduing host-derived proteolysis, with dose-dependent inhibition of neutrophil elastase from airway neutrophils of mechanically ventilated critically ill patients. Thus, a host matricellular protein provides dual levels of protection against pathogen-initiated and host-sustained proteolytic injury following microbial trigger. PMID:29415890
Exogenous lipoid pneumonia – a case report of a fire-eater
Pielaszkiewicz-Wydra, Magdalena; Homola-Piekarska, Bożena; Szcześniak, Ewa; Ciołek-Zdun, Monika; Fall, Andrzej
2012-01-01
Summary Background: Exogenous lipoid pneumonia is an uncommon condition caused by inhalation or aspiration of a fatty substance. It usually presents as chronic respiratory illness mimicking interstitial lung diseases. Acute exogenous lipoid pneumonia is uncommon and typically is caused by an episode of aspiration of a large quantity of a petroleum-based product. Radiological findings vary and may imitate many other diseases. Case Report: We present a rare case of acute exogenous lipoid pneumonia in a fire-eater who aspirated liquid paraffin during his flame-blowing show (fire-eater’s lung). He was admitted to the hospital with productive cough, fever, hemoptysis, chest pain and dyspnea. Diagnosis was made on the basis of history of exposure to fatty substance, characteristic findings in CT examination and presence of lipid-laden macrophages in bronchoalveolar lavage fluid. Conclusions: Acute exogenous lipoid pneumonia is a very rare disease that typically occurs in fire-eaters and is called a fire-eater’s lung. The diagnosis is made on the basis of typical history and radiological, as well as histopathological findings. PMID:23269939
Aetiology and risk factors of community-acquired pneumonia in hospitalized patients in Norway.
Røysted, Wenche; Simonsen, Øystein; Jenkins, Andrew; Sarjomaa, Marjut; Svendsen, Martin Veel; Ragnhildstveit, Eivind; Tveten, Yngvar; Kanestrøm, Anita; Waage, Halfrid; Ringstad, Jetmund
2016-11-01
In Norway, data on the aetiology of community-acquired pneumonia (CAP) in hospitalized patients are limited. The aims of this study were to investigate the bacterial aetiology of CAP in hospitalized patients in Norway, risk factors for CAP and possible differences in risk factors between patients with Legionnaire's disease and pneumonia because of other causes. Adult patients with radiologically confirmed CAP admitted to hospital were eligible for the study. Routine aerobic and Legionella culture of sputum, blood culture, urinary antigen test for Legionella pneumophila and Streptococcus pneumoniae, polymerase chain reaction detection of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis from throat specimens, and serology for L. pneumophila serogroup 1-6 were performed. A questionnaire, which included demographic and clinical data, risk factors and treatment, was completed. We included 374 patients through a 20-month study period in 2007-2008. The aetiological agent was detected in 37% of cases. S. pneumoniae (20%) was the most prevalent agent, followed by Haemophilus influenzae (6%) and Legionella spp. (6%). Eight Legionella cases were diagnosed by urinary antigen test, of which four also had positive serology. In addition, 13 Legionella cases were diagnosed by serology. The degree of comorbidity was high. An increased risk of hospital-diagnosed Legionella pneumonia was found among patients with a diagnosis of chronic congestive heart failure. Our results indicate that S. pneumoniae is the most common bacterial cause of pneumonia in hospitalized patients, and the prevalence of Legionella pneumonia is probably higher in Norway than recognized previously. © 2015 John Wiley & Sons Ltd.
Voiriot, Guillaume; Visseaux, Benoit; Cohen, Johana; Nguyen, Liem Binh Luong; Neuville, Mathilde; Morbieu, Caroline; Burdet, Charles; Radjou, Aguila; Lescure, François-Xavier; Smonig, Roland; Armand-Lefèvre, Laurence; Mourvillier, Bruno; Yazdanpanah, Yazdan; Soubirou, Jean-Francois; Ruckly, Stephane; Houhou-Fidouh, Nadhira; Timsit, Jean-François
2016-10-25
Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. Among 174 patients (132 men [76 %], age 63 [53-75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16-11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.
Canani, Roberto Berni; Cirillo, Pia; Roggero, Paola; Romano, Claudio; Malamisura, Basilio; Terrin, Gianluca; Passariello, Annalisa; Manguso, Francesco; Morelli, Lorenzo; Guarino, Alfredo
2006-05-01
Gastric acidity (GA) inhibitors, including histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor-induced hypochlorhydria has been suggested as a risk factor for severe gastrointestinal infections. In addition, a number of papers and a meta-analysis have shown an increased risk of pneumonia in H2-blocker-treated intensive care patients. More recently, an increased risk of community-acquired pneumonia associated with GA inhibitor treatment has been reported in a large cohort of adult patients. These findings are particularly relevant to pediatricians today because so many children receive some sort of GA-blocking agent to treat GERD. To test the hypothesis that GA suppression could be associated with an increased risk of acute gastroenteritis and pneumonia in children treated with GA inhibitors, we conducted a multicenter, prospective study. The study was performed by expert pediatric gastroenterologists from 4 pediatric gastroenterology centers. Children (aged 4-36 months) consecutively referred for common GERD-related symptoms (for example, regurgitation and vomiting, feeding problems, effortless vomiting, choking), from December 2003 to March 2004, were considered eligible for the study. Exclusion criteria were a history of GA inhibitors therapy in the previous 4 months, Helicobacter pylori infection, diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food allergy, congenital motility gastrointestinal disorders, neuromuscular diseases, or malnutrition. Control subjects were recruited from healthy children visiting the centers for routine examinations. The diagnosis of GERD was confirmed in all patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50 children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the physicians for 2 months. All enrolled children were evaluated during a 4-month follow-up. The end point was the number of patients presenting with acute gastroenteritis or community-acquired pneumonia during a 4-month follow-up study period. We obtained data in 186 subjects: 95 healthy controls and 91 GA-inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were comparable for age, gender, weight, length, and incidence of acute gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was significantly increased in patients treated with GA inhibitors compared with healthy controls during the 4-month follow-up period. In the GA inhibitor-treated group, the rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was increased when comparing the 4 months before and after enrollment. No differences were observed between H2 blocker and PPI users in acute gastroenteritis and pneumonia incidence in the previous 4 months and during the follow-up period. On the contrary, in healthy controls, the incidence of acute gastroenteritis and pneumonia remained stable. This is the first prospective study performed in pediatric patients showing that the use of GA inhibitors was associated with an increased risk of acute gastroenteritis and community-acquired pneumonia in GERD-affected children. It could be interesting to underline that we observed an increased incidence of intestinal and respiratory infection in otherwise healthy children taking GA inhibitors for GERD treatment. On the contrary, the majority of the previous data showed that the patients most at risk for pneumonia were those with significant comorbid illnesses such as diabetes or immunodeficiency, and this points to the importance of GA suppression as a major risk factor for infections. In addition, this effect seems to be sustained even after the end of therapy. The results of our study are attributable to many factors, including direct inhibitory effect of GA inhibitors on leukocyte functions and qualitative and quantitative gastrointestinal microflora modification. Additional studies are necessary to investigate the mechanisms of the increased risk of infections in children treated with GA inhibitors, and prophylactic measures could be considered in preventing them.
21 CFR 522.2260 - Sulfamethazine.
Code of Federal Regulations, 2012 CFR
2012-04-01
... of 5 consecutive days. (2) Indications for use. For cattle for treatment of bacterial pneumonia and bovine respiratory disease complex (shipping fever complex) (Pasteurella spp.), colibacillosis (bacterial...
21 CFR 522.2260 - Sulfamethazine.
Code of Federal Regulations, 2013 CFR
2013-04-01
... of 5 consecutive days. (2) Indications for use. For cattle for treatment of bacterial pneumonia and bovine respiratory disease complex (shipping fever complex) (Pasteurella spp.), colibacillosis (bacterial...
Nijman, Ruud G; Vergouwe, Yvonne; Thompson, Matthew; van Veen, Mirjam; van Meurs, Alfred H J; van der Lei, Johan; Steyerberg, Ewout W; Moll, Henriette A
2013-01-01
Objective To derive, cross validate, and externally validate a clinical prediction model that assesses the risks of different serious bacterial infections in children with fever at the emergency department. Design Prospective observational diagnostic study. Setting Three paediatric emergency care units: two in the Netherlands and one in the United Kingdom. Participants Children with fever, aged 1 month to 15 years, at three paediatric emergency care units: Rotterdam (n=1750) and the Hague (n=967), the Netherlands, and Coventry (n=487), United Kingdom. A prediction model was constructed using multivariable polytomous logistic regression analysis and included the predefined predictor variables age, duration of fever, tachycardia, temperature, tachypnoea, ill appearance, chest wall retractions, prolonged capillary refill time (>3 seconds), oxygen saturation <94%, and C reactive protein. Main outcome measures Pneumonia, other serious bacterial infections (SBIs, including septicaemia/meningitis, urinary tract infections, and others), and no SBIs. Results Oxygen saturation <94% and presence of tachypnoea were important predictors of pneumonia. A raised C reactive protein level predicted the presence of both pneumonia and other SBIs, whereas chest wall retractions and oxygen saturation <94% were useful to rule out the presence of other SBIs. Discriminative ability (C statistic) to predict pneumonia was 0.81 (95% confidence interval 0.73 to 0.88); for other SBIs this was even better: 0.86 (0.79 to 0.92). Risk thresholds of 10% or more were useful to identify children with serious bacterial infections; risk thresholds less than 2.5% were useful to rule out the presence of serious bacterial infections. External validation showed good discrimination for the prediction of pneumonia (0.81, 0.69 to 0.93); discriminative ability for the prediction of other SBIs was lower (0.69, 0.53 to 0.86). Conclusion A validated prediction model, including clinical signs, symptoms, and C reactive protein level, was useful for estimating the likelihood of pneumonia and other SBIs in children with fever, such as septicaemia/meningitis and urinary tract infections. PMID:23550046
2012-01-01
inflammatory response can effectively stabilize and overcome a K. pneumoniae wound infection. An impaired host cannot control this bacterial burden...IL-8), whose release are further augmented by the presence of bacterial endotoxins . In addition, macrophages and neutrophils react with and eliminate...state of bacteria in their “natural” habitats, creates a physical barrier that prevents effective phagocytosis by inflammatory Wound Rep Reg (2012) 20
Stergiopoulos, Stella; Calvert, Sara B; Brown, Carrie A; Awatin, Josephine; Tenaerts, Pamela; Holland, Thomas L; DiMasi, Joseph A; Getz, Kenneth A
2018-01-01
Abstract Background Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methods With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials. Results Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers. Conclusions Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs. PMID:29020279
Age-related risk factors for bacterial aetiology in community-acquired pneumonia.
Sahuquillo-Arce, José M; Menéndez, Rosario; Méndez, Raúl; Amara-Elori, Isabel; Zalacain, Rafael; Capelastegui, Alberto; Aspa, Javier; Borderías, Luis; Martín-Villasclaras, Juan J; Bello, Salvador; Alfageme, Inmaculada; de Castro, Felipe Rodriguez; Rello, Jordi; Molinos, Luis; Ruiz-Manzano, Juan; Torres, Antoni
2016-11-01
The objective of this study was to evaluate the effect of age and comorbidities, smoking and alcohol use on microorganisms in patients with community-acquired pneumonia (CAP). A prospective multicentre study was performed with 4304 patients. We compared microbiological results, bacterial aetiology, smoking, alcohol abuse and comorbidities in three age groups: young adults (<45 years), adults (45-64 years) and seniors (>65 years). Bacterial aetiology was identified in 1522 (35.4%) patients. In seniors, liver disease was independently associated with Gram-negative bacteria (Haemophilus influenzae and Enterobacteriaceae), COPD with Pseudomonas aeruginosa (OR = 2.69 (1.46-4.97)) and Staphylococcus aureus (OR = 2.8 (1.24-6.3)) and neurological diseases with S. aureus. In adults, diabetes mellitus (DM) was a risk factor for Streptococcus pneumoniae and S. aureus, and COPD for H. influenzae (OR = 3.39 (1.06-10.83)). In young adults, DM was associated with S. aureus. Smoking was a risk factor for Legionella pneumophila regardless of age. Alcohol intake was associated with mixed aetiology and Coxiella burnetii in seniors, and with S. pneumoniae in young adults. It should be considered that the bacterial aetiology may differ according to the patient's age, comorbidities, smoking and alcohol abuse. More extensive microbiological testing is warranted in those with risk factors for infrequent microorganisms. © 2016 Asian Pacific Society of Respirology.
Shak, Joshua R; Cremers, Amelieke J H; Gritzfeld, Jenna F; de Jonge, Marien I; Hermans, Peter W M; Vidal, Jorge E; Klugman, Keith P; Gordon, Stephen B
2014-01-01
Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.
Gonzalez-Juarbe, Norberto; Bradley, Kelley M; Riegler, Ashleigh N; Reyes, Luis F; Brissac, Terry; Park, Sang-Sang; Restrepo, Marcos I; Orihuela, Carlos J
2018-04-11
Pore-forming toxins are the most common virulence factor in pathogenic bacteria. They lead to membrane permeabilization and cell death. Herein, we show that respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)-induced necroptosis simultaneously experienced caspase activation independently of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected in an additive manner against PFT-induced death. Subsequently, cleaved versions of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by immunoblots and monoclonal antibody staining. Caspase activation was observed in lung samples from mice and non-human primates experiencing Gram-negative and Gram-positive bacterial pneumonia, respectively. During apoptosis, caspase activation normally leads to cell shrinkage, nuclear condensation, and immunoquiescent death. In contrast, caspase activity during PFT-induced necroptosis increased the release of alarmins to the extracellular milieu. Caspase-mediated alarmin release was found sufficient to activate resting macrophages, leading to Interleukin-6 production. In a mouse model of Gram-negative pneumonia, deletion of caspases -2 and -11, the mouse orthologue of caspase-4, reduced pulmonary inflammation, immune cell infiltration and lung damage. Thus, our study describes a previously unrecognized role for caspase activation in parallel to necroptosis, and indicates that their activity plays a critical pro-inflammatory role during bacterial pneumonia.
Becker-Dreps, Sylvia; Blette, Bryan; Briceño, Rafaela; Alemán, Jorge; Hudgens, Michael G; Moreno, Gilberto; Ordoñez, Ana; Rocha, Julio; Weber, David J; Amaya, Erick
2017-01-01
Streptococcus pneumoniae causes about 826,000 deaths of children in the world each year and many health facility visits. To reduce the burden of pneumococcal disease, many nations have added pneumococcal conjugate vaccines to their national immunization schedules. Nicaragua was the first country eligible for GAVI Alliance funding to introduce the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010, provided to infants at 2, 4, and 6 months of age. The goal of this study was to evaluate the population impact of the first five years of the program. Numbers of visits for pneumonia, pneumonia-related deaths, and bacterial meningitis in both children and adults, and infant deaths between 2008 and 2015 were collected from all 107 public health facilities in León Department. Vital statistics data provided additional counts of pneumonia-related deaths that occurred outside health facilities. Adjusted incidence rates and incidence rate ratios (IRRa) in the vaccine (2011-2015) and pre-vaccine periods (2008-2010) were estimated retrospectively using official population estimates as exposure time. The IRRa for pneumonia hospitalizations was 0.70 (95% confidence interval [CI]: 0.66, 0.75) for infants, and 0.92 (95% CI: 0.85, 0.99) for one year-olds. The IRRa for post-neonatal infant mortality was 0.56 (95% CI: 0.41, 0.77). In the population as a whole, ambulatory visits and hospitalizations for pneumonia, as well as pneumonia-related mortality and rates of bacterial meningitis were lower in the vaccine period. During the first five years of program implementation, reductions were observed in health facility visits for pneumonia in immunized age groups and infant mortality, which would be hard to achieve with any other single public health intervention. Future study is warranted to understand whether the lack of a booster dose (e.g., at 12 months) may be responsible for the small reductions in pneumonia hospitalizations observed in one year-olds as compared to infants.
Blette, Bryan; Briceño, Rafaela; Alemán, Jorge; Hudgens, Michael G.; Moreno, Gilberto; Ordoñez, Ana; Rocha, Julio; Weber, David J.; Amaya, Erick
2017-01-01
Background Streptococcus pneumoniae causes about 826,000 deaths of children in the world each year and many health facility visits. To reduce the burden of pneumococcal disease, many nations have added pneumococcal conjugate vaccines to their national immunization schedules. Nicaragua was the first country eligible for GAVI Alliance funding to introduce the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010, provided to infants at 2, 4, and 6 months of age. The goal of this study was to evaluate the population impact of the first five years of the program. Methods Numbers of visits for pneumonia, pneumonia-related deaths, and bacterial meningitis in both children and adults, and infant deaths between 2008 and 2015 were collected from all 107 public health facilities in León Department. Vital statistics data provided additional counts of pneumonia-related deaths that occurred outside health facilities. Adjusted incidence rates and incidence rate ratios (IRRa) in the vaccine (2011–2015) and pre-vaccine periods (2008–2010) were estimated retrospectively using official population estimates as exposure time. Results The IRRa for pneumonia hospitalizations was 0.70 (95% confidence interval [CI]: 0.66, 0.75) for infants, and 0.92 (95% CI: 0.85, 0.99) for one year-olds. The IRRa for post-neonatal infant mortality was 0.56 (95% CI: 0.41, 0.77). In the population as a whole, ambulatory visits and hospitalizations for pneumonia, as well as pneumonia-related mortality and rates of bacterial meningitis were lower in the vaccine period. Conclusions During the first five years of program implementation, reductions were observed in health facility visits for pneumonia in immunized age groups and infant mortality, which would be hard to achieve with any other single public health intervention. Future study is warranted to understand whether the lack of a booster dose (e.g., at 12 months) may be responsible for the small reductions in pneumonia hospitalizations observed in one year-olds as compared to infants. PMID:28813518
Community-acquired pneumonia requiring hospitalization among U.S. children.
Jain, Seema; Williams, Derek J; Arnold, Sandra R; Ampofo, Krow; Bramley, Anna M; Reed, Carrie; Stockmann, Chris; Anderson, Evan J; Grijalva, Carlos G; Self, Wesley H; Zhu, Yuwei; Patel, Anami; Hymas, Weston; Chappell, James D; Kaufman, Robert A; Kan, J Herman; Dansie, David; Lenny, Noel; Hillyard, David R; Haynes, Lia M; Levine, Min; Lindstrom, Stephen; Winchell, Jonas M; Katz, Jacqueline M; Erdman, Dean; Schneider, Eileen; Hicks, Lauri A; Wunderink, Richard G; Edwards, Kathryn M; Pavia, Andrew T; McCullers, Jonathan A; Finelli, Lyn
2015-02-26
Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).
Naito, Keisuke; Yamasaki, Kei; Yatera, Kazuhiro; Akata, Kentaro; Noguchi, Shingo; Kawanami, Toshinori; Fukuda, Kazumasa; Kido, Takashi; Ishimoto, Hiroshi; Mukae, Hiroshi
2017-01-01
Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, Moraxella catarrhalis was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of Haemophilus influenzae and Pseudomonas aeruginosa were unrelated to the severity of pulmonary emphysematous changes, and Streptococcus species – except for the S. anginosus group and S. pneumoniae – were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that M. catarrhalis is more frequently detected in pneumonia patients with moderate or severe emphysema than in those with no or mild emphysematous changes on chest CT. M. catarrhalis may play a major role in patients with pneumonia complicating severe pulmonary emphysema. PMID:28790814
[Experimental study on chemotherapy of acute glanders].
Iliukhin, V I; Rotov, K A; Senina, T V; Snatenkov, E A; Tikhonov, S N; Plekhanova, N G; Kulikova, A S; Shubnikova, E V; Korol', E V; Nekhezina, M O
2012-01-01
Glanders is a zoonotic infection inducing acute forms of the disease (pneumonia, sepsis) in humans and animals under certain conditions, which even with the use of modern chemotherapy have unfavourable prognosis. Insufficient of efficacy of antibiotics with in vitro low MIC for planktonic bacterial suspension of Burkholderia mallei in chemotherapy of acute forms of glanders was due to the capacity of the pathogen for intracellular survival and formation of biofilms. Under such conditions the susceptibility of B. mallei to antibiotics lowered by several orders of magnitude. Chemotherapy of the glanders acute forms in animals usually provided only an increase of the lifespan, while among the survivors there was recorded a high relapse rate. More favourable outcomes were observed with the use of in vitro effective antibiotics in the form of clathrate compounds or especially liposomal forms. In the experiments with golden hamsters the survival rate reached 100% in 1000 Dlm infection even with the treatment onset by meropenem liposomal form 48 hours after the infection. Chemotherapeutics in the liposomal form significantly lowered resistance of B. mallei in both the experiments with a suspension of planktonic organisms and the use of bacteria interned in eukaryotic cells (Tetrahymena pyriformis).
Innate Immune Signaling Activated by MDR Bacteria in the Airway
Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice
2015-01-01
Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation. PMID:26582515
Overkamp, Wout; Beilharz, Katrin; Detert Oude Weme, Ruud; Solopova, Ana; Karsens, Harma; Kovács, Ákos T.; Kok, Jan
2013-01-01
Green fluorescent protein (GFP) offers efficient ways of visualizing promoter activity and protein localization in vivo, and many different variants are currently available to study bacterial cell biology. Which of these variants is best suited for a certain bacterial strain, goal, or experimental condition is not clear. Here, we have designed and constructed two “superfolder” GFPs with codon adaptation specifically for Bacillus subtilis and Streptococcus pneumoniae and have benchmarked them against five other previously available variants of GFP in B. subtilis, S. pneumoniae, and Lactococcus lactis, using promoter-gfp fusions. Surprisingly, the best-performing GFP under our experimental conditions in B. subtilis was the one codon optimized for S. pneumoniae and vice versa. The data and tools described in this study will be useful for cell biology studies in low-GC-rich Gram-positive bacteria. PMID:23956387
The role of influenza in the epidemiology of pneumonia
Shrestha, Sourya; Foxman, Betsy; Berus, Joshua; van Panhuis, Willem G.; Steiner, Claudia; Viboud, Cécile; Rohani, Pejman
2015-01-01
Interactions arising from sequential viral and bacterial infections play important roles in the epidemiological outcome of many respiratory pathogens. Influenza virus has been implicated in the pathogenesis of several respiratory bacterial pathogens commonly associated with pneumonia. Though clinical evidence supporting this interaction is unambiguous, its population-level effects—magnitude, epidemiological impact and variation during pandemic and seasonal outbreaks—remain unclear. To address these unknowns, we used longitudinal influenza and pneumonia incidence data, at different spatial resolutions and across different epidemiological periods, to infer the nature, timing and the intensity of influenza-pneumonia interaction. We used a mechanistic transmission model within a likelihood-based inference framework to carry out formal hypothesis testing. Irrespective of the source of data examined, we found that influenza infection increases the risk of pneumonia by ~100-fold. We found no support for enhanced transmission or severity impact of the interaction. For model-validation, we challenged our fitted model to make out-of-sample pneumonia predictions during pandemic and non-pandemic periods. The consistency in our inference tests carried out on several distinct datasets, and the predictive skill of our model increase confidence in our overall conclusion that influenza infection substantially enhances the risk of pneumonia, though only for a short period. PMID:26486591
Smith, N Ms; Wasserman, G A; Coleman, F T; Hilliard, K L; Yamamoto, K; Lipsitz, E; Malley, R; Dooms, H; Jones, M R; Quinton, L J; Mizgerd, J P
2018-01-01
As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity. This protection was diminished by depletion of CD4 + cells prior to the final infection. The resolution of previous pneumococcal infections seeded the lungs with CD4 + resident memory T (T RM ) cells, which responded to heterotypic pneumococcus stimulation by producing multiple effector cytokines, particularly interleukin (IL)-17A. Following lobar pneumonias, IL-17-producing CD4 + T RM cells were confined to the previously infected lobe, rather than dispersed throughout the lower respiratory tract. Importantly, pneumonia protection also was confined to that immunologically experienced lobe. Thus regionally localized memory cells provide superior local tissue protection to that mediated by systemic or central memory immune defenses. We conclude that respiratory bacterial infections elicit CD4 + T RM cells that fill a local niche to optimize heterotypic protection of the affected tissue, preventing pneumonia.
Bacteriology of aspiration pneumonia in patients with acute coma.
Lauterbach, Enise; Voss, Frederik; Gerigk, Roland; Lauterbach, Michael
2014-12-01
Loss of protective airway reflexes in patients with acute coma puts these patients at risk of aspiration pneumonia complicating the course of the primary disease. Available data vary considerably with regard to bacteriology, role of anaerobic bacteria, and antibiotic treatment. Our objective was to research the bacteriology of aspiration pneumonia in acute coma patients who were not pre-treated with antibiotics or hospitalized within 30 days prior to the event. We prospectively analyzed 127 patient records from adult patients admitted, intubated and ventilated to a tertiary medical intensive care unit with acute coma. Bacteriology and antibiotic resistance testing from tracheal aspirate sampled within 24 h after admission, blood cultures, ICU scores (APACHE II, SOFA), hematology, and clinical chemistry were assessed. Patients were followed up until death or hospital discharge. The majority of patients with acute coma suffered from acute cardiovascular disorders, predominantly myocardial infarction, followed by poisonings, and coma of unknown cause. In a majority of our patients, microaspiration resulted in overt infection. Most frequently S. aureus, H. influenzae, and S. pneumoniae were isolated. Anaerobic bacteria (Bacteroides spec., Fusobacteria, Prevotella spec.) were isolated from tracheal aspirate in a minority of patients, and predominantly as part of a mixed infection. Antibiotic monotherapy with a 2nd generation cephalosporin, or a 3rd generation gyrase inhibitor, was most effective in our patients regardless of the presence of anaerobic bacteria.
Koo, Hyun Jung; Kim, Mi Young; Koo, Ja Hwan; Sung, Yu Sub; Jung, Jiwon; Kim, Sung-Han; Choi, Chang-Min; Kim, Hwa Jung
2017-01-01
Radiologists have used margin characteristics based on routine visual analysis; however, the attenuation changes at the margin of the lesion on CT images have not been quantitatively assessed. We established a CT-based margin analysis method by comparing a target lesion with normal lung attenuation, drawing a slope to represent the attenuation changes. This approach was applied to patients with invasive mucinous adenocarcinoma (n = 40) or bacterial pneumonia (n = 30). Correlations among multiple regions of interest (ROIs) were obtained using intraclass correlation coefficient (ICC) values. CT visual assessment, margin and texture parameters were compared for differentiating the two disease entities. The attenuation and margin parameters in multiple ROIs showed excellent ICC values. Attenuation slopes obtained at the margins revealed a difference between invasive mucinous adenocarcinoma and pneumonia (P<0.001), and mucinous adenocarcinoma produced a sharply declining attenuation slope. On multivariable logistic regression analysis, pneumonia had an ill-defined margin (odds ratio (OR), 4.84; 95% confidence interval (CI), 1.26-18.52; P = 0.02), ground-glass opacity (OR, 8.55; 95% CI, 2.09-34.95; P = 0.003), and gradually declining attenuation at the margin (OR, 12.63; 95% CI, 2.77-57.51, P = 0.001). CT-based margin analysis method has a potential to act as an imaging parameter for differentiating invasive mucinous adenocarcinoma and bacterial pneumonia.
NASA Astrophysics Data System (ADS)
Batubara, C. A.; Ritarwan, K.; Rambe, A. S.
2018-03-01
Stress ulcer is one ofacute stroke complications. Giving ranitidine or omeprazole may prevent stress ulcer, but may increase the occurrence of pneumonia. Thus, it will affect the outcome of acute stroke. The method was experimental with a randomized control-group pretest - posttest design. This study divided the subjects into two groups, ranitidine 300mg and omeprazole 20mg group.We observed the patients whether stress ulcer or pneumonia occurred during hospitalization. Then, we measured the outcome by the National Institutes of Health Stroke Scaleand modified Rankin Scale. There were 32 subjects in this study. Only 1 (3.1%) subject suffered stress ulcer, and 3 (3.1%) suffered pneumonia in ranitidine group. Moreover, 2 (6.2%) subjects suffered pneumonia in omeprazole group. The differences were not significant between the two groups (p = 0.31 and p = 0.54). There was no significant effect and difference effect on the administration of both medications to the outcome at day 14. These results indicate that ranitidine and omeprazole have anequal effectiveness in the prevention of stress ulcer and also have equal effect on the occurrence of pneumonia, and both have no effect on the outcome of acute stroke patients.
[Correlation between post-stroke pneumonia and outcome in patients with acute brain infarction].
Li, S J; Hu, H Q; Wang, X L; Cao, B Z
2016-09-20
Objective: To investigate the correlation between post-stroke pneumonia and outcome in patients with acute brain infarction. Methods: Consecutive acute cerebral infarction patients who were hospitalized in Department of Neurology, Jinan Military General Hospital were prospectively recruited from August 2010 to August 2014. The baseline data including age, sex, the National Institute of Health Stroke Scale (NIHSS) scores, type of Oxfordshire Community Stroke Project (OCSP: total anterior circulation infarct, partial anterior circulation infarct, posterior circulation infarct and lacunar infarct), fasting blood glucose etc. after admission were recorded. Post-stroke pneumonia was diagnosed by treating physician according to criteria for hospital-acquired pneumonia of the Centers for Disease Control and Prevention. Recovery was assessed by modified Rankin Scale (mRS) 180 days after stroke by telephone interview (mRS≤2 reflected good prognosis, and mRS>2 reflected unfavorable prognosis). Multinominal Logistic regression analysis, Kaplan-Meier curve and log rank test were used. Results: A total of 1 249 patients were enrolled, among them 173 patients were lost during follow-up. A total of 159 patients had post-stroke pneumonia, while 1 090 patients were without post-stroke. Compared with patients without post-stoke pneumonia, patients with post-stroke pneumonia were older (67±13 vs 63±12 years, P =0.000), more severe (NIHSS, 15(14) vs 4(4), P =0.000). Compared with patients without post-stoke pneumonia, more patients with post-stroke pneumonia suffered from heart failure (12.58% vs 3.40%, P =0.000), atrial fibrillation (26.42% vs 8.81%, P =0.000), myocardial infarction (10.06% vs 5.05%, P =0.016), recurrent brain infarction (30.19% vs 22.66%, P =0.045), total anterior circulation infarct type of OCSP (46.54% vs 19.63%, P =0.000), posterior circulation infarct of OCSP (39.62% vs 25.51%, P =0.001); more patients suffered from disorder of consciousness (60.38% vs 9.27%, P =0.000), dysphagia (34.59% vs 19.89%, P =0.000), vomiting (26.42% vs 8.81%, P =0.000), aphasia (35.85% vs 16.61%, P =0.000) since onset. The morbidity of post-stroke pneumonia among patients with unfavorable outcome (29.37%(111/378)) was significantly higher than that among patients with favorable outcome (3.73%(26/698)) ( P =0.000). Post-stroke pneumonia was an independent prognostic factor for long-term unfavorable outcome ( OR =2.414, 95% CI : 1.336-4.361, P =0.004) and long-term mortality ( OR =2.132, 95% CI : 1.229-3.699, P =0.007). According Kaplan-Meier estimation, the cumulative 180 days survival of patients with post-stroke pneumonia was lower than those without post-stroke pneumonia (62.04%(85/137) vs 93.29%(876/939)); Log-rank test: χ 2 =137.32, P =0.000. Conclusions: Acute brain infarction patients with post-stroke pneumonia are older, more severe; more suffering from heart failure, atrial fibrillation, myocardial infarction; more suffering from disorder of consciousness since onset. Post-stroke pneumonia is an independent prognostic factor for long-term unfavorable outcome and for long term mortality in patients with acute brain infarction.
Yang, Xiao-Yan; Sun, Bin; Zhang, Liang; Li, Nan; Han, Junlong; Zhang, Jing; Sun, Xuesong; He, Qing-Yu
2014-01-01
Iron is an essential nutrient for the growth of most bacteria. To obtain iron, bacteria have developed specific iron-transport systems located on the membrane surface to uptake iron and iron complexes such as ferrichrome. Interference with the iron-acquisition systems should be therefore an efficient strategy to suppress bacterial growth and infection. Based on the chemical similarity of iron and ruthenium, we used a Ru(II) complex R-825 to compete with ferrichrome for the ferrichrome-transport pathway in Streptococcus pneumoniae. R-825 inhibited the bacterial growth of S. pneumoniae and stimulated the expression of PiuA, the iron-binding protein in the ferrichrome-uptake system on the cell surface. R-825 treatment decreased the cellular content of iron, accompanying with the increase of Ru(II) level in the bacterium. When the piuA gene (SPD_0915) was deleted in the bacterium, the mutant strain became resistant to R-825 treatment, with decreased content of Ru(II). Addition of ferrichrome can rescue the bacterial growth that was suppressed by R-825. Fluorescence spectral quenching showed that R-825 can bind with PiuA in a similar pattern to the ferrichrome-PiuA interaction in vitro. These observations demonstrated that Ru(II) complex R-825 can compete with ferrichrome for the ferrichrome-transport system to enter S. pneumoniae, reduce the cellular iron supply, and thus suppress the bacterial growth. This finding suggests a novel antimicrobial approach by interfering with iron-uptake pathways, which is different from the mechanisms used by current antibiotics.
Driscoll, Amanda J; Deloria Knoll, Maria; Hammitt, Laura L; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; O'Brien, Katherine L; Scott, J Anthony G; Thea, Donald M; Howie, Stephen R C; Adrian, Peter V; Ahmed, Dilruba; DeLuca, Andrea N; Ebruke, Bernard E; Gitahi, Caroline; Higdon, Melissa M; Kaewpan, Anek; Karani, Angela; Karron, Ruth A; Mazumder, Razib; McLellan, Jessica; Moore, David P; Mwananyanda, Lawrence; Park, Daniel E; Prosperi, Christine; Rhodes, Julia; Saifullah, Md; Seidenberg, Phil; Sow, Samba O; Tamboura, Boubou; Zeger, Scott L; Murdoch, David R
2017-06-15
Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1-59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%-7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%-0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL. Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Ding, Yew Yoong; Abisheganaden, John; Chong, Wai Fung; Heng, Bee Hoon; Lim, Tow Keang
2013-01-01
We sought to compare the effectiveness of acute geriatric units with usual medical care in reducing short-term mortality among seniors hospitalized for pneumonia in the real world. In a retrospective cohort study, we merged chart and administrative data of seniors aged 65 years and older admitted to acute geriatric units and other medical units for pneumonia at three hospitals over 1 year. The outcome was 30-day mortality. Hierarchical logistic regression modeling was carried out to estimate the treatment effect of acute geriatric units for all seniors, those aged 80 years and older, and those with premorbid ambulation impairment, after adjusting for demographic and clinical characteristics, and accounting for clustering around hospitals. Among 2721 seniors, 30-day mortality was 25.5%. For those admitted to acute geriatric and other medical units, this was 24.2% and 25.8%, respectively. Using hierarchical logistic regression modeling, treatment in acute geriatric units was not associated with significant mortality reduction among all seniors (OR 0.72, 95% CI 0.52-1.00). However, significant mortality reduction was observed in the subgroups of those aged 80 years and older (OR 0.73, 95% CI 0.54-0.99), and with premorbid ambulation impairment (OR 0.65, 95% CI 0.46-0.93). Acute geriatric units reduced short-term mortality among seniors hospitalized for pneumonia who were aged 80 years and older or had premorbid ambulation impairment. Further research is required to determine if this beneficial effect extends to seniors hospitalized for other acute medical disorders. © 2012 Japan Geriatrics Society.
[The influence of Chlamydia pneumoniae infection on acute coronary syndromes].
Gajek, Jacek; Choroszy-Król, Irena; Zyśko, Dorota; Teryks-Wołyniec, Dorota; Halawa, Bogumił
2003-07-01
Chlamydia pneumoniae is one of the infectious factors the role of which is considered in the process of atherosclerosis and its complications. Of the study was to assess the incidence of Ch. pneumoniae infection in the patients with acute coronary events. The study was carried out in 36 patients, mean age 61.2 +/- 13.4 years, 27 men and 9 women hospitalised in our Department with the diagnosis of previous or recent acute myocardial infarction. The control group consisted of 19 subjects, aged 61.1 +/- 14.3 years, 10 men and 9 women hospitalised due to other reasons. In all studied patients during the first 24 hours venous blood was taken for the assessment of fibrinogen and C-reactive protein (CRP) concentrations and titres of IgA and IgG anti-Ch. pneumoniae antibodies, and pharyngeal swabs were done for Ch. pneumoniae assessment. Positive swab tests were found in 19% of the patients, positive IgG titres in 80% and IgA in 64% of the patients. In the control group the corresponding values were 11, 79, 42%, respectively. In the patients with positive IgG titres, negative IgA titre result was observed in 21% and in the control group in 53% (p < 0.05). The CRP level was significantly higher in the studied patients than in the control group (24.2 vs 4.2 mg/l; p < 0.05). 1. The high percentage of positive serologic tests and rare positive results of pharyngeal swabs indicate a frequent contact with Ch. pneumoniae in human population. 2. Ch. pneumoniae infection exerts no significant influence on the unspecific markers of inflammation. 3. The higher frequency of seroconversion-positive IgG and negative IgA titres--in the control group indicates the role of prolonged or acute Ch. pneumoniae infection in the development or progression of coronary atherosclerosis and its complications.
Mancuso, Peter; Curtis, Jeffrey L; Freeman, Christine M; Peters-Golden, Marc; Weinberg, Jason B; Myers, Martin G
2018-03-22
Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiologic functions including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. We observed higher lung and spleen bacterial burdens in LysM-LepRb-KO mice following an intratracheal challenge with S. pneumoniae. Although numbers of leukocytes recovered from bronchoalveolar lavage fluid did not differ between groups, we did observe higher levels of pulmonary IL-13 and TNFα in LysM-LepRb-KO mice 48 h post-infection. Phagocytosis and killing of ingested S. pneumoniae were also impaired in alveolar macrophages (AM)s from LysM-LepRb-KO mice in vitro, and was associated with reduced LTB4 and enhanced PGE2 synthesis in vitro. Pretreatment of AMs with LTB4 and the cyclooxygenase inhibitor, indomethacin, restored phagocytosis but not bacterial killing in vitro. These results, confirm our previous observations in leptin-deficient (ob/ob) and fasted mice, and demonstrate that decreased leptin action, as opposed to metabolic irregularities associated with obesity or starvation, are responsible for the defective host defense against pneumococcal pneumonia. They also provide novel targets for therapeutic intervention in humans with bacterial pneumonia.
Mahomed, Nasreen; Fancourt, Nicholas; de Campo, John; de Campo, Margaret; Akano, Aliu; Cherian, Thomas; Cohen, Olivia G; Greenberg, David; Lacey, Stephen; Kohli, Neera; Lederman, Henrique M; Madhi, Shabir A; Manduku, Veronica; McCollum, Eric D; Park, Kate; Ribo-Aristizabal, Jose Luis; Bar-Zeev, Naor; O'Brien, Katherine L; Mulholland, Kim
2017-10-01
Childhood pneumonia is among the leading infectious causes of mortality in children younger than 5 years of age globally. Streptococcus pneumoniae (pneumococcus) is the leading infectious cause of childhood bacterial pneumonia. The diagnosis of childhood pneumonia remains a critical epidemiological task for monitoring vaccine and treatment program effectiveness. The chest radiograph remains the most readily available and common imaging modality to assess childhood pneumonia. In 1997, the World Health Organization Radiology Working Group was established to provide a consensus method for the standardized definition for the interpretation of pediatric frontal chest radiographs, for use in bacterial vaccine efficacy trials in children. The definition was not designed for use in individual patient clinical management because of its emphasis on specificity at the expense of sensitivity. These definitions and endpoint conclusions were published in 2001 and an analysis of observer variation for these conclusions using a reference library of chest radiographs was published in 2005. In response to the technical needs identified through subsequent meetings, the World Health Organization Chest Radiography in Epidemiological Studies (CRES) project was initiated and is designed to be a continuation of the World Health Organization Radiology Working Group. The aims of the World Health Organization CRES project are to clarify the definitions used in the World Health Organization defined standardized interpretation of pediatric chest radiographs in bacterial vaccine impact and pneumonia epidemiological studies, reinforce the focus on reproducible chest radiograph readings, provide training and support with World Health Organization defined standardized interpretation of chest radiographs and develop guidelines and tools for investigators and site staff to assist in obtaining high-quality chest radiographs.
Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders
Kaarteenaho, Riitta; Kinnula, Vuokko L.
2011-01-01
It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal. PMID:21637367
Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C.; Sellati, Timothy J.; Harton, Jonathan A.
2016-01-01
Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566
Community-acquired bacterial meningitis in elderly patients: experience over 30 years.
Cabellos, Carmen; Verdaguer, Ricard; Olmo, Montse; Fernández-Sabé, Nuria; Cisnal, Maria; Ariza, Javier; Gudiol, Francesc; Viladrich, Pedro F
2009-03-01
Clinical characteristics, etiologies, evolution, and prognostic factors of community-acquired bacterial meningitis in elderly patients are not well known. To improve this knowledge, all episodes of community-acquired bacterial meningitis were prospectively recorded and cases occurring in patients >or=65 years old were selected. During the period 1977-2006, 675 episodes in adults (aged >or=18 yr) were recorded, with 185 (27%) in patients aged >or=65 years old; 76 were male and 109 were female, with a mean age of 73 +/- 6 years (range, 65-93 yr). Causative microorganisms were Streptococcus pneumoniae 74, Neisseria meningitidis 49, Listeria monocytogenes 17, other streptococcal 9, Escherichia coli 6, Haemophilus influenzae 4, Klebsiella pneumoniae and Staphylococcus aureus 2 each, Capnocytophaga canimorsus and Enterococcus faecalis 1 each, and unknown in 20. On admission 91% had had fever, 32% were in a coma (Glasgow Coma Scale
Nakao, Makoto; Sone, Kazuki; Kagawa, Yusuke; Kurokawa, Ryota; Sato, Hidefumi; Kunieda, Takefumi; Muramatsu, Hideki
2016-01-01
Diagnosing active tuberculosis in elderly patients presents problems due to nonspecific symptoms and complications such as aspiration pneumonia. The current study presents two cases of pulmonary tuberculosis with bilateral pulmonary infiltrates associated with aspiration pneumonia. The two elderly patients developed acute respiratory distress syndrome as a result of aspiration pneumonia. The diagnoses of pulmonary tuberculosis were delayed in both cases, as the patients were diagnosed with active tuberculosis following discharge from hospital. The sputum test for acid-fast bacillus at the time of administration was smear-negative/culture-positive in these patients. They were treated with isoniazid, rifampicin and ethambutol, and nosocomial transmission of tuberculosis from these patients was not reported. The number of elderly patients with aspiration pneumonia is predicted to increase rapidly, and aspiration pneumonia combined with pulmonary tuberculosis is a major medical and healthcare concern in Japan. The present study concludes that physicians should always consider the complication of pulmonary tuberculosis when treating pneumonia patients, in particular in treating elderly patients with pulmonary infiltrates. PMID:27446284
Itai, Junji; Ohshimo, Shinichiro; Kida, Yoshiko; Ota, Kohei; Iwasaki, Yasumasa; Hirohashi, Nobuyuki; Bonella, Francesco; Guzman, Josune; Costabel, Ulrich; Kohno, Nobuoki; Tanigawa, Koichi
2015-01-05
Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) might be beneficial for treating acute exacerbation (AE) of interstitial pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an emerging tool to avoid ventilator-induced lung injury. This is a report presenting the first three patients with AE of IP treated with a combined therapy of PMX-DHP and VV-ECMO. Patient 1 was a 68-year-old male with acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen vascular disease-associated interstitial pneumonia. All patients were severely hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP and VV-ECMO was initiated with support of intravenous corticosteroids and antibiotics. Radiological findings, oxygenation and laboratory findings markedly improved and all patients survived without severe complications. A combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of IP.
Performance in practice: bacteriological efficacy in patients with drug-resistant S. pneumoniae.
Garau, J
2004-04-01
Using pharmacokinetic/pharmacodynamic principles, pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily was designed to provide adequate levels of amoxicillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP, penicillin MICs > or = 2 mg/L) with amoxicillin MICs of at least 4 mg/L. The clinical efficacy of amoxicillin/clavulanate 2000/125 mg was evaluated in patients with respiratory tract infections caused by S. pneumoniae, including isolates with elevated penicillin (2-8 mg/L) MICs. Data from 10 clinical studies were combined: seven randomised (1:1), double-blind, controlled trials (efficacy intent-to-treat [ITT]N = 3376): amoxicillin/clavulanate 2000/125 mg twice daily vs. levofloxacin 500 mg once daily in acute bacterial sinusitis (ABS); levofloxacin 500 mg once daily in acute exacerbations of chronic bronchitis (AECB); clarithromycin 500 mg twice daily in AECB; amoxicillin/clavulanate 875/125 mg twice daily/three times daily and 1000/125 mg three times daily in community-acquired pneumonia (CAP) and three noncomparative studies (efficacy ITT N = 3024): two in ABS, one in CAP. The bacteriological per-protocol (PP) population at follow up (days 14-39) comprised 1295 patients for amoxicillin/clavulanate 2000/125 mg and 241 for comparators. With amoxicillin/clavulanate 2000/125 mg at follow-up, outcome was successful (clinical success and eradication/presumed eradication) in 85/90 (94.4%) patients with S. pneumoniae in comparative studies and 421/445 (94.6%) in noncomparative studies, and with comparators 58/70 (82.9%) were successes. In the amoxicillin/clavulanate 2000/125 mg group at follow up, 52/552 S. pneumoniae isolates were resistant to penicillin. At follow up, 50/52 (96.2%) patients with PRSP were successes, including 6/7 with amoxicillin MICs of 4 mg/L and 7/8 with amoxicillin MICs of 8 mg/L. Success rates for amoxicillin/clavulanate 2000/125 mg against PRSP were similar for CAP (96.0%[24/25]), AECB (100%[3/3]) and ABS (95.8%[23/24]). There were six PRSP isolates in the comparator group (two isolates were from one patient), and three of five patients in this group were successes. In conclusion, amoxicillin/clavulanate 2000/125 mg demonstrated combined clinical/bacteriological success against 50/52 patients with PRSP, including 13/15 strains with amoxicillin MICs of 4-8 mg/L. These results for the pharmacokinetic-enhanced formulation of amoxicillin/clavulanate 2000/125 mg are in line with the high efficacy against PRSP predicted using pharmacokinetic/pharmacodynamic parameters.
Code of Federal Regulations, 2010 CFR
2010-04-01
... improved feed efficiency; and for treatment of bacterial enteritis caused by E. coli and bacterial... for breeding. (e) Conditions of use. It is used in cattle being fed in confinement for slaughter as... Echerichia coli and bacterial pneumonia caused by Pasteurella multocida organisms susceptible to...
Code of Federal Regulations, 2011 CFR
2011-04-01
... improved feed efficiency; and for treatment of bacterial enteritis caused by E. coli and bacterial... for breeding. (e) Conditions of use. It is used in cattle being fed in confinement for slaughter as... Echerichia coli and bacterial pneumonia caused by Pasteurella multocida organisms susceptible to...
de Magalhães, Raquel F; Samary, Cynthia S; Santos, Raquel S; de Oliveira, Milena V; Rocha, Nazareth N; Santos, Cintia L; Kitoko, Jamil; Silva, Carlos A M; Hildebrandt, Caroline L; Goncalves-de-Albuquerque, Cassiano F; Silva, Adriana R; Faria-Neto, Hugo C; Martins, Vanessa; Capelozzi, Vera L; Huhle, Robert; Morales, Marcelo M; Olsen, Priscilla; Pelosi, Paolo; de Abreu, Marcelo Gama; Rocco, Patricia R M; Silva, Pedro L
2016-11-25
Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (V T ) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia. Thirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean V T = 6 mL/kg, PEEP = 5cmH 2 O, and FiO 2 = 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls. In both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3 [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum neutrophils (2.0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU) counts were comparable (7 [0-28] vs. 6 [0-26], p = 0.77). Compared to NV, VCV, but not VV, increased expression amphiregulin, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-1 (2.1 [1.6-2.5] vs. 0.9 [0.7-1.2], p = 0.025; 12.3 [7.9-22.0] vs. 0.8 [0.6-1.9], p = 0.006; and 4.4 [2.9-5.6] vs. 0.9 [0.8-1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV compared to NV animals (0.5 [0.3-0.8] vs. 1.3 [1.0-1.5], p = 0.01). In this rat model of pneumonia, VV improved pulmonary function and reduced lung damage as compared to VCV, without increasing bacterial translocation.
Streamlining antibiotic therapy with procalcitonin protocols: consensus and controversies.
Haubitz, Sebastian; Mueller, Beat; Schuetz, Philipp
2013-04-01
Accumulating evidence supports procalcitonin (PCT) as an accurate surrogate biomarker for likelihood and severity of bacterial infections. In community-acquired pneumonia and other respiratory infections, PCT-guided antibiotic therapy algorithms resulted in reduced antibiotic exposure while maintaining a similar or even better level of safety compared with standard care. Reductions in antibiotic use translate into lower treatment costs, decreased risk of side effects and decreased bacterial multiresistance. This is especially important, as acute respiratory infections represent the most frequent reason for antibiotic prescriptions worldwide. Still, there is some controversy about the benefits of PCT measurement in sepsis patients in the intensive care unit and for nonrespiratory infections. Highly sensitive PCT assays are readily available in many hospitals today, and point-of-care assays with high enough sensitivity for antibiotic guidance are expected to be available soon. Herein, the authors provide an overview of recent studies evaluating PCT in different clinical situations and an outlook of currently enrolling or upcoming interventional trials.
Effect of vaccines on bacterial meningitis worldwide.
McIntyre, Peter B; O'Brien, Katherine L; Greenwood, Brian; van de Beek, Diederik
2012-11-10
Three bacteria--Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis--account for most acute bacterial meningitis. Measurement of the effect of protein-polysaccharide conjugate vaccines is most reliable for H influenzae meningitis because one serotype and one age group account for more than 90% of cases and the incidence has been best measured in high-income countries where these vaccines have been used longest. Pneumococcal and meningococcal meningitis are caused by diverse serotypes and have a wide age distribution; measurement of their incidence is complicated by epidemics and scarcity of surveillance, especially in low-income countries. Near elimination of H influenzae meningitis has been documented after vaccine introduction. Despite greater than 90% reductions in disease attributable to vaccine serotypes, all-age pneumococcal meningitis has decreased by around 25%, with little data from low-income settings. Near elimination of serogroup C meningococcal meningitis has been documented in several high-income countries, boding well for the effect of a new serogroup A meningococcal conjugate vaccine in the African meningitis belt. Copyright © 2012 Elsevier Ltd. All rights reserved.
Perez, Federico; Endimiani, Andrea; Ray, Amy J; Decker, Brooke K; Wallace, Christopher J; Hujer, Kristine M; Ecker, David J; Adams, Mark D; Toltzis, Philip; Dul, Michael J; Windau, Anne; Bajaksouzian, Saralee; Jacobs, Michael R; Salata, Robert A; Bonomo, Robert A
2010-08-01
Resistance to carbapenems among Acinetobacter baumannii and Klebsiella pneumoniae presents a serious therapeutic and infection control challenge. We describe the epidemiology and genetic basis of carbapenem resistance in A. baumannii and K. pneumoniae in a six-hospital healthcare system in Northeast Ohio. Clinical isolates of A. baumannii and K. pneumoniae distributed across the healthcare system were collected from April 2007 to April 2008. Antimicrobial susceptibility testing was performed followed by molecular analysis of carbapenemase genes. Genetic relatedness of isolates was established with repetitive sequence-based PCR (rep-PCR), multilocus PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) and PFGE. Clinical characteristics and outcomes of patients were reviewed. Among 39 isolates of A. baumannii, two predominant genotypes related to European clone II were found. Eighteen isolates contained bla(OXA-23), and four isolates possessed bla(OXA-24/40). Among 29 K. pneumoniae isolates with decreased susceptibility to carbapenems, two distinct genotypes containing bla(KPC-2) or bla(KPC-3) were found. Patients with carbapenem-resistant A. baumannii and K. pneumoniae were elderly, possessed multiple co-morbidities, were frequently admitted from and discharged to post-acute care facilities, and experienced prolonged hospital stays (up to 25 days) with a high mortality rate (up to 35%). In this outbreak of carbapenem-resistant A. baumannii and K. pneumoniae across a healthcare system, we illustrate the important role post-acute care facilities play in the dissemination of multidrug-resistant phenotypes.
Perez, Federico; Endimiani, Andrea; Ray, Amy J.; Decker, Brooke K.; Wallace, Christopher J.; Hujer, Kristine M.; Ecker, David J.; Adams, Mark D.; Toltzis, Philip; Dul, Michael J.; Windau, Anne; Bajaksouzian, Saralee; Jacobs, Michael R.; Salata, Robert A.; Bonomo, Robert A.
2010-01-01
Background Resistance to carbapenems among Acinetobacter baumannii and Klebsiella pneumoniae presents a serious therapeutic and infection control challenge. We describe the epidemiology and genetic basis of carbapenem resistance in A. baumannii and K. pneumoniae in a six-hospital healthcare system in Northeast Ohio. Methods Clinical isolates of A. baumannii and K. pneumoniae distributed across the healthcare system were collected from April 2007 to April 2008. Antimicrobial susceptibility testing was performed followed by molecular analysis of carbapenemase genes. Genetic relatedness of isolates was established with repetitive sequence-based PCR (rep-PCR), multilocus PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) and PFGE. Clinical characteristics and outcomes of patients were reviewed. Results Among 39 isolates of A. baumannii, two predominant genotypes related to European clone II were found. Eighteen isolates contained blaOXA-23, and four isolates possessed blaOXA-24/40. Among 29 K. pneumoniae isolates with decreased susceptibility to carbapenems, two distinct genotypes containing blaKPC-2 or blaKPC-3 were found. Patients with carbapenem-resistant A. baumannii and K. pneumoniae were elderly, possessed multiple co-morbidities, were frequently admitted from and discharged to post-acute care facilities, and experienced prolonged hospital stays (up to 25 days) with a high mortality rate (up to 35%). Conclusion In this outbreak of carbapenem-resistant A. baumannii and K. pneumoniae across a healthcare system, we illustrate the important role post-acute care facilities play in the dissemination of multidrug-resistant phenotypes. PMID:20513702
Marandi, Farinaz Rashed; Rahbar, Mohammad; Sabourian, Roghieh; Saremi, Mahnaz
2010-01-01
To determine the ability of Iranian microbiology laboratories for identification and susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae as causative agents of bacterial meningitides. Two strains of bacteria including Haemophilus influenzae and Streptococcus pneumoniae as a common causative agents of meningitides were chosen and coded as strain number 1 and number 2. The strains were distributed among 679 microbiology laboratories. All laboratories were requested for identification of each unknown microorganism and susceptibility testing of S. pneumoniae against five commonly used antibiotics. Of 679 microbiology laboratories 310 (46%) laboratories participated in the survey and among these, 258 laboratories completely identified S. pneumoniae. About 85% laboratories produced correct susceptibility testing against oxacillin, erythromycin, tetracycline, and vancomycin. Of 310 received responses only 50 laboratories identified H. influenza correctly. The majority of the laboratories did not have the capacity to identification H. influenza. Microbiology laboratories in our country are qualified for identification and susceptibility testing of S. pneumoniae. However, majority of laboratories are not qualified for identification of H. influenzae.
Chang, Pin-Yu; Tsao, Shih-Ming; Chang, Jer-Hwa; Chien, Ming-Hsien; Hung, Wen-Yueh; Huang, Yi-Wen; Yang, Shun-Fa
2016-12-01
Community-acquired pneumonia (CAP) is characterized as an acute inflammation of the lung associated with the activation of macrophages and neutrophils. Intercellular adhesion molecule-1 (ICAM-1) is an essential adhesion molecule involved in immune cell recruitment in lung inflammation. We investigated whether ICAM-1 is a useful biomarker for assessing the disease severity of hospitalized adult patients with CAP. Plasma soluble ICAM-1 (sICAM-1) levels were measured in 78 patients with CAP and 69 healthy controls by using a commercial enzyme-linked immunosorbent assay. The pneumonia severity index scores were used to determine CAP severity in patients upon initial hospitalization. The sICAM-1 and C-reactive protein (CRP) levels decreased significantly in patients with CAP after antibiotic treatment. The plasma concentration of sICAM-1 alone, but not CRP, was correlated with CAP severity according to the pneumonia severity index scores (r=0.431, p<0.001). The sICAM-1 levels in patients with CAP with high mortality risk were significantly higher than those in patients with CAP with medium or low mortality risk. Moreover, the sICAM-1 level showed a significant correlation with the length of hospital stay (r=0.488, p<0.001). Mechanistic investigations found that bacterial lipopolysaccharide induced upregulation of ICAM-1 expression through the c-Jun N-terminal kinase pathway in RAW264.7 macrophages. Plasma sICAM-1 levels may play a role in the diagnosis and clinical assessment of CAP severity. Copyright © 2016 Elsevier B.V. All rights reserved.
Plasek, Jiri; Dvorackova, Jana; Jahoda, Jan; Trulikova, Kristina; Mokosova, Radka; Danek, Tomas; Hrabovsky, Vladimir; Martinek, Arnost
2011-12-01
Acute interstitial pneumonia is characterized by rapid progressive dyspnoea degenerating into respiratory failure requiring mechanical ventilation. Acute interstitial pneumonia (AIP) and idiopathic pulmonary fibrosis (IPF) are separate clinic/pathological entities although overlap may be present. It is well-known that patients with IPF have increased risk of lung carcinoma; Adenocarcinoma in connection with IPF is less common. Moreover the subtype of adenocarcinoma, diffuse bronchoalveolar carcinoma has not yet been described. We report the case of 45 yr old former hockey player with increased bilateral reticular shadowing on chest radiograph, dyspnoea, velcro-like crackles, restrictive respiratory disease and mixed high-resolution computed tomography finding. During brief in-patient treatment the patient developed acute respiratory failure accompanied by multiorgan failure and disseminated coagulopathy. Deterioration of the microcirculation was followed by loss of peripheral vascular resistance, which was irreversible even with normalization of the blood gases achieved by extracorporeal membrane oxygenation. At autopsy, bronchoalveolar carcinoma in usual interstitial pneumonia (UIP) combined with areas of alveolar damage with hyaline membranes was found. This case alerts clinicians to unusual idiopathic pulmonary fibrosis manifestations and its complications. Close collaboration between clinicians, pathologists and laboratory physicians is highly recommended for early diagnosis and appropriate treatment.
21 CFR 520.90f - Ampicillin trihydrate boluses.
Code of Federal Regulations, 2012 CFR
2012-04-01
... enteritis (colibacillosis) caused by E. coli. (ii) Limitations. Treated calves must not be slaughtered for... coli, bacterial enteritis caused by Salmonella spp., and bacterial pneumonia caused by Pasteurella spp...
21 CFR 520.90f - Ampicillin trihydrate boluses.
Code of Federal Regulations, 2010 CFR
2010-04-01
... enteritis (colibacillosis) caused by E. coli. (ii) Limitations. Treated calves must not be slaughtered for... coli, bacterial enteritis caused by Salmonella spp., and bacterial pneumonia caused by Pasteurella spp...
21 CFR 520.90f - Ampicillin trihydrate boluses.
Code of Federal Regulations, 2011 CFR
2011-04-01
... enteritis (colibacillosis) caused by E. coli. (ii) Limitations. Treated calves must not be slaughtered for... coli, bacterial enteritis caused by Salmonella spp., and bacterial pneumonia caused by Pasteurella spp...
García-Elorriaga, Guadalupe; Palma-Alaniz, Laura; García-Bolaños, Carlos; Ruelas-Vargas, Consuelo; Méndez-Tovar, Socorro; Del Rey-Pineda, Guillermo
Community-acquired pneumonia (CAP) is one of the most common infectious causes of morbidity and mortality in children <5 years of age. The aim of the study was to clarify the bacterial etiologic diagnosis in infants with CAP. A prospective, cross-sectional and descriptive study in patients 6 months to 2 years 11 months of age with CAP with poor outcome was conducted. Patients were admitted to the Pediatric Pneumology Service and underwent bronchoscopy with bronchoalveolar lavage (BAL), taking appropriate measures during the procedure to limit the risk of contamination. Aerobic bacteria isolated were Moraxella sp. 23%, Streptococcus mitis 23%, Streptococcus pneumoniae 18%, Haemophilus influenzae 12%, Streptococcus oralis 12%, and Streptococcus salivarius 12%. In contrast to other reports, we found Moraxella sp. to be a major bacterial pathogen, possibly because of improved detection with bronchoscopy plus BAL. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.
Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens
Fyfe, Corey; O’Brien, William; Hackel, Meredith; Minyard, Mary Beth; Waites, Ken B.; Dubois, Jacques; Murphy, Timothy M.; Slee, Andrew M.; Weiss, William J.; Sutcliffe, Joyce A.
2017-01-01
ABSTRACT TP-271 is a novel, fully synthetic fluorocycline antibiotic in clinical development for the treatment of respiratory infections caused by susceptible and multidrug-resistant pathogens. TP-271 was active in MIC assays against key community respiratory Gram-positive and Gram-negative pathogens, including Streptococcus pneumoniae (MIC90 = 0.03 µg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC90 = 0.25 µg/ml), methicillin-resistant S. aureus (MRSA; MIC90 = 0.12 µg/ml), Streptococcus pyogenes (MIC90 = 0.03 µg/ml), Haemophilus influenzae (MIC90 = 0.12 µg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 µg/ml). TP-271 showed activity (MIC90 = 0.12 µg/ml) against community-acquired MRSA expressing Panton-Valentine leukocidin (PVL). MIC90 values against Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae were 0.004, 1, and 4 µg/ml, respectively. TP-271 was efficacious in neutropenic and immunocompetent animal pneumonia models, generally showing, compared to the burden at the start of dosing, ~2 to 5 log10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log10 CFU reductions when given orally (p.o.). TP-271 was potent against key community-acquired bacterial pneumonia (CABP) pathogens and was minimally affected, or unaffected, by tetracycline-specific resistance mechanisms and fluoroquinolone or macrolide drug resistance phenotypes. IMPORTANCE Rising resistance rates for macrolides, fluoroquinolones, and β-lactams in the most common pathogens associated with community-acquired bacterial pneumonia (CABP) are of concern, especially for cases of moderate to severe infections in vulnerable populations such as the very young and the elderly. New antibiotics that are active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus are needed for use in the empirical treatment of the most severe forms of this disease. TP-271 is a promising new fluorocycline antibiotic demonstrating in vitro potency and nonclinical efficacy by intravenous and oral administration against the major pathogens associated with moderate to severe CABP. PMID:28251179
Zhu, Luchang; Lin, Jingjun; Kuang, Zhizhou; Vidal, Jorge E; Lau, Gee W
2015-07-01
The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 'late' competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes. © 2015 John Wiley & Sons Ltd.
Maestro, Beatriz; Sanz, Jesús M.
2016-01-01
Streptococcus pneumoniae (pneumococcus) is an important pathogen responsible for acute invasive and non-invasive infections such as meningitis, sepsis and otitis media, being the major cause of community-acquired pneumonia. The fight against pneumococcus is currently hampered both by insufficient vaccine coverage and by rising antimicrobial resistances to traditional antibiotics, making necessary the research on novel targets. Choline binding proteins (CBPs) are a family of polypeptides found in pneumococcus and related species, as well as in some of their associated bacteriophages. They are characterized by a structural organization in two modules: a functional module (FM), and a choline-binding module (CBM) that anchors the protein to the choline residues present in the cell wall through non-covalent interactions. Pneumococcal CBPs include cell wall hydrolases, adhesins and other virulence factors, all playing relevant physiological roles for bacterial viability and virulence. Moreover, many pneumococcal phages also make use of hydrolytic CBPs to fulfill their infectivity cycle. Consequently, CBPs may play a dual role for the development of novel antipneumococcal drugs, both as targets for inhibitors of their binding to the cell wall and as active cell lytic agents (enzybiotics). In this article, we review the current state of knowledge about host- and phage-encoded pneumococcal CBPs, with a special focus on structural issues, together with their perspectives for effective anti-infectious treatments. PMID:27314398
Canine H3N8 influenza virus infection in dogs and mice.
Castleman, W L; Powe, J R; Crawford, P C; Gibbs, E P J; Dubovi, E J; Donis, R O; Hanshaw, D
2010-05-01
An H3N8 influenza virus closely related to equine influenza virus was identified in racing greyhound dogs with respiratory disease in 2004 and subsequently identified in shelter and pet dogs. Pathologic findings in dogs spontaneously infected with canine influenza virus were compared with lesions induced in beagle and mongrel dogs following experimental inoculation with influenza A/canine/Florida/43/2004. BALB/c mice were inoculated with canine influenza virus to assess their suitability as an experimental model for viral pathogenesis studies. All dogs inoculated with virus developed necrotizing and hyperplastic tracheitis and bronchitis with involvement of submucosal glands as well as mild bronchiolitis and pneumonia. Viral antigen was identified in bronchial and tracheal epithelial cells of all dogs and in alveolar macrophages of several dogs. Many dogs that were spontaneously infected with virus also developed bacterial pneumonia, and greyhound dogs with fatal spontaneous infection developed severe pulmonary hemorrhage with hemothorax. Virus-inoculated BALB/c mice developed tracheitis, bronchitis, bronchiolitis, and mild pneumonia in association with viral antigen in airway epithelial cells and in type 2 alveolar epithelial cells. Virus was not detected in extrarespiratory sites in any animals. The results indicate that canine influenza virus infection consistently induces acute tracheitis and bronchitis in dogs. Mice may be a useful model for some pathogenesis studies on canine influenza virus infection.
[Current epidemiology of microbial low respiratory tract infections].
Trémolières, F
2006-01-01
The recent literature brings nothing new since it provides only fragmented, though undoubtedly useful, studies which remain within the prevalence interval for the different bacterias. The occurrence of germs varies with time and space; nevertheless, whatever the studied series and the site of the studies, the 3 most frequent causal germs belong to the following five strains: Streptococcus pneumoniae, Influenza A, Mycoplasma pneumoniae, Haemophilus influenzae, and Legionella pneumophila. Thus, 90% of all documented pneumoniae appear to be caused by the following pathogens: Pneumococcus; most frequent in hospitalized patients; Mycoplasma, Chlamydia and respiratory viruses were predominant in outpatients, with great variations; Staphylococcus and enterobacteriace may be encountered, mostly in elderlies with major debilitating diseases; association of germs, generally including pneumococcus, are increasingly identified. Last, in 25% to 50% of cases, the causal agent is not known. Recently, some Staphylococcus meticillin-resistant were identified. The diagnosis of viruses (as well as that of atypical bacterias) seems to have improved, thanks to the use of PCR though the interest of such a diagnosis remains questionable, except for epidemiological studies, as well as the relevance of this type of test in clinical practice. Nothing really new has come out on the epidemiology of acute bronchitis, while in bacterial exacerbation of COPD, attention focused on the colonizing or infective role of H. influenzae in the genesis of bronchus inflammation.
Leung, Anne K H; Ng, George W Y; Sin, K C; Au, S Y; Lai, K Y; Lee, K L; Law, K I
2015-04-01
We report a rare complication of factor V deficiency in a patient having Legionella pneumonia. This patient also had other complications like severe acute respiratory distress syndrome, acute kidney injury, and septic shock that required venous-venous extracorporeal membrane oxygenation support. This is the first reported case of acquired factor V deficiency in a patient receiving extracorporeal membrane oxygenation for Legionella pneumonia. With the combined use of intravenous immunoglobulin, rituximab and plasma exchange, we achieved rapid clearance of the factor V inhibitor within 1 week so as to allow safe decannulation of extracorporeal membrane oxygenation.
A pediatric case of Fascioliasis with eosinophilic pneumonia.
Bayhan, Gülsüm İclal; Batur, Abdulsamet; Taylan-Özkan, Ayşegül; Demirören, Kaan; Beyhan, Yunus Emre
2016-01-01
Fasciolia spp. are common trematode infestations worldwide. Fasciolia spp. may lead to hepatic diseases in the acute phase and may cause biliary diseases in the chronic phase. In addition, Fasciolia spp. may rarely cause extrahepatic signs and symptoms. The clinical manifestations of fascioliasis are divided into three groups: typical, atypical, and ectopic. Eosinophilic pneumonia is an atypical presentation of acute fascioliasis and it has been reported very rarely. Herein, we report a boy with marked blood eosinophilia and eosinophilic pneumonia who was diagnosed with fascioliasis by serologic tests and abdominal USG. The patient recovered completely following triclabendazole treatment.
Shak, Joshua R.; Cremers, Amelieke J. H.; Gritzfeld, Jenna F.; de Jonge, Marien I.; Hermans, Peter W. M.; Vidal, Jorge E.; Klugman, Keith P.; Gordon, Stephen B.
2014-01-01
Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study’s sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute. PMID:24915552
Mogensen, Trine H.; Berg, Randi S.; Paludan, Søren R.; Østergaard, Lars
2008-01-01
Excessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone significantly reduces mortality and morbidity from bacterial meningitis. Here we investigate the molecular mechanisms behind the inhibitory effect of dexamethasone upon the inflammatory responses evoked by Neisseria meningitidis and Streptococcus pneumoniae, two of the major causes of bacterial meningitis. The inflammatory cytokine response was dependent on Toll-like receptor signaling and was strongly inhibited by dexamethasone. Activation of the NF-κB pathway was targeted at several levels, including inhibition of IκB phosphorylation and NF-κB DNA-binding activity as well as upregulation of IκBα synthesis. Our data also revealed that the timing of steroid treatment relative to infection was important for achieving strong inhibition, particularly in response to S. pneumoniae. Altogether, we describe important targets of dexamethasone in the inflammatory responses evoked by N. meningitidis and S. pneumoniae, which may contribute to our understanding of the clinical effect and the importance of timing with respect to corticosteroid treatment during bacterial meningitis. PMID:17938219
Bielen, Luka; Likić, Robert; Erdeljić, Viktorija; Mareković, Ivana; Firis, Nataša; Grgić-Medić, Marijana; Godan, Ana; Tomić, Ivan; Hunjak, Blaženka; Markotić, Alemka; Bejuk, Danijela; Tičić, Vladimira; Balzar, Silvana; Bedenić, Branka
2018-01-01
Aim To determine in vitro susceptibility of multiresistant bacterial isolates to fosfomycin. Methods In this prospective in vitro study (local non-random sample, level of evidence 3), 288 consecutively collected multiresistant bacterial isolates from seven medical centers in Croatia were tested from February 2014 until October 2016 for susceptibility to fosfomycin and other antibiotics according to Clinical and Laboratory Standards Institute methodology. Susceptibility to fosfomycin was determined by agar dilution method, while disc diffusion were performed for in vitro testing of other antibiotics. Polymerase chain reaction and sequencing was performed for the majority of extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) and carbapenem-resistant isolates. Results The majority of 288 multiresistant bacterial isolates (82.6%) were susceptible to fosfomycin. The 236 multiresistant Gram-negative isolates showed excellent susceptibility to fosfomycin. Susceptibility rates were as follows: Escherichia coli ESBL 97%, K. pneumoniae ESBL 80%, Enterobacter species 85.7%, Citrobacter freundii 100%, Proteus mirabilis 93%, and Pseudomonas aeruginosa 60%. Of the 52 multiresistant Gram-positive isolates, methicillin-resistant Staphylococcus aureus showed excellent susceptibility to fosfomycin (94.4%) and vancomycin-resistant enterococcus showed low susceptibility to fosfomycin (31%). Polymerase chain reaction analysis of 36/50 ESBL-producing K. pneumoniae isolates showed that majority of isolates had CTX-M-15 beta lactamase (27/36) preceded by ISEcp insertion sequence. All carbapenem-resistant Enterobacter and Citrobacter isolates had blaVIM-1 metallo-beta-lactamase gene. Conclusion With the best in vitro activity among the tested antibiotics, fosfomycin could be an effective treatment option for infections caused by multiresistant Gram-negative and Gram-positive bacterial strains in the hospital setting. PMID:29740989
Santos, Guido; Lai, Xin; Eberhardt, Martin; Vera, Julio
2018-01-01
Pneumococcal infection is the most frequent cause of pneumonia, and one of the most prevalent diseases worldwide. The population groups at high risk of death from bacterial pneumonia are infants, elderly and immunosuppressed people. These groups are more vulnerable because they have immature or impaired immune systems, the efficacy of their response to vaccines is lower, and antibiotic treatment often does not take place until the inflammatory response triggered is already overwhelming. The immune response to bacterial lung infections involves dynamic interactions between several types of cells whose activation is driven by intracellular molecular networks. A feasible approach to the integration of knowledge and data linking tissue, cellular and intracellular events and the construction of hypotheses in this area is the use of mathematical modeling. For this paper, we used a multi-level computational model to analyse the role of cellular and molecular interactions during the first 10 h after alveolar invasion of Streptococcus pneumoniae bacteria. By “multi-level” we mean that we simulated the interplay between different temporal and spatial scales in a single computational model. In this instance, we included the intracellular scale of processes driving lung epithelial cell activation together with the scale of cell-to-cell interactions at the alveolar tissue. In our analysis, we combined systematic model simulations with logistic regression analysis and decision trees to find genotypic-phenotypic signatures that explain differences in bacteria strain infectivity. According to our simulations, pneumococci benefit from a high dwelling probability and a high proliferation rate during the first stages of infection. In addition to this, the model predicts that during the very early phases of infection the bacterial capsule could be an impediment to the establishment of the alveolar infection because it impairs bacterial colonization. PMID:29868515
Santos, Guido; Lai, Xin; Eberhardt, Martin; Vera, Julio
2018-01-01
Pneumococcal infection is the most frequent cause of pneumonia, and one of the most prevalent diseases worldwide. The population groups at high risk of death from bacterial pneumonia are infants, elderly and immunosuppressed people. These groups are more vulnerable because they have immature or impaired immune systems, the efficacy of their response to vaccines is lower, and antibiotic treatment often does not take place until the inflammatory response triggered is already overwhelming. The immune response to bacterial lung infections involves dynamic interactions between several types of cells whose activation is driven by intracellular molecular networks. A feasible approach to the integration of knowledge and data linking tissue, cellular and intracellular events and the construction of hypotheses in this area is the use of mathematical modeling. For this paper, we used a multi-level computational model to analyse the role of cellular and molecular interactions during the first 10 h after alveolar invasion of Streptococcus pneumoniae bacteria. By "multi-level" we mean that we simulated the interplay between different temporal and spatial scales in a single computational model. In this instance, we included the intracellular scale of processes driving lung epithelial cell activation together with the scale of cell-to-cell interactions at the alveolar tissue. In our analysis, we combined systematic model simulations with logistic regression analysis and decision trees to find genotypic-phenotypic signatures that explain differences in bacteria strain infectivity. According to our simulations, pneumococci benefit from a high dwelling probability and a high proliferation rate during the first stages of infection. In addition to this, the model predicts that during the very early phases of infection the bacterial capsule could be an impediment to the establishment of the alveolar infection because it impairs bacterial colonization.
Christensen, Sarah Friis; Jørgensen, Lars Christian; Cordoba, Gloria; Llor, Carl; Siersma, Volkert; Bjerrum, Lars
2013-12-01
In patients with lower respiratory tract infections (LRTIs) it is a challenge to identify who should be treated with antibiotics. According to international guidelines, antibiotics should be prescribed to patients with suspected pneumonia while acute bronchitis is considered a viral infection and should, generally, not be treated with antibiotics. Overdiagnosis of pneumonia in patients with LRTIs may lead to antibiotic overprescribing. To investigate the prevalence of presumed pneumonia in patients with LRTI in two countries with different antibiotic prescribing rates (Denmark and Spain) and to compare which symptoms and clinical tests are of most importance for the GP when choosing a diagnosis of pneumonia rather than acute bronchitis. A cross-sectional study including GPs from Denmark and Spain was conducted as part of the EU-funded project HAPPY AUDIT. A total of 2,698 patients with LRTI were included. In Denmark, 47% of the patients with LRTI were classified with a diagnosis of pneumonia compared with 11% in Spain. In Spain, fever and a positive x-ray weighted significantly more in the diagnosis of pneumonia than in Denmark. Danish GPs, however, attached more importance to dyspnoea/polypnoea and C-reactive protein levels >50mg/L. None of the other typical symptoms of pneumonia had a significant influence. Our results indicate that GPs' diagnostic criteria for pneumonia differ substantially between Denmark and Spain. The high prevalence of pneumonia among Danish patients with LRTI may indicate overdiagnosis of pneumonia which, in turn, may lead to antibiotic overprescribing.