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Sample records for azithromycin suppresses interleukin-12p40

  1. A protease-activated receptor 2 agonist (AC-264613) suppresses interferon regulatory factor 5 and decreases interleukin-12p40 production by lipopolysaccharide-stimulated macrophages: Role of p53.

    PubMed

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-06-01

    The transcription factor interferon regulatory factor 5 (IRF5) has a key role in the production of interleukin (IL)-12 by macrophages. IRF5 is also a central mediator of toll-like receptor signaling and is a direct target of p53. Activation of protease-activated receptor 2 (PAR-2) upregulates p53 and suppresses apoptosis. This study investigated the influence of human neutrophil elastase (HNE) and PAR-2 agonists on expression of IRF5 and IL-12p40 by macrophages stimulated with lipopolysaccharide. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophages showed upregulation of IRF5 expression, while HNE reduced expression of p53 and IRF5 in a concentration-dependent manner. HNE also caused a concentration-dependent decrease of IRF5 in macrophages transfected with small interfering RNA to silence p53, while silencing of β-arrestin 2 blunted the reduction of p53 or IRF5 by HNE. Incubation of macrophages with a PAR-2 agonist, AC-264613, caused a decrease of IRF5 expression and also significantly reduced p53 protein expression. HNE upregulated the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and caused transactivation of TLR4, while AC-264613 did not promote TLR4 transactivation. In conclusion, the PAR-2 agonist AC-264613 attenuated IRF5-associated IL-12p40 production by macrophages.

  2. Diagnostic value of interleukin-12 p40 in tuberculous pleural effusions.

    PubMed

    Valdés, L; San José, E; Alvarez Dobaño, J M; Golpe, A; Valle, J M; Penela, P; González Barcala, F J

    2009-04-01

    The diagnosis of tuberculous pleural effusion (TBPE) is frequently problematic. Several markers of TBPE in pleural fluid have been evaluated, with different results. Pleural effusions from 96 patients were classified on the basis of definitive diagnosis as tuberculous (n = 39), neoplastic (n = 42) or parapneumonic (n = 15). Adenosine deaminase (ADA), ADA isoform ADA-2, interferon (IFN)-gamma, CD3(+)/DR(+) T-lymphocytes and interleukin (IL)-12 p40 were determined in all 96 effusions. The efficiency of IL-12 p40 for diagnosis of TBPEs was evaluated, in comparison with those of the other parameters, by comparing the areas under their receiver operating characteristics. With the threshold value of 550 pg.mL(-1), IL-12 p40 had a sensitivity of 92.3% (36 out of 39) and specificity of 70.2% (17 false positives). The misclassification rate of IL-12 p40 was significantly greater than those of ADA-2 and ADA. Among TBPEs, ADA correlated significantly with ADA-2, and IFN-gamma with ADA and IL-12 p40. Although tuberculous pleural effusions show values of interleukin-12 p40 that are significantly higher than neoplastic and parapneumonic fluids, this parameter is less efficient than adenosine deaminase, adenosine deaminase isoform 2 and interferon-gamma. Its routine determination is, accordingly, not justified.

  3. Tumor Necrosis Factor-α, Interleukins-12(p40), 6, and 10 levels in cerebrospinal fluid and outcome prediction in Ossimi sheep with encephalitic listeriosis.

    PubMed

    Abdlla, Ossama A; Elboshy, Mohamed E; Reisha, Engy F; Gadlla, Hossam A; El-Khodery, Sabry A

    2015-06-01

    Encephalitic listeriosis in sheep is a life-threatening disease. However, little is known about the cytokine response and their predictive value in this disease. The aim of present study was to assess the prognostic significance of Tumor Necrosis Factor-α (TNF-α), Interleukin-12(p40) (IL-12 p40), Interleukin-6 (IL-6), and Interleukin 10 (IL-10) levels in cerebrospinal fluid (CSF) in sheep with encephalitic listeriosis. Fifty-nine ewes in 14 flocks were diagnosed clinically as having listeriosis. CSF was collected and subjected to bacteriological examination and estimation of selected cytokines. Twenty-eight ewes were confirmed to be infected with Listeria monocytogenes. Based on antimicrobial sensitivity test, sheep were treated and the outcome was recorded as survivors (n=10) and non-survivors (n=18). Cutoff points for CSF cytokines were determined by Receiver operating characteristic analysis (ROC). Association between levels of CSF cytokines and outcome of listeriosis was assessed by logistic regression. TNF-α, IL-6 and IL-12(p40) levels as well as TNF-α/IL-10 ratio were significantly higher in non-survivors than survivors (p=0.002, 0.0021, 0.0033, and 0.001, respectively). However, IL-10 level was significantly lower in non-survivors than survivors (p=0.0058). ROC analysis revealed that IL-6 and TNF-α/IL-10 ratio had the highest AUC values (0.98, 0.984, respectively). Final multivariate logistic regression model showed that TNF-α/IL-10 ratio was the only variable that has predictive value for mortality in diseased sheep (p: 0.001; OR: 7.2; 95% CI: 5.7-9.8). TNF-α showed a positive correlation with IL-12β (r=0.917) and IL-6 (r=0.965). IL-12 (p40) showed also a positive correlation with IL-6 (r=0.906). However, IL-10 showed a negative correlation with TNF-α (r=-0.915), IL-12(p40) (r=-0.790), and IL-6 (r=-0.902). In conclusion, TNF-α/IL-10 ratio may provide predictive information about outcome of encephalitic listeriosis in sheep. Copyright © 2015

  4. Azithromycin

    MedlinePlus

    ... cup (60 mL) of water to the same glass, mix, and consume the entire contents to ensure that you receive the entire dose.If you receive azithromycin extended-release suspension as a dry powder you must first add water to the bottle ...

  5. Azithromycin.

    PubMed

    Bakheit, Ahmed H H; Al-Hadiya, Badraddin M H; Abd-Elgalil, Ahmed A

    2014-01-01

    Azithromycin is an azalide, a subclass of macrolide antibiotics. It is derived from erythromycin, with a methyl-substituted nitrogen atom incorporated into the lactone ring, thus making the lactone ring 15-membered. It prevents bacteria from growing by interfering with their protein synthesis. It binds to the 50S subunit of the bacterial ribosome and thus inhibits translation of mRNA. Azithromycin is used to treat or prevent certain bacterial infections, most often those causing middle ear infections, strep throat, pneumonia, typhoid, bronchitis, and sinusitis. In recent years, it has been used primarily to prevent bacterial infections in infants and those with weaker immune systems. It is also effective against certain sexually transmitted infections, such as nongonococcal urethritis, chlamydia, and cervicitis. Recent studies have indicated it also to be effective against late-onset asthma, but these findings are controversial and not widely accepted. The present study gives a comprehensive profile of azithromycin, including detailed physico-chemical properties, nomenclature, formulae, methods of preparation, and methods of analysis (including compendial, electrochemical, spectroscopic, and chromatographic methods of analysis). Developed validated stability-indicating (HPLC and biodiffusion assay methods under accelerated acidic, alkaline, and oxidative conditions, in addition to effect of different types of light, temperature, and pH. Detailed clinical applications also presented (mechanism of action, ADME profile, clinical uses and doses, side effects, and drug interactions). Each of the above stages includes appropriate figures and tables. More than 80 references were given as a proof of the above-mentioned studies. © 2014 Elsevier Inc. All rights reserved.

  6. Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease

    PubMed Central

    Deshpande, Devyani; Pasipanodya, Jotam G.

    2016-01-01

    Mycobacterium avium complex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonary M. avium disease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses. PMID:26810646

  7. Comparative in vitro exoenzyme-suppressing activities of azithromycin and other macrolide antibiotics against Pseudomonas aeruginosa.

    PubMed Central

    Mizukane, R; Hirakata, Y; Kaku, M; Ishii, Y; Furuya, N; Ishida, K; Koga, H; Kohno, S; Yamaguchi, K

    1994-01-01

    The inhibitory effects of azithromycin (AZM), a new 15-membered macrolide antibiotic, on the production of exotoxin A, total protease, elastase, and phospholipase C by Pseudomonas aeruginosa were determined, and the virulence-suppressing effects of AZM were compared with those of erythromycin (EM), roxithromycin (RXM), and rokitamycin (RKM). The effect of exposure of P. aeruginosa PA103 or B16 in cultures to sub-MICs of these macrolide antibiotics on the production of exoenzymes was determined. AZM suppressed the in vitro production of extracellular and intracellular exotoxin A by P. aeruginosa PA103 more than did EM, even at a concentration of only 2 micrograms/ml. At concentrations of between 4 and 32 micrograms/ml, AZM also inhibited total protease, elastase, and phospholipase C production by P. aeruginosa B16 more than did EM, RXM, and RKM. AZM was effective in suppressing exotoxin A and total protease production through 24 h of incubation in the presence of drug at sub-MICs, but it had no significant effect on either the growth of P. aeruginosa or its total protein production. Moreover, at a concentration of 4 micrograms/ml, AZM suppressed exoenzyme production by other strains of P. aeruginosa more than did EM. These findings indicate that AZM, EM, RXM, and RKM each has an inhibitory effect on exoenzyme production separate from the antimicrobial effect and that, of these macrolides, AZM has the strongest virulence-suppressing effect. PMID:8203850

  8. Suppressive therapy using azithromycin in 2 rare cases of recurrent staphylococcal infections.

    PubMed

    Grobost, Vincent; Rigal, Emilie; Pavier, Yoann; Vidal, Magali; Mrozek, Natacha; Beytout, Jean; Laurichesse, Henri; Lesens, Olivier

    2014-05-01

    Recurrent staphylococcal skin and soft tissue infections may recur despite decontamination and multiple courses of antibiotic therapy and may dramatically impair the patient's quality of life. We report successful use of long-term azithromycin prophylaxis in a recurrent laryngitis and a scalp folliculitis due to methicillin-susceptible Staphylococcus aureus. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Inflammation and Elevation of Interleukin-12p40 in Patients with Schizophrenia.

    PubMed

    Bedrossian, Nora; Haidar, Mariam; Fares, Jawad; Kobeissy, Firas H; Fares, Youssef

    2016-01-01

    Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning, which suggests that it likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological contributors for psychiatric disorders, including schizophrenia. Although, the role of inflammation in schizophrenia is becoming evident, the number of studies in this area is relatively scarce, especially in Lebanon, and increased procedural thoroughness is needed. Cytokines play a key role in the activation of the immune system and strongly influence neurotransmission. Previous investigation of plasma levels showed dysregulation of interleukin (IL)-12. However, genotypical variations of this interleukin have not been investigated for patients with schizophrenia yet. Thus, in this paper, we aimed to compute and assess IL-12p40 levels in the sera of individuals with schizophrenia from different provinces in Lebanon and compare it to controls. Healthy subjects comprised 60 individuals with a male/female (M/F) ratio of 31/29, whereas patients with schizophrenia consisted of 63 subjects with an M/F ratio of 30/33. The mean age for healthy controls was 30 years, whereas that for patients with schizophrenia was 35 years. A standardized enzyme-linked immunosorbent assay (ELISA) technique was used to measure the concentration of IL-12p40 in all collected sera (n = 123). The mean IL-12p40 levels in patients with schizophrenia were significantly higher than in healthy controls (p = 0.002). Healthy females had a significantly higher concentration of IL-12p40 than healthy males (p = 0.009). Female patients with schizophrenia had significantly higher concentrations of IL-12p40 than their male counterparts (p < 0.001), healthy females (p = 0.018), and healthy males (p < 0.001), respectively. Male patients with schizophrenia had significantly higher concentrations of IL-12p40 than healthy males (p = 0.023). The study's results suggest that IL-12p40 has a putative role as a potential marker in schizophrenia and that its elevation may participate in its pathogenesis. IL-12p40 may be included in a panel to be evaluated in the sera of patients with schizophrenia and an appreciation of its independent function is important for improving our understanding of both protective and pathogenic immune responses. Future research should aim to assess this interleukin and understand its role in other mental illnesses that share a similar etiology to schizophrenia.

  10. Chronic Disseminated Salmonellosis in a Patient with Interleukin- 12p40 Deficiency.

    PubMed

    Alaki, Emadia Mohammad; Aljobair, Fahad; Alaklobi, Faisal; Al Shamrani, Mobarak; Al-Zahim, Fahad; Dongues, Aziza; Casanova, Jean-Laurent

    2017-07-18

    Interleukin (IL)-12 is composed of p35 and p40 subunit, in this case IL-12p40 deficiency is a rare genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD). Salmonellosis has been reported in almost half of these patients and mostly present in recurrent extra intestinal form. In this report, we described an 18 month old boy with absence of IL12p40 production suffering from chronic disseminated non-typhoidal salmonellosis. To the best of our knowledge this is the first reported case.

  11. Inflammation and Elevation of Interleukin-12p40 in Patients with Schizophrenia

    PubMed Central

    Bedrossian, Nora; Haidar, Mariam; Fares, Jawad; Kobeissy, Firas H.; Fares, Youssef

    2016-01-01

    Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning, which suggests that it likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological contributors for psychiatric disorders, including schizophrenia. Although, the role of inflammation in schizophrenia is becoming evident, the number of studies in this area is relatively scarce, especially in Lebanon, and increased procedural thoroughness is needed. Cytokines play a key role in the activation of the immune system and strongly influence neurotransmission. Previous investigation of plasma levels showed dysregulation of interleukin (IL)-12. However, genotypical variations of this interleukin have not been investigated for patients with schizophrenia yet. Thus, in this paper, we aimed to compute and assess IL-12p40 levels in the sera of individuals with schizophrenia from different provinces in Lebanon and compare it to controls. Healthy subjects comprised 60 individuals with a male/female (M/F) ratio of 31/29, whereas patients with schizophrenia consisted of 63 subjects with an M/F ratio of 30/33. The mean age for healthy controls was 30 years, whereas that for patients with schizophrenia was 35 years. A standardized enzyme-linked immunosorbent assay (ELISA) technique was used to measure the concentration of IL-12p40 in all collected sera (n = 123). The mean IL-12p40 levels in patients with schizophrenia were significantly higher than in healthy controls (p = 0.002). Healthy females had a significantly higher concentration of IL-12p40 than healthy males (p = 0.009). Female patients with schizophrenia had significantly higher concentrations of IL-12p40 than their male counterparts (p < 0.001), healthy females (p = 0.018), and healthy males (p < 0.001), respectively. Male patients with schizophrenia had significantly higher concentrations of IL-12p40 than healthy males (p = 0.023). The study’s results suggest that IL-12p40 has a putative role as a potential marker in schizophrenia and that its elevation may participate in its pathogenesis. IL-12p40 may be included in a panel to be evaluated in the sera of patients with schizophrenia and an appreciation of its independent function is important for improving our understanding of both protective and pathogenic immune responses. Future research should aim to assess this interleukin and understand its role in other mental illnesses that share a similar etiology to schizophrenia. PMID:27047333

  12. Azithromycin anaphylaxis in children.

    PubMed

    Mori, F; Pecorari, L; Pantano, S; Rossi, M E; Pucci, N; De Martino, M; Novembre, E

    2014-01-01

    Allergic reactions associated to the use of macrolides are uncommon; in particular only two cases of anaphylaxis with erithromycin and clarithromycin have been reported to date. The aim of this study was to investigate macrolide-induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive children were referred to the Allergy Unit of A. Meyer Children's Hospital because of a past history of reactions to macrolides. Allergy work-ups were carried out according to the European Network for Drug Allergy protocol. Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients completed the allergologic work-up and among them we investigated three cases of anaphylaxis due to azithromycin which included one child with anaphylaxis to both clarithromycin and azithromycin. In two of the children with anaphylaxis, the diagnosis was only confirmed with the skin prick test, the third was positive to the Intradermal Test. The azithromycin allergy shows a surprisingly high sensitivity to the in-vivo tests. Moreover, this study shows that cross-reactivity may occur between different macrolidic molecules; it has even been suggested that macrolide allergies are unlikely to be class allergies.

  13. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    PubMed

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease.

  14. Periodontal tissue disposition of azithromycin.

    PubMed

    Malizia, T; Tejada, M R; Ghelardi, E; Senesi, S; Gabriele, M; Giuca, M R; Blandizzi, C; Danesi, R; Campa, M; Del Tacca, M

    1997-12-01

    The tissue penetration of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients undergoing surgery for third-molar removal. Drug concentrations in plasma, saliva, and periodontal tissues were evaluated in 28 patients treated with azithromycin 500 mg/day per os for 3 consecutive days. Samples of blood, saliva, gingiva, and alveolar bone were collected during oral surgery, 12 hours, and 2.5, 4.5, and 6.5 days after the last dosing, and the azithromycin concentration was measured microbiologically by using Micrococcus luteus NCTC 8440 as the reference organism. The highest concentrations of azithromycin were observed 12 hours after the last dose in plasma, saliva, gingiva, and bone (0.33 +/- 0.04 mg/l, 2.14 +/- 0.30 mg/l, 6.47 +/- 0.57 mg/kg, and 1.86 +/- 0.15 mg/kg, respectively) and then declined gradually. However, consistent levels of the drug in saliva and periodontal tissues could be detected up to 6.5 days, indicating that azithromycin was retained in target tissues and fluids for a long time after the end of treatment. Among the samples examined, the highest concentration of azithromycin was found in the gingiva at each time studied. Moreover, the ratios of salivary or periodontal tissue levels versus plasma concentrations remained nearly unmodified from 12 hours up to 6.5 days. Overall, these results indicate a favorable disposition of azithromycin into saliva and periodontal tissues and suggest that this macrolide antibiotic represents a valuable option in the pharmacologic treatment of odontogenic infections.

  15. Azithromycin use in paediatrics: A practical overview.

    PubMed

    Ovetchkine, Philippe; Rieder, Michael J

    2013-06-01

    Azithromycin is an antibiotic that is commonly prescribed for upper and lower respiratory tract infections in children. While it has proven benefits, some concerns regarding azithromycin use have arisen in recent years. This practice point considers azithromycin therapy for acute respiratory infections in otherwise healthy children. Pharmacokinetics, spectrum of activity, the problem of resistant bacteria and clinical aspects are considered, along with recommendations for use and contraindications. Azithromycin should be avoided in patients with a significant risk of bacteremia. It is associated with pneumococcal resistance and, with stated exceptions, is generally not recommended for the treatment of acute pharyngitis, acute otitis media or pneumococcal community-acquired pneumonia in the paediatric population.

  16. Scavenger receptor for lipoteichoic acid is involved in the potent ability of Lactobacillus plantarum strain L-137 to stimulate production of interleukin-12p40.

    PubMed

    Hatano, Shinya; Hirose, Yoshitaka; Yamamoto, Yoshihiro; Murosaki, Shinji; Yoshikai, Yasunobu

    2015-04-01

    Heat-killed Lactobacillus plantarum strain L-137 (HK L-137) is a more potent inducer of interleukin (IL)-12 than other heat-killed Lactobacillus strains. To elucidate the mechanism involved in this IL-12p40 induction, we compared HK L-137 with heat-killed L. plantarum strain JCM1149 (HK JCM1149) by nuclear magnetic resonance and mass spectrometry. Results showed that HK L-137 contained lipoteichoic acid (LTA) with a chemical structure similar to that of JCM1149, except for a lower degree of glucosyl substitution in the poly(glycerol phosphate) backbone. Lysozyme sensitivity and electrophoretic moiety analysis revealed that HK L-137 exposed more LTA on its cell surface than HK JCM1149. Phagocytosis of HK L-137 by splenic adherent cells was significantly greater than that of HK JCM1149. Anti-LTA antibody and anti-scavenger receptor-A (SR-A) antibody selectively inhibited phagocytosis of HK L-137, as well as IL-12p40 production, by splenic adherent cells. Thus, a higher efficiency of phagocytosis of HK L-137 via SR-A for LTA is responsible for the potent IL-12p40 induction.

  17. The 3'UTR 1188 A/C polymorphism in the interleukin-12p40 gene (IL-12B) is associated with lepromatous leprosy in the west of Mexico.

    PubMed

    Alvarado-Navarro, Anabell; Montoya-Buelna, Margarita; Muñoz-Valle, José Francisco; López-Roa, Rocio Ivette; Guillén-Vargas, Cecilia; Fafutis-Morris, Mary

    2008-06-30

    Leprosy is a chronic infectious disease caused by Mycobacterium leprae. IL-12 participates in the immune response against M. leprae by regulating T cell differentiation into the Th1-type response. Several single nucleotide polymorphisms have been identified in the IL-12 gene such as 3'UTR 1188 A/C polymorphism, which is associated with different diseases. However, the relationship of this polymorphism with the immune response in leprosy has not been explored. In this case-control study, we evaluated 44 patients with lepromatous leprosy (LL) and 51 healthy subjects (HS). We aimed to determine the relationship between 3'UTR 1188 A/C polymorphism of IL-12 p40, mRNA expression, and soluble IL-12 concentration in LL patients and HS. Genotype frequencies were 41% A/A, 36% A/C, and 23% C/C in LL patients, and 47% A/A, 49% A/C, and 4% C/C in HS (p<0.05). LL patients had a lower mRNA expression of IL-12 p40 gene, whereas HS had a higher expression level. Soluble IL-12 p40 concentration was higher in LL patients than in HS (p<0.05). IL-12 p70 concentration did not differ between groups, and IL-12 p40 concentration was not significantly correlated with mRNA expression in either group. These data suggest that IL-12 p40 3'UTR 1188 A/C polymorphism is associated with greater susceptibility to lepromatous leprosy in patients from western Mexico, independently of IL-12 p40 and p70 expression levels.

  18. Cloning, promoter analysis and expression in response to bacterial exposure of sea bass (Dicentrarchus labrax L.) interleukin-12 p40 and p35 subunits.

    PubMed

    Nascimento, Diana S; do Vale, Ana; Tomás, Ana M; Zou, Jun; Secombes, Christopher J; dos Santos, Nuno M S

    2007-03-01

    Interleukin-12 (IL-12) is a heterodimeric cytokine pivotal in resistance to microbial and viral infections. In the search for immunoregulatory genes in sea bass the genes for the two IL-12 subunits p40 and p35 were cloned and sequenced. Molecular characterization of these two genes was performed at both the cDNA and genomic levels. Sea bass IL-12 p40 and p35 conserve most cysteines involved in the intra-chain disulfide bonds of human IL-12 subunits as well as the important structural residues for human IL-12 heterodimerization. The gene organization of sea bass IL-12 p40 is similar to the human orthologue, whilst the sea bass IL-12 p35 gene structure, as reported for pufferfish, differs from the human one in containing an additional exon and lacking a second copy of a duplicated exon present in the mammalian genes. The promoter analysis of both sea bass and pufferfish IL-12 genes showed the presence of the main cis-acting elements involved in the transcriptional regulation of human and mouse orthologues. The involvement of IL-12 in sea bass anti-bacterial immune responses was demonstrated by investigating the expression profiles of IL-1beta, IL-12 p40 and p35 in the head-kidney and spleen following intraperitoneal injection of UV-killed and live Photobacterium damselae ssp. piscicida (Phdp). Finally, the importance of nuclear factor (NF)-kappaB on UV-killed Phdp-induced IL-12 p40 and p35 gene transcription was shown by the use of pyrrolidine dithiocarbamate (PDTC).

  19. Effects of azithromycin on shiga toxin production by Escherichia coli and subsequent host inflammatory response.

    PubMed

    Ohara, Tatsuki; Kojio, Seiichi; Taneike, Ikue; Nakagawa, Saori; Gondaira, Fumio; Tamura, Yukiko; Gejyo, Fumitake; Zhang, Hui-Min; Yamamoto, Tatsuo

    2002-11-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the human intestinal mucosa, produces Stx from phage, and causes the development of hemolytic-uremic syndrome via Stx-induced inflammatory cytokine production. Azithromycin exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin. Azithromycin decreased the tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin significantly suppressed Stx-induced TNF-alpha, IL-1beta, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immature-mouse model), all mice died within 7 days postinfection. Azithromycin administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice. Azithromycin may have a beneficial effect on STEC-associated disease.

  20. Oral Azithromycin for Treatment of Intractable Rosacea

    PubMed Central

    Kim, Jae-Hong; Oh, Yoon Seok

    2011-01-01

    Rosacea is a common chronic cutaneous disorder that primarily occurs on the convex surfaces of the central face and is often characterized by exacerbations and remissions. A case of a 52-yr-old woman visited our clinic in February 2008 complaining typical features of rosacea including multiple pinhead to rice-sized erythematous papules. We applied various conventional treatments including topical benzoyl peroxide and metronidazole as well as oral metronidazole, isotretinoin, and doxycycline. The lesions were not controlled but were rather aggravated by complications from these treatments. Therefore, we prescribed oral azithromycin, which has anti-inflammatory effects and reduces reactive oxygen species. Ten weeks after the administration of oral azithromycin, 500 mg per day for 2 weeks, the lesions had mostly disappeared and no specific side effects related to the azithromycin were noted. Oral azithromycin dosing 500 mg/day for 2 weeks is effective for treatment of intractable rosacea. PMID:21532865

  1. Azithromycin for prevention of exacerbations of COPD.

    PubMed

    Albert, Richard K; Connett, John; Bailey, William C; Casaburi, Richard; Cooper, J Allen D; Criner, Gerard J; Curtis, Jeffrey L; Dransfield, Mark T; Han, Meilan K; Lazarus, Stephen C; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J; Madinger, Nancy E; McEvoy, Charlene; Niewoehner, Dennis E; Porsasz, Janos; Price, Connie S; Reilly, John; Scanlon, Paul D; Sciurba, Frank C; Scharf, Steven M; Washko, George R; Woodruff, Prescott G; Anthonisen, Nicholas R

    2011-08-25

    Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment

  2. Azithromycin for Prevention of Exacerbations of COPD

    PubMed Central

    Albert, Richard K.; Connett, John; Bailey, William C.; Casaburi, Richard; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Dransfield, Mark T.; Han, MeiLan K.; Lazarus, Stephen C.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; Madinger, Nancy E.; McEvoy, Charlene; Niewoehner, Dennis E.; Porsasz, Janos; Price, Connie S.; Reilly, John; Scanlon, Paul D.; Sciurba, Frank C.; Scharf, Steven M.; Washko, George R.; Woodruff, Prescott G.; Anthonisen, Nicholas R.

    2011-01-01

    BACKGROUND Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. METHODS We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. RESULTS A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George’s Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of −4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS Among selected subjects with COPD, azithromycin taken daily for

  3. [Azithromycin therapy in cystic fibrosis].

    PubMed

    Máiz Carro, Luis; Cantón Moreno, Rafael

    2004-03-06

    Progressive lung disease, caused by chronic endobronchial colonization, is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Several pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa are responsible for this effect. The steadily improving prognosis of CF has been attributed to the use of antibiotics with activity against these organisms. Despite a significant increase in the amount of published material demonstrating the potential role of macrolide antibiotics as antiinflammatory agents and their effects on bacterial virulence, their mechanism of action in CF patients is still unknown. Although there is a limited number of clinical trials assessing the efficacy and safety of azithromycin (AZM) in CF, increasing evidence suggests that 3 to 6-month AZM treatment in CF patients is safe and well tolerated. This treatment results in clinical improvement, decreasing the number of pulmonary exacerbations and increasing pulmonary function. Therefore, chronic treatment with AZM should be considered in CF patients added to conventional therapy. Clinical experience with macrolides other than AZM in CF patients is very limited.

  4. A case of clinical and microbiological failure of azithromycin therapy in Salmonella enterica serotype Typhi despite low azithromycin MIC.

    PubMed

    Manesh, Abi; Balaji, Veeraraghavan; Kumar, Devanga Ragupathi Naveen; Rupali, Priscilla

    2017-01-01

    Typhoid fever remains a serious problem in many developing countries. Due to resistance to multiple first line drugs, azithromycin has evolved as an important drug in the treatment of typhoid. While therapy with azithromycin is highly effective, no clinically validated mean inhibitory concentration (MIC) break points or disc diffusion cutoff guidelines are available so far. We describe an Indian adult with clinical and microbiological failure to azithromycin despite low azithromycin MIC.

  5. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery

    PubMed Central

    Tita, Alan T.N.; Szychowski, Jeff M.; Boggess, Kim; Saade, George; Longo, Sherri; Clark, Erin; Esplin, Sean; Cleary, Kirsten; Wapner, Ron; Letson, Kellett; Owens, Michelle; Abramovici, Adi; Ambalavanan, Namasivayam; Cutter, Gary; Andrews, William

    2016-01-01

    BACKGROUND The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. METHODS In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. RESULTS The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P = 0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P = 0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P = 0.63). CONCLUSIONS Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546.) PMID:27682034

  6. Oral azithromycin for treatment of posterior blepharitis.

    PubMed

    Igami, Thais Zamudio; Holzchuh, Ricardo; Osaki, Tammy Hentona; Santo, Ruth Miyuki; Kara-Jose, Newton; Hida, Richard Y

    2011-10-01

    To evaluate the effects of oral azithromycin in patients with posterior blepharitis. Twenty-six eyes of 13 patients with posterior blepharitis diagnosed by a qualified ophthalmologist were enrolled in this study. Patients were instructed to use oral azithromycin 500 mg per day for 3 days in 3 cycles with 7-day intervals. Subjective clinical outcomes were graded and scored 1 day before and 30 days after the end of the treatment (53 days after initiating the treatment) based on severity scores of: (1) eyelid debris; (2) eyelid telangiectasia; (3) swelling of the eyelid margin; (4) redness of the eyelid margin; and (5) ocular mucus secretion. For the assessment of global efficacy, patients were asked by the investigator to rate the subjective symptoms (eyelid itching, ocular itching, eyelid hyperemia, ocular hyperemia, ocular mucus secretion, photophobia, foreign body sensation, and dry eye sensation) on a scale of 0 (no symptoms) to 5 (severe symptoms). Break-up time, Schirmer I test, corneal fluorescein staining score, and rose bengal staining score were also performed in all patients. All clinical outcomes scoring showed statistically significant improvement after oral azithromycin, except for eyelid swelling. Average subjective symptom grading improved statistically after treatment with oral azithromycin, except for eyelid hyperemia, photophobia, and foreign body sensation. Average tear film break-up time values showed statistically significant improvement after the treatment with oral azithromycin. No statistically significant improvement was observed on average values of Schirmer I test, corneal fluorescein staining score, and rose bengal staining score. The combination of multiple clinical parameters shown in this study supports the clinical efficacy of pulsed oral azithromycin therapy for the management of posterior blepharitis.

  7. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery.

    PubMed

    Tita, Alan T N; Szychowski, Jeff M; Boggess, Kim; Saade, George; Longo, Sherri; Clark, Erin; Esplin, Sean; Cleary, Kirsten; Wapner, Ron; Letson, Kellett; Owens, Michelle; Abramovici, Adi; Ambalavanan, Namasivayam; Cutter, Gary; Andrews, William

    2016-09-29

    The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63). Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).

  8. Intracellular activity of azithromycin against bacterial enteric pathogens.

    PubMed Central

    Rakita, R M; Jacques-Palaz, K; Murray, B E

    1994-01-01

    Azithromycin, a new azalide antibiotic, is active in vitro against a variety of enteric bacterial pathogens. Since it is concentrated inside human neutrophils and other cells, it might be particularly useful in the treatment of infections caused by enteropathogens that invade host tissues. The intracellular activity of azithromycin against several enteric pathogens that had been phagocytosed by neutrophils was determined. Azithromycin was effective in reducing the intracellular viabilities of almost all strains tested, including representative strains of Salmonella, Shigella, and enteroinvasive, enteropathogenic, enterotoxigenic, and enterohemorrhagic Escherichia coli. Erythromycin was also effective in this model system, although azithromycin was generally more effective than erythromycin against strains of invasive enteric pathogens. Cefotaxime reduced intracellular bacterial viability to a lesser extent than either azithromycin or erythromycin. The presence of neutrophils did not significantly affect the activity of azithromycin in this system. Azithromycin may be a useful agent for the treatment of bacterial diarrhea, and clinical trials should be considered. PMID:7810998

  9. A new HPLC method for azithromycin quantitation.

    PubMed

    Zubata, Patricia; Ceresole, Rita; Rosasco, Maria Ana; Pizzorno, Maria Teresa

    2002-02-01

    A simple liquid chromatographic method was developed for the estimation of azithromycin raw material and in pharmaceutical forms. The sample was chromatographed on a reverse phase C18 column and eluants monitored at a wavelength of 215 nm. The method was accurate, precise and sufficiently selective. It is applicable for its quantitation, stability and dissolution tests.

  10. Cardiac risks associated with antibiotics: azithromycin and levofloxacin

    PubMed Central

    Lu, Zhiqiang Kevin; Yuan, Jing; Li, Minghui; Sutton, S Scott; Rao, Gowtham A; Jacob, Sony; Bennett, Charles L

    2015-01-01

    Introduction Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. Areas covered Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. Expert opinion Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood. PMID:25494485

  11. Azithromycin induced bullous fixed drug eruption.

    PubMed

    Das, Anupam; Sancheti, Karan; Podder, Indrashis; Das, Nilay Kanti

    2016-01-01

    Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin-induced bullous FDE; to the best of our knowledge, this is the first such case being reported.

  12. Azithromycin induced bullous fixed drug eruption

    PubMed Central

    Das, Anupam; Sancheti, Karan; Podder, Indrashis; Das, Nilay Kanti

    2016-01-01

    Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin-induced bullous FDE; to the best of our knowledge, this is the first such case being reported. PMID:26997729

  13. Corticosteroid and Azithromycin in Idiopathic Granulomatous Mastitis

    PubMed Central

    Salehi, Marzieh; Salehi, Maryam; Kalbasi, Nader; Hakamifard, Atousa; Salehi, Hassan; Salehi, Mohammad Mahdi; Sharifian, Jalil

    2017-01-01

    Background: Mastitis is an inflammatory disorder in breast tissues due to bacterial factors, mycobacterial infections or autoimmune diseases. Idiopathic granulomatous mastitis (IGM) is a form of mastitis which may be affected by systematic diseases such as sarcoidosis, and infectious causes such as mycobacterium and fungus. This study evaluates the efficacy of medical therapy with a combination of corticosteroid and Azithromycin in patients with IGM. Materials and Methods: This study is a clinical trial research carried out in Alzahra Hospital (Isfahan, Iran) in 2013 on granulomatous mastitis patients. It was administered 250 mg of Azithromycin per 12 hour and 60 mg of Prednisolone per day within 2 weeks. Next, they took 40 mg/day within 8 weeks, and this dosage was tapered during 6 months and the patients clinically and radiologically followed up. The studied patients were examined within 1 week, 2 weeks, 1 month, 3 months, and 6 months, from the beginning of treatment. Results: This study investigated granulomatous mastitis patients in Alzahra hospital in 2013. The mean age of these patients was 33.6 ± 8.9, and their age range was 18–56 years old. Among 26 studied patients, 24 persons (92.3%) according to follow-up the patients by physical examination and sonography responded to treatment of corticosteroid and Azithromycin. The remaining (7.7%) underwent surgery. Treatment periods in case of drug use were respectively, 8.5 ± 0.71 months. Conclusion: Treatment with corticosteroid and Azithromycin is an effective and appropriate treatment for IGM. PMID:28217653

  14. QT Interval Prolongation Associated with Azithromycin/Methadone Combination.

    PubMed

    Amer, S; Hassan, S; Shariffi, M; Chueca, L

    2013-11-01

    This report documents the occurrence of QT prolongation in a 57-year old man, on methadone replacement therapy, treated with azithromycin for community acquired pneumonia. This case highlights a hitherto unknown drug interaction. In light of ever-increasing use of azithromycin, it is imperative that azithromycin be used with caution in patients who are already on drugs that are known to cause QT prolongation or that cause torsades de pointes.

  15. Quality of life after tonsillectomy versus azithromycin

    PubMed Central

    El Hennawi, Diaa El Din Mohamed; Rifaat Ahmed, Mohamed

    2016-01-01

    Background Recurrent tonsillitis is a common disease with marked evidence of affecting children quality of life (QOL) such as their progression in school and increased burden to extended families. The aim of this study was to compare the QOL outcomes after conventional dissection tonsillectomy versus azithromycin treatment in controlling recurrent tonsillitis. Methods A double-blind, randomized clinical trial was carried out in 184 children with recurrent tonsillitis randomly divided into two groups: Group A was subjected to conventional dissection tonsillectomy, whereas Group B received single 250 mg (children ≤25 kg) and 500 mg (children ≥25 kg) of oral azithromycin once weekly. Results There were no significant differences between the groups with regard to ear, nose, and throat infections during the 5-year follow-up. Better QOL was observed in both groups when compared with the pretreatment, but similar QOL in both groups QOL after treatment. Conclusion Azithromycin is an effective method as a prophylaxis against recurrent tonsillitis with a great benefit for better QOL outcomes. PMID:28180002

  16. Use and safety of azithromycin in neonates: a systematic review

    PubMed Central

    Smith, Coral; Egunsola, Oluwaseun; Choonara, Imti; Kotecha, Sailesh; Jacqz-Aigrain, Evelyne; Sammons, Helen

    2015-01-01

    Objectives To identify the use and adverse drug reactions associated with azithromycin in neonates. Setting Databases MEDLINE (1948–August 2015), EMBASE (1980–August 2015) and Pubmed (August 2015) were searched for studies on azithromycin in neonates. Participants All studies involving neonates (<28 days old) who have received at least a single dose of azithromycin for which safety was evaluated. Primary and secondary outcome measures The primary outcome was adverse event (AE) associated with use of azithromycin. Use of azithromycin in neonates was the secondary outcome. Results A total of 11 articles involving 473 neonates were identified. 371 AEs were reported. Adverse events were mainly respiratory (358/1000 neonate), neurological (273/1000 neonates) and gastrointestinal (196/1000 neonates) in origin. Azithromycin significantly reduced the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates (RR=0.83, 95% CI 0.71 to 0.98, p=0.02). There was no significant difference in the incidence of elevated liver enzymes between the azithromycin and placebo group (p=0.76). There were four cases of infantile hypertrophic pyloric stenosis (IHPS). Conclusions Azithromycin significantly reduces the risk of BPD in preterm neonates. The relationship between azithromycin and IHPS requires further investigation. PMID:26656010

  17. Azithromycin and survival in Streptococcus pneumoniae pneumonia: a retrospective study

    PubMed Central

    Shorr, Andrew F; Zilberberg, Marya D; Kan, Jason; Hoffman, Justin; Micek, Scott T; Kollef, Marin H

    2013-01-01

    Objective Streptococcus pneumoniae (SP) represents a major pathogen in pneumonia. The impact of azithromycin on mortality in SP pneumonia remains unclear. Recent safety concerns regarding azithromycin have raised alarm about this agent's role with pneumonia. We sought to clarify the relationship between survival and azithromycin use in SP pneumonia. Design Retrospective cohort. Setting Urban academic hospital. Participants Adults with a diagnosis of SP pneumonia (January–December 2010). The diagnosis of pneumonia required a compatible clinical syndrome and radiographic evidence of an infiltrate. Intervention None. Primary and secondary outcome measures Hospital mortality served as the primary endpoint, and we compared patients given azithromycin with those not treated with this. Covariates of interest included demographics, severity of illness, comorbidities and infection-related characteristics (eg, appropriateness of initial treatment, bacteraemia). We employed logistic regression to assess the independent impact of azithromycin on hospital mortality. Results The cohort included 187 patients (mean age: 67.0±8.2 years, 50.3% men, 5.9% admitted to the intensive care unit). The most frequently utilised non-macrolide antibiotics included: ceftriaxone (n=111), cefepime (n=31) and moxifloxacin (n=22). Approximately two-thirds of the cohort received azithromycin. Crude mortality was lower in persons given azithromycin (5.6% vs 23.6%, p<0.01). The final survival model included four variables: age, need for mechanical ventilation, initial appropriate therapy and azithromycin use. The adjusted OR for mortality associated with azithromycin equalled 0.26 (95% CI 0.08 to 0.80, p=0.018). Conclusions SP pneumonia generally remains associated with substantial mortality while azithromycin treatment is associated with significantly higher survival rates. The impact of azithromycin is independent of multiple potential confounders. PMID:23794577

  18. Azithromycin kills invasive Aggregatibacter actinomycetemcomitans in gingival epithelial cells.

    PubMed

    Lai, Pin-Chuang; Walters, John D

    2013-03-01

    Aggregatibacter actinomycetemcomitans invades periodontal pocket epithelium and is therefore difficult to eliminate by periodontal scaling and root planing. It is susceptible to azithromycin, which is taken up by many types of mammalian cells. This led us to hypothesize that azithromycin accumulation by gingival epithelium could enhance the killing of intraepithelial A. actinomycetemcomitans. [(3)H]azithromycin transport by Smulow-Glickman gingival epithelial cells and SCC-25 oral epithelial cells was characterized. To test our hypothesis, we infected cultured Smulow-Glickman cell monolayers with A. actinomycetemcomitans (Y4 or SUNY 465 strain) for 2 h, treated them with gentamicin to eliminate extracellular bacteria, and then incubated them with azithromycin for 1 to 4 h. Viable intracellular bacteria were released, plated, and enumerated. Azithromycin transport by both cell lines exhibited Michaelis-Menten kinetics and was competitively inhibited by l-carnitine and several other organic cations. Cell incubation in medium containing 5 μg/ml azithromycin yielded steady-state intracellular concentrations of 144 μg/ml in SCC-25 cells and 118 μg/ml in Smulow-Glickman cells. Azithromycin induced dose- and time-dependent intraepithelial killing of both A. actinomycetemcomitans strains. Treatment of infected Smulow-Glickman cells with 0.125 μg/ml azithromycin killed approximately 29% of the intraepithelial CFU of both strains within 4 h, while treatment with 8 μg/ml azithromycin killed ≥82% of the CFU of both strains (P < 0.05). Addition of carnitine inhibited the killing of intracellular bacteria by azithromycin (P < 0.05). Thus, human gingival epithelial cells actively accumulate azithromycin through a transport system that facilitates the killing of intraepithelial A. actinomycetemcomitans and is shared with organic cations.

  19. Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses.

    PubMed

    Leclere, M; Magdesian, K G; Cole, C A; Szabo, N J; Ruby, R E; Rhodes, D M; Edman, J; Vale, A; Wilson, W D; Tell, L A

    2012-12-01

    Azithromycin is widely used in foals but has not been studied in adult horses. The goals of this study were to determine the pharmacokinetic profile and to make a preliminary assessment of the safety of azithromycin in adult horses. Azithromycin was administered intravenously (5 mg/kg) and intragastrically (10 mg/kg) to six healthy mares in a crossover design. Serial plasma samples, blood neutrophils, and pulmonary macrophages were collected for the measurement of azithromycin concentrations. Azithromycin was also administered orally (10 mg/kg) once a day for 5 days to five healthy mares for preliminary evaluation of safety in adult horses. The bioavailability of azithromycin following intragastric administration was 45 ± 12%. Concentrations within peripheral neutrophils and bronchoalveolar macrophages were several fold higher than that of plasma. Mild decreases in appetite (n = 3) and alterations in fecal consistency (n = 3) were noted following repeated oral administration. The pharmacokinetic profiles of azithromycin in adult horses, especially the slow elimination rate and intraneutrophil and intrapulmonary macrophage accumulation, demonstrate that it is conducive to use in this age group. Because of the gastrointestinal alterations noted, further studies are warranted before azithromycin can be recommended for use in adult horses.

  20. Azithromycin metabolite identification in plasma, bile, and tissues of the ball python (Python regius).

    PubMed

    Hunter, R P; Koch, D E; Coke, R L; Goatley, M A; Isaza, R

    2003-04-01

    Azithromycin is the first of a class of antibiotics classified as azalides. Six ball pythons (Python regius) were given a single dose of azithromycin at 10 mg/kg p.o. and i.v. in a crossover design. Serial blood samples were collected for unchanged azithromycin and to determine, if possible, the structure and number of circulating azithromycin metabolites. After a 4-month wash-out period, the snakes were given azithromycin p.o. as a single dose of 10 mg/kg for the study of azithromycin metabolism and metabolite tissue distribution. Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment. Unchanged azithromycin accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration. At both 24 and 72 h postadministration, azithromycin accounted for 70% of total azithromycin- associated material in bile. In liver and kidney, unchanged azithromycin accounted for 40% of the total azithromycin-associated material; this doubled in lung and skin. Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes. Four of these possible metabolites: 3'-desamine-3-ene-azithromycin, descladinose dehydroxy-2-ene-azithromycin, 3'-desamine-3-ene descladinose-azithromycin, and 3'-N-nitroso,9a-N-desmethyl-azithromycin are unique to this species. Descladinose-azithromycin, 3'-N-desmethyl,9a-N-desmethyl-azithromycin, and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin were the only metabolites identified in skin. Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin being identified only in the kidney. Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma. The percentage of unchanged azithromycin in bile is not different between the three species.

  1. Azalides from azithromycin to new azalide derivatives.

    PubMed

    Mutak, Stjepan

    2007-02-01

    Azalides are semi-synthetic macrolides, in which a nitrogen atom is introduced into a macrolactone ring via a Beckmann rearrangement. Starting from erythromycin, oximes, depending on the reaction conditions lactams, or bicyclic-imino-ethers were formed, which were further reduced to aminolactones. The cyclic amine 9a- became the precursor for novel, significantly more active derivatives, especially for 9-dihydro-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A with the generic name azithromycin. It showed a broad spectrum of antibacterial activity covering all significant bacteria causing respiratory tract infections. The greatest advantages of azithromycin are its unusual pharmacokinetics (high tissue distribution), metabolic stability and high tolerability. These properties have led in recent years to the widespread use of the azalide scaffold for the synthesis of new compounds with advantageous pharmacokinetics. The azalide scaffold possesses an amino and several hydroxyl groups, which could be substituted or transformed to obtain new compounds. Different derivatives were obtained by substitution on the nitrogen but a large variety of derivatives, such as ethers, esters and carbamates, were made by reactions with various hydroxyl groups. Substitutions on both nitrogen and hydroxyl or two hydroxyl groups yielded new, bridged compounds. The 4''-hydroxy group was oxidized to 4-oxo-, which was transformed via the oxime to 4-amino, or via epoxide to 4''-methylamino compounds. Cleavage of the cladinose sugar and further transformations gave 3-acyl or 3-oxo compounds, which were less active than 14-membered acylides or ketolides. Beckmann rearrangement of some 16-membered macrolide oximes yielded only 17-membered lactams, which were less active than starting macrolides, and could not be reduced to amines. Intramolecular rearrangement of azalide imino-ethers yielded 13-membered azalides. Some new 11a-azalides were obtained after oxidative cleavage of some 16-membered

  2. Topical azithromycin or ofloxacin for endophthalmitis prophylaxis after intravitreal injection

    PubMed Central

    Romero-Aroca, Pedro; Sararols, Laura; Arias, Lluis; Casaroli-Marano, Ricardo P; Bassaganyas, Francisca

    2012-01-01

    Background The number of patients who have undergone intravitreal injections has increased enormously in recent years, but a consensus is still lacking on prophylaxis for endophthalmitis. The aim of this prospective, observational study was to evaluate the prophylactic effect of azithromycin eye drops versus ofloxacin eye drops. Methods The study was conducted in five hospitals in Spain and included all patients undergoing intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib over one year. Patients received azithromycin 15 mg/g eye drops (twice daily on the day prior to injection and for another 2 days) or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days). Results In the azithromycin group, there were 4045 injections in 972 eyes of 701 patients. In the ofloxacin group, there were 4151 injections in 944 eyes of 682 patients. There were two cases of endophthalmitis (0.049%) in the azithromycin group and five (0.12%) in the ofloxacin group. The odds ratio of presenting with endophthalmitis in the ofloxacin group compared with the azithromycin group was 2.37 (95% confidence interval [CI] 1.32–3.72, P < 0.001). There were two cases of noninfectious uveitis after triamcinolone injection in the azithromycin group (0.049%) and two (0.048%) in the ofloxacin group; no significant differences were observed (odds ratio 0.902, 95% CI 0.622–1.407, P = 0.407). Conjunctival hyperemia was observed in 12 cases in the azithromycin group and none in the ofloxacin group. Conclusion The risk of endophthalmitis was significantly greater with ofloxacin than with azithromycin. These findings provide a valuable addition to the ever-increasing pool of information on endophthalmitis prophylaxis after intravitreal injection, although further large-scale studies are required to provide definitive conclusions. PMID:23109798

  3. Increased interferon-gamma, interleukin-12p40 and IL-8 production in Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris: host response but not bacterial species is the determinant factor of the disease.

    PubMed

    Sugisaki, Hitomi; Yamanaka, Keiichi; Kakeda, Masato; Kitagawa, Hiroshi; Tanaka, Kaori; Watanabe, Kunitomo; Gabazza, Esteban C; Kurokawa, Ichiro; Mizutani, Hitoshi

    2009-07-01

    Acne vulgaris is a multifactorial inflammatory disease of the sebaceous follicles of the face and torso that frequently occurs in adolescence. Initially, acne starts as a non-inflammatory comedo. Subsequently, inflammatory reactions evolve to pustules, granulomas and cystic lesions. Many pathogenic mechanisms have been proposed including sebum excretion, obstruction of hair follicles, impaired keratinization of hair epithelium, bacterial overgrowth and immunological mechanisms; the role of Propionibacterium acnes (P. acnes) is particularly important. Facultative anaerobic gram-positive rods have been implicated in acne pathogenesis. However, the host immune response to P. acnes has not been as yet elucidated. The aim of the present study is to evaluate the importance of the immune response to P. acnes and the bacteriological factor in the pathogenesis of acne. P. acnes isolated from acne lesions and healthy volunteers skin were cultured. The peripheral blood mononuclear cells (PBMC) from acne patients or healthy volunteers were stimulated with viable P. acnes, and cytokine production was evaluated using RT-PCR and ELISA. IFN-gamma, IL-12p40, and IL-8 mRNA and protein production were significantly increased in PBMC from acne patients compared to that from normal donors. However, different P. acnes species isolated from acne lesions or normal subjects showed no difference in cytokines production from acne patients and normal subjects PBMC. The inflammatory response of acne appears to be attributable to P. acnes-induced host immune response rather than P. acnes strains from normal skin or acne lesions.

  4. Synergistic regulation of the human interleukin-12 p40 promoter by NFkappaB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages.

    PubMed

    Gri, G; Savio, D; Trinchieri, G; Ma, X

    1998-03-13

    Monocytes/macrophages produce interleukin-12 (IL-12) in response to pathogenic stimulation, whereas most Epstein-Barr virus-transformed (EBV+) B cells constitutively secrete IL-12. The molecular mechanism regulating the constitutive IL-12 gene expression in EBV+ B cells has not been addressed. In this study, using the EBV+ B cell line RPMI-8866, we localized to the human IL-12 p40 promoter two essential cis elements, the NFkappaB site and the Ets site. The NFkappaB site was shown to interact with members of the NFkappaB family: p50 and c-Rel. The Ets site constitutively bound a multi-component Ets-2-containing complex. While the NFkappaB and Ets sites appear equally critical for inducible p40 promoter activity in macrophage cell lines, NFkappaB plays a more dominant role in the constitutive p40 promoter activity in EBV+ B cells. Transient expression of Ets-2 and c-Rel in B, T, and monocytic cell lines synergistically activated the IL-12 p40 promoter, apparently overcoming the requirement for cell type- or stimulant-specific transcription factors. These data provide new evidence that full activation of the human IL-12 p40 promoter may result primarily from the interplay between NFkappaB and Ets family members.

  5. Association of interferon γ T+874A and interleukin 12 p40 promoter CTCTAA/GC polymorphism with the need for respiratory support and perinatal complications in low birthweight neonates

    PubMed Central

    Bokodi, G; Derzbach, L; Bányász, I; Tulassay, T; Vásárhelyi, B

    2007-01-01

    Background Data support the role of interferon (IFN)γ and interleukin (IL)12 in perinatal complications. IFNγ T+874A and IL12 p40 promoter CTCTAA/GC polymorphisms may have an effect on cytokine production. Methods DNA was extracted from dried blood samples of 153 low birthweight (LBW) infants and 172 healthy term infants. IFNγ and IL12 genetic polymorphisms were determined to investigate the association between polymorphisms and ventilation characteristics, bronchopulmonary dysplasia (BPD) and other perinatal disorders. Results The IFNγ+874A allele was over‐represented in LBW infants. Carriers of the IFNγ+874T allele required mechanical ventilation and oxygen supplementation for time periods 41% and 35%, respectively, shorter than those required by those not carrying the IFNγ+874T allele. Stepwise logistic regression analysis showed that carriers of the IFNγ+874T allele were protected against BPD (odds ratio (OR) 0.35 (95% confidence interval (CI) (0.12 to 0.99))) and patent ductus arteriosus (OR 0.43 (95% CI 0.19 to 0.97)), whereas carriers of the IFNγ+874A allele were at higher risk of severe hypotension (OR 3.40 (95% CI 1.01 to 11.52)) and respiratory distress syndrome (OR 4.03 (95% CI 1.30 to 12.50)). Carriers of the IL12 GC allele were protected against pneumonia (OR 0.32 (95% CI 0.14 to 0.75)). Carriers of the IL12 CTCTAA allele were at higher risk of developing necrotising enterocolitis (NEC; OR 2.37 (95% CI 1.01 to 5.53)). Conclusions Carrier state of the IFNγ+874A allele presents an increased risk for premature birth and lung damage, as well as other perinatal complications. The risks of pneumonia and NEC are higher in heterozygotic carriers of the IL12 CTCTAA/GC polymorphism. Further studies are needed to determine whether these associations are the result of altered cytokine‐producing capacity in infants carrying the tested alleles. PMID:16754651

  6. Whole blood stimulation with Toll-like receptor (TLR)-7/8 and TLR-9 agonists induces interleukin-12p40 expression in plasmacytoid dendritic cells in rhesus macaques but not in humans.

    PubMed

    Koopman, G; Beenhakker, N; Burm, S; Bouwhuis, O; Bajramovic, J; Sommandas, V; Mudde, G; Mooij, P; 't Hart, B A; Bogers, W M J M

    2013-10-01

    Macaques provide important animal models in biomedical research into infectious and chronic inflammatory disease. Therefore, a proper understanding of the similarities and differences in immune function between macaques and humans is needed for adequate interpretation of the data and translation to the human situation. Dendritic cells are important as key regulators of innate and adaptive immune responses. Using a new whole blood assay we investigated functional characteristics of blood plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC) and monocytes in rhesus macaques by studying induction of activation markers and cytokine expression upon Toll-like receptor (TLR) stimulation. In a head-to-head comparison we observed that rhesus macaque venous blood contained relatively lower numbers of pDC than human venous blood, while mDC and monocytes were present at similar percentages. In contrast to humans, pDC in rhesus macaques expressed the interleukin (IL)-12p40 subunit in response to TLR-7/8 as well as TLR-9 stimulation. Expression of IL-12p40 was confirmed by using different monoclonal antibodies and by reverse transcription-polymerase chain reaction (RT-PCR). Both in humans and rhesus macaques, TLR-4 stimulation induced IL-12p40 expression in mDC and monocytes, but not in pDC. The data show that, in contrast to humans, pDC in macaques are able to express IL-12p40, which could have consequences for evaluation of human vaccine candidates and viral infection.

  7. The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

    PubMed Central

    Kirkcaldy, Robert D.; Weinstock, Hillard S.; Moore, Page C.; Philip, Susan S.; Wiesenfeld, Harold C.; Papp, John R.; Kerndt, Peter R.; Johnson, Shacondra; Ghanem, Khalil G.; Hook, Edward W.; Newman, Lori M.; Dowell, Deborah; Deal, Carolyn; Glock, Jonathan; Venkatasubramanian, Lalitha; McNeil, Linda; Perlowski, Charlotte; Lee, Jeannette Y.; Lensing, Shelly; Trainor, Nikole; Fuller, Shannon; Herrera, Amelia; Carlson, Jonathan S.; Harbison, Hanne; Lenderman, Connie; Dixon, Paula; Whittington, Allison; Macio, Ingrid; Priest, Carol; Jett, Abi; Campbell, Tracy; Uniyal, Apurva; Royal, LaShawnda; Mejia, Marisol; Vonghack, Jennifer; Tobias, Susan; Zenilman, Jonathan; Long, Jill; Harvey, Alesia; Pettus, Kevin; Sharpe, Samera

    2014-01-01

    Background. Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. Methods. We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15–60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10–17 days after treatment among 401 participants in the per protocol population. Results. Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. Conclusions. Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796. PMID

  8. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea.

    PubMed

    Kirkcaldy, Robert D; Weinstock, Hillard S; Moore, Page C; Philip, Susan S; Wiesenfeld, Harold C; Papp, John R; Kerndt, Peter R; Johnson, Shacondra; Ghanem, Khalil G; Hook, Edward W

    2014-10-15

    Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15-60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10-17 days after treatment among 401 participants in the per protocol population. Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796. Published by Oxford University Press on behalf of the Infectious

  9. Effect of Gingivitis on Azithromycin Concentrations in Gingival Crevicular Fluid

    PubMed Central

    Jain, Nidhi; Lai, Pin-Chuang; Walters, John D.

    2012-01-01

    Aim Macrolide antibiotics yield high concentrations in inflamed tissue, suggesting that their levels in gingival crevicular fluid (GCF) could be increased at gingivitis sites. However, the increased volume of GCF associated with gingivitis could potentially dilute macrolides. To determine whether these assumptions are correct, the bioavailability of systemically-administered azithromycin was compared in GCF from healthy and gingivitis sites. Materials and methods Experimental gingivitis was induced in one maxillary posterior sextant in nine healthy subjects. Contralateral healthy sextants served as controls. Subjects ingested 500 mg of azithromycin followed by a 250 mg dose 24 hours later. Four hours after the second dose, plaque was removed from experimental sites. GCF was collected from 8 surfaces in both the experimental and control sextants and pooled separately. GCF samples were subsequently collected on the 2nd, 3rd, 8th and 15th days and azithromycin content was determined by agar diffusion bioassay. Results On days 2 and 3, the pooled GCF volume at experimental sites was significantly higher than at control sites (P <0.01) and the total azithromycin mass in 30 second GCF samples pooled from experimental sites was significantly higher than at control sites (P < 0.02). However, there were no significant differences in azithromycin concentration between the experimental and control pools at any point. Concentrations exceeded 7.3 μg/ml on day 2 and 2.5 μg/ml on day 15. Conclusions Azithromycin concentrations are similar in GCF from gingivitis sites and healthy sites, suggesting that the processes that regulate GCF azithromycin concentration can compensate for local inflammatory changes. PMID:22220766

  10. Use of azithromycin ophthalmic solution in the treatment of chronic mixed anterior blepharitis.

    PubMed

    John, Thomas; Shah, Ami A

    2008-01-01

    We tested the efficacy of azithromycin ophthalmic solution for the treatment of chronic mixed anterior blepharitis. The findings suggest that patients with chronic mixed anterior blepharitis can be more effectively treated with azithromycin ophthalmic solution than erythromycin ophthalmic ointment. Patients treated with azithromycin ophthalmic solution show an extraordinary clinical response with shorter treatment duration.

  11. Azithromycin Activities against Orientia tsutsugamushi Strains Isolated in Cases of Scrub Typhus in Northern Thailand

    PubMed Central

    Watt, George; Kantipong, Pacharee; Jongsakul, Krisada; Watcharapichat, Pochaman; Phulsuksombati, Duangporn

    1999-01-01

    Azithromycin was given to mice and humans infected with strains of Orientia tsutsugamushi from northern Thailand, where drug-resistant scrub typhus occurs. Azithromycin and doxycycline yielded comparable mouse survival rates (73 and 79%, respectively; P > 0.5). Symptoms, signs, and fever in two pregnant women abated rapidly with azithromycin. Prospective human trials are needed. PMID:10543774

  12. Azithromycin reduces inflammation in a rat model of acute conjunctivitis

    PubMed Central

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

  13. Azithromycin reduces inflammation in a rat model of acute conjunctivitis.

    PubMed

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis.

  14. Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.

    PubMed Central

    Wenisch, C; Parschalk, B; Zedtwitz-Liebenstein, K; Weihs, A; el Menyawi, I; Graninger, W

    1996-01-01

    Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose. PMID:8878577

  15. Mechanism of azithromycin inhibition of HSL synthesis in Pseudomonas aeruginosa

    PubMed Central

    Zeng, Jianming; Zhang, Ni; Huang, Bin; Cai, Renxin; Wu, Binning; E, Shunmei; Fang, Chengcai; Chen, Cha

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of nosocomial infections. Unfortunately, P. aeruginosa has low antibiotic susceptibility due to several chromosomally encoded antibiotic resistance genes. Hence, we carried out mechanistic studies to determine how azithromycin affects quorum sensing and virulence in P. aeruginosa. lasI and rhlI single and double mutants were constructed. We then undertook a quantitative approach to determine the optimal concentration of azithromycin and culture time that can affect the expression of HSLs. Furthermore, based on the above results, the effect on quorum sensing was analyzed at a transcriptional level. It was found that 2 μg/mL azithromycin caused a 79% decrease in 3-oxo-C12-HSL secretion during cultivation, while C4-HSL secretion was strongly repressed in the early stages. Azithromycin acts on ribosomes; to determine whether this can elicit alternative modes of gene expression, transcriptional regulation of representative virulence genes was analyzed. We propose a new relationship for lasI and rhlI: lasI acts as a cell density sensor, and rhlI functions as a fine-tuning mechanism for coordination between different quorum sensing systems. PMID:27075730

  16. [National consensus regarding azithromycin use in cystic fibrosis].

    PubMed

    Abely, M; Jubin, V; Bessaci-Kabouya, K; Chiron, R; Bui, S; Fayon, M

    2015-06-01

    To propose a formalized consensus agreement regarding the prescription of azithromycin in cystic fibrosis (CF). Application of the Delphi method in 5 thematic fields: indications, contra-indications, dosage, precautions for use and treatment follow-up. Thirty identified French CF centers participated in the process on 49 (61%), which comprised 3 rounds. Experts validated azithromycin as a long-term anti-inflammatory agent in children aged over 6 years, presenting with the classical form of CF, irrespective of the bacteriological status of the patient (except for non-tuberculous mycobacteria). Azithromycin administration should not be routine in the milder forms of the disease, and avoided in the presence of severe hepatic or renal involvement. In children whose weight is below 40 kg, a strong consensus recommended a single daily oral dose, administered three times weekly. However, in adults, the level of agreement was weaker. Minimal duration of treatment is 6 months, after which the drug should be discontinued if no observable effect is noted on clinical parameters, exacerbation rate and/or FEV1. Clinical monitoring of treatment tolerance is recommended (nausea, diarrhea, skin rash, tinnitus, deafness, arthropathy), without increasing the frequency of surveillance of sputum bacteria. However, it is essential to monitor sputum for fungi (expectoration, Aspergillus, broncho-pulmonary allergic aspergillosis). This consensus statement defines an area for the prescription of azithromycin in CF, with the aim of better harmonization of its use. Published by Elsevier Masson SAS.

  17. Effects of azithromycin in Pseudomonas aeruginosa burn wound infection

    PubMed Central

    Nichols, DP; Caceres, S; Caverly, L; Fratelli, C; Kim, SH; Malcolm, KC; Poch, KR; Saavedra, M; Solomon, G; Taylor-Cousar, J; Moskowitz, SM; Nick, JA

    2013-01-01

    Background Cutaneous thermal injuries (i.e. burns) remain a common form of debilitating trauma and outcomes are often worsened by wound infection with environmental bacteria, chiefly Pseudomonas aeruginosa. Materials and Methods We tested the effects of early administration of a single dose of azithromycin, with or without subsequent anti-pseudomonal antibiotics, in a mouse model of standardized thermal injury infected with P. aeruginosa on both wound site and systemic infection. We also tested the antimicrobial effects of these antibiotics alone or combined in comparative biofilm and planktonic cultures in vitro. Results In our model, early azithromycin administration significantly reduced wound and systemic infection without altering wound site or circulating neutrophil activity. The antimicrobial effect of azithromycin was additive with ciprofloxacin but significantly reduced the antimicrobial effect of tobramycin. This pattern was reproduced in biofilm cultures and not observed in planktonic cultures of P. aeruginosa. Conclusion these data suggest that early administration of azithromycin following burn-related trauma and infection may reduce P. aeruginosa infection and potential interactions with other antibiotics should be considered when designing future studies. PMID:23478086

  18. Pharmacokinetics of azithromycin after intravenous and intramuscular administration to goats.

    PubMed

    Cárceles, C M; Font, A; Espuny, A; Fernández-Varón, E; Serrano, J M; Escudero, E

    2005-02-01

    Azithromycin is the first of a class of antimicrobial agents designated azalides. The aim of the present study was to investigate the disposition pharmacokinetics of azithromycin in goats and determine its bioavailability. A cross-over study was carried out in two phases separated by 30 days. Azithromycin was administered at a single dose of 20 mg/kg body weight by i.v. and i.m. routes. Plasma concentrations of azithromycin were determined by a modified agar diffusion bioassay. After a single i.v. dose plasma concentrations were best fitted to a three-compartment open model. A two-compartment open model with first-order absorption fitted best after i.m. administration. The values of the pharmacokinetic parameters after i.v. administration were: half-life 32.5 h, apparent volume of distribution at the steady-state 34.5 L/kg, clearance 0.85 L/kg. and mean residence time (MRT) 40.1 h. After i.m. administration half-life of 45.2 h, a MRT of 60.3 h, maximum plasma concentration 0.64 mg/L and a bioavalability 92.2% were obtained. The pharmacokinetic parameters of azithromycin after i.m. administration, principally its long half-life and high bioavailability, could provide an alternative to the oral route of administration in goats, although more studies are needed to establish a suitable pharmaceutical formulation, propose optimun dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

  19. Effects of Azithromycin on Gene Expression Profiles of Proinflammatory and Anti-inflammatory Mediators in the Eyelid Margin and Conjunctiva of Patients With Meibomian Gland Disease

    PubMed Central

    Zhang, Lili; Su, Zhitao; Zhang, Zongduan; Lin, Jing; Li, De-Quan; Pflugfelder, Stephen C.

    2017-01-01

    IMPORTANCE Topical application of azithromycin suppresses expression of proinflammatory mediators while restoring transforming growth factor β1 (TGF-β1) levels as evaluated by eyelid margin and conjunctival impression cytology. OBJECTIVE To explore the effects of azithromycin therapy on expression of proinflammatory and anti-inflammatory mediators in meibomian gland disease (MGD). DESIGN, SETTING, AND PARTICIPANTS Case-control study performed in a clinic setting from August 17, 2010, to December 31, 2010. Sixteen patients with posterior blepharitis and conjunctival inflammation due to MGD were treated with azithromycin, 1%, drops for 4 weeks. Impression cytology of the lower eyelid margin and tarsal conjunctiva to measure cytokine expression by quantitative real-time polymerase chain reaction as well as tear collection to measure matrix metalloproteinase 9 (MMP-9) activity were performed once in 8 asymptomatic healthy control participants and 5 times in the 16 symptomatic patients (every 2 weeks for 8 weeks), before, during, and after azithromycin treatment. EXPOSURE Azithromycin, 1%, drops for 4 weeks. MAIN OUTCOMES AND MEASURES Cytokine expression in the eyelid margin and conjunctiva, and MMP-9 activity in tears. RESULTS Compared with a 1-time measurement of 8 healthy participants, among 16 symptomatic patients, the mean (SD; 95% CI) fold change of expression of proinflammatory mediators interleukin 1β (IL-1β), IL-8, and MMP-9 increased to 13.26 (4.33; 11.14–15.38; P < .001), 9.38 (3.37; 7.73–11.03; P < .001), and 13.49 (4.92; 11.08–15.90; P < .001), respectively, in conjunctival cells and to 11.75 (3.96; 9.81–13.69; P < .001), 9.31 (3.28; 7.70–10.92; P < .001), and 11.52 (3.50; 9.81–13.24; P < .001), respectively, in the eyelid margin of patients with MGD. In contrast, the mean (SD; 96% CI) fold change of expression of TGF-β1 messenger RNA (mRNA) decreased to 0.58 (0.25; 0.46–0.70; P = .02) and 0.63 (0.14; 0.56–0.70; P = .02) in conjunctival

  20. [Azithromycin as an adjuvant therapy in cryptogenic organizing pneumonia].

    PubMed

    Vaz, A P; Morais, A; Melo, N; Caetano Mota, P; Souto Moura, C; Amorim, A

    2011-01-01

    There are literature data about the immunomodulatory properties of some macrolides in cryptogenic organizing pneumonia (COP) as an alternative to corticosteroids in mild disease or as adjuvant to standard therapy. A sixty-year-old female, with a controlled intrinsic asthma, presented with COP and recurrent respiratory exacerbations despite corticosteroid and immunossupressant therapy. Azithromycin (500mg, on alternate days) as an adjuvant to steroids was then started, with clinical and functional improvement and regression of lung infiltrates. Withdrawal of steroids was possible in one year, without evidence of relapse in the next six months. Azithromycin was maintained (three times per week) with no documentation of adverse side effects. This clinical case reinforces the potential role of macrolides anti-inflammatory properties in COP as corticosteroids adjuvant therapy. Copyright © 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  1. Effects of clarithromycin, azithromycin and rifampicin on terbutaline-induced sweating in foals.

    PubMed

    Stieler Stewart, A L; Sanchez, L C; Mallicote, M F; Muniz, A L; Westerterp, M S; Burrow, J A; MacKAY, R J

    2017-09-01

    Erythromycin (ERY) induces anhidrosis in foals. Azithromycin (AZI) and clarithromycin (CLA), often combined with rifampicin (RIF), are commonly used to treat Rhodococcus equi infections, but effects on sweating have not been investigated. To determine the effects of AZI, CLA and RIF on sweat responses in normal foals. Each experiment was a blinded, duplicated, six foal × three period counterbalanced within subjects design (12 foals/experiment). Antimicrobials were given orally for 5 days. In Experiment 1, ERY, AZI and CLA were given. In Experiment 2, ERY, RIF and ERY/RIF combination were used. Quantitative intradermal terbutaline sweat tests were performed daily for 3 days before and 1, 2, 5, 9, 24, and 39 days after treatment. Data were analysed by repeated measures analysis of variance procedures. Significance was P≤0.05. In Experiment 1, all macrolides suppressed sweating although CLA and AZI were less potent than ERY. In Experiment 2, significant sweat suppression occurred in foals given ERY with or without RIF, but there was no effect of RIF alone. Rifampicin reduced sweat suppression by ERY on Day 1 of treatment but not thereafter. Because ERY blood concentrations were not measured, effects of RIF on ERY-induced anhidrosis could not definitively be ascribed to altered ERY bioavailability. All macrolides commonly used to treat R. equi pneumonia, i.e. ERY, AZI and CLA, induce anhidrosis in foals. The potent anti-sudorific effect of ERY is delayed, but not substantially affected by concurrent RIF administration. © 2017 EVJ Ltd.

  2. Pilot study of azithromycin in the treatment of genital donovanosis.

    PubMed Central

    Bowden, F J; Mein, J; Plunkett, C; Bastian, I

    1996-01-01

    OBJECTIVES: To determine the effectiveness of azithromycin, an azalide antibiotic with long tissue half-life, in a pilot study of patients with genital donovanosis in the Northern Territory, Australia. DESIGN: Patients with histologically confirmed donovanosis were randomised to receive one of two open-label azithromycin dosage regimens: Regimen A--1.0 g once weekly for 4 weeks; or Regimen B--500 mg daily for 7 days. Patients were assessed at 6 weeks and classified as either "cured", "improved" or "failed". RESULTS: Seven patients received regimen A and 4 received regimen B. Six weeks after commencing treatment the genital ulcers of four patients receiving regimen A and one patient receiving regimen B had healed; the lesions of the other six patients (3 in each regimen) were "improved". No patient failed to respond and no significant adverse reaction was recognised. The eleven patients were reviewed after completing the six-week trial; all lesions had re-epithelialised without further antibiotic treatment, no relapses had occurred, the longest follow-up period being seven months. A further 17 patients with donovanosis who were unable to meet the entry criteria were also treated successfully with azithromycin during the study period. CONCLUSIONS: This is the first time that azithromycin has been shown to have clinical activity against donovanosis. Poor compliance with prolonged courses of antibiotics is one of the major barriers to control of the disease. Intermittent or short-course therapy, made possible by the long tissue half-life of the drug, could facilitate control of donovanosis in endemic populations if the high cost of medication can be addressed. PMID:8655160

  3. Evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis for experimental murine melioidosis.

    PubMed

    Kenny, Dermot J; Sefton, Armine M; Brooks, Timothy J G; Laws, Thomas R; Simpson, Andrew J H; Atkins, Helen S

    2010-07-01

    The efficacies of the azalide azithromycin and the fluoroquinolones trovafloxacin and grepafloxacin for pre- and post-exposure prophylaxis of infection with high or low challenge doses of Burkholderia pseudomallei strain 576 were assessed in an experimental mouse model. Trovafloxacin and grepafloxacin afforded significant levels of protection, whereas azithromycin was ineffective and potentially detrimental. Overall, the data suggest that some fluoroquinolones may have potential utility in prophylaxis of melioidosis and suggest that azithromycin would not be effective in prophylaxis of B. pseudomallei infection.

  4. Pharmaceutical development and optimization of azithromycin suppository for paediatric use.

    PubMed

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-30

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Inhaled therapies, azithromycin and Mycobacterium abscessus in cystic fibrosis patients.

    PubMed

    Catherinot, Emilie; Roux, Anne-Laure; Vibet, Marie-Anne; Bellis, Gil; Lemonnier, Lydie; Le Roux, Evelyne; Bernède-Bauduin, Claire; Le Bourgeois, Muriel; Herrmann, Jean-Louis; Guillemot, Didier; Gaillard, Jean-Louis

    2013-05-01

    Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

  6. Pharmaceutical development and optimization of azithromycin suppository for paediatric use

    PubMed Central

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B.; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J.; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-01

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. PMID:23220079

  7. Amorphous azithromycin with improved aqueous solubility and intestinal membrane permeability.

    PubMed

    Aucamp, Marique; Odendaal, Roelf; Liebenberg, Wilna; Hamman, Josias

    2015-01-01

    Azithromycin (AZM) is a poorly soluble macrolide antibacterial agent. Its low solubility is considered as the major contributing factor to its relatively low oral bioavailability. The aim of this study was to improve the solubility of this active pharmaceutical ingredient (API) by preparing an amorphous form by quench cooling of the melt and to study the influence of the improved solubility on membrane permeability. The amorphous azithromycin (AZM-A) exhibited a significant increase in water solubility when compared to the crystalline azithromycin dihydrate (AZM-DH). The influence that the improved solubility could have on membrane permeability was also studied. The apparent permeability coefficient (Papp) values of AZM-A were statistically significantly higher (p < 0.05) than crystalline AZM-DH at pH values of 6.8 and 7.2. The results therefore indicated that the improved solubility of AZM in the amorphous form also produced improved permeability across excised intestinal tissue at physiological pH values found in the small intestine.

  8. Preparation, characterization and taste-masking properties of microspheres containing azithromycin.

    PubMed

    Hu, Liandong; Pan, Jianbin; Liu, Ci; Xu, Hongxin; Luo, Liangzhao

    2009-12-01

    The aim of this study was to prepare a microsphere formulation in order to mask the bitter taste of azithromycin. Microspheres of azithromycin with ethyl cellulose were prepared by the modified solvent diffusion method. The microspheres were mixed with other excipients to form orally dry suspensions and the sensory test for taste masking was evaluated. Results demonstrated that the suspension could significantly mask the bitter taste of azithromycin and the relative bioavailability of suspensions to reference preparations was 102.7%. The results indicate that the microsphere formulation can be a promising drug carrier for masking the bitter taste of azithromycin.

  9. [Azithromycin: an anti-inflammatory effect in chronic recurrent multifocal osteomyelitis? A preliminary report].

    PubMed

    Schilling, F; Wagner, A D

    2000-10-01

    In this preliminary communication we report our experience with Azithromycin in patients with Chronic Recurring Multifocal Osteomyelitis (CRMO). Seven out of 13 patients, mainly teenager, showed a fast clinical improvement after they were started on Azithromycin. The immediate therapeutic effect of Azithromycin in patients with CRMO was surprising and lead us to the hypothesis that Azithromycin could have an antiphlogistic in addition to it's antibiotic effect in this disease setting. In patients with reactive chronic pelvic osteomyelitis Azithromycin obviously had a direct influence on the sympathic coxitis. Half of the patients reported an immediate reduction of pain and a significant improvement in range of movement after they were started on Azithromycin. In all cases the clinical and radiographic signs on MRI showed a reduction of the inflammatory process. Experimental animal models have recently shown that macrolids have independent additional antiinflammatory and immunomodulatory effects. The assumed local immunomodulatory effect of Azithromycin potentially is an additional activity to the already known synergistic antimicrobial and antiinflammatory effect. Right now we are in the process of collecting data from patients with SAPHO Syndrome who underwent bone-biopsies for microbiologic and histomorphologic investigations. All patients with the growth of propionibacterium acnes were started on a long-term antibiotic therapy with Azithromycin. This study will possibly help to answer the question of the additional antiphogistic/immunomodulatory effect of Azithromycin in this disease entity and the related CRMO.

  10. Intravenous azithromycin as salvage therapy in a patient with Legionnaire's disease

    PubMed Central

    Dorrell, L; Fulton, B; Ong, E L C

    1994-01-01

    A patient with proven Legionnaire's disease is described whose clinical condition improved with intravenous azithromycin after failure to respond to treatment with erythromycin and rifampicin. Images PMID:8016806

  11. Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia.

    PubMed

    Bohte, R; van't Wout, J W; Lobatto, S; Blussé van Oud Alblas, A; Boekhout, M; Nauta, E H; Hermans, J; van den Broek, P J

    1995-03-01

    Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

  12. Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy.

    PubMed

    Peters, D H; Friedel, H A; McTavish, D

    1992-11-01

    Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower

  13. Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy

    PubMed Central

    Das, Bidyut Kumar

    2011-01-01

    Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy. PMID:22144789

  14. Azithromycin augments rhinovirus-induced IFNβ via cytosolic MDA5 in experimental models of asthma exacerbation.

    PubMed

    Menzel, Mandy; Akbarshahi, Hamid; Tufvesson, Ellen; Persson, Carl; Bjermer, Leif; Uller, Lena

    2017-05-09

    Deficient production of anti-viral interferons (IFNs) may be involved in causing viral-induced asthma exacerbations. Hence, drugs inducing lung IFN production would be warranted. Azithromycin may reduce asthma exacerbations but its modus operandi is unknown. Here, we investigated if azithromycin induces IFNβ expression in vitro in rhinovirus-infected bronchial epithelial cells from asthmatic donors and in vivo in our allergic inflammation-based mouse model of viral stimulus-induced asthma exacerbations. Azithromycin dose-dependently augmented viral-induced IFNβ expression in asthmatic, but not in healthy bronchial epithelial cells. The effect negatively correlated with viral load. Knockdown of MDA5 and RIG-I by siRNA showed involvement of MDA5 but not RIG-I in azithromycin's IFN-inducing effects in vitro. In vivo azithromycin induced IFNβ protein, restoring a reduced lung IFN response exclusively in allergic exacerbating mice. This was associated with induction of interferon-stimulated genes and MDA5, but not RIG-I. We suggest that clinically relevant concentrations of azithromycin produce MDA5-dependent, anti-viral, IFN-inducing effects in bronchial epithelium distinctly from asthmatic donors. Similarly, azithromycin induced MDA5-associated IFN in virally stimulated lungs in vivo exclusively in allergic mice. Effects of azithromycin and MDA5-active drugs on viral-induced exacerbations deserve further research.

  15. The safety of azithromycin in the treatment of adults with community-acquired respiratory tract infections.

    PubMed

    Treadway, Glenda; Pontani, Dennis; Reisman, Arlene

    2002-03-01

    The comparative safety of azithromycin was assessed in adult patients (> or =12 years) with community-acquired respiratory tract infections. Of 3229 patients evaluated, 1616 received azithromycin 500 mg once daily for 3 days and 1613 received standard regimens of amoxycillin, amoxycillin/clavulanic acid, cefaclor, clarithromycin, or roxithromycin. A similar incidence of treatment-related adverse events occurred with azithromycin (10.3%) and comparators (11.5%). Significantly fewer patients were withdrawn from azithromycin than comparator treatment (0.4 versus 2.1%; P=0.0001). Most adverse events were mild/moderate in intensity and affected the gastrointestinal system. Azithromycin was as well tolerated as other antibiotics commonly used for bacterial infections in adults.

  16. Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

    PubMed

    Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

    2017-02-01

    From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

  17. Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge

    PubMed Central

    Balloy, V; Deveaux, A; Lebeaux, D; Tabary, O; le Rouzic, P; Ghigo, J M; Busson, P F; Boëlle, P Y; Guez, J Guez; Hahn, U; Clement, A; Chignard, M; Corvol, H; Burnet, M; Guillot, L

    2014-01-01

    Background and Purpose Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. Experimental Approach We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. Key Results In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg−1, i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1β levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1β levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. Conclusions and Implications Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases. PMID:24417187

  18. Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis.

    PubMed

    Luchs, Jodi

    2008-09-01

    Azithromycin, a broad-spectrum antibiotic with potent anti-inflammatory activities, has the potential to effectively treat blepharitis, an inflammatory disease of the eyelid with abnormal eyelid flora as an etiologic determinant. The present study compared the efficacy of topical azithromycin ophthalmic solution 1% (AzaSite; Inspire Pharmaceuticals, Inc, NC, USA) combined with warm compresses (azithromycin group) to warm compresses alone (compress group) in patients with posterior blepharitis. Twenty-one patients diagnosed with posterior blepharitis were randomized in an open-label study to receive either azithromycin plus warm compresses (10 patients), or compresses alone (11 patients). All patients were instructed to apply compresses to each eye for 5-10 minutes twice daily for 14 days. Each eye in the azithromycin group also received azithromycin solution (1 drop) twice daily for the first 2 days followed by once daily for the next 12 days. Patients were evaluated at study initiation (visit 1) and at end of treatment (visit 2) for the severity of five clinical signs: eyelid debris, eyelid redness, eyelid swelling, meibomian gland (MG) plugging, and the quality of MG secretion. At visit 2, patients also rated their degree of overall symptomatic relief. Twenty patients completed the study. At visit 2, patients in the azithromycin group demonstrated significant improvements in MG plugging, MG secretions, and eyelid redness as compared with the compress group. In the azithromycin group, MG plugging resolved completely in three patients and MG secretion returned to normal in two patients; no such results were seen in the compress group. Furthermore, a higher percentage of patients in the azithromycin group rated overall symptomatic relief as excellent or good. Visual acuity measurements and biomicroscopic evaluation revealed no ocular safety issues. Azithromycin ophthalmic solution in combination with warm compresses provided a significantly greater clinical benefit

  19. Randomized, multicentre study of the efficacy and tolerance of azithromycin versus clarithromycin in the treatment of adults with mild to moderate community-acquired pneumonia. Azithromycin Study Group.

    PubMed

    O'Doherty, B; Muller, O

    1998-12-01

    Adults with mild to moderate community-acquired pneumonia were treated with azithromycin (500 mg once daily for 3 days) or clarithromycin (250 mg twice daily for 10 days) and clinically assessed between days 3 and 7 and days 12 and 16. Patients classified as improved at the day 12-16 visit were also evaluated between days 19 and 23. Two hundred three patients were treated (101 with azithromycin, 102 with clarithromycin). A satisfactory clinical response was recorded at the end of therapy in 83 of 88 (94%) evaluable azithromycin-treated and 84 of 88 (95%) evaluable clarithromycin-treated patients (P=0.518). At day 19-23, only one patient in each treatment group had relapsed. Thirty-one of 32 (97%) pathogens isolated from patients in the azithromycin group were eradicated, compared with 32 of 35 (91%) isolated from clarithromycin patients. In all patients with atypical pneumonia, the clinical response was satisfactory at follow-up. Incidences of treatment-related adverse events were similar for the two groups (P=0.815). Two (2%) clarithromycin patients discontinued therapy due to severe treatment-related adverse events; none in the azithromycin group did. This study shows that a 3-day, once-daily course of azithromycin is as clinically effective and well tolerated as a 10-day, twice-daily course of clarithromycin in the treatment of mild to moderate community-acquired pneumonia.

  20. Pharmacokinetics of azithromycin in the blue and gold macaw (Ara ararauna) after intravenous and oral administration.

    PubMed

    Carpenter, James W; Olsen, John H; Randle-Port, Mary; Koch, David E; Isaza, Ramiro; Hunter, Robert P

    2005-12-01

    Azithromycin is classified as an azalide, a subclass of macrolide antimicrobials with a broad spectrum of activity in vitro against many potential bacterial pathogens including spirochetes, anaerobes, and Chlamydia trachomatis. Because of limited data on the use of azithromycin in avian medicine, this study was designed to determine the pharmacokinetics of azithromycin in blue and gold macaws (Ara ararauna), a species commonly seen in clinical practice. Azithromycin (10 mg/kg) was administered via crop lavage to five birds and intravenously to five birds, and blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr post-azithromycin administration. Following a 4-wk washout period, the study was repeated with a complete crossover study performed. Concentration of azithromycin in plasma samples was quantified using a validated liquid chromatography/mass spectrometry assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Based on the pharmacokinetic data generated from this study, a starting dose of azithromycin at 10 mg/kg p.o. every 48 hr for susceptible bacterial infections in blue and gold macaws is recommended.

  1. Does Mass Azithromycin Distribution Impact Child Growth and Nutrition in Niger? A Cluster-Randomized Trial

    PubMed Central

    Amza, Abdou; Yu, Sun N.; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E.; Zhou, Zhaoxia; West, Sheila K.; Bailey, Robin L.; Gaynor, Bruce D.; Keenan, Jeremy D.; Porco, Travis C.; Lietman, Thomas M.

    2014-01-01

    Background Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth. Methodology In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6–60 months of age. Principal Findings We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49). Conclusions/Significance We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association. PMID:25210836

  2. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients

    PubMed Central

    Menzel, Mandy; Akbarshahi, Hamid; Bjermer, Leif; Uller, Lena

    2016-01-01

    Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin’s emerging role in prevention of exacerbations of COPD. PMID:27350308

  3. Azithromycin: assessment of intrinsic cytotoxic effects on corneal epithelial cell cultures

    PubMed Central

    Mencucci, Rita; Pellegrini-Giampietro, Domenico E; Paladini, Iacopo; Favuzza, Eleonora; Menchini, Ugo; Scartabelli, Tania

    2013-01-01

    Purpose To compare the cytotoxic effects of preservative-free azithromycin on corneal epithelial cells in vivo with those of preservative-free netilmicin and levofloxacin, and the preservative benzalkonium chloride (BAK). Methods Rabbit corneal epithelial cells in vitro were incubated for 15 minutes or 6 hours with commercially available ophthalmic preservative-free netilmicin 0.3%, levofloxacin 0.3%, or azithromycin 1.5% preparations or different concentrations of unpreserved azithromycin and different concentrations of BAK. Qualitative analysis was undertaken using phase-contrast optics to examine the morphological aspects of cell cultures and quantitative analysis was undertaken by measuring the release of the cytoplasmic enzyme lactate dehydrogenase into the medium immediately and 24 hours after exposure to drugs. Finally, we observed the wound-healing rate of mechanically injured corneal epithelial cells exposed to each antibiotic ophthalmic preparation for 48 hours. Results Our results show that both the commercially available unpreserved mono-dose preparation of azithromycin and ophthalmic preparations of azithromycin up to a concentration of 1.5% were virtually devoid of harmful effects under our experimental conditions. This was not significantly different from the results obtained for the other antibiotic preparations (P > 0.05) tested, but was unlike the results obtained for BAK. Azithromycin 1.5% also showed good recovery properties after a mechanical wound test. Conclusion Under our experimental conditions, unpreserved azithromycin 1.5% showed a much lower toxicity than BAK and did not interfere with the wound-healing process. PMID:23737659

  4. Comparison of azithromycin versus clarithromycin in the treatment of patients with upper respiratory tract infections.

    PubMed

    Müller, O

    1993-06-01

    The efficacy and safety of azithromycin and clarithromycin were compared in an open multicentre study involving 380 adult patients with acute otitis media, acute sinusitis, or acute streptococcal pharyngitis or tonsillitis. Patients were assigned randomly to receive azithromycin as a single dose of 500 mg daily for three days, or clarithromycin 250 mg bid for ten days. Overall clinical efficacy was found to be similar in each treatment group at day 10-14, with a satisfactory outcome (cured or improved) in 95% of azithromycin and 96% of clarithromycin patients. Bacteriological efficacy was also similar, with eradication of the pathogen in 94% and 95% of isolates, respectively, in the azithromycin and clarithromycin groups. In otitis media, a satisfactory clinical response was seen in 97% of patients in each treatment group. Azithromycin therapy resulted in a clinical response rate of 93% in sinusitis patients, with bacteriological eradication in 93% of patients. Two patients (who were cured clinically) had persistent pathogens. Similarly, clarithromycin achieved clinical response and bacteriological eradication in 95% and 92% of sinusitis patients, respectively. Pathogens persisted in two patients with clinical cure, and in one case of clinical failure. In pharyngitis or tonsillitis, Streptococcus pyogenes was eradicated successfully in 95% of patients in both groups, and the clinical success rates were 96% and 97% for azithromycin and clarithromycin, respectively. No case of clinical failure was associated with persistence of S. pyogenes infection. At the follow-up assessment of this diagnosis group, reinfection had occurred in three (8%) azithromycin patients and one (3%) clarithromycin patient, and all but one patient remained asymptomatic. Both drugs were well-tolerated, with 8.4% of patients on azithromycin and 7.4% on clarithromycin reporting adverse events, mainly gastrointestinal. It was concluded that a three-day course of azithromycin was as effective and

  5. Evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis against experimental murine Brucella melitensis infection.

    PubMed

    Atkins, Helen S; Spencer, Stephen; Brew, Simon D; Jenner, Dominic C; Sefton, Armine M; MacMillan, Alastair P; Brooks, Timothy J G; Simpson, Andrew J H

    2010-07-01

    The prophylactic potential of the azalide azithromycin as well as the fluoroquinolones trovafloxacin and grepafloxacin was assessed for the control of infection with Brucella melitensis in an experimental mouse model, determined by reduction in splenic bacterial burden. Trovafloxacin showed limited protective efficacy when administered 2h following a low-dose B. melitensis challenge, whereas grepafloxacin was ineffective. In comparison, azithromycin provided significant control of infection both following low- and high-dose challenges. Overall, the data confirm the potential utility of azithromycin in the prophylaxis of brucellosis and suggest that neither trovafloxacin nor grepafloxacin would likely be valuable for post-exposure prophylaxis of Brucella infection.

  6. Azithromycin for the Prevention of COPD Exacerbations: The Good, Bad, and Ugly.

    PubMed

    Taylor, Stephanie Parks; Sellers, Eric; Taylor, Brice T

    2015-12-01

    Long-term azithromycin therapy has been shown to reduce exacerbations of chronic obstructive pulmonary disease (COPD), and is recommended by recent society guidelines for use in COPD patients who are at risk for recurrent exacerbations. However, concerns about adverse effects have limited its widespread adoption. Physicians deciding whether to use long-term azithromycin therapy must weigh each patient's individual risk of cardiovascular complications and both the individual and population impact of macrolide resistance against the expected benefit. This review will summarize evidence on the effectiveness and safety of chronic azithromycin for the prevention of COPD exacerbations. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated with Azithromycin

    NASA Astrophysics Data System (ADS)

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-06-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors, and natural products) are measured using phenotypic assays. However, advances in mass spectrometry-based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. Although previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reduce pathogenicity, we observed no clear decrease in specialized metabolite production.

  8. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated With Azithromycin

    PubMed Central

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-01-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors and natural products) are measured using phenotypic assays. However, advances in mass spectrometry based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. While previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reducing pathogenicity, we observed no clear decrease in specialized metabolite production. PMID:25801585

  9. Possible Involvement of the Drug Transporters P Glycoprotein and Multidrug Resistance-Associated Protein Mrp2 in Disposition of Azithromycin

    PubMed Central

    Sugie, Masami; Asakura, Emiko; Zhao, Ying Lan; Torita, Shoko; Nadai, Masayuki; Baba, Kenji; Kitaichi, Kiyoyuki; Takagi, Kenji; Takagi, Kenzo; Hasegawa, Takaaki

    2004-01-01

    P glycoprotein and multidrug resistance-associated protein 2 (Mrp2), ATP-dependent membrane transporters, exist in a variety of normal tissues and play important roles in the disposition of various drugs. The present study seeks to clarify the contribution of P glycoprotein and/or Mrp2 to the disposition of azithromycin in rats. The disappearance of azithromycin from plasma after intravenous administration was significantly delayed in rats treated with intravenous injection of cyclosporine, a P-glycoprotein inhibitor, but was normal in rats pretreated with intraperitoneal injection erythromycin, a CYP3A4 inhibitor. When rats received an infusion of azithromycin, cyclosporine and probenecid, a validated Mrp2 inhibitor, significantly decreased the steady-state biliary clearance of azithromycin to 5 and 40% of the corresponding control values, respectively. However, both inhibitors did not alter the renal clearance of azithromycin, suggesting the lack of renal tubular secretion of azithromycin. Tissue distribution experiments showed that azithromycin is distributed largely into the liver, kidney, and lung, whereas both inhibitors did not alter the tissue-to-plasma concentration ratio of azithromycin. Significant reduction in the biliary excretion of azithromycin was observed in Eisai hyperbilirubinemic rats, which have a hereditary deficiency in Mrp2. An in situ closed-loop experiment showed that azithromycin was excreted from the blood into the gut lumen, and the intestinal clearance of azithromycin was significantly decreased by the presence of cyclosporine in the loop. These results suggest that azithromycin is a substrate for both P glycoprotein and Mrp2 and that the biliary and intestinal excretion of azithromycin is mediated via these two drug transporters. PMID:14982769

  10. Long-term azithromycin use for treatment of bronchiolitis obliterans syndrome in lung transplant recipients.

    PubMed

    Shitrit, David; Bendayan, Daniele; Gidon, Sahar; Saute, Milton; Bakal, Ilana; Kramer, Mordechai R

    2005-09-01

    Short-term improvement in lung function was observed in 5 of 6 lung transplant recipients with bronchiolitis obliterans syndrome (BOS) who were treated with oral azithromycin. We assessed the long-term effect (mean duration 10 months) of treatment with oral azithromycin in 11 lung transplant recipients with BOS. Mean forced expiratory volume in 1 second (FEV1) was 40 +/- 9% at initiation of azithromycin treatment, 39 +/- 10% after 1 month, 39 +/- 12% after 4 months, 38 +/- 10% after 7 months and 38 +/- 10% after 10 months, respectively (statistically non-significant for all data). We conclude that long-term administration with oral azithromycin does not reverse BOS in lung transplant recipients, but may slow progression of the disease.

  11. Ureaplasma, bronchopulmonary dysplasia, and azithromycin in European neonatal intensive care units: a survey

    PubMed Central

    Pansieri, Claudia; Pandolfini, Chiara; Elie, Valery; Turner, Mark A.; Kotecha, Sailesh; Jacqz-Aigrain, Evelyne; Bonati, Maurizio

    2014-01-01

    A survey was set up to gauge the opinions of neonatologists on the role of Ureaplasma in bronchopulmonary dysplasia (BPD) development, the use of azithromycin for BPD prevention, and the factors influencing azithromycin use in European neonatal intensive care units (NICUs). 167 NICUs participated in the survey, representing 28 European countries. For respondents, the two major perceived risk factors for BPD were prematurity of <28 weeks and high oxygen requirements. Only 38% of NICUs had a protocol for BPD prevention and 47% routinely tested for Ureaplasma. In cases of infection, macrolides were the first choice. Most (78%) NICUs were interested in participating in a trial evaluating azithromycin safety and efficacy in reducing BPD rates. Opinions and clinical practice varied between European neonatal units, and differences in Ureaplasma treatment and prevention of BPD highlight the need for further azithromycin evaluation and for improved therapeutic knowledge in preterms. PMID:24518104

  12. Benefits of additional courses of systemic azithromycin in periodontal disease case report.

    PubMed

    Schmidt, Edgard F; Bretz, Walter A

    2007-01-01

    The strong association of subgingival anaerobic bacteria, such as Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, with destructive periodontal disease has been well documented in the literature. Several double-blind studies have also shown the beneficial use of systemic antimicrobials that are active against these microorganisms in conjunction with conventional periodontal treatment, especially when periodontal abscesses and/or suppuration upon probing are present. Four cases with periodontal abscesses were treated with scaling/root planing in conjunction with systemic azithromycin. Partial improvement led to retreatment with two additional courses of azithromycin. Bone formation was noted on periapical radiographs after the patients took additional courses of azithromycin. In view of the benefits of using additional courses of azithromycin in the treatment of destructive periodontal disease, we conclude that the single course of systemic antimicrobials currently used in periodontal therapy may be insufficient to reach necessary therapeutic levels in infected sites.

  13. Impact of Azithromycin Administration for Trachoma Control on the Carriage of Antibiotic-Resistant Streptococcus pneumoniae

    PubMed Central

    Batt, Sarah L.; Charalambous, Bambos M.; Solomon, Anthony W.; Knirsch, Charles; Massae, Patrick A.; Safari, Salesia; Sam, Noel E.; Everett, Dean; Mabey, David C. W.; Gillespie, Stephen H.

    2003-01-01

    Community distribution of azithromycin has an important role to play in trachoma control. Previous studies have suggested that this may increase the prevalence of macrolide-resistant Streptococcus pneumoniae. S. pneumoniae was isolated from children under 7 years of age in Rombo District, northern Tanzania, before and 2 and 6 months after community-wide administration of azithromycin. Overall carriage rates were 11, 12, and 7%, respectively. Only one macrolide-resistant isolate carrying the mef gene was obtained 6 months after azithromycin administration. This contrasted with cotrimoxazole and penicillin resistance, both of which were common (cotrimoxazole resistance, 42, 43, and 47%, and penicillin resistance, 21, 17, and 16% at baseline, 2 months, and 6 months, respectively). There was a significant association between cotrimoxazole and penicillin resistance (P < 0.0001, Fisher's exact). These data suggest that in communities where macrolide resistance is rare, azithromycin distribution for trachoma control is unlikely to increase the prevalence of resistant organisms. PMID:12936971

  14. Preparation and characterization of azithromycin nanodrug using solvent/antisolvent method

    NASA Astrophysics Data System (ADS)

    Pouretedal, Hamid Reza

    2014-03-01

    Nanoparticles of azithromycin are prepared using solvent/antisolvent precipitation method. The solubility of drug in water and the oral bioavailability are increased with decreasing particle size. The effect of type and concentration of surfactant and feed drug concentration are evaluated on the precipitated particle size. The nano-azithromycin in range 200-400 nm is obtained by the addition of absolute ethanol as solvent, water as antisolvent in presence of Tween® 80 as surfactant. The prepared nanoparticles are characterized by infra-red spectra, particle size distribution, scanning electron microscopy, X-ray diffraction and differential scanning calorimetry. The chemical structure of nanosized azithromycin does not show any change but the crystallinity reduces in comparison with raw drug. Dissolution of azithromycin nanoparticles in purified water and buffer phosphate (pH of 6.0) is 2.93 and 3.36, respectively, times of raw drug in 30 min.

  15. Azithromycin versus Sulfadiazine and Pyrimethamine for non-vision-threatening toxoplasmic retinochoroiditis: A pilot study

    PubMed Central

    Balaskas, Konstantinos; Vaudaux, Jean; Boillat-Blanco, Noémie; Guex-Crosier, Yan

    2012-01-01

    Summary Background The purpose of this pilot study is to compare the efficacy and tolerance of azithromycin alone as opposed to standard treatment with sulfadiazine and pyrimethamine for active, non-vision-threatening toxoplasmic retinochoroiditis. Material/Methods We conducted a prospective, randomized, institutional clinical study comparing azithromycin to sulfadiazine and pyrimethamine for active, non-vision-threatening toxoplasmic retinochoroiditis. Nineteen out of 75 patients fulfilled inclusion criteria and were randomized into 2 treatment regimens. Nine patients were treated with sulfadiazine and pyrimethamine and 10 patients with azithromycin at a dose of 500 mg qd. Main outcome measures assessed were time to sharpening of lesion borders, time to lesion scarring, time to disease inactivity, and treatment tolerance. Results Azithromycin monotherapy achieved lesion scarring and disease inactivity in all but 1 patient. Although no statistically significant difference was found between the 2 patient groups as regards main outcome measures for treatment efficacy, all median times to endpoints (days) were longer for the azithromycin group – time to sharpening of lesion borders on clinical evaluation (25.5 vs. 24) and masked evaluation of photographs (30.5 vs. 24), time to lesion scarring on clinical evaluation (73 vs. 47) and masked evaluation of photographs (71.5 vs. 36) and time to disease inactivity (73 vs. 49). Treatment tolerance was significantly better for the azithromycin group (p=0.0005). Conclusions Azithromycin monotherapy at a dose of 500 mg per day was shown to be effective and well-tolerated for the treatment of active, non-vision-threatening toxoplasmic retinochoroiditis. Duration of treatment was clinically longer for the azithromycin group. PMID:22534709

  16. Nasopharyngeal Pneumococcal Serotypes Before and After Mass Azithromycin Distributions for Trachoma

    PubMed Central

    Keenan, Jeremy D.; Sahlu, Ida; McGee, Lesley; Cevallos, Vicky; Vidal, Jorge E.; Chochua, Sopio; Hawkins, Paulina; Gebre, Teshome; Tadesse, Zerihun; Emerson, Paul M.; Gaynor, Bruce D.; Lietman, Thomas M.; Klugman, Keith P.

    2016-01-01

    Twenty-four Ethiopian communities were randomized to receive either (1) quarterly mass azithromycin distributions for trachoma for 1 year or (2) delayed treatment. Nasopharyngeal swabs collected from separate cross-sectional population-based samples of children were processed for Streptococcus pneumoniae. Mass azithromycin did not significantly alter the pneumococcal serotype distribution, and hence it would not be expected to alter vaccine coverage. PMID:27199475

  17. Comparison of azithromycin versus clarithromycin in the treatment of patients with lower respiratory tract infection.

    PubMed

    Bradbury, F

    1993-06-01

    The efficacy and safety of azithromycin and clarithromycin in lower respiratory tract infection (LRTI) were compared in an open, multicentre study. Five hundred and ten adult patients with a diagnosis of LRTI, including acute bronchitis, acute infective exacerbations of chronic bronchitis (AIECB) or pneumonia were enrolled. The patients were randomly assigned to receive either azithromycin (n = 252) as a single daily dose of 500 mg for three days, or clarithromycin (n = 258) 250 mg twice daily for ten days. In AIECB patients, baseline comparisons of the two treatment groups showed that there were no differences in the number of previous episodes of infection or in the incidence of current or past smokers. The overall clinical efficacy was found to be similar in each treatment group on day 10 to 14, with a satisfactory response (cured or improved) in 94% of azithromycin- and 97% of clarithromycin-treated patients. At follow-up evaluation (day 18 to 22), 97% of azithromycin- and 100% of clarithromycin-treated patients who had improved at day 10 to 14, showed satisfactory outcomes. Bacteriological efficacy was similar in both treatment groups, with eradication of 100% vs 95% of isolates in the azithromycin and clarithromycin groups, respectively. In AIECB, 100% of pathogens were eradicated by azithromycin, although one patient was clinically assessed as failed. Clarithromycin eradicated 93% of pathogens in this group; all patients being assessed as cured or improved. Both drugs were well tolerated, with 9% and 6% of patients reporting adverse events with azithromycin and clarithromycin, respectively. These adverse events were largely gastrointestinal in origin. It was concluded that a three-day course of azithromycin is as effective and well tolerated as a ten-day course of clarithromycin in adults with acute LRTIs.

  18. Effectiveness, tolerability and safety of azithromycin 1% in DuraSite® for acute bacterial conjunctivitis

    PubMed Central

    McLean, Susannah; Sheikh, Aziz

    2010-01-01

    Purpose: Bacterial eye infections are commonly treated with topical antibiotics, despite limited evidence of effectiveness. Azithromycin 1% in DuraSite® is a new formulation of azithromycin in a gel polymer designed for use in acute bacterial conjunctivitis. Methods: We conducted systematic searches of the Cochrane Database of Clinical Trials, PubMed and Google Scholar to find randomized controlled trials of “azithromycin DuraSite®”. These searches of published literature were supplemented with searches for unpublished trials and trials in progress. Results: We found six reports of randomized controlled trials investigating the role of azithromycin 1% in DuraSite® for the management of acute bacterial conjunctivitis. The quality of these trials was judged to be moderate to high. These trials assessed effectiveness, tolerability and safety outcomes, but we found no trials looking at cost-effectiveness. DuraSite® is a relatively stable formulation and so azithromycin 1% in DuraSite® has a simpler dosing schedule than other available topical antibiotics. It appears to be similar to other topical antibiotics in its effectiveness, but minor side effects are quite common. Conclusion: Acute bacterial conjunctivitis is a relatively mild, typically self-limiting, infection. Antibiotics should seldom be required. If, however, a decision to prescribe antibiotics is made, azithromycin 1% in DuraSite® is likely to be broadly comparable in its effectiveness to most other antibiotics used to treat acute bacterial conjunctivitis. Further research is needed to determine its cost-effectiveness. PMID:20517467

  19. Novel Effects of Azithromycin on Tight Junction Proteins in Human Airway Epithelia

    PubMed Central

    Asgrimsson, Valthor; Gudjonsson, Thorarinn; Gudmundsson, Gudmundur Hrafn; Baldursson, Olafur

    2006-01-01

    The macrolide antibiotic azithromycin improves lung function and prognosis among patients with cystic fibrosis or diffuse panbronchiolitis, independently of bacterial eradication. Anti-inflammatory effects have been implicated, but data from in vivo studies are scarce, and the link between abnormal electrolyte content in airway surface liquid and bronchial infections remains uncertain. In the present study, we treated human airway epithelia on filter supports with azithromycin and monitored transepithelial electrical resistance. We found that azithromycin increased transepithelial electrical resistance of airway epithelia in a dose-dependent manner. Immunocytochemistry and Western blotting showed that addition of azithromycin changed the locations of proteins in cell cultures and induced processing of the tight junction proteins claudin-1 and claudin-4, occludin, and junctional adhesion molecule-A. These effects were reversible, and no effect was seen when cells were treated with penicillin or erythromycin. The data indicate that azithromycin increases the transepithelial electrical resistance of human airway epithelia by changing the processing of tight junction proteins. The results are novel and may help explain the beneficial effects of azithromycin in patients with cystic fibrosis, diffuse panbronchiolitis, and community-acquired pneumonia. PMID:16641453

  20. Household willingness to pay for azithromycin treatment for trachoma control in the United Republic of Tanzania.

    PubMed Central

    Frick, Kevin D.; Lynch, Matthew; West, Sheila; Munoz, Beatriz; Mkocha, Harran A.

    2003-01-01

    OBJECTIVE: Household willingness to pay for treatment provides important information for programme planning. We tested for relationships between socioeconomic status, risk of trachoma, perceptions of the effects of azithromycin, and the household willingness to pay for future mass treatment with azithromycin. METHODS: We surveyed 394 households in 6 villages located in central United Republic of Tanzania regarding their willingness to pay for future azithromycin treatment. A random sample of households with children under 8 years of age was selected and interviewed following an initial treatment programme in each village. Data were gathered on risk factors for trachoma, socioeconomic status, and the perceived effect of the initial azithromycin treatment. Ordered probit regression analysis was used to test for statistically significant relationships. FINDINGS: 38% of responding households stated that they would not be willing to pay anything for future azithromycin treatment, although they would be willing to participate in the treatment. A proxy for cash availability was positively associated with household willingness to pay for future antibiotic treatment. Cattle ownership (a risk factor) and being a household headed by a female not in a polygamous marriage (lower socioeconomic status) were associated with a lower willingness to pay for future treatment. A perceived benefit from the initial treatment was marginally associated with a willingness to pay a higher amount. CONCLUSIONS: As those at greatest risk of active trachoma indicated the lowest willingness to pay, imposing a cost recovery fee for azithromycin treatment would likely reduce coverage and could prevent control of the disease at the community level. PMID:12751418

  1. Efficacy of oral azithromycin versus topical tetracycline in mass treatment of endemic trachoma.

    PubMed Central

    Fraser-Hurt, N.; Bailey, R. L.; Cousens, S.; Mabey, D.; Faal, H.; Mabey, D. C.

    2001-01-01

    OBJECTIVE: To compare the impact of mass treatment with oral azithromycin and topical tetracycline on the prevalence of active trachoma. METHODS: A total of 1803 inhabitants from 106 households of eight Gambian villages were randomized, in pairs, to receive either three doses of azithromycin at weekly intervals, or daily topical tetracycline over 6 weeks. Ocular examinations were conducted before treatment, and 2, 6 and 12 months after treatment. FINDINGS: Prior to treatment, 16% of the study participants had active trachoma. Two months after treatment, the prevalence of trachoma was 4.6% and 5.1% in the azithromycin and the tetracycline groups, respectively (adjusted odds ratio (OR) = 1.09; 95% confidence interval (CI) = 0.53, 2.02). Subsequently, the prevalence rose to 16% in the tetracycline group, while remaining at 7.7% in the azithromycin group (adjusted OR at 12 months = 0.52; 95% CI = 0.34, 0.80). At 12 months post-treatment, there were fewer new prevalent cases in the azithromycin group, and trachoma resolution was significantly better for this group (adjusted OR = 2.02; 95% CI = 1.42, 3.50). CONCLUSION: Oral azithromycin therefore appears to offer a means for controlling blinding trachoma. It is easy to administer and higher coverages may be possible than have been achieved hitherto. PMID:11477966

  2. Comparison of therapeutic effects of topical azithromycin solution and systemic doxycycline on posterior blepharitis

    PubMed Central

    Zandian, Mehdi; Rahimian, Neda; Soheilifar, Sanaz

    2016-01-01

    AIM To compare the effect of azithromycin drop and doxycycline capsule on treatment of posterior blepharitis. METHODS Fifty patients (100 eyes) with moderate posterior blepharitis, randomly divided into two therapeutic groups; all the patients got warm eyelid compress and massage three times a day for 3wk. In addition the first group got azithromycin 1% drop, twice daily for 1wk and then one drop daily for 2wk. The second group got oral doxycycline 100 mg daily for 3wk. At the end of the research, patients' signs and symptoms were compared together. ANOVA, Chi-square and Mann-Whitney tests were used for statistical analysis. RESULTS Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms after 3wk. There were no significant differences between symptoms healing rate and foreign body sensation healing in these two groups (P>0.05). However, azithromycin drop was more effective in reduction of eye redness and doxycycline was more effective in meibomian glands plugging healing and reducing the corneal staining. CONCLUSION Topical azithromycin could have similar effects as oral doxycycline on posterior blepharitis in improving subjective symptoms. However, doxycycline can reduce objective signs such as ocular surface staining and meibomian gland plugging more than azithromycin. PMID:27500111

  3. [Resistance to azithromycin of Neisseria gonorrhoeae strains isolated in Poland in 2012-2013 years].

    PubMed

    Młynarczyk-Bonikowska, Beata; Kujawa, Marlena; Młynarczyk, Grażyna; Malejczyk, Magdalena; Majewski, Sławomir

    2014-01-01

    Azithromycin is one of the most commonly used macrolide antibiotics. As other macrolides it inhibits bacterial proteins synthesis by binding with V domene of bacterial 23S rRNA. Resistance to azithromycin can be related to: 1. Mutations in gene encoding 23S rRNA. Significant effect on azithromycin MIC (minimal inhibitory concentration) is not observed when the mutation occurs only in 1 allele. In case of mutations occurring in 4 alleles, more common mutation C2611T is associated with MIC 2-16 mg/L and the second mutation A2059T results in high level resistance to azithromycin MIC > 256 mg/l 2. Over- production of membrane pumps proteins MtrCDE and MacAB, that remove antibiotics from bacterial cells. The mechanism is not able to cause azithromycin resistance itself but coexisting with other mechanisms of resistance can additionally increase MIC. 3. Synthesis of 23S rRNA methylases ErmB, ErmF, ErmC, ErmA. These enzymes cause demethylation of adenine (A2058) in V domain of 23S rRNA. The mechanism was common in the past, but it has been replaced by mutations in in V domain of 23S rRNA. Nowadays 23S rRNA methylases are very rare in N. gonorhoeae. Sixty five Neisseria gonorrhoeae strains isolated from patients of the Department of Dermatology and Venereology in Warsaw in the second half of 2012 and first of 2013 were investigated. The strains were cultured on chocolate agar plates in a 5% CO2 atmosphere at 37 °C and identified by colony morphology, Gram staining and oxidase reaction, followed by carbohydrate utilization test. Azithromycin susceptibility was determined by E-Tests (bioMerieux). Bacteria were incubated at 37°C in 5% CO2 for 24 h on chocolate agar plates. Tests were performed according to producers recommendations. The results (sensitive or resistant) were interpreted according to EUCAST recommendations. The MIC of azithromycin in investigated strains ranged from 0,064 to 4 mg/L, MIC50 = 0.5 mg/L, MIC90 = 2 mg/L. It was shown that only 38.5% of the strains

  4. Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men

    PubMed Central

    Rupasinghe, Thusitha W.; Simpson, Julie A.; Vodstrcil, Lenka A.; Fairley, Christopher K.; McConville, Malcolm J.; Hocking, Jane S.

    2017-01-01

    Chlamydia is the most common bacterial sexually transmitted infection among men who have sex with men. Repeat infection following treatment with 1g azithromycin is common and treatment failure of up to 22% has been reported. This study measured the pharmacokinetics of azithromycin in rectal tissue in men following a single 1g dose to assess whether azithromycin reaches the rectal site in adequate concentrations to kill chlamydia. Ten healthy men took a single oral dose of 1g azithromycin and provided nine self-collected swabs and one blood sample over 14 days. Participant demographics, medications, sexual behaviour, treatment side effects, lubricant use and douching practices were recorded with each swab. Drug concentration over time was determined using liquid chromatography–mass spectrometry and total exposure (AUC0-∞) was estimated from the concentration-time profiles. Following 1g of azithromycin, rectal concentrations peaked after a median of 24 hours (median 133mcg/g) and remained above the minimum inhibitory concentration for chlamydia (0.125mcg/mL) for at least 14 days in all men. AUC0-∞ was the highest ever reported in human tissue (13103((mcg/g).hr)). Tissue concentrations were not associated with weight (mg/kg), but data suggest that increased gastric pH could increase azithromycin levels and diarrhoea or use of water-based lubricants could decrease concentrations. High and sustained concentrations of azithromycin were found in rectal tissue following a single 1g dose suggesting that inadequate concentrations are unlikely to cause treatment failure. Factors effecting absorption (pH and diarrhoea) or drug depletion (douching and water-based lubricants) may be more important determinants of concentrations in situ. PMID:28350806

  5. Neisseria gonorrhoeae with reduced susceptibility to azithromycin--San Diego County, California, 2009.

    PubMed

    2011-05-13

    A single 2 g dose of azithromycin effectively treats genitourinary infections caused by susceptible Neisseria gonorrhoeae and has been used to treat uncomplicated gonorrhea in persons with cephalosporin allergy. However, azithromycin is not recommended as monotherapy because of concern over the emergence of resistance. Instead, a 1 g dose of azithromycin is recommended as a component of dual therapy for gonorrhea, in conjunction with a cephalosporin (i.e., 250 mg of ceftriaxone or 400 mg of cefixime, if ceftriaxone is not an option). During January 1992--July 2009, of 87,566 N. gonorrhoeae isolates tested for azithromycin susceptibility by CDC's national Gonoccoccal Isolate Surveillance Project (GISP), only 39 (0.04%) had minimum inhibitory concentrations (MICs) ≥8 µg/mL (including 25 with 8 µg/mL and 14 with 16 µg/mL), indicating reduced susceptibility; none of the isolates were collected in San Diego County, California (CDC, unpublished data, 2011). During August--October 2009, five of 55 (9.1%) N. gonorrhoeae isolates obtained from men with symptomatic urethritis tested at San Diego County's main municipal sexually transmitted disease (STD) clinic had high azithromycin MICs: three with 8µg/mL and two with 16 µg/mL. This report summarizes the laboratory and epidemiologic findings associated with this reduced susceptibility to azithromycin. In San Diego County, clinicians treating cephalosporin-allergic patients with a 2 g dose of azithromycin for uncomplicated gonorrhea are advised to obtain tests of cure 3 weeks after treatment and to recommend sexual abstinence until a negative test result for gonorrhea is achieved. Continued surveillance for antibiotic resistance and effective control efforts are critical for gonorrhea prevention.

  6. Once weekly azithromycin in secondary prevention of rheumatic fever.

    PubMed

    Gopal, Rakesh; Harikrishnan, S; Sivasankaran, S; Ajithkumar, V K; Titus, T; Tharakan, J M

    2012-01-01

    Rheumatic fever and rheumatic heart disease (RHD) are still important problems in developing countries. Secondary prophylaxis which is the most cost-effective method in preventing recurrences of rheumatic fever is fraught with problems of drug compliance. The utility of 500 mg once weekly azithromycin (AZT), an orally effective long-acting antibiotic was evaluated against oral penicillin (phenoxy methyl penicillin 250 mg twice daily) in this study. Forty-eight consecutive patients (44% males, mean age 29.4 years) with established RHD were randomised into two groups-26 patients received AZT and 22 received oral penicillin. Patients were evaluated at randomisation, at 1 month, 3 months, and 6 months, clinically, serologically and by throat swab culture. End points were absence of streptococcal colonisation, infection or fever at the end of 6 months. During the study, 4 patients (15.4%) in the AZT group developed sore throat and fever, had positive throat culture and positive serology indicating streptococcal infection. None satisfied the criteria for rheumatic fever reactivation. None in the oral penicillin group developed streptococcal infection. In conclusion, weekly 500 mg of AZT is not effective in the prevention of streptococcal throat infection compared to oral penicillin therapy in adult patients with established RHD.

  7. Efficacy and safety of intravenous azithromycin followed by oral azithromycin for the treatment of acute pelvic inflammatory disease and perihepatitis in Japanese women.

    PubMed

    Mikamo, Hiroshige; Iwasaku, Kazuhiro; Yamagishi, Yuka; Matsumizu, Miyako; Nagashima, Masahito

    2014-07-01

    Pelvic inflammatory disease (PID) is mainly caused by ascending infection from the vaginal flora including the sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, and lower genital tract endogenous anaerobes, leading to serious consequences including infertility and ectopic pregnancy. To evaluate the efficacy and safety of azithromycin in the treatment of PID that requires initial intravenous therapy, we conducted a multicenter, unblinded, non-comparative phase 3 trial. Intravenous azithromycin (500 mg, once daily) for 1 or 2 days followed by oral azithromycin (250 mg once daily) to complete a total of 7 days treatment was administered to 60 Japanese women with acute PID. The clinical and bacteriological responses were assessed at the end of treatment, and on Days 15 and 29. The most commonly detected baseline causative pathogens were C. trachomatis (12 strains), Prevotella bivia (10 strains), Streptococcus agalactiae (7 strains), N. gonorrhoeae and Peptostreptococcus anaerobius (6 strains each). The clinical success rate on Day 15 was 94.1% (48/51 subjects including perihepatitis). The clinical efficacy and bacterial eradication rates against C. trachomatis and N. gonorrhoeae (including 2 quinolone-resistant strains) were both 100%. Common treatment-related adverse events were diarrhoea, injection site pain, and nausea. All adverse events were mild or moderate in severity. Azithromycin intravenous-to-oral switch therapy demonstrated excellent clinical and bacteriological effects for PID caused by various etiologic agents including quinolone-resistant strains and strains with low susceptibility to azithromycin at in vitro testing. The therapy was well tolerated in the treatment of PID in Japanese women. NCT00871494. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. In vitro and in vivo activities of azithromycin, a new azalide antibiotic, against chlamydia.

    PubMed Central

    Niki, Y; Kimura, M; Miyashita, N; Soejima, R

    1994-01-01

    The in vitro and in vivo activities of azithromycin against chlamydia were investigated. The MIC of azithromycin for five standard strains of different species of chlamydia and six wild-type strains of Chlamydia pneumoniae was 0.125 microgram/ml, which was superior to that of erythromycin but inferior to those of clarithromycin and minocycline. However, the therapeutic effect of a 7-day course of azithromycin at a dose of 10 mg/kg of body weight administered orally once daily to mice with experimental Chlamydia psittaci pneumonia was excellent, with a 100% survival rate at 14 days after infection, which was the same as that for treatment with minocycline administered at 10 mg/kg twice daily; all erythromycin treated animals died within 10 days. When treatment was discontinued 3 days after the infection, the survival rate for mice treated with azithromycin was 90% and that for mice administered minocycline was 30%. These results suggest that azithromycin may be useful in the treatment of respiratory infections caused by intracellular pathogens, including chlamydia because of its excellent accumulation within host cells. PMID:7840560

  9. Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia.

    PubMed

    Taylor, W R; Richie, T L; Fryauff, D J; Picarima, H; Ohrt, C; Tang, D; Braitman, D; Murphy, G S; Widjaja, H; Tjitra, E; Ganjar, A; Jones, T R; Basri, H; Berman, J

    1999-01-01

    New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.

  10. Antimicrobial susceptibility to azithromycin among Salmonella enterica Typhi and Paratyphi A isolates from India.

    PubMed

    Misra, Richa; Prasad, Kashi Nath

    2016-12-01

    Decreased ciprofloxacin susceptibility (DCS) and multidrug resistance in typhoidal Salmonella isolates in areas of endemicity are significant therapeutic problems. Guidelines for azithromycin disc diffusion and MIC interpretive criteria for Salmonella enterica serovar Typhi were published recently by the Clinical and Laboratory Standards Institute in 2015. We investigated the antimicrobial susceptibility pattern of azithromycin in 100 isolates of Salmonella Typhi (n=80), Paratyphi A (n=18) and B (n=2) recovered from bloodstream infections from January 2013 to December 2015. Zone sizes were extrapolated against MIC values, and a scatter plot was constructed. The azithromycin MICs by Etest ranged from 2 to 16 µg ml-1, while the disc diffusion diameters were from 13 to 22 mm. We observed that the margin of the zone of inhibition around the azithromycin disc may not be very clear and therefore difficult to interpret and that there was wide variation in the zone sizes for the same MIC value in both serovars. DCS was observed in 85 % of Salmonella Typhi recovered (68/80) and in 15/18 (83.3 %) Paratyphi A isolates. Judicious use of azithromycin is advocated as an alternative oral agent in endemic areas where DCS is common.

  11. Efficacy and safety of azithromycin versus lymecyline in the treatment of genital chlamydial infections in women.

    PubMed

    Brihmer, C; Mårdh, P A; Kallings, I; Osser, S; Röbech, M; Sikström, B; Wanger, L

    1996-01-01

    To compare the clinical and microbiological efficacy of azithromycin in curing chlamydial infections in women with that of lymecycline, and with a view of the possibility of minimizing the problem of compliance by means of single-dose administration, 146 women with culture-positive Chlamydia trachomatis infections were randomly assigned to treatment with a 1 g bolus dose of azithromycin or a 10-day course of lymecycline 300 mg twice daily. Clinical and microbiological evaluations were performed and adverse effects monitored at check-ups after 15-35 and 40-65 days. Of the 146 patients enrolled in the study, 120 were evaluable. At the second check-up, C. trachomatis was found to have been eradicated in all patients in both treatment groups. Of the 51 patients who had clinical signs and symptoms of genital infection at enrolment, 96% (22/23) of those in the azithromycin group were considered cured (n = 18) or improved (n = 4), as compared with 100% (28/28) of those considered cured (n = 22) or improved (n = 6) in the lymecycline group. Adverse events related, or possibly related, to treatment were reported by 16 (21.6%) of the lymecycline group, but by only 6 (8.3%) of the azithromycin group. The 2 drugs were comparable with regard to microbiological and clinical efficacy in the treatment of genital chlamydial infection in women. The markedly lower rate of side-effects associated with azithromycin may be a feature conducive to patient compliance.

  12. [Susceptibility to azithromycin and other antibiotics in recent isolates of Salmonella, Shigella and Yersinia].

    PubMed

    Martín-Pozo, Angeles; Arana, David M; Fuentes, Miriam; Alós, Juan-Ignacio

    2014-01-01

    Azithromycin represents an alternative option to treat bacterial diarrhea when the antibiotic therapy is indicated. Little is known regarding the susceptibility to azithromycin in enteropathogens in Spain. The MICs of azithromycin were determined by E-test against Salmonella non-typhi (SNT), Shigella and Yersinia isolates collected over the last three years (2010-2012). In addition, the susceptibility to other antibiotics usually used to treat gastrointestinal diseases was determined in these isolates by using a microdilution method. A total of 139 strains of SNT, Shigella and Yersinia were studied. All of them, except one strain, had a MIC≤16mg/L of azithromycin. In the adult population, 14.7% and 40.6% of SNT and Shigella isolates, respectively, were resistant to at least 2 of following antibiotics: amoxicillin, trimethoprim-sulfamethoxazole and ciprofloxacin. In the pediatric population, 10% of SNT clinical isolates and 28.6% (2/7) of Shigella isolates were resistant to amoxicillin and trimethoprim-sulfamethoxazole. In our experience, azithromycin would be a useful antibiotic alternative to treat bacterial diarrhea. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. Azithromycin-Nonsusceptible Shigella flexneri 3a in Men Who Have Sex with Men, Taiwan, 2015–2016

    PubMed Central

    Liao, Ying-Shu; Liu, Yen-Yi; Lo, Yi-Chun

    2017-01-01

    We report an outbreak of azithromycin-nonsusceptible Shigella flexneri 3a infection in Taiwan associated with men who have sex with men. The bacterial strains belonged to the sublineage A of a recently reported outbreak lineage associated with men who have sex with men, characterized by reduced azithromycin susceptibility and circulation in shigellosis low-risk regions. PMID:28098533

  14. Azithromycin buccal patch in treatment of chronic periodontitis

    PubMed Central

    Latif, Sajith Abdul; Vandana, K. L.; Thimmashetty, J.; Dalvi, Priyanka Jairaj

    2016-01-01

    Aim: This study aims to explore the clinical, microbiological, and biochemical impact of azithromycin (AZM) buccal patch in chronic generalized patients as a monotherapy as well as an adjunct to nonsurgical therapy. Materials and Methods: A parallel design was used forty periodontitis patients were randomly allocated into five groups, namely Group 1 scaling root planing (SRP) alone, Group 2 (SRP + AZM patch group), Group 3 (SRP + AZM tablet group), Group 4 (AZM patch monotherapy), and Group 5 (AZM tablet as monotherapy). Plaque index, gingival bleeding index, modified gingival index, probing pocket depth (PPD), and clinical attachment level (CAL) were assessed at baseline and 21 and 90 days. Subgingival pooled plaque sample was collected to assess periodontopathogens like Porphyromonas gingivalis and Prevotella intermedia (Pi) by anaerobic culture method. Tumor necrosis factor alpha (TNF-α) was also evaluated at baseline and 21 days. Periodontal maintenance was performed in Group 1 until 90th day, and clinical parameter was assessed at the end of 90th day. Results: SRP + AZM tablets showed greater reduction in clinical parameters (P < 0.05) AZM as monotherapy did not offer clinical benefits over SRP. Baseline data were compared at the end, i.e., 90th day a significant reduction in plaque scores, gingival bleeding, and PPD was observed however no significant gain in the clinical attachment was observed. Conclusion: The monotherapy resulted in no improvement of periodontal parameters, microbial parameters, and TNF-α level. It is safe to use AZM + SRP as a mode of nonsurgical treatment in periodontitis patients. PMID:27127325

  15. [Clinical experience on treating Toxoplasma gondii infection during pregnancy by using acetyl spiramycin combined with azithromycin].

    PubMed

    Tang, Hong-xia; Xiong, Xue-feng; Qin, Zhi-qiang

    2013-10-01

    To explore an effective therapy for pregnant Toxoplasma gondii infection by using acetyl spiramycin combined with azithromycin. ELISA and PCR were used to diagnose and evaluate the therapy efficiency to toxoplasmosis in pregnant women. The serological test showed that the positive rates of specific antibodies IgM and IgG to Toxoplasma gondii in 285 pregnant women were 1.05% (3/285) and 5.97% (17/285), respectively. All the 3 cases of serum IgM positive pregnant women received the amniotic fluid PCR tests for Toxoplasma gondii DNA and 2 were positive, and they received spiramycin combined with azithromycin. After the therapy, their serum IgM antibody specific to Toxoplasma gondii and positive amniotic fluid PCR test for Toxoplasma gondii DNA turned to be negative. Acetyl spiramycin in combination with azithromycin is effective in the treatment of pregnant toxoplasmosis.

  16. Degradation studies of azithromycin and its spectrophotometric determination in pharmaceutical dosage forms.

    PubMed

    Sultana, Najma; Arayne, M Saeed; Hussain, Fida; Fatima, Aizaz

    2006-04-01

    A simple, accurate and rapid spectrophotometric method for the estimation of azithromycin has been developed by the acidic hydrolysis of the drug with sulfuric acid and monitoring the absorbance at 482 nm. All variables affecting the reaction conditions such as sulfuric acid concentration, heating time, temperature and dilution solvents were carefully studied. Analytical parameters such as stability, selectivity, accuracy and precision have been established for the method and evaluated statistically to assess the application of the method. The method was applied successfully for the assay of azithromycin dihydrate in pure and pharmaceutical dosage forms as tablets, capsules and suspensions. The method was found to have the advantages for simplicity, stability, sensitivity, reproducibility and accuracy for using as an alternate to the existing non-spectrophotometric methods for the routine analysis of the drug in pharmaceutical formulations and also in pharmaceutical investigations involving azithromycin dihydrate.

  17. Pharmacokinetics and tissue tolerance of azithromycin after intramuscular administration to rabbits.

    PubMed

    Escudero, E; Fernández-Varón, E; Marín, P; Espuny, A; Nájera, M D; Cárceles, C M

    2006-12-01

    The pharmacokinetics of azithromycin after intravenous and intramuscular injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits by using a modified agar diffusion bioassay for determining plasma concentrations. The plasma creatine kinase activity was determined after i.m. administration for the evaluation of the tissue tolerance. The elimination half-lives of azithromycin after intravenous and intramuscular administration were 24.1 and 25.1h, respectively. After intramuscular administration mean peak plasma concentration was 0.26+/-0.01 mg/L and bioavailability was 97.7%. Plasma CK activity rose sharply within 8h after i.m. injection of azithromycin; activity returned to pre-treatment level by 48-72 h post-treatment. The transient rise in serum CK activity indicates some degree of muscle tissue damage at the injection site.

  18. Tolerability of 3-day, once-daily azithromycin suspension versus standard treatments for community-acquired paediatric infectious diseases.

    PubMed

    Treadway, G; Reisman, A

    2001-11-01

    Tolerability of azithromycin oral suspension, 10 mg/kg once daily for 3 days, was assessed in paediatric patients (< or = 18 years) with respiratory or skin and soft-tissue infections. Of 2425 patients evaluated, 1213 received azithromycin and 1212 received standard regimens of amoxycillin/clavulanic acid, cefaclor, cefixime, ceftriaxone, clarithromycin, erythromycin, or penicillin V. The incidence of treatment-related adverse events was significantly lower in patients receiving azithromycin than comparators (7.9 vs. 11.5%, P=0.003), while discontinuation rates were similar (1.0 and 1.1%, respectively). Significantly fewer gastrointestinal events were recorded for azithromycin than comparators (6.5 vs. 9.9%, P=0.002), and their duration was significantly shorter (mean 2.3 vs. 5.0 days, P=0.0001). Azithromycin paediatric oral suspension is well tolerated and associated with significantly fewer adverse events than comparators.

  19. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis in the golden hamster model.

    PubMed

    Sinagra, Angel; Luna, Concepción; Abraham, David; Iannella, Maria del Carmen; Riarte, Adelina; Krolewiecki, Alejandro J

    2007-01-01

    New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions. It was concluded that azithromycin has activity against Leishmania (Viannia) braziliensis but not against Leishmania (Leishmania) amazonensis in this model.

  20. Pilot study of the use of community volunteers to distribute azithromycin for trachoma control in Ghana.

    PubMed Central

    Solomon, A. W.; Akudibillah, J.; Abugri, P.; Hagan, M.; Foster, A.; Bailey, R. L.; Mabey, D. C.

    2001-01-01

    OBJECTIVE: To assess the skills of community health volunteers in diagnosing active trachoma and distributing azithromycin in the Northern Region of Ghana. METHODS: Six community health volunteers from Daboya were trained to diagnose trachoma and to treat the disease using azithromycin. They were also informed of the drug's possible side-effects. Under supervision, each volunteer then examined, and if necessary treated, 15 households. The dose of azithromycin was determined by weight; height was also measured. Tablets were given in preference to suspension when possible. RESULTS: The volunteers' diagnostic sensitivity for active trachoma was 63%; their specificity was 96%. At the household level, their "decision to treat" was correct in 83% of households. In 344 treatment episodes, volunteers planned a dose of azithromycin outside the range 15-30 mg/kg on only seven occasions (2.0% of all planned treatments). The volunteers' drug management skills were good, the response of the community was excellent, and adverse reactions were infrequent. Diagnosis of active trachoma, record-keeping skills, and knowledge of side-effects were found to need greater emphasis in any future education programme. Most people aged four years or older were able to swallow tablets. For those taking tablets, the correlation between the data gathered for height and weight shows that calculating azithromycin doses by height is a valid alternative to calculating it by weight. CONCLUSION: Trained community health volunteers have a potential role in identifying active trachoma and distributing azithromycin. To simplify training and logistics, it may be better to base dosage schedules on height rather than weight for those taking tablets, which included most people aged four years or more in the population studied. PMID:11217675

  1. Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice

    PubMed Central

    Legssyer, Rachida; Huaux, François; Lebacq, Jean; Delos, Monique; Marbaix, Etienne; Lebecque, Patrick; Lison, Dominique; Scholte, Bob J; Wallemacq, Pierre; Leal, Teresinha

    2006-01-01

    Background Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. Methods We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the ΔF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. Results In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-α and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation. Conclusion Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation. PMID:17064416

  2. Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin.

    PubMed

    Aoyama, T; Sunakawa, K; Iwata, S; Takeuchi, Y; Fujii, R

    1996-11-01

    The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg per day for 2 weeks. The newly developed macrolides, clarithromycin and azithromycin, have been demonstrated to be superior to erythromycin because of improved absorption and a longer half-life. As a result, we conducted two separate comparison studies to evaluate the efficacies of clarithromycin, 10 mg/kg per day, twice a day for 7 days, and azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the standard erythromycin regimen. A total of 17 patients, including 10 infants 1 year of age or less, for whom pertussis had been confirmed by culture, were allocated to receive either clarithromycin or azithromycin treatment, and each patient was matched (age, sex, and immunization status) with historical control subjects who had been treated with erythromycin. Eradication rates examined at 1 week after treatment were as follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was detected in either group. All isolated strains of Bordetella pertussis were susceptible to clarithromycin, azithromycin, and erythromycin, and no change in drug susceptibility has been confirmed for the past 20 years in Japan. Because of the very low incidence of pertussis resulting from widespread use of acellular pertussis vaccination, this study did not enroll a large number of patients; however we conclude that short-term treatment with clarithromycin or azithromycin is expected to be equal or superior to the standard long-term erythromycin regimen for pertussis.

  3. Comparison between azithromycin and cefixime in the treatment of typhoid fever in children.

    PubMed

    Begum, B; Haque, M A; Ahmed, M S; Islam, M N; Ahsan, M M; Khan, A H; Hasan, M M; Akhtaruzzaman, M; Hossain, M A; Khaleque, M A; Choudhury, A M; Khatun, A A

    2014-07-01

    An intervention study was carried out in the department of paediatrics of Mymensingh Medical College Hospital, Mymensingh to compare the clinical efficacy of Azithromycin in the treatment of childhood typhoid fever with that of cefixime for a period of one year from January 2011 to December 2011. A total of 60 cases of typhoid fever were enrolled in to a randomized clinical trial and was divided into two groups. The inclusion criteria of the cases were: Documented fever for more than 4 days plus two or more of the following clinical features: toxic physical appearance, intestinal complaints, coated tongue, ceacal gurgling, hepatomegaly and splenomegaly, diarrhoea and constipation plus positive Widal test and/or blood culture positivity. Patients who had complication like GIT heamorrhage; intestinal perforaion and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg/day for a period of 07 days Cefixime was given at a dose of 20mg/kg/day in two divided dose for 14 days. The mean time of defervesence was 4.05+1.14 days with azithromycin and 3.41+0.95 with cefixime respectively. The minimum defervesence time was 02 days and maximum defervesence time was 07 days. Clinical cure rate was 87% in azithromycin group and 93% in cefixime group. No serious adverse effect was noted related to azithromycin and cefixime therapy except nausea, vomiting, diarrhoea and jaundice. It was found that azithromycin is almost as effective as cefixime in the treatment of typhoid fever.

  4. Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

    PubMed Central

    Pomares, Xavier; Montón, Concepción; Espasa, Mateu; Casabon, Jordi; Monsó, Eduard; Gallego, Miguel

    2011-01-01

    Background The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD). Methods We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy. Results Twenty patients who completed the 12-month treatment period were analyzed. No clinically significant adverse events were observed during azithromycin treatment. Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01). The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations. Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations. Conclusion Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD. PMID:22003290

  5. Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin.

    PubMed Central

    Pfefferkorn, E R; Borotz, S E

    1994-01-01

    Azithromycin and spiramycin markedly inhibited the growth of Toxoplasma gondii in cultured human fibroblasts. However, 3 days of treatment were required to reveal their full antitoxoplasma activity. This delayed onset of inhibition was similar to that previously reported for clindamycin. Mutants of T. gondii resistant to azithromycin (AziR-1) and spiramycin (SprR-1) were isolated and compared with a previously described mutant resistant to clindamycin (ClnR-2). Mutant ClnR-2 was cross-resistant to all three antibiotics, while AziR-1 was cross-resistant only to spiramycin and SprR-1 was cross-resistant only to azithromycin. In short-term studies of protein synthesis by freshly prepared extracellular parasites, clindamycin and azithromycin were effective only at concentrations much greater than their 50% inhibitory concentrations in infected cultures and the resistant mutants did not differ from the wild type in antibiotic sensitivity. Thus, protein synthesis on cytoplasmic ribosomes of the parasite did not seem to be the target of these antibiotics. To determine whether mitochondrial protein synthesis in T. gondii was inhibited by clindamycin or azithromycin, wild-type parasites were grown in cultured cells in the presence of antibiotic concentrations well above the 50% inhibitory concentrations. Mitochondrial function, measured by oxygen uptake per purified extracellular parasite, did not decrease substantially, after the parasites had multiplied 11-fold in the presence of antibiotic. Thus, mitochondrial protein synthesis did not seem to be the target of clindamycin or azithromycin. An alternative target is protein synthesis in the putative apicomplexan organelle that has a 35-kb genome. PMID:8141576

  6. [Azithromycin in prophylaxis of intravitreal injections in patients with wet age-related macular degeneration].

    PubMed

    Figurska, Małgorzata

    2011-01-01

    Endophthalmitis is one of the most dangerous complications after intravitreous drug injection. Preparing a patient to the injection general and topical endophtalmitis development risk factors should be eliminated. Antibiotic injection prophylaxis is still an important issue. This research has to evaluate effectiveness and tolerance of Azithromycin (Azyter, Thea), in injection as an antibiotic prophylaxis in patients suffering from age-related macular degeneration (AMD). The study was conducted in Ophtalmology Department (Medical Military Institute, Warsaw, Poland), in the group of 52 patients, who underwent 52 intraocular injections of anti-VEGF because of AMD. Topical Azithromycin had been administrated twice a day to both eyes in 2 days before injection. On the third day injection was performed in aseptic conditions. One drop of Azithromycin had been administrated to each eye directly before injection and one drop after the procedure. At that moment antibiotic prophylaxis was terminated. Topical tolerance and effectiveness were evaluated. In 2 cases (3.8%) intensive allergic reaction was reported (significant conjuctives oedema, itch, bloodshot), what caused change of antibiotic. In 5 cases (9%) light bloodshot was reported. 12 patients (23%) reported light or moderate foreign body sensation and in 2 cases (3.8%) the sensation was significant. No reaction of ophthalmic inflammation was reported 5 days after injection, moreover foreign body sensation and bloodshot were absent. 30 patients (57%) were satisfied with new and simplier scheme of antibiotic injection prophylaxis (twice a day for 3 days). Azithromycin is a comfortable alternative for other topical antibiotics, especially in repetitive procedures like anti-VEGF injections. High Azithromycin concentration in tissues, tear film, and on the ophthalmic surface, protects injection site and inhibits growth of primary and mutual bacterial colonies. Short-term exposition to Azithromycin decrases risk of drug

  7. Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia

    PubMed Central

    Mortensen, Eric M.; Halm, Ethan A.; Pugh, Mary Jo; Copeland, Laurel A.; Metersky, Mark; Fine, Michael J.; Johnson, Christopher S.; Alvarez, Carlos A.; Frei, Christopher R.; Good, Chester; Restrepo, Marcos I.; Downs, John R.; Anzueto, Antonio

    2014-01-01

    Importance Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. Objective The purpose of this study was to examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. Design Retrospective, cohort study comparing older patients hospitalized with pneumonia between fiscal years 2002–2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy Setting This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. Participants Patients were included if they were ≥65 years of age hospitalized with pneumonia and received antibiotic therapy concordant with national clinical practice guidelines. Main Outcome Measures Outcomes included 30 and 90-day all-cause mortality, and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. Results Out of the 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 azithromycin-exposed and 31,863 matched unexposed. There were no significant differences in potential confounders between groups after matching. 90-day mortality was significantly lower in those who received azithromycin (exposed- 17.4% vs. unexposed- 22.3%, odds ratio [OR] 0.73, 95% confidence interval [CI] 0.70–0.76). However, we found significant increased odds of myocardial infarctions (5.1% vs. 4.4%, OR 1.17, 95% CI 1.08–1.25) but not any cardiac event (43.0% vs. 42.7%, OR 1.01, 95% CI 0.98–1.05), cardiac arrhythmias (25

  8. Effects of food on a gastrically degraded drug: azithromycin fast-dissolving gelatin capsules and HPMC capsules.

    PubMed

    Curatolo, William; Liu, Ping; Johnson, Barbara A; Hausberger, Angela; Quan, Ernest; Vendola, Thomas; Vatsaraj, Neha; Foulds, George; Vincent, John; Chandra, Richa

    2011-07-01

    Commercial azithromycin gelatin capsules (Zithromax®) are known to be bioequivalent to commercial azithromycin tablets (Zithromax®) when dosed in the fasted state. These capsules exhibit a reduced bioavailability when dosed in the fed state, while tablets do not. This gelatin capsule negative food effect was previously proposed to be due to slow and/or delayed capsule disintegration in the fed stomach, resulting in extended exposure of the drug to gastric acid, leading to degradation to des-cladinose-azithromycin (DCA). Azithromycin gelatin capsules were formulated with "superdisintegrants" to provide fast-dissolving capsules, and HPMC capsule shells were substituted for gelatin capsule shells, in an effort to eliminate the food effect. Healthy volunteers were dosed with these dosage forms under fasted and fed conditions; pharmacokinetics were evaluated. DCA pharmacokinetics were also evaluated for the HPMC capsule subjects. In vitro disintegration of azithromycin HPMC capsules in media containing food was evaluated and compared with commercial tablets and commercial gelatin capsules. When the two fast-dissolving capsule formulations were dosed to fed subjects, the azithromycin AUC was 38.9% and 52.1% lower than after fasted-state dosing. When HPMC capsules were dosed to fed subjects, the azithromycin AUC was 65.5% lower than after fasted-state dosing. For HPMC capsules, the absolute fasting-state to fed-state decrease in azithromycin AUC (on a molar basis) was similar to the increase in DCA AUC. In vitro capsule disintegration studies revealed extended disintegration times for commercial azithromycin gelatin capsules and HPMC capsules in media containing the liquid foods milk and Ensure®. Interaction of azithromycin gelatin and HPMC capsules with food results in slowed disintegration in vitro and decreased bioavailability in vivo. Concurrent measurement of serum azithromycin and the acid-degradation product DCA demonstrates that the loss of azithromycin

  9. Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release.

    PubMed

    Criqui, G I; Solomon, C; Welch, B S; Ferrando, R E; Boushey, H A; Balmes, J R

    2000-05-01

    Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis. A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8. There were significant (p<0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables. The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.

  10. Antimicrobial susceptibility to azithromycin among Salmonella enterica isolated from the United States

    USDA-ARS?s Scientific Manuscript database

    Due to emerging resistance to traditional antimicrobial agents such as ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from human...

  11. Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA

    PubMed Central

    Papp, John R.; Abrams, A. Jeanine; Nash, Evelyn; Katz, Alan R.; Kirkcaldy, Robert D.; O’Connor, Norman P.; O’Brien, Pamela S.; Harauchi, Derek H.; Maningas, Eloisa V.; Soge, Olusegun O.; Kersh, Ellen N.; Komeya, Alan; Tomas, Juval E.; Wasserman, Glenn M.; Kunimoto, Gail Y.; Trees, David L.

    2017-01-01

    During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options. PMID:28418303

  12. Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA.

    PubMed

    Papp, John R; Abrams, A Jeanine; Nash, Evelyn; Katz, Alan R; Kirkcaldy, Robert D; O'Connor, Norman P; O'Brien, Pamela S; Harauchi, Derek H; Maningas, Eloisa V; Soge, Olusegun O; Kersh, Ellen N; Komeya, Alan; Tomas, Juval E; Wasserman, Glenn M; Kunimoto, Gail Y; Trees, David L; Whelen, A Christian

    2017-05-01

    During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.

  13. Clarithromycin versus azithromycin in the treatment of Mediterranean spotted fever in children: a randomized controlled trial.

    PubMed

    Cascio, Antonio; Colomba, Claudia; Antinori, Spinello; Paterson, David L; Titone, Lucina

    2002-01-15

    We conducted an open-label randomized controlled trial to compare the efficacy and safety of clarithromycin (15/mg/kg/day in 2 divided doses for 7 days) with those of azithromycin (10 mg/kg/day in 1 dose for 3 days) in the treatment of children with Mediterranean spotted fever. Until now, there has not been a gold-standard therapy for this rickettsial disease in children. Eighty-seven children were randomized to receive 1 of the 2 drugs. The mean time to defervescence (+/- standard deviation) was 46.2+/-36.4 h in the clarithromycin group and 39.3+/-31.3 h in the azithromycin group. These differences were not statistically significant and both drugs were equally well-tolerated. Clarithromycin and azithromycin could be acceptable therapeutic alternatives to chloramphenicol and tetracyclines for children aged < or =8 years with Mediterranean spotted fever. Azithromycin, because it has a long half-life, offers the advantages of administration in a single daily dose and a shorter duration of therapy, which could increase compliance in children.

  14. Azithromycin 1.5% ophthalmic solution: efficacy and treatment modalities in chronic blepharitis.

    PubMed

    Fadlallah, Ali; Rami, Hala El; Fahd, Daoud; Dunia, Ibrahim; Bejjani, Riad; Chlela, Elie; Waked, Naji; Jabbour, Elyse; Fahed, Sharbel

    2012-01-01

    To assess the efficacy of topical 1.5% azithromycin in the treatment of moderate to severe chronic blepharitis and to compare the efficacy of two different treatment modalities. A randomized clinical trial included 67 patients with chronic anterior and/or posterior blepharitis, followed-up for 3 months. Signs and symptoms were graded according to severity. Patients were randomized into two groups: 33 patients in group I and 34 patients in group II. Group I patients were treated with topical 1.5% azithromycin twice a day for three days, and Group II patients were treated with topical 1.5% azithromycin twice a day for three days then at bedtime for the rest of the month. All patients were instructed to apply warm compresses and an eye-friendly soap twice daily. Patients in both groups tolerated the treatment with minimal irritation. A significant improvement in signs and symptoms was noted at the one week follow-up visit. Group II showed a more pronounced and longer-lasting improvement that persisted after three months of follow-up. Topical 1.5% azithromycin ophthalmic solution is an effective treatment option for chronic blepharitis. In moderate to severe blepharitis, a one month treatment is safe and shows better improvement than the three-day protocol with no significant relapse until three months of follow-up.

  15. Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis.

    PubMed

    Cory, Theodore J; Birket, Susan E; Murphy, Brian S; Hayes, Don; Anstead, Michael I; Kanga, Jamshed F; Kuhn, Robert J; Bush, Heather M; Feola, David J

    2014-03-01

    Azithromycin treatment improves clinical parameters in patients with CF, and alters macrophage activation from a pro-inflammatory (M1) phenotype to a pro-fibrotic, alternatively activated (M2) phenotype. The transcriptional profile of cells from patients receiving azithromycin is unknown. Gene expression in association with macrophage polarization, inflammation, and tissue remodeling was assessed from sputum samples collected from patients with CF. Transcriptional profiles and clinical characteristics, including azithromycin therapy, were compared. Expression of NOS2 and TNFα was decreased in subjects receiving azithromycin, whereas expression of M2-associated genes was unaffected. Principal component analysis revealed gene expression profiles consistent with M1- (MMP9, NOS2, and TLR4) or M2-polarization (CCL18, fibronectin, and MR1) in select subject groups. These expression signatures did not significantly correlate with clinical characteristics. Pro-inflammatory gene expression was low in subjects receiving AZM. Genes were stratified into groupings characteristic of M1- or M2-polarization, suggesting that overall polarization status is distinct among patient groups. © 2013.

  16. Azithromycin-resistant syphilis-causing strains in Sydney, Australia: prevalence and risk factors.

    PubMed

    Read, Phillip; Jeoffreys, Neisha; Tagg, Kaitlin; Guy, Rebecca J; Gilbert, Gwendolyn L; Donovan, Basil

    2014-08-01

    Azithromycin has shown high efficacy in randomized trials when used for treating infectious syphilis in Africa. However, its use in clinical practice has been limited by the development of antimicrobial drug resistance. Resistance has not previously been reported from Australasia. The aim of this study was to determine the prevalence of and risk factors for azithromycin-resistant syphilis-causing strains in Sydney, Australia. We evaluated 409 samples that were PCR positive for Treponema pallidum DNA collected between 2004 and 2011 for the presence of the A2058G mutation, which confers resistance to macrolide antibiotics such as azithromycin. Overall, 84% of samples harbored the mutation. The prevalence of the mutation increased during the study period (P trend, 0.003). We also collected clinical and demographic data on 220 patients from whom these samples had been collected to determine factors associated with the A2058G mutation; 97% were from men who have sex with men. Reporting sex in countries other than Australia was associated with less macrolide resistance (adjusted odds ratio, 0.25; 95% confidence interval, 0.09 to 0.66; P = 0.005), with other study factors showing no association (age, HIV status, recent macrolide use, stage of syphilis, or history of prior syphilis). Azithromycin cannot be recommended as an alternative treatment for syphilis in Sydney. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  17. Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

    SciTech Connect

    Mahgoub, Afaf . E-mail: afaf_mahgoub@yahoo.com; El-Medany, Azza; Mustafa, Ali; Arafah, Maha; Moursi, Mahmoud

    2005-05-15

    Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNF{alpha}) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNF{alpha} was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNF{alpha} level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.

  18. Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects.

    PubMed Central

    Conte, J E; Golden, J; Duncan, S; McKenna, E; Lin, E; Zurlinden, E

    1996-01-01

    The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The maximum observed concentrations (mean +/- standard deviation) of azithromycin, clarithromycin, 14H, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 microgram/ml, respectively (all at 6 h). None of the antibiotics except clarithromycin (39.6 +/- 41.1 micrograms/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was different for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exhibited the greatest area under the curve (7,403 micrograms.hr ml-1). The peak concentration of clarithromycin (181 +/- 94.1 micrograms/ml) was greater and occurred earlier (6 h), but the area under the curve (2,006 micrograms.hr ml-1) was less than that observed for azithromycin. 14H was detectable in ACs at 6 h (40.3 +/- 5.2 micrograms/ml) and 12 h (32.8 +/- 57.2 micrograms/ml). The peak concentration of ciprofloxacin occurred at 6 h (4.3 +/- 5.2 micrograms/ml), and the area under the curve was 35.0 micrograms.hr ml-1. The data indicate that after the administration of a single dose, azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was

  19. Azithromycin and Levofloxacin Use and Increased Risk of Cardiac Arrhythmia and Death

    PubMed Central

    Rao, Gowtham A.; Mann, Joshua R.; Shoaibi, Azza; Bennett, Charles Lee; Nahhas, Georges; Sutton, S. Scott; Jacob, Sony; Strayer, Scott M.

    2014-01-01

    PURPOSE Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. METHODS We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days. RESULTS During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05–2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20–2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7–3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56–3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32–2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09–2.82). CONCLUSIONS Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period. PMID:24615307

  20. Influence of Body Weight, Ethnicity, Oral Contraceptives, and Pregnancy on the Pharmacokinetics of Azithromycin in Women of Childbearing Age

    PubMed Central

    Habibi, Mitra; Kilpatrick, Sarah J.; Tuomala, Ruth E.; Shier, Janice M.; Wollett, Lori; Fischer, Patricia A.; Khorana, Kinnari S.; Rodvold, Keith A.

    2012-01-01

    Women of childbearing age commonly receive azithromycin for the treatment of community-acquired infections, including during pregnancy. This study determined azithromycin pharmacokinetics in pregnant and nonpregnant women and identified covariates contributing to pharmacokinetic variability. Plasma samples were collected by using a sparse-sampling strategy from pregnant women at a gestational age of 12 to 40 weeks and from nonpregnant women of childbearing age receiving oral azithromycin for the treatment of an infection. Pharmacokinetic data from extensive sampling conducted on 12 healthy women were also included. Plasma samples were assayed for azithromycin by high-performance liquid chromatography. Population data were analyzed by nonlinear mixed-effects modeling. The population analysis included 53 pregnant and 25 nonpregnant women. A three-compartment model with first-order absorption and a lag time provided the best fit of the data. Lean body weight, pregnancy, ethnicity, and the coadministration of oral contraceptives were covariates identified as significantly influencing the oral clearance of azithromycin and, except for oral contraceptive use, intercompartmental clearance between the central and second peripheral compartments. No other covariate relationships were identified. Compared to nonpregnant women not receiving oral contraceptives, a 21% to 42% higher dose-adjusted azithromycin area under the plasma concentration-time curve (AUC) occurred in non-African American women who were pregnant or receiving oral contraceptives. Conversely, azithromycin AUCs were similar between pregnant African American women and nonpregnant women not receiving oral contraceptives. Although higher levels of maternal and fetal azithromycin exposure suggest that lower doses be administered to non-African American women during pregnancy, the consideration of azithromycin pharmacodynamics during pregnancy should guide any dose adjustments. PMID:22106226

  1. Comparative effectiveness of azithromycin for treating scrub typhus: A PRISMA-compliant systematic review and meta-analysis.

    PubMed

    Lee, Szu-Chia; Cheng, Yu-Jyun; Lin, Chao-Hsu; Lei, Wei-Te; Chang, Hung-Yang; Lee, Ming-Dar; Liu, Jui-Ming; Hsu, Ren-Jun; Chiu, Nan-Chang; Chi, Hsin; Peng, Chun-Chih; Tsai, Te-Lung; Lin, Chien-Yu

    2017-09-01

    Scrub typhus is a zoonotic disease that remains an important health threat in endemic areas. Appropriate anti-rickettsial treatment ensures a successful recovery. Doxycycline is a recommended drug, but it is contraindicated in pregnant women and young children. Azithromycin is a safer alternative drug, but its effectiveness remains largely unclear. Herein, we conducted a systematic review and meta-analysis to determine the effectiveness of azithromycin. Studies that investigated azithromycin in treating scrub typhus were systematically identified from electronic databases up to December 2016. Information regarding study population, disease severity, treatment protocols, and responses was extracted and analyzed. In this review, 5 studies were included, which comprised a total of 427 patients. When comparing the treatment failure rate, we observed a favorable outcome in patients treated with azithromycin (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.23-2.98). However, patients in the azithromycin group had longer time to defervescence (mean difference 4.38 hours, 95% CI -2.51 to 11.27) and higher rate of fever for more than 48 hours (RR 1.31, 95% CI 0.81-2.12). Moreover, patients treated with azithromycin had less adverse effects (RR 0.8, 95% CI 0.42-1.52). Azithromycin is as effective as other anti-rickettsial drugs with higher treatment success rates, lower frequency of adverse effects, and longer time to defervescence (GRADE 2B). Therefore, it is reasonable to use azithromycin as the first-line treatment against scrub typhus. Further studies are warranted to elucidate the effectiveness of azithromycin in specific patient groups, at high dose and influence of drug resistance.

  2. Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study

    PubMed Central

    Kvien, T; Gaston, J; Bardin, T; Butrimiene, I; Dijkmans, B; Leirisalo-Repo, M; Solakov, P; Altwegg, M; Mowinckel, P; Plan, P; Vischer, T

    2004-01-01

    Objective: To determine the efficacy of weekly treatment with oral azithromycin for 13 weeks on the severity and resolution of reactive arthritis (ReA). Methods: 186 patients from 12 countries were enrolled in a randomised, double blind, placebo controlled trial. Inclusion criteria were inflammatory arthritis of ⩽6 swollen joints, and disease duration of ⩽2 months. All patients received a single azithromycin dose (1 g) as conventional treatment for possible Chlamydia infection, and were then randomly allocated to receive weekly azithromycin or placebo. Clinical assessments were made at 4 week intervals for 24 weeks. Results: 152 patients were analysable (34 failed entry criteria), with a mean (SD) age of 33.8 (9.4) and duration of symptoms 30.7 (17.5) days. Mean C reactive protein (CRP) was 48 mg/l, and ∼50% of those typed were HLA-B27+, suggesting that the inclusion criteria successfully recruited patients with acute ReA. Treatment and placebo groups were well matched for baseline characteristics. There were no statistical differences for changes in any end point (swollen and tender joint count, joint pain, back pain, heel pain, physician and patient global assessments, and CRP) between the active treatment and placebo groups, analysed on an intention to treat basis or according to protocol completion. The time to resolution of arthritis and other symptoms or signs by life table analyses was also not significantly different. Adverse events were generally mild, but were more commonly reported in the azithromycin group. Conclusions: This large trial has demonstrated that prolonged treatment with azithromycin is ineffective in ReA. PMID:15308521

  3. Long term effects of azithromycin in patients with cystic fibrosis: a double blind, placebo controlled trial

    PubMed Central

    Clement, A; Tamalet, A; Leroux, E; Ravilly, S; Fauroux, B; Jais, J‐P

    2006-01-01

    Background Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis. Methods A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrolment were age older than 6 years and forced expiratory volume in 1 second (FEV1) of 40% or more. The active group received either 250 mg or 500 mg (body weight < or ⩾40 kg) of oral azithromycin three times a week for 12 months. The primary end point was change in FEV1. Results Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative change in FEV1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p<0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio 0.37 (95% CI 0.22 to 0.63), p<0.0001), and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status (count ratio 0.55 (95% CI 0.36 to 0.85), p<0.01). No severe adverse events were reported. Conclusion Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa. PMID:16809416

  4. Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep.

    PubMed

    Cárceles, C M; Font, A; Escudero, E; Espuny, A; Marín, P; Fernández-Varón, E

    2005-10-01

    The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.

  5. Revisit of fluoroquinolone and azithromycin susceptibility breakpoints for Salmonella enterica serovar Typhi.

    PubMed

    Das, Surojit; Ray, Ujjwayini; Dutta, Shanta

    2016-07-01

    In recent years, increase in occurrence of fluoroquinolone (FQ)-resistant S almonella Typhi isolates has caused considerable inconvenience in selecting appropriate antimicrobials for treatment of typhoid. The World Health Organization (WHO) recommends azithromycin for the empirical treatment option of uncomplicated typhoid. The CLSI updated the breakpoints of disc diffusion (DD) and MIC results of FQs and azithromycin for Salmonella Typhi in 2015, but DD breakpoints of ofloxacin and levofloxacin were not included. In this study, the inhibition zone diameters and MICs of nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin and azithromycin were determined in Salmonella Typhi Kolkata isolates (n =146) over a 16-year period (1998 to 2013) and the data were compared with the available CLSI breakpoints. Very major error and major error (ME) of FQs were not observed in the study isolates, but the minor error of ciprofloxacin (15.8 %) and ME of azithromycin (3.5 %) exceeded the acceptable limit. A positive correlation between MICs of FQ and mutations in the quinolone-resistance-determining region (QRDR) showed the reliability of MIC results to determine FQ susceptibility of Salmonella Typhi (n =74). Isolates showing decreased ciprofloxacin susceptibility (MIC 0.125-0.5 µg  ml-1) were likely to have at least one mutation in the QRDR region. The results on DD breakpoints of ofloxacin (resistant, ≤15 mm; intermediate, 16-24 mm, and susceptible, ≥25 mm) and levofloxacin (resistant, ≤18 mm; intermediate, 19-27 mm, and susceptible, ≥28 mm) corroborated those of earlier studies. In view of the emerging FQ- and azithromycin-resistant Salmonella Typhi isolates, DD and MIC breakpoints of those antimicrobials should be revisited routinely.

  6. Efficacy and safety of short duration azithromycin eye drops versus azithromycin single oral dose for the treatment of trachoma in children: a randomised, controlled, double-masked clinical trial.

    PubMed

    Cochereau, Isabelle; Goldschmidt, Pablo; Goepogui, André; Afghani, Tayyab; Delval, Laurent; Pouliquen, Pascale; Bourcier, Tristan; Robert, Pierre-Yves

    2007-05-01

    Efficacy and safety of a short-duration treatment of azithromycin 1.5% eye drops versus oral azithromycin to treat active trachoma. Randomised, controlled, double-masked, double-dummy, non-inferiority explanatory study including 670 children from Guinea Conakry and Pakistan if: 1-10 years old; active trachoma (TF+TI0 or TF+TI+ on simplified World Health Organisation (WHO) scale). Three groups received either: azithromycin 1.5% eye drops twice daily for 2 days, for 3 days or azithromycin single 20 mg/kg oral dose. Patients' contacts were treated whenever possible. Clinical evaluation was performed using a binocular loupe. Primary efficacy variable was the cure (no active trachoma (TF0)) at day 60. Non-inferiority margin for difference between cure rates was 10%. Cure rate in per protocol set was as follows: 93.0%, 96.3% and 96.6% in 2-day group 3-day group, and oral treatment group, respectively. Azithromycin 1.5% groups were non-inferior to oral azithromycin. The intend to treat (ITT) analysis supported the results. Clinical re-emergence rate was low: 4.2%. Ocular tolerance was similar for all groups. No treatment related adverse events were reported. Logistic regression analyses found prognostic factors such as: country (p<0.001) and trachoma severity (p = 0.003). In active trachoma, azithromycin eye drops twice daily for 2 or 3 days are as efficient as the WHO's reference treatment and represent an innovative alternative to oral azithromycin.

  7. Efficacy and safety of short duration azithromycin eye drops versus azithromycin single oral dose for the treatment of trachoma in children: a randomised, controlled, double‐masked clinical trial

    PubMed Central

    Cochereau, Isabelle; Goldschmidt, Pablo; Goepogui, André; Afghani, Tayyab; Delval, Laurent; Pouliquen, Pascale; Bourcier, Tristan; Robert, Pierre‐Yves

    2007-01-01

    Aims Efficacy and safety of a short‐duration treatment of azithromycin 1.5% eye drops versus oral azithromycin to treat active trachoma. Methods Randomised, controlled, double‐masked, double‐dummy, non‐inferiority explanatory study including 670 children from Guinea Conakry and Pakistan if: 1–10 years old; active trachoma (TF+TI0 or TF+TI+ on simplified World Health Organisation (WHO) scale). Three groups received either: azithromycin 1.5% eye drops twice daily for 2 days, for 3 days or azithromycin single 20 mg/kg oral dose. Patients' contacts were treated whenever possible. Clinical evaluation was performed using a binocular loupe. Primary efficacy variable was the cure (no active trachoma (TF0)) at day 60. Non‐inferiority margin for difference between cure rates was 10%. Results Cure rate in per protocol set was as follows: 93.0%, 96.3% and 96.6% in 2‐day group 3‐day group, and oral treatment group, respectively. Azithromycin 1.5% groups were non‐inferior to oral azithromycin. The intend to treat (ITT) analysis supported the results. Clinical re‐emergence rate was low: 4.2%. Ocular tolerance was similar for all groups. No treatment related adverse events were reported. Logistic regression analyses found prognostic factors such as: country (p<0.001) and trachoma severity (p = 0.003). Conclusions In active trachoma, azithromycin eye drops twice daily for 2 or 3 days are as efficient as the WHO's reference treatment and represent an innovative alternative to oral azithromycin. PMID:17005549

  8. In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum.

    PubMed

    Jesus, Francielli P K; Loreto, Érico S; Ferreiro, Laerte; Alves, Sydney H; Driemeier, David; Souza, Suyene O; França, Raqueli T; Lopes, Sonia T A; Pilotto, Maiara B; Ludwig, Aline; Azevedo, Maria I; Ribeiro, Tatiana C; Tondolo, Juliana S M; Santurio, Janio M

    2015-10-12

    The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.

  9. In Vitro and In Vivo Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum

    PubMed Central

    Jesus, Francielli P. K.; Loreto, Érico S.; Ferreiro, Laerte; Driemeier, David; Souza, Suyene O.; França, Raqueli T.; Lopes, Sonia T. A.; Pilotto, Maiara B.; Ludwig, Aline; Azevedo, Maria I.; Ribeiro, Tatiana C.; Tondolo, Juliana S. M.

    2015-01-01

    The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model. PMID:26459895

  10. Sub-MICs of Azithromycin Decrease Biofilm Formation of Streptococcus suis and Increase Capsular Polysaccharide Content of S. suis

    PubMed Central

    Yang, Yan-Bei; Chen, Jian-Qing; Zhao, Yu-Lin; Bai, Jing-Wen; Ding, Wen-Ya; Zhou, Yong-Hui; Chen, Xue-Ying; Liu, Di; Li, Yan-Hua

    2016-01-01

    Streptococcus suis (S. suis) caused serious disease symptoms in humans and pigs. S. suis is able to form thick biofilms and this increases the difficulty of treatment. After growth with 1/2 minimal inhibitory concentration (MIC) of azithromycin, 1/4 MIC of azithromycin, or 1/8 MIC of azithromycin, biofilm formation of S. suis dose-dependently decreased in the present study. Furthermore, scanning electron microscopy analysis revealed the obvious effect of azithromycin against biofilm formation of S. suis. Especially, at two different conditions (1/2 MIC of azithromycin non-treated cells and treated cells), we carried out comparative proteomic analyses of cells by using iTRAQ technology. Finally, the results revealed the existence of 19 proteins of varying amounts. Interestingly, several cell surface proteins (such as ATP-binding cassette superfamily ATP-binding cassette transporter (G7SD52), CpsR (K0FG35), Cps1/2H (G8DTL7), CPS16F (E9NQ13), putative uncharacterized protein (G7SER0), NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (G5L259), putative uncharacterized protein (G7S2D6), amino acid permease (B0M0G6), and NsuB (G5L351)) were found to be implicated in biofilm formation. More importantly, we also found that azithromycin affected expression of the genes cps1/2H, cpsR and cps16F. Especially, after growth with 1/2 MIC of azithromycin and 1/4 MIC of azithromycin, the capsular polysaccharide content of S. suis was significantly higher. PMID:27812354

  11. Comparison of Azithromycin and Amoxicillin Prior to Dental Implant Placement: An Exploratory Study of Bioavailability and Resolution of Postoperative Inflammation

    PubMed Central

    Escalante, Mariana Gil; Eubank, Tim D.; Leblebicioglu, Binnaz; Walters, John D.

    2015-01-01

    Background Studies suggest that a single prophylactic dose of amoxicillin reduces early implant complications, but it is unclear whether other antibiotics are also effective. This study compared the local antimicrobial and anti-inflammatory effects resulting from a single dose of azithromycin or amoxicillin prior to surgical placement of one-stage dental implants. Methods Healthy adult patients requiring one-stage dental implant placement were randomly allocated to receive either 2g amoxicillin (n=7) or 500mg azithromycin (n=6) prior to surgery. Peri-implant crevicular fluid (PICF) samples from the new implant and gingival crevicular fluid (GCF) from adjacent teeth were sampled on postoperative days 6, 13 and 20. Inflammatory mediators in the samples were analyzed by immunoassay and antibiotic levels were measured by bioassay. Results On day 6, azithromycin concentrations in GCF and PICF were 3.39±0.73μg/ml and 2.77±0.90μg/ml, respectively, while amoxicillin was below the limit of detection. During early healing, patents in the azithromycin group exhibited a significantly greater decrease in GCF volume (p=0.03, ANOVA). At specific times during healing, the azithromycin group exhibited significantly lower levels of IL-6 and IL-8 in GCF than the amoxicillin group and exhibited significantly lower levels of G-CSF, IL-8, MIP-1β and IP-10 in PICF. Conclusions Azithromycin was available at the surgical site for a longer period of time than amoxicillin, and patients taking azithromycin exhibited lower levels of specific pro-inflammatory cytokines and chemokines in GCF and PICF. Thus, preoperative azithromycin may enhance resolution of postoperative inflammation to a greater extent than amoxicillin. PMID:26252749

  12. Chloroquine-Azithromycin Combination Antimalarial Treatment Decreases Risk of Respiratory- and Gastrointestinal-Tract Infections in Malawian Children

    PubMed Central

    Gilliams, Elizabeth A.; Jumare, Jibreel; Claassen, Cassidy W.; Thesing, Phillip C.; Nyirenda, Osward M.; Dzinjalamala, Fraction K.; Taylor, Terrie; Plowe, Christopher V.; Tracy, LaRee A.; Laufer, Miriam K.

    2014-01-01

    Background. Chloroquine-azithromycin is being evaluated as combination therapy for malaria. It may provide added benefit in treating or preventing bacterial infections that occur in children with malaria. Objective. We aim to evaluate the effect of treating clinical malaria with chloroquine-azithromycin on the incidence of respiratory-tract and gastrointestinal-tract infections compared to treatment with chloroquine monotherapy. Methods. We compared the incidence density and time to first events of respiratory-tract and gastrointestinal-tract infections among children assigned to receive chloroquine-azithromycin or chloroquine for all symptomatic malaria episodes over the course of 1 year in a randomized longitudinal trial in Blantyre, Malawi. Results. The incidence density ratios of total respiratory-tract infections and gastrointestinal-tract infections comparing chloroquine-azithromycin to chloroquine monotherapy were 0.67 (95% confidence interval [CI], .48, .94) and 0.74 (95% CI, .55, .99), respectively. The time to first lower-respiratory-tract and gastrointestinal-tract infections were significantly longer in the chloroquine-azithromycin arm compared to the chloroquine arm (P = .04 and P = .02, respectively). Conclusions. Children treated routinely with chloroquine-azithromycin had fewer respiratory and gastrointestinal-tract infections than those treated with chloroquine alone. This antimalarial combination has the potential to reduce the burden of bacterial infections among children in malaria-endemic countries. PMID:24652498

  13. Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis.

    PubMed

    Upadhyay, Kirtikumar; Hiregoudar, Basu; Meals, Elizabeth; English, Boyce Keith; Talati, Ajay J

    2017-01-01

    Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation. TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end. GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005). Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

  14. Comparison of two azithromycin distribution strategies for controlling trachoma in Nepal.

    PubMed Central

    Holm, S. O.; Jha, H. C.; Bhatta, R. C.; Chaudhary, J. S.; Thapa, B. B.; Davis, D.; Pokhrel, R. P.; Yinghui, M.; Zegans, M.; Schachter, J.; Frick, K. D.; Tapert, L.; Lietman, T. M.

    2001-01-01

    OBJECTIVE: The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS: The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS: Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION: Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma. PMID:11285662

  15. Higher organism load associated with failure of azithromycin to treat rectal chlamydia.

    PubMed

    Kong, F Y S; Tabrizi, S N; Fairley, C K; Phillips, S; Fehler, G; Law, M; Vodstrcil, L A; Chen, M; Bradshaw, C S; Hocking, J S

    2016-09-01

    Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.

  16. Restoration of Chloride Efflux by Azithromycin in Airway Epithelial Cells of Cystic Fibrosis Patients▿

    PubMed Central

    Saint-Criq, Vinciane; Rebeyrol, Carine; Ruffin, Manon; Roque, Telma; Guillot, Loïc; Jacquot, Jacky; Clement, Annick; Tabary, Olivier

    2011-01-01

    Azithromycin (AZM) has shown promising anti-inflammatory properties in chronic obstructive pulmonary diseases, and clinical studies have presented an improvement in the respiratory condition of cystic fibrosis (CF) patients. The aim of this study was to investigate, in human airway cells, the mechanism by which AZM has beneficial effects in CF. We demonstrated that AZM did not have any anti-inflammatory effect on CF airway cells but restored Cl− efflux. PMID:21220528

  17. The HPLC assay of concentration of azithromycin from two different manufacturers in gingival crevicular fluid (GCF)

    PubMed Central

    Khosravi-Samani, Mahmoud; Dehshiri, Khashayar; Kazemi, Sohrab; Shiran, Mohamadreza; Mohgadamnia, Ali-Akbar

    2016-01-01

    Background: Azithromycin (AZM) is used in periodontal infections. The present study compared gingival crevicular fluid concentration of azithromycin of two pharmaceutical companies through the HPLC method. Methods: Two groups (n=15) of healthy volunteers participated in this study. The first group received an imported azithromycin (ImAZM) tablet (250 mg, PO) and the second group received an azithromycin tablet (250 mg PO) manufactured by an Iranian pharmaceutical company (IrAZM). Intrasulcular paper points (#30) were used in inter-proximal areas of molars and canines to collect gingival crevicular fluid samples at 6, 12, 36, 84 and 156 hours after drug administration. Results: The maximum concentration of AZM in gingival crevicular fluid was detected in each group 36 hour after administration. The concentration levels for the participants receiving ImAZM and IrAZM were 14.38±5.75 and 12.64±3.53 ng/mL, respectively. The pharmacokinetic (PK) modeling data showed half-life of AZM was 107.47 hr & 91.42 hr while the clearance was 113.02 hr &119.0 hr for the group receiving ImAZM and IrAZM, respectively. No significant differences were observed in other PK parameters, areas under the concentration time curves for the groups were almost identical. Conclusion: According to the results, there were no significant differences between the PK parameters of ImAZM and IrAZM products. It may be concluded that different doses of AZM have relatively similar PK parameters among the healthy participants. PMID:27999643

  18. Efficacy of Doxycycline, Azithromycin, or Trovafloxacin for Treatment of Experimental Rocky Mountain Spotted Fever in Dogs

    PubMed Central

    Breitschwerdt, E. B.; Papich, M. G.; Hegarty, B. C.; Gilger, B.; Hancock, S. I.; Davidson, M. G.

    1999-01-01

    Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration. PMID:10103185

  19. Review of Azithromycin Ophthalmic 1% Solution (AzaSite®) for the Treatment of Ocular Infections

    PubMed Central

    Opitz, Dominick L.; Harthan, Jennifer S.

    2012-01-01

    AzaSite® (azithromomycin 1.0%) ophthalmic solution was approved in 2007 by the US Food and Drug Administration (FDA) as the first commercially available formulation of ophthalmic azithromycin for the treatment of bacterial conjunctivitis. AzaSite® utilizes a vehicle delivery system called DuraSite®, which stabilizes and sustains the release of azithromycin to the ocular surface, leading to a longer drug residence time, less frequent dosing, and an increase in patient compliance. AzaSite® is a broad spectrum antibiotic, effective against Gram-positive, Gram-negative, and atypical bacteria. AzaSite® has been studied for the treatment of ocular conditions beyond its clinical indication. A number of clinical studies have evaluated its efficacy and safety in the management of ocular conditions such as bacterial conjunctivitis and blepharitis on both the pediatric and adult populations. This article aims to evaluate the peer-reviewed published literature on the use of azithromycin 1.0% ophthalmic for current and possible future ophthalmic uses. PMID:23650453

  20. Azithromycin for the treatment of eosinophilic nasal polyposis: Clinical and histologic analysis

    PubMed Central

    Borges Crosara, Paulo Fernando Tormin; Cassali, Geovanni Dantas; dos Reis, Diego Carlos; Rodrigues, Danilo Santana; Nunes, Flavio Barbosa; Guimarães, Roberto Eustáquio Santos

    2016-01-01

    Introduction: Macrolides used as immunomodulators are a promising tool for chronic inflammatory airway diseases. Eosinophilic nasal polyposis (ENP) is still considered a disease that is difficult to control with the currently standardized treatments. Objectives: To evaluate prolonged treatment with low-dose azithromycin for ENP based on clinical and histopathologic variables. Methods: The present investigation was a self-paired case study of 33 patients with ENP. A comparison was performed between patients before and after treatment with azithromycin for 8 weeks. The patients were subjected to clinical examinations, staging (three-dimensional imaging by endoscopy), application of the questionnaire, and biopsy of nasal polyps at the beginning and at the end of the treatment. Results: The treatment yielded a clinical improvement regarding the two variables studied: polyposis staging (69.7%) and questionnaire (57.6%). We did not find significant differences in the inflammatory pattern and in the percentage or absolute number of eosinophils per field between samples obtained before and after the treatment (p > 0.05). There was no difference between the answers obtained from groups with and without asthma and/or aspirin intolerance (p > 0.3). The patients with advanced initial staging exhibited lower subjective improvement index and staging reduction (p = 0.031 and p = 0.012, respectively). Conclusion: Based on this study, azithromycin may be considered as another therapeutic option for ENP. However, further studies are necessary to define the real mechanism of action involved. PMID:27465667

  1. Efficacy of a three day course of azithromycin in moderately severe community-acquired pneumonia.

    PubMed

    Rizzato, G; Montemurro, L; Fraioli, P; Montanari, G; Fanti, D; Pozzoli, R; Magliano, E

    1995-03-01

    This study was designed to evaluate the efficacy of a 3 day course of azithromycin in low to moderately severe community-acquired pneumonia. Forty patients with low to moderately severe community-acquired pneumonia (29 males, 11 females, mean age 46 +/- 17 yrs; 20 pretreated with betalactams for 2-10 days with no results before admission to hospital; 18 with evidence of co-morbidity) were enrolled in an open, randomized study with azithromycin, 500 mg q.d. oral therapy for 3 days, versus clarithromycin, 250 mg b.i.d. oral therapy for 10 +/- 2 days. The aetiology of pneumonia was identified in 18 patients by serology (nine Mycoplasma pneumoniae, four Chlamydia pneumoniae, five Legionella pneumophila; one patient with chlamydial infection also had Klebsiella pneumoniae bacteraemia). A presumptive aetiological diagnosis was obtained with sputum culture in three other patients (one Haemophilus influenzae, two Haemophilus parainfluenzae), all strains were sole isolates with 10(8) Colony forming units (CFU), and with Gram stain in one patient with Streptococcus pneumoniae. All patients in the azithromycin group (one after a second 3 day course), and all but two (of those available for evaluation) of the clarithromycin group were cured. Defervescence occurred after 2.6 +/- 1.6 days, and chest roentgenogram cleared after 8.9 +/- 3.3 days, with no difference between the two groups. Tolerance was good, and there were no withdrawals from therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

    PubMed Central

    Chico, R Matthew; Pittrof, Rudiger; Greenwood, Brian; Chandramohan, Daniel

    2008-01-01

    In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp. PMID:19087267

  3. A case of community-acquired pneumonia due to Legionella pneumophila serogroup 9 in which initial treatment with single-dose oral azithromycin appeared useful.

    PubMed

    Ito, Akihiro; Ishida, Tadashi; Tachibana, Hiromasa; Ito, Yuhei; Takaiwa, Takuya; Fujii, Hiroyuki; Hashimoto, Toru; Nakajima, Hiroshi; Amemura-Maekawa, Junko

    2017-09-11

    Legionella species are important causative pathogens for severe community-acquired pneumonia (CAP). Most cases of Legionella pneumonia are due to Legionella pneumophila serogroup 1, and CAP due to Legionella pneumophila serogroup 9 is rare. A fourth case of CAP due to Legionella pneumophila serogroup 9 is reported, and initial treatment using single-dose oral azithromycin appeared useful. Azithromycin injection or fluoroquinolone injection is usually recommended for the treatment of Legionella pneumonia, and no previous reports have shown the effectiveness of single-dose oral azithromycin. This case report is therefore valuable from the perspective of possible treatment for mild to moderate Legionella pneumonia using single-dose oral azithromycin.

  4. Case report: failure under azithromycin treatment in a case of bacteremia due to Salmonella enterica Paratyphi A

    PubMed Central

    2014-01-01

    Background Limited information is available regarding the clinical efficacy of azithromycin for the treatment of enteric fever due to fluoroquinolone-resistant Salmonella Typhi and Salmonella Paratyphi among travelers returning to their home countries. Case presentation We report a case of a 52-year-old Japanese man who returned from India, who developed a fever of 39°C with no accompanying symptoms 10 days after returning to Japan from a 1-month business trip to Delhi, India. His blood culture results were positive for Salmonella Paratyphi A. He was treated with 14 days of ceftriaxone, after which he remained afebrile for 18 days before his body temperature again rose to 39°C with no apparent symptoms. He was then empirically given 500 mg of azithromycin, but experienced clinical and microbiological failure of azithromycin treatment for enteric fever due to Salmonella Paratyphi A. However, the minimum inhibitory concentration (MIC) of azithromycin was not elevated (8 mg/L). He was again given ceftriaxone for 14 days with no signs of recurrence during the follow-up. Conclusion There are limited data available for the treatment of enteric fever using azithromycin in travelers from developed countries who are not immune to the disease, and thus, careful follow-up is necessary. In our case, the low azithromycin dose might have contributed the treatment failure. Additional clinical data are needed to determine the rate of success, MIC, and contributing factors for success and/or failure of azithromycin treatment for both Salmonella Typhi and Salmonella Paratyphi infections. PMID:25041573

  5. Azithromycin and loperamide are comparable to levofloxacin and loperamide for the treatment of traveler's diarrhea in United States military personnel in Turkey.

    PubMed

    Sanders, John W; Frenck, Robert W; Putnam, Shannon D; Riddle, Mark S; Johnston, James R; Ulukan, Sefa; Rockabrand, David M; Monteville, Marshall R; Tribble, David R

    2007-08-01

    The recommended treatment for traveler's diarrhea is the combination of an appropriate antibiotic (usually a fluoroquinolone) and loperamide. Azithromycin compared favorably with fluoroquinolones in trials that did not include the use of loperamide, but combination therapy has not, to our knowledge, been studied to date. A randomized, double-blind trial was conducted at Incirlik Air Base, Turkey, fromJ une 2003 through August 2004. Adults from the United States with noninflammatory diarrhea were randomized to receive a single dose of azithromycin (1000 mg; 106 persons) or levofloxacin (500 mg; 101 persons) plus loperamide (4 mg initially and as needed thereafter). Volunteers maintained a symptom diary and were evaluated on days 1, 3, and 7 after treatment. No differences were noted with respect to pretreatment symptoms or pathogen distribution. Enterotoxigenic Escherichia coli was the most common pathogen isolated (from 45% of patients in the azithromycin group and 42% of patients in the levofloxacin group), and Campylobacter species was the second most common pathogen isolated (from 6% of patients in the azithromycin group and 9% of patients in the levofloxacin group). Median time to last diarrheal stool (azithromycin group, 13 h; levofloxacin group, 3 h), median time to resolution of associated symptoms (2 days), and additional loperamide usage (azithromycin group, 39% of patients; levofloxacin group, 34% of patients) were similar between groups. Azithromycin use was associated with more nausea in the 30 min after dosing (azithromycin group, 8% of patients; levofloxacin group, 1% of patients; Pp.004), but no vomiting or other adverse events were noted in either group. Single-dose treatment with azithromycin (1000 mg) and loperamide is as effective as single-dose treatment with levofloxacin (500 mg) and loperamide for noninflammatory diarrhea. Although nausea after dosing is uncommon, it is more frequently associated with azithromycin than with levofloxacin

  6. Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen.

    PubMed

    Tribble, David R; Sanders, John W; Pang, Lorrin W; Mason, Carl; Pitarangsi, Chittima; Baqar, Shahida; Armstrong, Adam; Hshieh, Paul; Fox, Anne; Maley, Elisabeth A; Lebron, Carlos; Faix, Dennis J; Lawler, James V; Nayak, Gautam; Lewis, Michael; Bodhidatta, Ladaporn; Scott, Daniel A

    2007-02-01

    Traveler's diarrhea in Thailand is frequently caused by Campylobacter jejuni. Rates of fluoroquinolone (FQ) resistance in Campylobacter organisms have exceeded 85% in recent years, and reduced fluoroquinolone efficacy has been observed. Azithromycin regimens were evaluated in a randomized, double-blind trial of azithromycin, given as a single 1-g dose or a 3-day regimen (500 mg daily), versus a 3-day regimen of levofloxacin (500 mg daily) in military field clinics in Thailand. Outcomes included clinical end points (time to the last unformed stool [TLUS] and cure rates) and microbiological end points (pathogen eradication). A total of 156 patients with acute diarrhea were enrolled in the trial. Campylobacter organisms predominated (in 64% of patients), with levofloxacin resistance noted in 50% of Campylobacter organisms and with no azithromycin resistance noted. The cure rate at 72 h after treatment initiation was highest (96%) with single-dose azithromycin, compared with the cure rates of 85% noted with 3-day azithromycin and 71% noted with levofloxacin (P=.002). Single-dose azithromycin was also associated with the shortest median TLUS (35 h; P=.03, by log-rank test). Levofloxacin's efficacy was inferior to azithromycin's efficacy, except in patients with no pathogen identified during the first 24 h of treatment or in patients with levofloxacin-susceptible Campylobacter isolates, in whom it appeared to be equal to azithromycin. The rate of microbiological eradication was significantly better with azithromycin-based regimens (96%-100%), compared with levofloxacin (38%) (P=.001); however, this finding was poorly correlated with clinical outcome. A higher rate of posttreatment nausea in the 30 min after receipt of the first dose (14% vs. <6%; P=.06) was observed as a mild, self-limited complaint associated with single-dose azithromycin. Single-dose azithromycin is recommended for empirical therapy of traveler's diarrhea acquired in Thailand and is a reasonable first

  7. Two regimens of azithromycin prophylaxis against community-acquired respiratory and skin/soft-tissue infections among military trainees.

    PubMed

    Guchev, Igor A; Gray, Gregory C; Klochkov, Oleg I

    2004-04-15

    Epidemics of community-acquired pneumonia (CAP) are a frequent cause of morbidity among Russian military trainees. We evaluated azithromycin prophylaxis against CAP. In 2001-2002, incoming military trainees were randomized to 1 of 3 trial arms by training group: azithromycin, 500 mg per week for 8 weeks (R1); azithromycin, 1500 mg once at enrollment (R2); or no therapy (R3). During the 22 weeks of training, CAP was diagnosed in 20.2% of 678 subjects in the R3 group, 8.6% of 508 subjects in the R1 group, and 10.3% of 507 subjects in the R2 group. Throat carriage cultures revealed that the proportion of Streptococcus pneumoniae isolates with resistance to macrolides correspondingly increased during the study, from 0% (all) to 40% (R1) and 22.6% (R2) by week 20. Azithromycin prophylaxis is effective against CAP in a healthy population of young men at transient high risk of disease; however, azithromycin use must be tempered with the possible concomitant risk of selection for resistant endemic pathogens.

  8. An assessment of the tolerability of moxifloxacin 0.5% compared to azithromycin 1.0% in DuraSite.

    PubMed

    Granet, David; Lichtenstein, Steven J; Onofrey, Bruce; Katz, James A

    2007-12-01

    This subject-masked, randomized, active and placebo-controlled study compared subjects' perceptions of two antibiotic ophthalmic drops. One hundred and twenty-five healthy volunteers received two of the following solutions: moxifloxacin 0.5% ophthalmic solution (Vigamox((R)), Alcon Laboratories, Inc., Ft Worth, TX, USA), azithromycin 1% in DuraSite((R)) (AzaSite(), Inspire Pharmaceuticals, Inc., Durham, NC, USA), or Tears Naturale II((R)) (Alcon Laboratories, Inc., Ft. Worth, TX, USA) in contralateral eyes. Immediately following instillation and at 1, 3, 5, and 10 minutes thereafter, subjects rated comfort, acceptability, and blurring on 0-10 point analog scales stating their preference of treatment. Among subjects receiving moxifloxacin and azithromycin in contralateral eyes, 84% preferred moxifloxacin. Moxifloxacin was rated more comfortable and acceptable with less blurring than azithromycin (p < 0.0001). These differences were observed in both the adult and pediatric populations. Ocular adverse events (redness, irritation, stinging, burning, dryness, itching and chemosis) were observed in 18 (17.3%) eyes receiving azithromycin and 1 (1%) eye receiving moxifloxacin. Moxifloxacin was significantly more tolerable than azithromycin in healthy adult and pediatric eyes. Tolerability and patient acceptance affect compliance; thus these data should be of significance to the clinician.

  9. Frequency of development and associated physiological cost of azithromycin resistance in Chlamydia psittaci 6BC and C. trachomatis L2.

    PubMed

    Binet, Rachel; Maurelli, Anthony T

    2007-12-01

    Azithromycin is a major drug used in the treatment and prophylaxis of chlamydial infections. Spontaneous azithromycin-resistant mutants of Chlamydia psittaci 6BC were isolated in vitro in the plaque assay at a frequency of about 10(-8). Isogenic clonal variants with A(2058)C, A(2059)G, or A(2059)C mutations in the unique 23S rRNA gene (Escherichia coli numbering system) displayed MICs for multiple macrolides (i.e., azithromycin, erythromycin, josamycin, and spiramycin) at least 100 times higher than those of the parent strain and were also more resistant to the lincosamide clindamycin. Chlamydia trachomatis L2 variants with a Gln-to-Lys substitution in ribosomal protein L4 at position 66 (E. coli numbering system), conferring an eightfold decrease in azithromycin and erythromycin sensitivities and a fourfold decrease in josamycin and spiramycin sensitivities, were isolated following serial passage in subinhibitory concentrations of azithromycin. Each mutation was stably maintained in the absence of selection but severely affected chlamydial infectivity, as determined by monitoring the development of each isolate over 46 h in the absence of selection, in pure culture or in 1:1 competition with the isogenic parent. Data in this study support the hypothesis that the mechanisms which confer high-level macrolide resistance in chlamydiae carry a prohibitive physiological cost and may thus limit the emergence of highly resistant clones of these important pathogens in vivo.

  10. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia

    PubMed Central

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18–24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID:27405358

  11. In Vitro Synergism between Azithromycin or Terbinafine and Topical Antimicrobial Agents against Pythium insidiosum

    PubMed Central

    Itaqui, Sabrina R.; Verdi, Camila M.; Tondolo, Juliana S. M.; da Luz, Thaisa S.; Alves, Sydney H.; Santurio, Janio M.

    2016-01-01

    We describe here in vitro activity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC90 between 2 and 32 μg∕ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%). In vivo experimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused by Pythium insidiosum. PMID:27216049

  12. In Vitro Synergism between Azithromycin or Terbinafine and Topical Antimicrobial Agents against Pythium insidiosum.

    PubMed

    Itaqui, Sabrina R; Verdi, Camila M; Tondolo, Juliana S M; da Luz, Thaisa S; Alves, Sydney H; Santurio, Janio M; Loreto, Érico S

    2016-08-01

    We describe here in vitro activity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC90 between 2 and 32 μg∕ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%). In vivo experimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused by Pythium insidiosum. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. Efficacy of azithromycin 1% ophthalmic solution for treatment of ocular surface disease from posterior blepharitis.

    PubMed

    Opitz, Dominick L; Tyler, Keith F

    2011-03-01

    Posterior blepharitis is an eyelid disease primarily of the meibomian glands. Bacteria and chronic inflammation are contributing factors for meibomian gland disease, which leads to ocular surface and tear film alterations and chronic patient symptoms. Azithromycin 1.0% ophthalmic solution is a broad spectrum topical antibiotic with anti-inflammatory properties. The present study evaluates the efficacy of azithromycin 1.0% ophthalmic solution in the treatment of the clinical signs and symptoms, including vision-related function, associated with meibomian gland dysfunction. In an open label study, 33 patients with meibomian gland dysfunction were treated with azithromycin 1.0% ophthalmic solution twice a day for two days, then every evening for a total of 30 days. Tear break-up time, corneal staining, conjunctival staining, Schirmer scores with anaesthetic, meibomian gland score and patient's symptom scores were evaluated at baseline and after 30 days of treatment. The Ocular Surface Disease Index (OSDI) was administered at baseline, after two weeks of treatment and after 30 days of treatment. Twenty-six of 33 patients completed the study. Tear break-up time and Schirmer score increased by 52.7 per cent (p < 0.0001) and 24 per cent (p < 0.05), respectively. There was a reduction in corneal and conjunctival staining by 83.2 and 67.9 per cent, respectively (p < 0.0001). Lid margin scores were reduced by 33.9 per cent (p < 0.0001). The patient's symptom score improved from 2.73 at baseline to 2.21 after 30 days of treatment (p < 0.01). The mean OSDI at baseline was 34.44. After two weeks and 30 days of treatment, the ODSI was 14.51 and 13.15 respectively (p < 0.0001). These results demonstrate clinically and statistically significant improvement in the signs and symptoms associated with posterior blepharitis. Based on these results, azithromycin 1% ophthalmic solution offers a viable option for the treatment of posterior blepharitis. © 2010 The Authors. Clinical and

  14. Influence of the test medium on azithromycin and erythromycin regression statistics.

    PubMed

    Barry, A L; Fuchs, P C

    1991-10-01

    Azithromycin and erythromycin disk test results were compared to MIC values obtained in six different media. One hundred isolates were tested in triplicate, and geometric mean MICs were plotted against arithmetic mean zone diameters and regression statistics calculated. The test media evaluated did not markedly influence MIC values, but incubation in 5-7% CO2 resulted in a two- to four-fold decrease in the activity of both drugs. For testing Haemophilus influenzae and other species that need to be tested in 5-7% CO2, interpretive breakpoints for the macrolides and azalides should be modified to compensate for the anticipated decrease in activity.

  15. The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis.

    PubMed

    Kong, Fabian Yuh Shiong; Tabrizi, Sepehr N; Fairley, Christopher Kincaid; Vodstrcil, Lenka A; Huston, Wilhelmina M; Chen, Marcus; Bradshaw, Catriona; Hocking, Jane S

    2015-05-01

    There are increasing concerns about treatment failure following treatment for rectal chlamydia with 1 g of azithromycin. A systematic review and meta-analysis was conducted to investigate the efficacy of 1 g of azithromycin as a single dose or 100 mg of doxycycline twice daily for 7 days for the treatment of rectal chlamydia. Medline, Embase, PubMed, Cochrane Controlled Trials Register, Australia New Zealand Clinical Trial Register and ClinicalTrials.gov were searched to the end of April 2014. Studies using 1 g of azithromycin or 7 days of doxycycline for the treatment of rectal chlamydia were eligible. Gender, diagnostic test, serovar, symptomatic status, other sexually transmitted infections, follow-up time, attrition and microbial cure were extracted. Meta-analysis was used to calculate pooled (i) azithromycin and doxycycline efficacy and (ii) efficacy difference. All eight included studies were observational. The random-effects pooled efficacy for azithromycin (based on eight studies) was 82.9% (95% CI 76.0%-89.8%; I(2) = 71.0%; P < 0.01) and for doxycycline (based on five studies) was 99.6% (95% CI 98.6%-100%; I(2) = 0%; P = 0.571), resulting in a random-effects pooled efficacy difference (based on five studies) of 19.9% (95% CI 11.4%-28.3%; I(2) = 48.5%; P = 0.101) in favour of doxycycline. The efficacy of single-dose azithromycin may be considerably lower than 1 week of doxycycline for treating rectal chlamydia. However, the available evidence is very poor. Robust randomized controlled trials are urgently required. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells.

    PubMed

    Kitsiouli, Eirini; Antoniou, Georgia; Gotzou, Helen; Karagiannopoulos, Michalis; Basagiannis, Dimitris; Christoforidis, Savvas; Nakos, George; Lekka, Marilena E

    2015-07-01

    Azithromycin is a member of macrolides, utilized in the treatment of infections. Independently, these antibiotics also possess anti-inflammatory and immunomodulatory properties. Phospholipase A2 isotypes, which are implicated in the pathophysiology of inflammatory lung disorders, are produced by alveolar macrophages and other lung cells during inflammatory response and can promote lung injury by destructing lung surfactant. The aim of the study was to investigate whether in lung cells azithromycin can inhibit secretory and cytosolic phospholipases A2, (sPLA2) and (cPLA2), respectively, which are induced by an inflammatory trigger. In this respect, we studied the lipopolysaccharide (LPS)-mediated production or secretion of sPLA2 and cPLA2 from A549 cells, a cancer bronchial epithelial cell line, and alveolar macrophages, isolated from bronchoalveolar lavage fluid of ARDS and control patients without cardiopulmonary disease or sepsis. Pre-treatment of cells with azithromycin caused a dose-dependent decrease in the LPS-induced sPLA2-IIA levels in A549 cells. This inhibition was rather due to reduced PLA2G2A mRNA expression and secretion of sPLA2-IIA protein levels, as observed by western blotting and indirect immunofluorescence by confocal microscopy, respectively, than to the inhibition of the enzymic activity per se. On the contrary, azithromycin had no effect on the LPS-induced production or secretion of sPLA2-IIA from alveolar macrophages. The levels of LPS-induced c-PLA2 were not significantly affected by azithromycin in either cell type. We conclude that azithromycin exerts anti-inflammatory properties on lung epithelial cells through the inhibition of both the expression and secretion of LPS-induced sPLA2-IIA, while it does not affect alveolar macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015

    PubMed Central

    Wind, Carolien M; Schim van der Loeff, Maarten F; van Dam, Alje P; de Vries, Henry JC; van der Helm, Jannie J

    2017-01-01

    Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted. PMID:28079519

  18. Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015.

    PubMed

    Wind, Carolien M; Schim van der Loeff, Maarten F; van Dam, Alje P; de Vries, Henry Jc; van der Helm, Jannie J

    2017-01-05

    Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted. This article is copyright of The Authors, 2017.

  19. Use of whole-genome sequencing data to analyze 23S rRNA-mediated azithromycin resistance.

    PubMed

    Johnson, Steven R; Grad, Yonatan; Abrams, A Jeanine; Pettus, Kevin; Trees, David L

    2017-02-01

    The whole-genome sequences of 24 isolates of Neisseria gonorrhoeae with elevated minimum inhibitory concentrations (MICs) to azithromycin (≥2.0 µg/mL) were analyzed against a modified sequence derived from the whole-genome sequence of N. gonorrhoeae FA1090 to determine, by signal ratio, the number of mutant copies of the 23S rRNA gene and the copy number effect on 50S ribosome-mediated azithromycin resistance. Isolates that were predicted to contain four mutated copies were accurately identified compared with the results of direct sequencing. Fewer than four mutated copies gave less accurate results but were consistent with elevated MICs.

  20. Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography *

    PubMed Central

    Shen, Yan; Xu, Sheng-jie; Wang, Shi-chun; Tu, Jia-sheng

    2009-01-01

    A high-performance liquid chromatography (HPLC) system was used in the reversed phase mode for the determination of benzalkonium chloride (BKC) in azithromycin viscous ophthalmic drops. A Venusil-XBP(L)-C18 (150 mm×4.6 mm, 5 μm) column was used at 50 °C. The mobile phase consisted of a mixture of methanol-potassium phosphate (16:5, v/v). Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0~50 μg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 μg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops. PMID:19946951

  1. Anti Pneumococcal Activity of Azithromycin-Eudragit RS100 Nano-Formulations

    PubMed Central

    Adibkia, Khosro; Khorasani, Golrokh; Payab, Shahriar; Lotfipour, Farzaneh

    2016-01-01

    Purpose: Bacterial pneumonia is a common lung infection caused by different types of bacteria. Azithromycin (AZI), an azalide antibiotic, is widely used to manage pneumococcal infections. Studies have shown that antibiotics in nanocarriers may lead to increased antibacterial activity and reduced toxicity. The aim of this work was to valuate in vitro antibacterial performance azithromycin-Eudragit RS100 nano-formulations against Streptococcus pneumoniae and Staphylococcus aureus. Methods: AZI-Eudragit RS100 nanoparticles were prepared via electrospinning technique and the in vitro antibacterial performance against S. pneumoniae and S. aureus were assessed using agar dilution method. Results: Nanofibers in the sizes about 100-300 nm in diameter and micro scale in length and nanobeads in the range of 100-500 nm were achieved. The Minimum Inhibitory Concentrations (MIC) showed an enhancement in the antimicrobial effect of AZI-Eudragit RS100 nanofibers (40 µg/ml) compare to untreated AZI solution (>160 µg/ml) against S. pneumonia. The MIC value for AZI-Eudragit RS100 nanofibers against S. aureus was >128 µg/ml, same as that of the untreated AZI solution. Conclusion: The enhanced efficiency of AZI in nanofibers could be related to the more adsorption opportunity of nanofibers to S. pneumonia capsulated cell wall which provides an antibiotic depot on the bacterial surface compared to S. aureus. AZI-Eudragit RS100 nanofibers with enhanced antimicrobial effect against S. pneumonia can be considered as a candidate for in vivo evaluations in antibiotic therapy of Pneumococcal infections. PMID:27766231

  2. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    NASA Astrophysics Data System (ADS)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; de, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-03-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

  3. Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography.

    PubMed

    Shen, Yan; Xu, Sheng-jie; Wang, Shi-chun; Tu, Jia-sheng

    2009-12-01

    A high-performance liquid chromatography (HPLC) system was used in the reversed phase mode for the determination of benzalkonium chloride (BKC) in azithromycin viscous ophthalmic drops. A Venusil-XBP(L)-C(18) (150 mmx4.6 mm, 5 microm) column was used at 50 degrees C. The mobile phase consisted of a mixture of methanol-potassium phosphate (16:5, v/v). Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0 to approximately 50 microg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 microg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops.

  4. Efficacy and safety of azithromycin for uncomplicated typhoid fever: an open label non-comparative study.

    PubMed

    Aggarwal, Anju; Ghosh, Apurba; Gomber, Sunil; Mitra, Monjori; Parikh, A O

    2011-07-01

    An open-labelled, non-comparative study was conducted in 117 children aged 2-12 years to evaluate the efficacy and safety of azithromycin (20mg/ kg/day for 6 days) for the treatment of uncomplicated typhoid fever. Of the patients enrolled based on a clinical definition of typhoid fever, 109 (93.1%) completed the study.Mean (SD) of duration of fever at presentation was 9.1(4.5) days. Clinical cure was seen in 102 (93.5%) subjects, while 7 were withdrawn from the study because of clinical deterioration. Mean day of response was 3.45±1.97. BACTEC blood culture was positive for Salmonella typhi in 17/109 (15.5%) and all achieved bacteriological cure. No serious adverse event was observed. Global well being assessed by the investigator and subjects was good in 95% cases which was done at the end of the treatment. Azithromycin was found to be safe and efficacious for the management of uncomplicated typhoid fever.

  5. Azithromycin in DuraSite® for the treatment of blepharitis

    PubMed Central

    Luchs, Jodi

    2010-01-01

    Blepharitis is a common inflammatory disease of the eyelid. Posterior blepharitis affects the posterior lamella of the eyelid and involves inflammation of the meibomian glands, whereas anterior blepharitis affects the anterior lamella of the eyelid and the eyelashes; either version can be inflammatory or infectious in nature. Each of these conditions can incite or propagate the other; anterior blepharitis, if not treated, can lead to meibomian gland disease, and vice versa. Blepharitis is typically chronic, and can be associated with a variety of systemic diseases such as dermatitis, as well as ocular diseases such as dry eye, conjunctivitis, or keratitis. The standard treatment regimen historically consists of lid hygiene with warm compresses and eyelid scrubs, although these treatment modalities may have limited efficacy for many patients, especially those with more severe disease. Adjunctive treatment includes systemic and topical antibiotics, topical corticosteroids, and tear replacement therapy. Topical antibiotics are recommended to decrease the bacterial load, and topical corticosteroids may help in cases of severe inflammation. Azithromycin ophthalmic solution 1% in DuraSite® (AzaSite®; Inspire Pharmaceuticals, Durham, North Carolina, USA) has been proposed as a novel treatment for posterior blepharitis, based on its well-known anti-infective profile, its anti-inflammatory properties, its excellent tissue penetration, and its regulatory approval for the treatment of bacterial conjunctivitis. This review focuses on an off-label indication for topical azithromycin 1% in DuraSite for the treatment of blepharitis. PMID:20689782

  6. Evidence of improved small airways function after azithromycin treatment in diffuse panbronchiolitis.

    PubMed

    Hanon, Shane; Verbanck, Sylvia; Schuermans, Daniel; Vanden Berghe, Bram; Vanderhelst, Eef; Vincken, Walter

    2012-01-01

    A 67-year-old never-smoker was diagnosed with diffuse panbronchiolitis (DPB) and was started on 250 mg azithromycin twice weekly. Over a 16-month observation period, lung function was assessed monthly, including a dedicated small airways test, the multiple breath nitrogen washout (MBW) with indices S(cond) and S(acin) of ventilation heterogeneity at the level of the conductive and acinar air spaces, respectively. Baseline measurements indicated moderate airway obstruction, air trapping and considerable dysfunction of the small airways around the acinar entrance. Treatment resulted in excellent symptomatic improvement paralleled by marked improvements in FEV(1), FVC, RV/TLC, S(cond) and S(acin); by contrast, there were no consistent changes in FEF(75) or TL(CO). While improvements were such that S(cond) fell within normal limits after 5 months, S(acin) remained abnormal even after 16 months of treatment. This suggests a distinct acinar structural abnormality in DPB that cannot be reversed by azithromycin.

  7. Ion-activated In Situ Gelling Ophthalmic Delivery Systems of Azithromycin

    PubMed Central

    Vijaya, C.; Goud, K. Swetha

    2011-01-01

    Gelation of pectin caused by divalent cations especially calcium ions has been applied to develop an ophthalmic formulation of azithromycin in the present study. Rapid elimination of drug on instillation into cul de sac would be minimal with in situ gelling ophthalmic solution leading to increased precorneal contact time and prolonged drug delivery. In the formulation development studies pectin was used in different concentrations (1-5% w/v) and different proportions of the hydrocolloids hydroxypropyl methylcellulose and sodium carboxymethyl cellulose of different grades of viscosity were used. The primary criteria for formulation optimization were gelling capacity and rheological behaviour. In addition, formulations were evaluated for pH, and antimicrobial efficacy and drug release. The clarity, pH, gelation in simulated tear fluid and rheological properties of the optimized formulations were satisfactory. The formulations inhibited the growth of Staphylococcus aureus effectively in cup–plate method and were proved to be safe and non irritant on rabbit eyes. The results indicate that pectin based in situ gels can be successfully used to prolong the duration of action of azithromycin. PMID:23112394

  8. From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials

    PubMed Central

    Jelić, Dubravko; Antolović, Roberto

    2016-01-01

    Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins’ progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds—macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides. PMID:27598215

  9. Comparison effect of azithromycin gel 2% with clindamycin gel 1% in patients with acne

    PubMed Central

    Mokhtari, Fatemeh; Faghihi, Gita; Basiri, Akram; Farhadi, Sadaf; Nilforoushzadeh, Mohammadali; Behfar, Shadi

    2016-01-01

    Background: Acne vulgaris is the most common skin disease. Local and systemic antimicrobial drugs are used for its treatment. But increasing resistance of Propionibacterium acnes to antibiotics has been reported. Materials and Methods: In a double-blind clinical trial, 40 patients with mild to moderate acne vulgaris were recruited. one side of the face was treated with Clindamycin Gel 1% and the other side with Azithromycin Topical Gel 2% BID for 8 weeks and then they were assessed. Results: Average age was 21. 8 ± 7 years. 82.5% of them were female. Average number of papules, pustules and comedones was similarly reduced in both groups and, no significant difference was observed between the two groups (P > 0.05, repeated measurs ANOVA). The mean indexes of ASI and TLC also significantly decreased during treatment in both groups, no significant difference was observed between the two groups. (P > 0.05, repeated measurs ANOVA). Also, impact of both drugs on papules and pustules was 2-3 times greater than the effect on comedones. Average satisfaction score was not significant between the two groups (P = 0.6, repeated measurs ANOVA). finally, frequency distribution of complications was not significant between the two groups (P > 0.05, Fisher Exact test). Conclusion: Azithromycin gel has medical impact at least similar to Clindamycin Gel in treatment of mild to moderate acne vulgaris, and it may be consider as suitable drug for resistant acne to conventional topical therapy. PMID:27169103

  10. Tissue disposition of azithromycin after intravenous and intramuscular administration to rabbits.

    PubMed

    Cárceles, Carlos M; Fernández-Varón, Emilio; Marín, Pedro; Escudero, Elisa

    2007-07-01

    Tissue disposition of azithromycin after intravenous (IV) or intramuscular (IM) injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits using a modified agar diffusion bioassay for determining tissue concentrations. The pharmacokinetic behaviour of azithromycin was characterized by low and sustained plasma concentrations but high and persistent tissue concentrations. Kinetic parameters indicated a high retention of the drug in peripheral compartments. The plasma half-lives after IV and IM administrations were similar being 21.8h and 23.1h, respectively, while the half-lives obtained in tissues after IV and IM administration were at least 1.4 and 1.9 times longer than in plasma, respectively. The highest tissue concentrations were found in bile, liver and spleen whereas the lowest ones were found in skeletal muscle (although they were higher than those in plasma). From the results of the single administration in this study an IM dosage regimen can be proposed that achieves minimum concentrations over 2mg/L in rabbits: three doses of 4-5mg/kg/day would provide suitable therapeutic concentrations in pulmonary tissues over seven days.

  11. Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia

    PubMed Central

    Abera, Bayeh; Kibret, Mulugeta

    2014-01-01

    Aim: To determine profiles of non-chlamydia conjunctival bacteria and their antimicrobial susceptibility from adults who underwent trachomatous trichiasis surgery in rural areas of Ethiopia. Materials and Methods: A cross-sectional study was conducted in rural districts in West Gojjam administrative zone. Conjunctival swabs were collected during surgery and transported using Stuart transport broth (Oxoid, UK). Antibiotic susceptibility of conjunctival isolates was determined using the Kirby-Bauer disc-diffusion method. Results: Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31%) participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G), Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4%) were observed to ceftriaxone, tetracycline and cotrimoxazole. Conclusion: Fluoroquinolones that have activity against the majority of bacterial isolates were potent at in vitro. However, unacceptably high levels of resistance to azithromycin and chloramphenicol in rural community indicated a need for further study and antimicrobial resistance surveillance. PMID:23571246

  12. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    PubMed Central

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; De, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-01-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis. PMID:27000525

  13. A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus.

    PubMed

    Dunne, M; Fessel, J; Kumar, P; Dickenson, G; Keiser, P; Boulos, M; Mogyros, M; White Jr, A C; Cahn, P; O'Connor, M; Lewi, D; Green, S; Tilles, J; Hicks, C; Bissett, J; Schneider, M M; Benner, R

    2000-11-01

    Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.

  14. A comparative study of efficacy and safety of azithromycin and ofloxacin in uncomplicated typhoid Fever: a randomised, open labelled study.

    PubMed

    Chandey, Manish; Multani, A S

    2012-12-01

    To compare the efficacy and safety of azithromycin with ofloxacin in patients with uncomplicated typhoid fever. Forty adult patients with bacteriologically or serologically diagnosed, uncomplicated typhoid fever were included from Medicine out-patient department at Government medical college, Amritsar, India. They were randomized into 2 groups of 20 patients each. Group I: patients received ofloxacin 200mg orally twice daily for 7 days. Group II: Patients received Azithromycin orally 1 gm on day 1 and then 500 mg daily from day 2 to day 6. The following parameters were noted a) fever clearance time b) cure rate c) adverse drug reaction d) recurrence of symptoms, if any, during 4 weeks follow up. Nineteen out of 20 patients from group I were cured with mean fever clearance time of 3.68 days while all 20 patients from group II were cured with mean fever clearance time of 3.65 days. No significant side effects were noted in any of the patients. No relapse was recorded in the present study in a follow up period of 4 weeks in both study groups. Both ofloxacin and Azithromycin are almost equally efficacious and safe in treatment of typhoid fever with no major adverse effect. Azithromycin is an effective alternative in conditions where ofloxacin is contraindicated i.e., children, pregnant women and quinolone resistant cases of typhoid fever.

  15. Microbiological effects of periodontal therapy plus azithromycin in patients with diabetes: results from a randomized clinical trial.

    PubMed

    Hincapié, Juan P; Castrillón, Cesar A; Yepes, Fanny L; Roldan, Natalia; Becerra, María A; Moreno, Sandra M; Consuegra, Jessika; Contreras, Adolfo; Botero, Javier E

    2014-01-01

    Current evidence suggests that periodontal infection may aggravate diabetes control. The aim of this study was to determine the changes in the frequency with which Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Aggregatibacter actinomycetemcomitans were detected in patients with diabetes with the use of non-surgical therapy plus azithromycin in a randomized clinical trial. One hundred and five (105) patients with diabetes and chronic periodontitis were randomly assigned to three treatment groups: subgingival mechanical therapy with azithromycin, subgingival mechanical therapy with placebo and supragingival prophylaxis with azithromycin. Complete periodontal clinical examinations and detection of periodontal pathogens using polymerase chain reaction were carried out at baseline, 3, 6 and 9 months after periodontal therapy. The frequency with which Porphyromonas gingivalis, Treponemadenticola and Aggregatibacter actinomycetemcomitans were detected decreased at 3 months in all groups. Tannerella forsythia increased after3 months in all groups. All organisms had similar frequencies at 9 months in all groups. Subgingival mechanical therapy with adjunctive azithromycin had no additional effect on the frequency with which the periodontal pathogens investigated were detected in patients with diabetes.

  16. A CASE STUDY: CROP (LETTUCE, SPINACH, AND CARROTS) UPTAKE OF THREE MACROLIDE ANTIBIOTICS (AZITHROMYCIN, CLINDAMYCIN AND ROXITHROMYCIN) AND OTHER DRUGS

    EPA Science Inventory

    It has been shown that human-use macrolide antibiotics (azithromycin, clindamycin, and roxithromycin) are environmentally available in wastewaters, source waters, and biosolids. In order to better understand the fate of these compounds into food crops via root migration, we condu...

  17. A CASE STUDY: CROP (LETTUCE, SPINACH, AND CARROTS) UPTAKE OF THREE MACROLIDE ANTIBIOTICS (AZITHROMYCIN, CLINDAMYCIN AND ROXITHROMYCIN) AND OTHER DRUGS

    EPA Science Inventory

    It has been shown that human-use macrolide antibiotics (azithromycin, clindamycin, and roxithromycin) are environmentally available in wastewaters, source waters, and biosolids. In order to better understand the fate of these compounds into food crops via root migration, we condu...

  18. The role of Chlamydia pneumoniae in the etiology of acne rosacea: response to the use of oral azithromycin.

    PubMed

    Fernandez-Obregon, Adolfo; Patton, Dorothy L

    2007-02-01

    Acne rosacea is a chronic skin disorder that requires long-term therapy. Oral azithromycin has been used successfully to treat acne vulgaris. an observation that suggested an infectious agent may play an active role in the etiology of this disorder. Ten adults (not previously reported) with acne rosacea were selected to be treated with oral azithromycin. Nine of the 10 subjects received 250 mg 3 times weekly for periods ranging from 5 to 19 weeks, at which time follow-up examinations were performed on 8 of the 9 treated subjects: 1 subject was lost to follow-up. Prior to therapy. C pneumoniae antigen was detected in malar biopsy specimens in 4 of 10 subjects by immunoperoxidase technique (using monoclonal antibody to C pneumoniae). Serum antibodies against C pneumoniae were detected in 8 of 10 intent-to-treat subjects. Using polymerase chain reaction, C pneumoniae was not detected in peripheral blood mononuclear cells. The inflammatory response in tissues was characterized by a widespread infiltration of polymorphonuclear neutrophil cells, lymphocytes, and plasma cells, which support the clinical diagnosis of acne rosacea. Nine of 10 subjects treated with azithromycin showed moderate to marked improvement of their acne rosacea. No adverse reactions to azithromycin occurred. and the drug appeared to be safe and effective. These preliminary data suggest the need for further investigation with clinical trials to study long-term tolerability and efficacy and also strongly implicate C pneumoniae in the pathogenesis of acne rosacea.

  19. Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment

    PubMed Central

    Gensel, John C.; Kopper, Timothy J.; Zhang, Bei; Orr, Michael B.; Bailey, William M.

    2017-01-01

    Spinal cord injury (SCI) triggers a heterogeneous macrophage response that when experimentally polarized toward alternative forms of activation (M2 macrophages) promotes tissue and functional recovery. There are limited pharmacological therapies that can drive this reparative inflammatory state. In the current study, we used in vitro systems to comprehensively defined markers of macrophages with known pathological (M1) and reparative (M2) properties in SCI. We then used these markers to objectively define the macrophage activation states after SCI in response to delayed azithromycin treatment. Mice were subjected to moderate-severe thoracic contusion SCI. Azithromycin or vehicle was administered beginning 30 minutes post-SCI and then daily for 3 or 7 days post injury (dpi). We detected a dose-dependent polarization toward purportedly protective M2 macrophages with daily AZM treatment. Specifically, AZM doses of 10, 40, or 160 mg/kg decreased M1 macrophage gene expression at 3 dpi while the lowest (10 mg/kg) and highest (160 mg/kg) doses increased M2 macrophage gene expression at 7 dpi. Azithromycin has documented immunomodulatory properties and is commonly prescribed to treat infections in SCI individuals. This work demonstrates the utility of objective, comprehensive macrophage gene profiling for evaluating immunomodulatory SCI therapies and highlights azithromycin as a promising agent for SCI treatment. PMID:28057928

  20. Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction.

    PubMed

    Graziani, F; Corsi, L; Fornai, M; Antonioli, L; Tonelli, M; Cei, S; Colucci, R; Blandizzi, C; Gabriele, M; Del Tacca, M

    2005-12-01

    Combined treatments with non-steroidal anti-inflammatory drugs and antibiotics may offer significant benefits in the prevention of pain and infections associated with oral surgery. In this study, piroxicam and azithromycin were administered to patients undergoing dental extraction to examine the efficacy of piroxicam in the prevention of post-operative pain and inflammatory complications, either in the absence or in the presence of a concomitant antibiotic treatment. Thirty patients were randomly assigned to three groups and treated for 3 days, before impacted lower third molar removal, as follows: (1) sublingual piroxicam-FDDF (fast dissolving dosage formulation) 20 mg/day; (2) oral azithromycin 500 mg/day; (3) piroxicam-FDDF 20 mg/day plus azithromycin 500 mg/day. Oral acetaminophen (500 mg tablets) was allowed as rescue analgesic medication. Pain intensity was evaluated on a 100-mm visual-analogue scale after dental extraction (day 1), and at days 2, 3, 7 after surgery. Edema and trismus were estimated at days 2 and 7. At days 1 and 2, pain intensity was significantly lower in patients treated with piroxicam-FDDF, either alone (p < 0.05) or in combination with azithromycin (p < 0.05), than in patients administered with azithromycin alone. A higher acetaminophen consumption was also recorded in the latter group (p < 0.01). Pain intensity values did not differ among treatment groups at days 3 and 7. At day 2, the facial edema was significantly less intense in patients exposed to piroxicam-FDDF alone, as compared to patients treated with azithromycin, either alone (p < 0.05) or in combination with piroxicam-FDDF (p < 0.05). No significant differences were detected when comparing groups for trismus at days 2 and 7. The present results indicate that, when given alone in the pre-operative period, piroxicam-FDDF effectively counteracts post-surgical pain and inflammatory reactions in oral tissues. Upon combined treatment with piroxicam-FDDF and azithromycin, the

  1. A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis.

    PubMed

    Schwebke, J R; Desmond, R A

    2007-01-15

    Bacterial vaginosis (BV) is the most common cause of vaginitis worldwide. Currently recommended treatments have poor efficacy and are associated with high rates of BV recurrence. We examined whether a longer duration of treatment with metronidazole or combination therapy with metronidazole and azithromycin would enhance the cure rates for BV. In addition, we examined factors other than drug therapy associated with cure. Women with symptomatic BV (defined by a modified Amsel criteria) were enrolled in a 4-arm study that compared metronidazole for 7 days versus 14 days, plus or minus azithromycin on days 1 and 3. Data regarding interim behaviors were also obtained, as were vaginal specimens for Gram staining. At the first follow-up visit (7 days after the completion of therapy), there was a significant difference in cure rates among patients who received 7 days of metronidazole therapy, compared with those who received 14 days of therapy, combined across azithromycin therapy (P=.0003). There was no effect associated with azithromycin therapy. There were no differences in cure rates between any of the treatment groups at 21 days after completion of therapy. Abstinence or protected sex, refraining from douching, and a lower baseline Nugent score for the vaginal Gram stain were all significantly associated with cure. Cure rates for BV were significantly improved by 14 days of metronidazole treatment (compared with 7 days of treatment), but the effects were not sustained, suggesting that relapse or reinfection occurred. Combination therapy with the addition of azithromycin had no benefit. Lower baseline Nugent scores--presumably reflecting less complex vaginal flora--were significantly associated with cure, as was refraining from unprotected sex and from douching.

  2. Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis.

    PubMed

    Goyer, Isabelle; Ferland, Gabrielle; Ruo, Ni; Morin, Caroline; Brochet, Marie-Sophie; Morin, Lucie; Ferreira, Ema

    2016-09-13

    Since 2006, the empiric use of azithromycin in women at risk of premature birth has become prevalent in our institution without any evidence of its efficacy. Although antibiotics can prolong pregnancy in preterm prolonged rupture of membranes, no published data are available for women with intact membranes. To describe the purpose of adding azithromycin to the usual treatments (cerclage, tocolysis, rest, etc.) to prolong pregnancy in women with intact membranes who are at risk of or already in preterm labour. A retrospective observational cohort study was done at a Mother-Child University Hospital Centre. Patients admitted to obstetric ward who received azithromycin between January 1(st), 2006 and August 1(st), 2010 were included. A total of 127 exposed women were matched to 127 controls through medical records and pharmacy software. A time-to-event analysis was done to compare gestational age at the time of the recorded composite event (delivery, or rupture of membranes, or second intervention to prolong pregnancy). To compare proportions of composite event at different time points, χ(2) tests were used. Patients who received azithromycin had a more severe condition at presentation. Once adjusted for confounding factors, prolongation of pregnancy (HR =1.049; CI 95%: 0.774-1.421 [p=0.758]) and gestational age at the event (HR=1.200; CI 95%: 0.894-1.609 [p=0.225]) did not differ between the groups. The proportions of women with an event ≥7 days post-diagnosis or ≥37 gestational weeks were similar. Azithromycin was added to medical therapy in a more at-risk population and no clear benefit was measured.

  3. Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial

    PubMed Central

    2012-01-01

    Background The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. Methods/design We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12–24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4

  4. A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies

    PubMed Central

    WILTON, L. V.; PEARCE, G. L.; MANN, R. D.

    1996-01-01

    1 The safety in everyday clinical usage of three 4-quinolone antibiotics, (ciprofloxacin, norfloxacin and ofloxacin), was compared with similar data for azithromycin and cefixime, each agent being examined by Prescription-Event Monitoring (PEM) during the early post-marketing period. 2 In PEM the exposure data are derived from general practitioner prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are provided by questionnaires (green forms) on which the prescribing medical practitioner records event data. When necessary, further information is obtained from a number of sources which include follow-up of all pregnancies and the patients' life-time medical record. 3 The main outcome measures were demographic information, including the patient's date of birth and sex; the indication for prescribing the drug being monitored; the reason for stopping treatment; the start and stop dates of treatment and the events recorded during and after treatment. 4 The final cohort for each of the five antibiotics exceeded 11000 patients. The only event significantly related to the use of all five antibiotics was nausea/vomiting. This was also the most frequent adverse event causing treatment to be discontinued with norfloxacin, ofloxacin and azithromycin (relevant information was not requested in the studies of ciprofloxacin and cefixime). Vaginal candidiasis was significantly more frequently associated with the use of the three 4-quinolones than with azithromycin and cefixime but it was frequently delayed until the week or two after the cessation of therapy. Within each event, as recorded in these studies, the highest event rates (the number of events per 1000 patients) in the week following the start of therapy were: 9.2 for diarrhoea with cefixime; 4.9 for nausea/vomiting with ofloxacin; 2.4 for rash with azithromycin; 2.2 for abdominal pain with norfloxacin; 1.5 for headache/migraine with ofloxacin; 1.4 for malaise/lassitude with

  5. Effect of azithromycin on enhancement of methane production from waste activated sludge.

    PubMed

    Nguyen, Minh Tuan; Maeda, Toshinari; Mohd Yusoff, Mohd Zulkhairi; Ogawa, Hiroaki I

    2014-07-01

    In the methane production from waste activated sludge (WAS), complex bacterial interactions in WAS have been known as a major contribution to methane production. Therefore, the influence of bacterial community changes toward methane production from WAS was investigated by an application of antibiotics as a simple means for it. In this study, azithromycin (Azm) as an antibiotic was mainly used to observe the effect on microbial changes that influence methane production from WAS. The results showed that at the end of fermentation, Azm enhanced methane production about twofold compared to control. Azm fostered the growth of acid-producing bacterial communities, which synthesized more precursors for methane formation. DGGE result showed that the hydrolysis as well as acetogenesis stage was improved by the dominant of B1, B2 and B3 strains, which are Clostridium species. In the presence of Azm, the total population of archaeal group was increased, resulting in higher methane productivity achievement.

  6. Formulation and biopharmaceutical evaluation of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets.

    PubMed

    Tung, Nguyen-Thach; Tran, Cao-Son; Nguyen, Tran-Linh; Hoang, Tung; Trinh, Thanh-Dat; Nguyen, Thi-Ngan

    2017-03-27

    The objective of this study was to prepare and evaluate some physiochemical and biopharmaceutical properties of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets. In the first stage of the study, the bitter taste masking microparticles were prepared by solvent evaporation and spray drying method. When compared to the bitter threshold (32.43µg/ml) of azithromycin (AZI), the microparticles using AZI:Eudragit L100=1:4 and having a size distribution of 45-212µm did significantly mask the bitter taste of AZI. Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy ((1)H NMR) proved that the taste masking of microparticles resulted from the intermolecular interaction of the amine group in AZI and the carbonyl group in Eudragit L100. Differential scanning calorimeter (DSC) analysis was used to display the amorphous state of AZI in microparticles. Images obtaining from optical microscopy and scanning electron microscopy (SEM) indicated the existence of microparticles in regular cube shape with many layers. In the second stage, dispersible tablets containing microparticles (DTs-MP) were prepared by direct compression technique. Stability study was conducted to screen pH modulators for DTs-MP, and a combination of alkali agents (CaCO3:NaH2PO4, 2:1) was added into DTs-MP to create microenvironment pH of 5.0-6.0 for the tablets. The disintegration time of optimum DTs-MP was 53±5.29s and strongly depended on the kinds of lubricant and diluent. The pharmacokinetic study in the rabbit model using liquid chromatography tandem mass spectrometry showed that the mean relative bioavailability (AUC) and mean maximum concentration (Cmax) of DTs-MP were improved by 2.19 and 2.02 times, respectively, compared to the reference product (Zithromax®, Pfizer). Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Update and critical appraisal of the use of topical azithromycin ophthalmic 1% (AzaSite) solution in the treatment of ocular infections.

    PubMed

    Utine, Canan Asli

    2011-01-01

    Azithromycin is an azalide that acts by binding to the 50S ribosomal subunit of susceptible microorganisms and interfering with microbial protein synthesis. Azithromycin is also noted by anti-inflammatory and immunomodulatory activity. AzaSite(®) (Inspire Pharmaceuticals, Inc, Durham, NC) is azithromycin ophthalmic solution, 1% formulated in polycarbophil (the aqueous mucoadhesive polymer contained in DuraSite(®)) that delivers high and prolonged azithromycin concentrations in a variety of ocular tissues, including the conjunctiva, cornea and particularly the eyelid. AzaSite was approved by the Food and Drug Administration (FDA) in the US in 2007, for the treatment of bacterial conjunctivitis caused by susceptible isolates. This article aims to evaluate the peer-reviewed published scientific literature and to define well-established uses of AzaSite eye drops in the field of ocular infections.

  8. Update and critical appraisal of the use of topical azithromycin ophthalmic 1% (AzaSite®) solution in the treatment of ocular infections

    PubMed Central

    Utine, Canan Asli

    2011-01-01

    Azithromycin is an azalide that acts by binding to the 50S ribosomal subunit of susceptible microorganisms and interfering with microbial protein synthesis. Azithromycin is also noted by anti-inflammatory and immunomodulatory activity. AzaSite® (Inspire Pharmaceuticals, Inc, Durham, NC) is azithromycin ophthalmic solution, 1% formulated in polycarbophil (the aqueous mucoadhesive polymer contained in DuraSite®) that delivers high and prolonged azithromycin concentrations in a variety of ocular tissues, including the conjunctiva, cornea and particularly the eyelid. AzaSite was approved by the Food and Drug Administration (FDA) in the US in 2007, for the treatment of bacterial conjunctivitis caused by susceptible isolates. This article aims to evaluate the peer-reviewed published scientific literature and to define well-established uses of AzaSite eye drops in the field of ocular infections. PMID:21750614

  9. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial.

    PubMed

    Gibson, Peter G; Yang, Ian A; Upham, John W; Reynolds, Paul N; Hodge, Sandra; James, Alan L; Jenkins, Christine; Peters, Matthew J; Marks, Guy B; Baraket, Melissa; Powell, Heather; Taylor, Steven L; Leong, Lex E X; Rogers, Geraint B; Simpson, Jodie L

    2017-08-12

    Exacerbations of asthma cause a substantial global illness burden. Adults with uncontrolled persistent asthma despite maintenance treatment require additional therapy. Since macrolide antibiotics can be used to treat persistent asthma, we aimed to assess the efficacy and safety of oral azithromycin as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high dose inhaled corticosteroids plus a long-acting bronchodilator. We did a randomised, double-blind, placebo controlled parallel group trial to determine whether oral azithromycin decreases the frequency of asthma exacerbations in adults (≥18 years) with symptomatic asthma despite current use of inhaled corticosteroid and long-acting bronchodilator, and who had no hearing impairment or abnormal prolongation of the corrected QT interval. Patients were randomly assigned (1:1) to receive azithromycin 500 mg or placebo three times per week for 48 weeks. Patients were centrally allocated using concealed random allocation from a computer-generated random numbers table with permuted blocks of 4 or 6 and stratification for centre and past smoking. Primary efficacy endpoints were the rate of total (severe and moderate) asthma exacerbations over 48 weeks and asthma quality of life. Data were analysed on an intention-to-treat basis. The trial is registered at the Australian and New Zealand Clinical Trials Registry (ANZCTR), number 12609000197235. Between June 12, 2009, and Jan 31, 2015, 420 patients were randomly assigned (213 in the azithromycin group and 207 in the placebo group). Azithromycin reduced asthma exacerbations (1·07 per patient-year [95% CI 0·85-1·29]) compared with placebo (1·86 per patient-year [1·54-2·18]; incidence rate ratio [IRR] 0·59 [95% CI 0·47-0·74]; p<0·0001). The proportion of patients experiencing at least one asthma exacerbation was reduced by azithromycin treatment (127 [61%] patients in the placebo group vs 94 [44%] patients in the azithromycin group, p<0

  10. The comparison of treatments with and without azithromycin in irritable bowel syndrome with diarrhea-predominant in gastrointestinal Clinic of Al-Zahra Hospital, Isfahan, Iran

    PubMed Central

    Yazdani, Mohamadreza; Aramesh, Amirhossein; Rafiei, Rahmatollah; Daghaghzadeh, Hamed; Adibi, Peyman

    2016-01-01

    Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Recent studies suggest the importance of gut flora in the pathophysiology of it. Therefore, antibiotics have demonstrated a substantial benefit to reduce gut flora. Having few side effects, and applying one-dose per day, we studied the effect of azithromycin to treat IBS. Materials and Methods: One hundred and twenty-six patients enrolled a randomized, double-blind, placebo-controlled study. The treatment group received azithromycin in addition to common treatment. Patients were followed for 12 weeks. Patients completed daily diaries documenting their symptoms. Results: One hundred and thirteen patients completed the study. The onset of relief occurred significantly sooner, and duration of relief was significantly longer in azithromycin group. Movement, abdominal pain, bloating, and gas were significantly better in azithromycin group. Monthly results showed superior relief in bloating, gas, overall symptom, and overall bloating during 3 months. Significantly more patients in azithromycin group felt relief in bloating and gas and had greater consistency relief in almost all weeks. Conclusion: In our study, azithromycin significantly relieved most symptoms, such as abdominal pain, bloating, and gas. Overall symptom and overall bloating were relieved significantly in more patients in the intervention group in all weeks. PMID:28028528

  11. No depletion of Wolbachia from Onchocerca volvulus after a short course of rifampin and/or azithromycin.

    PubMed

    Richards, Frank O; Amann, Josef; Arana, Byron; Punkosdy, George; Klein, Robert; Blanco, Carlos; Lopez, Beatriz; Mendoza, Carlos; Domínguez, Alfredo; Guarner, Jeannette; Maguire, James H; Eberhard, Mark

    2007-11-01

    Endosymbionic Wolbachia bacteria inside adult Onchocerca volvulus worms (causing river blindness) are necessary for female worm fertility. We evaluated whether rifampin and/or azithromycin used in a five-day course could kill Wolbachia. In an open-label trial in Guatemala, 73 patients with 134 palpable onchocercal nodules were randomized into four treatment groups: rifampin, azithromycin, a combination of the two drugs, and controls (multivitamins). After five days of antibiotic treatment, all participants received a single dose of ivermectin on day 6. Nine months after treatment, the nodules were removed and the worms were examined. Skin snips to determine microfilariae were obtained at baseline and nine months. There were no significant differences between any of the treatment groups in the condition of the worms in the nodules, the presence of Wolbachia surface protein, or the number of microfilariae in skin. Short courses with these antibiotics will not clear Wolbachia from O. volvulus.

  12. Evaluation of the improvement of quality of life with Azithromycin in the treatment of eosinophilic nasal polyposis.

    PubMed

    Oliveira, Isamara Simas de; Crosara, Paulo Fernando Tormin Borges; Cassali, Geovanni Dantas; Reis, Diego Carlos dos; Resende, Camilo Brandão de; Nunes, Flavio Barbosa; Guimarães, Roberto Eustáquio Santos

    2016-01-01

    The Sino-Nasal Outcome Test 22 (SNOT-22) is an important tool in assessing the quality of life (QoL) of patients with chronic rhinosinusitis with a validated version in Brazil. The eosinophilic nasal polyposis (ENP) represents most of the cases of nasal polyposis (85-90%) and belongs to the group of chronic rhinosinusitis. It is a chronic inflammatory disease that impacts the QoL of patients, not only causing localized symptoms, but also resulting in a general malaise. The standard treatments (corticosteroids and nasal endoscopic surgery) lead to partial control of symptoms, but relapses are frequent. Macrolide acting as an immunomodulator is a promising tool for more effective control of this disease. Studies are still lacking to assess the real impact on the QoL in patients treated with macrolides. To evaluate the improvement of QL, evaluated using SNOT-22, in patients with PNSE treated with immunomodulatory dose azithromycin. This is a paired experimental study in patients with ENP. Comparison of pre-treatment and post-treatment with azithromycin was performed. Patients completed the SNOT-22 questionnaire before the start of treatment and returned for evaluation after eight weeks of treatment. Azithromycin was prescribed at a dose of 500 mg, orally, three times a week, for 8 weeks. SNOT-22 score decreased 20.3 points on average. There was a significant decrease in the SNOT-22 (difference greater than 14 points) in 19 patients (57.6%). There was no significant difference in improvement in SNOT in subgroups with or without asthma/aspirin intolerance. Azithromycin resulted in significant improvement of QoL, assessed by SNOT-22, in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  13. Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report

    PubMed Central

    2014-01-01

    Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities including eosinophilia and/or atypical lymphocytosis, and extensive organ involvement. The drugs most often responsible for causing drug reaction with eosinophilia and systemic symptoms syndrome are anticonvulsants, antimicrobial agents and antipyretic or anti-inflammatory analgesics. Although azithromycin is widely prescribed in clinical practice, serious cutaneous reactions from this agent have been rarely described. We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin. Case presentation A 44-year-old previously healthy Caucasian man with history of tobacco use presented to his primary care physician with fever and productive cough. He was prescribed azithromycin, promethazine hydrochloride and dextromethorphan hydrobromide syrup. One week later, he developed a blistering erythematous rash over both hands, which over the next two weeks spread to involve nearly his entire body surface, sparing only his face. He was admitted to an outside hospital with signs of systemic inflammatory response syndrome and severe sepsis, presumably from a skin infection. Despite aggressive therapy he deteriorated, with worsening diffuse erythema, and was transferred to our institution. He developed multiple organ failure requiring ventilatory and hemodynamic support. Pertinent laboratory studies included a leukocytosis with a white blood cell count of 17.6×109/L and 47% eosinophils. A skin biopsy showed evidence of spongiotic lichenoid dermatitis with eosinophils and neutrophils, compatible with a systemic drug-induced hypersensitivity reaction. Our patient was started on high-dose steroids and showed dramatic improvement within 48 hours. Conclusions We report the first adult case of

  14. Surface plasmon resonance based selective and sensitive colorimetric determination of azithromycin using unmodified silver nanoparticles in pharmaceuticals and human plasma

    NASA Astrophysics Data System (ADS)

    Chavada, Vijay D.; Bhatt, Nejal M.; Sanyal, Mallika; Shrivastav, Pranav S.

    2017-01-01

    In this article we report a novel method for colorimetric sensing and selective determination of a non-chromophoric drug-azithromycin, which lacks native absorbance in the UV-Visible region using unmodified silver nanoparticles (AgNPs). The citrate-capped AgNps dispersed in water afforded a bright yellow colour owing to the electrostatic repulsion between the particles due to the presence of negatively charged surface and showed surface plasmon resonance (SPR) band at 394 nm. Addition of positively charged azithromycin at a concentration as low as 0.2 μM induced rapid aggregation of AgNPs by neutralizing the negative charge on the particle surface. This phenomenon resulted in the colour change from bright yellow to purple which could be easily observed by the naked eye. This provided a simple platform for rapid determination of azithromycin based on colorimetric measurements. The factors affecting the colorimetric response like pH, volume of AgNPs suspension and incubation time were suitably optimized. The validated method was found to work efficiently in the established concentration range of 0.2-100.0 μM using two different calibration models. The selectivity of the method was also evaluated by analysis of nanoparticles-aggregation response upon addition of several anions, cations and some commonly prescribed antibiotics. The method was successfully applied for the analysis of azithromycin in pharmaceuticals and spiked human plasma samples with good accuracy and precision. The simplicity, efficiency and cost-effectiveness of the method hold tremendous potential for the analysis of such non-chromophoric pharmaceuticals.

  15. Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report.

    PubMed

    Sriratanaviriyakul, Narin; Nguyen, Lam-Phuong; Henderson, Mark C; Albertson, Timothy E

    2014-10-08

    Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities including eosinophilia and/or atypical lymphocytosis, and extensive organ involvement. The drugs most often responsible for causing drug reaction with eosinophilia and systemic symptoms syndrome are anticonvulsants, antimicrobial agents and antipyretic or anti-inflammatory analgesics. Although azithromycin is widely prescribed in clinical practice, serious cutaneous reactions from this agent have been rarely described. We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin. A 44-year-old previously healthy Caucasian man with history of tobacco use presented to his primary care physician with fever and productive cough. He was prescribed azithromycin, promethazine hydrochloride and dextromethorphan hydrobromide syrup. One week later, he developed a blistering erythematous rash over both hands, which over the next two weeks spread to involve nearly his entire body surface, sparing only his face. He was admitted to an outside hospital with signs of systemic inflammatory response syndrome and severe sepsis, presumably from a skin infection. Despite aggressive therapy he deteriorated, with worsening diffuse erythema, and was transferred to our institution. He developed multiple organ failure requiring ventilatory and hemodynamic support. Pertinent laboratory studies included a leukocytosis with a white blood cell count of 17.6 × 10(9)/L and 47% eosinophils. A skin biopsy showed evidence of spongiotic lichenoid dermatitis with eosinophils and neutrophils, compatible with a systemic drug-induced hypersensitivity reaction. Our patient was started on high-dose steroids and showed dramatic improvement within 48 hours. We report the first adult case of drug reaction with eosinophilia and

  16. A Cluster-Randomized Controlled Trial Evaluating the Effects of Mass Azithromycin Treatment on Growth and Nutrition in Niger

    PubMed Central

    Amza, Abdou; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E.; Yu, Sun N.; Zhou, Zhaoxia; West, Sheila K.; Mabey, David C. W.; Bailey, Robin L.; Keenan, Jeremy D.; Porco, Travis C.; Lietman, Thomas M.; Gaynor, Bruce D.

    2013-01-01

    Antimicrobials are used primarily to treat infectious disease, but they have other effects. Here, we assess anthropometry measurements in children 6–60 months in 24 communities randomized to one or two mass azithromycin distributions over a 1-year period in Niger. We compared the prevalence of wasting, low mid-upper arm circumference, stunting, and underweight in communities in the two treatment arms. We were unable to prove that there was a difference in the prevalence of wasting in the 12 communities that received one mass azithromycin distribution versus the 12 communities that received two mass azithromycin distributions (odds ratio = 0.75, 95% confidence interval = 0.46–1.23). Likewise, we were unable to detect a difference in the two treatment arms for low mid-upper arm circumference, stunting, and underweight. There may not be an association between antibiotic use and improved growth in humans, or this trial was not powerful enough to detect an association if it exists. PMID:23208876

  17. A Robust Liquid Chromatographic Method for Confirmation of Drug Stability of Azithromycin in Bulk Samples, Tablets and Suspensions

    PubMed Central

    Okaru, Alex O.; Abuga, Kennedy O.; Kamau, Franco N.; Ndwigah, Stanley N.; Lachenmeier, Dirk W.

    2017-01-01

    A simple, isocratic and robust RP-HPLC method for the analysis of azithromycin was developed, validated and applied for the analysis of bulk samples, tablets and suspensions. The optimum chromatographic conditions for separation were established as a mobile phase comprised of acetonitrile-0.1 M KH2PO4 pH 6.5–0.1 M tetrabutyl ammonium hydroxide pH 6.5-water (25:15:1:59 v/v/v/v) delivered at a flow rate of 1.0 mL/min. The stationary phase consisted of reverse-phase XTerra® (250 mm × 4.6 mm i.d., 5 µm particle size) maintained at a temperature of 43 °C with a UV detection at 215 nm. The method was found to be linear in the range 50%–150% (r2 = 0.997). The limits of detection and quantification were found to be 0.02% (20 µg) and 0.078% (78 µg), respectively, with a 100.7% recovery of azithromycin. Degradation products of azithromycin in acidic and oxidative environments at 37 °C were resolved from the active pharmaceutical ingredient and thus the method is fit for the purpose of drug stability confirmation. PMID:28245574

  18. Development, in vitro and in vivo evaluation of novel injectable smart gels of azithromycin for chronic periodontitis.

    PubMed

    Venkatesh, M P; Kumar, T M Pramod; Avinash, B S; Kumar, G Sheela

    2013-04-01

    Periodontitis is an inflammatory condition affecting teeth resulting in progressive destruction of periodontal ligaments, resorption of alveolar bone and loss of teeth. Treatment of periodontitis includes surgical and non surgical management. Systemic antibiotics are also used for the treatment of periodontitis. The aim of this research was to formulate smart gel system of azithromycin (AZT) and to evaluate in vitro and in vivo for non-surgical treatment of chronic periodontitis. Azithromycin dihydrate, used systemically in the treatment of periodontitis, was formulated into smart gels using biodegradable, thermosensitive polymer Pluronic® F-127 (PF-127) and Hydroxy Ethyl Cellulose (HEC) as copolymer. The prepared smart gels were evaluated for sterility, content uniformity, gelation temperature and time, syringeability, rheological behavior, in vitro diffusion and in vivo efficacy in human patients. The prepared smart gels were clear and transparent, sterile, thermoresponsive and injectable. Viscosity of gels increased with increase in concentration of polymer/co-polymer and also with temperature. They gelled in short response time below the body temperature. In vitro release studies showed controlled drug release which was influenced significantly by the properties and concentration of PF-127 and HEC. In vivo efficacy studies showed a significant improvement (p <0.001) in clinical parameters such as gingival index, probing pocket depth, clinical attachment level, bleeding index and plaque index. The developed azithromycin smart gel system is a novel approach for the treatment of chronic periodontitis since it reduces the dose and side effects, bypasses the usual surgical procedures and improves patient compliance.

  19. Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine.

    PubMed Central

    Brown, S T; Edwards, F F; Bernard, E M; Tong, W; Armstrong, D

    1993-01-01

    Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections. PMID:8384809

  20. Determination of azithromycin residue in pork using a molecularly imprinted monolithic microcolumn coupled to liquid chromatography with tandem mass spectrometry.

    PubMed

    Zhou, Tong; Yang, Haicui; Jin, Zhen; Liu, Qingying; Song, Xuqin; He, Limin; Fang, Binghu; Meng, Chenying

    2016-04-01

    Using spiramycin as a dummy template, a molecularly imprinted polymer monolithic micro-column with high selection to azithromycin was prepared in a micropipette tip. The imprinting factor of the monolithic micro-column prepared was approximately 2.67 and the morphological structure of the polymers was characterized by scanning electron microscopy. A simple, sensitive, and reproducible method based on the imprinted monolithic micro-column coupled to liquid chromatography with tandem mass spectrometry was developed for determining the residues of azithromycin in pork. Pork samples were extracted with acetonitrile, cleaned up under the optimal monolithic micro-column conditions, and analyzed using liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode. The assay exhibited a linear dynamic range of 0.50-50 μg/L with the correlation coefficient (r(2) ) above 0.99. In the three spiking levels of 0.50, 1.0, and 10 μg/kg, the average recoveries of azithromycin from pork samples were between 85.8 and 96.5% with a relative standard deviation below 10%. The limit of detection and limit of quantitation were 0.03 and 0.1 μg/kg, respectively.

  1. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses

    PubMed Central

    Mauger, David T.; Boehmer, Susan; Beigelman, Avraham; Fitzpatrick, Anne M.; Jackson, Daniel J.; Baxi, Sachin N.; Benson, Mindy; Burnham, Carey-Ann D.; Cabana, Michael; Castro, Mario; Chmiel, James F.; Covar, Ronina; Daines, Michael; Gaffin, Jonathan M.; Gentile, Deborah Ann; Holguin, Fernando; Israel, Elliot; Kelly, H. William; Lazarus, Stephen C.; Lemanske, Robert F.; Ly, Ngoc; Meade, Kelley; Morgan, Wayne; Moy, James; Olin, Tod; Peters, Stephen P.; Phipatanakul, Wanda; Pongracic, Jacqueline A.; Raissy, Hengameh H.; Ross, Kristie; Sheehan, William J.; Sorkness, Christine; Szefler, Stanley J.; Teague, W. Gerald; Thyne, Shannon; Martinez, Fernando D.

    2016-01-01

    IMPORTANCE Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child’s signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12-through 18-month period. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for

  2. Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression

    PubMed Central

    El-Shitany, Nagla A.; El-Desoky, Karema

    2016-01-01

    The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms. PMID:27274777

  3. Azithromycin and risk of COPD exacerbations in patients with and without Helicobacter pylori.

    PubMed

    Ra, Seung Won; Sze, Marc A; Lee, Eun Chong; Tam, Sheena; Oh, Yeni; Fishbane, Nick; Criner, Gerard J; Woodruff, Prescott G; Lazarus, Stephen C; Albert, Richard; Connett, John E; Han, Meilan K; Martinez, Fernando J; Aaron, Shawn D; Reed, Robert M; Man, S F Paul; Sin, Don D

    2017-05-30

    Helicobacter pylori (HP) infection is associated with reduced lung function and systemic inflammation in chronic obstructive pulmonary disease (COPD) patients. Azithromycin (AZ) is active against HP and reduces the risk of COPD exacerbation. We determined whether HP infection status modifies the effects of AZ in COPD patients. Plasma samples from 1018 subjects with COPD who participated in the Macrolide Azithromycin (MACRO) in COPD Study were used to determine the HP infection status at baseline and 12 months of follow-up using a serologic assay. Based on HP infection status and randomization to either AZ or placebo (PL), the subjects were divided into 4 groups: HP+/AZ, HP-/AZ, HP+/PL, and HP-/PL. Time to first exacerbation was compared across the 4 groups using Kaplan-Meier survival analysis and a Cox proportional hazards model. The rates of exacerbation were compared using both the Kruskal-Wallis test and negative binomial analysis. Blood biomarkers at enrolment and at follow-up visits 3, 12, and 13 (1 month after treatment was stopped) months were measured. One hundred eighty one (17.8%) patients were seropositive to HP. Non-Caucasian participants were nearly three times more likely to be HP seropositive than Caucasian participants (37.4% vs 13.6%; p < 0.001). The median time to first exacerbation was significantly different across the four groups (p = 0.001) with the longest time in the HP+/AZ group (11.2 months, 95% CI; 8.4-12.5+) followed by the HP-/AZ group (8.0 months, 95% CI; 6.7-9.7). Hazard ratio (HR) for exacerbations was lowest in the HP+/AZ group after adjustment for age, sex, smoking status, ethnicity, history of peptic ulcer, dyspnea, previous hospital admission, GOLD grade of severity, and forced vital capacity (HR, 0.612; 95% CI, 0.442-0.846 vs HR, 0.789; 95% CI, 0.663-0.938 in the HP-/AZ group). Circulating levels of soluble tumor necrosis factor receptor-75 were reduced only in the HP+/AZ group after 3 months of AZ treatment (-0.87

  4. The Effect of Azithromycin in Adults with Stable Neutrophilic COPD: A Double Blind Randomised, Placebo Controlled Trial

    PubMed Central

    Simpson, Jodie L.; Powell, Heather; Baines, Katherine J.; Milne, David; Coxson, Harvey O.; Hansbro, Philip M.; Gibson, Peter G.

    2014-01-01

    Background Chronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis. Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD. Despite current available therapies to control inflammation, neutrophilic bronchitis remains common. This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as bacterial load. We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis. Methods Eligible participants (n = 30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications. Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment. Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit. Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment. A sub-group of participants underwent chest computed tomography scans (n = 15). Results Nine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×107 cfu/mL. Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load. The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI): 0.37 (0.11,1.21), p = 0.062). For participants who underwent chest CT

  5. Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization

    PubMed Central

    Merchan, L. Marcela; Hassan, Hazem E.; Terrin, Michael L.; Waites, Ken B.; Kaufman, David A.; Ambalavanan, Namasivayam; Donohue, Pamela; Dulkerian, Susan J.; Schelonka, Robert; Magder, Laurence S.; Shukla, Sagar; Eddington, Natalie D.

    2014-01-01

    The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg0.75, 1.88 liters · kg, 1.79 liters/h · kg0.75, and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating Ureaplasma spp

  6. WGS for surveillance of antimicrobial resistance: a pilot study to detect the prevalence and mechanism of resistance to azithromycin in a UK population of non-typhoidal Salmonella.

    PubMed

    Nair, Satheesh; Ashton, Philip; Doumith, Michel; Connell, Steve; Painset, Anais; Mwaigwisya, Solomon; Langridge, Gemma; de Pinna, Elizabeth; Godbole, Gauri; Day, Martin

    2016-12-01

    WGS and phenotypic methods were used to determine the prevalence of azithromycin resistance in Salmonella enterica isolates from the UK and to identify the underlying mechanisms of resistance. WGS by Illumina HiSeq was carried out on 683 Salmonella spp. isolates. Known genes associated with azithromycin resistance were detected by WGS using a mapping-based approach. Macrolide resistance determinants were identified and the genomic context of these elements was assessed by various bioinformatics tools. Susceptibility testing was in accordance with EUCAST methodology (MIC ≤16 mg/L). Fifteen isolates of non-typhoidal Salmonella enterica belonging to serovars Salmonella Blockley, Salmonella Typhimurium, Salmonella Thompson, Salmonella Ridge and Salmonella Kentucky showed resistance or decreased susceptibility to azithromycin (from 6 to >16 mg/L) due to the presence of macrolide resistance genes mphA, mphB or mefB. These genes were either plasmid or chromosomally mediated. Azithromycin-resistant Salmonella Blockley isolates harboured a macrolide inactivation gene cluster, mphA-mrx-mphr(A), within a novel Salmonella azithromycin resistance genomic island (SARGI) determined by MinION sequencing. This is the first known chromosomally mediated mphA gene cluster described in salmonellae. Phylogenetic analysis and epidemiological information showed that mphA Salmonella Blockley isolates were not derived from a single epidemiologically related event. The azithromycin MICs of the 15 Salmonella spp. isolates showed that the presence of the mphA gene was associated with MIC ≥16 mg/L, while the presence of mefB or mphB was not. Azithromycin resistance due to acquisition of known macrolide resistance genes was seen in four different Salmonella serovars and can be either plasmid-encoded or chromosomally encoded. © Crown copyright 2016.

  7. Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells

    PubMed Central

    Sugiyama, K; Shirai, R; Mukae, H; Ishimoto, H; Nagata, T; Sakamoto, N; Ishii, H; Nakayama, S; Yanagihara, K; Mizuta, Y; Kohno, S

    2007-01-01

    The macrolide antibiotics are now well known to have anti-inflammatory effects. Because dendritic cells (DCs) orchestrate immune responses, we examined the in vitro effects of clarithromycin (CAM), azithromycin (AZM) and midecamycin (MDM) on the expression of co-stimulatory molecules and production of cytokines [interleukin (IL)-10, IL-6, interferon (IFN)-γ, IL-12p40, tumour necrosis factor (TNF)-α] of murine bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation. A 15-membered macrolide, AZM, and a 14-membered macrolide, CAM, significantly enhanced the intensity of a co-stimulatory molecule, CD80, on DCs but not CD86 and CD40. AZM significantly increased the production of IL-10 and CAM significantly inhibited the production of IL-6 by DCs. However, a 16-membered macrolide, MDM, did not have any significant effect on these surface markers and cytokine productions. Moreover, AZM increased IL-10 and CAM decreased IL-2 productions significantly, when naive T cells derived from spleen were co-cultured with DCs treated in advance with LPS and these macrolides. These findings suggest that 14-membered and 15-membered, but not 16-membered macrolides play as anti-inflammatory agents, at least in part, through modulating the functions of DCs. However, each macrolide affects them in different ways. PMID:17302905

  8. Study on rectal administration of azithromycin by suppository for pediatric use.

    PubMed

    Maeda, Miyuki; Nakano, Yukitaka; Aoyama, Takahiko; Matsumoto, Yoshiaki; Fujito, Hiroshi

    2016-04-01

    Azithromycin (AZM) is widely used as a first-line treatment option for children with mycoplasma pneumonia. Although pharmacists perform medication counseling in the pediatric ward, children often experience vomiting as a result of oral AZM administration. Drugs that are administered rectally are generally considered to enter the circulation system without passing through the liver first. The aim of our study was to prepare an AZM suppository and investigate the pharmaceutical properties and well as pharmacokinetics of the rectal administration route in humans. Five healthy volunteers were enrolled in the study. All subjects provided written informed consent before participating in the study. Subjects were randomly assigned to either oral administration of oral AZM 500-mg tablet or rectal administration of 125-mg, 250-mg, or 500-mg AZM suppository. Blood samples for preparation of serum were collected predose as well as at 1, 2, 3, 4, 6, 12, and 24 hours following the first rectal dose. Serum concentrations of AZM were determined by high-performance liquid chromatography (HPLC) with electrochemical detection. The bioavailability of the AZM suppository through rectal administration was 20.3% compared to oral administration. We hypothesize that the surface area where AZM is absorbed also affects the absorption by rectal administration. Although further investigation is necessary to improve the absorption of AZM by the rectum and to ensure safety in children, the AZM suppository may be an effective preparation in cases where oral administration is not tolerated.

  9. Preparation and characterization of azithromycin--Aerosil 200 solid dispersions with enhanced physical stability.

    PubMed

    Li, Xuechao; Peng, Huanhuan; Tian, Bin; Gou, Jingxin; Yao, Qing; Tao, Xiaoguang; He, Haibing; Zhang, Yu; Tang, Xing; Cai, Cuifang

    2015-01-01

    The main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). For solid dispersions prepared with both methods, no crystalline of AZI was detected (except for AZI: Aerosil 200=75:25) by DSC or PXRD, indicating the amorphous state of AZI in solid dispersions. The FT-IR results demonstrated the loss of crystallization water and the formation of hydrogen bonds between Aerosil 200 and AZI during the preparation of solid dispersions. After 4 weeks storage under accelerated condition, the degree of crystallinity of AZI increased in solid dispersions prepared by BM, whereas for solid dispersions containing AZI, Aerosil 200 and glyceryl behenate (GB) prepared by HME, no crystalline of AZI was identified. This high stability can be attributed to the hydrophobic properties of GB and the presence of hydrogen bonds. Based on the above results, it is inferred the protection of hydrogen bonds between AZI and Aerosil 200 formed during preparation process effectively inhibited the recrystallization of AZI and improved the physical stability of amorphous AZI in the presence of Aerosil 200.

  10. Emergence of Clinical Salmonella enterica Serovar Typhimurium Isolates with Concurrent Resistance to Ciprofloxacin, Ceftriaxone, and Azithromycin

    PubMed Central

    Wong, Marcus Ho Yin; Yan, Meiying; Chan, Edward Wai Chi; Biao, Kan

    2014-01-01

    Salmonella infection is an important public health issue for which the needs of antimicrobial treatment are increasing. A total of 546 human clinical S. enterica serovar Typhimurium isolates were recovered from patients in hospitals in China during the period of 2005 to ∼2011. Twenty percent of the isolates exhibited resistance to ciprofloxacin, and 4% were resistant to ceftriaxone. Importantly, for the first time, 12 (2%) S. Typhimurium isolates resistant to both ciprofloxacin and ceftriaxone were recovered; among these 12 isolates, two were also resistant to azithromycin, and one was resistant to all other drugs tested. The combined effects of various transferrable extended-spectrum β-lactamase determinants and a novel efflux-based ciprofloxacin resistance mechanism encoded by the mobile efflux gene oqxAB were responsible for the emergence of these extremely (highly) drug-resistant (XDR) S. Typhimurium isolates. The dissemination of resistance genes, such as those encoding ESBLs and the OqxAB pump, among Salmonella organisms will speed up the selection of XDR Salmonella, posing a huge threat to public health and Salmonella infection control. PMID:24752251

  11. New method for ophthalmic delivery of azithromycin by poloxamer/carbopol-based in situ gelling system.

    PubMed

    Cao, Feng; Zhang, Xiaolin; Ping, Qineng

    2010-01-01

    This study focused on preparation and evaluation of a thermosensitive and mucoadhesive in situ gelling ophthalmic system of azithromycin (ATM). Poloxamer 407 (P407) and poloxamer 188 (P188) were used as gelling agents. Addition of Carbopol 974P (CP 974P) to the gelling systems could increase the solubility of ATM by salt effect and enhance the mucoadhesive property of the systems. Gelation temperature of these systems ranged from 31.21-36.31 degrees C depending on the ratio of P407 and P188. Mucoadhesion force of the system composed of P407/P188/CP 974P (21/5/0.3%, w/v) was 2.3-fold that without carbopol 974P. Viscosity of the formulation was in a suitable range at 25 degrees C and pseudoplastic behavior was observed at 35 degrees C. The formulation exhibited a 24-h sustained release of ATM. In vivo resident experiments showed AUC(0-12) of ATM in rabbit tears increased by 1.78-fold for in situ gel compared with eye drop. At 12 h, tear concentrations exceeded minimum inhibitory concentration (MIC) breakpoint for the most common causative pathogens of bacterial conjunctivitis by 2.8-fold. Results in vitro and in vivo indicated that this droppable gel performed better than ATM eye drop did.

  12. Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers.

    PubMed

    Salman, Sam; Davis, Timothy M E; Page-Sharp, Madhu; Camara, Bully; Oluwalana, Claire; Bojang, Abdoulie; D'Alessandro, Umberto; Roca, Anna

    2015-12-28

    Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.).

  13. Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers

    PubMed Central

    Page-Sharp, Madhu; Camara, Bully; Oluwalana, Claire; Bojang, Abdoulie; D'Alessandro, Umberto; Roca, Anna

    2015-01-01

    Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.) PMID:26711756

  14. [Investigation of Intravenous Azithromycin Treatment Safety When Reducing Solvent for Intensive Care Unit Patients].

    PubMed

    Haruki, Yuto; Hagiya, Hideharu; Sakuma, Akiko; Haruki, Mai; Oka, Yasue; Sugiyama, Tetsuhiro; Kawakami, Yasuhiro; Kondo, Sachiyo

    2015-01-01

    Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

  15. IncA/C plasmids conferring high azithromycin resistance in vibrio cholera.

    PubMed

    Wang, Ruibai; Liu, Haican; Zhao, Xiuqin; Li, Jie; Wan, Kanglin

    2017-09-14

    Azithromycin (AZM) is a clinically important antibiotic to Vibrio cholerae especially for inhibiting colonization of V. cholerae in intestine and the treatment of severe cholera in children and pregnant women. One IncA/C plasmid was isolated from both of the high MIC AZM resistant V cholerae strains of the two mainly pathogenic serogroups, O1 and O139. In the 172 predicted ORFs, 16 genes were related to antibiotic resistance in which 5 were well-defined genes associated with macrolide resistance. The 5 macrolide resistant genes disturbed in two clusters, mphR-mrx-mph(K) and mel-mph2, flanking by insertion sequence (IS) and involving two kinds of mechanisms. The deletion of the complete region of the two clusters deceased the MIC of AZM from ≥64µg/ml to ≤ 0.5µg/ml. This IncA/C plasmid showed great ability to accumulate antibiotic resistant genes. Besides 11 genes to other antibiotics, five macrolide resistant genes with different function were gathered repeatedly through transposition on one plasmid. This genotype could not be simply explained by antibiotic stress applied on the host from the environment or treatment. These phosphorylase and transmembrane transports might be involved in the transport and metabolism of other non-antibiotic substances, enabling this kind of plasmid to propagate better in the host. Copyright © 2017. Published by Elsevier B.V.

  16. High azithromycin concentration in lungs by way of bovine serum albumin microspheres as targeted drug delivery: lung targeting efficiency in albino mice.

    PubMed

    Ramaiah, Balakeshwa; Nagaraja, Sree Harsha; Kapanigowda, Usha Ganganahalli; Boggarapu, Prakash Rao; Subramanian, Rajarajan

    2016-05-05

    Following administration, the antibiotic travels freely through the body and also accumulates in other parts apart from the infection site. High dosage and repeated ingestion of antibiotics in the treatment of pneumonia leads to undesirable effects and inappropriate disposition of the drug. By way of targeted lung delivery, this study was intended to eliminate inappropriate azithromycin disposition and to achieve higher azithromycin concentration to treat deeper airway infections. The Azithromycin Albumin Microspheres (AAM) was prepared by emulsion polymerization technique. The optimized AAM was subjected to in vitro release study, release kinetics, XRD and stability studies. Further, in vivo pharmacokinetics and tissue distribution of azithromycin released from AAM and azithromycin solution in albino mice was investigated to prove suitability of moving forward the next steps in the clinic. The mean particle size of the optimized AAM was 10.02 μm, an optimal size to get deposited in the lungs by mechanical entrapment. The maximum encapsulation efficiency of 82.3 % was observed in this study. The release kinetic was significant and best fitted for Korsmeyer-Peppas model (R(2) = 0.9962, n = 0.41). The XRD and stability study showed favorable results. Azithromycin concentration in mice lungs (40.62 μg g(-1), 30 min) of AAM was appreciably higher than other tissues and plasma. In comparison with control, azithromycin concentration in lungs was 30.15 μg g(-1) after 30 min. The azithromycin AUC (929.94 μg h mL(-1)) and intake rate (re) (8.88) for lung were higher and statistically significant in AAM group. Compared with spleen and liver, the targeting efficacy (te) in mice lung increased by a factor of 40.15 and ~14.10 respectively. Subsequently by a factor of 8.94, the ratio of peak concentration (Ce) in lung was higher in AAM treated mice. The AAM lung tissue histopathology did not show any degenerative changes. High azithromycin concentration in

  17. Azithromycin treatment is able to control the infection by two genotypes of Toxoplasma gondii in human trophoblast BeWo cells.

    PubMed

    Ribeiro, Mayara; Franco, Priscila Silva; Lopes-Maria, Janice Buiate; Angeloni, Mariana Bodini; Barbosa, Bellisa de Freitas; Gomes, Angelica de Oliveira; Castro, Andressa Silva; Silva, Rafaela José da; Oliveira, Fernanda Chaves de; Milian, Iliana Claudia Balga; Martins-Filho, Olindo Assis; Ietta, Francesca; Mineo, José Roberto; Ferro, Eloisa Amália Vieira

    2017-10-01

    Trophoblast infection by Toxoplasma gondii plays a pivotal role in the vertical transmission of toxoplasmosis. Here, we investigate whether the antibiotic therapy with azithromycin, spiramycin and sulfadiazine/pyrimethamine are effective to control trophoblast infection by two Brazilian T. gondii genotypes, TgChBrUD1 or TgChBrUD2. Two antibiotic protocols were evaluated, as follow: i) pre-treatment of T. gondii-tachyzoites with selected antibiotics prior trophoblast infection and ii) post-treatment of infected trophoblasts. The infection index/replication and the impact of the antibiotic therapy on the cytokine milieu were characterized. It was observed that TgChBrUD2 infection induced lower infection index/replication as compared to TgChBrUD1. Regardless the therapeutic protocol, azithromycin was more effective to control the trophoblast infection with both genotypes when compared to conventional antibiotics. Azithromycin induced higher IL-12 production in TgChBrUD1-infected cells that may synergize the anti-parasitic effect. In contrast, the effectiveness of azithromycin to control the TgChBrUD2-infection was not associated with the IL-12 production. BeWo-trophoblasts display distinct susceptibility to T. gondii genotypes and the azithromycin treatment showed to be more effective than conventional antibiotics to control the T. gondii infection/replication regardless the parasite genotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Development and validation of a reversed-phase HPLC method for simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet dosage form.

    PubMed

    Shaikh, K A; Patil, S D; Devkhile, A B

    2008-12-15

    A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet formulations. The chromatographic separation was achieved on a Xterra RP18 (250 mm x 4.6 mm, 5 microm) analytical column. A Mixture of acetonitrile-dipotassium phosphate (30 mM) (50:50, v/v) (pH 9.0) was used as the mobile phase, at a flow rate of 1.7 ml/min and detector wavelength at 215 nm. The retention time of ambroxol and azithromycin was found to be 5.0 and 11.5 min, respectively. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The linear dynamic ranges were from 30-180 to 250-1500 microg/ml for ambroxol hydrochloride and azithromycin, respectively. The percentage recovery obtained for ambroxol hydrochloride and azithromycin were 99.40 and 99.90%, respectively. Limit of detection and quantification for azithromycin were 0.8 and 2.3 microg/ml, for ambroxol hydrochloride 0.004 and 0.01 microg/ml, respectively. The developed method can be used for routine quality control analysis of titled drugs in combination in tablet formulation.

  19. Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines.

    PubMed

    Mal, Pinky; Dutta, Kallol; Bandyopadhyay, Debasish; Basu, Anirban; Khan, Rajni; Bishayi, Biswadev

    2013-03-01

    To determine alternate therapeutic measures to combat Staphylococcus aureus induced arthritis. Thus, azithromycin was combined with riboflavin, which may combat the ROS production and inflammation. An in vivo model of S. aureus infection-induced arthritis was set up by infecting mice with 5 × 10⁶ bacterial cell/mouse. S. aureus was administered intravenously. Azithromycin and riboflavin was injected intraperitoneally at a single dose of 100 and 20 mg/kg body, respectively. The mice were sacrificed at 3, 9, 15 days post infection (dpi). TNF-α, IFN-γ, IL-6 and IL-10 from serum and SOD, catalase and reduced glutathione concentration were observed in hepatic, cardiac, renal and splenic tissue. CFU was found very prominent in spleen and joints and reduced in blood at 3 and 9 dpi. However, treatment with azithromycin and riboflavin completely eradicated the bacteria from blood and spleen. TNF-α, IFN-γ, IL-6, and MCP-1 were induced due to infection which were downregulated by treatment with azithromycin and riboflavin. Infected mice were also found to have altered antioxidant status, measured in terms of reduced glutathione and anti-oxidant enzymes such as SOD and catalase. These changes were found to be ameliorated when the animals were co-treated with azithromycin and riboflavin.

  20. Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion.

    PubMed

    Arguedas, A; Loaiza, C; Rodriguez, F; Herrera, M L; Mohs, E

    1997-02-01

    The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media.

  1. Azithromycin inhibits expression of the GacA-dependent small RNAs RsmY and RsmZ in Pseudomonas aeruginosa.

    PubMed

    Pérez-Martínez, Isabel; Haas, Dieter

    2011-07-01

    Azithromycin at clinically relevant doses does not inhibit planktonic growth of the opportunistic pathogen Pseudomonas aeruginosa but causes markedly reduced formation of biofilms and quorum-sensing-regulated extracellular virulence factors. In the Gac/Rsm signal transduction pathway, which acts upstream of the quorum-sensing machinery in P. aeruginosa, the GacA-dependent untranslated small RNAs RsmY and RsmZ are key regulatory elements. As azithromycin treatment and mutational inactivation of gacA have strikingly similar phenotypic consequences, the effect of azithromycin on rsmY and rsmZ expression was investigated. In planktonically growing cells, the antibiotic strongly inhibited the expression of both small RNA genes but did not affect the expression of the housekeeping gene proC. The azithromycin treatment resulted in reduced expression of gacA and rsmA, which are known positive regulators of rsmY and rsmZ, and of the PA0588-PA0584 gene cluster, which was discovered as a novel positive regulatory element involved in rsmY and rsmZ expression. Deletion of this cluster resulted in diminished ability of P. aeruginosa to produce pyocyanin and to swarm. The results of this study indicate that azithromycin inhibits rsmY and rsmZ transcription indirectly by lowering the expression of positive regulators of these small RNA genes.

  2. Impact of Azithromycin on the Quorum Sensing-Controlled Proteome of Pseudomonas aeruginosa

    PubMed Central

    Swatton, J. E.; Davenport, P. W.; Maunders, E. A.; Griffin, J. L.; Lilley, K. S.; Welch, M.

    2016-01-01

    The macrolide antibiotic, azithromycin (AZM), has been reported to improve the clinical outcome of cystic fibrosis patients, many of whom are chronically-infected with Pseudomonas aeruginosa. However, the highest clinically-achievable concentrations of this drug are well-below the minimum inhibitory concentration for P. aeruginosa, raising the question of why AZM exhibits therapeutic activity. One possibility that has been raised by earlier studies is that AZM inhibits quorum sensing (QS) by P. aeruginosa. To explicitly test this hypothesis the changes brought about by AZM treatment need to be compared with those associated with specific QS mutants grown alongside in the same growth medium, but this has not been done. In this work, we used quantitative 2D-difference gel electrophoresis and 1H-NMR spectroscopy footprint analysis to examine whether a range of clinically-relevant AZM concentrations elicited proteomic and metabolomic changes in wild-type cultures that were similar to those seen in cultures of defined QS mutants. Consistent with earlier reports, over half of the AZM-induced spot changes on the 2D gels were found to affect QS-regulated proteins. However, AZM modulated very few protein spots overall (compared with QS) and collectively, these modulated proteins comprised only a small fraction (12–13%) of the global QS regulon. We conclude that AZM perturbs a sub-regulon of the QS system but does not block QS per se. Reinforcing this notion, we further show that AZM is capable of attenuating virulence factor production in another Gram-negative species that secretes copious quantities of exoenzymes (Serratia marcescens), even in the absence of a functional QS system. PMID:26808156

  3. Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus

    PubMed Central

    Liu, Xiaowei; Li, Zhan; Wang, Xiaodong; Chen, Yujuan; Wu, Fengbo; Men, Ke; Xu, Ting; Luo, Yan; Yang, Li

    2016-01-01

    Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro. In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections. PMID:28008253

  4. Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

    PubMed Central

    Euba, Begoña; Moleres, Javier; Viadas, Cristina; Barberán, Montserrat; Caballero, Lucía; Grilló, María-Jesús; Bengoechea, José Antonio; de-Torres, Juan Pablo; Liñares, Josefina; Leiva, José

    2015-01-01

    Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection. PMID:25712355

  5. Short-Term Azithromycin Treatment Promotes Cornea Allograft Survival in the Rat

    PubMed Central

    Hildebrand, Antonia; Eberwein, Philipp; Reinhard, Thomas; Schwartzkopff, Johannes

    2013-01-01

    Background Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats. Methods Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45+, CD4+, CD8+, CD25+, CD161+ and CD163+ cells were quantified via immunohistochemistry. Results AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls. Conclusions Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans. PMID:24349336

  6. [Efficacy and safety of azithromycin infusion in patients with mild or moderate community-acquired pneumonia].

    PubMed

    Noguchi, Shingo; Yatera, Kazuhiro; Kawanami, Toshinori; Yamasaki, Kei; Uchimura, Keigo; Hata, Ryosuke; Tachiwada, Takashi; Oda, Keishi; Hara, Kanako; Suzuki, Yu; Akata, Kentarou; Ogoshi, Takaaki; Tokuyama, Susumu; Inoue, Naoyuki; Nishida, Chinatsu; Orihashi, Takeshi; Yoshida, Yugo; Kawanami, Yukiko; Taura, Yusuke; Ishimoto, Hiroshi; Obata, Hideto; Tsuda, Toru; Yoshii, Chiharu; Mukae, Hiroshi

    2014-06-01

    Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

  7. Zika virus cell tropism in the developing human brain and inhibition by azithromycin

    PubMed Central

    Retallack, Hanna; Di Lullo, Elizabeth; Arias, Carolina; Knopp, Kristeene A.; Laurie, Matthew T.; Sandoval-Espinosa, Carmen; Mancia Leon, Walter R.; Krencik, Robert; Ullian, Erik M.; Spatazza, Julien; Pollen, Alex A.; Mandel-Brehm, Caleigh; Nowakowski, Tomasz J.; Kriegstein, Arnold R.; DeRisi, Joseph L.

    2016-01-01

    The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation. In the brain, ZIKV preferentially infected neural stem cells, astrocytes, oligodendrocyte precursor cells, and microglia, whereas neurons were less susceptible to infection. These findings suggest mechanisms for microcephaly and other pathologic features of infants with congenital ZIKV infection that are not explained by neural stem cell infection alone, such as calcifications in the cortical plate. Furthermore, we find that blocking the glia-enriched putative viral entry receptor AXL reduced ZIKV infection of astrocytes in vitro, and genetic knockdown of AXL in a glial cell line nearly abolished infection. Finally, we evaluate 2,177 compounds, focusing on drugs safe in pregnancy. We show that the macrolide antibiotic azithromycin reduced viral proliferation and virus-induced cytopathic effects in glial cell lines and human astrocytes. Our characterization of infection in the developing human brain clarifies the pathogenesis of congenital ZIKV infection and provides the basis for investigating possible therapeutic strategies to safely alleviate or prevent the most severe consequences of the epidemic. PMID:27911847

  8. Safety, tolerability and pharmacokinetic properties of coadministered azithromycin and piperaquine in pregnant Papua New Guinean women.

    PubMed

    Moore, Brioni R; Benjamin, John M; Auyeung, Siu On; Salman, Sam; Yadi, Gumul; Griffin, Suzanne; Page-Sharp, Madhu; Batty, Kevin T; Siba, Peter M; Mueller, Ivo; Rogerson, Stephen J; Davis, Timothy Me

    2016-07-01

    The aim of the present study was to investigate the safety, tolerability and pharmacokinetics of coadministered azithromycin (AZI) and piperaquine (PQ) for treating malaria in pregnant Papua New Guinean women. Thirty pregnant women (median age 22 years; 16-32 weeks' gestation) were given three daily doses of 1 g AZI plus 960 mg PQ tetraphosphate with detailed monitoring/blood sampling over 42 days. Plasma AZI and PQ were assayed using liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively. Pharmacokinetic analysis was by population-based compartmental models. The treatment was well tolerated. The median (interquartile range) increase in the rate-corrected electrocardiographic QT interval 4 h postdose [12 (6-26) ms(0) (.5) ] was similar to that found in previous studies of AZI given in pregnancy with other partner drugs. Six women with asymptomatic malaria cleared their parasitaemias within 72 h. Two apararasitaemic women developed late uncomplicated Plasmodium falciparum infections on Days 42 and 83. Compared with previous pregnancy studies, the area under the concentration-time curve (AUC0-∞ ) for PQ [38818 (24354-52299) μg h l(-1) ] was similar to published values but there was a 52% increase in relative bioavailability with each dose. The AUC0-∞ for AZI [46799 (43526-49462) μg h l(-1) ] was at least as high as reported for higher-dose regimens, suggesting saturable absorption and/or concentration-dependent tissue uptake and clearance from the central compartment. AZI-PQ appears to be well tolerated and safe in pregnancy. Based on the present/other data, total AZI doses higher than 3 g for the treatment and prevention of malaria may be unnecessary in pregnant women, while clearance of parasitaemia could improve the relative bioavailability of PQ. © 2016 The British Pharmacological Society.

  9. Surveillance and Azithromycin Treatment for Newcomers and Travelers Evaluation (ASANTE) Trial: Design and Baseline Characteristics.

    PubMed

    Ervin, Ann-Margret; Mkocha, Harran; Munoz, Beatriz; Dreger, Kurt; Dize, Laura; Gaydos, Charlotte; Quinn, Thomas C; West, Sheila K

    2016-12-01

    Immigrants and travelers may be sources of re-emergent infection in trachoma-endemic communities close to trachoma elimination. The primary objective of the A Surveillance and Azithromycin Treatment for Newcomers and Travelers Evaluation (ASANTE) trial was to determine whether a newcomer and traveler surveillance and treatment program in addition to annual mass drug administration (MDA) would reduce Chlamydia trachomatis infection when compared to MDA alone. ASANTE was a randomized controlled trial in 52 communities in Kongwa, Tanzania. In 26 intervention communities, monitors treated everyone in new households, in-coming children and guardians in existing households, and all persons in households who had traveled between annual MDA events. A total of 26 usual practice communities received MDA only. Surveys of 100 1-9-year-olds from each community were conducted at baseline and every 6 months up to 2 years to assess clinical trachoma and C. trachomatis infection. Data on demographics and environmental factors were also collected. Mean prevalences of trachomatous inflammation - follicular (TF) and C. trachomatis were equivalent between the two arms (5.2% and 3.7% in intervention, and 4.9% and 3.6% in usual practice communities, respectively). Of 318 children with TF, 36.5% tested positive for C. trachomatis. TF prevalence was higher among households without a bicycle (p = 0.03) and lower with increasing child's age (p < 0.001). Infection prevalence was higher among households >30 minutes from water (p = 0.015). TF and infection prevalence decreased with increasing years of education (p = 0.004 and p = 0.002, respectively). The ASANTE trial will inform guidance on the surveillance and treatment of persons traveling or newly arriving to communities hypo-endemic for trachoma.

  10. Multiple resistance to betalactam antibiotics, azithromycin or moxifloxacin in implant associated bacteria.

    PubMed

    Karbach, Julia; Callaway, Angelika S; Willershausen, Brita; Wagner, Wilfried; Al-Nawas, Bilal

    2013-01-01

    Antibiotics are more and more frequently prescribed in dentistry for prevention and treatment of oral diseases. Bacterial resistance to these agents is clearly increasing, including even previously susceptible micro-organisms and true pathogens. The aim of the present investigation was to examine resistant bacterial strains with respect to possible multiple antibiotic resistance. In a previous investigation, implant-associated bacteria were tested first as mixed cultures and again as pure isolates (n = 138) for resistance to one of five antibiotics (ampicillin/AM, ampicillin + sulbactam/AB, azithromycin/AZ, penicillin/PG, moxifloxacin/MX) using the Etest. The resistance of most of the pure isolates was lower than in mixed culture, but 31.2% had retained their original resistance. Subsequently, all 138 isolates were tested for resistance or susceptibility to the other four antibiotics, again using the Etest. 27.6% (38/138) of the isolates retained their original antibiotic resistance and were resistant to at least one other antibiotic (MIC > or = 128 microg/mL for AB, AM or AZ, > or = 32 microg/mL PG, > or = 24 microg/mL MX). 2.2% (3/138) strains had lost their original antibiotic resistance, but were resistant to at least one other antibiotic (MIC > 128 microg/mL for AB, AM, or AZ, > or = 32 microg/mL PG, > or = 24 microg/mL MX). Some of the isolates belonging to the implant-associated microflora were multi-resistant, even though the patients had not received any antibiotics six weeks prior to the sampling. The exact mechanisms that lead to multiple resistance need to be examined in further studies.

  11. Microbiological and Clinical Effects of Sitafloxacin and Azithromycin in Periodontitis Patients Receiving Supportive Periodontal Therapy

    PubMed Central

    Okui, Takafumi; Ito, Harue; Nakajima, Mayuka; Honda, Tomoyuki; Shimada, Yasuko; Tabeta, Koichi; Akazawa, Kohei

    2016-01-01

    Sitafloxacin (STFX) is a newly developed quinolone that has robust antimicrobial activity against periodontopathic bacteria. We previously reported that oral administration of STFX during supportive periodontal therapy was as effective as conventional mechanical debridement under local anesthesia microbiologically and clinically for 3 months. The aim of the present study was to examine the short-term and long-term microbiological and clinical effects of systemic STFX and azithromycin (AZM) on active periodontal pockets during supportive periodontal therapy. Fifty-one patients receiving supportive periodontal therapy were randomly allocated to the STFX group (200 mg/day of STFX for 5 days) or the AZM group (500 mg/day of AZM for 3 days). The microbiological and clinical parameters were examined until 12 months after the systemic administration of each drug. The concentration of each drug in periodontal pockets and the antimicrobial susceptibility of clinical isolates were also analyzed. The proportions of red complex bacteria, i.e., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are the representative periodontopathic bacteria, were significantly reduced at 1 month and remained lower at 12 months than those at baseline in both the STFX and AZM groups. Clinical parameters were significantly improved over the 12-month period in both groups. An increase in the MIC of AZM against clinical isolates was observed in the AZM group. These results indicate that monotherapy with systemic STFX and AZM might be an alternative treatment during supportive periodontal therapy in patients for whom invasive mechanical treatment is inappropriate. (This study has been registered with the University Hospital Medical Information Network-Clinical Trials Registry [UMIN-CTR] under registration number UMIN000007834.) PMID:26729495

  12. Impact of azithromycin resistance mutations on the virulence and fitness of Chlamydia caviae in guinea pigs.

    PubMed

    Binet, Rachel; Bowlin, Anne K; Maurelli, Anthony T; Rank, Roger G

    2010-03-01

    Azithromycin (AZM) is a major drug used in the treatment and prophylaxis of infections caused by Chlamydia, yet no significant clinical resistance has been reported for these obligate intracellular bacteria. Nevertheless, spontaneous AZM resistance (Azm(r)) arose in vitro at frequencies ranging from 3 x 10(-8) to 8 x 10(-10) for clonal isolates of Chlamydia caviae, which is a natural pathogen of guinea pigs. Sequencing of the unique 23S rRNA gene copy in 44 independent Azm(r) isolates identified single mutations at position A(2058) or A(2059) (Escherichia coli numbering system). While SP(6)AZ(1) (A(2058)C) and SP(6)AZ(2) (A(2059)C) Azm(r) mutants showed growth defects in cell culture and were less pathogenic in the guinea pig ocular infection model than in the parent SP(6), the three isogenic C. caviae isolates grew equally well in the animal. On the other hand, coinoculation of the C. caviae parent strain with one of the Azm(r) strains was detrimental for the mutant strain. This apparent lack of association between pathology and bacterial load in vivo showed that virulence of the two Azm(r) mutants of C. caviae was attenuated. While chlamydial growth in vitro reflects the ability of the bacteria to multiply in permissive cells, survival in the host is a balance between cellular multiplication and clearance by the host immune system. The obligate intracellular nature of Chlamydia may therefore limit emergence of resistance in vivo due to the strength of the immune response induced by the wild-type antibiotic-sensitive bacteria at the time of antibiotic treatment.

  13. Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial.

    PubMed

    Roca, A; Oluwalana, C; Bojang, A; Camara, B; Kampmann, B; Bailey, R; Demba, A; Bottomley, C; D'Alessandro, U

    2016-06-01

    Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa. Asymptomatic bacterial colonization is an intermediate step towards sepsis. We conducted a phase III, double-blind, placebo-controlled randomized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus, GBS or S. pneumoniae in the newborn at day 6 postpartum. Study participants were recruited in a health facility in western Gambia. They were followed for 8 weeks and samples were collected during the first 4 weeks. Between April 2013 and April 2014 we recruited 829 women who delivered 843 babies, including 13 stillbirths. Sixteen babies died during the follow-up period. No maternal deaths were observed. No serious adverse events related to the intervention were reported. According to the intent-to-treat analysis, prevalence of nasopharyngeal carriage of the bacteria of interest in the newborns at day 6 was lower in the intervention arm (28.3% versus 65.1% prevalence ratio 0.43; 95% CI 0.36-0.52, p <0.001). At the same time-point, prevalence of any bacteria in the mother was also lower in the azithromycin group (nasopharynx, 9.3% versus 40.0%, p <0.001; breast milk, 7.9% versus 21.6%, p <0.001; and the vaginal tract, 13.2% versus 24.2%, p <0.001). Differences between arms lasted for at least 4 weeks. Oral azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and may lower the risk of neonatal sepsis. Trial registrationClinicalTrials.gov Identifier NCT01800942.

  14. Synthesis and antibacterial activity of novel 4″-O-(1-aralkyl-1,2,3-triazol-4-methyl-carbamoyl) azithromycin analogs.

    PubMed

    Wang, Yinhu; Cong, Chao; Chai, Wern Chern; Dong, Ruiqian; Jia, Li; Song, Di; Zhou, Ziteng; Ma, Shutao

    2017-08-15

    Three novel structural series of 4″-O-(1-aralkyl-1,2,3-triazol-4-methyl-carbamoyl) azithromycin analogs were designed, synthesized and evaluated for their in vitro antibacterial activity. All the target compounds exhibited excellent activity against erythromycin-susceptible Streptococcus pyogenes, and significantly improved activity against three phenotypes of erythromycin-resistant Streptococcus pneumoniae compared with clarithromycin and azithromycin. Among the three series of azithromycin analogs, the novel series of 11,4″-disubstituted azithromycin analogs 9a-k exhibited the most effective and balanced activity against susceptible and resistant bacteria. Among them, compound 9j showed the most potent activity against Staphylococcus aureus ATCC25923 (0.008µg/mL) and Streptococcus pyogenes R2 (1µg/mL). Besides, all the 11,4″-disubstituted azithromycin analogs 9a-k except 9f shared the identical activity with the MIC value <0.002µg/mL against Streptococcus pyogenes S2. Furthermore, compounds 9g, 9h, 9j and 9k displayed significantly improved activity compared with the references against all the three phenotypes of resistant S. pneumoniae. Particularly, compound 9k was the most effective (0.06, 0.03 and 0.125µg/mL) against all the erythromycin-resistant S. pneumoniae expressing the erm gene, the mef gene and the erm and mef genes, exhibiting 2133, 133 and 2048-fold more potent activity than azithromycin, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Comparison of Azithromycin Pharmacokinetics following Single Oral Doses of Extended-Release and Immediate-Release Formulations in Children with Acute Otitis Media▿

    PubMed Central

    Liu, Ping; Fang, Annie F.; LaBadie, Robert R.; Crownover, Penelope H.; Arguedas, Adriano G.

    2011-01-01

    An azithromycin extended-release (ER) oral suspension was developed to improve the gastrointestinal tolerability profile without substantially compromising systemic exposure. A single dose of 30 mg/kg azithromycin immediate-release (IR) oral suspension has been used in children to treat acute otitis media (AOM). This study was conducted to compare the pharmacokinetics of a 60-mg/kg azithromycin ER single dose with a 30-mg/kg azithromycin IR single dose in children with AOM aged 6 months to 6 years (n = 19 per treatment). Serum samples were collected at 1, 2, 3, 4, 8, 24, 48, and 72 h after dosing. The area under the curve from time zero to 72 h postdosing (AUC0-72) was calculated based on a noncompartmental method. One-way analysis of variance (ANOVA) was used to compare exposure parameters (e.g., AUC0-72 and peak concentration) as well as concentrations at each time point. The adjusted geometric mean ratio of the ER/IR AUC0-72 was 157.98% (90% confidence interval [CI], 98.87%, 252.44%), which met the predefined criterion of the lower boundary of the 90% CI of ≥80%. As expected, due to the slower-release profile of the ER formulation, the concentrations of the ER formulation during the first 3 h were lower than those of the IR formulation. After 3 h postdosing, the lower boundaries of the 90% CI for the ER/IR concentration ratios were greater than 100%. These results indicated that a 60-mg/kg single dose of ER azithromycin provides similar or greater systemic exposure in children than the 30-mg/kg single dose of IR azithromycin. PMID:21859932

  16. A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana.

    PubMed

    Kwakye-Maclean, Cynthia; Agana, Nsiire; Gyapong, John; Nortey, Priscilia; Adu-Sarkodie, Yaw; Aryee, Esther; Asiedu, Kingsley; Ballard, Roland; Binka, Fred

    2017-01-01

    Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting. We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%. The mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority. A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular

  17. A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana

    PubMed Central

    2017-01-01

    Background Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting. Methodology We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1–15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%. Findings The mean age of participants was 9.5 years (S.D.3.1, range: 1–15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2–100) in the azithromycin group and 96.9% (95% CI: 94.1–99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9–64.9) in the azithromycin group and 49.1% (95% CI: 41.2–56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority. Conclusions A single oral dose of azithromycin, at a dosage of 30mg

  18. Resolution of spontaneous hemoabdomen secondary to peliosis hepatis following surgery and azithromycin treatment in a Bartonella species infected dog.

    PubMed

    Berkowitz, Steven T; Gannon, Kristi M; Carberry, Carol A; Cortes, Yonaira

    2016-11-01

    To describe a case of hemoperitonium in a dog with Bartonellosis and peliosis hepatis (PH) lesions that resolved following antimicrobial therapy. A 3-year-11-month-old 22.5 kg female spayed mixed breed dog presented for progressive lethargy and vomiting. An abdominal ultrasonographic examination revealed moderate ascites, which when sampled was nonclotting hemorrhagic fluid. An exploratory laparotomy revealed a large volume of nonclotted blood in the dog's abdomen and blood-filled vesicular lesions dispersed diffusely along multiple lobes of the liver. Biopsies revealed lesions indicative of PH. Serology testing for Bartonella species was positive. Treatment with azithromycin resulted in Bartonella serology negative status and no further evidence of hemoperitonium at recheck examination 12 months after initial presentation. This is the first reported case of PH and hemoperitoneum in a Bartonella species serology positive dog wherein treatment with azithromycin resulted in serology negative status. There have been no subsequent episodes of hemoperitoneum in the 12 months since treatment. © Veterinary Emergency and Critical Care Society 2016.

  19. Human serum activity of telithromycin, azithromycin and amoxicillin/clavulanate against common aerobic and anaerobic respiratory pathogens.

    PubMed

    Stein, Gary E; Schooley, Sharon; Tyrrell, Kerin L; Citron, Diane M; Goldstein, Ellie J C

    2007-01-01

    Telithromycin is a new ketolide antimicrobial with a good in vitro activity against both aerobic and anaerobic respiratory pathogens. In this study, we evaluated the antibacterial activity over time of telithromycin (800mg), azithromycin (500mg), and amoxicillin/clavulanate (875/125mg) in serum following single oral doses of these agents to 10 healthy subjects. Inhibitory and bactericidal titers were determined at 2, 6, 12, and 24h after each dose and the median titer was used to determine antibacterial activity. Against two azithromycin-resistant strains of Streptococcus pneumoniae, both telithromycin (MIC=0.25 and 0.5 microg/mL) and amoxicillin/clavulanate exhibited inhibitory and cidal activity for at least 6h. All three antibiotics provided prolonged (>or=12h) inhibitory activity against strains of Hemophilus influenzae (telithromycin MIC=4.0 microg/ml). Both telithromycin and amoxicillin/clavulanate exhibited rapid and prolonged inhibitory activity (>or=12h) against each of the anaerobes studied (Finegoldia [Peptostreptococcus] magna Peptostreptococcus micros, Prevotella bivia, and Prevotella melaninogenica). Moreover, both agents provided bactericidal activity against both Prevotella species. In this ex vivo pharmacodynamic study, we found that telithromycin provided rapid and prolonged antibacterial activity in serum against macrolide-resistant strains of S. pneumoniae, beta-lactamase-positive and -negative strains of H. influenzae, and common respiratory anaerobic pathogens. These findings suggest that telithromycin could have clinical utility in the treatment of community-acquired mixed aerobic-anaerobic respiratory tract infections, including chronic sinusitis and aspiration pneumonia.

  20. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients.

    PubMed

    Vafaeimanesh, Jamshid; Jalalzadeh, Mojgan; Nazarian, Morteza

    2014-01-01

    To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis (HD) patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg) and urease breath test (UBT). The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years). Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0). The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients.

  1. Optimization and validation of a stability-indicating RP-HPLC method for determination of azithromycin and its related compounds.

    PubMed

    El-Gindy, Alaa; Attia, Khalid A; Nassar, Mohammad Wafaa; Al Abasawi, Nasr M; Al-Shabrawi, Maisra

    2011-01-01

    A validated stability-indicating HPLC method was developed for the analysis of azithromycin (AZ) and its related compounds in raw materials, capsule, and suspension using an Xterra RP C18 column at 50 degrees C with UV detection at 215 nm. Isocratic elution was employed using the mobile phase 14 mM disodium hydrogen phosphate (pH 10.5, adjusted by 1 M NaOH)-methanol-acetonitrile-tetrahydrofuran (40.0 + 30.0 + 30.0 + 0.1, v/v/v/v). AZ and 14 of its related compounds were separated and quantified. The described method was linear over the range of 2-1800 microg/mL AZ with (r = 0.9999). The stability of AZ was studied under accelerated acidic, alkaline, and oxidative conditions. The proposed method was used to investigate the kinetics of acidic and alkaline hydrolysis process of AZ at different temperatures, and the apparent pseudo first-order rate constant, half-life, and activation energy were calculated. The major peak detected from the degradation of AZ in alkaline and acidic conditions was decladinosylazithromycine, while azithromycin N-oxide was detected from the oxidative degradation. Long-term stability studies for capsule and oral suspension were carried out. The proposed stability-indicating method was completely validated according to the U.S. Food and Drug Administration requirements.

  2. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma

    PubMed Central

    Sokana, Oliver; Nachamkin, Eli; Puiahi, Elliot; Kilua, Georgina; Pillay, Allan; Bottomley, Christian; Solomon, Anthony W.; Mabey, David C.

    2016-01-01

    Introduction Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. Methods This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1–14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. Results A total of 1,284 children were enrolled in the study. Amongst children aged 5–14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6–47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1–8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1–4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6–7.1%). This did not differ significantly from the

  3. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma.

    PubMed

    Marks, Michael; Sokana, Oliver; Nachamkin, Eli; Puiahi, Elliot; Kilua, Georgina; Pillay, Allan; Bottomley, Christian; Solomon, Anthony W; Mabey, David C

    2016-08-01

    Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%). This did not differ significantly from the seroprevalence in this age group that had been

  4. Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study.

    PubMed

    Baker, Kate S; Dallman, Timothy J; Ashton, Philip M; Day, Martin; Hughes, Gwenda; Crook, Paul D; Gilbart, Victoria L; Zittermann, Sandra; Allen, Vanessa G; Howden, Benjamin P; Tomita, Takehiro; Valcanis, Mary; Harris, Simon R; Connor, Thomas R; Sintchenko, Vitali; Howard, Peter; Brown, Jeremy D; Petty, Nicola K; Gouali, Malika; Thanh, Duy Pham; Keddy, Karen H; Smith, Anthony M; Talukder, Kaisar A; Faruque, Shah M; Parkhill, Julian; Baker, Stephen; Weill, François-Xavier; Jenkins, Claire; Thomson, Nicholas R

    2015-08-01

    Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK. We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships. We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated

  5. Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease.

    PubMed

    Jeong, Byeong-Ho; Jeon, Kyeongman; Park, Hye Yun; Moon, Seong Mi; Kim, Su-Young; Lee, Soo-Youn; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung

    2016-10-01

    Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. The effect of carbon dioxide on susceptibility testing of azithromycin, clarithromycin and roxithromycin against clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes by broth microdilution and the Etest: Artemis Project-first-phase study.

    PubMed

    Johnson, Jack; Bouchillon, Sam; Pontani, Dennis

    1999-06-01

    OBJECTIVE: To evaluate the effect of carbon dioxide on the susceptibility testing, using broth microdilution and the Etest (AB Biodisk, Solna, Sweden), of azithromycin, clarithromycin and roxithromycin against Streptococcus pneumoniae and Streptococcus pyogenes. METHODS: Fresh clinical isolates collected from 36 hospital laboratories in 12 countries were evaluated using the Etest in the presence of carbon dioxide. The isolates were retested under ambient conditions (absence of carbon dioxide) using broth microdilution and/or the Etest. RESULTS: Carbon dioxide falsely elevated azithromycin, clarithromycin and roxithromycin MIC90S for S. pneumoniae, determined by the Etest, approximately 12-fold. Also, the azithromycin MIC90 for S. pyogenes was increased fourfold; the effect was less marked for clarithromycin and roxithromycin. When isolates were retested in the absence of carbon dioxide, using the Etest or microdilution, susceptibilities to azithromycin were comparable to those to clarithromycin (S. pneumoniae, 93.4% versus 91.3%; S. pyogenes, 96.4% versus 95.8%). Both organisms were less susceptible to roxithromycin (S. pneumoniae, 71.3%; S. pyogenes, 85.7%). An internal standard control, consisting of 50 isolates each of S. pneumoniae, S. pyogenes and Haemophilus influenzae, confirmed that azithromycin susceptibility testing resulted in falsely elevated MICs. CONCLUSIONS: Carbon dioxide falsely elevated azithromycin MICs for S. pneumoniae and S. pyogenes, with an apparent reduction in susceptibility. When the in vitro activity of azithromycin and other macrolides against S. pneumoniae and S. pyogenes is being evaluated, awareness of the pH effect is essential.

  7. Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

    PubMed Central

    2010-01-01

    Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP) is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed. PMID:21029476

  8. In vitro characterization of pH-sensitive azithromycin-loaded methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) micelles.

    PubMed

    Teng, Fangfang; Deng, Peizong; Song, Zhimei; Zhou, Feilong; Feng, Runliang; Liu, Na

    2017-02-09

    In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment.

  9. Topical azithromycin and clarithromycin inhibit acute and chronic skin inflammation in sensitized mice, with apparent selectivity for Th2-mediated processes in delayed-type hypersensitivity.

    PubMed

    Ivetić Tkalčević, Vanesa; Cužić, Snježana; Kramarić, Miroslava Dominis; Parnham, Michael J; Eraković Haber, Vesna

    2012-02-01

    Macrolide antibiotics inhibit the secretion of Th1 cytokines while their effects on the release of Th2 cytokines are variable. We investigated molecular and cellular markers of Th1- and Th2-mediated inflammatory mechanisms and the anti-inflammatory activity of azithromycin and clarithromycin in phorbol 12-myristate 13-acetate (PMA) and oxazolone (OXA)-induced skin inflammation. Dexamethasone (50 μg/ear), azithromycin, and clarithromycin (500 μg/ear) reduced TNF-α and interleukin (IL)-1β concentration in ear tissue by inhibiting inflammatory cell accumulation in PMA-induced inflammation. In OXA-induced early delayed-type hypersensitivity (DTH), the macrolides (2 mg/ear) and dexamethasone (25 μg/ear) reduced ear tissue inflammatory cell infiltration and secretion of IL-4 while clarithromycin also decreased IFN-γ concentration. Macrolides showed better activity when administered after the challenge. In OXA-induced chronic DTH, azithromycin (1 mg/ear) reduced the number of ear tissue mast cells and decreased the concentration of IL-4 in ear tissue and of immunoglobulin (Ig)E in serum. Clarithromycin (1 mg/ear) reduced serum IgE concentration, possibly by a mechanism independent of IL-4, while both macrolides attenuated mast cell degranulation. In conclusion, azithromycin and clarithromycin attenuate pro-inflammatory cytokine production and leukocyte infiltration during innate immune reactions, while selectively affecting Th2 rather than Th1 immunity in DTH reactions.

  10. A sensitive and selective voltammetric sensor based on multiwall carbon nanotubes decorated with MgCr₂O₄ for the determination of azithromycin.

    PubMed

    Ensafi, Ali A; Allafchian, Ali R; Rezaei, B

    2013-03-01

    In this report, we synthesized MgCr(2)O(4) nanoparticles and then multiwall carbon nanotubes were decorated with the MgCr(2)O(4) nanoparticles. The characteristics of the new materials were studied with different techniques such as transmission electron microscopy, Fourier transform infrared spectroscopy, atomic force microscopy and electrochemical impedance spectroscopy. The multiwall carbon nanotubes decorated with MgCr(2)O(4) nanoparticles were used as a new mediator for voltammetric determination of azithromycin. The oxidation peak of azithromycin was appeared at a potential of about 720 mV at a surface of the modified electrode. Differential pulse voltammetry exhibited two wide linear dynamic ranges of 0.25-4.0 and 4.0-10.0 μmol L(-1) azithromycin with a detection limit of 0.07 μmol L(-1) at pH 7.0. The influence of potential interfering compounds on the selectivity was studied. Finally, the modified electrode showed good sensitivity, selectivity and stability for the determination of azithromycin in real samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Failure of oral antibiotic therapy, including azithromycin, in the treatment of a recurrent breast abscess caused by Salmonella enterica serotype Paratyphi A

    PubMed Central

    Fernando, Shelanah; Molland, Janice Gail; Gottlieb, Thomas

    2012-01-01

    We report a case of recurrent, multifocal Salmonella enterica serotype Paratyphi A breast abscesses, resistant to ciprofloxacin, which relapsed despite surgery, aspiration and multiple courses of antibiotics, including co-trimoxazole and azithromycin. The patient was cured after a prolonged course of intravenous ceftriaxone. PMID:23182142

  12. A Case-Control Study of Molecular Epidemiology in Relation to Azithromycin Resistance in Neisseria gonorrhoeae Isolates Collected in Amsterdam, the Netherlands, between 2008 and 2015.

    PubMed

    Wind, Carolien M; Bruisten, Sylvia M; Schim van der Loeff, Maarten F; Dierdorp, Mirjam; de Vries, Henry J C; van Dam, Alje P

    2017-06-01

    Neisseria gonorrhoeae resistance to ceftriaxone and azithromycin is increasing, which threatens the recommended dual therapy. We used molecular epidemiology to identify N. gonorrhoeae clusters and associations with azithromycin resistance in Amsterdam, the Netherlands. N. gonorrhoeae isolates (n = 143) were selected from patients visiting the Amsterdam STI Outpatient Clinic from January 2008 through September 2015. We included all 69 azithromycin-resistant isolates (MIC ≥ 2.0 mg/liter) and 74 frequency-matched susceptible controls (MIC ≤ 0.25 mg/liter). The methods used were 23S rRNA and mtrR sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), N. gonorrhoeae multilocus variable-number tandem-repeat analysis (NG-MLVA), and a specific PCR to detect mosaic penA genes. A hierarchical cluster analysis of NG-MLVA related to resistance and epidemiological characteristics was performed. Azithromycin-resistant isolates had C2611T mutations in 23S rRNA (n = 62, 89.9%, P < 0.001) and were NG-MAST genogroup G2992 (P < 0.001), G5108 (P < 0.001), or G359 (P = 0.02) significantly more often than susceptible isolates and were more often part of NG-MLVA clusters (P < 0.001). Two resistant isolates (2.9%) had A2059G mutations, and five (7.3%) had wild-type 23S rRNA. No association between mtrR mutations and azithromycin resistance was found. Twenty-four isolates, including 10 azithromycin-resistant isolates, showed reduced susceptibility to extended-spectrum cephalosporins. Of these, five contained a penA mosaic gene. Four of the five NG-MLVA clusters contained resistant and susceptible isolates. Two clusters consisting mainly of resistant isolates included strains from men who have sex with men and from heterosexual males and females. The co-occurrence of resistant and susceptible strains in NG-MLVA clusters and the frequent occurrence of resistant strains outside of clusters suggest that azithromycin resistance develops independently from the background genome

  13. 3‐day treatment with azithromycin 1.5% eye drops versus 7‐day treatment with tobramycin 0.3% for purulent bacterial conjunctivitis: multicentre, randomised and controlled trial in adults and children

    PubMed Central

    Cochereau, Isabelle; Meddeb‐Ouertani, Amel; Khairallah, Moncef; Amraoui, Abdelouahed; Zaghloul, Khalid; Pop, Mihai; Delval, Laurent; Pouliquen, Pascale; Tandon, Radhika; Garg, Prashant; Goldschmidt, Pablo; Bourcier, Tristan

    2007-01-01

    Aim To compare the efficacy and safety of Azyter, azithromycin 1.5% eye drops, for 3 days with tobramycin 0.3% for 7 days to treat purulent bacterial conjunctivitis. Methods This was a multicentre, randomised, investigator‐masked study including 1043 children and adults with purulent bacterial conjunctivitis. Patients received either azithromycin 1.5% twice‐daily for 3 days or tobramycin 0.3%, 1 drop every two hours for 2 days, then four times daily for 5 days. Clinical signs were evaluated and cultures obtained at D0, D3 and D9 (where D refers to “day”). Primary variable was the clinical cure at the Test‐of‐Cure (TOC)‐visit (D9±1), for patients with D0‐positive cultures. The cure was defined as: bulbar conjunctival injection and discharge scores of 0. Results Among 471 patients with D0‐positivity in the per protocol set, 87.8% of the azithromycin 1.5% group and 89.4% of the tobramycin group were clinically cured at the TOC‐visit. Azithromycin was non‐inferior to tobramycin for clinical and bacteriological cure. Clinical cure was significantly higher with azithromycin 1.5% at D3. The safety profile of azithromycin was satisfactory with a good patient and investigator's acceptability. Conclusions Azithromycin 1.5% for 3 days was as effective and as safe as tobramycin for 7 days. Furthermore, more azithromycin than tobramycin patients presented an early clinical cure at Day 3. Due to its twice daily dosing regimen for 3 days, azithromycin represents a step forward in the management of purulent bacterial conjunctivitis, especially in children. PMID:17050578

  14. How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?

    PubMed

    Zhou, Qi Tony; Loh, Zhi Hui; Yu, Jiaqi; Sun, Si-Ping; Gengenbach, Thomas; Denman, John A; Li, Jian; Chan, Hak-Kim

    2016-09-01

    Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprises two drugs in the designed mass ratio, which is supported by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. XPS and ToF-SIMS measurements also revealed that 50% by weight (or 35% by molecular fraction) of azithromycin in the formulation provided a near complete coating of 96.5% (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in fine particle fraction (FPF)recovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20% w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture.

  15. How much surface coating of hydrophobic azithromycin is sufficient to prevent moisture-induced decrease in aerosolisation of hygroscopic colistin powder?

    PubMed Central

    Zhou, Qi (Tony); Loh, Zhi Hui; Yu, Jiaqi; Sun, Si-ping; Gengenbach, Thomas; Denman, John A.; Li, Jian; Chan, Hak-Kim

    2017-01-01

    Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprise two drugs in the designed mass ratio, which is supported by XPS and ToF-SIMS data. XPS and ToF-SIMS measurements also revealed that 50 % by weight (or 35 % by molecular fraction) of azithromycin in the formulation provided a near-complete coating of 96.5 % (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in FPFrecovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20 %w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture. PMID:27255350

  16. Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages.

    PubMed Central

    Perronne, C; Gikas, A; Truffot-Pernot, C; Grosset, J; Vilde, J L; Pocidalo, J J

    1991-01-01

    The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection. PMID:1656860

  17. Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophages in chronic obstructive pulmonary disease subjects.

    PubMed

    Hodge, Sandra; Reynolds, Paul N

    2012-07-01

    Chronic inflammation and reduced airways integrity in chronic obstructive pulmonary disease (COPD) potentially results from secondary necrosis as a result of impaired phagocytosis of apoptotic material by airway macrophages, and increased bacterial colonization. We have previously shown that administration of low-dose azithromycin to subjects with COPD improved macrophage phagocytosis of apoptotic airway epithelial cells, reduced inflammation and increased expression of macrophage mannose receptor. We firstly investigated whether there were defects in the ability of both alveolar (AM) and monocyte-derived macrophages (MDM) to phagocytose bacteria in COPD, as we have previously reported for phagocytosis of apoptotic cells. We then assessed the effects of administration of low-dose azithromycin to COPD patients on the ability of AM and MDM to phagocytose bacteria. Azithromycin (250 mg orally daily for 5 days then 2× weekly (total 12 weeks)) was administered to 11 COPD subjects and phagocytosis of fluorescein isothiocyanate-labelled Escherichia coli assessed by flow cytometry. COPD subjects had a significant defect in the ability of both AM and MDM to phagocytose bacteria that was significantly improved by administration of low-dose azithromycin The data provide further support for the long-term use of low dose azithromycin as an attractive adjunct treatment option for COPD. Improved clearance of both apoptotic cells and bacteria in the airway may have a dual effect; reducing the risk of secondary necrosis and release of toxic cell contents that perpetuate inflammation as well as contributing to a reduction in the rate of exacerbations in COPD. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

  18. Killing of Streptococcus pneumoniae by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin using drug minimum inhibitory concentrations and mutant prevention concentrations.

    PubMed

    Blondeau, J M; Shebelski, S D; Hesje, C K

    2015-06-01

    Streptococcus pneumoniae continues to be a significant respiratory pathogen, and increasing antimicrobial resistance compromises the use of β-lactam and macrolide antibiotics. Bacterial eradication impacts clinical outcome, and bacterial loads at the site of infection may fluctuate. Killing of two macrolide- and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin against varying bacterial densities was determined using the measured minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). For kill experiments, 10(6)-10(9) CFU/mL were exposed to the drug and were sampled at 0, 0.5, 1, 2, 3, 4, 6, 12 and 24 h following drug exposure. The log(10) reduction and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L) for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin were 0.063-0.125/0.5-1, 0.031-0.063/0.25-0.5, 0.063/0.25-0.5, 0.008/0.016 and 0.031/0.25, respectively. Killing 10(6)-10(9) CFU/mL of bacteria by the drug MIC yielded incomplete killing, however log10 reductions occurred by 12 h and 24 h for all drugs. Exposure of 10(6)-10(9) CFU/mL to MPC drug concentrations resulted in the following log(10) reduction by 6h of drug exposure: azithromycin, 1.3-3.9; clarithromycin, 1.9-5.8; erythromycin, 0.8-4.7; telithromycin, 0.3-1.7; and gemifloxacin, 1.8-4.2. Bacterial loads at the site of infection may range from 10(6) to 10(9), and kill experiments utilising a higher bacterial inoculum provided a more accurate measure of antibiotic performance in high biomass situations. Killing was slower with telithromycin. Kill was greater and fastest with MPC versus MIC drug concentrations. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  19. RETRACTED: Azithromycin 1.5% Ophthalmic Solution for Blepharitis Treatment: Comparison of 14- Versus 30-Day Treatment.

    PubMed

    Altay, Yesim; Demirok, Gulizar; Balta, Ozgur; Bolu, Hulya

    2017-06-05

    The online-ahead-of-print published article, "Azithromycin 1.5% Ophthalmic Solution for Blepharitis Treatment: Comparison of 14- Versus 30-Day Treatment," by Altay Yesim, Demirok Gulizar, Balta Ozgur, and Bolu Hulya (DOI: 10.1089/jop.2015.0099) is being officially retracted from Journal of Ocular Pharmacology and Therapeutics (JOPT) due to post-publication authorship disputes and the discovery of simultaneous submission to both JOPT and the International Journal of Ophthalmology, which is a violation of the proper protocols of peer review. Journal of Ocular Pharmacology and Therapeutics and its editorial leadership are committed to maintaining the highest levels of scientific reporting and publishing, and therefore officially retracts the article based on the infringements listed herein.

  20. Development of NIRS method for quality control of drug combination artesunate–azithromycin for the treatment of severe malaria

    PubMed Central

    Boyer, Chantal; Gaudin, Karen; Kauss, Tina; Gaubert, Alexandra; Boudis, Abdelhakim; Verschelden, Justine; Franc, Mickaël; Roussille, Julie; Boucher, Jacques; Olliaro, Piero; White, Nicholas J.; Millet, Pascal; Dubost, Jean-Pierre

    2012-01-01

    Near infrared spectroscopy (NIRS) methods were developed for the determination of analytical content of an antimalarial-antibiotic (artesunate and azithromycin) co-formulation in hard gelatin capsule (HGC). The NIRS consists of pre-processing treatment of spectra (raw spectra and first-derivation of two spectral zones), a unique principal component analysis model to ensure the specificity and then two partial least-squares regression models for the determination content of each active pharmaceutical ingredient. The NIRS methods were developed and validated with no reference method, since the manufacturing process of HGC is basically mixed excipients with active pharmaceutical ingredients. The accuracy profiles showed β-expectation tolerance limits within the acceptance limits (±5%). The analytical control approach performed by reversed phase (HPLC) required two different methods involving two different preparation and chromatographic methods. NIRS offers advantages in terms of lower costs of equipment and procedures, time saving, environmentally friendly. PMID:22579599

  1. Lipopolysaccharide loss produces partial colistin dependence and collateral sensitivity to azithromycin, rifampicin and vancomycin in Acinetobacter baumannii.

    PubMed

    García-Quintanilla, Meritxell; Carretero-Ledesma, Marta; Moreno-Martínez, Patricia; Martín-Peña, Reyes; Pachón, Jerónimo; McConnell, Michael J

    2015-12-01

    Treatment options for multidrug-resistant (MDR) strains of Acinetobacter baumannii that acquire resistance to colistin are limited. Acinetobacter baumannii can become highly resistant to colistin through complete loss of lipopolysaccharide (LPS) owing to mutations in the genes encoding the first three enzymes involved in lipid A biosynthesis (lpxA, lpxC and lpxD). The objective of this study was to characterise the susceptibility to 15 clinically relevant antibiotics and 6 antimicrobial peptides (AMPs) of MDR A. baumannii clinical isolates that acquired colistin resistance due to mutations in lpxA, lpxC and lpxD as well as their colistin-susceptible counterparts. A dramatic increase in antibiotic susceptibility (≥16-fold increase) was observed upon LPS loss for azithromycin, rifampicin and vancomycin, whereas a moderate increase in susceptibility was seen for amikacin, ceftazidime, imipenem, cefepime and meropenem. Importantly, concentrations ranging from 8 mg/L to 32 mg/L of the six AMPs were able to reduce bacterial viability by ≥3 log10 in growth curve assays. We also demonstrate that colistin resistance results in partial colistin dependence for growth in LPS-deficient strains containing mutations in lpxA, lpxC and lpxD, but not when colistin resistance occurs via LPS modification due to mutations in the PmrA/B two-component system. The results of this study indicate that loss of LPS expression results in collateral sensitivity to azithromycin, rifampicin and vancomycin, and that the six AMPs tested retain activity against LPS-deficient strains, indicating that these antibiotics may be viable treatment options for infections caused by these strains. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62,993), and A-56268) on Toxoplasma gondii

    SciTech Connect

    Chang, H.R.; Pechere, J.C.

    1988-04-01

    The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with (/sup 3/H)uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

  3. Increasing Spectrum in Antimicrobial Resistance of Shigella Isolates in Bangladesh: Resistance to Azithromycin and Ceftriaxone and Decreased Susceptibility to Ciprofloxacin

    PubMed Central

    Mahbubur, Rahman; Shoma, Shereen; Rashid, Harunur; Arifeen, Shams El; Baqui, A.H.; Siddique, A.K.; Nair, G.B.; Sack, D.A.

    2007-01-01

    Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p<0.01) and nalidixic acid (from 19% to 51%, p<0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to ≥3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p<0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] ≥32 μg/mL) and had 10-fold higher MIC90 (0.25 μg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 μg/mL) and nalidixic acid (MIC 128 μg/mL) and low to ceftriaxone (MIC 0.023 μg/mL). Conjugative R-plasmids-encoded extended-spectrum ß-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution. PMID:17985817

  4. Prevalence of Trachoma in Car-Nicobar Island, India after Three Annual Rounds of Mass Drug Administration with Azithromycin

    PubMed Central

    Malhotra, Sumit; Vashist, Praveen; Gupta, Noopur; Kalaivani, Mani; Satpathy, Gita; Shah, Anita; Krishnan, Sujaya; Azad, Rajvardhan

    2016-01-01

    Background A high proportion of active trachoma infection in children of Car-Nicobar Island was reported through the Trachoma Rapid Assessment survey conducted in year 2010 by the same researchers. Annual mass drug treatment with azithromycin was administered from years 2010–12 to all individuals residing in this island for reducing the burden of active trachoma infection. A cross-sectional prevalence survey was conducted in the year 2013 to assess the post-treatment burden of trachoma in this population. Methods In the 15 randomly selected compact segments from each village of the island, children aged 1–9 years were examined for evidence of active trachoma infection and participants aged ten years and above were examined for trachomatous trichiasis and corneal opacity. Results A total of 809 children (1–9 years) and 2735 adults were examined. Coverage with azithromycin for all the three rounds was more than 80%. The prevalence of active trachoma infection in children aged 1–9 years old was 6.8% (95% CI 5.1, 8.5) and Trachomatous Trichiasis (TT) was 3.9% (95% CI 3.2, 4.6). The risk factors associated with active trachoma infection were older age and unclean faces. The risk factors associated with TT were older age and lower literacy level. Conclusion Trachoma has not been eliminated from Car-Nicobar Island in accordance to ‘Global Elimination of Trachoma, 2020’ guidelines. Sustained efforts and continuous surveillance admixed with adequate programmatic response is imperative for elimination of trachoma in the island. PMID:27391274

  5. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin [CP-62,993], and A-56268) on Toxoplasma gondii.

    PubMed Central

    Chang, H R; Pechère, J C

    1988-01-01

    The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with [3H]uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism. PMID:2837140

  6. Vibrio cholerae O1 with Reduced Susceptibility to Ciprofloxacin and Azithromycin Isolated from a Rural Coastal Area of Bangladesh

    PubMed Central

    Rashed, Shah M.; Hasan, Nur A.; Alam, Munirul; Sadique, Abdus; Sultana, Marzia; Hoq, Md. Mozammel; Sack, R. Bradley; Colwell, Rita R.; Huq, Anwar

    2017-01-01

    Cholera outbreaks occur each year in the remote coastal areas of Bangladesh and epidemiological surveillance and routine monitoring of cholera in these areas is challenging. In this study, a total of 97 Vibrio cholerae O1 isolates from Mathbaria, Bangladesh, collected during 2010 and 2014 were analyzed for phenotypic and genotypic traits, including antimicrobial susceptibility. Of the 97 isolates, 95 possessed CTX-phage mediated genes, ctxA, ace, and zot, and two lacked the cholera toxin gene, ctxA. Also both CTX+ and CTX− V. cholerae O1 isolated in this study carried rtxC, tcpAET, and hlyA. The classical cholera toxin gene, ctxB1, was detected in 87 isolates, while eight had ctxB7. Of 95 CTX+ V. cholerae O1, 90 contained rstRET and 5 had rstRCL. All isolates, except two, contained SXT related integrase intSXT. Resistance to penicillin, streptomycin, nalidixic acid, sulfamethoxazole-trimethoprim, erythromycin, and tetracycline varied between the years of study period. Most importantly, 93% of the V. cholerae O1 were multidrug resistant. Six different resistance profiles were observed, with resistance to streptomycin, nalidixic acid, tetracycline, and sulfamethoxazole-trimethoprim predominant every year. Ciprofloxacin and azithromycin MIC were 0.003–0.75 and 0.19–2.00 μg/ml, respectively, indicating reduced susceptibility to these antibiotics. Sixteen of the V. cholerae O1 isolates showed higher MIC for azithromycin (≥0.5 μg/ml) and were further examined for 10 macrolide resistance genes, erm(A), erm(B), erm(C), ere(A), ere(B), mph(A), mph(B), mph(D), mef(A), and msr(A) with none testing positive for the macrolide resistance genes. PMID:28270803

  7. A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam.

    PubMed

    Dolecek, Christiane; Tran, Thi Phi La; Nguyen, Ngoc Rang; Le, Thi Phuong; Ha, Vinh; Phung, Quoc Tuan; Doan, Cong Du; Nguyen, Thi Be Bay; Duong, Thanh Long; Luong, Bich Ha; Nguyen, Trung Binh; Nguyen, Thi Anh Hong; Pham, Ngoc Dung; Mai, Ngoc Lanh; Phan, Van Be Bay; Vo, Anh Ho; Nguyen, Van Minh Hoang; Tran, Thu Thi Nga; Tran, Thuy Chau; Schultsz, Constance; Dunstan, Sarah J; Stepniewska, Kasia; Campbell, James Ian; To, Song Diep; Basnyat, Buddha; Nguyen, Van Vinh Chau; Nguyen, Van Sach; Nguyen, Tran Chinh; Tran, Tinh Hien; Farrar, Jeremy

    2008-05-21

    Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. Controlled-Trials.com ISRCTN67946944.

  8. Azithromycin 1.5g Over 5 Days Compared to 1g Single Dose in Urethral Mycoplasma genitalium: Impact on Treatment Outcome and Resistance.

    PubMed

    Read, Tim R H; Fairley, Christopher K; Tabrizi, Sepehr N; Bissessor, Melanie; Vodstrcil, Lenka; Chow, Eric P F; Grant, Mieken; Danielewski, Jennifer; Garland, Suzanne M; Hocking, Jane S; Chen, Marcus Y; Bradshaw, Catriona S

    2017-02-01

    We evaluated the impact of extended azithromycin (1.5g over 5 days) on selection of macrolide resistance and microbiological cure in men with Mycoplasma genitalium urethritis during 2013-2015 and compared this to cases treated with azithromycin 1g in 2012-2013. Microbiological cure was determined for men with M. genitalium urethritis treated with azithromycin 1.5g using quantitative polymerase chain reaction specific for M. genitalium DNA on samples 14-100 days post-treatment. Pre- and post-treatment macrolide resistance mutations were detected by sequencing the 23 S gene. There was no difference in proportions with microbiological cure between azithromycin 1.5g and 1g: 62/106 (58%; 95% confidence interval [CI], 49%, 68%) and 56/107 (52%; 95%CI 42-62%), P = .34, respectively. Also, there was no difference in the proportion of wild-type 23 S rRNA (presumed macrolide sensitive) infections cured after 1.5g and azithromycin 1g: 28/34 (82%; 95%CI 65-92%) and 49/60 (82%; 95%CI 70-90%), P=1.0, respectively. There was no difference between 1.5g and 1g in the proportions of wild-type infections with post-treatment resistance mutations: 4/34 (12%; 95%CI 3-27%) and 11/60 (18%; 95%CI 10-30%), respectively, P = .40. Pre-treatment resistance was present in 51/98 (52%; 95%CI 42-62%) cases in 2013-2015 compared to 47/107 (44%; 95%CI 34-54%) in 2012-2013, P = .25. Extended azithromycin 1.5g was no more effective than a single 1g dose at achieving cure of M. genitalium urethritis and importantly did not reduce the selection of macrolide resistance. Nonmacrolide and new approaches for the treatment of M. genitalium urethritis are required. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  9. Azithromycin vs. Placebo for the Clinical Outcome in Campylobacter concisus Diarrhoea in Adults: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

    PubMed Central

    Nielsen, Hans Linde; Kirk, Karina Frahm; Bodilsen, Jacob; Ejlertsen, Tove; Nielsen, Henrik

    2016-01-01

    Campylobacter concisus has been associated with prolonged mild diarrhoea, but investigations regarding the efficacy of antimicrobial treatment have not been reported previously. We initiated a phase 3, single-centre, randomized, double-blinded, placebo-controlled study comparing the efficacy of 500 mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days. If symptoms persisted at day ten, the patient was offered cross-over study treatment of three days and another ten-day follow-up period. The primary efficacy endpoint was the clinical response, defined as time to cessation of diarrhoea (<3 stools/day or reversal of accompanying symptoms). Our estimated sample size was 100 patients. We investigated a total of 10,036 diarrheic stool samples from 7,089 adult patients. Five-hundred and eighty-eight C. concisus positive patients were assessed for eligibility, of which 559 were excluded prior to randomization. The three main reasons for exclusion were duration of diarrhoea longer than 21 days (n = 124), previous antibiotic treatment (n = 113), and co-pathogens in stools (n = 87). Therefore, 24 patients completed the trial with either azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16–19). One person in the azithromycin group and four from the placebo group chose to continue with crossover medication after the initial ten-day period. In the azithromycin group, there was a mean of seven days (95% CI: 5–9) to clinical cure and for the placebo group it was ten days (95% CI: 6–14) (OR—3 (95% CI: -7–1). We observed no differences in all examined outcomes between azithromycin treatment and placebo. However, due to unforeseen recruitment difficulties we did not reach our estimated sample size of 100 patients and statistical power to conclude on

  10. In Vitro Susceptibilities of Bordetella pertussis and Bordetella parapertussis to Two Ketolides (HMR 3004 and HMR 3647), Four Macrolides (Azithromycin, Clarithromycin, Erythromycin A, and Roxithromycin), and Two Ansamycins (Rifampin and Rifapentine)

    PubMed Central

    Hoppe, Jörg E.; Bryskier, André

    1998-01-01

    When tested by agar dilution on Mueller-Hinton agar supplemented with 5% horse blood, the ketolides HMR 3004 and HMR 3647 were slightly more active (MIC at which 90% of the isolates were inhibited [MIC90], 0.03 μg/ml) against Bordetella pertussis than azithromycin, clarithromycin, erythromycin A, and roxithromycin. Azithromycin (MIC90, 0.06 μg/ml) was the most active compound against B. parapertussis. Rifampin and rifapentine were considerably less active. PMID:9559823

  11. Influence of rhlR and lasR on Polymyxin Pharmacodynamics in Pseudomonas aeruginosa and Implications for Quorum Sensing Inhibition with Azithromycin.

    PubMed

    Bulman, Zackery P; Ly, Neang S; Lenhard, Justin R; Holden, Patricia N; Bulitta, Jürgen B; Tsuji, Brian T

    2017-04-01

    The impact of quorum sensing on polymyxin and azithromycin pharmacodynamics was assessed in Pseudomonas aeruginosa PAO1 and an isogenic rhlR/lasR double knockout. For polymyxin B, greater killing against the rhlR/lasR knockout than against PAO1 was observed at 10(8) CFU/ml (polymyxin B half-maximal effective concentration [EC50], 5.61 versus 12.5 mg/liter, respectively; P < 0.005). Polymyxin B combined with azithromycin (256 mg/liter) was synergistic against each strain, significantly reducing the respective polymyxin B EC50 compared to those with monotherapy (P < 0.005), and is a promising strategy by which to combat P. aeruginosa. Copyright © 2017 American Society for Microbiology.

  12. Septic arthritis of the hip in a Cambodian child caused by multidrug-resistant Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin treated with ceftriaxone and azithromycin.

    PubMed

    Pocock, J M; Khun, P A; Moore, C E; Vuthy, S; Stoesser, N; Parry, C M

    2014-08-01

    Septic arthritis is a rare complication of typhoid fever. A 12-year-old boy without pre-existing disease attended a paediatric hospital in Cambodia with fever and left hip pain. A hip synovial fluid aspirate grew multidrug-resistant Salmonella enterica ser. Typhi with intermediate susceptibility to ciprofloxacin. Arthrotomy, 2 weeks of intravenous ceftriaxone and 4 weeks of oral azithromycin led to resolution of symptoms. The optimum management of septic arthritis in drug-resistant typhoid is undefined.

  13. A Retrospective Review of Treatment Failures Using Azithromycin and Doxycycline in the Treatment of Rectal Chlamydia Infections in Women and Men Who Have Sex With Men.

    PubMed

    Gratrix, Jennifer; Brandley, Judith; Dane, Marla; Plitt, Sabrina S; Smyczek, Petra; Read, Ron; Singh, Ameeta E

    2016-02-01

    We examined the prevalence of rectal chlamydia treatment failures in men who have sex with men and women attending Alberta sexually transmitted infection clinics. Among those completing a test of cure, there was no significant difference among patients treated initially with azithromycin (treatment failure, 39/460 [8.5%]; 95% confidence interval, 5.9%-11.0%) compared with patients treated with doxycycline (0/16; 95% confidence interval, 0%-0.2%; P = 0.63).

  14. Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis.

    PubMed

    Haque, Reza M; Torkildsen, Gail L; Brubaker, Kurt; Zink, Richard C; Kowalski, Regis P; Mah, Francis S; Pflugfelder, Stephen C

    2010-08-01

    To evaluate the effect of 4 weeks of treatment with azithromycin ophthalmic solution 1% on eyelid bacterial load, tear cytokines, and signs and symptoms of blepharitis. Twenty-six subjects (mean age 64.2 years; 65% female; 100% white) with moderate to severe blepharitis received azithromycin ophthalmic solution 1% in the absence of warm compresses or eyelid scrubs for 28 days (twice a day on days 1 and 2 and once a day on days 3-28). Blepharitis signs and symptoms were evaluated at baseline (day 1) and compared with end of treatment (day 29) and 2 follow-up visits (2 and 4 weeks posttreatment). Tear collection and eyelid margin bacterial cultures were performed at baseline and end of treatment. Tear cytokines were measured by a multiplex immunobead assay. Four-week azithromycin treatment demonstrated significant decreases from baseline in investigator-rated signs of meibomian gland plugging, eyelid margin redness, palpebral conjunctival redness, and ocular discharge (P < or = 0.002) at day 29, which persisted 4 weeks posttreatment (P < or = 0.006). Subject-reported symptoms of eyelid itching, foreign body sensation/sandiness/grittiness, ocular dryness, ocular burning/pain, and swollen/heavy eyelids also demonstrated significant improvement from baseline (P < 0.001 for all symptoms and time points, except P = 0.037 for ocular dryness at visit 4). Eyelid margin culture exhibited significant decreases in coagulase-negative staphylococci and Corynebacterium xerosis bacteria. Changes in tear cytokine concentrations were not observed. Twelve subjects experienced 19 adverse events, 15 of which were ocular and none of which were serious. Azithromycin provided significant improvement in signs and symptoms of blepharitis after 4 weeks of treatment compared with baseline and persisted in the 4-week follow-up period.

  15. Quantitative analysis of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin (LY333328) activities against intracellular Staphylococcus aureus in mouse J774 macrophages.

    PubMed

    Seral, Cristina; Van Bambeke, Françoise; Tulkens, Paul M

    2003-07-01

    Using J774 macrophages, the intracellular activities of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin (LY333328) against Staphylococcus aureus (strain ATCC 25923) have been quantitatively assessed in a 24-h model. S. aureus was positively localized in phagolysosomes by confocal and electron microscopy, and extracellular growth was prevented with 0.5 mg of gentamicin/liter (1x MIC) in controls. When tested at extracellular concentrations equivalent to their maximum concentrations in human serum, all antibiotics except azithromycin caused a significant reduction of the postphagocytosis inoculum within 24 h, albeit to markedly different extents (telithromycin [2 mg/liter], 0.60 log; ciprofloxacin [4.3 mg/liter], 0.81 log; gentamicin [18 mg/liter], 1.21 log; moxifloxacin [4 mg/liter], 1.51 log; oritavancin [25 mg/liter], 3.49 log). Intracellular activities were not systematically related to drug accumulation (apparent cellular-to-extracellular concentration ratios in infected cells: ciprofloxacin, 3.2; gentamicin, 6.8; telithromycin, 8.7; moxifloxacin, 13.4; azithromycin, 50; oritavancin, 348). Intracellular activity was not directly correlated to extracellular activity as measured in broth. Conditions of pH 5 (i.e., mimicking that of phagolysosomes) markedly reduced the activity of gentamicin, azithromycin, and telithromycin (>or=32 x) and fairly extensively reduced that of ciprofloxacin and moxifloxacin (>or=4 x) but did not affect oritavancin activity. We conclude that the cellular accumulation of antibiotics is not the only parameter to take into account for intracellular activity but that local environmental conditions (such as pH) and other factors can also prove critical.

  16. Resistance to Ceftriaxone and Azithromycin in Neisseria gonorrhoeae Isolates From 7 Countries of South America and the Caribbean: 2010-2011.

    PubMed

    Thakur, Sidharath Dev; Araya, Pamela; Borthagaray, Graciela; Galarza, Patricia; Hernandez, Alina Llop; Payares, Daisy; Sanabria Cruz, Olga Marina; Carvallo, Maria Elena Trigoso; Corredor, Aura Helena; Dillon, Jo-Anne R

    2017-03-01

    Seven countries in Latin America and the Caribbean report on (2010 and 2011) the susceptibility of 2235 isolates of Neisseria gonorrhoeae to 6 antibiotics. Thirteen isolates had ceftriaxone minimum inhibitory concentrations (MICs) of 0.125 to ≥ 0.25 mg/L. The percentage of resistant isolates to the following antibiotics was: azithromycin, 1.0% to 1.7%; ciprofloxacin, 42.1% to 36.2%; penicillin, 31% to 35%; tetracycline, 21.8% to 22.6%.

  17. Development of a Simple RP-HPLC-UV Method for Determination of Azithromycin in Bulk and Pharmaceutical Dosage forms as an Alternative to the USP Method.

    PubMed

    Ghari, Tayebeh; Kobarfard, Farzad; Mortazavi, Seyed Alireza

    2013-01-01

    The present study was designed to develop a simple, validated liquid chromatographic method for the analysis of azithromycin in bulk and pharmaceutical dosage forms using ultraviolet detector. The best stationary phase was determined as C18 column, 5 μm, 250 mm × 4.6 mm. Mobile phase was optimized to obtain a fast and selective separation of the drug. Flow rate was 1.5 mL/min, Wavelength was set at 210 nm and the volume of each injection was 500 μL. An isocratic methanol/buffer mobile phase at the ratio of 90:10 v/v gave the best separation and resolution. The proposed method was accurate, precise, sensitive, and linear over a wide range of concentration of azithromycin. The developed method has the advantage of using UV detector compared to the USP method in which electrochemical detector has been used. The validated method was successfully applied to the determination of azithromycin in bulk and pharmaceutical dosage forms.

  18. Changes in the intestinal microbiota following the administration of azithromycin in a randomised placebo-controlled trial among infants in south India.

    PubMed

    Parker, Edward P K; Praharaj, Ira; John, Jacob; Kaliappan, Saravanakumar Puthupalayam; Kampmann, Beate; Kang, Gagandeep; Grassly, Nicholas C

    2017-08-23

    Macrolides are among the most widely prescribed antibiotics worldwide. However, their impact on the gut's bacterial microbiota remains uncertain. We characterised the intestinal microbiota in 6-11 month-old infants in India who received a 3-day course of azithromycin or placebo during a randomised trial of oral poliovirus vaccine immunogenicity (CTRI/2014/05/004588). In 60 infants per study arm, we sequenced the V4 region of the bacterial 16S rRNA gene in stool samples collected before and 12 days after finishing treatment. We also tested for the presence of common bacterial, viral, and eukaryotic enteropathogens in the same samples using real-time PCR in a Taqman array card (TAC) format. Azithromycin induced a modest decline in microbiota richness and a shift in taxonomic composition driven by a reduction in the relative abundance of Proteobacteria and Verrucomicrobia (specifically Akkermansia muciniphila). The former phylum includes pathogenic strains of Escherichia coli and Campylobacter spp. that declined in prevalence based on the TAC assay. These findings differ from previous observations among older children and adults in Europe and North America, suggesting that the effects of azithromycin on the bacterial microbiota may be specific to the age and geographic setting of its recipients.

  19. Development of a Simple RP-HPLC-UV Method for Determination of Azithromycin in Bulk and Pharmaceutical Dosage forms as an Alternative to the USP Method

    PubMed Central

    Ghari, Tayebeh; Kobarfard, Farzad; Mortazavi, Seyed Alireza

    2013-01-01

    The present study was designed to develop a simple, validated liquid chromatographic method for the analysis of azithromycin in bulk and pharmaceutical dosage forms using ultraviolet detector. The best stationary phase was determined as C18 column, 5 μm, 250 mm × 4.6 mm. Mobile phase was optimized to obtain a fast and selective separation of the drug. Flow rate was 1.5 mL/min, Wavelength was set at 210 nm and the volume of each injection was 500 μL. An isocratic methanol/buffer mobile phase at the ratio of 90:10 v/v gave the best separation and resolution. The proposed method was accurate, precise, sensitive, and linear over a wide range of concentration of azithromycin. The developed method has the advantage of using UV detector compared to the USP method in which electrochemical detector has been used. The validated method was successfully applied to the determination of azithromycin in bulk and pharmaceutical dosage forms. PMID:24250672

  20. Single-dose (30 mg/kg) azithromycin compared with 10-day amoxicillin/clavulanate for the treatment of uncomplicated acute otitis media: a double-blind, placebo-controlled, randomized clinical trial☆

    PubMed Central

    Block, Stan L; Arrieta, Antonio; Seibel, Matthew; McLinn, Samuel; Eppes, Stephen; Murphy, Mary J

    2003-01-01

    Background: The long half-life of azithromycin allows for single-dose oral therapy for acute otitis media (AOM). Objective: This study was designed to compare the efficacy and tolerability of single-dose azithromycin with 10-day, twice-daily amoxicillin/clavulanate for the treatment of new-onset, uncomplicated AOM in children. Methods: Children aged 6 months to 12 years with new-onset AOM were randomly assigned to receive either a single 30-mg/kg dose of azithromycin or standard-dose amoxicillin/clavulanate (45 mg/kg administered BID for 10 days) in a double-blind, double-placebo, multicenter clinical trial. The diagnosis of AOM was based on specific clinical signs and symptoms, and was confirmed by pneumatic otoscopy and acoustic reflectometry (level ≥3). Clinical response was assessed on days 12–16 and 28–32. Results: Mean (SD) age of children receiving azithromycin (n = 173) or amoxicillin/clavulanate (n = 173) was 2.7 (2.3) years and 3.4 (2.8) years, respectively, with 43% and 36% ≤2 years of age. Most (53.2%) of the children were boys, and most (51.2%) were white. Clinical success rates (intent-to-treat) for azithromycin and amoxicillin/clavulanate, respectively, were 87% and 88% (95% CI, −9.2 to 6.5) on day 12–16 and 75% and 75% (95% CI, −10.2 to 10.5) on day 28–32. The incidences of treatment-related adverse events for azithromycin and amoxicillin/clavulanate were 16.8% and 22.5%, respectively. Corresponding rates of diarrhea were 6.4% and 12.7%, respectively. Vomiting, which was generally mild, occurred in 7 children in each group. One azithromycin patient and 5 amoxicillin/clavulanate patients discontinued treatment because of adverse events. The compliance rate for azithromycin was significantly higher than that for amoxicillin/clavulanate (99% vs 83%; P<0.001). Conclusions: In this trial comparing the efficacy of single-dose azithromycin (30 mg/kg) with twice-daily amoxicillin/clavulanate (45 mg/kg) for the treatment of new

  1. Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in pediatric patients

    PubMed Central

    Koseki, Naoko; Kaiho, Miki; Ariga, Tadashi; Kikuta, Hideaki; Togashi, Takehiro; Oba, Koji; Morita, Keisuke; Nagano, Naoko; Nakanishi, Masanori; Hara, Kazuya; Hazama, Kyosuke; Watanabe, Toru; Yamanaka, Tatsuru; Sasaki, Satoshi; Furuyama, Hideto; Shibata, Mutsuo; Shida, Satoru; Ishizaka, Akihito; Tabata, Yuichi; Aoyagi, Hayato; Naito, Hiroyuki; Yoshioka, Mikio; Horino, Atsuko; Kenri, Tsuyoshi

    2017-01-01

    Objective To clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients. Methods A prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured. Results Mean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were <0.000125 and 0.001 μg/ml, respectively. The MIC90s of minocycline and tosufloxacin among the 27 isolates of MRMP were 1.0 and 0.25 μg/ml, respectively, and those among the 23 isolates of MSMP were 1.0 and 0.5 μg/ml, respectively. Conclusion Both minocycline and tosufloxacin showed good in vitro activities against MRMP. Minocycline, but not tosufloxacin, shortened the duration of fever in pediatric patients infected with MRMP compared to the duration of fever in patients treated with macrolides. PMID:28288170

  2. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Stokholm, Jakob; Chawes, Bo L; Vissing, Nadja H; Bjarnadóttir, Elín; Pedersen, Tine M; Vinding, Rebecca K; Schoos, Ann-Marie M; Wolsk, Helene M; Thorsteinsdóttir, Sunna; Hallas, Henrik W; Arianto, Lambang; Schjørring, Susanne; Krogfelt, Karen A; Fischer, Thea K; Pipper, Christian B; Bønnelykke, Klaus; Bisgaard, Hans

    2016-01-01

    Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period. In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297. Between Nov 17, 2010, and Jan 28, 2014, we randomly

  3. The efficacy of oral azithromycin in clearing ocular chlamydia: Mathematical modeling from a community-randomized trachoma trial

    PubMed Central

    Liu, Fengchen; Porco, Travis C.; Mkocha, Harran A.; Muñoz, Beatriz; Ray, Kathryn J.; Bailey, Robin L; Lietman, Thomas M.; West, Sheila K.

    2015-01-01

    Mass oral azithromycin distributions have dramatically reduced the prevalence of the ocular strains of chlamydia that cause trachoma. Assessing efficacy of the antibiotic in an individual is important in planning trachoma elimination. However, the efficacy is difficult to estimate, because post-treatment laboratory testing may be complicated by nonviable organisms or reinfection. Here, we monitored ocular chlamydial infection twice a year in pre-school children in 32 communities as part of a cluster-randomized clinical trial in Tanzania (prevalence in children was lowered from 22.0% to 4.7% after 3-year of annual treatment). We used a mathematical transmission model to estimate the prevalence of infection immediately after treatment, and found the effective field efficacy of antibiotic in an individual to be 67.6% (95% CI: 56.5–75.1%) in this setting. Sensitivity analyses suggested that these results were not dependent on specific assumptions about the duration of infection. We found no evidence of decreased efficacy during the course of the trial. We estimated an 89% chance of elimination after 10 years of annual treatment with 95% coverage. PMID:24593917

  4. Short-term malaria reduction by single-dose azithromycin during mass drug administration for trachoma, Tanzania.

    PubMed

    Schachterle, Stephen E; Mtove, George; Levens, Joshua P; Clemens, Emily; Shi, Lirong; Raj, Amrita; Dumler, J Stephen; Munoz, Beatriz; West, Shelia; Sullivan, David J

    2014-06-01

    Single-dose mass drug administration of azithromycin (AZT) is underway to eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause childhood deaths after administration. To examine the effect of single-dose AZ MDA on prevalent malaria infections in a large prospective cohort of children and parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of malaria parasitemia by real-time PCR for 6 months after single-dose AZT. In the first month after treatment but not in subsequent months, Plasmodium falciparum infections were reduced by 73% (95% CI 43%-89%) in treatment versus control villages and differences remained significant (p = 0.00497) in multivariate models with village-level random effects. Genetic sequencing of P. falciparum ribosomal L4 protein showed no mutations associated with AZT resistance. AZT mass drug administration caused a transient, 1-month antimalarial effect without selecting for P. falciparum ribosomal L4 resistance mutations in a region with a 10-year history of treating trachoma with this drug.

  5. Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014

    PubMed Central

    Demczuk, Walter; Martin, Irene; Peterson, Shelley; Bharat, Amrita; Van Domselaar, Gary; Graham, Morag; Lefebvre, Brigitte; Allen, Vanessa; Hoang, Linda; Tyrrell, Greg; Horsman, Greg; Wylie, John; Haldane, David; Archibald, Chris; Wong, Tom; Unemo, Magnus

    2016-01-01

    The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZMr) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZMr strains. The genomes of 213 AZMr and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZMr (MICs ≥ 256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One isolate with high-level AZMr collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate levels of AZMr (MICs = 2 to 4 and 8 to 32 μg/ml, respectively). Low-level AZMr was also associated with mtrR promoter mutations, including the −35A deletion and the presence of Neisseria meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZMr strains arise independently and can then rapidly expand clonally in a region through local sexual networks. PMID:26935729

  6. Azithromycin Attenuates Lung Inflammation in a Mouse Model of Ventilator-Associated Pneumonia by Multidrug-Resistant Acinetobacter baumannii

    PubMed Central

    Yamada, Koichi; Kaku, Norihito; Harada, Yosuke; Migiyama, Yohei; Nagaoka, Kentaro; Morinaga, Yoshitomo; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Izumikawa, Koichi; Kakeya, Hiroshi; Hasegawa, Hiroo; Mikamo, Hiroshige; Kohno, Shigeru

    2013-01-01

    Acinetobacter baumannii is one of the main pathogens that cause ventilator-associated pneumonia (VAP) and is associated with a high rate of mortality. Little is known about the efficacy of macrolides against A. baumannii. In order to confirm the efficacy of azithromycin (AZM) against VAP caused by multidrug-resistant A. baumannii (MDRAB), we used a mouse model that mimics VAP by placement of a plastic tube in the bronchus. AZM (10 and 100 mg/kg of body weight) was administered subcutaneously every 24 h beginning at 3 h after inoculation. Phosphate-buffered saline was administered as the control. Survival was evaluated over 7 days. At 48 h postinfection, mice were sacrificed and the numbers of viable bacteria in lungs and bronchoalveolar lavage fluid were compared. Histopathological analysis of lung specimens was also performed. The treatment groups displayed significantly longer survival than the control group (P < 0.05). AZM did not have an antimicrobial effect. Histopathological examination of lung specimens indicated that the progression of lung inflammation was prevented in the AZM-treated groups. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in bronchoalveolar lavage fluid were significantly decreased (P < 0.05) in the AZM-treated groups. AZM may have a role for the treatment of VAP with MDRAB because of its anti-inflammatory effects. PMID:23733468

  7. The efficacy of oral azithromycin in clearing ocular chlamydia: mathematical modeling from a community-randomized trachoma trial.

    PubMed

    Liu, Fengchen; Porco, Travis C; Mkocha, Harran A; Muñoz, Beatriz; Ray, Kathryn J; Bailey, Robin L; Lietman, Thomas M; West, Sheila K

    2014-03-01

    Mass oral azithromycin distributions have dramatically reduced the prevalence of the ocular strains of chlamydia that cause trachoma. Assessing efficacy of the antibiotic in an individual is important in planning trachoma elimination. However, the efficacy is difficult to estimate, because post-treatment laboratory testing may be complicated by nonviable organisms or reinfection. Here, we monitored ocular chlamydial infection twice a year in pre-school children in 32 communities as part of a cluster-randomized clinical trial in Tanzania (prevalence in children was lowered from 22.0% to 4.7% after 3-year of annual treatment). We used a mathematical transmission model to estimate the prevalence of infection immediately after treatment, and found the effective field efficacy of antibiotic in an individual to be 67.6% (95% CI: 56.5-75.1%) in this setting. Sensitivity analyses suggested that these results were not dependent on specific assumptions about the duration of infection. We found no evidence of decreased efficacy during the course of the trial. We estimated an 89% chance of elimination after 10 years of annual treatment with 95% coverage.

  8. An optimal LC-MS/MS method for determination of azithromycin in white blood cells: application to pediatric samples.

    PubMed

    Legrand, Tiphaine; Elie, Valery; Kotecha, Sailesh; Junot, Christophe; Jacqz-Aigrain, Evelyne; Pruvost, Alain

    2014-08-01

    Studies suggest that particular antimicrobial and anti-inflammatory properties of azithromycin (AZM) can be related to its extensive accumulation in white blood cells (WBCs). However, available methods for determination of AZM in WBCs require large blood volumes unsuited to a pediatric context. Therefore, an LC-MS/MS method was developed for determination of AZM in WBCs. WBCs were isolated from 500 µl of whole blood by lysing red blood cells. Then, lysis of WBCs was performed with methanol/buffer containing AZM-d3-(13)C as internal standard. After reversed phase LC, detection was performed under multiple reaction monitoring conditions in positive electrospray mode. Linearity ranged from 0.5 to 200 ng per WBC sample. Within-run and overall accuracy and precision ranged from 95.3 to 101.1% and from 1.6 to 4.7%, respectively. All validation parameters fulfilled international requirements. This method can be easily performed on small samples and provides reliable data, including in children and neonates.

  9. Comparison of adjunctive azithromycin and amoxicillin/metronidazole for patients with chronic periodontitis: preliminary randomized control trial.

    PubMed

    Saleh, A; Rincon, J; Tan, A; Firth, M

    2016-12-01

    There are insufficient guidelines for the use of adjunctive systemic antibiotics for patients with periodontal disease. The aim of this study was to compare clinical outcomes for patients with moderate-advanced chronic periodontitis treated with: scaling and root planing (SRP), SRP with amoxicillin and metronidazole (A+M), SRP with Azithromycin (Az). Thirty-seven non-smokers with generalized moderate to advanced chronic periodontitis were divided into three treatment groups: SRP, A+M and Az. Patients received the medications after the last SRP session and were reviewed three months later. Changes in clinical parameters were compared between the groups. Separate analyses were executed for: 'all sites', 'molar sites', 'sites with different PPD severities' and 'number of sites with shallow, moderate and deep PPD'. The three groups exhibited improvements in most clinical parameters. At three months, A+M showed a higher reduction in PPD compared to Az in the 'all sites analysis'. Molars exhibited better reduction in BOP and PPD with A+M than SRP. Pocket depth of the 4-6 mm category reduced more in the A+M than SRP. A+M experienced a higher increase in the number of sites with PPD 1-3 mm than Az. Adjunctive systemic antibiotics in the initial phase of treatment may result in improved clinical outcomes. © 2016 Australian Dental Association.

  10. Effects of irrigation with an antiseptic and oral administration of azithromycin on bacteremia caused by scaling and root planing.

    PubMed

    Morozumi, Toshiya; Kubota, Takehiko; Abe, Daisuke; Shimizu, Taro; Komatsu, Yasutaka; Yoshie, Hiromasa

    2010-11-01

    Transient bacteremia frequently occur secondary to several periodontal procedures. The purpose of the present study is to investigate the effects of irrigation with an essential oil-containing antiseptic (EO) and oral administration of azithromycin (AZM) on bacteremia caused by scaling and root planing (SRP). Thirty patients with chronic periodontitis were randomly assigned to three groups (control, EO, and AZM). The EO group received quadrant subgingival irrigation with EO, and mouthrinsing was continued at home for 1 week. Oral administration of AZM was started 3 days before SRP in the AZM group. No adjunctive treatment was performed before SRP in the control group. Peripheral blood and subgingival plaque were collected at baseline and after 1 week. The second blood sample was taken 6 minutes after the initiation of quadrant SRP. The blood samples were cultured and analyzed for bacteremia. Quantitative analysis of periodontopathic bacteria in the sulcus was performed using the polymerase chain reaction Invader method. Bacteremia incidence rates were 90%, 70%, and 20% for the control, EO, and AZM groups, respectively. Significant reduction of the incidence of bacteremia was shown in the AZM group only (P <0.01). Subgingival bacterial counts significantly decreased in both the EO and AZM groups (P <0.01). Quadrant SRP frequently induced bacteremia. Although AZM was effective in reducing bacteremia incidence, EO showed less effectiveness.

  11. Azithromycin Blocks Quorum Sensing and Alginate Polymer Formation and Increases the Sensitivity to Serum and Stationary-Growth-Phase Killing of Pseudomonas aeruginosa and Attenuates Chronic P. aeruginosa Lung Infection in Cftr−/− Mice▿

    PubMed Central

    Hoffmann, Nadine; Lee, Baoleri; Hentzer, Morten; Rasmussen, Thomas Bovbjerg; Song, Zhijun; Johansen, Helle Krogh; Givskov, Michael; Høiby, Niels

    2007-01-01

    The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM) has been shown to improve the lung function of CF patients. The present study was conducted in accordance with previous in vitro studies suggesting that the effect of AZM may be the inhibition of alginate production, blockage of quorum sensing (QS), and increased sensitivity to hydrogen peroxide and the complement system. Moreover, we show that AZM may affect the polymerization of P. aeruginosa alginate by the incomplete precipitation of polymerized alginate and high levels of readily dialyzable uronic acids. In addition, we find that mucoid bacteria in the stationary growth phase became sensitive to AZM, whereas cells in the exponential phase did not. Interestingly, AZM-treated P. aeruginosa lasI mutants appeared to be particularly resistant to serum, whereas bacteria with a functional QS system did not. We show in a CF mouse model of chronic P. aeruginosa lung infection that AZM treatment results in the suppression of QS-regulated virulence factors, significantly improves the clearance of P. aeruginosa alginate biofilms, and reduces the severity of the lung pathology compared to that in control mice. We conclude that AZM attenuates the virulence of P. aeruginosa, impairs its ability to form fully polymerized alginate biofilms, and increases its sensitivity to complement and stationary-phase killing, which may explain the clinical efficacy of AZM. PMID:17620382

  12. Dexamethasone suppression test

    MedlinePlus

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  13. Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers.

    PubMed

    Rajesh, A Michael; Popat, Kiritkumar Mangaldas

    2017-05-01

    The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug. Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI. In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37 ± 1.02% within 45 min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be "<28% and <60%", respectively. The release kinetics showed Fickian diffusion profile for ionically cross-linked beads and zero-order release mechanism for GA cross-linking beads. DRCs can be effectively used for taste masking and newly formulated IPN beads demonstrated sustained release of AZI.

  14. Azithromycin Treatment Alters Gene Expression in Inflammatory, Lipid Metabolism, and Cell Cycle Pathways in Well-Differentiated Human Airway Epithelia

    PubMed Central

    Ribeiro, Carla Maria P.; Hurd, Harry; Wu, Yichao; Martino, Mary E. B.; Jones, Lisa; Brighton, Brian; Boucher, Richard C.; O'Neal, Wanda K.

    2009-01-01

    Prolonged macrolide antibiotic therapy at low doses improves clinical outcome in patients affected with diffuse panbronchiolitis and cystic fibrosis. Consensus is building that the therapeutic effects are due to anti-inflammatory, rather than anti-microbial activities, but the mode of action is likely complex. To gain insights into how the macrolide azithromycin (AZT) modulates inflammatory responses in airways, well-differentiated primary cultures of human airway epithelia were exposed to AZT alone, an inflammatory stimulus consisting of soluble factors from cystic fibrosis airways, or AZT followed by the inflammatory stimulus. RNA microarrays were conducted to identify global and specific gene expression changes. Analysis of gene expression changes revealed that the AZT treatment alone altered the gene profile of the cells, primarily by significantly increasing the expression of lipid/cholesterol genes and decreasing the expression of cell cycle/mitosis genes. The increase in cholesterol biosynthetic genes was confirmed by increased filipin staining, an index of free cholesterol, after AZT treatment. AZT also affected genes with inflammatory annotations, but the effect was variable (both up- and down-regulation) and gene specific. AZT pretreatment prevented the up-regulation of some genes, such as MUC5AC and MMP9, triggered by the inflammatory stimulus, but the up-regulation of other inflammatory genes, e.g., cytokines and chemokines, such as interleukin-8, was not affected. On the other hand, HLA genes were increased by AZT. Notably, secreted IL-8 protein levels did not reflect mRNA levels, and were, in fact, higher after AZT pretreatment in cultures exposed to the inflammatory stimulus, suggesting that AZT can affect inflammatory pathways other than by altering gene expression. These findings suggest that the specific effects of AZT on inflamed and non-inflamed airway epithelia are likely relevant to its clinical activity, and their apparent complexity may help

  15. Development of a Population Pharmacokinetic Model To Describe Azithromycin Whole-Blood and Plasma Concentrations over Time in Healthy Subjects

    PubMed Central

    Anic-Milic, T.; Oreskovic, K.; Padovan, J.; Brouwer, K. L. R.; Zuo, P.; Schmith, V. D.

    2013-01-01

    Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [Cb]) and plasma (concentration in plasma [Cp]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI Cb and Cp were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose, Cb was greater than Cp. Importantly, Cb, but not Cp, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC24) was ∼2-fold greater than the plasma AUC24, but simulations suggested that Cb was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described Cp and Cb, but Cp was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI Cb in healthy subjects, the distribution parameters between Cp and Cb, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict Cb from Cp for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.) PMID:23629714

  16. Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation.

    PubMed

    Williams, Kirsten M; Cheng, Guang-Shing; Pusic, Iskra; Jagasia, Madan; Burns, Linda; Ho, Vincent T; Pidala, Joseph; Palmer, Jeanne; Johnston, Laura; Mayer, Sebastian; Chien, Jason W; Jacobsohn, David A; Pavletic, Steven Z; Martin, Paul J; Storer, Barry E; Inamoto, Yoshihiro; Chai, Xiaoyu; Flowers, Mary E D; Lee, Stephanie J

    2016-04-01

    Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM. Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.

  17. An analysis of policies for cotrimoxazole, amoxicillin and azithromycin use in Namibia's public sector: Findings and therapeutic implications.

    PubMed

    Kibuule, Dan; Mubita, Mwangana; Naikaku, Ester; Kalemeera, Francis; Godman, Brian B; Sagwa, Evans

    2017-02-01

    Despite Namibia's robust medicine use systems and policies, antibiotic use indicators remain suboptimal. Recent medicine use surveys rank cotrimoxazole, amoxicillin and azithromycin (CAA) among the most used medicines. However, there is rising resistance to CAA (55.9%-96.7%). Unfortunately, to date, there have been limited studies evaluating policies to improve antibiotic use in Namibia. To evaluate public sector pharmaceutical policies and guidelines influencing the therapeutic use of CAA antibiotics in Namibia. Evaluate Namibia's pharmaceutical policies and guidelines for CAA use through quantitative text analysis. The main outcome variables were the existence of antibiotic policies, therapeutic indications per antibiotic and the type/level of healthcare facility allowed to use the antibiotic. Policies for antibiotic use were limited, with only the draft Namibia Medicines Policy having a statement on antibiotic use. Several essential antibiotics had no therapeutic indications mentioned in the guidelines. Twenty-nine antibiotics were listed for 69 therapeutic indications; CAA (49.3%) antibiotics and ATC J01C/J01D (48%) having the highest indications per antibiotic. For CAA antibiotics, this suggested use was mainly for acute respiratory infections (n=22, 37.2%). Published policies (58.6%-17/29) recommended antibiotics for use at the primary healthcare (PHC) level, with CAA antibiotics recommended mostly for respiratory tract infections and genitourinary infections. Policy and guidelines for antibiotic use in Namibia are not comprehensive and are skewed towards PHCs. Existing policies promote the wide use of CAA antibiotics, which may inadvertently result in their inappropriate use enhancing resistance rates. This calls for the development of more comprehensive antibiotic guidelines and essential medicine lists in tandem with local antimicrobial resistance patterns. In addition, educational initiatives among all key stakeholder groups. © 2017 John Wiley & Sons Ltd.

  18. Effect of azithromycin on gingival overgrowth induced by cyclosporine A + nifedipine combination therapy: A morphometric analysis in rats

    PubMed Central

    Ratre, Madhu Singh; Mehta, Dhoom Singh

    2016-01-01

    Background: Drug-induced gingival overgrowth (DIGO) is a well-known adverse effect of cyclosporine A (CsA) and nifedipine (Nf) therapy. The aim of the present morphometric study was to evaluate the effect of azithromycin (Azi) on the combined GO in rats induced by CsA + Nf combination. Materials and Methods: Thirty Sprague-Dawley male rats were randomly divided equally into three groups. Group 1 (control) received olive oil only; Group 2 received a combination of CsA and Nf in olive oil throughout the study period; Group 3 received CsA + Nf combination therapy, and Azi was added for 1 week in the 5th week. All the drugs were delivered by oral route. Impressions of the mandibular central incisal regions were taken, and study models were prepared at baseline and biweekly up to the 8 weeks. Statistical analysis was done by one-way analysis of variance and intergroup comparisons were made using Tukey's post hoc analysis. Results: Significant GO was evident in Group 2 and Group 3 rats when compared to Group 1. However, in Group 3 (Azi), GO was observed up to the 4th week, but a significant decrease in GO was noticed during 6–8th week after the administration of Azi in 5th week. Conclusion: Azi is an effective drug in the remission of DIGO induced by combined therapy of CsA + Nf and thereby can be considered as a useful therapeutic regimen in minimizing the DIGO in transplant patients. PMID:28298821

  19. Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on an In Vitro Polymicrobial Subgingival Biofilm Model

    PubMed Central

    Teles, Flavia; Starr, Jacqueline R.; Feres, Magda; Patel, Michele; Martin, Lynn

    2015-01-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs. PMID:25733510

  20. Optimal Antimalarial Dose Regimens for Sulfadoxine-Pyrimethamine with or without Azithromycin in Pregnancy Based on Population Pharmacokinetic Modeling.

    PubMed

    Salman, Sam; Baiwog, Francisca; Page-Sharp, Madhu; Griffin, Susan; Karunajeewa, Harin A; Mueller, Ivo; Rogerson, Stephen J; Siba, Peter M; Ilett, Kenneth F; Davis, Timothy M E

    2017-05-01

    Optimal dosing of sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment in pregnancy remains to be established, particularly when coadministered with azithromycin (AZI). To further characterize SP pharmacokinetics in pregnancy, plasma concentration-time data from 45 nonpregnant and 45 pregnant women treated with SP-AZI (n = 15 in each group) and SP-chloroquine (n = 30 in each group) were analyzed. Population nonlinear mixed-effect pharmacokinetic models were developed for pyrimethamine (PYR), sulfadoxine (SDOX), and N-acetylsulfadoxine (the SDOX metabolite NASDOX), and potential covariates were included. Pregnancy increased the relative clearance (CL/F) of PYR, SDOX, and NASDOX by 48, 29, and 70%, respectively, as well as the relative volumes of distribution (V/F) of PYR (46 and 99%) and NASDOX (46%). Coadministration of AZI resulted in a greater increase in PYR CL/F (80%) and also increased NASDOX V/F by 76%. Apparent differences between these results and those of published studies of SP disposition may reflect key differences in study design, including the use of an early postpartum follow-up study rather than a nonpregnant comparator group. Simulations based on the final population model demonstrated that, compared to conventional single-dose SP in nonpregnant women, two such doses given 24 h apart should ensure that pregnant women have similar drug exposure, while three daily SP doses may be required if SP is given with AZI. The results of past and ongoing trials using recommended adult SP doses with or without AZI in pregnant women may need to be interpreted in light of these findings and consideration given to using increased doses in future trials. Copyright © 2017 American Society for Microbiology.

  1. Azithromycin pharmacokinetics in the serum and its distribution to the skin in healthy dogs and dogs with pyoderma.

    PubMed

    Zur, Gila; Soback, Stefan; Weiss, Yfat; Perry, Elad; Lavy, Eran; Britzi, Malka

    2014-04-01

    Serum and skin tissue azithromycin (AZM) concentrations were analysed in healthy and pyoderma affected dogs to determine AZM pharmacokinetics and to establish the effect of disease on AZM skin disposition. AZM was administered orally to two groups of healthy dogs: (1) at 7.02 mg/kg (n=7) and (2) at 11.2mg/kg (n=9). A crossover design was used on five of them. Seven dogs with pyoderma were treated with AZM at 10.7 mg/kg. The two groups of healthy dogs received AZM once daily over three consecutive days and dogs with pyoderma received the same treatment repeated twice with an interval of 1 week. AZM concentrations were determined by liquid chromatography-tandem mass spectrometry. AZM was rapidly absorbed and slowly excreted. In healthy dogs, maximum serum concentrations appeared 2h after administration and were (mean ± standard deviation) 0.60 ± 0.25 μg/mL and 1.03 ± 0.43 μg/mL, and the half-lives were 49.9 ± 5.10 and 51.9 ± 6.69 h for doses of 7.02 and 11.2mg/kg, respectively. Clearance (CL0-24/F) was similar in both dosing groups (1.24 ± 0.24 and 1.29 ± 0.24 L/h/kg) and the respective mean residence time (MRT0-24) was 11.1 ± 0.8 and 8.4 ± 2.2h. The skin concentration in healthy dogs was 3.5-6.5 and 5.0-12.0 times higher than the corresponding serum concentration after the two doses and increased after the cessation of AZM administration. The ratio increased significantly in inflamed tissue (9.5-26.2).

  2. Studies on ocular and parenteral application potentials of azithromycin- loaded anionic, cationic and neutral-charged emulsions.

    PubMed

    Tamilvanan, Shunmugaperumal; Khanum, Ramona; Senthilkumar, Sudalimuthu Ramachandran; Muthuraman, Marimuthu; Rajasekharan, Thenrajan

    2013-10-01

    Ocular and parenteral application potentials of azithromycin-containing, non-phospholipid-based cationic nanosized emulsion in comparison to the phospholipid-based anionic and neutral-charged nanosized emulsions were investigated. Various physical, chemical, nonclinical toxicity and antimicrobial activity studies (mean droplet diameter, surface charge, creaming index, entrapment efficiency, accelerated, long-term and freeze-thaw cycling stabilities, TLC study, modified hen's egg chorioallantoic membrane (HET-CAM) test, in vitro hemolysis test, in vitro and in vivo myotoxicity, and in vitro antimicrobial activity) were conducted for assessing the potentials of these three types of emulsions. Following autoclave sterilization, all of these emulsions exhibited a nanometer range mean particle diameter (200 ± 29 to 434 ± 13 nm). While the anionic and cationic emulsions did show high negative (-34.2 ± 1.23 mV) and positive zeta potential (42.6 ± 1.45 mV) values, the neutral-charged emulsion did not. Even with 5 freeze-thaw cycles, the cationic emulsion remained stable whereas other two emulsions underwent phase-separation. The hen's egg chorioallantoic membrane test revealed an irritation score value that was higher for the anionic emulsion than for cationic or neutral-charged emulsion. A significantly higher % hemolysis value was also noticed for the anionic emulsion when compared to the % hemolysis value of cationic emulsion (ANOVA, P ‹ 0.05). However, all of the emulsions showed a lesser intracellular creatine kinase (CK) release/plasma CK level in comparison to the positive control (phenytoin) indicating their lesser myotoxicity at the injection site . When compared to anionic and neutral-charged emulsions, the possible controlled drug release from cationic emulsion delayed the in vitro antimicrobial action against H.influenzae and S.pneumoniae.

  3. Effects of azithromycin, metronidazole, amoxicillin, and metronidazole plus amoxicillin on an in vitro polymicrobial subgingival biofilm model.

    PubMed

    Soares, Geisla M S; Teles, Flavia; Starr, Jacqueline R; Feres, Magda; Patel, Michele; Martin, Lynn; Teles, Ricardo

    2015-05-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs.

  4. Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy.

    PubMed

    Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Spiller, O Brad; Ireland, Demelza J; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A; Newnham, John P

    2014-11-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  5. Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Spiller, O. Brad; Ireland, Demelza J.; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A.; Newnham, John P.

    2014-01-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  6. Killing of Staphylococcus aureus in murine macrophages by chloroquine used alone and in combination with ciprofloxacin or azithromycin

    PubMed Central

    Dey, Somrita; Bishayi, Biswadev

    2015-01-01

    This study aimed to determine any alteration in the killing of Staphylococcus aureus in murine peritoneal macrophages when chloroquine (CQ) is used alone compared with when it is used in combination with ciprofloxacin (CIP) or azithromycin (AZM). The study also aimed to find out the implication of reactive oxygen species (ROS) production and cytokine release in the intracellular killing of S. aureus in macrophages. We present here data obtained with a model of S. aureus-infected mouse peritoneal macrophages in which the intracellular growth of the bacteria and the influence of antibiotics was monitored for 30, 60, and 90 minutes in the presence or absence of CQ along with the production of ROS and alteration in levels of antioxidant enzymes and cytokines. It was observed that S. aureus-triggered cytokine response was regulated when macrophages were co-cultured with CQ and AZM as compared with CQ stimulation only. It can be suggested that action of AZM in mediating bacterial killing is enhanced by the presence of CQ, indicating enhanced uptake of AZM during early infection that may be essential for bacteria killing by AZM. Reduction of oxidative stress burden on the S. aureus-infected macrophages may pave the way for better killing of internalized S. aureus by CQ plus ciprofloxacin (CIP) or CQ plus AZM. Based on these observations, one may speculate that in an inflammatory milieu, CQ loaded with AZM elicits a stronger proinflammatory response by increasing the intracellular uptake of AZM or CIP, thus enabling the immune system to mount a more robust and prolonged response against intracellular pathogens. PMID:25653549

  7. Development of a population pharmacokinetic model to describe azithromycin whole-blood and plasma concentrations over time in healthy subjects.

    PubMed

    Pene Dumitrescu, T; Anic-Milic, T; Oreskovic, K; Padovan, J; Brouwer, K L R; Zuo, P; Schmith, V D

    2013-07-01

    Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [Cb]) and plasma (concentration in plasma [Cp]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI Cb and Cp were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose, Cb was greater than Cp. Importantly, Cb, but not Cp, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC24) was ∼2-fold greater than the plasma AUC24, but simulations suggested that Cb was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described Cp and Cb, but Cp was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI Cb in healthy subjects, the distribution parameters between Cp and Cb, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict Cb from Cp for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.).

  8. Notes from the Field: Outbreaks of Shigella sonnei Infection with Decreased Susceptibility to Azithromycin Among Men Who Have Sex with Men - Chicago and Metropolitan Minneapolis-St. Paul, 2014.

    PubMed

    Bowen, Anna; Eikmeier, Dana; Talley, Pamela; Siston, Alicia; Smith, Shamika; Hurd, Jacqueline; Smith, Kirk; Leano, Fe; Bicknese, Amelia; Norton, J Corbin; Campbell, Davina

    2015-06-05

    Increasing rates of shigellosis among adult males, particularly men who have sex with men (MSM), have been documented in the United States, Canada, and Europe, and MSM appear to be at greater risk for infection with shigellae that are not susceptible to ciprofloxacin or azithromycin. Azithromycin is the first-line empiric antimicrobial treatment for shigellosis among children and is a second-line treatment among adults. Isolates collected in 2014 in two U.S. cities from outbreaks of shigellosis displayed highly similar pulsed-field gel electrophoresis (PFGE) patterns and decreased susceptibility to azithromycin (DSA). This report summarizes and compares the findings from investigations of the two outbreaks, which occurred among MSM in metropolitan Minneapolis-St. Paul, Minnesota, and Chicago, Illinois.

  9. Comparative Intracellular (THP-1 Macrophage) and Extracellular Activities of β-Lactams, Azithromycin, Gentamicin, and Fluoroquinolones against Listeria monocytogenes at Clinically Relevant Concentrations

    PubMed Central

    Carryn, Stéphane; Van Bambeke, Françoise; Mingeot-Leclercq, Marie-Paule; Tulkens, Paul M.

    2002-01-01

    The activities of ampicillin, meropenem, azithromycin, gentamicin, ciprofloxacin, and moxifloxacin against intracellular hemolysin-positive Listeria monocytogenes were measured in human THP-1 macrophages and were compared with the extracellular activities observed in broth. All extracellular concentrations were adjusted to explore ranges that are clinically achievable in human serum upon conventional therapy. In broth, ampicillin, meropenem, and azithromycin were only bacteriostatic, whereas gentamicin, ciprofloxacin, and moxifloxacin were strongly bactericidal in a concentration-dependent manner. In cells, ampicillin, meropenem, azithromycin, and ciprofloxacin were slightly bactericidal (0.3- to 0.8-log CFU reductions), moxifloxacin was strongly bactericidal (2.1-log CFU reduction), and gentamicin was virtually inactive. The difference in the efficacies of moxifloxacin and ciprofloxacin in cells did not result from a difference in levels of accumulation in cells (6.96 ± 1.05 versus 7.75 ± 1.03) and was only partially explainable by the difference in the MICs (0.58 ± 0.04 versus 1.40 ± 0.17 mg/liter). Further analysis showed that intracellular moxifloxacin expressed only approximately 1/7 of the activity demonstrated against extracellular bacteria and ciprofloxacin expressed only 1/15 of the activity demonstrated against extracellular bacteria. Gentamicin did not increase the intracellular activities of the other antibiotics tested. The data suggest (i) that moxifloxacin could be of potential interest for eradication of the intracellular forms of L. monocytogenes, (ii) that the cellular accumulation of an antibiotic is not the only determinant of its intracellular activity (for fluoroquinolones, it is actually a self-defeating process as far as activity is concerned), and (iii) that pharmacodynamics (activity-to-concentration relationships) need to be considered for the establishment of efficacy against intracellular bacteria, just as they are for the

  10. Azithromycin and spiramycin induce anti-inflammatory response in human trophoblastic (BeWo) cells infected by Toxoplasma gondii but are able to control infection.

    PubMed

    Franco, P S; Gomes, A O; Barbosa, B F; Angeloni, M B; Silva, N M; Teixeira-Carvalho, A; Martins-Filho, O A; Silva, D A O; Mineo, J R; Ferro, E A V

    2011-11-01

    Toxoplasma gondii is an important pathogen which may cause fetal infection if primary infection. Our previous studies have used human choriocarcinoma trophoblastic cells (BeWo cell line) as experimental model of T. gondii infection involving placental microenvironment. This study aimed to examine the effects of azithromycin and spiramycin against T. gondii infection in BeWo cells. Cells were treated with different concentrations of the macrolide antibiotics and analyzed first for cell viability using thiazolyl blue tetrazole (MTT) assay. As cell viability was significantly decreased with drug concentrations higher than 400 μg/mL, the concentration range used in further experiments was from 50 to 400 μg/mL. The number of infected cells and intracellular replication of T. gondii decreased after treatment with each drug. The infection induced up-regulation of the macrophage migration inhibitory factor (MIF), which was also enhanced in infected cells after treatment with azithromycin, but not with spiramycin. Analysis of the cytokine profile showed increase TNF-α, IL-10 and IL-4 production, but decreased IFN-γ levels, were detected in infected cells and treated with each drug. In conclusion, treatment of human trophoblastic BeWo cells with with azithromycin or spiramycin is able to control the infection and replication of T. gondii. In addition, treatment with these macrolides, especially with azityromycin induces an anti-inflammatory response and high MIF production, which can be important for the establishment and maintenance of a viable pregnancy during T. gondii infection.

  11. The comparison of single-dose ceftriaxone, five-day azithromycin, and ten-day amoxicillin/clavulanate for the treatment of children with acute otitis media.

    PubMed

    Biner, Betül; Celtik, Coşkun; Oner, Naci; Küçükuğurluoğlu, Yasemin; Güzel, Ahmet; Yildirim, Cetin; Adali, Mustafa Kemal

    2007-01-01

    The aim of the study was to evaluate the efficacy of short-course antimicrobial therapies [single intramuscular dose of ceftriaxone (50 mg/kg, not exceeding 1 g), 5 days of azithromycin (10 mg/kg on day 1, then 5 mg/kg daily on days 2-5) and the traditional 10-day course of amoxicillin/clavulanate (90/6.4 mg/kg/day in 2 doses)] in children with acute otitis media (AOM). The study was conducted as a prospective, comparative, open randomized trial between February 2001 and April 2003, and 104 children were enrolled, with a mean age of 3.8 (2.3) years. The clinical and otoscopic assessments of the children were made on days 0, 3, 11 and 30 after admission, and tympanometry was performed on day 30. The patients were diagnosed and followed with a scoring system. Clinical success was achieved in 29/34 patients (85.3%) in the ceftriaxone group, 27/31 patients (87.1%) in the azithromycin group and 34/39 children (87.2%) in the amoxicillin/clavulanate group. The rate of persistence of middle-ear fluid did not differ between the three groups (p>0.05). During the one-month period, no recurrent case was observed. The most common drug-related adverse effects were associated with the gastrointestinal system. In conclusion, for the treatment of children with AOM, the clinical success of single-dose intramuscular ceftriaxone and of five-day azithromycin treatments was comparable to that of the traditional 10-day therapy with high-dose amoxicillin/clavulanate.

  12. Azithromycin as the first-line treatment of non-gonococcal urethritis (NGU): a study of follow-up rates, contact attendance and patients' treatment preference.

    PubMed

    Carlin, E M; Barton, S E

    1996-01-01

    To identify any differences in follow-up rates or sexual contact attendance rates in men presenting with non-gonococcal urethritis (NGU) after treatment by single dose azithromycin rather than longer standard duration therapies and to identify patients' treatment preferences. A prospective study was performed on 200 consecutive men attending a genito-urinary medicine (GUM) clinic with new episode, microscopically confirmed NGU. The first 100 patients were treated with standard duration therapy (Group S) whilst the second 100 patients received a single 1 g oral dose of azithromycin (Group A). Patient-led contact tracing was arranged and patients were asked to return for review when a test of cure was performed, contact attendance noted and the patient's treatment preference ascertained. Both groups were predominantly heterosexual and over 60% gave a history of previous sexually transmitted disease (STD). There were no significant differences in efficacy between Groups S and A. However, the index follow-up rate and percentage of traceable sexual contacts attending was higher in Group A. In both groups contacts of homosexual men were more likely to attend the GUM clinic. More additional visits were made by Group S due to mislaid medication or compliance problems. Over 70% of patients questioned expressed a preference for single dose therapy. Single dose therapy with 1 g of azithromycin is as efficacious as longer duration therapies with advantages in patient follow-up rates and contact attendance and for the majority of patients would be their treatment of choice. A cost analysis supports the practical application of this regimen.

  13. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim

    2016-01-01

    Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485

  14. Antipneumococcal activities of two novel macrolides, GW 773546 and GW 708408, compared with those of erythromycin, azithromycin, clarithromycin, clindamycin, and telithromycin.

    PubMed

    Matic, Vlatka; Kosowska, Klaudia; Bozdogan, Bulent; Kelly, Linda M; Smith, Kathy; Ednie, Lois M; Lin, Gengrong; Credito, Kim L; Clark, Catherine L; McGhee, Pamela; Pankuch, Glenn A; Jacobs, Michael R; Appelbaum, Peter C

    2004-11-01

    The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with erm(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were >/=0.5 microg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No mef(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two mef(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 microg/ml. Single-step studies showed mutation frequencies <5.0 x 10(-10) to 3.5 x 10(-7) for GW 773546, GW 708408, and telithromycin for macrolide-susceptible strains and 1.1 x 10(-7) to >4.3 x 10(-3) for

  15. Efficacy and safety of azithromycin 1 g once daily for 3 days in the treatment of community-acquired pneumonia: an open-label randomised comparison with amoxicillin-clavulanate 875/125 mg twice daily for 7 days.

    PubMed

    Paris, R; Confalonieri, M; Dal Negro, R; Ligia, G P; Mos, L; Todisco, T; Rastelli, V; Perna, G; Cepparulo, M

    2008-02-01

    This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.

  16. Fire Suppression and Response

    NASA Technical Reports Server (NTRS)

    Ruff, Gary A.

    2004-01-01

    This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

  17. Fire Suppression, District 5

    Treesearch

    Roy Headley

    1916-01-01

    The increasing effectiveness of suppression practice is shown by the fact that in 1915 fire suppression cost one-third as much as in 1914, and damage to Government property was kept down to one-fourth the 1914 figure. The seasons were approximately equal in danger. Is further progress to be expected?

  18. Combination therapy with ampicillin and azithromycin in an experimental pneumococcal pneumonia is bactericidal and effective in down regulating inflammation in mice

    PubMed Central

    2014-01-01

    Objectives Emergence of multidrug resistance among Streptococcus pneumoniae (SP), has limited the available options used to treat infections caused by this organism. The objective of this study was to compare the role of monotherapy and combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating bacterial burden and down regulating lung inflammation in a murine experimental pneumococcal infection model. Methods Balb/C mice were infected with 106 CFU of SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50 mg/kg) either alone or in combination was initiated 18 h post infection, animals were sacrificed from 0 – 6 h after initiation of treatment. AMP and AZM were quantified in serum by microbiological assay. Levels of TNF-α, IFN-γ IL-6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell count in broncho alveolar lavage fluid, COX-2 and histopathological changes in lungs were estimated. Results Combination therapy down regulated lung inflammation and accelerated bacterial clearance. This approach also significantly decreased TNF-α, IFN-γ, IL-6 and increased IL-10 level in serum and lungs along with decreased myeloperoxidase, pulmonary vascular permeability, inflammatory cell numbers and COX-2 levels in lungs. Conclusions Combinatorial therapy resulted in comparable bactericidal activity against the multi-drug resistant isolate and may represent an alternative dosing strategy, which may help to alleviate problems with pneumococcal pneumonia. PMID:24565171

  19. A Cross-Sectional Study of ‘Yaws’ in Districts of Ghana Which Have Previously Undertaken Azithromycin Mass Drug Administration for Trachoma Control

    PubMed Central

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W.; Bailey, Robin L.; Agana, Nsiire; Mabey, David C. W.; Chen, Cheng-Yen

    2015-01-01

    Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5–17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes. PMID:25632942

  20. A switch therapy protocol with intravenous azithromycin and ciprofloxacin combination for severe, relapsing chronic bacterial prostatitis: a prospective non-comparative pilot study.

    PubMed

    Kolumbić Lakos, A; Skerk, V; Maleković, G; Dujnić Spoljarević, T; Kovacic, D; Pasini, M; Markotić, A; Magri, V; Perletti, G

    2011-12-01

    Chronic bacterial prostatitis (CBP) is characterized by intense clinical symptoms, frequent relapse episodes and poor quality of life. Aggressive antibacterial therapy is warranted to eradicate the causative pathogens and to achieve a permanent cure. We administered a "switch-therapy" protocol to 30 patients showing severe CBP symptoms and two or more relapse episodes in the previous 12 months. Patients received intravenous azithromycin (500 mg/day) and ciprofloxacin (800 mg/day) for 3 days, followed by oral ciprofloxacin (1 g/day) for 25 days.Twenty-seven (90%) patients showed pathogen eradication at test-of-cure (TOC) visit. Five cases of infection relapse were detected at follow-up. At the TOC visit, 25 patients (83%) showed mild/absent symptoms, measured with the NIH-chronic prostatitis symptom index.These results indicate the efficacy of a "switch-therapy" protocol, based on combined azithromycin and ciprofloxacin. Comparative studies on larger CBP patient populations are warranted to confirm these encouraging results.

  1. Comparative in vitro activities of azithromycin, Bay y 3118, levofloxacin, sparfloxacin, and 11 other oral antimicrobial agents against 194 aerobic and anaerobic bite wound isolates.

    PubMed Central

    Goldstein, E J; Nesbit, C A; Citron, D M

    1995-01-01

    The activities of sparfloxacin, levofloxacin, Bay y 3118, azithromycin, cefprozil, loracarbef, and nine other oral antimicrobial agents against 194 aerobic and anaerobic clinical bite wound isolates were determined by the agar dilution method. Sparfloxacin, levofloxacin, and Bay y 3118 were active against all aerobic isolates (MICs at which 90% of the isolates are inhibited [MIC90], < or = 1.0 microgram/ml for sparfloxacin and levofloxacin and 0.1 microgram/ml for Bay y 3118) and many anaerobic isolates, with the exception of the fusobacteria. Azithromycin was more active than erythromycin by 1 to 2 dilutions against many aerobes, including Pasteurella multocida and Eikenella corrodens, and by 2 to 4 dilutions against anaerobic isolates. Cefprozil was more active (MIC90, < or = 1 microgram/ml) than loracarbef (MIC90, < or = 4 micrograms/ml) against aerobic gram-positive isolates, but both had poor activity (MIC90, > or = 16 micrograms/ml) against peptostreptococci. Both cefprozil and loracarbef had MIC90s of < or = 0.5 micrograms/ml against P. multocida. PMID:7625795

  2. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    PubMed

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W; Bailey, Robin L; Agana, Nsiire; Mabey, David C W; Chen, Cheng-Yen; Adu-Sarkodie, Yaw; Marks, Michael

    2015-01-01

    Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

  3. Effect of Adjunctive Systemic Azithromycin With Periodontal Surgery in the Treatment of Chronic Periodontitis in Smokers: A Pilot Study

    PubMed Central

    Dastoor, Sarosh F.; Travan, Suncica; Neiva, Rodrigo F.; Rayburn, Lindsay A.; Giannobile, William V.; Wang, Hom-Lay

    2008-01-01

    Background Along with conventional surgical therapy, systemic antibiotics may provide more effective treatment in smokers by targeting tissue- invasive bacteria. The aim of this randomized, placebo-controlled, double-masked clinical trial was to evaluate the adjunctive effects of systemic azithromycin (AZM) in combination with periodontal pocket reduction surgery in the treatment of chronic periodontitis in smokers. Methods Thirty patients with a greater than one pack/day smoking habit and generalized moderate to severe chronic periodontitis were randomized to the test (surgery plus 3 days of AZM, 500 mg) or control group (surgery plus 3 days of placebo). Full-mouth probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), plaque index, and wound healing indices (WHI) were assessed at baseline and at 2 weeks and 1, 3, and 6 months following surgical intervention. Plaque and gingival crevicular fluid were collected for trypsin-like enzyme activity (benzoyl-dl-arginine naphthylamine) and bone biomarker (cross-linked telopeptide of type I collagen [ICTP]) analyses, respectively, at baseline, 2 weeks, and 1, 3, and 6 months. Results Surgical treatment of moderate (PD = 4 to 6 mm) and deep (PD >6 mm) pockets significantly improved clinical parameters of treated and untreated teeth (CAL gain, PD reduction, and reduction of BOP). The additional use of AZM did not enhance this improvement nor did it promote reduction of ICTP levels. Compared to the control group, the test group had significantly better WHI scores at 1 month, significantly less GI at 2 weeks, and sustained reductions of red-complex bacteria with trypsin-like enzyme activity at 3 months. For non-surgery teeth, only the test group showed significant gains in overall CAL compared to baseline. Conclusions The findings of this pilot study demonstrated that in heavy smokers, adjunctive systemic AZM in combination with pocket reduction surgery did not significantly

  4. In Vitro Activity of Fosfomycin Alone and in Combination with Ceftriaxone or Azithromycin against Clinical Neisseria gonorrhoeae Isolates

    PubMed Central

    Hauser, Christoph; Hirzberger, Lea; Unemo, Magnus; Furrer, Hansjakob

    2014-01-01

    New therapeutic strategies are needed to combat the emergence of infections due to multidrug-resistant Neisseria gonorrhoeae. In this study, fosfomycin (FOS) was tested against 89 N. gonorrhoeae isolates using the Etest method, showing MIC50/MIC90s of only 8/16 μg/ml (range, ≤1 to 32 μg/ml). FOS in combination with ceftriaxone (CRO) or azithromycin (AZT) was then evaluated using the checkerboard method for eight strains, including N. gonorrhoeae F89 (CRO-resistant) and AZT-HLR (high-level AZT-resistant). All combinations that included FOS gave indifferent effects (fractional inhibitory concentration [FIC] index values, 1.2 to 2.3 for FOS plus CRO, 1.8 to 3.2 for FOS plus AZT). Time-kill experiments for FOS, CRO, AZT, and their combinations (at 0.5×, 1×, 2×, and 4× the MIC) were performed against N. gonorrhoeae strain ATCC 49226, one N. gonorrhoeae multiantigen sequence typing (NG-MAST) sequence type 1407 (ST1407) strain, F89, and AZT-HLR. For all strains, at 24 h, the results indicated that (i) FOS was bactericidal at 2× the MIC, but after >24 h, there was regrowth of bacteria; (ii) CRO was bactericidal at 0.5× the MIC; (iii) AZT was bactericidal at 4× the MIC; (iv) CRO plus AZT was less bactericidal than was CRO alone; (v) FOS plus AZT was bactericidal at 2× the MIC; and (vi) CRO plus AZT and FOS plus CRO were both bactericidal at 0.5× the MIC, but FOS plus CRO had more rapid effects. FOS is appealing for use in the management of N. gonorrhoeae infections because of its single and oral formulation. However, our results suggest it be used in combination with CRO. After the appropriate clinical trials are conducted, this strategy could be implemented for the treatment of infections due to isolates possessing resistance to CRO and/or AZT. PMID:25547354

  5. Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial.

    PubMed

    Unger, Holger W; Ome-Kaius, Maria; Wangnapi, Regina A; Umbers, Alexandra J; Hanieh, Sarah; Suen, Connie S N Li Wai; Robinson, Leanne J; Rosanas-Urgell, Anna; Wapling, Johanna; Lufele, Elvin; Kongs, Charles; Samol, Paula; Sui, Desmond; Singirok, Dupain; Bardaji, Azucena; Schofield, Louis; Menendez, Clara; Betuela, Inoni; Siba, Peter; Mueller, Ivo; Rogerson, Stephen J

    2015-01-16

    Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa. Low birthweight (LBW, <2,500 g) is common in Papua New Guinea (PNG) and contributing factors include malaria and reproductive tract infections. From November 2009 to February 2013, we conducted a parallel group, randomised controlled trial in pregnant women (≤ 26 gestational weeks) in PNG. Sulphadoxine-pyrimethamine (1,500/75 mg) plus azithromycin (1 g twice daily for 2 days) (SPAZ) monthly from second trimester (intervention) was compared against sulphadoxine-pyrimethamine and chloroquine (450 to 600 mg, daily for three days) (SPCQ) given once, followed by SPCQ placebo (control). Women were assigned to treatment (1:1) using a randomisation sequence with block sizes of 32. Participants were blinded to assignments. The primary outcome was LBW. Analysis was by intention-to-treat. Of 2,793 women randomised, 2,021 (72.4%) were included in the primary outcome analysis (SPCQ: 1,008; SPAZ: 1,013). The prevalence of LBW was 15.1% (305/2,021). SPAZ reduced LBW (risk ratio [RR]: 0.74, 95% CI: 0.60-0.91, P = 0.005; absolute risk reduction (ARR): 4.5%, 95% CI: 1.4-7.6; number needed to treat: 22), and preterm delivery (0.62, 95% CI: 0.43-0.89, P = 0.010), and increased mean birthweight (41.9 g, 95% CI: 0.2-83.6, P = 0.049). SPAZ reduced maternal parasitaemia (RR: 0.57, 95% CI: 0.35-0.95, P = 0.029) and active placental malaria (0.68, 95% CI: 0.47-0.98, P = 0.037), and reduced carriage of gonorrhoea (0.66, 95% CI: 0.44-0.99, P = 0.041) at second visit. There were no treatment-related serious adverse events (SAEs), and the number of SAEs (intervention 13.1% [181/1,378], control 12.7% [174/1,374], P = 0.712) and AEs (intervention 10.5% [144/1,378], control 10.8% [149/1,374], P = 0.737) was similar. A major limitation of the study was the high loss to follow-up for birthweight. SPAZ was efficacious and safe in reducing LBW, possibly acting through multiple mechanisms including the effect on

  6. Growth hormone suppression test

    MedlinePlus

    GH suppression test; Glucose loading test; Acromegaly - blood test; Gigantism - blood test ... drink anything. You then drink a solution containing glucose (sugar). You may be told to drink slowly ...

  7. Jet noise suppression

    NASA Astrophysics Data System (ADS)

    Gliebe, P. R.; Brausch, J. F.; Majjigi, R. K.; Lee, R.

    1991-08-01

    The objectives of this chapter are to review and summarize the jet noise suppression technology, to provide a physical and theoretical model to explain the measured jet noise suppression characteristics of different concepts, and to provide a set of guidelines for evolving jet noise suppression designs. The underlying principle for all jet noise suppression devices is to enhance rapid mixing (i.e., diffusion) of the jet plume by geometric and aerothermodynamic means. In the case of supersonic jets, the shock-cell broadband noise reduction is effectively accomplished by the elimination or mitigation of the shock-cell structure. So far, the diffusion concepts have predominantly concentrated on jet momentum and energy (kinetic and thermal) diffusion, in that order, and have yielded better noise reduction than the simple conical nozzles. A critical technology issue that needs resolution is the effect of flight on the noise suppression potential of mechanical suppressor nozzles. A more thorough investigation of this mechanism is necessary for the successful development and design of an acceptable noise suppression device for future high-speed civil transports.

  8. Jet Noise Suppression

    NASA Technical Reports Server (NTRS)

    Gliebe, P. R.; Brausch, J. F.; Majjigi, R. K.; Lee, R.

    1991-01-01

    The objectives of this chapter are to review and summarize the jet noise suppression technology, to provide a physical and theoretical model to explain the measured jet noise suppression characteristics of different concepts, and to provide a set of guidelines for evolving jet noise suppression designs. The underlying principle for all jet noise suppression devices is to enhance rapid mixing (i.e., diffusion) of the jet plume by geometric and aerothermodynamic means. In the case of supersonic jets, the shock-cell broadband noise reduction is effectively accomplished by the elimination or mitigation of the shock-cell structure. So far, the diffusion concepts have predominantly concentrated on jet momentum and energy (kinetic and thermal) diffusion, in that order, and have yielded better noise reduction than the simple conical nozzles. A critical technology issue that needs resolution is the effect of flight on the noise suppression potential of mechanical suppressor nozzles. A more thorough investigation of this mechanism is necessary for the successful development and design of an acceptable noise suppression device for future high-speed civil transports.

  9. Poor outcomes of empiric ceftriaxone ± azithromycin for community-acquired pneumonia caused by methicillin-susceptible Staphylococcus aureus.

    PubMed

    So, Wonhee; Crandon, Jared L; Nicolau, David P

    2016-06-01

    While ceftriaxone 1 g q24h is commonly used for hospitalized patients with community-acquired pneumonia (CAP), the prescribing information recommends 2-4 g a day to treat methicillin-susceptible Staphylococcus aureus (MSSA). Similarly, recent pharmacodynamic analyses suggest shortcomings of 1 g q24h against the bulk of the MSSA. We evaluated the outcomes of empiric ceftriaxone 1 g q24h ± azithromycin in patients with MSSA pneumonia, as compared with Streptococcus pneumoniae. Adult patients admitted to Hartford Hospital from 1/2005 to 12/2014 with respiratory culture for MSSA or S. pneumoniae were considered for inclusion. Non-ICU, CAP patients were included. Early clinical failure (ECF) was defined as persistent signs/symptoms or change of antibiotic due to poor response at 72-96 h. A multivariate analysis was performed to evaluate predictors of ECF. Over the study period, 403 MSSA and 227 S. pneumoniae positive respiratory cultures were identified. The majority of patients were excluded due to the following: no signs/symptoms of pneumonia, hospital-acquired pneumonia, alternative antibiotics, and polymicrobial infection. Thirty-nine patients met inclusion/exclusion criteria. All but three patients in the S. pneumoniae group received ceftriaxone + azithromycin. ECF was greater in the MSSA group (53 vs. 4 %, P = 0.003), as was length of stay (7.5 ± 5.4 vs. 4.6 ± 3.3 days, P = 0.006). When controlling for disease severity and macrolide non-susceptibility in a multivariate analysis, MSSA was significantly correlated with ECF (OR 12.3, 95 % CI 0.8-188.8). Poor clinical outcomes were observed in patients empirically treated with ceftriaxone ± azithromycin for MSSA CAP. Despite the popularity of ceftriaxone 1 g q24h, these data suggest this dose or compound may be inadequate for CAP caused by MSSA.

  10. Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: Study protocol of a randomized efficacy trial.

    PubMed

    Roca, Anna; Oluwalana, Claire; Camara, Bully; Bojang, Abdoulie; Burr, Sarah; Davis, Timothy M E; Bailey, Robin; Kampmann, Beate; Mueller, Jenny; Bottomley, Christian; D'Alessandro, Umberto

    2015-11-19

    Neonatal deaths, estimated at approximately 4 million annually, now account for almost 40% of global mortality in children aged under-five. Bacterial sepsis is a leading cause of neonatal mortality. Assuming the mother is the main source for bacterial transmission to newborns, the primary objective of the trial is to determine the impact of one oral dose of azithromycin, given to women in labour, on the newborn's bacterial carriage in the nasopharynx. Secondary objectives include the impact of the intervention on bacterial colonization in the baby and the mother during the first month of life. This is a Phase III, double -blind, placebo controlled randomized clinical trial in which 830 women in labour were randomized to either a single dose of 2 g oral azithromycin or placebo (ratio 1:1). The trial included pregnant women in labour aged 18 to 45 years attending study health centres in the Western Gambia. A post-natal check of the mother and baby was conducted at the health centre by study clinicians before discharge and 8-10 days after delivery. Home follow up visits were conducted daily during the first week and then weekly until week 8 after delivery. Vaginal swabs and breast milk samples were collected from the mothers, and the pathogens Streptococcus pneumoniae, Group B Streptococcus (GBS) and Staphylococcus aureus were isolated from the study samples. For bacterial isolates, susceptibility pattern to azithromycin was determined using disk diffusion and E-test. Eye swabs were collected from newborns with eye discharge during the follow up period, and Chlamydial infection was assessed using molecular methods. This is a proof-of-concept study to assess the impact of antibiotic preventive treatment of women during labour on bacterial infections in the newborn. If the trial confirms this hypothesis, the next step will be to assess the impact of this intervention on neonatal sepsis. The proposed intervention should be easily implementable in developing countries

  11. Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study

    PubMed Central

    Knoops, Sofie; Aldinucci Buzzo, João L.; Boon, Lise; Martens, Erik; Opdenakker, Ghislain; Kolaczkowska, Elzbieta

    2017-01-01

    Gelatinase B or matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin) and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM), the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2) activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations. PMID:28369077

  12. Azithromycin assay in drug formulations: Validation of a HPTLC method with a quadratic polynomial calibration model using the accuracy profile approach.

    PubMed

    Bouklouze, A; Kharbach, M; Cherrah, Y; Vander Heyden, Y

    2017-03-01

    Many different assaying high performance thin layer chromatography (HPTLC) methods have been developed and validated in order to be used in routine analysis in different analytical fields. Validation often starts by the evaluation of the linearity of the calibration curve. Frequently, if the correlation coefficient is close to one, the linear calibration curve model is considered to be proper to predict the unknown concentration in the sample. But is this simple model effective to assess the behavior of the response of an HPTLC method as a function of concentration. To answer this question, a method for the determination of azithromycin by HPTLC has been developed and validated following both the classical approach and that based on the accuracy profile. Silica gel plates with fluorescence indicator F254 and chloroform - ethanol - 25% ammonia 6:14:0.2 (v/v/v) as mobile phase were used. Analysis was carried out in reflectance mode at 483nm. The RF of azithromycin was 0.53. The validation based on the classical approach, shows that the behavior is not linear, even though r(2)=0.999 because the lack of fit test is significant (P<0.05). Validation based on the accuracy profile approach considering both the straight line and the quadratic regression model, show that the former results is a β-expectation tolerance interval outside the acceptance limits, while with the latter, this interval is within the limits of ±5% acceptability for a range which extends from 0.2 to 1.0μg/zone. With the quadratic model, the method showed to be precise and accurate. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  13. Explosion suppression system

    DOEpatents

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  14. The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder.

    PubMed

    Ishizaka, Toshihiko; Okada, Sachie; Takemoto, Eri; Tokuyama, Emi; Tsuji, Eriko; Mukai, Junji; Uchida, Takahiro

    2007-10-01

    The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.

  15. Sensory suppression during feeding

    PubMed Central

    Foo, H.; Mason, Peggy

    2005-01-01

    Feeding is essential for survival, whereas withdrawal and escape reactions are fundamentally protective. These critical behaviors can compete for an animal's resources when an acutely painful stimulus affects the animal during feeding. One solution to the feeding-withdrawal conflict is to optimize feeding by suppressing pain. We examined whether rats continue to feed when challenged with a painful stimulus. During feeding, motor withdrawal responses to noxious paw heat either did not occur or were greatly delayed. To investigate the neural basis of sensory suppression accompanying feeding, we recorded from brainstem pain-modulatory neurons involved in the descending control of pain transmission. During feeding, pain-facilitatory ON cells were inhibited and pain-inhibitory OFF cells were excited. When a nonpainful somatosensory stimulus preactivated ON cells and preinhibited OFF cells, rats interrupted eating to react to painful stimuli. Inactivation of the brainstem region containing ON and OFF cells also blocked pain suppression during eating, demonstrating that brainstem pain-modulatory neurons suppress motor reactions to external stimulation during homeostatic behaviors. PMID:16275919

  16. Pressure suppression containment system

    DOEpatents

    Gluntz, D.M.; Townsend, H.E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

  17. Pressure suppression containment system

    DOEpatents

    Gluntz, Douglas M.; Townsend, Harold E.

    1994-03-15

    A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto.

  18. Drug Insight: appetite suppressants.

    PubMed

    Bray, George A

    2005-02-01

    The term 'appetite suppressant' is used to denote drugs that act primarily on the neurochemical transmitters of the central nervous system to reduce food intake. In addition to drugs that release or mimic the effect of norepinephrine (noradrenaline), this could include drugs that inhibit: reuptake of norepinephrine or 5-hydroxytryptamine (also known as serotonin); bind to the gamma-aminobutyric acid receptors or the cannabinoid receptors; and some peptides that reduce food intake. The sympathomimetic drugs phentermine, diethylpropion, benzphetamine, and phendimetrazine--so named because they mimic many effects of norepinephrine--are only approved in a few countries, and then only for short-term use. Sibutramine, a norepinephrine-5-hydroxytryptamine reuptake inhibitor, is approved for long-term use. Several new mechanisms for drug action are under investigation. Appetite suppressants should be viewed as useful adjuncts to diet and physical activity and might help selected patients to achieve and maintain weight loss.

  19. Learning motion discrimination with suppressed and un-suppressed MT.

    PubMed

    Thompson, Benjamin; Liu, Zili

    2006-06-01

    Perceptual learning of motion direction discrimination is generally thought to rely on the middle temporal area of the brain (MT/V5). A recent study investigating learning of motion discrimination when MT was psychophysically suppressed found that learning was possible with suppressed MT, but only when the task was sufficiently easy [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. We investigated whether this effect was indeed due to MT suppression or whether it could be explained by task difficulty alone. By comparing learning of motion discrimination when MT was suppressed vs. un-suppressed, at different task difficulties, we found that task difficulty alone could not explain the effects. At the highest difficulty, learning was not possible with suppressed MT, confirming [Lu, H., Qian, N., Liu, Z. (2004). Learning motion discrimination with suppressed MT. Vision Research 44, 1817-1825]. In comparison, learning was possible with un-suppressed MT at the same difficulty level. At the intermediate task difficulty, there was a clear learning disadvantage when MT was suppressed. Only for the easiest level of difficulty, did learning become equally possible for both suppressed and un-suppressed conditions. These findings suggest that MT plays an important role in learning to discriminate relatively fine differences in motion direction.

  20. Suppression Workshop Summary

    DTIC Science & Technology

    1987-04-07

    the sodium is just about as effective as potassium in accelerating the OH decay rates . These results can be used to validate the kinetic suppression... rate of reaction of the combustibles. It represents the proportion of combustibles in the breech. It was found that a very strong effect on the blast...accelerating the CH decay rate decreased with continued potassium addition. They also found that, for a Fg c amount of potassium added to the flames, the

  1. Quantitative determination of the macrolide antibiotics erythromycin, roxithromycin, azithromycin and clarithromycin in human serum by high-performance liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl chloride and fluorescence detection.

    PubMed

    Sastre Toraño, J; Guchelaar, H J

    1998-12-11

    A validated, highly sensitive and precise high-performance liquid chromatographic (HPLC) method for the determination of the macrolides erythromycin, azithromycin, clarithromycin and roxithromycin in human serum is described. A diethyl ether extract, obtained from serum using a saturated sodium carbonate solution, was treated with 9-fluorenylmethyl-oxycarbonyl chloride (FMOC-Cl) for 40 min at 40 degrees C and chromatographed on a base-deactivated octadecyl column, maintained at 50 degrees C during elution, using an eluent composed of acetonitrile-hydrogenphosphate buffer, pH 7.5, with 0.125% triethylamine (3:2, v/v). Fluorescence detection was used at an excitation wavelength of 255 nm and an emission wavelength of 315 nm. Erythromycin, clarithromycin, roxithromycin and azithromycin were found to have retention times of 8.8, 15.7, 17.1 and 20.7 min, respectively. Recoveries ranging from 93 to 104% were found with reproducibility coefficients of variation of 1.1-5%. Mean correlation coefficients of 0.9997, 0.9998, 0.9996 and 0.9994 were found for the linear calibration curves (n = 2) of erythromycin (0.320-16.1 mg/l), roxithromycin (3.24-19.4 mg/l), clarithromycin (0.190-19.4 mg/l) and azithromycin (0.0988-4.94 mg/l), respectively.

  2. Tremor suppression in ECG

    PubMed Central

    Dotsinsky, Ivan A; Mihov, Georgy S

    2008-01-01

    Background Electrocardiogram recordings are very often contaminated by high-frequency noise usually power-line interference and EMG disturbances (tremor). Specific method for interference cancellation without affecting the proper ECG components, called subtraction procedure, was developed some two decades ago. Filtering out the tremor remains a priori partially successful since it has a relatively wide spectrum, which overlaps the useful ECG frequency band. Method The proposed method for tremor suppression implements the following three procedures. Contaminated ECG signals are subjected to moving averaging (comb filter with linear phase characteristic) with first zero set at 50 Hz to suppress tremor and PL interference simultaneously. The reduced peaks of QRS complexes and other relatively high and steep ECG waves are then restored by an introduced by us procedure called linearly-angular, so that the useful high frequency components are preserved in the range specified by the embedded in the ECG instrument filter, usually up to 125 Hz. Finally, a Savitzky-Golay smoothing filter is applied for supplementary tremor suppression outside the QRS complexes. Results The results obtained show a low level of the residual EMG disturbances together with negligible distortion of the wave shapes regardless of rhythm and morphology changes. PMID:19019218

  3. Activities of two novel macrolides, GW 773546 and GW 708408, compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin against Haemophilus influenzae.

    PubMed

    Kosowska, Klaudia; Credito, Kim; Pankuch, Glenn A; Hoellman, Dianne; Lin, Gengrong; Clark, Catherine; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

    2004-11-01

    The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW 773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x 10(-9) to 2.2 x 10(-6) with

  4. Activities of Two Novel Macrolides, GW 773546 and GW 708408, Compared with Those of Telithromycin, Erythromycin, Azithromycin, and Clarithromycin against Haemophilus influenzae

    PubMed Central

    Kosowska, Klaudia; Credito, Kim; Pankuch, Glenn A.; Hoellman, Dianne; Lin, Gengrong; Clark, Catherine; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R.; Appelbaum, Peter C.

    2004-01-01

    The MIC at which 50% of strains are inhibited (MIC50) and the MIC90 of GW 773546, a novel macrolide, were 1.0 and 2.0 μg/ml, respectively, for 223 β-lactamase-positive, β-lactamase-negative, and β-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC50s and MIC90s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 μg/ml, respectively, while the MIC50 and MIC90 of azithromycin were 1.0 and 2.0 μg/ml, respectively. The MIC50 and MIC90 of erythromycin were 4.0 and 8.0 μg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 μg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 × 10−9 to 2.2 × 10−6 with GW 773546, 1.5 × 10−9 to 6.0

  5. Evaluation of clinical efficacy and safety of tobramycin/dexamethasone ophthalmic suspension 0.3%/0.05% compared to azithromycin ophthalmic solution 1% in the treatment of moderate to severe acute blepharitis/blepharoconjunctivitis.

    PubMed

    Torkildsen, Gail L; Cockrum, Paul; Meier, Edward; Hammonds, William M; Silverstein, Bruce; Silverstein, Steven

    2011-01-01

    To evaluate the clinical efficacy and safety of tobramycin/dexamethasone (TobraDex ST ; 'ST') ophthalmic suspension 0.3%/0.05% compared to azithromycin (Azasite) ophthalmic solution (1%) in the treatment of moderate to severe blepharitis/blepharoconjunctivitis. The study was a multicenter, randomized, investigator-masked, and active-controlled, 15-day study. Enrolled in the study were 122 adult subjects (at least 18 years of age) diagnosed with moderate to severe blepharitis/blepharoconjunctivitis, defined by a minimum score of at least '1' for one of the lid signs, one of the conjunctival signs, and one of the symptoms in at least one eye and a minimum global score (total signs and symptoms score) of '5' in the same eye. One group of 61 subjects received ST with instructions to dose 1  drop four times daily (QID) for 14 days. The other group of 61 subjects received azithromycin and dosed with 1 drop twice daily (BID) for 2 days followed by once daily (QD) dosing for 12 days. Visits were conducted at Day 1 (baseline), Day 8 and Day 15. The a priori primary outcome parameter of the study was the seven-item global score defined as the total score of lid margin redness, bulbar conjunctival redness, palpebral conjunctival redness, ocular discharge (0-3 scale), and lid swelling, itchy eyelids, and gritty eyes (0-4 scale). The study utilized standardized, validated photograph control scales developed by Ora, Inc. (Andover, MA). The study was registered at ClinicalTrials.gov under the registry number NCT01102244. A statistically significant lower mean global score (p = 0.0002) was observed in subjects treated with ST compared to subjects treated with azithromycin at Day 8. No serious adverse events were reported during the course of the study in either group. ST provides a fast and effective treatment of acute blepharitis compared to azithromycin. Initial therapy with the combination of tobramycin/dexamethasone provides faster inflammation relief than azithromycin

  6. Next generation fire suppressants

    NASA Technical Reports Server (NTRS)

    Brown, Jerry A.

    1995-01-01

    Spectrex, Inc., located in Cedar Grove, NJ is a manufacturer of fire detection and suppression equipment. Spectrex is one of the original pioneers in high speed fire detection and suppression systems for combat vehicles. Spectrex has installed fire suppressions systems in thousands of combat vehicles and ships throughout the world. Additionally, they manufacture flame explosion detectors, ship damage control systems, and optical gas and vapor detectors. The culmination of several years of research and development has recently produced an innovative electro-optical continuous monitoring systems called SharpEye 20/20I IR(sup 3) and SAFEYE that provide fast and reliable gas, vapor, aerosol, flame, and explosion detection. SharpEye 20/20I IR(sup 3) is a self-contained triple spectrum flame detector which scans for oscillating IR radiation (1 to 10 Hz) in the spectral bands ranging from 4.0 to 5.0 microns and uses programmed algorithms to check the ratio and correlation of data received by the three sensors to make the system highly immune to false alarms. It is extremely sensitive as it can detect a 1 x 1 square foot gasoline pan fire at 200 feet in less than 3 seconds. The sensitivity is user programmable, offering 4 ranges of detection. SAFEYE is comprised of a selected number of multispectral ban microprocessors controlled detectors which are in communication with one or more radiation sources that is projected along a 600 feet optical path. The signals from the selected narrow bands are processed and analyzed by highly sophisticated algorithms. It is ideal for high risk, remote, large areas such as petroleum and chemical manufacturing sites, waste dumps, aircraft cargo bays, and ship compartments. The SAFEYE will perform direct readings of the presence or rate of rise of concentrations of gases, vapors, or aerosols at the range of parts per million and provide alarms at various set points at different levels of concentrations.

  7. Enhancing thought suppression with hypnosis.

    PubMed

    Bryant, Richard A; Wimalaweera, Subodha

    2006-10-01

    Much research indicates that attempts to suppress thoughts lead to increased accessibility of those thoughts, especially when additional cognitive load is present. On the premise that hypnosis may permit more effective management of cognitive load, it was hypothesized that hypnosis may enhance more effective thought suppression. The present research examined whether the obstacle of cognitive load could be bypassed using hypnosis to facilitate successful thought suppression. Thirty-nine high and 40 low hypnotizable participants were hypnotized and received either a suppression instruction or no instruction for a memory of an embarrassing experience and subsequently completed a sentence-unscrambling task that indexed accessibility of embarrassing thoughts. Whereas lows instructed to suppress displayed a delayed increase in suppressed thoughts, highs did not. These findings support the proposition that hypnosis facilitates thought suppression.

  8. Facile synthesis of the necklace-like graphene oxide-multi-walled carbon nanotube nanohybrid and its application in electrochemical sensing of azithromycin.

    PubMed

    Zhang, Kaixin; Lu, Limin; Wen, Yangping; Xu, Jingkun; Duan, Xuemin; Zhang, Long; Hu, Dufen; Nie, Tao

    2013-07-17

    A novel electrochemical platform was designed for the determination of Azithromycin (Azi), a widely used macrolide antibiotic, by combining the hydrophilic properties of graphene oxide (GO) and the excellent electronic and antifouling properties of multi-walled carbon nanotubes (MWCNTs). Stable MWCNTs aqueous dispersion has been prepared using GO nano-sheets as surfactant and the obtained GO-MWCNTs nanohybrid was characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, transmission electron microscopy and electrochemical impedance spectroscopy, which confirmed that GO nano-sheets were attached onto the wall of MWCNTs to form a necklace-like structure. Electrochemical results obviously reveal that the oxidation peak currents of Azi obtained at the GC electrode modified with GO-MWCNTs hybrid are much higher than those at the MWCNTs/GC, GO/GC and bare GC electrodes. Under optimized conditions, the anodic peak current was linear to the concentration of Azi in the range from 0.1 to 10 μM with the detection limit of 0.07 μM. To further validate its possible application, the proposed method was successfully used for the determination of Azi in pharmaceutical formulations with satisfactory results. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. A new on-line, in-tube pre-column derivatization technique for high performance liquid chromatographic determination of azithromycin in human serum.

    PubMed

    Bahrami, Gholamreza; Mohammadi, Bahareh

    2006-01-18

    Pre-column derivatization methods for high performance liquid chromatographic assay of specific pharmaceutical agents using 9-fluorenylmethyl chloroformate (FMOC-Cl) have received special attention because highly fluorescent and stable adducts are provided by these methods. However, unlike the post-column on-line techniques, long derivatization time is needed and the reaction cannot be well controlled. A new, sensitive and fast pre-column on-line derivatization technique coupled with high-performance liquid chromatography using FMOC-Cl as labeling agent is described and validated for determination of azithromycin in human serum. After extraction of the drug from serum, the residue was reconstituted in mixture of acetonitrile-phosphate buffer (3:1, v/v; pH 8.5) and directly injected onto the chromatographic system. Continuous on-line derivatization and analysis of the compounds were successfully performed using in-tube elution of FMOC-Cl. The total time needed for derivatization and chromatographic analysis of the drug was 13 min. The assay was reliable and reproducible, with limit of quantification of 10 ng/ml. The described technique may offer significant advantages over existing off-line derivatization methods using FMOC-Cl.

  10. Anti-bacterial performance of azithromycin nanoparticles as colloidal drug delivery system against different gram-negative and gram-positive bacteria

    PubMed Central

    Azhdarzadeh, Morteza; Lotfipour, Farzaneh; Zakeri-Milani, Parvin; Mohammadi, Ghobad; Valizadeh, Hadi

    2012-01-01

    Purpose: Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gram negative bacteria in comparison with Erythromycin. The purpose of this research was to prepare AZI nanoparticles (NPs) using PLGA polymer and to compare the effectiveness of prepared nanoparticles with untreated AZI solution. Methods: AZI NPs were prepared by Modified Quasi-Emulsion Solvent Diffusion method. The antibacterial activities of prepared NPs in comparison with AZI solution were assayed against indicator bacteria of Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623) and Streptococcus pneumoniae (PTCC 1240) using agar well diffusion. Inhibition zone diameters (IZD) of nano-formulation were compared to the corresponding untreated AZI. Mean Inhibitory Concentration (MIC) values of AZI were also determined using serial dilution method in nutrient broth medium. Results: Mean IZD of nano-formulations for all indicator bacteria were significantly higher than that of untreated AZI (P<0.01). The enhanced antibacterial efficacy was more dominant in the gram positive species. The MIC values of NPs against the tested bacteria were reduced 8 times in comparison to those of untreated AZI. Conclusion: These results indicated an improved potency of AZI NPs which could be attributed to the modified surface characteristics as well as increased drug adsorption and uptake. PMID:24312766

  11. Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens.

    PubMed

    Lin, Leo; Nonejuie, Poochit; Munguia, Jason; Hollands, Andrew; Olson, Joshua; Dam, Quang; Kumaraswamy, Monika; Rivera, Heriberto; Corriden, Ross; Rohde, Manfred; Hensler, Mary E; Burkart, Michael D; Pogliano, Joe; Sakoulas, George; Nizet, Victor

    2015-07-01

    Antibiotic resistance poses an increasingly grave threat to the public health. Of pressing concern, rapid spread of carbapenem-resistance among multidrug-resistant (MDR) Gram-negative rods (GNR) is associated with few treatment options and high mortality rates. Current antibiotic susceptibility testing guiding patient management is performed in a standardized manner, identifying minimum inhibitory concentrations (MIC) in bacteriologic media, but ignoring host immune factors. Lacking activity in standard MIC testing, azithromycin (AZM), the most commonly prescribed antibiotic in the U.S., is never recommended for MDR GNR infection. Here we report a potent bactericidal action of AZM against MDR carbapenem-resistant isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. This pharmaceutical activity is associated with enhanced AZM cell penetration in eukaryotic tissue culture media and striking multi-log-fold synergies with host cathelicidin antimicrobial peptide LL-37 or the last line antibiotic colistin. Finally, AZM monotherapy exerts clear therapeutic effects in murine models of MDR GNR infection. Our results suggest that AZM, currently ignored as a treatment option, could benefit patients with MDR GNR infections, especially in combination with colistin.

  12. [A randomized comparative study of 3 days of azithromycin treatment and 10 days of cefuroxime treatment in exacerbations in patients with chronic obstructive pulmonary disease].

    PubMed

    Alvarez Gutiérrez, F J; Soto Campos, G; del Castillo Otero, D; Sánchez Gómez, J; Calderón Osuna, E; Rodríguez Becerra, E; Castillo Gómez, J

    1999-07-03

    The aim of this study was to prospectively evaluate the clinical and gasometric evolution and the side effects of two treatment schedules in the exacerbations of patients with chronic obstructive pulmonary disease (COPD): 500 mg/24 h of azithromycin (AZM) for three days versus 500 mg/12 h of acetyl cefuroxime (ACF) for 10 days. Patients were randomized included into each therapeutic schedule. The patients were seen three times (days 1 and 4, and at 15-21 days) to evaluate clinical symptoms scores. Forced spirometry and arterial gasometry were performed the first and the last time the patients were seen. The number of patients requiring admission during follow up and the secondary effects of each antibiotic were quantified. A total de 50 patients were treated with AZM and 51 with ACF. The evolution of the symptoms was similar although with a trend to greater improvement in those treated with AZM. This improvement was significant for the characteristics of expectoration (p < 0.05). Functional and gasometric evolution was similar in the two schedules. Three patients treated with AZM required hospital admission, as did 5 treated with ACF. A greater number of secondary effects were observed in patients treated with ACF (18%) than in those receiving AZM (10%), with gastrointestinal side effects being the most commonly observed. Treatment with short schedule of AZM may have the same activity as longer schedule of ACF, with fewer secondary effects thereby suggesting that AZM may be an effective alternative in the treatment of exacerbations in patients with COPD.

  13. Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens

    PubMed Central

    Lin, Leo; Nonejuie, Poochit; Munguia, Jason; Hollands, Andrew; Olson, Joshua; Dam, Quang; Kumaraswamy, Monika; Rivera, Heriberto; Corriden, Ross; Rohde, Manfred; Hensler, Mary E.; Burkart, Michael D.; Pogliano, Joe; Sakoulas, George; Nizet, Victor

    2015-01-01

    Antibiotic resistance poses an increasingly grave threat to the public health. Of pressing concern, rapid spread of carbapenem-resistance among multidrug-resistant (MDR) Gram-negative rods (GNR) is associated with few treatment options and high mortality rates. Current antibiotic susceptibility testing guiding patient management is performed in a standardized manner, identifying minimum inhibitory concentrations (MIC) in bacteriologic media, but ignoring host immune factors. Lacking activity in standard MIC testing, azithromycin (AZM), the most commonly prescribed antibiotic in the U.S., is never recommended for MDR GNR infection. Here we report a potent bactericidal action of AZM against MDR carbapenem-resistant isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. This pharmaceutical activity is associated with enhanced AZM cell penetration in eukaryotic tissue culture media and striking multi-log-fold synergies with host cathelicidin antimicrobial peptide LL-37 or the last line antibiotic colistin. Finally, AZM monotherapy exerts clear therapeutic effects in murine models of MDR GNR infection. Our results suggest that AZM, currently ignored as a treatment option, could benefit patients with MDR GNR infections, especially in combination with colistin. PMID:26288841

  14. Suppression subtractive hybridization.

    PubMed

    Ghorbel, Mohamed T; Murphy, David

    2011-01-01

    Comparing two RNA populations that differ from the effects of a single independent variable, such as a drug treatment or a specific genetic defect, can establish differences in the abundance of specific transcripts that vary in a population dependent manner. There are different methods for identifying differentially expressed genes. These methods include microarray, Serial Analysis of Gene Expression (SAGE), and quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Herein, the protocol describes an easy and cost-effective alternative that does not require prior knowledge of the transcriptomes under examination. It is specifically relevant when low levels of RNA starting material are available. This protocol describes the use of Switching Mechanism At RNA Termini Polymerase Chain Reaction (SMART-PCR) to amplify cDNA from small amounts of RNA. The amplified cDNA populations under comparison are then subjected to Suppression Subtractive Hybridization (SSH-PCR). SSH-PCR is a technique that couples subtractive hybridization with suppression PCR to selectively amplify fragments of differentially expressed genes. The resulting products are cDNA populations enriched for significantly overrepresented transcripts in either of the two input RNAs. These cDNA populations can then be cloned to generate subtracted cDNA library. Microarrays made with clones from the subtracted forward and reverse cDNA libraries are then screened for differentially expressed genes using targets generated from tester and driver total RNAs.

  15. Planck-suppressed operators

    SciTech Connect

    Assassi, Valentin; Baumann, Daniel; Green, Daniel; McAllister, Liam E-mail: dbaumann@damtp.cam.ac.uk E-mail: mcallister@cornell.edu

    2014-01-01

    We show that the recent Planck limits on primordial non-Gaussianity impose strong constraints on light hidden sector fields coupled to the inflaton via operators suppressed by a high mass scale Λ. We study a simple effective field theory in which a hidden sector field is coupled to a shift-symmetric inflaton via arbitrary operators up to dimension five. Self-interactions in the hidden sector lead to non-Gaussianity in the curvature perturbations. To be consistent with the Planck limit on local non-Gaussianity, the coupling to any hidden sector with light fields and natural cubic couplings must be suppressed by a very high scale Λ > 10{sup 5}H. Even if the hidden sector has Gaussian correlations, nonlinearities in the mixing with the inflaton still lead to non-Gaussian curvature perturbations. In this case, the non-Gaussianity is of the equilateral or orthogonal type, and the Planck data requires Λ > 10{sup 2}H.

  16. Pharmacology of appetite suppression.

    PubMed

    Halford, J C; Blundell, J E

    2000-01-01

    Despite a rising worldwide epidemic of obesity there is currently only a very small number of anti-obesity drugs available to manage the problem. Large numbers of differing pharmacological agents reliably produce a reduction in food intake when administered acutely to animals, and when administered chronically they result in a significant decrease in body mass. Behavioural analysis of drug-induced anorexia in animals demonstrates that various compounds profoundly effect feeding behaviour in differing ways. This indicates the variety of mechanisms by which pharmacological agents can induce changes in food intake, body weight and eventually body composition. Some of the same drugs produce decreases in food intake and weight loss in humans. Some of these drugs do so by modifying the functioning of the appetite system as measured by subjective changes in feelings of hunger and fullness (indices of satiety). Such drugs can be considered as "appetite suppressants" with clinical potential as anti-obesity agents. Other drugs induce changes in food intake and body weight through various physiological mechanisms inducing feelings of nausea or even by side effect related malaise. Of the drugs considered suitable candidates for appetite suppressants are agents which act via peripherally satiety peptide systems (such as CCK, Bombesin/GRP, Enterostatin and GLP-1), or alter the CNS levels of various hypothalamic neuropeptides (NPY, Galanin, Orexin and Melanocortins) or levels of the key CNS appetite monoamine neurotransmitters such as serotonin (5-HT) and noradrenaline (NA). Recently, the hormone leptin has been regarded as a hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The peptide itself stimulates leptin receptors and it links with POMC and MC-4 receptors. These receptors may also provide drug targets for the control of appetite. Any changes induced by a potential appetite suppressant should be considered in terms of the (i

  17. Ultrasonic Frost Suppression

    NASA Astrophysics Data System (ADS)

    Adachi, Kazunari; Saiki, Kazushi; Sato, Hiroki; Ito, Takahiro

    2003-02-01

    The authors have observed the accumulation of frost on the surface of a rectangular aluminum alloy (duralumin) plate flexurally vibrating at approximately 37 kHz in an atmosphere of almost 100% relative humidity at 2°C. The plate surface, which had been prepolished with abrasive slurry for maintaining its average surface roughness of about 100 nm, was refrigerated at a temperature of -20°C with cold carbon-dioxide gas as coolant. Experiments have been conducted with and without fine silver oxide powder spread on the plate surface so as to examine the effect of artificial ice crystal nuclei. Ultrasonic vibrations with an amplitude of 3.4 μm (rms) are found to suppress frost accumulation by approximately 60%. The phenomenon cannot be ascribed directly to the heat generation caused by high-amplitude vibration, but may have a complex mechanical and/or acoustical effect on small ice crystals.

  18. Pressure suppression system

    DOEpatents

    Gluntz, D.M.

    1994-10-04

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

  19. Pressure suppression system

    DOEpatents

    Gluntz, Douglas M.

    1994-01-01

    A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

  20. ZERO SUPPRESSION FOR RECORDERS

    DOEpatents

    Fort, W.G.S.

    1958-12-30

    A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

  1. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  2. The site of saccadic suppression.

    PubMed

    Thilo, Kai V; Santoro, Loredana; Walsh, Vincent; Blakemore, Colin

    2004-01-01

    During rapid eye movements, or saccades, stable vision is maintained by active reduction of visual sensitivity. The site of this saccadic suppression remains uncertain. Here we show that phosphenes--small illusory visual perceptions--induced by transcranial magnetic stimulation (TMS) to the human occipital cortex are immune to saccadic suppression, whereas phosphenes induced by retinal stimulation are not, thus providing direct physiological evidence that saccadic suppression occurs between the retina and the occipital visual cortex.

  3. [Effects of azithromycin and Chlorella vulgaris treatment on certain cytokine values and NK cell activity in an acute murine toxoplasmosis model].

    PubMed

    Çelik Payçu, Deniz Gözde; Büyükbaba Boral, Özden

    2017-01-01

    Toxoplasmosis is a common infection with a complicated treatment process. Azithromycin (AZT) is a macrolide antibiotic that can be effectively used in patients with cerebral and ocular toxoplasmosis and has fewer side effects. Chlorella vulgaris (CV), a single-cell green algae that contains nutrients and has various biological effects. CV extract (CVE) has been shown to have protective effects against infections via immune enhancement by increasing the cytotoxicity of NK cells, IL-12 and IFN-γ levels. The aim of this study was to investigate the protective effects of AZT and CV, individually and in combination, against acute toxoplasmosis in mice, and their effects on NK cell cytotoxixity, IL-12, IFN-γ, and IL-2 levels. Six groups of mice (Balb/c) were formed. With the exception of the healthy control (HC) group, all other groups were infected with 1 ml (11 x 104 trofozoit/ml) Toxoplasma gondii RH strain trophozoites. No further action was performed for infected control (IC) group. After 24 hours from trophozoite infection, CVE was given to CV group, AZT to azithromycin group and CVE + AZT combination to CV + AZT group by oral gavage for 6 days. All of the mice from IC, CV, AZT and CV + AZT groups were sacrified on the 8th day of the infection and serum, peritoneal fluid and spleen samples were collected. Trophozoite count of the groups were determined in all groups except HC group and the average growth inhibition activity was calculated by using the growth inhibition formula. In all groups IL-12, IFN-γ, IL-2 levels were measured with ELISA method and cytotoxicity of the NK cells were measured using Cytotox 96 Non-Radioactive Cytotoxicity Assay. The number of trophozoites were significantly lower in the CV group than the IC group (p< 0.001), and also significantly lower in CV + AZT combination group than the AZT group. According to the growth inhibition calculations CV treatment showed 88.6%, AZT treatment 98.46%, AZT + CV combination treatment 99

  4. Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery.

    PubMed

    Li, Xiaojian; Vogt, Frederick G; Hayes, Don; Mansour, Heidi M

    2014-02-14

    The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides, respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morphology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (<10 μm) with smaller MMAD values for SD AZI powders in contrast to SD TOB powders. Positive linear correlations were observed between the aerosol dispersion performance parameter of FPF with increasing spray-drying pump rates and also with the difference between thermal parameters expressed as Tg-To (i.e. the difference between the glass transition temperature and outlet temperature) for SD AZI powders. The aerosol dispersion performance for SD TOB appeared to be influenced by its high water vapor sorption behavior (hygroscopicity) and pump rates or To. Aerosol dispersion performance of SD powders were distinct for both antibiotic drug aerosol systems and also between different pump rates for each system. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung

    PubMed Central

    Segal, Leopoldo N; Clemente, Jose C; Wu, Benjamin G; Wikoff, William R; Gao, Zhan; Li, Yonghua; Ko, Jane P; Rom, William N; Blaser, Martin J; Weiden, Michael D

    2017-01-01

    Introduction Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema. The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects. Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways. Methods 20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks. Bronchoalveolar lavage (BAL) was performed at baseline and after treatment. Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites. The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed. Results Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens. Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-α, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid. Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-α, IL-13 and IL-12p40. Conclusion AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects. Trial registration number NCT02557958. PMID:27486204

  6. Fabrication of a Selective and Sensitive Sensor Based on Molecularly Imprinted Polymer/Acetylene Black for the Determination of Azithromycin in Pharmaceuticals and Biological Samples

    PubMed Central

    Zhou, Tingting; Tao, Yun; Jin, Hua; Song, Bin; Jing, Tao; Luo, Dan; Zhou, Yusun; Zhou, Yikai; Lee, Yong-Ill; Mei, Surong

    2016-01-01

    A new selective and sensitive sensor based on molecularly imprinted polymer/acetylene black (MIP/AB) was developed for the determination of azithromycin (AZM) in pharmaceuticals and biological samples. The MIP of AZM was synthesized by precipitation polymerization. MIP and AB were then respectively introduced as selective and sensitive elements for the preparation of MIP/AB-modified carbon paste (MIP/ABP) electrode. The performance of the obtained sensor was estimated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. Compared with non-molecularly imprinted polymer (NIP) electrodes, NIP/ABP electrodes, and MIP-modified carbon paste electrodes, MIP/ABP electrode exhibited excellent current response toward AZM. The prepared sensor also exhibited good selectivity for AZM in comparison with structurally similar compounds. The effect of electrode composition, extraction parameters, and electrolyte conditions on the current response of the sensor was investigated. Under the optimized conditions, the prepared sensor showed two dynamic linear ranges of 1.0 × 10−7 mol L−1 to 2.0 × 10−6 mol L−1 and 2.0 × 10−6 mol L−1 to 2.0 × 10−5 mol L−1, with a limit of detection of 1.1 × 10−8 mol L−1. These predominant properties ensured that the sensor exhibits excellent reliability for detecting AZM in pharmaceuticals and biological fluids without the assistance of any separation techniques. The results were validated by the high-performance liquid chromatography–tandem mass spectrometry method. PMID:26820753

  7. Community mass treatment with azithromycin for trachoma: Factors associated with change in participation of children from the first to the second round

    PubMed Central

    Ssemanda, Elizabeth N.; Mkocha, Harran; Levens, Joshua; Munoz, Beatriz; West, Sheila K.

    2013-01-01

    Background Mass drug administration (MDA) with azithromycin is an important part of trachoma control programs. Maintaining high participation among children is challenging. Aim We assessed factors identifying households with a child who changed participation from the first MDA to the second MDA compared to households where all children participated at both MDAs. Methods Two case-control comparisons were conducted in 11 Tanzanian communities, which underwent MDA in 2008 and 2009. The first case group (n=165) was a random sample of households with a child who changed from a 2008 non-participant to a 2009 participant (delayed participant). The second case group (n=165) was a random sample of households with a child who went from a 2008 participant to a 2009 non-participant (change to non-participant). Controls (n=330) were a random sample of households where all children participated in both rounds. Risk factors were assessed using questionnaires asked of children’s guardians. Logistic models with a random-intercept were used to estimate odds ratios and 95% confidence intervals. Results Households with delayed participation were more likely to be in communities with fewer treatment days (OR=2.98, 95% CI=1.80–4.92) and assigned to Community Treatment Assistants (CTA) with a wide area to cover (OR=1.88, 95% CI=1.09–3.23). Households with change to non-participation were more likely to live further from the distribution site (OR=3.17, 95% CI=1.19–8.46), have the guardian born outside the village with short-term residency (OR=2.64, 95% CI=1.32–5.31), and be assigned to a male CTA (OR=1.75, 95% CI=1.08–2.83). Conclusions Factors related to program accessibility were associated with delayed participation and maintaining participation. PMID:26462290

  8. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  9. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  10. An Alternative to Thought Suppression?

    ERIC Educational Resources Information Center

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  11. STRV Cryocooler Tip Motion Suppression

    NASA Technical Reports Server (NTRS)

    Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

    1994-01-01

    The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

  12. Suppressing Display Cockpit Reflections

    NASA Astrophysics Data System (ADS)

    Hartmann, Rudolf

    1987-09-01

    Modern aircraft displays with relatively high visual brightness levels present day and night sensor images (generated by electro-optical systems) to crew members for navigation and fire control purposes. A heads out display (HOD) on a cathode ray tube (CRT) screen, while effective for one crew member, may distract or irritate another crew member if the image is reflected off a canopy panel into his eyes, particularly at night. This paper presents one solution applied to canopy reflection suppression encountered in the U.S. Army's APACHE Advanced Attack Helicopter where the co-pilot's HOD reflections interfered with the pilot's vision. When the co-pilot would move his head away from the screen, the reflected image path to the pilot, sitting above and behind the co-pilot, would no longer be blocked and distract him. A variety of polarizers were studied and the problem was solved by placing a linear polarizer over the CRT with its axis crossed relative to the skipping vector of the reflection, letting the canopy panel act as an analyzer. Reflected luminance was reduced by more than 25 times.

  13. Painful consequences of anger suppression.

    PubMed

    Quartana, Phillip J; Burns, John W

    2007-05-01

    The authors experimentally examined the effects of anger suppression on pain perception. On the basis of ironic process theory, they proposed that efforts to suppress experiential or expressive components of anger may paradoxically enhance cognitive accessibility of anger-related thoughts and feelings, thereby contaminating perception of succeeding pain in an anger-congruent manner. Participants were randomly assigned to nonsuppression or experiential or expressive suppression conditions during mental arithmetic with or without harassment. A cold-pressor task followed. Results revealed that participants instructed to suppress experiential or expressive components of emotion during harassment not only reported the greatest pain levels, but also rated the anger-specific dimensions of pain uniquely strong. Results suggest that attempts to suppress anger may amplify pain sensitivity by ironically augmenting perception of the irritating and frustrating qualities of pain.

  14. Inducing amnesia through systemic suppression

    PubMed Central

    Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

    2016-01-01

    Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

  15. Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice.

    PubMed Central

    Terao, Hajime; Asano, Kazuhito; Kanai, Ken-ichi; Kyo, Yoshiyuki; Watanabe, So; Hisamitsu, Tadashi; Suzaki, Harumi

    2003-01-01

    BACKGROUND: Low-dose and long-term administration of macrolide antibiotics into patients with chronic airway inflammatory diseases could favorably modify their clinical conditions. However, the therapeutic mode of action of macrolides is not well understood. Free oxygen radicals, including nitric oxide (NO), are well recognized as the important final effector molecules in the development and the maintenance of inflammatory diseases. PURPOSE: The influence of macrolide antibiotics on NO generation was examined in vivo. METHODS: Male ICR mice, 5 weeks of age, were orally administered with either roxithromycin, clarithromycin, azithromycin or josamycin once a day for 2-4 weeks. The mice were then injected intraperitoneally with 5.0 mg/kg lipopolysaccharide (LPS) and the plasma NO level was examined 6 h later. RESULTS: Although pre-treatment of mice with macrolide antibiotics for 2 weeks scarcely affected NO generation by LPS injection, the administration of macrolide antibiotics, except for josamycin, for 4 weeks significantly inhibited LPS-induced NO generation. The data in the present study also showed that pre-treatment of mice with macrolide antibiotics for 4 weeks significantly suppresses not only production of pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, but also inducible nitric oxide synthase mRNA expressions, which are enhanced by LPS injection. CONCLUSION: These results strongly suggest that suppressive activity of macrolide antibiotics on NO generation in response to LPS stimulation in vivo may, in part, account for the clinical efficacy of macrolides on chronic inflammatory diseases. PMID:14514469

  16. In Vivo Treg Suppression Assays

    PubMed Central

    Workman, Creg J.; Collison, Lauren W.; Bettini, Maria; Pillai, Meenu R.; Rehg, Jerold E.; Vignali, Dario A.A.

    2011-01-01

    To fully examine the functionality of a regulatory T cell (Treg) population, one needs to assess their ability to suppress in a variety of in vivo models. We describe five in vivo models that examine the suppressive capacity of Tregs upon different target cell types. The advantages and disadvantages of each model includ ing resources, time, and technical expertise required to execute each model are also described. PMID:21287333

  17. Azithromycin impairs TLR7 signaling in dendritic cells and improves the severity of imiquimod-induced psoriasis-like skin inflammation in mice.

    PubMed

    Huang, Shi-Wei; Chen, Yi-Ju; Wang, Sin-Ting; Ho, Li-Wei; Kao, Jun-Kai; Narita, Miwako; Takahashi, Masuhiro; Wu, Chun-Ying; Cheng, Hsuan-Yu; Shieh, Jeng-Jer

    2016-10-01

    The activation of Toll-like receptor 7 (TLR7) in dendritic cells (DCs) plays a crucial role in the pathogenesis of psoriasis. The macrolide antibiotic azithromycin (AZM) had been demonstrated to inhibit the TLR4 agonist-induced maturation and activation of murine bone marrow-derived DCs (BMDCs). To investigate the effects of AZM on the induction of DC maturation and activation by imiquimod (IMQ), a synthetic TLR7 agonist, as well as its potential as a therapeutic agent for psoriasis. The effects of AZM on IMQ-induced DC activation were investigated based on the expression of cell surface markers and cytokine secretion. The lysosomal pH, post-translational processing of TLR7, and TLR7 signaling were also examined in DCs. The therapeutic effects of AZM on psoriasis were evaluated in a murine model of IMQ-induced psoriasis-like skin inflammation. AZM significantly inhibited the expression of co-stimulatory molecules (CD40 and CD80) and reduced TNF-α, IL-10, IL-12p40, IL-12p70, IL-23p19 in BMDCs and IFN-α production in plasmacytoid DCs. AZM treatment impaired lysosomal acidification, interrupted TLR7 maturation in the lysosome, and ultimately blocked the IMQ-induced NF-κB and IRF-7 nuclear translocation in DCs. AZM treatment decreased signs of IMQ-induced skin inflammation in BALB/c mice. In addition to decreasing keratinocyte hyper-proliferation and restoring their terminal differentiation, AZM treatment decreased the accumulation of DCs as well as CD4, CD8 T cells and IL-17 producing cells in psoriatic skin lesions. AZM treatment improved splenomegaly, decreased the populations of Th17 and γδ T cells, and reduced the expression of cytokines known to be involved in the pathogenesis of psoriasis, such as IL-17A, IL-17F, IL-22 and IL-23, in the skin and spleen. AZM impaired IMQ-induced DC activation by decreasing lysosomal acidification and disrupting TLR7 maturation and signaling. AZM significantly improved the IMQ-induced psoriasis-like inflammation in mice. AZM

  18. Creative solutions to extraordinary challenges in clinical trials: methodology of a phase III trial of azithromycin and chloroquine fixed-dose combination in pregnant women in Africa.

    PubMed

    Chandra, Richa S; Orazem, John; Ubben, David; Duparc, Stephan; Robbins, Jeffery; Vandenbroucke, Pol

    2013-04-11

    Malaria in pregnancy is one of the most common preventable causes of maternal and neonatal morbidity and mortality in sub-Saharan Africa. To prevent its adverse effects, such as maternal anaemia, placental parasitaemia and low birth weight (LBW) neonates, the World Health Organization recommends effective malaria case management, use of insecticide-treated bed nets and intermittent preventive therapy in pregnancy (IPTp). Sulphadoxine-pyrimethamine (SP) has been the standard for IPTp in several countries, but parasite resistance to SP is growing. Therefore, new IPTp therapies are urgently needed. One candidate being evaluated for IPTp is a fixed-dose combination of azithromycin and chloroquine (AZCQ). This paper describes the challenges and the innovative solutions implemented in designing and conducting a pivotal AZCQ-IPTp trial, sponsored by Pfizer Inc and co-funded by Pfizer Inc and the Medicines for Malaria Venture. The AZCQ-IPTp pivotal trial is a multicentre, multicountry, phase III, open-label, randomized superiority study of AZCQ-IPTp versus SP-IPTp in pregnant women of sub-Saharan Africa. The trial was designed to meet stringent regulatory agency scientific advice and IPTp policy makers' recommendations, and incorporates an innovative adaptive design to manage programme risk, maintain the operating characteristics of the study and optimize resources. The trial's novel composite primary endpoint is the proportion of participants with a suboptimal pregnancy outcome (abortion [≤28 weeks], stillbirths [>28 weeks], premature [<37 weeks] deliveries, LBW [<2,500 g] live neonates, missing neonatal birth weight data or loss to follow-up). The study employs a prospective group sequential design with three unblinded analyses when 50%, 70% and 100% of participants achieve the primary endpoint; the study team will remain blinded to the analyses until after the completion of the study. The number of participants randomized will be adaptive, based on the blinded

  19. Maternal Intravenous Treatment with either Azithromycin or Solithromycin Clears Ureaplasma parvum from the Amniotic Fluid in an Ovine Model of Intrauterine Infection

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Keelan, Jeffrey A.; Noe, Andres; Carter, Sean; Watts, Rory; Spiller, Owen B.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Newnham, John P.

    2014-01-01

    Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n = 5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and

  20. In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne Management.

    PubMed

    Shunmugaperumal, Tamilvanan; Kaur, Varinder

    2016-06-01

    The objectives of the current investigation are (1) to prepare and characterize (particle size, surface charge (potential zeta), surface morphology by transmission electron microscopy, drug content, and drug release) the azithromycin (AZM, 100 mg)-loaded oil-in-water (o/w) macroemulsion, (2) to assess the toxicity of macroemulsion with or without AZM using RBC lysis test in comparison with AZM in phosphate buffer solution of pH 7.4, (3) to compare the in vitro antimicrobial activity (in Escherichia coli using zone inhibition assay) of AZM-loaded macroemulsion with its aqueous solution, and (4) to assess the in vitro anti-inflammatory effect (using egg albumin denaturation bioassay) of the AZM-loaded macroemulsion in comparison with diclofenac sodium in phosphate buffer solution of pH 7.4. The AZM-loaded macroemulsion possessed the dispersed oil droplets with a mean diameter value of 52.40 ± 1.55 μm. A reversal in the zeta potential value from negative (-2.16 ± 0.75 mV) to positive (+6.52 ± 0.96 mV) was noticed when AZM was added into the macroemulsion. At a 1:5 dilution ratio, 2.06 ± 0.03 mg of drug was released from macroemulsion followed by 1.01 ± 0.01 and 0.25 ± 0.08 mg, respectively, for 1:10 and 1:40 dilution ratios. Antimicrobial activity maintenance and significant reduction of RBC lysis property were noticed for AZM after loaded in the macroemulsion. However, an increment in the absorbance values for emulsion-treated samples in comparison to the control samples was noticed in the anti-inflammatory test. This speculates the potential of the AZM-loaded emulsion to manage inflammatory conditions produced at Acne vulgaris.

  1. Suppressed Charmed B Decay

    SciTech Connect

    Snoek, Hella Leonie

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  2. Menstrual suppression in special circumstances.

    PubMed

    Kirkham, Yolanda A; Ornstein, Melanie P; Aggarwal, Anjali; McQuillan, Sarah

    2014-10-01

    To provide a Canadian consensus document for health care providers with recommendations for menstrual suppression in patients with physical and/or cognitive challenges or those who are undergoing cancer treatment in whom menstruation may have a deleterious effect on their health. This document reviews the options available for menstrual suppression, its specific indications, contraindications, and side effects, both immediate and long-term, and the investigations and monitoring necessary throughout suppression. Clinicians will be better informed about the options and indications for menstrual suppression in patients with cognitive and/or physical disabilities and patients undergoing chemotherapy, radiation, or other treatments for cancer. Published literature was retrieved through searches of Medline, EMBASE, OVID, and the Cochrane Library using appropriate controlled vocabulary and key words (heavy menstrual bleeding, menstrual suppression, chemotherapy/radiation, cognitive disability, physical disability, learning disability). Results were restricted to systematic reviews, randomized controlled trials, observation studies, and pilot studies. There were no language or date restrictions. Searches were updated on a regular basis and new material was incorporated into the guideline until September 2013. Grey (unpublished) literature was identified through searching websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). There is a need for specific guidelines on menstrual suppression in at-risk populations for health care providers. Recommendations 1. Menstrual suppression and therapeutic amenorrhea should be considered safe and viable options for women who need or want to have

  3. Visual Surround Suppression in Schizophrenia

    PubMed Central

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  4. Vibration suppression using smart structures

    NASA Astrophysics Data System (ADS)

    Garcia, Ephrahim; Inman, Daniel J.; Dosch, Jeffrey

    The control of structures for vibration suppression is discussed in the context of using smart materials and structures. Here the use of smart structures refers to using embedded piezoelectric devices as both control actuators and sensors. Using embedded sensors and actuators allows great improvements in performance over traditional structures (both passive and active) for vibration suppression. The application of smart structures to three experimental flexible structures is presented. The first is a flexible beam, the second is a flexible beam undergoing slewing motion, the third is a ribbed antenna. A simple model of a piezoelectric actuator/sensor is presented. The equations of motion for each structure is presented. The control issues considered as those associated with multi-input, multi-output control, PID control and LQR control implementation. A modern control analysis illustrates the usefulness of smart structures for vibration suppression.

  5. Vibration suppression using smart structures

    NASA Technical Reports Server (NTRS)

    Garcia, Ephrahim; Inman, Daniel J.; Dosch, Jeffrey

    1991-01-01

    The control of structures for vibration suppression is discussed in the context of using smart materials and structures. Here the use of smart structures refers to using embedded piezoelectric devices as both control actuators and sensors. Using embedded sensors and actuators allows great improvements in performance over traditional structures (both passive and active) for vibration suppression. The application of smart structures to three experimental flexible structures is presented. The first is a flexible beam, the second is a flexible beam undergoing slewing motion, the third is a ribbed antenna. A simple model of a piezoelectric actuator/sensor is presented. The equations of motion for each structure is presented. The control issues considered as those associated with multi-input, multi-output control, PID control and LQR control implementation. A modern control analysis illustrates the usefulness of smart structures for vibration suppression.

  6. The amphetamine appetite suppressant saga.

    PubMed

    2004-02-01

    (1) In 1999, all amphetamine derivatives still sold in France as appetite suppressants were withdrawn from the market because of serious cardiovascular adverse effects. Sibutramine, marketed in France since 2001, is closely related to this group of drugs. (2) The adverse effects shared by these drugs are mainly neuropsychiatric (due to a psychostimulant action) and cardiovascular (arterial hypertension and tachycardia). (3) More specific cardiovascular adverse effects, such as pulmonary hypertension and severe cardiac valve damage, emerged after several years of use. The first reports date back to the 1960s. (4) The pulmonary hypertension associated with appetite suppressants can be fatal or necessitate transplantation. (5) Cardiac valve damage due to appetite suppressants is generally irreversible and sometimes requires surgery.

  7. Noise suppressing capillary separation system

    DOEpatents

    Yeung, Edward S.; Xue, Yongjun

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

  8. Conditioned suppression, punishment, and aversion

    NASA Technical Reports Server (NTRS)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  9. Suppressing explosive synchronization by contrarians

    NASA Astrophysics Data System (ADS)

    Zhang, Xiyun; Guan, Shuguang; Zou, Yong; Chen, Xiaosong; Liu, Zonghua

    2016-01-01

    Explosive synchronization (ES) has recently received increasing attention and studies have mainly focused on the conditions of its onset so far. However, its inverse problem, i.e. the suppression of ES, has not been systematically studied so far. As ES is usually considered to be harmful in certain circumstances such as the cascading failure of power grids and epileptic seizure, etc., its suppression is definitely important and deserves to be studied. We here study this inverse problem by presenting an efficient approach to suppress ES from a first-order to second-order transition, without changing the intrinsic network structure. We find that ES can be suppressed by only changing a small fraction of oscillators into contrarians with negative couplings and the critical fraction for the transition from the first order to the second order increases with both the network size and the average degree. A brief theory is presented to explain the underlying mechanism. This finding underlines the importance of our method to improve the understanding of neural interactions underlying cognitive processes.

  10. High temperature suppression of dioxins.

    PubMed

    Zhan, Ming-Xiu; Chen, Tong; Fu, Jian-Ying; Lin, Xiao-Qing; Lu, Sheng-Yong; Li, Xiao-Dong; Yan, Jian-Hua; Buekens, Alfons

    2016-03-01

    Combined Sulphur-Nitrogen inhibitors, such as sewage sludge decomposition gases (SDG), thiourea and amidosulphonic acid have been observed to suppress the de novo synthesis of dioxins effectively. In this study, the inhibition of PCDD/Fs formation from model fly ash was investigated at unusually high temperatures (650 °C and 850 °C), well above the usual range of de novo tests (250-400 °C). At 650 °C it was found that SDG evolving from dried sewage sludge could suppress the formation of 2,3,7,8-substituted PCDD/Fs with high efficiency (90%), both in weight units and in I-TEQ units. Additionally, at 850 °C, three kinds of sulphur-amine or sulphur-ammonium compounds were tested to inhibit dioxins formation during laboratory-scale tests, simulating municipal solid waste incineration. The suppression efficiencies of PCDD/Fs formed through homogeneous gas phase reactions were all above 85% when 3 wt. % of thiourea (98.7%), aminosulphonic acid (96.0%) or ammonium thiosulphate (87.3%) was added. Differences in the ratio of PCDFs/PCDDs, in weight average chlorination level and in the congener distribution of the 17 toxic PCDD/Fs indicated that the three inhibitors tested followed distinct suppression pathways, possibly in relation to their different functional groups of nitrogen. Furthermore, thiourea reduced the (weight) average chlorinated level. In addition, the thermal decomposition of TUA was studied by means of thermogravimetry-fourier transform infrared spectroscopy (TG-FTIR) and the presence of SO2, SO3, NH3 and nitriles (N≡C bonds) was shown in the decomposition gases; these gaseous inhibitors might be the primary dioxins suppressants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  12. Suppression of operant vs consummatory behavior.

    PubMed

    DeCosta, M J; Ayres, J J

    1971-07-01

    The magnitude and variability of conditioned suppression of bar pressing and dipper licking were compared. In two steady-state experiments, suppression of bar pressing was more profound and more stable from day to day. The two measures of suppression were uncorrelated as indexed by Pearson product-moment correlation coefficients computed for adjacent trials. Correlations within measures (internal consistency) were somewhat higher for the bar-press system except when a high proportion of rats completely suppressed on one of the correlated trials. In a transient state experiment in which possible adventitious punishment of both response systems was eliminated, suppression of bar pressing was again more profound and considerably slower to extinguish.

  13. Wakefield suppression using beatwave structures

    SciTech Connect

    Yu, D.; Kim, J.S.

    1991-12-31

    A proposed method of suppressing transverse wakefields in an accelerating structure makes use of the fact that superposition of long-range wakes excited by an electron bunch transversing a series of accelerating cells with different transverse frequencies can produce interference cancellation, thereby significantly reducing the magnitudes of the harmful wake potentials. Analytic calculations as well as time-domain and modal sum simulations are performed to the beatwave effects produced by detuned, disk-loaded cavities as function of their transverse frequency spread and the population density.

  14. Fire suppression and detection equipment

    SciTech Connect

    E.E. Bates

    2006-01-15

    Inspection and testing guidelines go beyond the 'Code of Federal Regulation'. Title 30 of the US Code of Federal Regulations (30 CFR) contains requirements and references to national standards for inspection, testing and maintenance of fire suppression and detection equipment for mine operators. However, federal requirements have not kept pace with national standards and best practices. The article lists National Fire Protection (NFPA) standards that are referenced by the US Mine Safety and Health Administration (MSHA) in 30 CFR. It then discusses other NFPA Standards excluded from 30 CFR and explains the NFPA standard development process. 2 refs., 3 tabs., 5 photos.

  15. Suppression effects on musical and verbal memory.

    PubMed

    Schendel, Zachary A; Palmer, Caroline

    2007-06-01

    Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues.

  16. Orientation-tuned suppression in binocular rivalry reveals general and specific components of rivalry suppression.

    PubMed

    Stuit, Sjoerd M; Cass, John; Paffen, Chris L E; Alais, David

    2009-10-16

    During binocular rivalry (BR), conflicting monocular images are alternately suppressed from awareness. During suppression of an image, contrast sensitivity for probes is reduced by approximately 0.3-0.5 log units relative to when the image is in perceptual dominance. Previous studies on rivalry suppression have led to controversies concerning the nature and extent of suppression during BR. We tested for feature-specific suppression using orthogonal rivaling gratings and measuring contrast sensitivity to small grating probes at a range of orientations in a 2AFC orientation discrimination task. Results indicate that suppression is not uniform across orientations: suppression was much greater for orientations close to that of the suppressed grating. The higher suppression was specific to a narrow range around the suppressed rival grating, with a tuning similar to V1 orientation bandwidths. A similar experiment tested for spatial frequency tuning and found that suppression was stronger for frequencies close to that of the suppressed grating. Interestingly, no tuned suppression was observed when a flicker-and-swap paradigm was used, suggesting that tuned suppression occurs only for lower-level, interocular rivalry. Together, the results suggest there are two components to rivalry suppression: a general feature-invariant component and an additional component specifically tuned to the rivaling features.

  17. Glucose Suppression of Glucagon Secretion

    PubMed Central

    Le Marchand, Sylvain J.; Piston, David W.

    2010-01-01

    Glucagon is released from α-cells present in intact pancreatic islets at glucose concentrations below 4 mm, whereas higher glucose levels inhibit its secretion. The mechanisms underlying the suppression of α-cell secretory activity are poorly understood, but two general types of models have been proposed as follows: direct inhibition by glucose or paracrine inhibition from non-α-cells within the islet of Langerhans. To identify α-cells for analysis, we utilized transgenic mice expressing fluorescent proteins targeted specifically to these cells. Measurements of glucagon secretion from pure populations of flow-sorted α-cells show that contrary to its effect on intact islets, glucose does stimulate glucagon secretion from isolated α-cells. This observation argues against a direct inhibition of glucagon secretion by glucose and supports the paracrine inhibition model. Imaging of cellular metabolism by two-photon excitation of NAD(P)H autofluorescence indicates that glucose is metabolized in α-cells and that glucokinase is the likely rate-limiting step in this process. Imaging calcium dynamics of α-cells in intact islets reveals that inhibiting concentrations of glucose increase the intracellular calcium concentration and the frequency of α-cell calcium oscillations. Application of candidate paracrine inhibitors leads to reduced glucagon secretion but did not decrease the α-cell calcium activity. Taken together, the data suggest that suppression occurs downstream from α-cell calcium signaling, presumably at the level of vesicle trafficking or exocytotic machinery. PMID:20231269

  18. Water Mist fire suppression experiment

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Water Mist commercial research program is scheduled to fly an investigation on STS-107 in 2002. This investigation will be flown as an Experimental Mounting Structure (EMS) insert into the updated Combustion Module (CM-2), a sophisticated combustion chamber plus diagnostic equipment. (The investigation hardware is shown here mounted in a non-flight frame similar to the EMS.) Water Mist is a commercial research program by the Center for Commercial Applications of Combustion in Space (CCACS), a NASA Commercial Space Center located at the Colorado School of Mines, in Golden, CO and Industry Partner Environmental Engineering Concepts. The program is focused on developing water mist as a replacement for bromine-based chemical fire suppression agents (halons). By conducting the experiments in microgravity, interference from convection currents is minimized and fundamental knowledge can be gained. This knowledge is incorporated into models, which can be used to simulate a variety of physical environments. The immediate objective of the project is to study the effect of a fine water mist on a laminar propagating flame generated in a propane-air mixture at various equivalence ratios. The effects of droplet size and concentration on the speed of the flame front is used as a measure of the effectiveness of fire suppression in this highly controlled experimental environment.

  19. Methods of suppressing automotive interference

    NASA Astrophysics Data System (ADS)

    Taggart, H. E.

    1981-11-01

    Automotive manufacturers utilize several techniques to reduce EMI emanating from the vehicle. The techniques include resistor spark plugs, resistor spark plug cables, use of silicone lubricant in the distributor, use of capacitors as filters, placement of grounding straps at key locations, conductive fan belt discharge, and tire static-charge reduction. If even further reduction is needed to obtain the maximum capability of a specific mobile communication system, additional suppression techniques are discussed which are effective at frequencies from approximately 30 to 1000 MHz. Measurement results show that the EMI from a new production-line automobile, measured in accordance with SAE Standard J551g, can be reduced as much as 10 to 15 dB by employing these suppression techniques. The amount of degradation to a mobile narrow-band FM receiver, such as the type used by law enforcement agencies, can be measured using the measurement technique described. This same technique can then be used as a tool to further reduce EMI from the vehicle components.

  20. Suppressed epidemics in multirelational networks

    NASA Astrophysics Data System (ADS)

    Xu, Elvis H. W.; Wang, Wei; Xu, C.; Tang, Ming; Do, Younghae; Hui, P. M.

    2015-08-01

    A two-state epidemic model in networks with links mimicking two kinds of relationships between connected nodes is introduced. Links of weights w1 and w0 occur with probabilities p and 1 -p , respectively. The fraction of infected nodes ρ (p ) shows a nonmonotonic behavior, with ρ drops with p for small p and increases for large p . For small to moderate w1/w0 ratios, ρ (p ) exhibits a minimum that signifies an optimal suppression. For large w1/w0 ratios, the suppression leads to an absorbing phase consisting only of healthy nodes within a range pL≤p ≤pR , and an active phase with mixed infected and healthy nodes for p pR . A mean field theory that ignores spatial correlation is shown to give qualitative agreement and capture all the key features. A physical picture that emphasizes the intricate interplay between infections via w0 links and within clusters formed by nodes carrying the w1 links is presented. The absorbing state at large w1/w0 ratios results when the clusters are big enough to disrupt the spread via w0 links and yet small enough to avoid an epidemic within the clusters. A theory that uses the possible local environments of a node as variables is formulated. The theory gives results in good agreement with simulation results, thereby showing the necessity of including longer spatial correlations.

  1. Water Mist fire suppression experiment

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Water Mist commercial research program is scheduled to fly an investigation on STS-107 in 2002. This investigation will be flown as an Experimental Mounting Structure (EMS) insert into the updated Combustion Module (CM-2), a sophisticated combustion chamber plus diagnostic equipment. (The investigation hardware is shown here mounted in a non-flight frame similar to the EMS.) Water Mist is a commercial research program by the Center for Commercial Applications of Combustion in Space (CCACS), a NASA Commercial Space Center located at the Colorado School of Mines, in Golden, CO and Industry Partner Environmental Engineering Concepts. The program is focused on developing water mist as a replacement for bromine-based chemical fire suppression agents (halons). By conducting the experiments in microgravity, interference from convection currents is minimized and fundamental knowledge can be gained. This knowledge is incorporated into models, which can be used to simulate a variety of physical environments. The immediate objective of the project is to study the effect of a fine water mist on a laminar propagating flame generated in a propane-air mixture at various equivalence ratios. The effects of droplet size and concentration on the speed of the flame front is used as a measure of the effectiveness of fire suppression in this highly controlled experimental environment.

  2. Detection of Anorectal and Cervicovaginal Chlamydia Trachomatis Infections following Azithromycin Treatment: Prospective Cohort Study with Multiple Time-Sequential Measures of rRNA, DNA, Quantitative Load and Symptoms

    PubMed Central

    Dukers-Muijrers, Nicole H. T. M.; Speksnijder, Arjen G. C. L.; Morré, Servaas A.; Wolffs, Petra F. G.; van der Sande, Marianne A. B.; Brink, Antoinette A. T. P.; van den Broek, Ingrid V. F.; Werner, Marita I. L. S.; Hoebe, Christian J. P. A.

    2013-01-01

    Background Determination of Chlamydia trachomatis (Ct) treatment success is hampered by current assessment methods, which involve a single post-treatment measurement only. Therefore, we evaluated Ct detection by applying multiple laboratory measures on time-sequential post-treatment samples. Methods A prospective cohort study was established with azithromycin-treated (1000 mg) Ct patients (44 cervicovaginal and 15 anorectal cases). Each patient provided 18 self-taken samples pre-treatment and for 8 weeks post-treatment (response: 96%; 1,016 samples). Samples were tested for 16S rRNA (TMA), bacterial load (quantitative PCR; Chlamydia plasmid DNA) and type (serovar and multilocus sequence typing). Covariates (including behavior, pre-treatment load, anatomic site, symptoms, age, and menstruation) were tested for their potential association with positivity and load at 3–8 weeks using regression analyses controlling for repeated measures. Findings By day 9, Ct positivity decreased to 20% and the median load to 0.3 inclusion-forming units (IFU) per ml (pre-treatment: 170 IFU/ml). Of the 35 cases who reported no sex, sex with a treated partner or safe sex with a new partner, 40% had detection, i.e. one or more positive samples from 3–8 weeks (same Ct type over time), indicating possible antimicrobial treatment failure. Cases showed intermittent positive detection and the number of positive samples was higher in anorectal cases than in cervicovaginal cases. The highest observed bacterial load between 3–8 weeks post-treatment was 313 IFU/ml, yet the majority (65%) of positive samples showed a load of ≤2 IFU/ml. Pre-treatment load was found to be associated with later load in anorectal cases. Conclusions A single test at 3–8 weeks post-treatment frequently misses Ct. Detection reveals intermittent low loads, with an unknown risk of later complications or transmission. These findings warrant critical re-evaluation of the clinical management of single dose

  3. Parasitological Clearance Rates and Drug Concentrations of a Fixed Dose Combination of Azithromycin-Chloroquine in Asymptomatic Pregnant Women with Plasmodium Falciparum Parasitemia: An Open-Label, Non-Comparative Study in Sub-Saharan Africa

    PubMed Central

    Phiri, Kamija; Kimani, Joshua; Mtove, George A.; Zhao, Qinying; Rojo, Ricardo; Robbins, Jeffery; Duparc, Stephan; Ayoub, Ayman; Vandenbroucke, Pol

    2016-01-01

    Background Malaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority. Methods and Findings This was an open-label, non-comparative study (NCT01103713) in 5 countries in East and sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) to assess parasitological response and drug concentrations of a single, 3-day course of four tablets of a fixed-dose combination of azithromycin-chloroquine (AZCQ) 250/155 mg given during the second or third trimester to women with asymptomatic Plasmodium falciparum parasitemia in their first or second pregnancy. Parasitemia was determined by microscopy and molecular genotyping was performed to characterize parasites relative to the baseline infection. Weekly follow-up visits took place until day 42 after first dose and additional follow-up occurred after delivery. Systemic concentrations of azithromycin (AZ), chloroquine (CQ), and the CQ metabolite, desethyl CQ (DECQ) were evaluated at Day 0 (pre-dose), at Day 2 (pre-dose, 2 and 8 hours) and randomly at Days 7 and 14. Systemic concentrations of CQ and DECQ were also measured randomly at Day 21 and Day 28. In total, 404 women were screened for eligibility and 168 were treated, 155 of whom completed the study. PCR-adjusted parasitological response in the modified intent-to-treat population at day 28 (the primary efficacy endpoint) was estimated by the Kaplan-Meier method as 99.35% (95% confidence interval [CI]: 97.76, 100.00). PCR-adjusted parasitological response remained high at day 42 (95.19%; 95% CI: 91.35, 99.03). In

  4. A randomized, double-masked, parallel-group, comparative study to evaluate the clinical efficacy and safety of 1% azithromycin–0.1% dexamethasone combination compared to 1% azithromycin alone, 0.1% dexamethasone alone, and vehicle in the treatment of subjects with blepharitis

    PubMed Central

    Hosseini, Kamran; Lindstrom, Richard L; Foulks, Gary; Nichols, Kelly K

    2016-01-01

    Purpose To evaluate the clinical efficacy and safety of a 1% azithromycin–0.1% dexamethasone combination in DuraSite (“combination”) compared to 0.1% dexamethasone in DuraSite, 1% azithromycin in DuraSite, and vehicle in the treatment of subjects with blepharitis. Materials and methods This was a Phase III, double-masked, vehicle-controlled, four-arm study in which 907 subjects with blepharitis were randomized to combination (n=305), 0.1% dexamethasone (n=298), 1% azithromycin (n=155), or vehicle (n=149). Ten study visits were scheduled: screening visit, days 1 and 4 (dosing phase) and 15, and months 1–6 (follow-up phase). On day 1, subjects applied one drop of the study drug to the eyelid of the inflamed eye(s) twice daily, and continued with twice-daily dosing for 14 days. After completing 14 days of dosing, subjects were followed for 6 months for efficacy and safety. Results A total of 57 subjects (6.3%) had complete clinical resolution at day 15: 25 (8.2%), 17 (5.7%), 8 (5.2%), and 7 (4.7%) subjects in the combination-, 0.1% dexamethasone-, 1% azithromycin-, and vehicle-treatment groups, respectively. The combination was superior to 1% azithromycin and vehicle alone, but not to 0.1% dexamethasone alone. Mean composite (total) clinical sign and symptom scores improved in all four treatment groups during the post-treatment evaluation phase for the intent-to-treat population, but outcomes were superior when a drop containing 0.1% dexamethasone was utilized. Clinical response was noted as early as day 4, and persisted as long as 6 months. Most adverse events were considered mild in severity and not related to the study drug. Conclusion A higher percentage of subjects in the combination group achieved complete clinical resolution of the signs and symptoms of blepharitis at day 15 than with 1% azithromycin and vehicle, but outcomes were similar to treatment with 0.1% dexamethasone alone. The combination was well tolerated. PMID:27570444

  5. How to suppress undesired synchronization.

    PubMed

    Louzada, V H P; Araújo, N A M; Andrade, J S; Herrmann, H J

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network.

  6. How to suppress undesired synchronization

    PubMed Central

    Louzada, V. H. P.; Araújo, N. A. M.; Andrade, J. S.; Herrmann, H. J.

    2012-01-01

    Examples of synchronization can be found in a wide range of phenomena such as neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks and two real ones, namely, the Routers of the Internet and a neuronal network. PMID:22993685

  7. Elastic Suppression of Viscous Fingering

    NASA Astrophysics Data System (ADS)

    Peng, Gunnar; Lister, John

    2016-11-01

    Consider peeling an elastic tape or beam away from a rigid base to which it is stuck by a film of viscous liquid. The peeling motion requires air to invade the viscous liquid and is thus susceptible to the Saffman-Taylor fingering instability. We analyse the fundamental travelling-wave solution and show that the advancing air-liquid interface remains linearly stable at higher capillary numbers than in a standard Hele-Shaw cell. A short-wavelength expansion yields an analytical expression for the growth rate which is valid for all unstable modes throughout the parameter space, allowing us to identify and quantify four distinct physical mechanisms that each help suppress the instability. Applying our method to the experiments by Pihler-Puzovic et al. (2012) reveals that the radial geometry and time-variation stabilize the system further.

  8. MEK5 suppresses osteoblastic differentiation

    SciTech Connect

    Kaneshiro, Shoichi; Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki; Higuchi, Chikahisa

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  9. Multiple treg suppressive modules and their adaptability

    PubMed Central

    Wing, James B.; Sakaguchi, Shimon

    2012-01-01

    Foxp3+ regulatory T cells (Tregs) are a constitutively immunosuppressive cell type critical for the control of autoimmunity and inflammatory pathology. A range of mechanisms of Treg suppression have been identified and it has not always been clear how these different mechanisms interact in order to properly suppress autoimmunity and excessive inflammation. In recent years it has become clear that, while all Tregs seem to share some core suppressive mechanisms, they are also able to adapt to their surroundings in response to a variety of stimuli by homing to the sites of inflammation and exerting ancillary suppressive functions. In this review, we discuss the relevance and possible modes of Treg adaptability and put forward a modular model of Treg suppressive function. Understanding this flexibility may hold the key to understanding the full spectrum of Treg suppressive behavior. PMID:22754556

  10. Tactile stimulation can suppress visual perception

    PubMed Central

    Ide, Masakazu; Hidaka, Souta

    2013-01-01

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities. PMID:24336391

  11. Tactile stimulation can suppress visual perception.

    PubMed

    Ide, Masakazu; Hidaka, Souta

    2013-12-13

    An input (e.g., airplane takeoff sound) to a sensory modality can suppress the percept of another input (e.g., talking voices of neighbors) of the same modality. This perceptual suppression effect is evidence that neural responses to different inputs closely interact with each other in the brain. While recent studies suggest that close interactions also occur across sensory modalities, crossmodal perceptual suppression effect has not yet been reported. Here, we demonstrate that tactile stimulation can suppress the percept of visual stimuli: Visual orientation discrimination performance was degraded when a tactile vibration was applied to the observer's index finger of hands. We also demonstrated that this tactile suppression effect on visual perception occurred primarily when the tactile and visual information were spatially and temporally consistent. The current findings would indicate that neural signals could closely and directly interact with each other, sufficient to induce the perceptual suppression effect, even across sensory modalities.

  12. Acoustic Suppression Systems and Related Methods

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R. (Inventor); Kern, Dennis L. (Inventor)

    2013-01-01

    An acoustic suppression system for absorbing and/or scattering acoustic energy comprising a plurality of acoustic targets in a containment is described, the acoustic targets configured to have resonance frequencies allowing the targets to be excited by incoming acoustic waves, the resonance frequencies being adjustable to suppress acoustic energy in a set frequency range. Methods for fabricating and implementing the acoustic suppression system are also provided.

  13. Shot noise suppression in avalanche photodiodes.

    PubMed

    Ma, Feng; Wang, Shuling; Campbell, Joe C

    2005-10-21

    We identify a new shot noise suppression mechanism in a thin (approximately 100 nm) heterostructure avalanche photodiode. In the low-gain regime the shot noise is suppressed due to temporal correlations within amplified current pulses. We demonstrate in a Monte Carlo simulation that the effective excess noise factors can be < 1, and reconcile the apparent conflict between theory and experiments. This shot noise suppression mechanism is independent of known mechanisms such as Coulomb interaction, or reflection at heterojunction interfaces.

  14. Two Techniques For Suppressing Vibrations In Structures

    NASA Technical Reports Server (NTRS)

    Chen, Gun-Shing; Garba, John A.; Wada, Ben K.

    1991-01-01

    Two techniques intended to be used together to suppress vibrations in large, complicated truss structure involve combination of active and passive damping. Based on bridge feedback and criterion for placement of actuators. Research continues to develop system using these and other techniques to suppress vibrations in, and help control shape of, truss structure in outer space that supports precise, segmented reflector of communication antenna. On Earth, developmental techniques applicable to suppression of vibrations in bridges and tall buildings.

  15. A Computer Model of Saccadic Suppression.

    DTIC Science & Technology

    1981-01-01

    suppression could be produced by "normal" saccadic eye movements and by "saccading" the visual image across the retina during eye fixation. Mitrari...Visual Threshold by Displacement of Retinal Image ," Nature, 225, 90-92, 1970. Matin, E., "Saccadic Suppression: A Review and an Analysis," Psychol., Bull...1975. Stark, L., Kong, R., Scnwartz, S., Hendry, D., Bridgemen, B., "Saccadic Suppression of Image Displacement," Vis. Res., 16, 1185-1187, 1976

  16. Two Techniques For Suppressing Vibrations In Structures

    NASA Technical Reports Server (NTRS)

    Chen, Gun-Shing; Garba, John A.; Wada, Ben K.

    1991-01-01

    Two techniques intended to be used together to suppress vibrations in large, complicated truss structure involve combination of active and passive damping. Based on bridge feedback and criterion for placement of actuators. Research continues to develop system using these and other techniques to suppress vibrations in, and help control shape of, truss structure in outer space that supports precise, segmented reflector of communication antenna. On Earth, developmental techniques applicable to suppression of vibrations in bridges and tall buildings.

  17. Issues in Numerical Simulation of Fire Suppression

    SciTech Connect

    Tieszen, S.R.; Lopez, A.R.

    1999-04-12

    This paper outlines general physical and computational issues associated with performing numerical simulation of fire suppression. Fire suppression encompasses a broad range of chemistry and physics over a large range of time and length scales. The authors discuss the dominant physical/chemical processes important to fire suppression that must be captured by a fire suppression model to be of engineering usefulness. First-principles solutions are not possible due to computational limitations, even with the new generation of tera-flop computers. A basic strategy combining computational fluid dynamics (CFD) simulation techniques with sub-grid model approximations for processes that have length scales unresolvable by gridding is presented.

  18. Transient noise suppression algorithm in speech system

    NASA Astrophysics Data System (ADS)

    Cao, Keyu; Wang, Mingjiang

    2017-08-01

    In this paper, I mainly introduce the algorithm of transient noise suppression in speech system. Firstly, it divides into impulsive noise and other types of transient noise according to the characteristics of transient noise. In the impulse noise suppression algorithm, I mainly use the averaging energy threshold method to detect the impulse noise, and then I use the amplitude threshold method to reduce the impulse noise which was detected. In the other types of transient noise suppression algorithm, I mainly use the Optimally Modified-Log Spectral Amplitude estimation (OM-LSA) algorithm and the Minimum Control Recursive Average (MCRA) algorithm to suppress the transient noise.

  19. ISS Update: Burning and Suppression of Solids

    NASA Image and Video Library

    ISS Update Commentator Pat Ryan interviews Paul Ferkul, Principal Investigator for the Burning and Suppression of Solids (BASS) experiment, about performing combustion experiments in microgravity. ...

  20. Synthesis and antibacterial activity of novel 15-membered macrolide derivatives: 4''-carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin.

    PubMed

    Ma, Shutao; Ma, Ruixin; Liu, Zhaopeng; Ma, Chenchen; Shen, Xuecui

    2009-10-01

    4''-Carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin were designed, synthesized and evaluated. The 4''-carbamate analogs retained excellent activity against erythromycin-susceptible Staphylococcus pneumoniae and showed improved activity against erythromycin-resistant Staphylococcus pneumoniae. Compared with 4''-carbamate analogs, 11,12-cyclic carbonate-4''-carbamate analogs exhibited improved activity against erythromycin-resistant Staphylococcus pneumoniae encoded by the mef gene or the erm and mef genes, and 11,4''-di-O-arylalkylcarbamoyl analogs showed greatly improved activity (0.25-0.5 microg/mL) against erythromycin-resistant Staphylococcus pneumoniae encoded by the erm gene. Among them, the novel series of 11,4''-di-O-arylalkylcarbamoyl analogs 7a-k exhibited potent and balanced activity against susceptible and resistant bacteria. In particular, compounds 7f and 7k were the most effective against susceptible bacteria and resistant bacteria encoded by the erm gene or the mef gene.

  1. Characterization of Staphylococcus aureus Strains Isolated from Czech Cystic Fibrosis Patients: High Rate of Ribosomal Mutation Conferring Resistance to MLS(B) Antibiotics as a Result of Long-Term and Low-Dose Azithromycin Treatment.

    PubMed

    Tkadlec, Jan; Vařeková, Eva; Pantůček, Roman; Doškař, Jiří; Růžičková, Vladislava; Botka, Tibor; Fila, Libor; Melter, Oto

    2015-08-01

    Staphylococcus aureus is one of the most frequent pathogens infecting the respiratory tract of patients with cystic fibrosis (CF). This study was the first to examine S. aureus isolates from CF patients in the Czech Republic. Among 100 S. aureus isolates from 92 of 107 observed patients, we found a high prevalence of resistance to macrolide-lincosamide-streptogramin B (MLS(B)) antibiotics (56%). More than half of the resistant strains (29 of 56) carried a mutation in the MLS(B) target site. The emergence of MLS(B) resistance and mutations conferring resistance to MLS(B) antibiotics was associated with azithromycin treatment (p=0.000000184 and p=0.000681, respectively). Methicillin resistance was only detected in 3% of isolates and the rate of resistance to other antibiotics did not exceed 12%. The prevalence of small-colony variant (SCV) strains was relatively low (9%) and eight of nine isolates with the SCV phenotype were thymidine dependent. The study population of S. aureus was heterogeneous in structure and both the most prevalent community-associated and hospital-acquired clonal lineages were represented. Of the virulence genes, enterotoxin genes seg (n=52), sei (n=49), and sec (n=16) were the most frequently detected among the isolates. The PVL genes (lukS-PV and lukF-PV) have not been revealed in any of the isolates.

  2. Bone suppression technique for chest radiographs

    NASA Astrophysics Data System (ADS)

    Huo, Zhimin; Xu, Fan; Zhang, Jane; Zhao, Hui; Hobbs, Susan K.; Wandtke, John C.; Sykes, Anne-Marie; Paul, Narinder; Foos, David

    2014-03-01

    High-contrast bone structures are a major noise contributor in chest radiographic images. A signal of interest in a chest radiograph could be either partially or completely obscured or "overshadowed" by the highly contrasted bone structures in its surrounding. Thus, removing the bone structures, especially the posterior rib and clavicle structures, is highly desirable to increase the visibility of soft tissue density. We developed an innovative technology that offers a solution to suppress bone structures, including posterior ribs and clavicles, on conventional and portable chest X-ray images. The bone-suppression image processing technology includes five major steps: 1) lung segmentation, 2) rib and clavicle structure detection, 3) rib and clavicle edge detection, 4) rib and clavicle profile estimation, and 5) suppression based on the estimated profiles. The bone-suppression software outputs an image with both the rib and clavicle structures suppressed. The rib suppression performance was evaluated on 491 images. On average, 83.06% (±6.59%) of the rib structures on a standard chest image were suppressed based on the comparison of computer-identified rib areas against hand-drawn rib areas, which is equivalent to about an average of one rib that is still visible on a rib-suppressed image based on a visual assessment. Reader studies were performed to evaluate reader performance in detecting lung nodules and pneumothoraces with and without a bone-suppression companion view. Results from reader studies indicated that the bone-suppression technology significantly improved radiologists' performance in the detection of CT-confirmed possible nodules and pneumothoraces on chest radiographs. The results also showed that radiologists were more confident in making diagnoses regarding the presence or absence of an abnormality after rib-suppressed companion views were presented

  3. Attentional selection by distractor suppression.

    PubMed

    Caputo, G; Guerra, S

    1998-03-01

    Selective attention was studied in displays containing singletons popping out for their odd form or color. The target was defined as the form-singleton, the distractor as the color-singleton. The task was to discriminate the length of a longer line inside the target. Target-distractor similarity was controlled using a threshold measurement as dependent variable in experiments in which distractor presence vs absence, bottom-up vs top-down selection (through knowledge of target features), and target-distractor distance were manipulated. The results in the bottom-up condition showed that length threshold was elevated when a distractor was present and that this elevation progressively increased as the number of distractors was increased from one to two. This set-size effect was not accounted by the hypothesis that selective attention intervenes only at the stage of decision before response. Selective attention produced a suppressive surround in which discriminability of neighboring objects was strongly reduced, and a larger surround in which discriminability was reduced by an approximately constant amount. Different results were found in the top-down condition in which target discriminability was unaffected by distractor presence and no effect of target-distractor distance was found. On the other hand, response times in both bottom-up and top-down conditions were slower the shorter the target-distractor distance was. On the basis of the experimental results, selective attention is a parallel process of spatial filtering at an intermediate processing level operating after objects have been segmented. This filtering stage explores high level interactions between objects taking control on combinatorial explosion by operating over only a limited spatial extent: it picks out a selected object and inhibits the neighboring objects; then, non-selected objects are suppressed across the overall image. When no feature-based selection is available in the current behavior, this

  4. Growth suppression caused by corticosteroid eye drops.

    PubMed

    Wolthers, Ole D

    2011-01-01

    Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year.

  5. Simulation analysis of a wildfire suppression system

    Treesearch

    Abílio Pereira Pacheco; João Claro; Tiago. Oliveira

    2013-01-01

    Rekindles and false alarms are unusually high in the Portuguese wildfire management system, representing a high burden on suppression resources in particular, and fire management resources in general. In 20,049 occurrences that the suppression system handled in the summer of 2010, 12.5% were false alarms and 15.0% were rekindles. We present a discreteevent simulation...

  6. Ferromagnetic resonance probe liftoff suppression apparatus

    DOEpatents

    Davis, Thomas J.; Tomeraasen, Paul L.

    1985-01-01

    A liftoff suppression apparatus utilizing a liftoff sensing coil to sense the amount a ferromagnetic resonance probe lifts off the test surface during flaw detection and utilizing the liftoff signal to modulate the probe's field modulating coil to suppress the liftoff effects.

  7. Foam as a Fire Suppressant: An Evaluation

    Treesearch

    Paul Schlobohm; Ron Rochna

    1987-01-01

    The ability of fire suppressant foams to improve ground-applied fire control efforts was evaluated. Foaming agents and foam-generating systems were examined. Performance evaluations were made for direct attack, indirect attack, and mop-up. Foam was determined to suppress and repel fire in situations where water did not. Cost comparisons of mop-up work showed straight...

  8. Suppressive soils: back on the radar screen

    USDA-ARS?s Scientific Manuscript database

    Suppressive soils are those in which a pathogen does not establish or persist, establishes but causes little or no damage, or establishes and causes disease for a while but thereafter the disease is less important, although the pathogen may persist in the soil (Weller, 2002). ‘General suppression,’ ...

  9. New approaches to hard bubble suppression

    NASA Technical Reports Server (NTRS)

    Henry, R. D.; Besser, P. J.; Warren, R. G.; Whitcomb, E. C.

    1973-01-01

    Description of a new double-layer method for the suppression of hard bubbles that is more versatile than previously reported suppression techniques. It is shown that it may be possible to prevent hard bubble generation without recourse to exchange coupling of multilayer films.

  10. The hidden consequences of fire suppression

    Treesearch

    Carol Miller

    2012-01-01

    Wilderness managers need a way to quantify and monitor the effects of suppressing lightning-caused wildfires, which can alter natural fire regimes, vegetation, and habitat. Using computerized models of fire spread, weather, and fuels, it is now possible to quantify many of the hidden consequences of fire suppression. Case study watersheds in Yosemite and Sequoia-Kings...

  11. Transport suppression by shear reduction

    NASA Astrophysics Data System (ADS)

    Martinell, Julio; Del-Castillo-Negrete, Diego

    2009-11-01

    The relationship between transport and shear is a problem of considerable interest to magnetically confined plasmas. It is well known that there are cases in which an increase of flow shear can lead to a reduction of turbulent transport. However, this is not a generic result, and there are transport problems in which the opposite is the case. In particular, as originally discussed in Ref. footnotetextdel-Castillo-Negrete and Morrison, Phys. Fluids A 5, 948 (1993), barriers to chaotic transport typically form in regions of vanishing shear. This property, which is generic to the so-called non-twist Hamiltonian systems footnotetextdel-Castillo-Negrete, Greene, and Morrison, Physica D 91, 1 (1996), explains the observed resilience of transport barriers in non-monotonic zonal flows in plasmas and fluids and the robustness of shearless magnetic surfaces in reverse shear configurations. Here we study the role of finite Larmor radius (FLR) effects on the suppression of chaotic transport by shear reduction in a simplified model. Following Ref. footnotetextdel-Castillo-Negrete, Phys. Plasmas, 7, 1702 (2000) we consider a model consisting of a superposition of drift waves and a non-monotonic zonal flow. The FLR effects are incorporated by gyroaveraging the E xB velocity, and transport is studied by following the evolution of ensembles of test particles.

  12. Multicopy Suppression Underpins Metabolic Evolvability

    PubMed Central

    Patrick, Wayne M.; Quandt, Erik M.; Swartzla