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Sample records for aureus ca-mrsa infections

  1. Practical management: community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA): the latest sports epidemic.

    PubMed

    Benjamin, Holly J; Nikore, Vineet; Takagishi, Josh

    2007-09-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has gained international recognition as a superbug that causes serious infectious outbreaks in high-risk populations such as athletes. Clusters of cases in various athletic teams, particularly contact sports, have been reported since 1993 in the United States and more recently in Canada. CA-MRSA infections are not limited to North America, and all athletes are considered high risk. Skin-to-skin contact appears to be the primary mode of transmission. While typical infections are local skin and soft-tissue abscesses, CA-MRSA infections can spread systemically and lead to significant morbidity and mortality if not promptly identified and treated. The gold standard of treatment for all abscesses is incision and drainage with wound culture for bacterial identification and antibiotic sensitivity testing. A limited number of antibiotics are currently useful in the treatment of CA-MRSA and are reviewed. Geographical variation in patterns of antibiotic resistance further complicates the treatment. Meticulous, consistent use of infection prevention strategies is critical to control outbreaks in the athletic population. Good hygiene, prompt identification of infection, limited exposure to infected persons and contaminated objects, and proper treatment combined with close follow-up of infected athletes will help contain CA-MRSA outbreaks. Future research is needed to explore person-to-person and fomite transmission risks, to define the significance of nasal carriage and skin colonization in relation to CA-MRSA infections, and to further investigate antibiotic resistance patterns. Universal education is needed for all athletes and personnel who provide care in the athletic setting to help control this widespread epidemic. PMID:17873553

  2. CA-MRSA. The new sports pathogen.

    PubMed

    Kurkowski, Christina

    2007-01-01

    Skin infections in athletes caused by community-associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) have been observed within many cities throughout the United States and within many countries throughout the world (Centers for Disease Control and Prevention [CDC], 2003). As the incidence rises in the athletic population, clinicians must learn to identify risk factors for CA-MRSA, diagnosis and treat infections with judicious use of antimicrobial agents and facilitate strategies to limit transmission. Recently, a new consensus guideline for handling CA-MRSA outbreaks in sports has been released by the CDC (Gorwitz et al., 2006). This article includes a review of the evolution of MRSA; distinguishes between healthcare associated Methicillin-resistant Staphylococcus aureus (HA-MRSA) and CA-MRSA; and reviews the diagnosis, management, and prevention strategies to limit transmission of CA-MRSA. PMID:17921891

  3. Staphylococcus aureus and Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in and Around Therapeutic Whirlpools in College Athletic Training Rooms

    PubMed Central

    Kahanov, Leamor; Kim, Young Kyun; Eberman, Lindsey; Dannelly, Kathleen; Kaur, Haninder; Ramalinga, A.

    2015-01-01

    Context: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a leading cause of skin and soft tissue infection in the nonhospitalized community. Care of the athletes in athletic training rooms is specifically designed with equipment tailored to the health care needs of the athletes, yet recent studies indicate that CA-MRSA is still prevalent in athletic facilities and that cleaning methods may not be optimal. Objective: To investigate the prevalence of Staphylococcus aureus and CA-MRSA in and around whirlpools in the athletic training room. Design: Cross-sectional study. Setting: National Collegiate Athletic Association Division I university. Patients or Other Participants: Student-athletes (n = 109) consisting of 46 men (42%) and 63 women (58%) representing 6 sports. Main Outcome Measure(s): Presence of MRSA and Staphylococcus aureus in and around the whirlpool structures relative to sport and number of athletes using the whirlpools. Results: We identified Staphylococcus aureus in 22% (n = 52/240) of the samples and MRSA in 0.8% (n = 2/240). A statistically significant difference existed between the number of athletes using the whirlpool and the presence of Staphylococcus aureus in and around the whirlpools (F2,238 = 2.445, P = .007). However, Staphylococcus aureus was identified regardless of whether multiple athletes used a whirlpool or no athletes used a whirlpool. We did not identify a relationship between the number of athletes who used a whirlpool and Staphylococcus aureus or MRSA density (P = .134). Conclusions: Staphylococcus aureus and MRSA were identified in and around the whirlpools. Transmission of the bacteria can be reduced by following the cleaning and disinfecting protocols recommended by the Centers for Disease Control and Prevention. Athletic trainers should use disinfectants registered by the Environmental Protection Agency to sanitize all whirlpools between uses. PMID:25710853

  4. Systemic CA-MRSA infection following trauma during soccer match in inner Brazil: clinical and molecular characterization.

    PubMed

    Camargo, Carlos Henrique; da Cunha, Maria de Lourdes Ribeiro de Souza; Bonesso, Mariana Fávero; da Cunha, Fabiana Picoli; Barbosa, Alexandre Naime; Fortaleza, Carlos Magno Castelo Branco

    2013-07-01

    Even though community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) was described a decade ago, reports from Brazil are scarce and cases occurred in large urban centers. We report MRSA sepsis in a 16-year-old male from a small town and who had no history of exposure to healthcare or recent travel. After trauma during a soccer match, he presented swelling in the right thigh, which evolved in a month to cellulitis complicated by local abscess, orchitis and pneumonia. The patient presented severe sepsis, with fever and respiratory failure. Laboratory findings included blood leukocyte counts above 40,000/mm(3) and thrombocytopenia. He was submitted to mechanical ventilation and therapy with vancomycin and imipenem. He had a slow but favorable response to therapy and was discharged after six weeks of hospitalization. MRSA grew from blood cultures and respiratory aspirates obtained before antimicrobial therapy. The isolate belonged to sequence type 5, spa type t311, harbored SCCmec type IV and genes for Panton-Valentine leukocidin and Enterotoxin A. The pulsed-field gel electrophoresis pattern was distinct from North American classic CA-MRSA clones. However, the sequence type and the spa type revealed that the clone belong to the same clonal complex isolated in Argentina. This is the first CA-MRSA infection reported in that region, with significant epidemiologic and clinical implications. PMID:23602786

  5. Potential therapeutic drug target identification in Community Acquired-Methicillin Resistant Staphylococcus aureus (CA-MRSA) using computational analysis

    PubMed Central

    Yadav, Pramod Kumar; Singh, Gurmit; Singh, Satendra; Gautam, Budhayash; Saad, Esmaiel IF

    2012-01-01

    The emergence of multidrug-resistant strain of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strain has highlighted the urgent need for the alternative and effective therapeutic approach to combat the menace of this nosocomial pathogen. In the present work novel potential therapeutic drug targets have been identified through the metabolic pathways analysis. All the gene products involved in different metabolic pathways of CA-MRSA in KEGG database were searched against the proteome of Homo sapiens using the BLASTp program and the threshold of E-value was set to as 0.001. After database searching, 152 putative targets were identified. Among all 152 putative targets, 39 genes encoding for putative targets were identified as the essential genes from the DEG database which are indispensable for the survival of CA-MRSA. After extensive literature review, 7 targets were identified as potential therapeutic drug target. These targets are Fructose-bisphosphate aldolase, Phosphoglyceromutase, Purine nucleoside phosphorylase, Uridylate kinase, Tryptophan synthase subunit beta, Acetate kinase and UDP-N-acetylglucosamine 1-carboxyvinyltransferase. Except Uridylate kinase all the identified targets were involved in more than one metabolic pathways of CA-MRSA which underlines the importance of drug targets. These potential therapeutic drug targets can be exploited for the discovery of novel inhibitors for CA-MRSA using the structure based drug design (SBDD) strategy. PMID:23055607

  6. Comparison of Methicillin Resistant Staphylococcus Aureus in Healthy Community Hospital Visitors [CA-MRSA] and Hospital Staff [HA-MRSA

    PubMed Central

    Pathare, Nirmal A; Tejani, Sara; Asogan, Harshini; Al Mahruqi, Gaitha; Al Fakhri, Salma; Zafarulla, Roshna; Pathare, Anil V.

    2015-01-01

    Background The prevalence of community-associated methicillin-resistant Staphylococcus aureus [CA-MRSA] is unknown in Oman. Methods Nasal and cell phones swabs were collected from hospital visitors and health-care workers on sterile polyester swabs and directly inoculated onto a mannitol salt agar containing oxacillin, allowing growth of methicillin-resistant microorganisms. Antibiotic susceptibility tests were performed using Kirby Bauer’s disc diffusion method on the isolates. Minimum inhibitory concentration (MIC) was determined for vancomycin and teicoplanin against the resistant isolates of MRSA by the Epsilometer [E] test. A brief survey questionnaire was requested be filled to ascertain the exposure to known risk factors for CA-MRSA carriage. Results Overall, nasal colonization with CA-MRSA was seen in 34 individuals (18%, 95% confidence interval [CI] =12.5%–23.5%), whereas, CA-MRSA was additionally isolated from the cell phone surface in 12 participants (6.3%, 95% CI =5.6%–6.98%). Nasal colonization prevalence with hospital-acquired [HA] MRSA was seen in 16 individuals (13.8%, 95% confidence interval [CI] =7.5%–20.06%), whereas, HA-MRSA was additionally isolated from the cell phone surface in 3 participants (2.6%, 95% CI =1.7–4.54). Antibiotic sensitivity was 100% to linezolid and rifampicin in the CA-MRSA isolates. Antibiotic resistance to vancomycin and clindamycin varied between 9–11 % in the CA-MRSA isolates. Mean MIC for vancomycin amongst CA- and HA-MRSA were 6.3 and 9.3 μg/ml, whereas for teicoplanin they were 13 and 14 μg/ml respectively by the E-test. There was no statistically significant correlation between CA-MRSA nasal carriage and the risk factors (P>0.05, Chi-square test). Conclusions The prevalence of CA-MRSA in the healthy community hospital visitors was 18 % (95% CI, 12.5% to 23.5%) as compared to 13.8% HA-MRSA in the hospital health-care staff. Despite a significant prevalence of CA-MRSA, these strains were mostly sensitive

  7. Molecular modeling, dynamics studies and virtual screening of Fructose 1, 6 biphosphate aldolase-II in community acquired- methicillin resistant Staphylococcus aureus (CA-MRSA).

    PubMed

    Yadav, Pramod Kumar; Singh, Gurmit; Gautam, Budhayash; Singh, Satendra; Yadav, Madhu; Srivastav, Upasana; Singh, Brijendra

    2013-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as a nosocomial pathogen to the community which commonly causes skin and soft-tissue infections (SSTIs). This strain (MW2) has now become resistant to the most of the beta-lactam antibiotics; therefore it is the urgent need to identify the novel drug targets. Recently fructose 1,6 biphosphate aldolase-II (FBA) has been identified as potential drug target in CA-MRSA. The FBA catalyses the retro-ketolic cleavage of fructose-1,6-bisphosphate (FBP) to yield dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) in glycolytic pathway. In the present research work the 3D structure of FBA was predicted using the homology modeling method followed by validation. The molecular dynamics simulation (MDS) of the predicted model was carried out using the 2000 ps time scale and 1000000 steps. The MDS results suggest that the modeled structure is stable. The predicted model of FBA was used for virtual screening against the NCI diversity subset-II ligand databases which contain 1364 compounds. Based on the docking energy scores, it was found that top four ligands i.e. ZINC01690699, ZINC13154304, ZINC29590257 and ZINC29590259 were having lower energy scores which reveal higher binding affinity towards the active site of FBA. These ligands might act as potent inhibitors for the FBA so that the menace of antimicrobial resistance in CA-MRSA can be conquered. However, pharmacological studies are required to confirm the inhibitory activity of these ligands against the FBA in CA-MRSA. PMID:23423142

  8. THE FREQUENCY OF COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (CA-MRSA) AMONG SAMPLES IN INSTITUTE FOR PUBLIC HEALTH IN CANTON SARAJEVO

    PubMed Central

    Bektas, Sabaheta; Obradovic, Amina; Aljicevic, Mufida; Numanovic, Fatima; Hodzic, Dunja; Sporisevic, Lutvo

    2016-01-01

    Background: The increase in the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections lacking risk factors for exposure to the health care system has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). These strains have been distinguished from health care-associated MRSA (HA-MRSA) strains by epidemiological, molecular and genetic means as well as by antibiotic susceptibility profile, tissue tropism and virulence traits. Objective: To assess prevalence and antibiotic susceptibility profile of CA-MRSA in Canton Sarajevo, Bosnia and Herzegovina. Results: Out of 1.905 positive Staphylococcus aureus isolates from various samples of outpatients collected during six months, 279 (14,64%) were MRSA isolates. Out of 279 MRSA samples, 133 (47,67%) were found in nasal swabs, from which 48 (36,09%) were in the age group <1 year and 39 (29,32 %) are in the age 1-5 year. Rate of the positive skin swabs was highest among the subject of age group <1 year (46 or 54,12 %) and 1-5 year (18 or 21,18 %). Predominantly antibiotic types among MRSA strains are resistant to penicillin and cefoxitin (36,90 %) and to penicillin, cefoxitin and erythromycin (61,35 %). Conclusion: Continued monitoring of epidemiology and emerging drug resistance data is critical for the effective management of these infections. PMID:27047271

  9. The role of primary care prescribers in the diagnosis and management of community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections.

    PubMed

    Lawrence, Kenneth R; Golik, Monica V; Davidson, Lisa

    2009-01-01

    Nosocomial infections caused by methicillin-resistant Staphylococcus aureus were first reported in the United States in the early 1960s. Beginning in the 1990s, healthy individuals from the community with no risk factors for resistant bacteria began presenting with methicillin-resistant Staphylococcus aureus infections, acquiring the name "community-associated methicillin-resistant Staphylococcus aureus" (CA-MRSA). CA-MRSA has a tendency to affect the skin and skin structures, generally in the form of abscesses and furuncles, carbuncles, and cellulitis. Cases of invasive infections including bacteremia, endocarditis, and necrotizing pneumonia have also been reported. A patient complaint of a "spider bite" is frequently associated with CA-MRSA. CA-MRSA and the traditional health care-associated methicillin-resistant Staphylococcus aureus are distinguished by their genetic composition, virulence factors, and susceptibility patterns to non-beta-lactam antibiotics. Appropriate management of CA-MRSA skin and skin structure infections includes incision and drainage of infected tissue and appropriate antimicrobial therapy. It has been suggested that when prevalence of CA-MRSA within a community eclipses 10%-15%, empiric use of non-beta-lactam antibiotics with in vitro activity against CA-MRSA be initiated when treating skin and skin structure infections. CA-MRSA retains susceptibility to a range of older antibiotics available in oral formulations such as minocycline, doxycycline, sulfamethoxazole-trimethoprim, moxifloxacin, levofloxacin, and clindamycin. Local susceptibility patterns and individual patient factors should guide the selection of antibiotics. PMID:19617720

  10. Replacement of HA-MRSA by CA-MRSA Infections at an Academic Medical Center in the Midwestern United States, 2004-5 to 2008

    PubMed Central

    David, Michael Z.; Cadilla, Adriana; Boyle-Vavra, Susan; Daum, Robert S.

    2014-01-01

    We noted anecdotally that infections designated as health care-associated (HA-) MRSA by epidemiologic criteria seemed to be decreasing in incidence at the University of Chicago Medical Center (UCMC) after 2004. We compared MRSA patients seen at any site of clinical care at UCMC and the isolates that caused their infections in 2004-5 (n = 545) with those in 2008 (n = 135). The percent of patients with MRSA infections cultured > 2 days after hospital admission decreased from 19.5% in 2004-5 to 7.4% in 2008 (p = 0.001). The percent in 2004-5 compared with 2008 who had a hospitalization (49.1% to 26.7%, p = 0.001) or surgery (43.0% to 14.1%, p<0.001) in the previous year decreased. In 2008 a greater percent of patients was seen in the emergency department (23.1% vs. 39.3%) and a smaller percent both in intensive care units (15.6% vs. 6.7%) and in other inpatient units (40.7% vs. 32.6%) (p<0.001). The percent of patients with CA-MRSA infections by the CDC epidemiologic criteria increased from 36.5% in 2004-5 to 62.2% in 2008 (p<0.001). The percent of MRSA isolates sharing genetic characteristics of USA100 decreased from 27.9% (152/545) to 12.6% (17/135), while the percent with CA-MRSA (USA300) characteristics increased from 53.2% (290/545) to 66.7% (90/135). The percent of infections that were invasive did not change significantly. Our data suggest that HA-MRSA infections, both by epidemiologic and microbiologic criteria, relative to CA-MRSA, decreased between 2004-5 and 2008 at UCMC. PMID:24755631

  11. Application of the Random Amplified Polymorphic DNA (RAPD) Fingerprinting to Analyze Genetic Variation in Community Associated-Methicillin Resistant Staphylococcus Aureus (CA-MRSA) Isolates in Iran

    PubMed Central

    Mobasherizadeh, Sina; Shojaei, Hasan; Havaei, Seyed Asghar; Mostafavizadeh, Kamyar; Davoodabadi, Fazollah; Khorvash, Farzin; Ataei, Behrooz; Daei-Naser, Abbas

    2016-01-01

    The aim of this study was to apply RAPD technique to analyze the genetic variability among the Iranian CA-MRSA isolates. The RAPD amplification was implemented on 25 strains isolated from the anterior nares of 410 healthy children using four randomly selected oligonucleotide primers from the stocks available in our laboratory, including the primers 1254, GE6, OLP6 and OLP13 from our stock. The amplified PCR products were detected on a 1.5% agarose gel and subjected to further analysis to establish the band profiles and genetic relationships using the Gel Compar® program. The Iranian CA-MRSA isolates produced distinct RAPD patterns which varied based on the primer used, however, the primer 1254 revealed highly polymorphic patterns consisting 5 discernable RAPD types (RT), “RT1” (12, 48%), “RT2” (8, 32%), “RT3” (3, 12%), and “RT4 and RT5”, (a single RAPD type each, 4%). Phylogenetic analysis based on RAPD profiles divided most of the CA-MRSA isolates into 2 distinct but related RAPD clusters, a small group and two single unrelated RAPD types. This study shows that the simple and cost-effective but rather difficult to optimize RAPD fingerprinting could be used to evaluate genetic and epidemiological relationships of CA-MRSA isolates on condition that the patterns are obtained from carefully optimized laboratory tests. PMID:27045409

  12. The emerging ST8 methicillin-resistant Staphylococcus aureus clone in the community in Japan: associated infections, genetic diversity, and comparative genomics.

    PubMed

    Iwao, Yasuhisa; Ishii, Rumiko; Tomita, Yusuke; Shibuya, Yasuhiro; Takano, Tomomi; Hung, Wei-Chun; Higuchi, Wataru; Isobe, Hirokazu; Nishiyama, Akihito; Yano, Mio; Matsumoto, Tetsuya; Ogata, Kikuyo; Okubo, Takeshi; Khokhlova, Olga; Ho, Pak-Leung; Yamamoto, Tatsuo

    2012-04-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major concern worldwide. In the United States, ST8 CA-MRSA with SCCmecIVa (USA300) has been predominant, affecting the entire United States. In this study, we investigated Japanese ST8 CA-MRSA with new SCCmecIVl (designated ST8 CA-MRSA/J), which has emerged in Japan since 2003. Regarding community spread and infections, ST8 CA-MRSA/J spread in 16.2-34.4% as a major genotype in the community in Japan, and was associated with skin and soft tissue infections (SSTIs), colitis, and invasive infections (sepsis, epidural abscesses, and necrotizing pneumonia), including influenza prodrome cases and athlete infections, similar to USA300. It spread to even public transport and Hong Kong through a Japanese family. Regarding genetic diversity, ST8 CA-MRSA/J included ST and spa variants and was classified into at least three pulsed-field gel electrophoresis types, ST8 Jα to γ. Of those, ST8 Jβ was associated with severe invasive infections. As for genomics, ST8 CA-MRSA/J showed high similarities to USA300, but with marked diversity in accessory genes; e.g., ST8 CA-MRSA/J possessed enhanced cytolytic peptide genes of CA-MRSA, but lacked the Panton-Valentine leukocidin phage and arginine catabolic mobile element, unlike USA300. The unique features of ST8 CA-MRSA/J included a novel mosaic SaPI (designated SaPIj50) carrying the toxic shock syndrome toxin-1 gene with high expression; the evolution included salvage (through recombination) of hospital-acquired MRSA virulence. The data suggest that ST8 CA-MRSA/J has become a successful native clone in Japan, in association with not only SSTIs but also severe invasive infections (posing a threat), requiring attention. PMID:22350401

  13. Differential Distribution and Expression of Panton-Valentine Leucocidin among Community-Acquired Methicillin-Resistant Staphylococcus aureus Strains

    PubMed Central

    Saïd-Salim, Battouli; Mathema, Barun; Braughton, Kevin; Davis, Stacy; Sinsimer, Daniel; Eisner, William; Likhoshvay, Yekaterina; DeLeo, Frank R.; Kreiswirth, Barry N.

    2005-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat worldwide. CA-MRSA strains differ from hospital-acquired MRSA strains in their antibiotic susceptibilities and genetic backgrounds. Using several genotyping methods, we clearly define CA-MRSA at the genetic level and demonstrate that the prototypic CA-MRSA strain, MW2, has spread as a homogeneous clonal strain family that is distinct from other CA-MRSA strains. The Panton-Valentine leucocidin (PVL)-encoding genes, lukF and lukS, are prevalent among CA-MRSA strains and have previously been associated with CA-MRSA infections. To better elucidate the role of PVL in the pathogenesis of CA-MRSA, we first analyzed the distribution and expression of PVL among different CA-MRSA strains. Our data demonstrate that PVL genes are differentially distributed among CA-MRSA strains and, when they are present, are always transcribed, albeit with strain-to-strain variability of transcript levels. To directly test whether PVL is critical for the pathogenesis of CA-MRSA, we evaluated the lysis of human polymorphonuclear leukocytes (PMNs) during phagocytic interaction with PVL-positive and PVL-negative CA-MRSA strains. Unexpectedly, there was no correlation between PVL expression and PMN lysis, suggesting that additional virulence factors underlie leukotoxicity and, thus, the pathogenesis of CA-MRSA. PMID:16000462

  14. Methicillin-Resistant Staphylococcus aureus Ocular Infection in Taiwan

    PubMed Central

    Kang, Yu-Chuan; Hsiao, Ching-Hsi; Yeh, Lung-Kun; Ma, David H.K.; Chen, Phil Y.F.; Lin, Hsin-Chiung; Tan, Hsin-Yuan; Chen, Hung-Chi; Chen, Shin-Yi; Huang, Yhu-Chering

    2015-01-01

    Abstract Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important public health issue. This observational study aimed to characterize clinical features, antibiotic susceptibility, and genotypes of ocular infections caused by MRSA based on the clinical and molecular definitions of community-associated (CA) and healthcare-associated (HA) strains. Fifty-nine patients with culture-proven S aureus ocular infection were enrolled from January 1, 2010 to December 31, 2011 at Chang Gung Memorial Hospital, Taiwan. Antibiotic susceptibility was verified using disk diffusion/E test. For characterization, staphylococcal cassette chromosome mec (SCCmec), pulsed-field gel electrophoresis (PFGE), multilocus sequence type (MLST), and Panton–Valentine leukocidin (PVL) gene, were performed. MRSA isolates from the patients with HA factors were classified as clinically defined HA-MRSA, and those carrying SCCmec type I to III as molecularly defined HA-MRSA. Thirty-four patients with MRSA ocular infection were identified. The most common clone of CA-MRSA and HA-MRSA isolates was ST59/PFGE type D/SCCmec IV,VT/PVL (+) (n = 12) and CC 239/PFGE type A/SCCmec III, IIIA/PVL(−) (n = 10), respectively. All the 11 patients with molecularly defined HA-MRSA infections and 50% of the 22 patients with molecularly defined CA-MRSA infections were found to have HA factors (P = .005). CA-MRSA tended to cause lid infections, whereas HA-MRSA tended to cause corneal infections. Contrary to HA-MRSA isolates, nearly all the CA-MRSA isolates were susceptible to trimethoprim/sulfamethoxazole and fluoroquinolones under either clinical or molecular classifications. In Taiwan, CA-MRSA isolates exhibited considerably higher susceptibility to fluoroquinolones when compared with HA-MRSA isolates. A strong correlation was observed between the HA factors and molecularly defined HA-MRSA isolates. PMID:26496268

  15. Combating CA-MRSA in Physical Education, Sports, and Dance

    ERIC Educational Resources Information Center

    Andrews, Amanda K.; Howard-Shaughnessy, Candice; Adams, Jon E.

    2007-01-01

    By now most people have heard about the deadly bacteria that can fester in locker rooms, on sports equipment, and in dance facilities, among other places. This article was written to help PERD professionals become better informed about these bacteria, called community-acquired methicillin-resistant "Staphylococcus aureus" (CA-MRSA). Readers will…

  16. Methicillin-resistant Staphylococcus aureus ST30-SCCmec IVc clone as the major cause of community-acquired invasive infections in Argentina.

    PubMed

    Fernandez, S; de Vedia, L; Lopez Furst, M J; Gardella, N; Di Gregorio, S; Ganaha, M C; Prieto, S; Carbone, E; Lista, N; Rotrying, F; Stryjewski, M E; Mollerach, M

    2013-03-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have become a major concern worldwide. We conducted a prospective multicenter study of invasive CA-MRSA to evaluate clinical features and genotype of strains causing invasive infections in Argentina. A total of 55 patients with invasive CA-MRSA infections were included. Most patients (60%) had bloodstream infections, 42% required admission to intensive care unit and 16% died. No CA-MRSA isolates were multiresistant (resistant ⩾3 classes of antibiotics). All isolates carried Panton-Valentine leukocidin (PVL) genes and staphylococcal cassette chromosome (SCCmec) type IV. The majority CA-MRSA strains belonged to ST30 and had identical pulsed-field gel electrophoresis (PFGE) patterns, qualifying as a clonal dissemination of a highly transmissible strain. The main clone recovered from patients with CA-MRSA invasive infections was genotyped as pulsed-field gel electrophoresis type C-ST30, SCCmec type IVc-spa type 019, PVL positive. It has become predominant and replaced the previously described CA-MRSA clone (PFGE type A, ST5, SCCmec type IV, spa type 311). PMID:23340226

  17. Ceftaroline Fosamil Use in 2 Pediatric Patients With Invasive Methicillin-Resistant Staphylococcus aureus Infections.

    PubMed

    Williams, Amanda W; Newman, Patrick M; Ocheltree, Sara; Beaty, Rachel; Hassoun, Ali

    2015-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common pathogens causing pediatric infections including skin and soft tissue infections, pyogenic arthritis, osteomyelitis, and septic shock. For decades, patients were treated with antibiotics such as vancomycin and clindamycin, but there is an increasing incidence of resistance to these traditional therapies. We describe 2 cases of patients with CA-MRSA invasive infections with bacteremia who experienced vancomycin therapy failure but who were successfully treated with ceftaroline fosamil. Case 1 involves an 8-year-old Hispanic male who was diagnosed with CA-MRSA bacteremia, thigh abscess, and osteomyelitis. The patient was admitted to the pediatric intensive care unit in septic shock. Case 2 involves an 8-year-old Caucasian male who was diagnosed with CA-MRSA sepsis, right arm abscess, and osteomyelitis. We were able to successfully treat both patients with CA-MRSA sepsis and invasive infection-who failed vancomycin therapy-with ceftaroline fosamil with no adverse efiects. Despite the positive outcome in both pediatric patients, clinical trials with ceftaroline fosamil are needed to further support its use in pediatric patients. PMID:26766937

  18. Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Japanese Girl with Disseminating Multiple Organ Infection: A Case Report and Review of Japanese Pediatric Cases

    PubMed Central

    Yonezawa, Ryuta; Kuwana, Tsukasa; Kawamura, Kengo; Inamo, Yasuji

    2015-01-01

    Pediatric invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is very serious and occasionally fatal. This infectious disease is still a relatively rare and unfamiliar infectious disease in Japan. We report a positive outcome in a 23-month-old Japanese girl with meningitis, osteomyelitis, fasciitis, necrotizing pneumonia, urinary tract infection, and bacteremia due to CA-MRSA treated with linezolid. PCR testing of the CA-MRSA strain was positive for PVL and staphylococcal enterotoxin b and negative for ACME. SCC mec was type IVa. This case underscores the selection of effective combinations of antimicrobial agents for its treatment. We need to be aware of invasive CA-MRSA infection, which rapidly progresses with a serious clinical course, because the incidence of the disease may be increasing in Japan. PMID:26819794

  19. Ceftaroline Fosamil Use in 2 Pediatric Patients With Invasive Methicillin-Resistant Staphylococcus aureus Infections

    PubMed Central

    Newman, Patrick M.; Ocheltree, Sara; Beaty, Rachel; Hassoun, Ali

    2015-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common pathogens causing pediatric infections including skin and soft tissue infections, pyogenic arthritis, osteomyelitis, and septic shock. For decades, patients were treated with antibiotics such as vancomycin and clindamycin, but there is an increasing incidence of resistance to these traditional therapies. We describe 2 cases of patients with CA-MRSA invasive infections with bacteremia who experienced vancomycin therapy failure but who were successfully treated with ceftaroline fosamil. Case 1 involves an 8-year-old Hispanic male who was diagnosed with CA-MRSA bacteremia, thigh abscess, and osteomyelitis. The patient was admitted to the pediatric intensive care unit in septic shock. Case 2 involves an 8-year-old Caucasian male who was diagnosed with CA-MRSA sepsis, right arm abscess, and osteomyelitis. We were able to successfully treat both patients with CA-MRSA sepsis and invasive infection—who failed vancomycin therapy—with ceftaroline fosamil with no adverse efiects. Despite the positive outcome in both pediatric patients, clinical trials with ceftaroline fosamil are needed to further support its use in pediatric patients. PMID:26766937

  20. Emerging ST121/agr4 community-associated methicillin-resistant Staphylococcus aureus (MRSA) with strong adhesin and cytolytic activities: trigger for MRSA pneumonia and fatal aspiration pneumonia in an influenza-infected elderly.

    PubMed

    Wan, T-W; Tomita, Y; Saita, N; Konno, K; Iwao, Y; Hung, W-C; Teng, L-J; Yamamoto, T

    2016-09-01

    The pathogenesis of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia in influenza-infected elderly individuals has not yet been elucidated in detail. In the present study, a 92-year-old man infected with influenza developed CA-MRSA pneumonia. His CA-MRSA was an emerging type, originated in ST121/agr4 S. aureus, with diversities of Panton-Valentine leucocidin (PVL)(-)/spat5110/SCCmecV(+) versus PVL(+)/spat159((etc.))/SCCmec (-), but with common virulence potentials of strong adhesin and cytolytic activities. Resistance to erythromycin/clindamycin (inducible-type) and gentamicin was detected. Pneumonia improved with the administration of levofloxacin, but with the subsequent development of fatal aspiration pneumonia. Hence, characteristic CA-MRSA with strong adhesin and cytolytic activities triggered influenza-related sequential complications. PMID:27358743

  1. Skin Infections in Young People (Aged 14-18 Years): An Integrative Review

    ERIC Educational Resources Information Center

    Lambe, Catherine I.; Hoare, Karen J.

    2014-01-01

    Skin infections are a major cause of preventable hospitalization, with young people being particularly susceptible. Community-associated methicillin-resistant "Staphylococcus aureus" (CA-MRSA) infection typically presents as skin infection. CA-MRSA infection rates have increased rapidly in the past decade. Exploration of literature…

  2. Methicillin-Resistant Staphylococcus aureus Recovered from Healthcare- and Community-Associated Infections in Egypt.

    PubMed

    Abdel-Maksoud, Mohamed; El-Shokry, Mona; Ismail, Ghada; Hafez, Soad; El-Kholy, Amani; Attia, Ehab; Talaat, Maha

    2016-01-01

    Background. Methicillin-resistant Staphylococcus aureus (MRSA) has created significant epidemiological, infection-control, and therapeutic management challenges during the past three decades. Aim. To analyze the pattern of resistance of healthcare- and community-associated MRSA in Egypt and the trend of resistance of HA-MRSA over time (2005-2013). Methods. MRSA isolates were recovered from healthcare-associated (HA) and community-associated (CA) Staphylococcus aureus (S. aureus) infections. They were tested against 11 antimicrobial discs and the minimal inhibitory concentration (MIC) of vancomycin was determined. Inducible clindamycin resistance (iMLSB) was also screened using D-test. Findings. Of 631 S. aureus, MRSA was identified in 343 (76.6%) and 21 (11.5%) of HA and CA S. aureus isolates, respectively. The proportion of HA-MRSA increased significantly from 48.6% in 2005 to 86.8% in 2013 (p value < 0.001). Multidrug resistance (MDR) was observed in 85.8% of HA-MRSA and 48.6% of CA-MRSA. Vancomycin intermediate resistant S. aureus (VISA) was detected in 1.2% of HA-MRSA and none was detected in CA-MRSA. Among HA-MRSA strains, 5.3% showed iMLSB compared to 9.5% among CA-MRSA. Conclusion. The upsurge of the prevalence rates of HA-MRSA over time is alarming and urges for an effective infection control strategy and continuous monitoring of antimicrobial use. PMID:27433480

  3. Methicillin-Resistant Staphylococcus aureus Recovered from Healthcare- and Community-Associated Infections in Egypt

    PubMed Central

    Abdel-Maksoud, Mohamed; Ismail, Ghada; Hafez, Soad; El-Kholy, Amani; Attia, Ehab; Talaat, Maha

    2016-01-01

    Background. Methicillin-resistant Staphylococcus aureus (MRSA) has created significant epidemiological, infection-control, and therapeutic management challenges during the past three decades. Aim. To analyze the pattern of resistance of healthcare- and community-associated MRSA in Egypt and the trend of resistance of HA-MRSA over time (2005–2013). Methods. MRSA isolates were recovered from healthcare-associated (HA) and community-associated (CA) Staphylococcus aureus (S. aureus) infections. They were tested against 11 antimicrobial discs and the minimal inhibitory concentration (MIC) of vancomycin was determined. Inducible clindamycin resistance (iMLSB) was also screened using D-test. Findings. Of 631 S. aureus, MRSA was identified in 343 (76.6%) and 21 (11.5%) of HA and CA S. aureus isolates, respectively. The proportion of HA-MRSA increased significantly from 48.6% in 2005 to 86.8% in 2013 (p value < 0.001). Multidrug resistance (MDR) was observed in 85.8% of HA-MRSA and 48.6% of CA-MRSA. Vancomycin intermediate resistant S. aureus (VISA) was detected in 1.2% of HA-MRSA and none was detected in CA-MRSA. Among HA-MRSA strains, 5.3% showed iMLSB compared to 9.5% among CA-MRSA. Conclusion. The upsurge of the prevalence rates of HA-MRSA over time is alarming and urges for an effective infection control strategy and continuous monitoring of antimicrobial use. PMID:27433480

  4. Molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus strains isolated from outpatients with skin and soft tissue infections in Wuhan, China.

    PubMed

    Liu, Xiaoli; Liang, Jiansheng; Jiang, Yuanshan; Wang, Bin; Yuan, Hong; Zhang, Lihua; Zhou, Yanfei; Xu, Huiqiong; Zhou, Wang

    2016-06-01

    This study aims to investigate the antimicrobial susceptibility, molecular characteristics and virulence genes of community-acquired methicillin-resistant ITALIC! Staphylococcus aureus(CA-MRSA) isolates with skin and soft tissue infections (SSTIs). Outpatients with SSTIs visiting five medical and health institutions were enrolled from 2011 to 2013. Available ITALIC! S. aureus isolates were characterized by antimicrobial susceptibility testing, and detection of PVL genes. For CA-MRSA isolates, we performed typing of staphylococcal cassette chromosome ITALIC! mec(SCC ITALIC! mec), multi locus sequence typing (MLST) and carriage of 27 virulence genes. A total of 203 ITALIC! S. aureusstrains were isolated from 1400 outpatients with SSTIs, and 21 (10.3%) were CA-MRSA isolates. The positive rate of PVL genes among ITALIC! S. aureus, CA-MRSA and methicillin-susceptible ITALIC! S. aureus(MSSA) isolates were 39.4%, 71.4% and 35.7%, respectively. CA-MRSA strains had greater sensitivity to non-β-lactam antimicrobial agents. All CA-MRSA isolates belonged to SCC ITALIC! mecIV and V, accounting for 47.6% and 52.4%, respectively. ST59 was the most common lineage accounting for 76.2%; ST59-SCC ITALIC! mecIVa-PVL-positive clone was found to be the predominant clone, accounting for 38.1%. All CA-MRSA isolates were found to be positive for one or more virulence genes, 28.6% of isolates carried PVL, ITALIC! seb, ITALIC! sek, ITALIC! seq, ITALIC! hla, ITALIC! hlb, ITALIC! hldand ITALIC! hlg-2. CA-MRSA infections were relatively uncommon in outpatients with SSTIs, but they carried many virulence genes, ST59-SCC ITALIC! mecIV a-PVL-positive clone was the predominant clone in Wuhan, China. PMID:27060098

  5. Incidence of community-acquired methicillin-resistant Staphylococcus aureus carrying Pantone-Valentine leucocidin gene at a referral hospital in United Arab Emirates.

    PubMed

    Dash, Nihar; Panigrahi, Debadatta; Al Zarouni, Mansour; Yassin, Faten; Al-Shamsi, Moza

    2014-04-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen in hospitalized patients worldwide. The present study was undertaken to identify CA-MRSA in hospitalized patients in a 350-bed tertiary care hospital in Sharjah, UAE over a 2-year period from January 2011 to December 2012. CA-MRSA was defined based on identification within first 48 h of admission in the hospital. Staphylococcal cassette chromosome (SCC) mec typing of the CA-MRSA isolates was carried out by multiplex polymerase chain reaction (PCR). Detection of PVL and mecA genes was done by PCR using the GenoType(®) MRSA test system (Hain Lifescience). Patient's clinical data and antimicrobial susceptibility pattern of the CA-MRSA isolates were also evaluated. Fifty seven of the 187 MRSA isolates were identified as CA-MRSA. All the CA-MRSA strains in our study belonged to SCCmecIV type and were positive for both PVL and mecA genes. The patients with CA-MRSA infections were young (median age, 32 years) and the majority of infections involved the skin and soft tissue (36%). Antimicrobial susceptibility pattern of the CA-MRSA isolates showed a better susceptibility profile to the non-beta-lactam antimicrobials with the exception of ciprofloxacin having 28% resistance. This study evidently strengthens the recent observation of an increase in CA-MRSA emergence among hospitalized patients in the UAE. PMID:23919760

  6. Prospective Multicenter Study of Community-Associated Skin and Skin Structure Infections due to Methicillin-Resistant Staphylococcus aureus in Buenos Aires, Argentina

    PubMed Central

    López Furst, María José; de Vedia, Lautaro; Fernández, Silvina; Gardella, Noella; Ganaha, María Cristina; Prieto, Sergio; Carbone, Edith; Lista, Nicolás; Rotryng, Flavio; Morera, Graciana I.; Mollerach, Marta; Stryjewski, Martín E.

    2013-01-01

    Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina prospective, multicenter clinical studies have only been conducted in pediatric populations. Objective Primary: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA. Materials and Methods Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires) between March 2010 and October 2011. Patients were included if they were ≥14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined. Results A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone. Conclusions CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina. PMID:24324543

  7. Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59

    PubMed Central

    Li, Min; Dai, Yingxin; Zhu, Yuanjun; Fu, Chih-Lung; Tan, Vee Y.; Wang, Yanan; Wang, Xing; Hong, Xufen; Liu, Qian; Li, Tianming; Qin, Juanxiu; Ma, Xiaowei; Fang, Jingyuan; Otto, Michael

    2016-01-01

    Understanding virulence is vital for the development of novel therapeutics to target infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which cause an ongoing epidemic in the United States and are on a global rise. However, what defines virulence particularly of global CA-MRSA lineages is poorly understood. Threatening a vast population, the predominant Asian CA-MRSA lineage ST59 is of major epidemiological importance. However, there have been no molecular analyses using defined virulence gene deletion mutants in that lineage as of yet. Here, we compared virulence in skin, lung, and blood infection models of ST59 CA-MRSA isolates with geographically matched hospital-associated MRSA isolates. We selected a representative ST59 CA-MRSA isolate based on toxin expression and virulence characteristics, and produced isogenic gene deletion mutants of important CA-MRSA virulence determinants (α-toxin, PSM α, Agr) in that isolate for in-vitro and in-vivo analyses. Our results demonstrate strongly enhanced virulence of ST59 CA-MRSA over hospital-associated lineages, supporting the notion that enhanced virulence is characteristic for CA-MRSA. Furthermore, they show strong and significant contribution of Agr, α-toxin, and PSMα to pathogenesis of ST59 CA-MRSA skin, lung, and blood infection, emphasizing the value of drug development efforts targeted toward those virulence determinants. PMID:27296890

  8. Clinical features and molecular characteristics of invasive community-acquired methicillin-resistant Staphylococcus aureus infections in Taiwanese children.

    PubMed

    Chen, Chih-Jung; Su, Lin-Hui; Chiu, Cheng-Hsun; Lin, Tzou-Yien; Wong, Kin-Sun; Chen, Yi-Ywan M; Huang, Yhu-Chering

    2007-11-01

    Highly virulent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has been associated with morbidity and mortality in various countries of the world. We characterized the clinical and molecular features of pediatric invasive CA-MRSA infections in Taiwan. Between July 2000 and June 2005, 31 previously healthy children with invasive CA-MRSA infections were identified from 423 children with community-onset methicillin-resistant S. aureus infections. The medical records were reviewed. The clinical isolates, if available, were collected for molecular characterization. Sixteen (51.6%) patients were male, and the mean age was 5.7 years. Adolescents accounted for 9 (29%) cases. Eighteen children had bone and/or joint infections, 14 had deep-seated soft tissue infections, 11 had pneumonia, and 2 had central nervous system infections. Multiorgan involvement was identified in 8 of 20 bacteremic cases. Twenty-two patients (71%) required surgical interventions. The mean hospital stay was 27.4 days. All of the 15 available isolates were classified as sequence type (ST) 59 or its single locus variant and belonged to 2 previously reported community-associated clones containing staphylococcal cassette chromosome mec (SCCmec) type IV or type V(T) in Taiwan. Most of the isolates were multiresistant to clindamycin (94%) and erythromycin (97%). Eleven (73.3%) isolates carried pvl genes, and the strains harboring pvl genes were significantly associated with lung involvement. In conclusion, invasive CA-MRSA infections in pediatric population were not limited to young children. Surgical interventions were often required, and a prolonged course of antibiotic therapy was needed. A multiresistant CA-MRSA clone characterized as ST59 was identified from these children in Taiwan. PMID:17662565

  9. Practices and Procedures to Prevent the Transmission of Skin and Soft Tissue Infections in High School Athletes

    ERIC Educational Resources Information Center

    Fritz, Stephanie A.; Long, Marcus; Gaebelein, Claude J.; Martin, Madeline S.; Hogan, Patrick G.; Yetter, John

    2012-01-01

    Skin and soft tissue infections (SSTIs) are frequent in student athletes and are often caused by community-associated methicillin-resistant "Staphylococcus aureus" (CA-MRSA). We evaluated the awareness of CA-MRSA among high school coaches and athletic directors in Missouri (n = 4,408) and evaluated hygiene practices affecting SSTI transmission. Of…

  10. Immunopathogenesis of Staphylococcus aureus pulmonary infection

    PubMed Central

    Parker, Dane; Prince, Alice

    2013-01-01

    Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia. PMID:22037948

  11. Risk Factors for Community-Associated Staphylococcus aureus Skin Infection in Children of Maui

    PubMed Central

    Seifried, Steven E

    2012-01-01

    The prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection, and Staphylococcus aureus (S. aureus) infection overall, has dramatically increased in the past 10 years. Children and Native Hawaiians and Pacific Islanders (NHPI) are disproportionately affected by CA-MRSA infection. The purpose of this case-control study was to identify risk factors for CA-S. aureus skin infections in children of Maui, Hawai‘i, as a foundation for reducing the transmission of these infections. Survey data were obtained from patients in pediatric clinician offices over an 8-month period. NHPI participants were well-represented as 58% of cases and 54% of controls. Chi-square analysis and logistic regression were used to identify risk factors. Significant risk factors predictive of infection among all participants were (a) skin abrasions or wounds, (b) household contact, and (c) overweight or obesity. Risk factors predictive of infection among NHPI were (a) skin abrasions or wounds, (b) antibiotic use within 6 months, (c) overweight or obesity, and (d) a history of eczema or other skin disorder. The role of overweight or obesity in S. aureus skin infections among NHPI has not been identified in previous research and indicates a focus for additional education. Further research is needed to better understand the role of eczema, antibiotic use, overweight and obesity, and socio-cultural factors in these infections. PMID:22900237

  12. Epidemiology, clinical manifestations, and treatment options for skin and soft tissue infection caused by community-acquired methicillin-resistant Staphylococcus aureus

    PubMed Central

    Farley, Jason E.

    2009-01-01

    Purpose: This article reviews the evolving epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and the appropriate outpatient management of CA-MRSA skin and soft tissue infection. Further, the paper will provide the basis upon which an individualized patient educational plan may be developed. Data Sources: To complete this review, a search of English language publications was conducted through Medline and CINAHL databases (1966–2006). Conclusions: The epidemiology of CA-MRSA is becoming increasingly complex. Research that addresses the impact of this organism in high-risk populations and within families is urgently needed. Implications for Practice: Nurse practitioners must remain informed of the epidemiology of common and emerging drug-resistant organisms in their patient populations. PMID:18271763

  13. Community-Associated Methicillin-Resistant Staphylococcus aureus Case Studies

    PubMed Central

    Sowash, Madeleine G.; Uhlemann, Anne-Catrin

    2014-01-01

    Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations. PMID:24085688

  14. METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS INFECTIONS OF THE EYE AND ORBIT (AN AMERICAN OPHTHALMOLOGICAL SOCIETY THESIS)

    PubMed Central

    Blomquist, Preston Howard

    2006-01-01

    Purpose To ascertain if methicillin-resistant Staphyloccocus aureus (MRSA) ophthalmic infections are increasing. Methods A retrospective review of all patients with a culture positive for MRSA in the Parkland Health and Hospital System, the urban public healthcare system for Dallas County, Texas, for the years 2000 through 2004 was performed. Patients with ocular, orbital, and ocular adnexal infection were identified, and isolates were categorized as nosocomial or community-acquired (CA). Results A total of 3,640 patients with a culture positive for MRSA were identified, with 1,088 patients (30%) considered to have acquired the isolate via nosocomial transmission and 2,552 patients (70%) considered to have CA-MRSA. Forty-nine patients (1.3%) had ophthalmic MRSA involvement. For both ophthalmic and nonophthalmic cases, the number of CA-MRSA patients increased each year, whereas the numbers of nosocomial patients remained fairly constant. Patients with ophthalmic MRSA tended to be younger than other MRSA patients (P = .023). The most common manifestation of ophthalmic MRSA infection was preseptal cellulitis and/or lid abscess followed by conjunctivitis, but sight-threatening infections, including corneal ulcers, endophthalmitis, orbital cellulitis, and blebitis, also occurred. Empirical antibiotic coverage was initially prescribed in 48 (98%) of ophthalmic cases and did not adequately cover for the MRSA isolate in 24 (50%). Conclusions CA-MRSA is becoming increasingly prevalent, and ophthalmologists will see more ophthalmic MRSA infections. Although ophthalmic CA-MRSA commonly presents as preseptal lid infection and conjunctivitis, sight-threatening infections also occur. Ophthalmologists must identify MRSA patients, adjust empirical treatment regimens where MRSA is endemic, and take steps to control emergence of resistant organisms in both inpatient and outpatient practices. PMID:17471350

  15. Community-associated methicillin-resistant Staphylococcus aureus necrotizing pneumonia without evidence of antecedent viral upper respiratory infection

    PubMed Central

    Toro, Cristina Moran; Janvier, Jack; Zhang, Kunyan; Fonseca, Kevin; Gregson, Dan; Church, Deirdre; Laupland, Kevin; Rabin, Harvey; Elsayed, Sameer; Conly, John

    2014-01-01

    BACKGROUND: USA300 community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains causing necrotizing pneumonia have been reported in association with antecedent viral upper respiratory tract infections (URI). METHODS: A case series of necrotizing pneumonia presenting as a primary or coprimary infection, secondary to CA-MRSA without evidence of antecedent viral URI, is presented. Cases were identified through the infectious diseases consultation service records. Clinical and radiographic data were collected by chart review and electronic records. MRSA strains were isolated from sputum, bronchoalveolar lavage, pleural fluid or blood cultures and confirmed using standard laboratory procedures. MRSA strains were characterized by susceptibility testing, pulsed-field gel electrophoresis, spa typing, agr typing and multilocus sequence typing. Testing for respiratory viruses was performed by appropriate serological testing of banked sera, or nucleic acid testing of nasopharyngeal or bronchoalveloar lavage specimens. RESULTS: Ten patients who presented or copresented with CA necrotizing pneumonia secondary to CA-MRSA from April 2004 to October 2011 were identified. The median length of stay was 22.5 days. Mortality was 20.0%. Classical risk factors for CA-MRSA were identified in seven of 10 (70.0%) cases. Chest tube placement occurred in seven of 10 patients with empyema. None of the patients had historical evidence of antecedent URI. In eight of 10 patients, serological or nucleic acid testing testing revealed no evidence of acute viral coinfection. Eight strains were CMRSA-10 (USA300). The remaining two strains were a USA300 genetically related strain and a USA1100 strain. CONCLUSION: Pneumonia secondary to CA-MRSA can occur in the absence of an antecedent URI. Infections due to CA-MRSA are associated with significant morbidity and mortality. Clinicians need to have an awareness of this clinical entity, particularly in patients who are in risk

  16. In vivo bioluminescence imaging to evaluate systemic and topical antibiotics against community-acquired methicillin-resistant Staphylococcus aureus-infected skin wounds in mice.

    PubMed

    Guo, Yi; Ramos, Romela Irene; Cho, John S; Donegan, Niles P; Cheung, Ambrose L; Miller, Lloyd S

    2013-02-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents. PMID:23208713

  17. Community-Associated Methicillin-Resistant Staphylococcus aureus Lacking PVL, as a Cause of Severe Invasive Infection Treated with Linezolid

    PubMed Central

    Gavino, Alexandra; Miragaia, Maria; Varandas, Luis; de Lencastre, Herminia; Brito, Maria Joao

    2013-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging public health problem worldwide. Severe invasive infections have been described, mostly associated with the presence of Panton-Valentine leukocidin (PVL). In Portugal limited information exists regarding CA-MRSA infections. In this study we describe the case of a previously healthy 12-year-old female, sport athlete, who presented to the hospital with acetabulofemoral septic arthritis, myositis, fasciitis, acetabulum osteomyelitis, and pneumonia. The MRSA isolated from blood and synovial fluid was PVL negative and staphylococcal enterotoxin type P (SEP) and type L (SEL) positive, with a vancomycin MIC of 1.0 mg/L and resistant to clindamycin and ciprofloxacin. The patient was submitted to multiple surgical drainages and started on vancomycin, rifampicin, and gentamycin. Due to persistence of fever and no microbiological clearance, linezolid was started with improvement. This is one of the few reported cases of severe invasive infection caused by CA-MRSA in Portugal, which was successfully treated with linezolid. In spite of the severity of infection, the MRSA isolate did not produce PVL. PMID:23509655

  18. The changing face of community-acquired methicillin-resistant Staphylococcus aureus.

    PubMed

    Kale, P; Dhawan, B

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of infection, both in hospitalised patients with significant healthcare exposure and in patients without healthcare risk factors. Community-acquired methicillin-resistant S. aureus (CA-MRSA) are known for their rapid community transmission and propensity to cause aggressive skin and soft tissue infections and community-acquired pneumonia. The distinction between the healthcare-associated (HA)-MRSA and CA-MRSA is gradually fading owing to the acquisition of multiple virulence factors and genetic elements. The movement of CA-MRSA strains into the nosocomial setting limits the utility of using clinical risk factors alone to designate community or HA status. Identification of unique genetic characteristics and genotyping are valuable tools for MRSA epidemiological studies. Although the optimum pharmacotherapy for CA-MRSA infections has not been determined, many CA-MRSA strains remain broadly susceptible to several non-β-lactam antibacterial agents. This review aimed at illuminating the characteristic features of CA-MRSA, virulence factors, changing clinical settings and molecular epidemiology, insurgence into the hospital settings and therapy with drug resistance. PMID:27514947

  19. Hyperexpression of α-hemolysin explains enhanced virulence of sequence type 93 community-associated methicillin-resistant Staphylococcus aureus

    PubMed Central

    2014-01-01

    Background The community-associated methicillin-resistant S. aureus (CA-MRSA) ST93 clone is becoming dominant in Australia and is clinically highly virulent. In addition, sepsis and skin infection models demonstrate that ST93 CA-MRSA is the most virulent global clone of S. aureus tested to date. While the determinants of virulence have been studied in other clones of CA-MRSA, the basis for hypervirulence in ST93 CA-MRSA has not been defined. Results Here, using a geographically and temporally dispersed collection of ST93 isolates we demonstrate that the ST93 population hyperexpresses key CA-MRSA exotoxins, in particular α-hemolysin, in comparison to other global clones. Gene deletion and complementation studies, and virulence comparisons in a murine skin infection model, showed unequivocally that increased expression of α-hemolysin is the key staphylococcal virulence determinant for this clone. Genome sequencing and comparative genomics of strains with divergent exotoxin profiles demonstrated that, like other S. aureus clones, the quorum sensing agr system is the master regulator of toxin expression and virulence in ST93 CA-MRSA. However, we also identified a previously uncharacterized AraC/XylS family regulator (AryK) that potentiates toxin expression and virulence in S. aureus. Conclusions These data demonstrate that hyperexpression of α-hemolysin mediates enhanced virulence in ST93 CA-MRSA, and additional control of exotoxin production, in particular α-hemolysin, mediated by regulatory systems other than agr have the potential to fine-tune virulence in CA-MRSA. PMID:24512075

  20. Establishment of ST30 as the predominant clonal type among community-associated methicillin-resistant Staphylococcus aureus isolates in Singapore.

    PubMed

    Hsu, Li-Yang; Koh, Yin-Ling; Chlebicka, Nidhi Loomba; Tan, Thean-Yen; Krishnan, Prabha; Lin, Raymond Tzer-Pin; Tee, Nancy; Barkham, Timothy; Koh, Tse-Hsien

    2006-03-01

    The number of infections attributable to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Singapore is progressively increasing. Most cases in the past 2 years were caused by Panton-Valentine leukocidin-positive isolates belonging to sequence type 30, according to multilocus sequence typing. This has clearly become the predominant sequence type among CA-MRSA isolates in Singapore. PMID:16517901

  1. Epicutaneous model of community-acquired Staphylococcus aureus skin infections.

    PubMed

    Prabhakara, Ranjani; Foreman, Oded; De Pascalis, Roberto; Lee, Gloria M; Plaut, Roger D; Kim, Stanley Y; Stibitz, Scott; Elkins, Karen L; Merkel, Tod J

    2013-04-01

    Staphylococcus aureus is one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority of S. aureus community-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models of S. aureus SSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involve methods that are difficult to replicate. For these reasons, we sought to develop a murine model of community-acquired methicillin-resistant S. aureus SSTI (CA-MRSA SSTI) that can be consistently reproduced with a high degree of precision. We utilized this model to begin to characterize the host immune response to this type of infection. We infected mice via epicutaneous challenge of the skin on the outer ear pinna using Morrow-Brown allergy test needles coated in S. aureus USA300. When mice were challenged in this model, they developed small, purulent, self-clearing lesions with predictable areas of inflammation that mimicked a human infection. CFU in the ear pinna peaked at day 7 before dropping by day 14. The T(h)1 and T(h)17 cytokines gamma interferon (IFN-γ), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-α), IL-17A, IL-6, and IL-21 were all significantly increased in the draining lymph node of infected mice, and there was neutrophil recruitment to the infection site. In vivo neutrophil depletion demonstrated that neutrophils play a protective role in preventing bacterial dissemination and fatal invasive infection. PMID:23381997

  2. Nasal colonization in children with community acquired methicillin-resistant Staphylococcus aureus

    PubMed Central

    Davoodabadi, Fazlollah; Mobasherizadeh, Sina; Mostafavizadeh, Kamyar; Shojaei, Hasan; Havaei, Seyed Asghar; Koushki, Ali Mehrabi; Moghadasizadeh, Zahra; Meidani, Mohsen; Shirani, Kiana

    2016-01-01

    Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infections. The changing epidemiology of MRSA became evident in the 1990s when CA-MRSA cases were first reported. Nasal carriage of CA-MRSA is associated with an increased risk for development of infections in various populations. Materials and Methods: Anterior nares culture for the presence of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA was taken from 345 children attending kindergartens, who didn’t have any known risk factor for MRSA colonization. Also, children demographic variables were recorded. Identification of SA and community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) with standard microbiological test was performed. Finally, the susceptibility of isolated to various antibiotics determined. The data were analyzed with Whonet 5.6 software. Results: Of 345 children, 20 children (5.8%) were colonized with CA-MRSA, 86 children (24.9%) with MSSA and 239 cases (69.3%) didn’t have SA colonization. The highest rate of MSSA and MRSA colonization was obtained at the age of 6 years. The frequency distribution of SA (MSSA and MRSA) colonization prevalence didn’t have any significant differences based on age, gender and the admission time (P > 0.05); but it was significantly different in the urban areas (P < 0.001). The lowest resistance rate of CA-MRSA isolates, with a frequency of 10%, was detected with gentamicin, rifampin, and trimethoprim-sulfamethoxazole. Conclusions: In summary, CA-MRSA colonization was observed in child care centers remarkably. Therefore, by facing various infections due to SA especially in areas of low socio-economic status, it must be considered. Based on antibiogram test, empirical treatment with rifampin, gentamicin and ciprofloxacin is recommended during CA-MRSA infections. PMID:27274501

  3. Capsaicin Protects Mice from Community-Associated Methicillin-Resistant Staphylococcus aureus Pneumonia

    PubMed Central

    Xing, Yan; Leng, Bingfeng; Dong, Jing; Li, Hongen; Luo, Mingjing; Zhang, Yu; Dai, Xiaohan; Luo, Yonghuang; Deng, Xuming

    2012-01-01

    Background α-toxin is one of the major virulence factors secreted by most Staphylococcus aureus strains, which played a central role in the pathogenesis of S. aureus pneumonia. The aim of this study was to investigate the impact of capsaicin on the production of α-toxin by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA 300 and to further assess its performance in the treatment of CA-MRSA pneumonia in a mouse model. Methodology/Principal Findings The in vitro effects of capsaicin on α-toxin production by S. aureus USA 300 were determined using hemolysis, western blot, and real-time RT-PCR assays. The influence of capsaicin on the α-toxin-mediated injury of human alveolar epithelial cells was determined using viability and cytotoxicity assays. Mice were infected intranasally with S. aureus USA300; the in vivo protective effects of capsaicin against S. aureus pneumonia were assessed by monitoring the mortality, histopathological changes and cytokine levels. Low concentrations of capsaicin substantially decreased the production of α-toxin by S. aureus USA 300 without affecting the bacterial viability. The addition of capsaicin prevented α-toxin-mediated human alveolar cell (A549) injury in co-culture with S. aureus. Furthermore, the in vivo experiments indicated that capsaicin protected mice from CA-MRSA pneumonia caused by strain USA 300. Conclusions/Significance Capsaicin inhibits the production of α-toxin by CA-MRSA strain USA 300 in vitro and protects mice from CA-MRSA pneumonia in vivo. However, the results need further confirmation with other CA-MRSA lineages. This study supports the views of anti-virulence as a new antibacterial approach for chemotherapy. PMID:22427935

  4. Incidence and risk factors for community-associated methicillin-resistant Staphylococcus aureus in New York City, 2006-2012.

    PubMed

    Baker, P; Cohen, B; Liu, J; Larson, E

    2016-04-01

    This study aims to describe changes in incidence and risk factors for community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections upon admission to two New York City hospitals from 2006 to 2012. We examined the first hospitalization for adult patients using electronic health record and administrative data and determined the annual incidence/1000 admissions of total S. aureus, total MRSA, and CA-MRSA (within 48 h of admission) in clinical specimens over the study period. Logistic regression was used to identify factors associated with CA-MRSA in 2006 and 2012. In 137 350 admissions, the incidence of S. aureus, MRSA, and CA-MRSA/1000 admissions were 15·6, 7·0, and 3·5, respectively. The total S. aureus and MRSA isolations decreased significantly over the study period (27% and 25%, respectively) while CA-MRSA incidence was unchanged. CA-MRSA increased as a proportion of all MRSA between 2006 (46%) and 2012 (62%), and was most frequently isolated from respiratory (1·5/1000) and blood (0·7/1000) cultures. Logistic regression analysis of factors associated with isolation of CA-MRSA showed that age ⩾65 years [odds ratio (OR) 2·3, 95% confidence interval (CI) 1·2-4·5], male gender (OR 1·8, 95% CI 1·2-2·8) and history of renal failure (OR 2·6, 95% CI 1·6-4·2) were significant predictors of infection in 2006. No predictors were identified in 2012. PMID:26364503

  5. Multiplex PCR for rapid detection of Staphylococcus aureus isolates suspected to represent community-acquired strains.

    PubMed

    Strommenger, B; Braulke, C; Pasemann, B; Schmidt, C; Witte, W

    2008-02-01

    The continuous spread of community-acquired methicillin-resistant Staphylococcus aureus (caMRSA) and the introduction of these highly virulent isolates into hospitals represent increasing threats. The timely recognition of caMRSA strains is crucial for infection control purposes. Thus, we developed a PCR-based assay for the easy and rapid determination of those caMRSA clones that currently are the most prevalent in Germany and Central Europe. This assay was able to correctly identify the majority of the isolates as caMRSA of sequence type 80 (ST80), clonal complex 1 (USA400), and ST8 (USA300). In combination with spa typing-BURP (based upon repeat pattern) analysis and resistance typing, it provides a means for the extensive characterization of suspicious isolates. Thus, this assay represents a reliable tool for monitoring the emergence and spread of different caMRSA clones. The resulting information, in combination with careful interpretation of the epidemiological records, might help to prevent the further spread of those highly virulent caMRSA clones. PMID:18032620

  6. Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection

    PubMed Central

    Tseng, Ching Wen; Kolar, Stacey L.; Müller, Sabrina; Rodriguez, Maria D.; Rezai-Zadeh, Kavon; Fan, Xuemo; Beenhouwer, David O.; Town, Terrence; Liu, George Y.

    2015-01-01

    Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL) elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA), exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD)/severe combined immune deficiency (SCID)/IL2rγnull (NSG) mice engrafted with human CD34+ umbilical cord blood cells. These “humanized” NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor. PMID:26618545

  7. Community-associated methicillin-resistant Staphylococcus aureus in non-outbreak skin infections

    PubMed Central

    Bonesso, Mariana Fávero; Marques, Silvio Alencar; Camargo, Carlos Henrique; Fortaleza, Carlos Magno Castelo Branco; da Cunha, Maria de Lourdes Ribeiro de Souza

    2014-01-01

    The aim of this study was to determine the prevalence of Staphylococcus aureus and risk factors for the acquisition of MRSA (Methicillin Resistant Staphylococcus aureus) as the main cause of skin and soft tissue infections. S. aureus were characterized for the presence of PVL, TSST-1 and mecA genes. SCCmec typing was carried out in mecA positive strains and PFGE was performed only in these strains. During the study period, 127 outpatients attending a dermatology clinical the Botucatu Medical School, a regional tertiary hospital in Botucatu, Sao Paulo, Brazil, were diagnosed with active skin infections. A total 66 (56.9%) S. aureus strains were isolated. The methicillin resistance gene mecA was detected in seven (10.6%) S. aureus strains. The SCCmec types detected in the seven mecA-positive S. aureus strains were type Ia in one, type II in three, and type IV in three. The PVL gene was detected in 10 (15.1%) in sensitive strains. Pulsed field gel electrophoresis revealed non-clonal diversity among the isolates. The risk factors associated with MRSA acquisition in this study were previous ciprofloxacin use and working in a healthcare environment. The risk factors indicate plausible routes of CA-MRSA transmission among the subjects studied. PMID:25763047

  8. Community-associated methicillin-resistant Staphylococcus aureus in non-outbreak skin infections.

    PubMed

    Bonesso, Mariana Fávero; Marques, Silvio Alencar; Camargo, Carlos Henrique; Fortaleza, Carlos Magno Castelo Branco; da Cunha, Maria de Lourdes Ribeiro de Souza

    2014-01-01

    The aim of this study was to determine the prevalence of Staphylococcus aureus and risk factors for the acquisition of MRSA (Methicillin Resistant Staphylococcus aureus) as the main cause of skin and soft tissue infections. S. aureus were characterized for the presence of PVL, TSST-1 and mecA genes. SCCmec typing was carried out in mecA positive strains and PFGE was performed only in these strains. During the study period, 127 outpatients attending a dermatology clinical the Botucatu Medical School, a regional tertiary hospital in Botucatu, Sao Paulo, Brazil, were diagnosed with active skin infections. A total 66 (56.9%) S. aureus strains were isolated. The methicillin resistance gene mecA was detected in seven (10.6%) S. aureus strains. The SCCmec types detected in the seven mecA-positive S. aureus strains were type Ia in one, type II in three, and type IV in three. The PVL gene was detected in 10 (15.1%) in sensitive strains. Pulsed field gel electrophoresis revealed non-clonal diversity among the isolates. The risk factors associated with MRSA acquisition in this study were previous ciprofloxacin use and working in a healthcare environment. The risk factors indicate plausible routes of CA-MRSA transmission among the subjects studied. PMID:25763047

  9. Detection and genetic characterization of PVL-positive ST8-MRSA-IVa and exfoliative toxin D-positive European CA-MRSA-Like ST1931 (CC80) MRSA-IVa strains in Bangladesh.

    PubMed

    Paul, Shyamal Kumar; Ghosh, Souvik; Kawaguchiya, Mitsuyo; Urushibara, Noriko; Hossain, Mohammad Akram; Ahmed, Salma; Mahmud, Chand; Jilani, Md Shariful Alam; Haq, Jalaluddin Ashraful; Ahmed, Abdullah Akhtar; Kobayashi, Nobumichi

    2014-08-01

    Severe skin lesions caused by Staphylococcus aureus infection are associated with production from bacterial cells of Panton-Valentine leukocidin (PVL), a typical virulence factor of community-acquired methicillin-resistant S. aureus (CA-MRSA), as well as other toxins represented by exfoliative toxins. Through a retrospective study of 26 S. aureus strains isolated from skin lesions of diabetic patients admitted to a hospital in Bangladesh, 2 PVL-gene-positive MRSA-IVa strains and 8 PVL-negative, exfoliative toxin D (ETD) gene (etd)-positive MRSA-IVa strains were isolated. A PVL-positive MRSA-IVa strain had a type I arginine catabolic mobile element (ACME), belonged to ST8/agr-type I/spa-type t121 (a variant of t008), and harbored blaZ, tet(K), msrA, and aph(3')-IIIa, which are mostly typical characteristics found in USA300, a predominant CA-MRSA clone in the United States. Another PVL-positive MRSA strain, belonging to ST1929 (CC88)/agr-type III/spa-type t3341, was negative for ACME, but possessed blaZ and tet(K). The etd-positive MRSA-IVa strains possessed the epidermal cell differentiation inhibitor B (EDIN-B)-encoding gene (edinB) and belonged to ST1931 (CC80)/agr-type III/spa-type t11023 (a variant of t044), which was genetic trait similar to that of the European CA-MRSA ST80 clone. However, unlike the European ST80 strains, the etd-positive MRSA strains detected in the present study harbored seb, sek, and seq, while they were negative for tet(K), aph(3')-IIIa, and fusB, showing susceptibility to fusidic acid. These findings suggested that etd-positive ST1931 MRSA strains belong to the same lineage as the European ST80 MRSA clone, evolving from a common ancestral clone via acquisition of a different pathogenicity island. This is the first report of a USA300-like MRSA-IV strain, PVL-positive ST1929 (CC88) MRSA-IV, and European ST80 CA-MRSA-like etd-positive ST1931 (CC80) MRSA-IV strains isolated in Bangladesh. PMID:24552553

  10. Community-acquired methicillin-resistant Staphylococcus aureus in a Malaysian tertiary centre.

    PubMed

    Rashid, Zetti Zainol; Bahari, Norazlah; Othman, Amizah; Jaafar, Roslinda; Mohamed, Nurul Azmawati; Jabbari, Idimaz; Sulong, Anita; Hashim, Rohaidah; Ahmad, Norazah

    2013-01-01

    Abstract. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a pathogen recognized to be distinct in both phenotype and genotype from hospital-acquired MRSA. We have identified CA-MRSA cases in Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, including their antibiotic susceptibility patterns and genotypic characteristics. Cases were identified during January to December 2009 from routine clinical specimens, where culture and antibiotic susceptibility results yielded pauci-resistant MRSA isolates suspected as being CA-MRSA. The patients' clinical data were collected and their specimens were sent for molecular confirmation and analysis. Five cases of CA-MRSA were identified, which had a multi-sensitive pattern on antibiotic susceptibility tests and were resistant to only penicillin and oxacillin. All cases were skin and soft-tissue infections, including diabetic foot with gangrene, infected scalp hematoma, philtrum abscess in a healthcare worker, thrombophlebitis complicated with abscess and infected bedsore. All five cases were confirmed MRSA by detection of mecA. SCCmec typing (ccr and mec complex) revealed SCCmec type IV for all cases except the infected bedsore case. Panton-Valentine leukocidin gene was positive in all isolates. As clinical features among methicillin-sensitive Staphylococcus aureus, CA-MRSA and "nosocomial CA-MRSA" are indistinct, early recognition is necessary in order to initiate appropriate antibiotics and infection control measures. Continual surveillance of pauci-resistant MRSA and molecular analysis are necessary in order to identify emerging strains as well as their epidemiology and transmission, both in the community and in healthcare setting. PMID:23682444

  11. Pediatric Staphylococcus aureus Isolate Genotypes and Infections from the Dawn of the Community-Associated Methicillin-Resistant S. aureus Epidemic Era in Chicago, 1994 to 1997

    PubMed Central

    Acree, Mary Ellen; Sieth, Julia J.; Boxrud, Dave J.; Dobbins, Ginette; Lynfield, Ruth; Boyle-Vavra, Susan; Daum, Robert S.

    2015-01-01

    Widespread infections with community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) have occurred in the United States with the dissemination of the USA300 strain beginning in 2000. We examined 105 isolates obtained from children treated at the University of Chicago from 1994 to 1997 (75 methicillin-susceptible S. aureus [MSSA] and 30 MRSA isolates) in order to investigate for possible evidence of USA300 during this period. Infections were defined epidemiologically based on medical record review. The isolates underwent multilocus sequence typing (MLST), as well as assays for the Panton-Valentine leukocidin (PVL) genes, the protein A gene (spa), and arcA and opp3, proxy markers for the arginine catabolic mobile element (ACME), characteristic of USA300 MRSA. MRSA isolates also underwent staphylococcal cassette chromosome mec (SCCmec) typing and pulsed-field gel electrophoresis (PFGE) subtyping. MSSA isolates belonged to 17 sequence type (ST) groups. The 12 epidemiologically defined CA-MRSA infection isolates were either ST1 (n = 4) or ST8 (n = 8). They belonged to 3 different PFGE types: USA100 (n = 1), USA400 (n = 5), and USA500 (n = 6). Among the CA-MRSA infection isolates, 8 (67%) were PVL+. None of the MRSA or MSSA isolates contained arcA or opp3. Only one MRSA isolate was USA300 by PFGE. This was a health care-associated (HA) MRSA isolate, negative for PVL, that carried SCCmec type II. USA300 with its characteristic features was not identified in the collection from the years 1994 to 1997. PMID:26019202

  12. Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry*

    PubMed Central

    Gonzalez, David J.; Okumura, Cheryl Y.; Hollands, Andrew; Kersten, Roland; Akong-Moore, Kathryn; Pence, Morgan A.; Malone, Cheryl L.; Derieux, Jaclyn; Moore, Bradley S.; Horswill, Alexander R.; Dixon, Jack E.; Dorrestein, Pieter C.; Nizet, Victor

    2012-01-01

    Staphylococcus aureus causes a wide range of human disease ranging from localized skin and soft tissue infections to potentially lethal systemic infections. S. aureus has the biosynthetic ability to generate numerous virulence factors that assist in circumventing the innate immune system during disease pathogenesis. Recent studies have uncovered a set of extracellular peptides produced by community-associated methicillin-resistant S. aureus (CA-MRSA) with homology to the phenol-soluble modulins (PSMs) from Staphylococcus epidermidis. CA-MRSA PSMs contribute to skin infection and recruit and lyse neutrophils, and truncated versions of these peptides possess antimicrobial activity. In this study, novel CA-MRSA PSM derivatives were discovered by the use of microbial imaging mass spectrometry. The novel PSM derivatives are compared with their parent full-length peptides for changes in hemolytic, cytolytic, and neutrophil-stimulating activity. A potential contribution of the major S. aureus secreted protease aureolysin in processing PSMs is demonstrated. Finally, we show that PSM processing occurs in multiple CA-MRSA strains by structural confirmation of additional novel derivatives. This work demonstrates that IMS can serve as a useful tool to go beyond genome predictions and expand our understanding of the important family of small peptide virulence factors. PMID:22371493

  13. Modeling the transmission of community-associated methicillin-resistant Staphylococcus aureus: a dynamic agent-based simulation

    PubMed Central

    2014-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) has been a deadly pathogen in healthcare settings since the 1960s, but MRSA epidemiology changed since 1990 with new genetically distinct strain types circulating among previously healthy people outside healthcare settings. Community-associated (CA) MRSA strains primarily cause skin and soft tissue infections, but may also cause life-threatening invasive infections. First seen in Australia and the U.S., it is a growing problem around the world. The U.S. has had the most widespread CA-MRSA epidemic, with strain type USA300 causing the great majority of infections. Individuals with either asymptomatic colonization or infection may transmit CA-MRSA to others, largely by skin-to-skin contact. Control measures have focused on hospital transmission. Limited public health education has focused on care for skin infections. Methods We developed a fine-grained agent-based model for Chicago to identify where to target interventions to reduce CA-MRSA transmission. An agent-based model allows us to represent heterogeneity in population behavior, locations and contact patterns that are highly relevant for CA-MRSA transmission and control. Drawing on nationally representative survey data, the model represents variation in sociodemographics, locations, behaviors, and physical contact patterns. Transmission probabilities are based on a comprehensive literature review. Results Over multiple 10-year runs with one-hour ticks, our model generates temporal and geographic trends in CA-MRSA incidence similar to Chicago from 2001 to 2010. On average, a majority of transmission events occurred in households, and colonized rather than infected agents were the source of the great majority (over 95%) of transmission events. The key findings are that infected people are not the primary source of spread. Rather, the far greater number of colonized individuals must be targeted to reduce transmission. Conclusions Our findings suggest

  14. The dominant Australian community-acquired methicillin-resistant Staphylococcus aureus clone ST93-IV [2B] is highly virulent and genetically distinct.

    PubMed

    Chua, Kyra Y L; Seemann, Torsten; Harrison, Paul F; Monagle, Shaun; Korman, Tony M; Johnson, Paul D R; Coombs, Geoffrey W; Howden, Brian O; Davies, John K; Howden, Benjamin P; Stinear, Timothy P

    2011-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159) to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs) distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding α-hemolysin, Panton-Valentine leukocidin (PVL) and α-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total). These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300) share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2). This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid dissemination of a

  15. Cutaneous Immune Defenses Against Staphylococcus aureus Infections

    PubMed Central

    Choi, Ji Hae; Seo, Ho Seong; Lim, Sang Young; Park, Kyungho

    2014-01-01

    Staphylococcus aureus (S. aureus) is a virulent bacterium that abundantly colonizes inflammatory skin diseases. Since S. aureus infections occur in an impaired skin barrier, it is important to understand the protective mechanism through cutaneous immune responses against S. aureus infections and the interaction with Staphylococcal virulence factors. In this review, we summarize not only the pathogenesis and key elements of S. aureus skin infections, but also the cutaneous immune system against its infections and colonization. The information obtained from this area may provide the groundwork for further immunomodulatory therapies or vaccination strategies to prevent S. aureus infections. PMID:26064853

  16. Antimicrobial activity of tigecycline against community-acquired methicillin-resistant Staphylococcus aureus isolates recovered from North American medical centers.

    PubMed

    Mendes, Rodrigo E; Sader, Helio S; Deshpande, Lalitagauri; Jones, Ronald N

    2008-04-01

    A total of 1989 community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) were susceptibility tested by broth microdilution. Pulsed-field gel electrophoresis, SCCmec type, and polymerase chain reaction for Panton-Valentine leukocidin (PVL) genes were also performed. The overall tigecycline susceptibility rate was 98.2%. Glycopeptides, quinupristin/dalfopristin, linezolid, and chloramphenicol were also active against this collection (< or =0.7% resistant). The vast majority (70.8%) of the CA-MRSA was SCCmec type IV, from which 88.4% belonged to the USA300-0114 clone and 94.7% were PVL positive. Tigecycline showed in vitro activity comparable with other highly active parenteral agents and represents an option for treating complicated infections caused by CA-MRSA. PMID:18068326

  17. Antimicrobial Resistance and Molecular Characteristics of Nasal Staphylococcus aureus Isolates From Newly Admitted Inpatients.

    PubMed

    Chen, Xu; Sun, Kangde; Dong, Danfeng; Luo, Qingqiong; Peng, Yibing; Chen, Fuxiang

    2016-05-01

    Staphylococcus aureus, or methicillin-resistant S. aureus (MRSA), is a significant pathogen in both nosocomial and community infections. Community-associated MRSA (CA-MRSA) strains tend to be multi-drug resistant and to invade hospital settings. This study aimed to assess the antimicrobial resistance and molecular characteristicsof nasal S. aureus among newlyadmitted inpatients.In the present study, 66 S. aureus isolates, including 10 healthcare-associated MRSA (HA-MRSA), 8 CA-MRSA, and 48 methicillin-sensitive S. aureus (MSSA) strains, were found in the nasal cavities of 62 patients by screening 292 newlyadmitted patients. Antimicrobial resistance and molecular characteristics of these isolates, including spa-type, sequence type (ST) and SCCmec type, were investigated. All isolates were sensitive to linezolid, teicoplanin, and quinupristin/dalfopristin, but high levels of resistance to penicillin and erythromycin were detected. According to D-test and erm gene detection results, the cMLS(B) and iMLS(B) phenotypes were detected in 24 and 16 isolates, respectively. All 10 HA-MRSA strains displayed the cMLS(B) phenotypemediated by ermA or ermA/ermC, while the cMLS(B) CA-MRSA and MSSA strains carried the ermB gene. Molecular characterization revealedall 10 HA-MRSA strains were derived from the ST239-SCCmec III clone, and four out of eight CA-MRSA strains were t437-ST59-SCCmec V. The results suggest that patients play an indispensable role in transmitting epidemic CA-MRSA and HA-MRSA strains. PMID:26915614

  18. Antimicrobial Resistance and Molecular Characteristics of Nasal Staphylococcus aureus Isolates From Newly Admitted Inpatients

    PubMed Central

    Chen, Xu; Sun, Kangde; Luo, Qingqiong; Peng, Yibing

    2016-01-01

    Staphylococcus aureus, or methicillin-resistant S. aureus (MRSA), is a significant pathogen in both nosocomial and community infections. Community-associated MRSA (CA-MRSA) strains tend to be multi-drug resistant and to invade hospital settings. This study aimed to assess the antimicrobial resistance and molecular characteristicsof nasal S. aureus among newlyadmitted inpatients.In the present study, 66 S. aureus isolates, including 10 healthcare-associated MRSA (HA-MRSA), 8 CA-MRSA, and 48 methicillin-sensitive S. aureus (MSSA) strains, were found in the nasal cavities of 62 patients by screening 292 newlyadmitted patients. Antimicrobial resistance and molecular characteristics of these isolates, including spa-type, sequence type (ST) and SCCmec type, were investigated. All isolates were sensitive to linezolid, teicoplanin, and quinupristin/dalfopristin, but high levels of resistance to penicillin and erythromycin were detected. According to D-test and erm gene detection results, the cMLSB and iMLSB phenotypes were detected in 24 and 16 isolates, respectively. All 10 HA-MRSA strains displayed the cMLSB phenotypemediated by ermA or ermA/ermC, while the cMLSB CA-MRSA and MSSA strains carried the ermB gene. Molecular characterization revealedall 10 HA-MRSA strains were derived from the ST239-SCCmec III clone, and four out of eight CA-MRSA strains were t437-ST59-SCCmec V. The results suggest that patients play an indispensable role in transmitting epidemic CA-MRSA and HA-MRSA strains. PMID:26915614

  19. Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic

    PubMed Central

    David, Michael Z.; Daum, Robert S.

    2010-01-01

    Summary: Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention. PMID:20610826

  20. Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012.

    PubMed

    Coombs, Geoffrey W; Daly, Denise A; Pearson, Julie C; Nimmo, Graeme R; Collignon, Peter J; McLaws, Mary-Louise; Robinson, James O; Turnidge, John D

    2014-03-01

    In 2012, the Australian Group on Antimicrobial Resistance (AGAR) conducted a community-onset period-prevalence survey of clinical Staphylococcus aureus isolated from hospital outpatients and general practice patients including nursing homes, long term care facilities and hospice patients. Day surgery and dialysis patients were excluded. Twenty-nine medical microbiology laboratories from all state and mainland territories participated. Isolates were tested by Vitek2® (AST-P612 card). Results were compared with previous AGAR community surveys. Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) increased significantly from 11.5% in 2000 to 17.9% in 2012 (P<0.0001). Resistance to the non-ß-lactam antimicrobials varied between regions. No resistance was detected to vancomycin, teicoplanin or linezolid. Resistance in methicillin susceptible S. aureus was rare apart from erythromycin (12.8%) and was absent for vancomycin, teicoplanin, linezolid and daptomycin. The proportion of S. aureus characterised as health care-associated MRSA (HA-MRSA) was 5.1%. Three HA-MRSA clones were characterised, with 72.9% and 26.4% of HA-MRSA classified as ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA) respectively. Multi-clonal community-associated MRSA (CA-MRSA) accounted for 12.5% of all S. aureus. Regional variation in resistance in MRSA was primarily due to the differential distribution of the 2 major HA-MRSA clones; ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials, and ST22-IV [2B] (EMRSA-15), which is resistant to ciprofloxacin and typically erythromycin. Although the majority of CA-MRSA were non-multi-resistant, a significant expansion of Panton-Valentine leukocidin (PVL) positive CA-MRSA clones has occurred nationally. The mean age of patients (31.7 years, 95% CI 28.9-34.5) with a PVL positive CA-MRSA infection was significantly lower (P<0.0001), than the mean age of patients with a PVL

  1. High frequency of Panton-Valentine leukocidin in Staphylococcus aureus causing pediatric infections in the city of Cartagena-Colombia.

    PubMed

    Correa-Jiménez, Oscar; Pinzón-Redondo, Hernando; Reyes, Niradiz

    2016-01-01

    Panton-Valentine leucocidin (PVL) is a pore-forming toxin that has been epidemiologically associated with CA-MRSA infections. However, its role in the pathogenicity of Staphylococcus aureus is still unclear. We evaluated the prevalence of PVL-coding genes in methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) isolates that cause infections in pediatric patients in the city of Cartagena, Colombia. We obtained S. aureus isolates from patients at the Napoleon Franco Pareja Children's Hospital in Cartagena. Then, we evaluated the presence of the nuc, mecA, and PVL genes in these isolates by multiplex PCR and determined the antibiotic susceptibility profiles using CLSI standards. We further correlated methicillin susceptibility and the presence of PVL genes with clinical variables. Overall PVL prevalence in S. aureus isolates was 73.91%, with a frequency of 80.92% among MRSA isolates and 67.59% among MSSA. We found a correlation between erythromycin resistance and lack of PVL and found that PVL+ cases were more common in older patients. We found a high PVL prevalence in both MRSA and MSSA isolates, in concordance with previous regional reports. PMID:26631434

  2. Community-based intervention to manage an outbreak of MRSA skin infections in a county jail.

    PubMed

    Elias, Abdallah F; Chaussee, Michael S; McDowell, Emily J; Huntington, Mark K

    2010-07-01

    This article describes a community-based intervention to manage an outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections in a midwestern county jail. A systematic investigation conducted by a family medicine residency program identified 64 total cases and 19 MRSA cases between January 1 and December 31, 2007. Factors contributing to MRSA transmission included inadequate surveillance, lack of antibacterial soap, and a defective laundry process. All 19 isolates were CA-MRSA and all seven tested by pulsed-field gel electrophoresis (PFGE) were USA300. Four of the seven isolates showed variation of their PFGE patterns. A primary care approach using community-based resources effectively reduced the number of cases in this heterogeneous outbreak of CA-MRSA, with the last MRSA being isolated in October 2007. PMID:20466702

  3. Community-Based Intervention to Manage an Outbreak of MRSA Skin Infections in a County Jail

    PubMed Central

    Elias, Abdallah F.; Chaussee, Michael S.; McDowell, Emily J.; Huntington, Mark K.

    2012-01-01

    This article describes a community-based intervention to manage an outbreak of communityassociated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections in a midwestern county jail. A systematic investigation conducted by a family medicine residency program identified 64 total cases and 19 MRSA cases between January 1 and December 31, 2007. Factors contributing to MRSA transmission included inadequate surveillance, lack of antibacterial soap, and a defective laundry process. All 19 isolates were CA-MRSA and all seven tested by pulsed-field gel electrophoresis (PFGE) were USA300. Four of the seven isolates showed variation of their PFGE patterns. A primary care approach using community-based resources effectively reduced the number of cases in this heterogeneous outbreak of CA-MRSA, with the last MRSA being isolated in October 2007. PMID:20466702

  4. Origin and Evolution of European Community-Acquired Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Wirth, Thierry; Andersen, Paal S.; Skov, Robert L.; De Grassi, Anna; Simões, Patricia Martins; Tristan, Anne; Petersen, Andreas; Aziz, Maliha; Kiil, Kristoffer; Cirković, Ivana; Udo, Edet E.; del Campo, Rosa; Vuopio-Varkila, Jaana; Ahmad, Norazah; Tokajian, Sima; Peters, Georg; Schaumburg, Frieder; Olsson-Liljequist, Barbro; Givskov, Michael; Driebe, Elizabeth E.; Vigh, Henrik E.; Shittu, Adebayo; Ramdani-Bougessa, Nadjia; Rasigade, Jean-Philippe; Price, Lance B.; Vandenesch, Francois; Larsen, Anders R.; Laurent, Frederic

    2014-01-01

    ABSTRACT Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. PMID:25161186

  5. A Case of Acute Pyogenic Sacroiliitis and Bacteremia Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Kim, Suyoung; Lee, Kang Lock; Baek, Hae Lim; Jang, Seung Jun; Moon, Song Mi

    2013-01-01

    Pyogenic sacroiliitis is a rare osteoarticular infection, occurring most frequently in children and young adults. Diagnosis of the disease is challenging because of a general lack of awareness of the disease and its nonspecific signs and symptoms. Staphylococcus aureus is the most common causative bacteria in pyogenic sacroiliitis. Methicillin-resistant S. aureus (MRSA) has typically been considered a hospital-associated pathogen; however, community-acquired (CA)-MRSA infections are becoming increasingly common in Korea. We report the first domestic case of acute pyogenic sacroiliitis with abscess and bacteremia caused by CA-MRSA. The pathogen carried the type IV-A staphylococcal cassette chromosome mec (SCCmec) without the Panton-Valentine leukocidin (PVL) gene, and was identified as sequence type (ST) 72 by multilocus sequence typing. PMID:24475359

  6. A study of community-associated methicillin-resistant Staphylococcus aureus in patients with pyoderma

    PubMed Central

    Venniyil, Prasanth V.; Ganguly, Satyaki; Kuruvila, Sheela; Devi, Sheela

    2016-01-01

    Background: Health care–associated methicillin-resistant Staphylococcus aureus(HA-MRSA) are resistant to multiple antibiotics, therefore infections caused by them are difficult to treat resulting in high morbidity and mortality. While most of the research activities and public health initiatives are focused on HA-MRSA, the newly emerging pathogen, community-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) is gaining in significance in respect to patient morbidity. There is a significant paucity of data regarding CA-MRSA in the developing parts of the world. Aim: To study the proportions of HA-MRSA and CA-MRSA infections among patients with culture-proven S. aureus infection and to find out how many of these patients showed presence of MRSA in nasal cultures of healthy contacts. Materials and Methods: Clinical details of 227 patients were recorded in the study, such as the duration and recurrence of the infection, history of antibiotic intake, and the presence of other medical illnesses. A pus swab was taken from each lesion and sent for culture and sensitivity. If the culture grew S. aureus, they were screened for methicillin resistance. A swab from the anterior nares of the healthy contact of each patient, whenever available, was collected and it was screened for MRSA. Results: Furunculosis was most common among the primary pyodermas (53/134; 39. 5%). Out of 239 pus culture samples obtained from 227 patients, 192 (84.58%) grew S. aureus; of these 150 (78.12%) were methicillin-sensitive S. aureus (MSSA), whereas 42 (21.98%) were MRSA. Out of the 42 MRSA isolated, 33 turned out to be CA-MRSA (78%) and 9 (22%) were HA-MRSA. Nasal swabs of healthy contacts of 34 MRSA patients were cultured. Out of them, two grew MRSA in the culture. Conclusion: The isolation rate of S. aureus was high in our study. Furthermore, our study, although hospital based, clearly indicated the substantial magnitude of the CA-MRSA problem in the local population. PMID:27294048

  7. Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection.

    PubMed

    Ibberson, Carolyn B; Parlet, Corey P; Kwiecinski, Jakub; Crosby, Heidi A; Meyerholz, David K; Horswill, Alexander R

    2016-06-01

    Staphylococcus aureus is a leading cause of chronic biofilm infections. Hyaluronic acid (HA) is a large glycosaminoglycan abundant in mammalian tissues that has been shown to enhance biofilm formation in multiple Gram-positive pathogens. We observed that HA accumulated in an S. aureus biofilm infection using a murine implant-associated infection model and that HA levels increased in a mutant strain lacking hyaluronidase (HysA). S. aureus secretes HysA in order to cleave HA during infection. Through in vitro biofilm studies with HA, the hysA mutant was found to accumulate increased biofilm biomass compared to the wild type, and confocal microscopy showed that HA is incorporated into the biofilm matrix. Exogenous addition of purified HysA enzyme dispersed HA-containing biofilms, while catalytically inactive enzyme had no impact. Additionally, induction of hysA expression prevented biofilm formation and also dispersed an established biofilm in the presence of HA. These observations were corroborated in the implant model, where there was decreased dissemination from an hysA mutant biofilm infection compared to the S. aureus wild type. Histopathology demonstrated that infection with an hysA mutant caused significantly reduced distribution of tissue inflammation compared to wild-type infection. To extend these studies, the impact of HA and S. aureus HysA on biofilm-like aggregates found in joint infections was examined. We found that HA contributes to the formation of synovial fluid aggregates, and HysA can disrupt aggregate formation. Taken together, these studies demonstrate that HA is a relevant component of the S. aureus biofilm matrix and HysA is important for dissemination from a biofilm infection. PMID:27068096

  8. Genomic insights into the emergence and spread of international clones of healthcare-, community- and livestock-associated meticillin-resistant Staphylococcus aureus: Blurring of the traditional definitions.

    PubMed

    Bal, A M; Coombs, G W; Holden, M T G; Lindsay, J A; Nimmo, G R; Tattevin, P; Skov, R L

    2016-09-01

    The evolution of meticillin-resistant Staphylococcus aureus (MRSA) from meticillin-susceptible S. aureus has been a result of the accumulation of genetic elements under selection pressure from antibiotics. The traditional classification of MRSA into healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) is no longer relevant as there is significant overlap of identical clones between these groups, with an increasing recognition of human infection caused by livestock-associated MRSA (LA-MRSA). Genomic studies have enabled us to model the epidemiology of MRSA along these lines. In this review, we discuss the clinical relevance of genomic studies, particularly whole-genome sequencing, in the investigation of outbreaks. We also discuss the blurring of each of the three epidemiological groups (HA-MRSA, CA-MRSA and LA-MRSA), demonstrating the limited relevance of this classification. PMID:27530849

  9. Evidence based approach to the treatment of community-associated methicillin-resistant Staphylococcus aureus.

    PubMed

    Peppard, William J; Daniels, Anne; Fehrenbacher, Lynne; Winner, Jamie

    2009-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have increased dramatically over the last two decades. The types of infections can range from complicated skin and skin structure infections (cSSSI) to pneumonia and endocarditis. Oral antimicrobial therapy, such as trimethoprim-sulfamethoxazole, clindamycin, long-acting tetracyclines, or linezolid may provide enhanced benefit to those with uncomplicated cutaneous lesions when used in conjunction with incision and drainage in an outpatient setting. However, resistance, susceptibilities, patient-specific circumstances, and adverse effects can impact a healthcare professional's choice of antibiotics. In patients with complicated infections requiring hospitalization or parenteral treatment, vancomycin remains the drug of choice, even though increased resistance and decreased efficacy have crept into clinical practice. Linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline are alternative intravenous agents for the treatment of CA-MRSA. Investigational agents such as dalbavancin, telavancin, oritivancin, iclaprim, ceftobiprole, ceftaroline, and others may expand our therapeutic armamentarium for the treatment of infections caused by CA-MRSA in the future. PMID:21694885

  10. Kinin receptor expression during Staphylococcus aureus infection

    PubMed Central

    Bengtson, Sara H.; Phagoo, Stephen B.; Norrby-Teglund, Anna; Påhlman, Lisa; Mörgelin, Matthias; Zuraw, Bruce L.; Leeb-Lundberg, L. M. Fredrik; Herwald, Heiko

    2006-01-01

    An inappropriate host response to invading bacteria is a critical parameter that often aggravates the outcome of an infection. Staphylococcus aureus is a major human Gram-positive pathogen that causes a wide array of community- and hospital-acquired diseases ranging from superficial skin infections to severe conditions such as staphylococcal toxic shock. Here we find that S aureus induces inflammatory reactions by modulating the expression and response of the B1 and B2 receptors, respectively. This process is initiated by a chain of events, involving staphylococcal-induced cytokine release from monocytes, bacteria-triggered contact activation, and conversion of bradykinin to its metabolite desArg9bradykinin. The data of the present study implicate an important and previously unknown role for kinin receptor regulation in S aureus infections. PMID:16735595

  11. Low prevalence of methicillin-resistant Staphylococcus aureus among men who have sex with men attending an STI clinic in Amsterdam: a cross-sectional study

    PubMed Central

    Joore, I K C W; van Rooijen, Martijn Sebastiaan; Schim van der Loeff, Maarten Franciscus; de Neeling, A J; van Dam, Alje; de Vries, Henry J C

    2013-01-01

    Objective Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is common among men who have sex with men (MSM) in the USA. It is unknown whether this is also the case in Amsterdam, the Netherlands. Design Cross-sectional study. Setting Sexually transmitted infection outpatient low-threshold clinic, Amsterdam, the Netherlands. Participants Between October 2008 and April 2010, a total of 211 men were included, in two groups: (1) 74 MSM with clinical signs of a skin or soft tissue infection (symptomatic group) and (2) 137 MSM without clinical signs of such infections (asymptomatic group). Primary outcome measures S aureus and MRSA infection and/or colonisation. Swabs were collected from the anterior nasal cavity, throat, perineum, penile glans and, if present, from infected skin lesions. Culture for S aureus was carried out on blood agar plates and for MRSA on selective chromagar plates after enrichment in broth. If MRSA was found, the spa-gene was sequenced. Secondary outcome measures Associated demographic characteristics, medical history, risk factors for colonisation with S aureus and high-risk sexual behaviour were collected through a self-completed questionnaire. Results The prevalence of S aureus colonisation in the nares was 37%, the pharynx 11%, the perianal region 12%, the glans penis 10% and in skin lesions 40%. In multivariable analysis adjusting for age, anogenital S aureus colonisation was significantly associated with the symptomatic group (p=0.01) and marginally with HIV (p=0.06). MRSA was diagnosed in two cases: prevalence 0.9% (95% CI 0.1% to 3.4%)). Neither had CA-MRSA strains. Conclusions CA-MRSA among MSM in Amsterdam is rare. Genital colonisation of S aureus is not associated with high-risk sexual behaviour. PMID:23468471

  12. Skin infections in young people (aged 14-18 years): an integrative review.

    PubMed

    Lambe, Catherine I; Hoare, Karen J

    2014-06-01

    Skin infections are a major cause of preventable hospitalization, with young people being particularly susceptible. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection typically presents as skin infection. CA-MRSA infection rates have increased rapidly in the past decade. Exploration of literature specific to young people aged 14-18 years is therefore timely. Integrative review using the methods described by Whittemore and Knafl was undertaken. Electronic databases of Medline, CINAHL, Scopus, Cochrane Database of Systematic Reviews, and Google databases were searched for English-language articles published after 1990. Twenty primary studies were included and the findings are reported here. Data analysis revealed factors influencing skin infections in young people may be host-, transmission-, or pathogen-specific. Strategies to address host and transmission factors may be effective in controlling skin infection rates in young people. PMID:23945044

  13. Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice

    PubMed Central

    van den Berg, Sanne; de Vogel, Corné P.; van Belkum, Alex; Bakker-Woudenberg, Irma A. J. M.

    2015-01-01

    Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P) or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG) levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect. PMID:26060995

  14. Antimicrobial therapy of Staphylococcus aureus bloodstream infection.

    PubMed

    Tacconelli, Evelina; Cataldo, Maria A

    2007-10-01

    Staphylococcus aureus bloodstream infection (BSI) contributes significantly to the morbidity and mortality of in-patients. The optimal therapy for methicillin-susceptible S. aureus BSI consists of penicillins. The efficacy of these drugs is well documented from several published data and supported from a long clinical experience. Methicillin-resistant S. aureus (MRSA) strains are responsible for the majority of nosocomial BSI and are recovered with increasing frequency at hospital admission. Although glycopeptides still represent the drugs of choice, there are several concerns on the treatment of MRSA BSI: reports of clinical failure with vancomycin treatment, regardless of the in vitro susceptibility; increasing reports of MRSA strains with reduced vancomycin susceptibility; difficulty in therapeutic dosage monitoring of teicoplanin; lack of evidence on the efficacy of combination therapy. Recently, new drugs have been introduced in the therapeutic arsenal for MRSA infections, but their clinical use is not yet clearly established for BSI. The review summarises evidence on present therapeutic options for the treatment of S. aureus BSI. PMID:17931086

  15. Staphylococcus aureus Infections in New Zealand, 2000–2011

    PubMed Central

    Zhang, Jane; Ritchie, Stephen R.; Roberts, Sally A.; Fraser, John D.; Baker, Michael G.

    2014-01-01

    The incidence rate for invasive and noninvasive Staphylococcus aureus infections in New Zealand is among the highest reported in the developed world. Using nationally collated hospital discharge data, we analyzed the epidemiology of serious S. aureus infections in New Zealand during 2000–2011. During this period, incidence of S. aureus skin and soft tissue infections increased significantly while incidence of staphylococcal sepsis and pneumonia remained stable. We observed marked ethnic and sociodemographic inequality across all S. aureus infections; incidence rates for all forms of S. aureus infections were highest among Māori and Pacific Peoples and among patients residing in areas of high socioeconomic deprivation. The increased incidence of S. aureus skin and soft tissue infections, coupled with the demographic disparities, is of considerable concern. Future work should aim to reduce this disturbing national trend. PMID:24960446

  16. Molecular epidemiology and antimicrobial susceptibility profiles of methicillin-resistant Staphylococcus aureus blood culture isolates: results of the Quebec Provincial Surveillance Programme.

    PubMed

    Lévesque, S; Bourgault, A M; Galarneau, L A; Moisan, D; Doualla-Bell, F; Tremblay, C

    2015-05-01

    The objectives of this study were to characterize methicillin-resistant Staphylococcus aureus (MRSA) blood culture isolates and to determine their relative importance in both nosocomial and community-acquired infections. A total of 535 MRSA blood culture isolates were analysed. In vitro susceptibility to 14 agents was determined. The genes nuc, mecA and coding for PVL toxin were identified by PCR. All isolates were characterized by PFGE or spa typing to assess their genomic relationships. Most MRSA isolates were retrieved from nosocomial bloodstream infections (474, 89%) and were of the CMRSA2 genotype. Healthcare-associated (HA)-MRSA bloodstream infections were associated with older age (70-89 years, P = 0·002) and most often secondary to central line infections (P = 0·005). Among MRSA strains associated with community-acquired (CA)-MRSA, 28·8% were isolated in intravenous drug users. CA-MRSA genotypes were more frequently found in young adults (20-39 years, P < 0·0001) with skin/soft tissue as the primary sources of infection (P = 0·006). CMRSA10 genotype was the predominant CA-MRSA strain. All MRSA isolates were susceptible to doxycycline, tigecycline, trimethoprim/sulfamethoxazole and vancomycin. Both the presence of the genes coding for PVL toxin (89·8%) and susceptibility to clindamycin (86·5%) were predictive of CA-MRSA genotypes. Whereas in the USA, HA-MRSA have been replaced by USA300 (CMRSA10) clone as the predominant MRSA strain type in positive blood cultures from hospitalized patients, this phenomenon has not been observed in the province of Quebec. PMID:25140694

  17. Livestock-associated methicillin-resistant Staphylococcus aureus responsible for human colonization and infection in an area of Italy with high density of pig farming

    PubMed Central

    2013-01-01

    Background Livestock-Associated MRSA (LA-MRSA) belonging to ST398 lineage, common among pigs and other animals, emerged in Central and Northern Europe, becoming a new risk factor for MRSA among farm workers. Strains belonging to ST398 can be responsible for human colonization and infection, mainly in areas with high livestock-farming. The aim of this study was to investigate the occurrence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) human colonization and infections in an area of the Lombardy Region (Italy), the Italian region with the highest density of pig farming. Methods In the period March-April 2010, 879 nasal swabs were taken from subjects at admission to a local hospital serving an area of the Lombardy Region devoted to agriculture and farming. In the period March 2010-February 2011, all MRSA strains from community-acquired infection (CAI) observed in the same hospital, were collected. Molecular characterization of the isolates included SCCmec typing, spa typing and multilocus sequence typing (MLST). Results Out of 879 nasal swabs examined, 9 (1%) yielded MRSA. Five strains were assigned to sequence type (ST)398 (spa t899, 3 isolates; t108 and t2922, 1 isolate each) and were therefore categorized as LA-MRSA. The other 4 isolates were likely of hospital origin. No strains were positive for Panton-Valentine Leukocidin genes. Twenty MRSA isolates were detected from CAI, 17 were from skin and soft-tissue infections and 3 from other infections. An MRSA isolate from otitis externa was t899/ST398 and PVL-negative, hence categorized as LA-MRSA. Four isolates were assigned to t127/ST1. Eight strains were PVL-positive community acquired (CA)-MRSA and belonged to different clones, the most frequent being ST8. Conclusions In an area of Italy with high density of pig farming, LA-MRSA is able to colonize the population and rarely to produce infections. Typical CA-MRSA is more common than LA-MRSA among CAI. PMID:23731504

  18. Retrospective study of necrotizing fasciitis and characterization of its associated Methicillin-resistant Staphylococcus aureus in Taiwan

    PubMed Central

    2011-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a prevalent pathogen of necrotizing fasciitis (NF) in Taiwan. A four-year NF cases and clinical and genetic differences between hospital acquired (HA)- and community-acquired (CA)-MRSA infection and isolates were investigated. Methods A retrospective study of 247 NF cases in 2004-2008 and antimicrobial susceptibilities, staphylococcal chromosomal cassette mec (SCCmec) types, pulsed field gel electrophoresis (PFGE) patterns, virulence factors, and multilocus sequence typing (MLST) of 16 NF-associated MRSA in 2008 were also evaluated. Results In 247 cases, 42 microbial species were identified. S. aureus was the major prevalent pathogen and MRSA accounted for 19.8% of NF cases. Most patients had many coexisting medical conditions, including diabetes mellitus, followed by hypertension, chronic azotemia and chronic hepatic disease in order of decreasing prevalence. Patients with MRSA infection tended to have more severe clinical outcomes in terms of amputation rate (p < 0.05) and reconstruction rate (p = 0.001) than those with methicillin-sensitive S. aureus or non-S. aureus infection. NF patients infected by HA-MRSA had a significantly higher amputation rate, comorbidity, C-reactive protein level, and involvement of lower extremity than those infected by CA-MRSA. In addition to over 90% of MRSA resistant to erythromycin and clindamycin, HA-MRSA was more resistant than CA-MRSA to trimethoprim-sulfamethoxazole (45.8% vs. 4%). ST59/pulsotype C/SCCmec IV and ST239/pulsotype A/SCCmec III isolates were the most prevalent CA- and HA-MRSA, respectively in 16 isolates obtained in 2008. In contrast to the gene for γ-hemolysin found in all MRSA, the gene for Panton-Valentine leukocidin was only identified in ST59 MRSA isolates. Other three virulence factors TSST-1, ETA, and ETB were occasionally identified in MRSA isolates tested. Conclusion NF patients with MRSA infection, especially HA-MRSA infection

  19. Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

    PubMed Central

    2014-01-01

    Background Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization. Results We found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and a significantly higher (100 fold) level of live intracellular S. aureus was detected in macrophages compared to osteoblasts. However, the percentage of S. aureus survival after infection was significantly lower in macrophages compared to osteoblasts at post-infection days 1–6. Interestingly, macrophages had relatively lower viability in shorter infection time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer infection time periods (i.e. 6–8 h; significant at 8 h) compared to osteoblasts. In addition, S. aureus infection led to significant changes in reactive oxygen species production in both macrophages and osteoblasts. Moreover, infected osteoblasts had significantly lower alkaline phosphatase activity at post-infection day 7 and infected macrophages had higher phagocytosis activity compared to non-infected cells. Conclusions S. aureus was found to internalize and survive within osteoblasts and macrophages and led to differential responses between osteoblasts and macrophages. These findings may assist in evaluation of the pathogenesis of chronic and recurrent infections which may be related to the intracellular persistence of bacteria within host cells. PMID:25059520

  20. Simulated Antibiotic Exposures in an In Vitro Hollow-Fiber Infection Model Influence Toxin Gene Expression and Production in Community-Associated Methicillin-Resistant Staphylococcus aureus Strain MW2

    PubMed Central

    Pichereau, Solen; Pantrangi, Madhulatha; Couet, William; Badiou, Cedric; Lina, Gerard; Shukla, Sanjay K.

    2012-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain MW2 harbors a plethora of toxins to mediate its virulence. However, toxin expression and regulation with simulated clinical antimicrobial exposures are unclear. This study evaluated these relationships using an in vitro pharmacodynamic hollow-fiber infection model. Clinical doses of clindamycin, linezolid, minocycline, trimethoprim-sulfamethoxazole (SXT), and vancomycin were simulated over 72 h against MW2 in the hollow fiber model. Expression levels of lukSF-PV and enterotoxin genes sec4, sek, seq, and sel2 were quantified by real-time PCR. Panton-Valentine leukocidin (PVL) was quantified by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was determined on polymorphonuclear cells (PMNs). Vancomycin produced the maximum MW2 killing (2.53 log10 CFU/ml) after the first dose, but the greatest sustained killing over 72 h occurred with linezolid and clindamycin. Vancomycin and minocycline induced gene upregulation from 0 to 8 h, followed by downregulation for the remaining simulation period. Clindamycin decreased gene expression in the first 24 h, followed by moderate increases (2.5-fold) thereafter. Linezolid increased gene expression 11.4- to 200.4-fold but inhibited PVL production (0.6 ± 0.3 versus 5.9 ± 0.2 μg/ml, linezolid versus control at 72 h; P < 0.05). Similar effects on PVL production occurred with clindamycin and minocycline. SXT increased PVL production at 48 h (2.8-fold) and 72 h (4.9-fold) of treatment (P < 0.05), resulting in increased PVL cytotoxicity on PMNs. Linezolid, clindamycin, and minocycline were the most effective agents on decreasing the virulence potential in CA-MRSA, notably after 8 h of treatment. SXT had minimal effects on toxin gene regulation, but it increased production and cytotoxicity of PVL toxin in the model and may enhance virulence when it is used to treat severe infections. PMID:22064533

  1. Epidemiology of emerging methicillin-resistant Staphylococcus aureus (MRSA) in Denmark: a nationwide study in a country with low prevalence of MRSA infection.

    PubMed

    Faria, Nuno A; Oliveira, Duarte C; Westh, Henrik; Monnet, Dominique L; Larsen, Anders R; Skov, Robert; de Lencastre, Hermínia

    2005-04-01

    Strict infection control measures introduced during the 1970s have kept the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections extremely low in Denmark. Nevertheless, similarly to other countries, MRSA infections began to appear in the community in the late 1990s. A nationwide surveillance program has collected and stored all MRSA isolates since 1988 and, since 1999, clinical information has been also recorded. We used this information and isolates in a detailed epidemiological and molecular analysis of the 81 MRSA infections identified in Denmark in 2001. MRSA isolates were characterized by pulsed-field gel electrophoresis (PFGE), spa typing, multilocus sequence typing, and SCCmec typing. Comparison of the 45 community-onset MRSA (CO-MRSA) infections with the 36 hospital-acquired MRSA (HA-MRSA) infections showed several striking contrasts. Most CO-MRSA were recovered from skin and soft tissue infections caused by isolates carrying the Panton-Valentine leucocidin toxin genes, and the majority (84%) of isolates belonged to a single clonal type, ST80-IV, which has been found in the community in other European countries. Clone ST80-IV could be traced in Denmark back to 1993. ST80-IV was rarely found in HA-MRSA infections, which belonged to a large number of clonal types, including some pandemic MRSA clones. The low number of HA-MRSA infections and the diversity of MRSA clones in Danish hospitals may be the result of successful infection control measures that prevent spread of clones in hospitals. The mechanism of spread of the ST80-IV clone in the Danish community is not known, and new control measures are needed to control further spread of this and other CA-MRSA clones. PMID:15815005

  2. Panton-valentine leukocidin-positive and toxic shock syndrome toxin 1-positive methicillin-resistant Staphylococcus aureus: a French multicenter prospective study in 2008.

    PubMed

    Robert, Jérôme; Tristan, Anne; Cavalié, Laurent; Decousser, Jean-Winoc; Bes, Michèle; Etienne, Jerome; Laurent, Frédéric

    2011-04-01

    The epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) differs from country to country. We assess the features of the ST80 European clone, which is the most prevalent PVL-positive CA-MRSA clone in Europe, and the TSST-1 ST5 clone that was recently described in France. In 2008, all MRSA strains susceptible to fluoroquinolones and gentamicin and resistant to fusidic acid that were isolated in 104 French laboratories were characterized using agr alleles, spa typing, and the staphylococcal cassette chromosome mec element and PCR profiling of 21 toxin genes. Three phenotypes were defined: (i) kanamycin resistant, associated with the ST80 clone; (ii) kanamycin and tobramycin resistant, associated with the ST5 clone; and (iii) aminoglycoside susceptible, which was less frequently associated with the ST5 clone. Among the 7,253 MRSA strains isolated, 91 (1.3%) were ST80 CA-MRSA (89 phenotype 1) and 190 (2.6%) were ST5 CA-MRSA (146 phenotype 2, 42 phenotype 3). Compared to the latter, ST80 CA-MRSAs were more likely to be community acquired (80% versus 46%) and found in young patients (median age, 26.0 years versus 49.5 years) with deep cutaneous infections (48% versus 6%). They were less likely to be tetracycline susceptible (22% versus 85%) and to be isolated from respiratory infections (6% versus 27%). The TSST-1 ST5 clone has rapidly emerged in France and has become even more prevalent than the ST80 European clone, whose prevalence has remained stable. The epidemiological and clinical patterns of the two clones differ drastically. Given the low prevalence of both among all staphylococcal infections, no modification of antibiotic recommendations is required yet. PMID:21220529

  3. Panton-Valentine Leukocidin-Positive and Toxic Shock Syndrome Toxin 1-Positive Methicillin-Resistant Staphylococcus aureus: a French Multicenter Prospective Study in 2008▿

    PubMed Central

    Robert, Jérôme; Tristan, Anne; Cavalié, Laurent; Decousser, Jean-Winoc; Bes, Michèle; Etienne, Jerome; Laurent, Frédéric

    2011-01-01

    The epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) differs from country to country. We assess the features of the ST80 European clone, which is the most prevalent PVL-positive CA-MRSA clone in Europe, and the TSST-1 ST5 clone that was recently described in France. In 2008, all MRSA strains susceptible to fluoroquinolones and gentamicin and resistant to fusidic acid that were isolated in 104 French laboratories were characterized using agr alleles, spa typing, and the staphylococcal cassette chromosome mec element and PCR profiling of 21 toxin genes. Three phenotypes were defined: (i) kanamycin resistant, associated with the ST80 clone; (ii) kanamycin and tobramycin resistant, associated with the ST5 clone; and (iii) aminoglycoside susceptible, which was less frequently associated with the ST5 clone. Among the 7,253 MRSA strains isolated, 91 (1.3%) were ST80 CA-MRSA (89 phenotype 1) and 190 (2.6%) were ST5 CA-MRSA (146 phenotype 2, 42 phenotype 3). Compared to the latter, ST80 CA-MRSAs were more likely to be community acquired (80% versus 46%) and found in young patients (median age, 26.0 years versus 49.5 years) with deep cutaneous infections (48% versus 6%). They were less likely to be tetracycline susceptible (22% versus 85%) and to be isolated from respiratory infections (6% versus 27%). The TSST-1 ST5 clone has rapidly emerged in France and has become even more prevalent than the ST80 European clone, whose prevalence has remained stable. The epidemiological and clinical patterns of the two clones differ drastically. Given the low prevalence of both among all staphylococcal infections, no modification of antibiotic recommendations is required yet. PMID:21220529

  4. Staphylococcus aureus ST121: a globally disseminated hypervirulent clone.

    PubMed

    Rao, Qing; Shang, Weilong; Hu, Xiaomei; Rao, Xiancai

    2015-12-01

    Staphylococcus aureus is a leading cause of bacterial infections in hospitals and communities worldwide. With the development of typing methods, several pandemic clones have been well characterized, including the extensively spreading hospital-associated meticillin-resistant S. aureus (HA-MRSA) clone ST239 and the emerging hypervirulent community-associated (CA) MRSA clone USA300. The multilocus sequence typing method was set up based on seven housekeeping genes; S. aureus groups were defined by the sharing of alleles at ≥ 5 of the seven loci. In many cases, the predicted founder of a group would also be the most prevalent ST within the group. As a predicted founder of major S. aureus groups, approximately 90 % of ST121 strains was meticillin-susceptible S. aureus (MSSA). The majority of ST121 strains carry accessory gene regulator type IV, whereas staphylococcal protein A gene types for ST121 are exceptionally diverse. More than 90 % of S. aureus ST121 strains have Panton-Valentine leukocidin; other enterotoxins, haemolysins, leukocidins and exfoliative toxins also contribute to the high virulence of ST121 strains. Patients suffering from S. aureus ST121 infections often need longer hospitalization and prolonged antimicrobial therapy. In this review, we tried to summarize the epidemiology of the S. aureus clone ST121 and focused on the molecular types, toxin carriage and disease spectrum of this globally disseminated clone. PMID:26445995

  5. Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus infection.

    PubMed

    Kim, Min-Ho; Yamayoshi, Itsukyo; Mathew, Steven; Lin, Hubert; Nayfach, Joseph; Simon, Scott I

    2013-03-01

    The incidence of wound infections that do not adequately respond to standard-of-care antimicrobial treatment has been increasing. To address this challenge, a novel antimicrobial magnetic thermotherapy platform has been developed in which a high-amplitude, high-frequency, alternating magnetic field is used to rapidly heat magnetic nanoparticles that are bound to Staphylococcus aureus (S. aureus). The antimicrobial efficacy of this platform was evaluated in the treatment of both an in vitro culture model of S. aureus biofilm and a mouse model of cutaneous S. aureus infection. We demonstrated that an antibody-targeted magnetic nanoparticle bound to S. aureus was effective at thermally inactivating S. aureus and achieving accelerated wound healing without causing tissue injury. PMID:23149904

  6. Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus infection

    PubMed Central

    Kim, Min-Ho; Yamayoshi, Itsukyo; Mathew, Steven; Liln, Hubert; Nayfach, Joseph; Simon, Scott I.

    2013-01-01

    The incidence of wound infections that do not adequately respond to standard-of-care antimicrobial treatment has been increasing. To address this challenge, a novel antimicrobial magnetic thermotherapy platform has been developed in which a high-amplitude, high-frequency, alternating magnetic field (AMF) is used to rapidly heat magnetic nanoparticles that are bound to Staphylococcus aureus (S. aureus). The antimicrobial efficacy of this platform was evaluated in the treatment of both an in vitro culture model of S. aureus biofilm and a mouse model of cutaneous S. aureus infection. We demonstrated that an antibody-targeted magnetic nanoparticle bound to S. aureus was effective at thermally inactivating S. aureus and achieving accelerated wound healing without causing tissue injury. PMID:23149904

  7. Lysostaphin in treatment of neonatal Staphylococcus aureus infection.

    PubMed

    Oluola, Okunola; Kong, Lingkun; Fein, Mindy; Weisman, Leonard E

    2007-06-01

    This study describes lysostaphin's effect against methicillin-sensitive Staphylococcus aureus in suckling rats. Standard techniques determined minimal inhibitory and bactericidal concentrations, pharmacokinetics, and efficacy. The numbers of surviving rats after vancomycin, oxacillin, and lysostaphin treatment were comparable and were different from that of controls (P < 0.00001). Lysostaphin appears effective in the treatment of neonatal S. aureus infection. PMID:17420212

  8. Community-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 80 Type IV (CC80-MRSA-IV) Isolated from the Middle East: A Heterogeneous Expanding Clonal Lineage

    PubMed Central

    Harastani, Houda H.; Tokajian, Sima T.

    2014-01-01

    Background The emergence of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has caused a change in MRSA epidemiology worldwide. In the Middle East, the persistent spread of CA-MRSA isolates that were associated with multilocus sequence type (MLST) clonal complex 80 and with staphylococcal cassette chromosome mec (SCCmec) type IV (CC80-MRSA-IV), calls for novel approaches for infection control that would limit its spread. Methodology/Principal Findings In this study, the epidemiology of CC80-MRSA-IV was investigated in Jordan and Lebanon retrospectively covering the period from 2000 to 2011. Ninety-four S. aureus isolates, 63 (67%) collected from Lebanon and 31 (33%) collected from Jordan were included in this study. More than half of the isolates (56%) were associated with skin and soft tissue infections (SSTIs), and 73 (78%) were Panton-Valentine Leukocidin (PVL) positive. Majority of the isolates (84%) carried the gene for exofoliative toxin d (etd), 19% had the Toxic Shock Syndrome Toxin-1 gene (tst), and seven isolates from Jordan had a rare combination being positive for both tst and PVL genes. spa typing showed the prevalence of type t044 (85%) and pulsed-field gel electrophoresis (PFGE) recognized 21 different patterns. Antimicrobial susceptibility testing showed the prevalence (36%) of a unique resistant profile, which included resistance to streptomycin, kanamycin, and fusidic acid (SKF profile). Conclusions The genetic diversity among the CC80 isolates observed in this study poses an additional challenge to infection control of CA-MRSA epidemics. CA-MRSA related to ST80 in the Middle East was distinguished in this study from the ones described in other countries. Genetic diversity observed, which may be due to mutations and differences in the antibiotic regimens between countries may have led to the development of heterogeneous strains. Hence, it is difficult to maintain “the European CA-MRSA clone” as a uniform clone and it

  9. Can Panton Valentine Leukocidin Gene And Clindamycin Susceptibility Serve As Predictors of Community Origin of MRSA From Skin and Soft Tissue Infections?

    PubMed Central

    Shashindran, Nandita; Nagasundaram, Niveditha; Thappa, Devinder Mohan

    2016-01-01

    Introduction Community associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have begun to replace Hospital Associated MRSA (HA-MRSA) strains in hospital settings all over the world. With the epidemiological distinctions between these strains beginning to become ill-defined, the categorisation of a strain as CA-MRSA or HA-MRSA is dependent on molecular methods to detect the presence of SCCmec (Staphylococcal Cassette Chromosome mec) elements. However other markers like the presence of Panton Valentine Leukocidin toxin (pvl) genes or Clindamycin susceptibility may also be associated with community origin of MRSA. Aim To determine the prevalence of CA-MRSA among MRSA strains isolated from skin and soft tissue infections and to evaluate the usefulness of Panton Valentine Leukocidin and Clindamycin susceptibility as markers of community origin of MRSA. Materials and Methods One hundred isolates of MRSA from skin and soft tissue were studied for the presence of SCCmec IV and V genes and Panton valentine leukocidin gene by Polymerase chain reaction. Inducible clindamycin resistance was screened for using the D-test. Statistical analysis used Fischer’s exact test. A p-value <0.05 was considered significant Results Eighteen out of 100 MRSA strains were found to be CA-MRSA based on presence of SCCmecV. The proportion of Panton Valentine Leukocidin gene carriage among CA- MRSA as compared to HA-MRSA was found to be statistically significant (p<0.0001). Among the CA-MRSA strains, 94.4% were found to be susceptible to Clindamycin as against only 13.4% of the HA-MRSA strains (p<0.0001). The odds of an MRSA strain being CA-MRSA if it was both Clindamycin susceptible and PVL gene positive was calculated to be 68.25 (p<0.0001). Conclusion Both Clindamycin susceptibility and pvl gene carriage were found to be independent predictors of community origin of MRSA, but taken together the association was highly significant. PMID:26894063

  10. Recurrent Furunculosis Caused by a Community-Acquired Staphylococcus aureus Strain Belonging to the USA300 Clone

    PubMed Central

    Balachandra, Shirish; Pardos de la Gandara, Maria; Salvato, Scott; Urban, Tracie; Parola, Claude; Khalida, Chamanara; Kost, Rhonda G.; Evering, Teresa H.; Pastagia, Mina; D'Orazio, Brianna M.; Tomasz, Alexander; de Lencastre, Herminia

    2015-01-01

    Background: A 24-year-old female with recurrent skin and soft tissue infections (SSTI) was enrolled as part of a multicenter observational cohort study conducted by a practice-based research network (PBRN) on community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Methods: Strains were characterized by pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing. MRSA strains were analyzed for SCCmec type and the presence of the Panton-Valentine leukocidin (PVL) and arginine catabolic mobile element (ACME) using PCR. Results: In the first episode, S. aureus was recovered from the wound and inguinal folds; in the second, S. aureus was recovered from a lower abdomen furuncle, inguinal folds, and patellar fold. Molecular typing identified CA-MRSA clone USA300 in all samples as spa-type t008, ST8, SCCmecIVa, and a typical PFGE pattern. The strain carried virulence genes pvl and ACME type I. Five SSTI episodes were documented despite successful resolution by antibiotic treatment, with and without incision and drainage. Conclusions: The source of the USA300 strain remains unknown. The isolate may represent a persistent strain capable of surviving extensive antibiotic pressure or a persistent environmental reservoir may be the source, possibly in the patient's household, from which bacteria were repeatedly introduced into the skin flora with subsequent infections. PMID:25668150

  11. Impact of Staphylococcus aureus on Pathogenesis in Polymicrobial Infections

    PubMed Central

    Nair, Nisha; Biswas, Raja; Götz, Friedrich

    2014-01-01

    Polymicrobial infections involving Staphylococcus aureus exhibit enhanced disease severity and morbidity. We reviewed the nature of polymicrobial interactions between S. aureus and other bacterial, fungal, and viral cocolonizers. Microbes that were frequently recovered from the infection site with S. aureus are Haemophilus influenzae, Enterococcus faecalis, Pseudomonas aeruginosa, Streptococcus pneumoniae, Corynebacterium sp., Lactobacillus sp., Candida albicans, and influenza virus. Detailed analyses of several in vitro and in vivo observations demonstrate that S. aureus exhibits cooperative relations with C. albicans, E. faecalis, H. influenzae, and influenza virus and competitive relations with P. aeruginosa, Streptococcus pneumoniae, Lactobacillus sp., and Corynebacterium sp. Interactions of both types influence changes in S. aureus that alter its characteristics in terms of colony formation, protein expression, pathogenicity, and antibiotic susceptibility. PMID:24643542

  12. Molecular epidemiologic study of community-associated methicillin-resistant Staphylococcus aureus with Panton-Valentine leukocidin gene among family members in Japan.

    PubMed

    Uehara, Yuki; Ito, Teruyo; Ogawa, Yu; Hirotaki, Shintaro; Shoji, Takayo; Tame, Tomoyuki; Horikoshi, Yuho; Hiramatsu, Keiichi

    2015-09-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the worldwide concerns of antimicrobial chemotherapy. An accumulation of ten patients in five families (A-E) suffering from skin and soft tissue infection (SSTI) of CA-MRSA was experienced in 2012, in Fuchu-shi, Tokyo, Japan. Molecular epidemiological investigation was performed for the 10 MRSA strains obtained from 8 children and 2 of their parents to assess endemic patterns of CA-MRSA in the community. Results of molecular typing, presence of toxin genes and antimicrobial susceptibilities were analyzed combined with the patients' clinical information. Each family had its own unique MRSA strain: A, ST30-SCCmec IVd; B, ST8-SCCmec IVd; C, ST8-SCCmec IVa; D, ST8-SCCmec IVl; E, ST8-SCCmec IVl and ST858-SCCmec IVl. Seven strains from the families A-C carried Panton-Valentine leukocidin gene. Three strains from the families D and E carried toxic shock syndrome toxin gene. Strains belonged to the same family demonstrated genetically related banding patterns of pulsed-filed gel electrophoresis. The family C experienced intrafamilial transmission of USA300-0114. Our data showed the MRSA clones disseminating in this community were highly diverse. They contained USA300-0114 clone, the rapidly distributing clone in the world, as well as MRSA clones identified in Japan. Our results suggested intrafamilial transmission of MRSA could be initial phenomenon of wide transmission in a community, therefore CA-MRSA SSTI in children and their family members should be monitored closely in order to notice the spread of highly pathogenic and transmittable strains. PMID:26091885

  13. Vitamin D sufficiency and Staphylococcus aureus infection in children.

    PubMed

    Wang, Jeffrey W; Hogan, Patrick G; Hunstad, David A; Fritz, Stephanie A

    2015-05-01

    Vitamin D promotes epithelial immunity by upregulating antimicrobial peptides, including LL-37, which have bactericidal activity against Staphylococcus aureus. We found that children with vitamin D deficiency or insufficiency [25-hydroxyvitamin D <30 ng/mL] were more likely to present with recurrent, rather than primary, S. aureus skin or soft tissue infection. Vitamin D sufficiency may be one of a myriad of host and environmental factors that can be directly impacted to reduce the frequency of S. aureus skin and soft tissue infection. PMID:25860535

  14. Staphylococcus aureus small colony variants in diabetic foot infections

    PubMed Central

    Cervantes-García, Estrella; García-Gonzalez, Rafael; Reyes-Torres, Angélica; Resendiz-Albor, Aldo Arturo; Salazar-Schettino, Paz María

    2015-01-01

    Background Staphylococcus aureus (S. aureus) is one of the major pathogens causing chronic infections. The ability of S. aureus to acquire resistance to a diverse range of antimicrobial compounds results in limited treatment options, particularly in methicillin-resistant S. aureus (MRSA). A mechanism by which S. aureus develops reduced susceptibility to antimicrobials is through the formation of small colony variants (SCVs). Infections by SCVs of S. aureus are an upcoming problem due to difficulties in laboratory diagnosis and resistance to antimicrobial therapy. Methods A prospective study was performed on 120 patients diagnosed with both type 2 diabetes mellitus and infected diabetic foot ulcers. The study was carried out from July 2012 to December 2013 in Hospital General de Mexico. The samples were cultured in blood agar, mannitol salt agar, and MacConkey agar media, and incubated at 37°C in aerobic conditions. Results We describe the first known cases of diabetic foot infections caused by MRSA-SCVs in patients diagnosed with type 2 diabetes mellitus and infected diabetic foot ulcers. In all of our cases, the patients had not received any form of gentamicin therapy. Conclusions The antibiotic therapy commonly used in diabetic patients with infected diabetic foot ulcers fails in the case of MRSA-SCVs because the intracellular location protects S. aureus-SCVs from the host's defenses and also helps them resist antibiotics. The cases studied in this article add to the spectrum of persistent and relapsing infections attributed to MRSA-SCVs and emphasizes that these variants may also play a relevant role in diabetic foot infections. PMID:25787018

  15. Staphylococcus aureus small colony variants in diabetic foot infections.

    PubMed

    Cervantes-García, Estrella; García-Gonzalez, Rafael; Reyes-Torres, Angélica; Resendiz-Albor, Aldo Arturo; Salazar-Schettino, Paz María

    2015-01-01

    Background : Staphylococcus aureus (S. aureus) is one of the major pathogens causing chronic infections. The ability of S. aureus to acquire resistance to a diverse range of antimicrobial compounds results in limited treatment options, particularly in methicillin-resistant S. aureus (MRSA). A mechanism by which S. aureus develops reduced susceptibility to antimicrobials is through the formation of small colony variants (SCVs). Infections by SCVs of S. aureus are an upcoming problem due to difficulties in laboratory diagnosis and resistance to antimicrobial therapy. Methods : A prospective study was performed on 120 patients diagnosed with both type 2 diabetes mellitus and infected diabetic foot ulcers. The study was carried out from July 2012 to December 2013 in Hospital General de Mexico. The samples were cultured in blood agar, mannitol salt agar, and MacConkey agar media, and incubated at 37°C in aerobic conditions. Results : We describe the first known cases of diabetic foot infections caused by MRSA-SCVs in patients diagnosed with type 2 diabetes mellitus and infected diabetic foot ulcers. In all of our cases, the patients had not received any form of gentamicin therapy. Conclusions : The antibiotic therapy commonly used in diabetic patients with infected diabetic foot ulcers fails in the case of MRSA-SCVs because the intracellular location protects S. aureus-SCVs from the host's defenses and also helps them resist antibiotics. The cases studied in this article add to the spectrum of persistent and relapsing infections attributed to MRSA-SCVs and emphasizes that these variants may also play a relevant role in diabetic foot infections. PMID:25787018

  16. Characterization of Staphylococcus aureus infections in children with Down syndrome.

    PubMed

    Johnston, Jeffrey N; Kaplan, Sheldon L; Mason, Edward O; Hulten, Kristina G

    2015-11-01

    Staphylococcus aureus infections in the Down syndrome (DS) population have not been well characterized. This study determined clinical and molecular characteristics of S. aureus infections in children with DS followed at Texas Children's Hospital (TCH), from 2001 to 2011. Patients were retrospectively identified from an ongoing S. aureus surveillance study. Medical records were reviewed. Isolates were characterized by antimicrobial susceptibility, pulsed-field gel electrophoresis patterns, and detection of PVL genes (pvl), mupA (high-level mupirocin resistance gene), smr (chlorhexidine resistance conferring gene), and Staphylococcal Chromosomal Cassette mec (SCCmec) type. Twenty-six patients with DS had a total of 34 S. aureus infections (8 recurrent); 61% were MRSA. DS patients represented 16.8 per 10,000 community onset S. aureus infections seen at TCH. Among 26 initial infections 17 were skin and soft tissue (SSTI), 7 were outer or middle ear and 2 were invasive infections. Seventeen patients were hospitalized. Thirteen (65%) of 20 available isolates were USA300, 14 were pvl+, 5 were mupA+, and 8 were smr+. Five of 8 (63%) recurrent infections were ear infections. All 4 recurrent ear isolates available for study were smr+, ciprofloxacin non-susceptible and treated with ciprofloxacin otic drops. S. aureus infections among patients with DS were similar in presentation to other patient groups, except for a greater proportion being associated with ear infections. Seventy percent of ear fluid isolates carried antiseptic and fluoroquinolone resistance genes. A study of a greater number of DS patients is warranted to further explore these findings. PMID:26386776

  17. Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community.

    PubMed

    Uhlemann, Anne-Catrin; Dordel, Janina; Knox, Justin R; Raven, Kathy E; Parkhill, Julian; Holden, Matthew T G; Peacock, Sharon J; Lowy, Franklin D

    2014-05-01

    During the last 2 decades, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have dramatically increased the global burden of S. aureus infections. The pandemic sequence type (ST)8/pulsed-field gel type USA300 is the dominant CA-MRSA clone in the United States, but its evolutionary history and basis for biological success are incompletely understood. Here, we use whole-genome sequencing of 387 ST8 isolates drawn from an epidemiological network of CA-MRSA infections and colonizations in northern Manhattan to explore short-term evolution and transmission patterns. Phylogenetic analysis predicted that USA300 diverged from a most common recent ancestor around 1993. We found evidence for multiple introductions of USA300 and reconstructed the phylogeographic spread of isolates across neighborhoods. Using pair-wise single-nucleotide polymorphism distances as a measure of genetic relatedness between isolates, we observed that most USA300 isolates had become endemic in households, indicating their critical role as reservoirs for transmission and diversification. Using the maximum single-nucleotide polymorphism variability of isolates from within households as a threshold, we identified several possible transmission networks beyond households. Our study also revealed the evolution of a fluoroquinolone-resistant subpopulation in the mid-1990s and its subsequent expansion at a time of high-frequency outpatient antibiotic use. This high-resolution phylogenetic analysis of ST8 has documented the genomic changes associated with USA300 evolution and how some of its recent evolution has been shaped by antibiotic use. By integrating whole-genome sequencing with detailed epidemiological analyses, our study provides an important framework for delineating the full diversity and spread of USA300 and other emerging pathogens in large urban community populations. PMID:24753569

  18. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

    PubMed Central

    Davis, Joshua S.; Eichenberger, Emily; Holland, Thomas L.

    2015-01-01

    SUMMARY Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions. PMID:26016486

  19. Antibiotic Combinations with Daptomycin for Treatment of Staphylococcus aureus Infections

    PubMed Central

    Nadrah, Kristina; Strle, Franc

    2011-01-01

    Daptomycin is a lipopeptide antibiotic with a unique mechanism of action on Gram-positive bacteria. It is approved for treatment of skin and soft-tissue infections with Gram-positive bacteria, bacteraemia and right-sided infective endocarditis caused by Staphylococcus aureus. Diminishing susceptibility of S. aureus to daptomycin during treatment of complicated infections and clinical failure have been described. Combinations of daptomycin with other antibiotics including gentamicin, rifampin, beta-lactams, trimethoprim/sulfamethoxazole (TMP-SMX), or clarithromycin present a new approach for therapy. In vitro and animal studies have shown that such combinations may, in some cases, be superior to daptomycin monotherapy. In this paper we focus on the antibiotic combinations for complicated S. aureus infections. PMID:22312555

  20. Acute haematogenous community-acquired methicillin-resistant Staphylococcus aureus osteomyelitis in an adult: Case report and review of literature

    PubMed Central

    2012-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) has of late emerged as a cause of community-acquired infections among immunocompetent adults without risk factors. Skin and soft tissue infections represent the majority of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clinical presentations, whilst invasive and life-threatening illness like necrotizing pneumonia, necrotizing fasciitis, pyomyositis, osteomyelitis and sepsis syndrome are less common. Although more widely described in the pediatric age group, the occurrence of CA-MRSA osteomyelitis in adults is an uncommonly reported entity. Case presentation We describe an invasive CA-MRSA infection in a 28 year-old previously healthy male, manifesting with bacteraemia, osteomyelitis of femur, pyomyositis and septic arthritis of the knee. Initially a preliminary diagnosis of osteosarcoma was suggested by imaging studies and patient underwent a bone biopsy. MRSA was subsequently isolated from blood cultures taken on day of admission, bone, tissue and pus cultures. Incision and drainage of abscess was performed and patient was treated with vancomycin, with fusidic acid added later. It took 6 months for the inflammatory markers to normalize, warranting 6-months of anti-MRSA therapy. Patient was a fervent deer hunter and we speculate that he acquired this infection from extensive direct contact with deer. Molecular characterization of this isolate showed that it belonged to multilocus sequence type (MLST) ST30 and exhibited the staphylococcal chromosome cassette mec (SCCmec) type IV, staphylococcus protein A (spa) type t019, accessory gene regulator (agr) type III and dru type dt10m. This strain harbored Panton-Valentine leukocidin (pvl) genes together with 3 other virulent genes; sei (enterotoxin), hlg (hemolysin) and fnbA (fibronectin binding protein). Conclusion This case study alerts physicians that beyond the most commonly encountered skin and soft tissue infections, pvl

  1. Antimicrobial susceptibility of Staphylococcus aureus and characterization of methicillin-resistant Staphylococcus aureus isolated from bovine mastitis in Korea.

    PubMed

    Nam, Hyang-Mi; Lee, Ae-Li; Jung, Suk-Chan; Kim, Mal-Nam; Jang, Geum-Chan; Wee, Sung-Hwan; Lim, Suk-Kyung

    2011-02-01

    A total of 402 Staphylococcus aureus isolates from bovine mastitis milk collected during 2003-2009 in Korea were tested for susceptibility to 20 antimicrobial agents. All S. aureus isolates were susceptible to 11 of 20 antimicrobials tested; no resistance was observed against pirlimycin, telithromycin, novobiocin, penicillin/novobiocin, quinupristin/dalfopristin, clindamycin, rifampin, ciprofloxacin, trimethprim/sulfamethoxazol, vancomycin, and linezolid. Over 66% of the S. aureus isolates were resistant to penicillin. Resistance was also seen for gentamicin (11.9%), erythromycin (7.7%), methicillin (oxacillin and cefoxitin, 6.2%), and tetracycline (4.2%). No noticeable change was observed in penicillin, gentamicin, and erythromycin resistance over the 7-year period. Tetracycline resistance appeared to decrease consistently, whereas methicillin resistance was observed from 2005. About 2.7% (11/402) were resistant to three or more antimicrobials. Genotyping of the 17 methicillin-resistant S. aureus (MRSA) isolated from each cow revealed two staphylococcal cassette chromosome mec (SCCmec) types (IV and IVa), three spa types (t286, t324, and untypable), and two sequence types (ST1 and ST72). Eleven of 17 (64.7%) MRSA strains belonged to SCCmec IVa-t324-ST72. The rest of strains belonged to SCCmec IVa-t286-ST1 (n = 3) and SCCmec IV-untypable-ST72 (n = 3). None of the MRSA carried the Panton-Valentine leukocidin gene. These characteristics are the same as those found in community-acquired (CA) MRSA strains prevalent in humans in Korea. Three pulsed-field gel electrophoresis types (A-C) were observed among the 17 MRSA strains examined, and 14 strains belonged to the same pulsed-field gel electrophoresis pattern regardless of their geographical origin and year of isolation. The results of this study provide evidence of CA-MRSA infection in dairy cattle for the first time in Korea. PMID:21034263

  2. Zosteriform Staphylococcus aureus Cutaneous Infection: Report of Two Patients With Dermatomal Bacterial Infection.

    PubMed

    Schepp, Elizabeth D; Cohen, Philip R

    2015-01-01

    The aim of this study was to describe cutaneous infections, which are zosteriform in distribution, including two patients with dermatomal Staphylococcus aureus infection. Herpes zoster infectious lesions usually occur in a dermatomal distribution. Other viruses, such as herpes simplex virus, can also appear with zosteriform lesions and closely mimic the clinical presentation of herpes zoster. Additionally, other skin infections, less commonly, are zosteriform. Two patients who developed zosteriform S aureus skin infection are described. A medical literature search for zosteriform dermatomal infections yielded other cutaneous infections with a zosteriform presentation. Two patients had S aureus and methicillin-resistant S aureus infection with skin lesions occupying the T11-T12 dermatomes and the T4 dermatome, respectively. They responded to antibacterial agents and adjuvant therapy. Patients with viral, fungal, and spirochete zosteriform infections are summarized. In addition to varicella-zoster virus infection, zosteriform skin infection can occur with viral (varicella-zoster virus, herpes simplex virus, and Epstein-Barr virus), superficial (dermatophyte), and deep (phaeohyphomycosis and zygomycosis) fungal, and bacterial (S aureus and methicillin-resistant S aureus) infections. These infections should be considered in the differential diagnosis of a zosteriform infection that does not present with the classic clinical picture for herpes zoster or that does not respond to standard treatments for varicellazoster virus. PMID:26861424

  3. Staphylococcus aureus infection of the feet following fish pedicure.

    PubMed

    Veraldi, S; Nazzaro, G; Çuka, E

    2014-10-01

    We report a case of Staphylococcus aureus infection of the feet that appeared after a "fish pedicure" (immersion of the feet in a tank with the fish Garra rufa, that nibbles off dead skin). Clinical picture was characterized by maceration, purulent discharge, scales, crusts, itching and burning sensation. Bacteriological examinations were positive for Staphylococcus aureus. Mycological examinations were negative. The patient was successfully treated with ciprofloxacin. Only one case of skin foot infection after fish pedicure was reported so far. Fish pedicure can be a potentially dangerous procedure in immunocompromised or diabetic patients. PMID:24771416

  4. The agr Inhibitors Solonamide B and Analogues Alter Immune Responses to Staphylococccus aureus but Do Not Exhibit Adverse Effects on Immune Cell Functions

    PubMed Central

    Baldry, Mara; Kitir, Betül; Frøkiær, Hanne; Christensen, Simon B.; Taverne, Nico; Meijerink, Marjolein; Franzyk, Henrik; Olsen, Christian A.; Wells, Jerry M.; Ingmer, Hanne

    2016-01-01

    Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure–function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization. PMID:26731096

  5. The agr Inhibitors Solonamide B and Analogues Alter Immune Responses to Staphylococccus aureus but Do Not Exhibit Adverse Effects on Immune Cell Functions.

    PubMed

    Baldry, Mara; Kitir, Betül; Frøkiær, Hanne; Christensen, Simon B; Taverne, Nico; Meijerink, Marjolein; Franzyk, Henrik; Olsen, Christian A; Wells, Jerry M; Ingmer, Hanne

    2016-01-01

    Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization. PMID:26731096

  6. Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.

    PubMed

    Cohen, Taylor S; Hilliard, Jamese J; Jones-Nelson, Omari; Keller, Ashley E; O'Day, Terrence; Tkaczyk, Christine; DiGiandomenico, Antonio; Hamilton, Melissa; Pelletier, Mark; Wang, Qun; Diep, Binh An; Le, Vien T M; Cheng, Lily; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2016-03-01

    Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists. PMID:26962155

  7. Nuclease Modulates Biofilm Formation in Community-Associated Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Kiedrowski, Megan R.; Kavanaugh, Jeffrey S.; Malone, Cheryl L.; Mootz, Joe M.; Voyich, Jovanka M.; Smeltzer, Mark S.; Bayles, Kenneth W.; Horswill, Alexander R.

    2011-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S. aureus strains, biofilm formation was inhibited. Following fractionation and mass spectrometry analysis, the major anti-biofilm factor identified in the spent media was secreted thermonuclease (Nuc). Considering reports that extracellular DNA (eDNA) is an important component of the biofilm matrix, we investigated the regulation and role of Nuc in USA300. The expression of the nuc gene was increased in a sigB mutant, repressed by glucose supplementation, and was unaffected by the agr quorum-sensing system. A FRET assay for Nuc activity was developed and confirmed the regulatory results. A USA300 nuc mutant was constructed and displayed an enhanced biofilm-forming capacity, and the nuc mutant also accumulated more high molecular weight eDNA than the WT and regulatory mutant strains. Inactivation of nuc in the USA300 sigB mutant background partially repaired the sigB biofilm-negative phenotype, suggesting that nuc expression contributes to the inability of the mutant to form biofilm. To test the generality of the nuc mutant biofilm phenotypes, the mutation was introduced into other S. aureus genetic backgrounds and similar increases in biofilm formation were observed. Finally, using multiple S. aureus strains and regulatory mutants, an inverse correlation between Nuc activity and biofilm formation was demonstrated. Altogether, our findings confirm the important role for eDNA in the S. aureus biofilm matrix and indicates Nuc is a regulator of biofilm formation. PMID:22096493

  8. Staphylococcus aureus Clumping Factor A Remains a Viable Vaccine Target for Prevention of S. aureus Infection

    PubMed Central

    Scully, Ingrid L.; Buurman, Ed T.; Eiden, Joseph; Jansen, Kathrin U.

    2016-01-01

    ABSTRACT In a recent article, X. Li et al. [mBio 7(1):e02232-15, 2016, http://dx.doi.org/10.1128/mBio.02232-15] investigate the utility of a vaccine composed of the Staphylococcus aureus protein clumping factor A (ClfA) in protecting mice from S. aureus infection. ClfA, one of the first proteins to be identified as a potential vaccine antigen for S. aureus prophylaxis, is currently a component of several investigational vaccines. The authors conclude that ClfA may not be effective for S. aureus prophylaxis. In contrast, previously published papers reporting positive data suggested that ClfA was potentially an important vaccine target to prevent invasive S. aureus disease. This commentary addresses the observed differences between the findings of Li et al. and those from other publications, highlighting the importance for preclinical vaccine antigen assessments to reflect the biological role of said antigen in virulence and, consequently, the importance of choosing appropriate preclinical disease models to test such antigens. PMID:26956591

  9. Methicillin-resistant Staphylococcus aureus in HIV-infected patients

    PubMed Central

    Hidron, Alicia I; Kempker, Russell; Moanna, Abeer; Rimland, David

    2010-01-01

    Concordant with the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting, colonization and infections with this pathogen have become a prevalent problem among the human immunodeficiency virus (HIV)-positive population. A variety of different host- and, possibly, pathogen-related factors may play a role in explaining the increased prevalence and incidence observed. In this article, we review pathophysiology, epidemiology, clinical manifestations, and treatment of MRSA in the HIV-infected population. PMID:21694896

  10. Community-Acquired Methicillin-Resistant "Staphylococcus aureus": Considerations for School Nurses

    ERIC Educational Resources Information Center

    Alex, Aniltta; Letizia, MariJo

    2007-01-01

    Methicillin-resistant "Staphylococcus aureus" (MRSA) is a disease-causing organism that has been present in hospital settings since the 1960s. However, a genetically distinct strain of MRSA, called community-acquired methicillin-resistant "Staphylococcus aureus" (CA-MRSA), has emerged in recent years in community settings among healthy…

  11. Polyclonal non multiresistant methicillin resistant Staphylococcus aureus isolates from clinical cases of infection occurring in Palermo, Italy, during a one-year surveillance period

    PubMed Central

    2012-01-01

    Background The evolving epidemiology of methicillin resistant Staphylococcus aureus (MRSA) is characterized by the emergence of infections caused by non multiresistant MRSA carrying staphylococcal chromosomal cassette (SCC)mec IV or V in the healthcare settings. A molecular epidemiological analysis of non multiresistant MRSA isolates from four acute general hospitals was performed in Palermo, Italy, during a one year period. Methods For the purpose of the study, MRSA isolates were defined as non multiresistant when they were susceptible to at least three classes of non β-lactam antibiotics. Seventy-five isolates were submitted to antimicrobial susceptibility testing, multilocus sequence typing (MLST) and polymerase chain reaction (PCR) for SCCmec, accessory gene regulator (agr) groups, arginine catabolic mobile element (ACME) and Panton Valentine leukocidin (PVL) toxin genes. For epidemiological typing, Multiple-Locus Variable-Number Tandem Repeat Fingerprinting (MLVF) was performed on all isolates and pulsed field gel electrophoresis (PFGE) on ST8 isolates. Results Non multiresistant MRSA isolates were isolated from all hospitals. Resistances to ciprofloxacin, macrolides and tetracycline were the most prevalent. MLST attributed 46 isolates with ST22, 13 with ST8, eight with ST1, three with ST50 and three with ST398. SCCmec type IV was found in all isolates. PVL was detected in one ST22 isolate. All isolates tested negative for the ACME element. MLVF identified 31 different patterns, some subtype clusters ranging in size between two and 22 isolates. The closely related PFGE patterns of the ST8 isolates differed from USA300. Conclusions A polyclonal circulation of non multiresistant MRSA along with blurring of boundaries between healthcare associated (HA)-MRSA and community associated (CA)-MRSA appear to be occurring in our epidemiological setting. A better understanding of spread of MRSA with the support of molecular typing can provide invaluable information in

  12. Characterization of methicillin resistant Staphylococcus aureus strains among inpatients and outpatients in a referral hospital in Tehran, Iran.

    PubMed

    Rahimi, Fateh; Shokoohizadeh, Leili

    2016-08-01

    Methicillin resistant Staphylococcus aureus is one of the most common causes of a variety of infections ranging from wound infections to urinary tract infections (UTI) in hospital and community. In this study during 3 years we characterized the antibiotic resistance patterns of 491 hospital acquired MRSA and community associated MRSA strains by the guidelines of clinical and laboratory standard institute. A combination of high resolution PhP typing method and SCCmec typing were used for clonal dissemination of isolates. Among all 491 MRSA strains, diverse PhP types consisting of 29 common types (CTs) and 4 single types (STs) and also 2 different SCCmec types (III and IVa) were detected. In addition, 18 CTs were common among CA- and HA-MRSA strains and the presence of all 4 STs was limited to HA-MRSA strains. All isolates were resistant to penicillin and high level resistance was observed against ciprofloxacin, erythromycin, tobramycin and kanamycin and the rate of resistance to most of the antibiotic tested among HA-MRSA was significantly higher than CA-MRSA isolates. Moreover, all isolates showed susceptibility to linezolid, vancomycin and quinupristin-dalfopristin and very low resistance to fusidic acid, nitrofurantoin and chloramphenicol were detected. Our findings illustrated the increasing rate of clonal dissemination and persistence of highly antibiotic resistant CA-MRSA strains in Tehran hospitals, and also indicated the important role of the hospitals as the reservoir of MRSA strains. PMID:27265678

  13. Characterization of Staphylococcus aureus Biofilm Formation in Urinary Tract Infection

    PubMed Central

    YOUSEFI, Masoud; POURMAND, Mohammad Reza; FALLAH, Fatemeh; HASHEMI, Ali; MASHHADI, Rahil; NAZARI-ALAM, Ali

    2016-01-01

    Background: The aim of this study was to investigate the antibiotic susceptibility pattern as well as the phenotypic and genotypic biofilm formation ability of Staphylococcus aureus isolates from patients with urinary tract infection (UTI). Methods: A total of 39 isolates of S. aureus were collected from patients with UTI. The antibiotic susceptibility patterns of the isolates were determined by the Kirby-Bauer disk-diffusion. We used the Modified Congo red agar (MCRA) and Microtiter plate methods to assess the ability of biofilm formation. All isolates were examined for determination of biofilm related genes, icaA, fnbA, clfA and bap using PCR method. Results: Linezolid, quinupristin/dalfopristin and chloramphenicol were the most effective agents against S. aureus isolates. Overall, 69.2% of S. aureus isolates were biofilm producers. Resistance to four antibiotics such as nitrofurantoin (71.4% vs. 28.6%, P=0.001), tetracycline (57.7% vs. 42.3%, P=0.028), erythromycin and ciprofloxacin (56% vs. 44%, P=0.017) was higher among biofilm producers than non-biofilm producers. The icaA, fnbA and clfA genes were present in all S. aureus isolates. However, bap gene was not detected in any of the isolates. Conclusion: Our findings reinforce the role of biofilm formation in resistance to antimicrobial agents. Trimethoprimsulfamethoxazole and doxycycline may be used as an effective treatment for UTI caused by biofilm producers S. aureus. Our results suggest that biofilm formation is not dependent to just icaA, fnbA, clfA and bap genes harbor in S. aureus strains. PMID:27252918

  14. Superantigen profiling of Staphylococcus aureus infective endocarditis isolates.

    PubMed

    Chung, Jin-Won; Karau, Melissa J; Greenwood-Quaintance, Kerryl E; Ballard, Alessandro D; Tilahun, Ashenafi; Khaleghi, Shahryar Rostamkolaei; David, Chella S; Patel, Robin; Rajagopalan, Govindarajan

    2014-06-01

    The frequency of superantigen production among Staphylococcus aureus isolates associated with endocarditis is not well defined. We tested 154 S. aureus isolates from definite infective endocarditis cases for the presence of staphylococcal enterotoxins A-E, H, and TSST-1 by PCR, enzyme-linked immunosorbent assay, and using an HLA-DR3 transgenic mouse splenocyte proliferation assay. Sixty-three isolates (50.8%) tested positive for at least 1 superantigen gene, with 21 (16.9%) testing positive for more than 2. tst (28.6%) was most common, followed by seb (27%), sea (22.2%), sed (20.6%), see (17.5%), and sec (11.1%). Of 41 methicillin-resistant S. aureus, 21 had superantigen genes, with sed being more frequently detected in this group compared to methicillin-susceptible S. aureus (P < 0.05). Superantigen genes were not associated with mortality (P = 0.81). 75% of PCR-positive isolates induced robust splenocyte proliferation. Overall, more than half of S. aureus isolates causing endocarditis carry superantigen genes, of which most are functional. PMID:24745820

  15. Demography and Intercontinental Spread of the USA300 Community-Acquired Methicillin-Resistant Staphylococcus aureus Lineage

    PubMed Central

    Glaser, Philippe; Martins-Simões, Patrícia; Villain, Adrien; Barbier, Maxime; Tristan, Anne; Bouchier, Christiane; Ma, Laurence; Bes, Michele; Laurent, Frederic; Guillemot, Didier; Wirth, Thierry

    2016-01-01

    ABSTRACT Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized worldwide during the 1990s; in less than a decade, several genetically distinct CA-MRSA lineages carrying Panton-Valentine leukocidin genes have emerged on every continent. Most notably, in the United States, the sequence type 18-IV (ST8-IV) clone known as USA300 has become highly prevalent, outcompeting methicillin-susceptible S. aureus (MSSA) and other MRSA strains in both community and hospital settings. CA-MRSA bacteria are much less prevalent in Europe, where the European ST80-IV European CA-MRSA clone, USA300 CA-MRSA strains, and other lineages, such as ST22-IV, coexist. The question that arises is whether the USA300 CA-MRSA present in Europe (i) was imported once or on very few occasions, followed by a broad geographic spread, anticipating an increased prevalence in the future, or (ii) derived from multiple importations with limited spreading success. In the present study, we applied whole-genome sequencing to a collection of French USA300 CA-MRSA strains responsible for sporadic cases and micro-outbreaks over the past decade and United States ST8 MSSA and MRSA isolates. Genome-wide phylogenetic analysis demonstrated that the population structure of the French isolates is the product of multiple introductions dating back to the onset of the USA300 CA-MRSA clone in North America. Coalescent-based demography of the USA300 lineage shows that a strong expansion occurred during the 1990s concomitant with the acquisition of the arginine catabolic mobile element and antibiotic resistance, followed by a sharp decline initiated around 2008, reminiscent of the rise-and-fall pattern previously observed in the ST80 lineage. A future expansion of the USA300 lineage in Europe is therefore very unlikely. PMID:26884428

  16. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection.

    PubMed

    Kim, Choon K; Karau, Melissa J; Greenwood-Quaintance, Kerryl E; Tilahun, Ashenafi Y; David, Chella S; Mandrekar, Jayawant N; Patel, Robin; Rajagopalan, Govindarajan

    2015-03-01

    Staphylococcus aureus is a common cause of prosthetic joint infection (PJI). The prevalence of superantigens (SAgs) among PJI-associated S. aureus is unknown. Eighty-four S. aureus isolates associated with PJI isolated between 1999 and 2006 were studied. SAg genes, sea, seb, sec, sed, see, seg, seh, sei, and tst, were assayed by PCR. Seventy-eight (92.9%) isolates carried at least 1 SAg gene studied, with 61 (72.6%) harboring more than 1. seg was most commonly (70.2%), and seh was least frequently (4.8%) detected. tst-positive isolates were associated with early infection and increased erythrocyte sedimentation rate at diagnosis (P=0.006 and P=0.021, respectively). seg and sei were associated with methicillin resistance (P=0.008 and P=0.002, respectively). A majority of PJI-associated isolates studied produced biologically active SAgs in both planktonic and biofilm growth modes. SAg genes are prevalent in S. aureus causing PJI. PMID:25619753

  17. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection

    PubMed Central

    Kim, Choon K.; Karau, Melissa J.; Greenwood-Quaintance, Kerryl E.; Tilahun, Ashenafi Y.; David, Chella S.; Mandrekar, Jayawant N.; Patel, Robin; Rajagopalan, Govindarajan

    2014-01-01

    Staphylococcus aureus is a common cause of prosthetic joint infection (PJI). The prevalence of superantigens (SAgs) among PJI-associated S. aureus is unknown. Eighty-four S. aureus isolates associated with PJI isolated between 1999 and 2006 were studied. SAg genes, sea, seb, sec, sed, see, seg, seh, sei and tst, were assayed by PCR. Seventy-eight (92.9%) isolates carried at least one SAg gene studied, with 61 (72.6%) harboring more than one. seg was most commonly (70.2%) and seh was least frequently (4.8%) detected. tst-positive isolates were associated with early infection and increased ESR at diagnosis (P = 0.006 and P = 0.021, respectively). seg and sei were associated with methicillin resistance (P = 0.008 and 0.002, respectively). SAg genes are prevalent in S. aureus causing PJI; a majority of PJI-associated isolates produce biologically active SAgs in both planktonic and biofilm growth modes. PMID:25619753

  18. Molecular epidemiology of methicillin-resistant Staphylococcus aureus in a university hospital in northwestern Spain.

    PubMed

    Ariza-Miguel, Jaime; Hernández, Marta; Fernández-Natal, Isabel; Rodríguez-Lázaro, David

    2014-09-01

    Continuous monitoring of methicillin-resistant Staphylococcus aureus (MRSA) is necessary to understand the clonal evolution of successful lineages. In this study, we identified the MRSA clones circulating in a Spanish hospital during a 2-year period, assessed their relationship with antimicrobial resistance profiles, and investigated the presence of the emerging community-associated and livestock-associated MRSA lineages (CA-MRSA, LA-MRSA). CC5-MRSA-IV isolates were the most frequently recovered, which supports the previously reported prevalence of this clone in Spanish hospitals. We observed ST125 isolates that harbored specific cassette chromosome recombinase (ccr) gene elements of the staphylococcal cassette chromosome mec (SCCmec) types IV and VI. That clone, which was first detected only recently, has increased resistance to erythromycin. Furthermore, 94% of the infections were caused by non-multiresistant isolates. Neither CA-MRSA nor LA-MRSA isolates were observed. These findings, along with related events over the last decade, suggest the establishment of a clonal endemic population in the Spanish clinical environment. PMID:26419454

  19. Population structure of methicillin-susceptible Staphylococcus aureus (MSSA) in Portugal over a 19-year period (1992-2011).

    PubMed

    Tavares, A; Faria, N A; de Lencastre, H; Miragaia, M

    2014-03-01

    Despite their clinical relevance, few studies have addressed the epidemiology of methicillin-susceptible S. aureus (MSSA). In particular, it is not clear how MSSA population structure has evolved over time and how it might have been shaped by the emergence of MRSA in the community (CA-MRSA). In the present study we have evaluated the MSSA population structure over time, its geographical distribution and relatedness with MRSA in Portugal. A total of 465 MSSA from infection and colonization, collected over a 19-year period (1992-2011) in the northern, central and southern regions of Portugal were analyzed. Isolates were characterized by spa typing and multilocus-sequence typing (MLST). Isolates with predominant spa types were characterized by pulsed-field gel electrophoresis (PFGE). Isolates relatedness was analyzed by eBURST and BURP. The 172 spa types found among the 465 MSSA were grouped into 18 spa-CC (clonal complexes). Ten clonal types were more prevalent (40 %): one major clone (ST30-t012) was present in the entire study period and all over the country and the other nine were intermittently detected over time (ST5-t002, ST8-t008, ST15-t084, ST34-t166, ST72-t148, ST1-t127, ST7-t091, ST398-t571 and ST34-t136). Interestingly, three MSSA clonal types observed only after 1996 were closely related with CA-MRSA epidemic strains (ST8-t008, ST72-t148 and ST1-t127) found currently in Portugal. The MSSA population in Portugal is genetically diverse; however, some dominant clonal types have been established and widely disseminated for almost two decades. We identified MSSA isolates that were related with emergent CA-MRSA clones found in Portugal. PMID:24057140

  20. Vitamin A deficiency predisposes to Staphylococcus aureus infection.

    PubMed Central

    Wiedermann, U; Tarkowski, A; Bremell, T; Hanson, L A; Kahu, H; Dahlgren, U I

    1996-01-01

    We have investigated the consequences of vitamin A deficiency in a rat model of T-cell-dependent and superantigen-mediated Staphylococcus aureus arthritis. After intravenous inoculation of enterotoxin A-producing staphylococci, the vitamin-A-deficient rats showed a decreased weight gain compared with the paired fed controls despite equal food consumption. The control rats developed arthritis in the first few days after bacterial inoculation, with a peak frequency at day 5, and then gradually recovered; however, the frequency of arthritis 18 days after bacterial inoculation was 86% among the vitamin A-deficient rats and 44% among the control rats. During this period, 3 of 10 deficient rats and 1 of 10 control rats died. Further in vitro analysis revealed that T-cell responses to S. aureus were significantly higher in the vitamin A-deficient rats than in the control animals. In contrast, B-cell reactivity, measured as immunoglobulin levels, autoantibody levels, and specific antibacterial antibody levels in serum, did not differ between the groups. Interestingly, the innate host defense mechanisms against S. aureus were also profoundly affected by vitamin A deficiency. Thus, despite a larger number of circulating phagocytic cells in the vitamin-A-deficient group, the capacity to phagocytize and exert intracellular killing of S. aureus was significantly decreased in comparison with the control rats. Furthermore, serum from the vitamin A-deficient rats inoculated with Staphylococcus aureus displayed decreased complement lysis activity. Our results suggest that the increased susceptibility to S. aureus infection observed in the vitamin-A-deficient rats is due to a concerted action of antigen-specific T-cell hyperactivity, impaired function of the phagocytes, and decreased complement activity. PMID:8557341

  1. Manipulation of Autophagy in Phagocytes Facilitates Staphylococcus aureus Bloodstream Infection

    PubMed Central

    O'Keeffe, Kate M.; Wilk, Mieszko M.; Leech, John M.; Murphy, Alison G.; Laabei, Maisem; Monk, Ian R.; Massey, Ruth C.; Lindsay, Jodi A.; Foster, Timothy J.; Geoghegan, Joan A.

    2015-01-01

    The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in the host. To date, the majority of work on S. aureus-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium. Using bone marrow-derived DCs (BMDCs), we demonstrate for the first time that DCs can effectively kill S. aureus but that certain strains of S. aureus have the capacity to evade DC (and macrophage) killing by manipulation of autophagic pathways. Strains with high levels of Agr activity were capable of causing autophagosome accumulation, were not killed by BMDCs, and subsequently escaped from the phagocyte, exerting significant cytotoxic effects. Conversely, strains that exhibited low levels of Agr activity failed to accumulate autophagosomes and were killed by BMDCs. Inhibition of the autophagic pathway by treatment with 3-methyladenine restored the bactericidal effects of BMDCs. Using an in vivo model of systemic infection, we demonstrated that the ability of S. aureus strains to evade phagocytic cell killing and to survive temporarily within phagocytes correlated with persistence in the periphery and that this effect is critically Agr dependent. Taken together, our data suggest that strains of S. aureus exhibiting high levels of Agr activity are capable of blocking autophagic flux, leading to the accumulation of autophagosomes. Within these autophagosomes, the bacteria are protected from phagocytic killing, thus providing an intracellular survival niche within professional phagocytes, which ultimately facilitates dissemination. PMID:26099586

  2. Fluoroquinolone Therapy in Staphylococcus aureus Infections: Where Do We Stand?

    PubMed Central

    Gade, Neeta D; Qazi, Mohiuddin S

    2013-01-01

    Aim: The study aimed to evaluate the utility of various commonly used fluoroquinolones against Staphylococcus aureus isolates. Materials and Methods: A total of 250 isolates of S. aureus were studied from different clinical specimens like blood, pus, wound swabs, sputum, ear swabs, and body fluids between November 2009 and December 2011. All the isolates were tested for their susceptibility to fluoroquinolones and other antimicrobial agents by Kirby-Bauer disc diffusion method using criteria of standard zone of inhibition. Methicillin-resistant S. aureus (MRSA) detection was done by cefoxitin disk diffusion method. The MRSA isolates were tested for minimum inhibitory concentration (MIC) to vancomycin by E-test strips. All the MRSA strains were sent to National Staphylococcal Phage-typing Centre, Maulana Azad Medical College, New Delhi for phage typing. Results: A total of 107 strains of S. aureus (42.8%) were detected as MRSA. Multidrug resistance was observed among the MRSA strains more commonly than among the MSSA stains. Among the fluoroquinolones, maximum resistance in MRSA was seen to ciprofloxacin (92.5%), followed by ofloxacin (80.4%). None of the S. aureus isolates showed resistance to vancomycin and linezolid. The MICs of vancomycin for the MRSA tested ranged from 0.5 to 2 μg/ml. Phage typing pattern of 107 MRSA isolates revealed that 37 (34.6%) MRSA isolates were nontypeable and 70 (65.4%) were typeable. Conclusion: Ciprofloxacin can no longer be used in empirical therapy against MRSA infections. Use of other members of fluoroquinolone should be limited only to those strains that show laboratory confirmation of their susceptibility. Vancomycin remains the drug of choice to treat MRSA infections. PMID:24701103

  3. Cataract surgery during active methicillin-resistant Staphylococcus aureus infection

    PubMed Central

    Mansour, Ahmad M; Salti, Haytham I

    2014-01-01

    We present two patients with active, foul-smelling, methicillin-resistant Staphylococcus aureus (MRSA) wounds of the forehead and sternum following craniotomy or open heart surgery. Both had debilitating cataracts and were told by the infectious diseases team that cataract surgery is very risky. Both underwent sequential bilateral phacoemulsification with no sign of infection. Patients with active MRSA wound infections may safely undergo cataract surgery with additional precautions observed intraoperatively (good wound construction) and postoperatively (topical antibiotics and close observation). Banning such surgeries can unnecessarily jeopardize the lifestyles of such patients. PMID:24790402

  4. Superior in vitro activity of carbapenems over anti-methicillin-resistant Staphylococcus aureus (MRSA) and some related antimicrobial agents for community-acquired MRSA but not for hospital-acquired MRSA.

    PubMed

    Takano, Tomomi; Higuchi, Wataru; Yamamoto, Tatsuo

    2009-02-01

    Eighty-eight strains of Panton-Valentine leukocidin (PVL)-positive and -negative community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and 152 strains of hospital-acquired MRSA (HA-MRSA) were examined for susceptibility to carbapenems, oxacillin, and other antimicrobial agents. CA-MRSA strains were more susceptible to carbapenems (MIC(90), 1-4 microg/ml) than HA-MRSA strains (MIC(90), 32-64 microg/ml). Among the carbapenems examined, CA-MRSA strains were most susceptible to imipenem (MIC(50), 0.12 microg/ml; MIC(90), 1 microg/ml). A similar tendency was observed with oxacillin, but less markedly (MIC(90): 32 microg/ml for CA-MRSA and > or =256 microg/ml for HA-MRSA). This difference was also observed between CA-MRSA and HA-MRSA in susceptibility levels to cephems, erythromycin, clindamycin, and levofloxacin, but not to ampicillin, vancomycin, teicoplanin, linezolid, and arbekacin. The data indicate that, in terms of MIC(50) or MIC(90) values, CA-MRSA is 64-256 times more susceptible to imipenem than HA-MRSA, and for CA-MRSA, some carbapenems, e.g., imipenem, show better in vitro activity than anti-MRSA or some related agents. PMID:19280303

  5. Identification of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

    NASA Astrophysics Data System (ADS)

    Kong, Cin; Rahman, Noorsaadah Abd; Nathan, Sheila

    2014-09-01

    The alarming increase of antibiotic-resistant Staphylococcus aureus and a delay in antibiotics development point to the need for novel therapeutic approaches to combat infection. To discover novel anti-infective agents, we screened a number of synthetic compounds comprising mainly of chalcone derivatives to explore their potential in promoting the survival of the nematode Caenorhabditis elegans upon infection by S. aureus. Screening of seven chalcone derivatives using both agar- and liquid-based assays revealed three positive hits that significantly prolonged the survival of S. aureus-infected nematodes. All the hits did not interfere with bacterial growth in vitro, proposing that the three compounds identified most probably act through mechanisms distinct from conventional antibiotics that target bacterial replication.

  6. Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections.

    PubMed

    Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves; Felden, Brice

    2016-09-01

    Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202

  7. Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections

    PubMed Central

    Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves

    2016-01-01

    Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202

  8. Personal Hygiene and Methicillin-resistant Staphylococcus aureus Infection

    PubMed Central

    Lin, Mei; Wolkoff, Barbara; Dodson, Douglas; Gladbach, Stephen; Zhu, Bao-Ping

    2006-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections outside the healthcare setting are an increasing concern. We conducted a case-control study to investigate an MRSA outbreak during 2002–2003 in a Missouri prison and focused on hygiene factors. Information on sociodemographic characteristics, medical history, and hygiene practices of study participants was collected by interview and medical record review. Logistic regression was used to evaluate MRSA infection in relation to hygiene factors individually and as a composite hygiene score; potential confounding factors were controlled. Selected MRSA isolates were analyzed by pulsed-field gel electrophoresis (PFGE). MRSA infection was significantly associated with a low composite hygiene score. Transmission among prison inmates appeared to be responsible for this outbreak. PFGE analysis showed that isolates were indistinguishable and associated with community-onset MRSA infections in other US prisons. Improving hygiene practices and environmental conditions may help prevent and interrupt future MRSA outbreaks in prison settings. PMID:16704779

  9. Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice.

    PubMed

    Lambrechts, Saskia A G; Demidova, Tatiana N; Aalders, Maurice C G; Hasan, Tayyaba; Hamblin, Michael R

    2005-07-01

    The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence. PMID:15986057

  10. Staphylococcus aureus Nasal Colonization and Subsequent Infection in Intensive Care Unit Patients: Does Methicillin Resistance Matter?

    PubMed Central

    Honda, Hitoshi; Krauss, Melissa J.; Coopersmith, Craig M.; Kollef, Marin H.; Richmond, Amy M.; Fraser, Victoria J.; Warren, David K.

    2014-01-01

    Objective Staphylococcus aureus is a significant cause of infection in intensive care unit (ICU) patients. Colonization with methicillin-resistant S. aureus (MRSA) is a risk factor for subsequent S. aureus infection. However, MRSA-colonized patients may have more co-morbidities than methicillin-susceptible S. aureus (MSSA)-colonized, or non-colonized patients and therefore more susceptible to infection on that basis. Design Prospective cohort study Setting A 24-bed surgical ICU (SICU) and 19-bed medical ICU (MICU) of a 1252-bed, academic hospital. Patients Patients had nasal swab cultures for S. aureus performed upon ICU admission from December 2002 to August 2007 Methods Patients in the ICU for > 48 hours were examined for an ICU-acquired S. aureus infection, defined as development of S. aureus infection > 48 hours after ICU admission. Results One thousand four hundred thirty-three (27.8%) of 5,161 patients had S. aureus colonization at admission [674 (47.0%) with MRSA; 759 (53.0%) with MSSA]. An ICU-acquired S. aureus infection developed in 113 (2.2%) patients. 75 (66.4%) of 113 had an infection due to MRSA. Risk factors associated with an ICU-acquired S. aureus infection included MRSA colonization at admission [adjusted hazard ratio (aHR), 4.70; 95% confidence interval (CI), 3.07–7.21] and MSSA colonization at admission (aHR, 2.47; 95% CI, 1.52–4.01). Conclusion ICU patients colonized with S. aureus were at greater risk of developing a S. aureus infection in the ICU. Even after adjusting for patient-specific risk factors, MRSA-colonized patients were more likely to develop S. aureus infection compared to MSSA-colonized or non-colonized patients. PMID:20426656

  11. Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

    PubMed Central

    2014-01-01

    Background The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen. Methods We established a C. elegans – S. aureus liquid-based assay to screen for potential anti-infectives against S. aureus. The assay was utilized to screen 37 natural extracts and 29 synthetic compounds for the ability to extend the lifespan of infected nematodes. Disc diffusion and MIC microdilution tests were used to evaluate the anti-microbial properties of these natural extracts and synthetic compounds whilst in vivo bacterial CFU within the C. elegans gut were also enumerated. Results We screened a total of 37 natural extracts and 29 synthetic compounds for anti-infective properties. The screen successfully revealed 14 natural extracts from six plants (Nypa fruticans, Swietenia macrophylla, Curcuma longa, Eurycoma longifolia, Orthosiphon stamineus and Silybum eburneum) and one marine sample (Faunus ater) that improved the survival of S. aureus-infected worms by at least 2.8-fold as well as 14 synthetic compounds that prolonged the survival of S. aureus-infected nematodes by 4-fold or greater. An anti-microbial screen of all positive hits demonstrated that 8/28 hits had no effect on S. aureus growth. Of these 8 candidates, 5 of them also protected the worms from MRSA infection. We also noted that worms exposed to N. fruticans root and O. stamineus leaf extracts showed reduced intestinal colonization by live S. aureus. This suggests that these extracts could possibly activate host immunity to eliminate the bacteria or interfere with factor/s that prevents pathogen accumulation. Conclusion We have successfully

  12. Draft Genome Sequence of Isolate Staphylococcus aureus LHSKBClinical, Isolated from an Infected Hip

    PubMed Central

    Stipetic, Laurence H.; Hamilton, Graham; Dalby, Matthew J.; Davies, Robert L.; Meek, R. M. Dominic; Ramage, Gordon; Smith, David G. E.

    2015-01-01

    We report here the genome sequence of a clinical isolate of Staphylococcus aureus from an orthopedic infection. Phenotypically diverse Staphylococcus aureus strains are associated with orthopedic infections and subsequent implant failure, and some are highly resistant to antibiotics. This genome sequence will support further analyses of strains causing orthopedic infections. PMID:25931597

  13. Staphylococcus aureus Panton-Valentine Leukocidin Is a Very Potent Cytotoxic Factor for Human Neutrophils

    PubMed Central

    Löffler, Bettina; Hussain, Muzaffar; Grundmeier, Matthias; Brück, Michaela; Holzinger, Dirk; Varga, Georg; Roth, Johannes; Kahl, Barbara C.; Proctor, Richard A.; Peters, Georg

    2010-01-01

    The role of the pore-forming Staphylococcus aureus toxin Panton-Valentine leukocidin (PVL) in severe necrotizing diseases is debated due to conflicting data from epidemiological studies of community-associated methicillin-resistant S. aureus (CA-MRSA) infections and various murine disease-models. In this study, we used neutrophils isolated from different species to evaluate the cytotoxic effect of PVL in comparison to other staphylococcal cytolytic components. Furthermore, to study the impact of PVL we expressed it heterologously in a non-virulent staphylococcal species and examined pvl-positive and pvl-negative clinical isolates as well as the strain USA300 and its pvl-negative mutant. We demonstrate that PVL induces rapid activation and cell death in human and rabbit neutrophils, but not in murine or simian cells. By contrast, the phenol-soluble modulins (PSMs), a newly identified group of cytolytic staphylococcal components, lack species-specificity. In general, after phagocytosis of bacteria different pvl-positive and pvl-negative staphylococcal strains, expressing a variety of other virulence factors (such as surface proteins), induced cell death in neutrophils, which is most likely associated with the physiological clearing function of these cells. However, the release of PVL by staphylococcal strains caused rapid and premature cell death, which is different from the physiological (and programmed) cell death of neutrophils following phagocytosis and degradation of virulent bacteria. Taken together, our results question the value of infection-models in mice and non-human primates to elucidate the impact of PVL. Our data clearly demonstrate that PVL acts differentially on neutrophils of various species and suggests that PVL has an important cytotoxic role in human neutrophils, which has major implications for the pathogenesis of CA-MRSA infections. PMID:20072612

  14. Longitudinal Antibiotic Susceptibility Profiles of Staphylococcus aureus Cutaneous Infections in a Pediatric Outpatient Population.

    PubMed

    Slater, Nathaniel A; Gilligan, Peter H; Morrell, Dean S

    2016-09-01

    This longitudinal update on Staphylococcus aureus prevalence and antibiotic resistance patterns surveyd 291 cultures from 188 patients in a pediatric outpatient dermatology clinic with suspected skin and soft tissue infections. The prevalence of methicillin-resistant Staphylococcus aureus remained stable at 24%. Staphylococcus aureus resistance to tetracyclines modestly but demonstrably increased in the interval since 2009. PMID:27384814

  15. Molecular characterization of methicillin-resistant Staphylococcus aureus isolated from tertiary care hospitals

    PubMed Central

    Asghar, Atif H.

    2014-01-01

    Background and Objectives: Methicillin-resistant S. aureus (MRSA) tends to be resistant to multiple antibiotics. Methicillin resistance is conferred by the acquisition of the mecA gene, which is carried by a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec). There are five major types of SCCmec elements (I–V). The majority of hospital-acquired MRSA (HA-MRSA) strains carry SCCmec types I, II, or III, whereas community-acquired MRSA (CA-MRSA) strains carry SCCmec types IV or V. In addition, Panton-Valentine Leucocidin (PVL) is a gene encoding a powerful cytotoxin that is strongly associated with CA-MRSA strains. The present study was aimed to identify the types of SCCmec and PVL genes among clinical MRSA isolates. Methods: This study was conducted in 5 tertiary care hospitals in Makkah city from March to September of 2012. A total of 206 S. aureus clinical isolates were analysed using standard microbiological methods. Multiplex PCR was performed on genomic DNA from MRSA isolates in order to identify the types of SCCmec. In addition, PCR was performed to detect the PVL gene among the isolates. Results: Of the 206 S. aureus isolates, 114 (55.3%) were MRSA, and 100 of the MRSA isolates carried the mecA gene. Results from SCCmec typing revealed that 3% were type I; 9% were type II; 47% were type III, and 29% were type IV. Nineteen per cent of the isolates harboured the PVL gene. Furthermore, there was a statistically significant correlation between the presence of the PVL gene and SCCmec type IV. Conclusion: The virulence of MRSA strains is increasing in both hospital and community settings in Makkah, highlighting the importance of their rapid identification in order to appropriately control infection. PMID:25097499

  16. Blue Light Phototherapy Kills Methycillin Resistant Staphylococcus Aureus (MRSA)

    NASA Astrophysics Data System (ADS)

    Enwemeka, Chukuka S.; Williams, Debora; Enwemeka, Sombiri K.; Hollosi, Steve; Yens, David

    2010-05-01

    Background: Methycillin resistant staphylococcus aureus (MRSA) bacteria continue to defy most available antibiotics. As a result infections with MRSA remain a growing public health concern. As a paradigm shift and a significant departure from the on-going trend to develop stronger drug-based therapies, we studied the effect of 405 nm and 470 nm wavelengths of blue light on two strains of MRSA—US-300 strain of CA-MRSA and the IS853 strain of HA-MRSA—in vitro. Methods: We cultured and plated each strain, following which bacteria colonies were irradiated with 0, 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 25, 30, 35, 40, 45, 50, 55, or 60 Jcm-2 energy densities—just once. Specimens were incubated at 35° C for 24 h. Then, digital images obtained were quantified to obtain colony counts and the aggregate area occupied by bacteria colonies. Results: Each wavelength produced a statistically significant dose-dependent reduction in both the number and the aggregate area of colonies formed by each bacteria strain (P<0.001). Maximum eradication of the US-300 (92.1%) and the IS-853 colonies (93.5%) was achieved within 10 minutes of irradiation with each wavelength. The longer the irradiation the more bacteria were eradicated. However, the effect was non-linear as increases of energy densities between 1.0 and 15 J cm-2 resulted in more bacteria death than similar increases between 15 J cm-2 and 60 J cm-2. Conclusion: At low doses, blue light photo-destroys HA-MRSA and CA-MRSA in vitro; raising the prospect that phototherapy may be an effective clinical tool in the on-going effort to stem MRSA infections.

  17. Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection

    PubMed Central

    Fu, Xiu-jun; Fang, Yong; Yao, Min

    2013-01-01

    Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug resistant bacteria both in hospitals and in the community. In the last two decades, there has been growing concern about the increasing resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection poses a serious problem for physicians and their patients. Photosensitizer-mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and innovative approach for treating multidrug resistant infection. In spite of encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large in vitro studies, there are only few in vivo studies. Therefore, applying PDT in the clinic for MRSA infection is still a long way off. PMID:23555074

  18. Staphylococcus aureus infections: transmission within households and the community

    PubMed Central

    Knox, Justin; Uhlemann, Anne-Catrin; Lowy, Franklin D.

    2015-01-01

    Staphylococcus aureus , both methicillin susceptible and resistant, are now major community-based pathogens worldwide. The basis for this is multifactorial and includes the emergence of epidemic clones with enhanced virulence, antibiotic resistance, colonization potential, or transmissibility. Household reservoirs of these unique strains are crucial to their success as community-based pathogens. Staphylococci become resident in households, either as colonizers or environmental contaminants, increasing the risk for recurrent infections. Interactions of household members with others in different households or at community sites including schools and daycare facilities play a critical role in the ability of these strains to become endemic. Colonization density at these sites appears to play an important role in facilitating transmission. The integration of research tools including whole genome sequencing, mathematical modeling and social network analysis have provided additional insight into the transmission dynamics of these strains. Thus far, interventions designed to reduce recurrent infections among household members have had limited success, likely due to the multiplicity of potential sources for recolonization. The development of better strategies to reduce the number of household-based infections will depend on greater insight into the different factors that contribute to the success of these uniquely successful epidemic clones of S. aureus. PMID:25864883

  19. Staphylococcus aureus infections: transmission within households and the community.

    PubMed

    Knox, Justin; Uhlemann, Anne-Catrin; Lowy, Franklin D

    2015-07-01

    Staphylococcus aureus, both methicillin susceptible and resistant, are now major community-based pathogens worldwide. The basis for this is multifactorial and includes the emergence of epidemic clones with enhanced virulence, antibiotic resistance, colonization potential, or transmissibility. Household reservoirs of these unique strains are crucial to their success as community-based pathogens. Staphylococci become resident in households, either as colonizers or environmental contaminants, increasing the risk for recurrent infections. Interactions of household members with others in different households or at community sites, including schools and daycare facilities, have a critical role in the ability of these strains to become endemic. Colonization density at these sites appears to have an important role in facilitating transmission. The integration of research tools, including whole-genome sequencing (WGS), mathematical modeling, and social network analysis, has provided additional insight into the transmission dynamics of these strains. Thus far, interventions designed to reduce recurrent infections among household members have had limited success, likely due to the multiplicity of potential sources for recolonization. The development of better strategies to reduce the number of household-based infections will depend on greater insight into the different factors that contribute to the success of these uniquely successful epidemic clones of S. aureus. PMID:25864883

  20. Antimicrobial susceptibility patterns of community- and hospital-acquired methicillin-resistant Staphylococcus aureus from United States Hospitals: results from the AWARE Ceftaroline Surveillance Program (2012-2014).

    PubMed

    Sader, Helio S; Mendes, Rodrigo E; Jones, Ronald N; Flamm, Robert K

    2016-09-01

    Among 8437 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 143 medical centers in the United States (2012-2014), 7116 and 1321 were reported as community-acquired (CA) and hospital-acquired (HA) MRSA, respectively. CA-/HA-MRSA were most often isolated from patients with skin and skin structure infections (SSSI; 68.4/26.9%), pneumonia (13.7/49.0%) and bacteremia (10.0/17.7%). Overall, susceptibility rates were generally lower among HA-MRSA compared to CA-MRSA strains, especially for clindamycin (44.6 vs. 66.1%) and levofloxacin (21.4 vs. 35.5%). Also, susceptibility rates were lower for these two compounds among isolates from pneumonia compared to SSSI and bacteremia. Ceftaroline was broadly active against 98.0% of CA-MRSA and 94.3% of HA-MRSA (MIC50/90, 1μg/mL for both; no resistant isolate) overall, with little variation among infection type subsets. PMID:27394637

  1. Schistosoma spindale infection in a captive jackal (Canis aureus).

    PubMed

    Vimalraj, P G; Latchumikanthan, A

    2015-03-01

    This report is based on the findings from a captive jackal (Canis aureus) housed in Amirthi Zoological Park, Javadu Hills, Vellore. The animal was reported to be dull, depressed and also had diarrhea. Fecal samples were collected in 10 % formalin and subjected to direct and sedimentation method of faecal examination and was examined for endoparasitic infection. Surprisingly, fecal examination revealed two spindle shaped eggs having terminal spine with a size of 250μ by 60μ. The eggs were identified as belonging to Schistosoma spindale and as per the standard keys (Soulsby 1982). PMID:25698875

  2. Staphylococcus aureus Colonization in Children with Community-Associated Staphylococcus aureus Skin Infections and Their Household Contacts

    PubMed Central

    Fritz, Stephanie A.; Hogan, Patrick G.; Hayek, Genevieve; Eisenstein, Kimberly A.; Rodriguez, Marcela; Krauss, Melissa; Garbutt, Jane; Fraser, Victoria J.

    2013-01-01

    Objectives To measure prevalence of Staphylococcus aureus colonization in household contacts of children with acute S. aureus skin and soft tissue infections (SSTI), determine risk factors for S. aureus colonization in household contacts, and assess anatomic sites of S. aureus colonization in patients and household contacts. Design Cross-sectional study. Setting St. Louis Children’s Hospital Emergency Department and ambulatory wound center and nine community pediatric practices affiliated with a practice-based research network. Participants Patients with community-associated S. aureus SSTI and S. aureus colonization (in the nose, axilla, and/or inguinal folds) and their household contacts. Outcome Measures Colonization of household contacts of pediatric patients with S. aureus colonization and SSTI. Results Of 183 index patients, 61% were colonized with methicillin-resistant S. aureus (MRSA), 30% with methicillin-sensitive S. aureus (MSSA), and 9% with both MRSA and MSSA. Of 609 household contacts, 323 (53%) were colonized with S. aureus: 115 (19%) with MRSA, 195 (32%) with MSSA, and 13 (2%) with both. Parents were more likely than other household contacts to be colonized with MRSA (OR 1.72, 95% CI 1.12, 2.63). MRSA colonized the inguinal folds more frequently than MSSA (OR 1.67, 95% CI 1.16, 2.41), and MSSA colonized the nose more frequently than MRSA (OR 1.75, 95% CI 1.19, 2.56). Conclusions Household contacts of children with S. aureus SSTI had a high rate of MRSA colonization compared to the general population. The inguinal fold is a prominent site of MRSA colonization, which may be an important consideration for active surveillance programs in hospitals. PMID:22665030

  3. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

    PubMed Central

    Lalor, Stephen J.; Leech, John M.; O’Keeffe, Kate M.; Mac Aogáin, Micheál; O’Halloran, Dara P.; Lacey, Keenan A.; Tavakol, Mehri; Hearnden, Claire H.; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P.; van Wamel, Willem J.; Foster, Timothy J.; Geoghegan, Joan A.; Lavelle, Ed C.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

  4. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

    PubMed

    Brown, Aisling F; Murphy, Alison G; Lalor, Stephen J; Leech, John M; O'Keeffe, Kate M; Mac Aogáin, Micheál; O'Halloran, Dara P; Lacey, Keenan A; Tavakol, Mehri; Hearnden, Claire H; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P; van Wamel, Willem J; Foster, Timothy J; Geoghegan, Joan A; Lavelle, Ed C; Rogers, Thomas R; McLoughlin, Rachel M

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

  5. Clearance of experimental cutaneous Staphylococcus aureus infections in mice

    PubMed Central

    Onunkwo, Charles C.; Hahn, Beth L.

    2010-01-01

    Staphylococcal skin infections are quite common in human patients. These infections often clear spontaneously, but may also progress locally and/or disseminate to cause serious and sometimes fatal deep infections. The present studies were undertaken to examine the clearance phase of experimental cutaneous Staphylococcus aureus infections in a mouse model system. Previous work in this system has shown that staphylococci applied to the skin rapidly disseminate to the spleen and kidney. In the present experiments the bacteria were found to persist at the skin infection site at a time (8 days after inoculation) when they had disappeared from the spleen and kidney. Examination of the infected skin at earlier times revealed rapid (within 6 h) invasion into the stratum corneum, stratum Malpighii, and dermis, but subsequent redistribution of bacteria (at 1–2 days) to more superficial sites, particularly crusts located just above the skin surface. The crusts seen in these infections were of two distinct types, which were termed type 1 and type 2. Type 1 crusts appeared first, consisted of bacteria, inflammatory cells, and debris, and developed over an intact epidermis. Type 2 crusts arose from the process of dermal necrosis previously reported to take place at 2 days in this model system. In the latter situation the bacteria were not really cleared from the epidermis and dermis; rather those layers were transformed into a superficial crust that contained the bacteria. Deep hair follicle infections in the dermis were found in these infections, but they did not persist and did not seem to be a reservoir for organisms in the dermis. Resolution of these experimental infections appeared to involve redistribution of invading bacteria to more superficial locations in crusts above the skin surface, marked proliferation of the epidermis, loss of the bacteria-laden crusts from the skin, and eventual healing of the cutaneous damage. PMID:20130894

  6. Use of mupirocin-chlorhexidine treatment to prevent Staphylococcus aureus surgical-site infections.

    PubMed

    Bertrand, X; Slekovec, C; Talon, D

    2010-05-01

    Evaluation of: Bode LGM, Kluytmans JAJW, Wertheim HFL et al.: Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N. Engl. J. Med. 362, 9-17 (2010). Staphylococcus aureus is the main pathogen responsible for surgical-site infections and nasal carriage is a major risk factor for subsequent infection with this bacteria. Mupirocin is considered to be the topical antibacterial agent of choice for eradication of nasal S. aureus. The paper by Bode et al. provides strong evidence that the combination of a rapid identification of a S. aureus nasal carrier, mupirocin nasal ointment and chlorhexidine gluconate soap, significantly reduces the rate of S. aureus surgical-site infection by nearly 60%. In conclusion, mupirocin nasal ointment use in S. aureus carriers before surgery has numerous advantages with few side effects. PMID:20441543

  7. MOLECULAR CHARACTERIZATION OF STAPHYLOCOCCUS AUREUS STRAINS ISOLATED FROM INFECTIVE ENDOCARDITIS.

    PubMed

    Oprea, Mihaela; Patriche, David Sebastian; Străuţ, Monica; Antohe, Felicia

    2014-01-01

    Infective endocarditis (IE) is an infection of the heart endothelium and valves and is frequently a consequence of a sanguine flow turbulence and injury of endocardium. Recent studies revealed an increase of Staphylococcus aureus strains involved in IE, but no evident correlations between the genetic background of this bacterium and IE involvement of certain strains have been found yet. In this study we analyzed the virulence profile, including adhesins, exotoxins, superantigens and biofilm determinants, along with agr type detection, for S. aureus strains isolated from IE, versus non-IE originating strains. We performed also bacterial typing (SCCmec typing, spa-typing and MLST typing), in order to compare our strains with international databases repositories. Although the study was carried out on a reduced number of isolates, our observations confirm the previous works, showing that no major differences were observed between the genetic backgrounds of the two groups of strains analyzed. Notably, the added value of this study was optimization of two new multiplex PCR protocols, and the enrichment of international databases with three new spa-types, three new MLST alleles and four new MLST sequence types. PMID:26201122

  8. [Clonal eosinophilia revealed by recurrent Staphylococcus aureus infection].

    PubMed

    Vandenbos, F; Figueredo, M; Dumon-Gubeno, M-C; Nicolle, I; Tarhini, A; Medioni, L-D; Naman, H; Mouroux, J

    2011-06-01

    Acquired eosinophilia is currently classified into secondary (reactional to underlying diseases), clonal (presence of a bone marrow histological, cytogenetic or molecular marker of a myeloid malignancy) and idiopathic (neither secondary nor clonal) categories. We report the case of a 47-year-old male who was admitted to the hospital for Staphylococcus aureus recurring infections. An hypereosinophilia was discovered and led to molecular analysis. The identification of FIP1L1-PDGFRA fusion gene permitted the diagnostic of clonal eosinophilia. Treatment by imatinib mesylate induced an haematological remission, the control of the infection and thoracotomy cicatrization. This case is original because of its infectious presentation and the efficacy of imatinib mesylate to control the infectious process. PMID:21665081

  9. Beta-Hemolysin Promotes Skin Colonization by Staphylococcus aureus

    PubMed Central

    Katayama, Yuki; Sekine, Miwa; Fukuda, Minoru; Hiramatsu, Keiichi

    2013-01-01

    Colonization by Staphylococcus aureus is a characteristic feature of several inflammatory skin diseases and is often followed by epidermal damage and invasive infection. In this study, we investigated the mechanism of skin colonization by a virulent community-acquired methicillin-resistant S. aureus (CA-MRSA) strain, MW2, using a murine ear colonization model. MW2 does not produce a hemolytic toxin, beta-hemolysin (Hlb), due to integration of a prophage, ϕSa3mw, inside the toxin gene (hlb). However, we found that strain MW2 bacteria that had successfully colonized murine ears included derivatives that produced Hlb. Genome sequencing of the Hlb-producing colonies revealed that precise excision of prophage ϕSa3mw occurred, leading to reconstruction of the intact hlb gene in their chromosomes. To address the question of whether Hlb is involved in skin colonization, we constructed MW2-derivative strains with and without the Hlb gene and then subjected them to colonization tests. The colonization efficiency of the Hlb-producing mutant on murine ears was more than 50-fold greater than that of the mutant without hlb. Furthermore, we also showed that Hlb toxin had elevated cytotoxicity for human primary keratinocytes. Our results indicate that S. aureus Hlb plays an important role in skin colonization by damaging keratinocytes, in addition to its well-known hemolytic activity for erythrocytes. PMID:23292775

  10. Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution.

    PubMed

    Khokhlova, Olga E; Hung, Wei-Chun; Wan, Tsai-Wen; Iwao, Yasuhisa; Takano, Tomomi; Higuchi, Wataru; Yachenko, Svetlana V; Teplyakova, Olga V; Kamshilova, Vera V; Kotlovsky, Yuri V; Nishiyama, Akihito; Reva, Ivan V; Sidorenko, Sergey V; Peryanova, Olga V; Reva, Galina V; Teng, Lee-Jene; Salmina, Alla B; Yamamoto, Tatsuo

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a common multidrug-resistant (MDR) pathogen. We herein discussed MRSA and its infections in Krasnoyarsk, Siberian Russia between 2007 and 2011. The incidence of MRSA in 3,662 subjects was 22.0% and 2.9% for healthcare- and community-associated MRSA (HA- and CA-MRSA), respectively. The 15-day mortality rates for MRSA hospital- and community-acquired pneumonia (HAP and CAP) were 6.5% and 50%, respectively. MRSA CAP cases included pediatric deaths; of the MRSA pneumonia episodes available, ≥27.3% were associated with bacteremia. Most cases of HA-MRSA examined exhibited ST239/spa3(t037)/SCCmecIII.1.1.2 (designated as ST239Kras), while all CA-MRSA cases examined were ST8/spa1(t008)/SCCmecIV.3.1.1(IVc) (designated as ST8Kras). ST239Kras and ST8Kras strongly expressed cytolytic peptide (phenol-soluble modulin α, PSMα; and δ-hemolysin, Hld) genes, similar to CA-MRSA. ST239Kras pneumonia may have been attributed to a unique set of multiple virulence factors (MVFs): toxic shock syndrome toxin-1 (TSST-1), elevated PSMα/Hld expression, α-hemolysin, the staphylococcal enterotoxin SEK/SEQ, the immune evasion factor SCIN/SAK, and collagen adhesin. Regarding ST8Kras, SEA was included in MVFs, some of which were common to ST239Kras. The ST239Kras (strain OC3) genome contained: a completely unique phage, φSa7-like (W), with no att repetition; S. aureus pathogenicity island SaPI2R, the first TSST-1 gene-positive (tst+) SaPI in the ST239 lineage; and a super copy of IS256 (≥22 copies/genome). ST239Kras carried the Brazilian SCCmecIII.1.1.2 and United Kingdom-type tst. ST239Kras and ST8Kras were MDR, with the same levofloxacin resistance mutations; small, but transmissible chloramphenicol resistance plasmids spread widely enough to not be ignored. These results suggest that novel MDR and MVF+ HA- and CA-MRSA (ST239Kras and ST8Kras) emerged in Siberian Russia (Krasnoyarsk) associated with fatal pneumonia, and also with ST

  11. Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution

    PubMed Central

    Khokhlova, Olga E.; Hung, Wei-Chun; Wan, Tsai-Wen; Iwao, Yasuhisa; Takano, Tomomi; Higuchi, Wataru; Yachenko, Svetlana V.; Teplyakova, Olga V.; Kamshilova, Vera V.; Kotlovsky, Yuri V.; Nishiyama, Akihito; Reva, Ivan V.; Sidorenko, Sergey V.; Peryanova, Olga V.; Reva, Galina V.; Teng, Lee-Jene; Salmina, Alla B.; Yamamoto, Tatsuo

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a common multidrug-resistant (MDR) pathogen. We herein discussed MRSA and its infections in Krasnoyarsk, Siberian Russia between 2007 and 2011. The incidence of MRSA in 3,662 subjects was 22.0% and 2.9% for healthcare- and community-associated MRSA (HA- and CA-MRSA), respectively. The 15-day mortality rates for MRSA hospital- and community-acquired pneumonia (HAP and CAP) were 6.5% and 50%, respectively. MRSA CAP cases included pediatric deaths; of the MRSA pneumonia episodes available, ≥27.3% were associated with bacteremia. Most cases of HA-MRSA examined exhibited ST239/spa3(t037)/SCCmecIII.1.1.2 (designated as ST239Kras), while all CA-MRSA cases examined were ST8/spa1(t008)/SCCmecIV.3.1.1(IVc) (designated as ST8Kras). ST239Kras and ST8Kras strongly expressed cytolytic peptide (phenol-soluble modulin α, PSMα; and δ-hemolysin, Hld) genes, similar to CA-MRSA. ST239Kras pneumonia may have been attributed to a unique set of multiple virulence factors (MVFs): toxic shock syndrome toxin-1 (TSST-1), elevated PSMα/Hld expression, α-hemolysin, the staphylococcal enterotoxin SEK/SEQ, the immune evasion factor SCIN/SAK, and collagen adhesin. Regarding ST8Kras, SEA was included in MVFs, some of which were common to ST239Kras. The ST239Kras (strain OC3) genome contained: a completely unique phage, φSa7-like (W), with no att repetition; S. aureus pathogenicity island SaPI2R, the first TSST-1 gene-positive (tst+) SaPI in the ST239 lineage; and a super copy of IS256 (≥22 copies/genome). ST239Kras carried the Brazilian SCCmecIII.1.1.2 and United Kingdom-type tst. ST239Kras and ST8Kras were MDR, with the same levofloxacin resistance mutations; small, but transmissible chloramphenicol resistance plasmids spread widely enough to not be ignored. These results suggest that novel MDR and MVF+ HA- and CA-MRSA (ST239Kras and ST8Kras) emerged in Siberian Russia (Krasnoyarsk) associated with fatal pneumonia, and also with ST

  12. The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens

    PubMed Central

    Lacey, Keenan A.; Geoghegan, Joan A.; McLoughlin, Rachel M.

    2016-01-01

    Staphylococcus aureus (S. aureus) causes the vast majority of skin and soft tissue infections (SSTIs) in humans. S. aureus has become increasingly resistant to antibiotics and there is an urgent need for new strategies to tackle S. aureus infections. Vaccines offer a potential solution to this epidemic of antimicrobial resistance. However, the development of next generation efficacious anti-S. aureus vaccines necessitates a greater understanding of the protective immune response against S. aureus infection. In particular, it will be important to ascertain if distinct immune mechanisms are required to confer protection at distinct anatomical sites. Recent discoveries have highlighted that interleukin-17-producing T cells play a particularly important role in the immune response to S. aureus skin infection and suggest that vaccine strategies to specifically target these types of T cells may be beneficial in the treatment of S. aureus SSTIs. S. aureus expresses a large number of cell wall-anchored (CWA) proteins, which are covalently attached to the cell wall peptidoglycan. The virulence potential of many CWA proteins has been demonstrated in infection models; however, there is a paucity of information regarding their roles during SSTIs. In this review, we highlight potential candidate antigens for vaccines targeted at protection against SSTIs. PMID:26901227

  13. Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus

    PubMed Central

    Highlander, Sarah K; Hultén, Kristina G; Qin, Xiang; Jiang, Huaiyang; Yerrapragada, Shailaja; Mason, Edward O; Shang, Yue; Williams, Tiffany M; Fortunov, Régine M; Liu, Yamei; Igboeli, Okezie; Petrosino, Joseph; Tirumalai, Madhan; Uzman, Akif; Fox, George E; Cardenas, Ana Maria; Muzny, Donna M; Hemphill, Lisa; Ding, Yan; Dugan, Shannon; Blyth, Peter R; Buhay, Christian J; Dinh, Huyen H; Hawes, Alicia C; Holder, Michael; Kovar, Christie L; Lee, Sandra L; Liu, Wen; Nazareth, Lynne V; Wang, Qiaoyan; Zhou, Jianling; Kaplan, Sheldon L; Weinstock, George M

    2007-01-01

    Background Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. Results We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. Conclusion USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens. PMID:17986343

  14. [Severe infection by methicillin sensitive Staphylococcus aureus producing Panton-Valentine leukocidin: reports of two cases].

    PubMed

    Brizuela, Martín; Pérez, Guadalupe; Ruvinsky, Silvina; Sarkis, Claudia; Romero, Romina; Mastroianni, Alejandra; Casimir, Lidia; Venuta, María E; Gómez Bonduele, Verónica; Bologna, Rosa

    2016-08-01

    Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria. PMID:27399020

  15. Sequence type 72 community-associated meticillin-resistant Staphylococcus aureus emerged as a predominant clone of nasal colonization in newly admitted patients.

    PubMed

    Park, S Y; Chung, D R; Yoo, J R; Baek, J Y; Kim, S H; Ha, Y E; Kang, C-I; Peck, K R; Lee, N Y; Song, J-H

    2016-08-01

    Current knowledge of community-associated (CA) meticillin-resistant Staphylococcus aureus (MRSA) carriage in hospitalized patients is incomplete. Genotypic characteristics of 637 nasal MRSA isolates from newly admitted patients in South Korea were investigated. Sequence type (ST) 72 accounted for 52.1%, 46.3%, and 52.8% of the isolates during the periods of 2007-2008, 2009-2010, and 2013-2014, respectively. Instead of classic MRSA clones responsible for healthcare-associated infections, including ST5 and ST239, MRSA with community genotype ST72 was the predominant strain in newly admitted patients regardless of age and home province of the patients. Active strategies are needed to prevent healthcare-associated infection by CA-MRSA. PMID:26874934

  16. Dissemination of methicillin-resistant Staphylococcus aureus SCCmec type IV and SCCmec type V epidemic clones in a tertiary hospital: challenge to infection control.

    PubMed

    Dhawan, B; Rao, C; Udo, E E; Gadepalli, R; Vishnubhatla, S; Kapil, A

    2015-01-01

    Two-hundred MRSA strains from inpatients with healthcare-associated (HA) and 100 MRSA strains from outpatients with community-associated (CA) skin and soft tissue infections (SSTIs) were tested for antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) typing, Panton-Valentine leucocidin (PVL) toxin, seh and arcA genes. Based on SCCmec typing, HA-MRSA isolates were further divided into HA-SCCmec I/II/III MRSA and HA-SCCmec IV/V MRSA, and CA-MRSA isolates into CA-SCCmec I/II/III MRSA and CA-SCCmec IV/V MRSA. SCCmec types were further characterized by pulsed-field gel electrophoresis, spa typing and multi-locus sequence typing. Seventy-five (37·5%) HA-MRSA isolates and 83/100 CA-MRSA isolates were SCCmec IV/V genotype. HA-SCCmec IV/V MRSA was associated with malignancy (P = 0·03) and bone fractures (P = 0·02) compared to CA-SCCmec IV/V MRSA. HA-SCCmec IV/V MRSA was associated with PVL gene carriage compared to HA-SCCmec I/II/III MRSA (P < 0·001). ST22-MRSA-IV (EMRSA-15), ST772-MRSA-V, and ST36-MRSA-IV and ST239:EMRSA-I:III were the major clones identified. Our study documents the emergence of SCCmec IV and SCCmec V MRSA clones in an Indian hospital. PMID:24690229

  17. Inflammasome Activation Can Mediate Tissue-Specific Pathogenesis or Protection in Staphylococcus aureus Infection.

    PubMed

    Melehani, Jason H; Duncan, Joseph A

    2016-01-01

    Staphylococcus aureus is a Gram-positive coccus that interacts with human hosts on a spectrum from quiet commensal to deadly pathogen. S. aureus is capable of infecting nearly every tissue in the body resulting in cellulitis, pneumonia, osteomyelitis, endocarditis, brain abscesses, bacteremia, and more. S. aureus has a wide range of factors that promote infection, and each site of infection triggers a different response in the human host. In particular, the different patterns of inflammasome activation mediate tissue-specific pathogenesis or protection in S. aureus infection. Although still a nascent field, understanding the unique host-pathogen interactions in each infection and the role of inflammasomes in mediating pathogenesis may lead to novel strategies for treating S. aureus infections. Reviews addressing S. aureus virulence and pathogenesis (Thammavongsa et al. 2015), as well as epidemiology and pathophysiology (Tong et al. 2015), have recently been published. This review will focus on S. aureus factors that activate inflammasomes and their impact on innate immune signaling and bacterial survival. PMID:27460814

  18. Expanded Glucose Import Capability Affords Staphylococcus aureus Optimized Glycolytic Flux during Infection

    PubMed Central

    Vitko, Nicholas P.; Grosser, Melinda R.; Khatri, Dal; Lance, Thurlow R.

    2016-01-01

    ABSTRACT Acquisition of numerous virulence determinants affords Staphylococcus aureus greater pathogenicity than other skin-colonizing staphylococci in humans. Additionally, the metabolic adaptation of S. aureus to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide, iron chelation) has been implicated as contributing to S. aureus virulence. Specifically, S. aureus has been shown to ferment glycolytic substrates in nonrespiratory environments encountered within the host. Here, we show that S. aureus has acquired unique carbohydrate transporters that facilitate the maximal uptake of host sugars and serve to support nonrespiratory growth in inflamed tissue. The carbohydrate substrates of 11 S. aureus transporters were identified, and at least four of their genes encode S. aureus glucose transporters (glcA, glcB, glcC, and glcU). Moreover, two transporter genes (glcA and glcC) are unique to S. aureus and contribute disproportionately to the nonrespiratory growth of S. aureus on glucose. Targeted inactivation of sugar transporters reduced glucose uptake and attenuated S. aureus in a murine model of skin and soft tissue infections. These data expand the evidence for metabolic adaptation of S. aureus to invasive infection and demonstrate the specific requirement for the fermentation of glucose over all other available carbohydrates. Ultimately, acquisition of foreign genes allows S. aureus to adopt a metabolic strategy resembling that of infiltrating host immune cells: high glycolytic flux coupled to lactate excretion. PMID:27329749

  19. New antimicrobial approaches to gram positive respiratory infections.

    PubMed

    Liapikou, Adamantia; Cilloniz, Catia; Mensa, Josep; Torres, Antonio

    2015-06-01

    Nowadays, we face growing resistance among gram-positive and gram-negative pathogens that cause respiratory infection in the hospital and in the community. The spread of penicillin- and macrolide-resistant pneumococci, Community-acquired methicillin-resistant staphylococcus aureus (Ca-MRSA), the emergence of glycopeptide-resistant staphylococci underline the need for underline the need for therapeutic alternatives. A number of new therapeutic agents, with activity against the above Gram (+) respiratory pathogens, as ceftaroline, ceftopibrole, telavancin, tedizolid have become available, either in clinical trials or have been approved for clinical use. Especially, the development of new oral antibiotics, as nemonaxacin, omadacyclin, cethromycin and solithromycin will give a solution to the lack of oral drugs for outpatient treatment. In the future the clinician needs to optimize the use of old and new antibiotics to treat gram (+) respiratory serious infections. PMID:24878422

  20. Role of BrnQ1 and BrnQ2 in branched-chain amino acid transport and virulence in Staphylococcus aureus.

    PubMed

    Kaiser, Julienne C; Omer, Sameha; Sheldon, Jessica R; Welch, Ian; Heinrichs, David E

    2015-03-01

    The branched-chain amino acids (BCAAs; Ile, Leu, and Val) not only are important nutrients for the growth of Staphylococcus aureus but also are corepressors for CodY, which regulates virulence gene expression, implicating BCAAs as an important link between the metabolic state of the cell and virulence. BCAAs are either synthesized intracellularly or acquired from the environment. S. aureus encodes three putative BCAA transporters, designated BrnQ1, BrnQ2, and BrnQ3; their functions have not yet been formally tested. In this study, we mutated all three brnQ paralogs so as to characterize their substrate specificities and their roles in growth in vitro and in vivo. We demonstrated that in the community-associated, methicillin-resistant S. aureus (CA-MRSA) strain USA300, BrnQ1 is involved in uptake of all three BCAAs, BrnQ2 transports Ile, and BrnQ3 does not have a significant role in BCAA transport under the conditions tested. Of the three, only BrnQ1 is essential for USA300 to grow in a chemically defined medium that is limited for Leu or Val. Interestingly, we observed that a brnQ2 mutant grew better than USA300 in media limited for Leu and Val, owing to the fact that this mutation leads to overexpression of brnQ1. In a murine infection model, the brnQ1 mutant was attenuated, but in contrast, brnQ2 mutants had significantly increased virulence compared to that of USA300, a phenotype we suggest is at least partially linked to enhanced in vivo scavenging of Leu and Val through BrnQ1. These data uncover a hitherto-undiscovered connection between nutrient acquisition and virulence in CA-MRSA. PMID:25547798

  1. The therapeutic effect of chlorogenic acid against Staphylococcus aureus infection through sortase A inhibition

    PubMed Central

    Wang, Lin; Bi, Chongwei; Cai, Hongjun; Liu, Bingrun; Zhong, Xiaobo; Deng, Xuming; Wang, Tiedong; Xiang, Hua; Niu, Xiaodi; Wang, Dacheng

    2015-01-01

    The emergence and wide spread of multi-drug resistant Staphylococcus aureus (S. aureus) requires the development of new therapeutic agents with alternative modes of action. Anti-virulence strategies are hoped to meet that need. Sortase A (SrtA) has attracted great interest as a potential drug target to treat infections caused by S. aureus, as many of the surface proteins displayed by SrtA function as virulence factors by mediating bacterial adhesion to specific organ tissues, invasion of host cells, and evasion of the host-immune responses. It has been suggested that inhibitors of SrtA might be promising candidates for the treatment and/or prevention of S. aureus infections. In this study, we report that chlorogenic acid (CHA), a natural compound that lacks significant anti-S. aureus activity, inhibit the activity of SrtA in vitro (IC50 = 33.86 ± 5.55 μg/ml) and the binding of S. aureus to fibrinogen (Fg). Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that CHA binds to the binding sites of C184 and G192 in the SrtA. In vivo studies demonstrated that CHA prevent mice from S. aureus-induced renal abscess, resulting in a significant survival advantage. These findings indicate that CHA is a promising therapeutic compound against SrtA during S. aureus infections. PMID:26528244

  2. Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin Colonization and Infection

    PubMed Central

    Popov, Lauren; Kovalski, Joanna; Grandi, Guido; Bagnoli, Fabio; Amieva, Manuel R.

    2014-01-01

    Staphylococcus aureus is both a major bacterial pathogen as well as a common member of the human skin microbiota. Due to its widespread prevalence as an asymptomatic skin colonizer and its importance as a source of skin and soft tissue infections, an improved understanding of how S. aureus attaches to, grows within, and breaches the stratified layers of the epidermis is of critical importance. Three-dimensional organotypic human skin culture models are informative and tractable experimental systems for future investigations of the interactions between S. aureus and the multi-faceted skin tissue. We propose that S. aureus virulence factors, primarily appreciated for their role in pathogenesis of invasive infections, play alternative roles in promoting asymptomatic bacterial growth within the skin. Experimental manipulations of these cultures will provide insight into the many poorly understood molecular interactions occurring at the interface between S. aureus and stratified human skin tissue. PMID:24567733

  3. Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin Colonization and Infection.

    PubMed

    Popov, Lauren; Kovalski, Joanna; Grandi, Guido; Bagnoli, Fabio; Amieva, Manuel R

    2014-01-01

    Staphylococcus aureus is both a major bacterial pathogen as well as a common member of the human skin microbiota. Due to its widespread prevalence as an asymptomatic skin colonizer and its importance as a source of skin and soft tissue infections, an improved understanding of how S. aureus attaches to, grows within, and breaches the stratified layers of the epidermis is of critical importance. Three-dimensional organotypic human skin culture models are informative and tractable experimental systems for future investigations of the interactions between S. aureus and the multi-faceted skin tissue. We propose that S. aureus virulence factors, primarily appreciated for their role in pathogenesis of invasive infections, play alternative roles in promoting asymptomatic bacterial growth within the skin. Experimental manipulations of these cultures will provide insight into the many poorly understood molecular interactions occurring at the interface between S. aureus and stratified human skin tissue. PMID:24567733

  4. Methamphetamine Alters the Antimicrobial Efficacy of Phagocytic Cells during Methicillin-Resistant Staphylococcus aureus Skin Infection

    PubMed Central

    Mihu, Mircea Radu; Roman-Sosa, Jessica; Varshney, Avanish K.; Eugenin, Eliseo A.; Shah, Bhavikkumar P.; Ham Lee, Hiu; Nguyen, Long N.; Guimaraes, Allan J.; Fries, Bettina C.; Nosanchuk, Joshua D.

    2015-01-01

    ABSTRACT Methamphetamine (METH) is a major drug of abuse in the United States and worldwide. Furthermore, Staphylococcus aureus infections and METH use are coemerging public health problems. S. aureus is the single most important bacterial pathogen in infections among injection drug users, with skin and soft tissue infections (SSTI) being extremely common. Notably, the incidence of SSTI, especially in drug users, is difficult to estimate because such infections are often self-treated. Although there is substantial information on the behavioral and cognitive defects caused by METH in drug users, there is a dearth of knowledge regarding its impact on bacterial infections and immunity. Therefore, we hypothesized that METH exacerbates S. aureus skin infection. Using a murine model of METH administration and wound infection, we demonstrated that METH reduces wound healing and facilitates host-mediated collagen degradation by increased expression and production of matrix metalloproteinase-2 (MMP-2). Additionally, we found that METH induces S. aureus biofilm formation and leads to detrimental effects on the functions of human and murine phagocytic cells, enhancing susceptibility to S. aureus infection. Our findings provide empirical evidence of the adverse impact of METH use on the antimicrobial efficacy of the cells that comprise innate immunity, the initial host response to combat microbial infection. PMID:26507236

  5. The effect of inoculum volume on the microbiologic detection of naturally occurring Staphylococcus aureus intramammary infections.

    PubMed

    Walker, Jennifer B; Rajala-Schultz, Päivi J; DeGraves, Fred J

    2010-09-01

    Currently no standard definitions for the diagnosis of Staphylococcus aureus intramammary infection (IMI) exist. As a result, criteria applied in research to diagnose S. aureus IMIs have varied making comparisons between published works difficult. The goal of the current study was to define the optimal inoculum volume used in the diagnosis of naturally occurring S. aureus IMIs. Microbiologic results from 2 field studies examining S. aureus IMIs were used to examine the effects of inoculum volume on the microbiologic detection of S. aureus. A total of 1,583 milk samples were included in the analysis, and the results of using a 0.01-ml and a 0.1-ml inoculum are presented. Using a 0.01-ml inoculum resulted in a sensitivity of 91% (95% confidence interval [CI]: 88.6-93%) and a specificity of 99.4% (95% CI: 98.6-99.8%). Using the larger 0.1-ml inoculum resulted in a sensitivity of 96.8% (95% CI: 95.2-97.9%) and a specificity of 99.3% (95% CI: 98.4-99.7%). All false-positive samples were from S. aureus-negative quarters in S. aureus-positive cows. There were no false-positive cultures from S. aureus-negative cows. Of the false-negative samples, the majority (77%) were from 6 of the 34 S. aureus-positive quarters. Results from the current study of naturally occurring S. aureus IMIs support the hypothesis that, when using quarter level milk samples, a S. aureus IMI is most accurately diagnosed using a 0.1-ml inoculum. Regardless of inoculum volume, a single quarter sample culture that is positive with S. aureus (>or=1 colony-forming unit) is sufficient to diagnose a S. aureus IMI. PMID:20807927

  6. Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data

    PubMed Central

    Tosas Auguet, Olga; Betley, Jason R.; Stabler, Richard A.; Patel, Amita; Ioannou, Avgousta; Marbach, Helene; Hearn, Pasco; Aryee, Anna; Goldenberg, Simon D.; Otter, Jonathan A.; Desai, Nergish; Karadag, Tacim; Grundy, Chris; Gaunt, Michael W.; Cooper, Ben S.; Edgeworth, Jonathan D.; Kypraios, Theodore

    2016-01-01

    Background Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. Methods and Findings This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with

  7. Community-Acquired Methicillin-Resistant Staphylococcus aureus: Prevalence and Risk Factors

    PubMed Central

    Beam, Joel W; Buckley, Bernadette

    2006-01-01

    Reference/Citation: Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis.20033613113912522744. Clinical Question: What are the prevalence rates and risk factors associated with community-acquired methicillin-resistant Staphylococcus aureus (MRSA)? Data Sources: Studies were identified by searching MEDLINE (January 1966–February 2002) and abstracts from scientific meetings (1996–2001). Reviews of citations and reference lists were performed to identify additional eligible studies. The search terms included Staphylococcus aureus , infection, colonization, methicillin resistance, community-acquired, community-onset, prevalence, frequency, and risk factors. Study Selection: The search was limited to English-language investigations identified from the electronic and manual searches. Studies were divided into 2 groups, as follows: group 1, retrospective or prospective studies that reported the prevalence of community-acquired MRSA (CA-MRSA) among hospital patients who were colonized (presence of bacteria without infection) or infected with MRSA; and group 2, studies that reported the prevalence of MRSA colonization in the community. The studies were evaluated independently by 2 authors, and case reports were excluded. Data Extraction: Data extraction and study quality assessment procedures were not fully explained. The outcome measures for hospital patients were definitions of CA-MRSA used in the study, prevalence of CA-MRSA, sample size, number and type of risk factors assessed, and number of patients with ≥1 health care–associated risk factor. The studies were grouped based on type, retrospective or prospective. The pooled prevalence of CA-MRSA was calculated for each group (retrospective or prospective) and was limited to the prevalence among patients with MRSA. The proportion of patients who reported ≥1 health care–associated risk factor was also

  8. Epidemiological and molecular characteristics of meticillin-resistant Staphylococcus aureus in Turkey: A multicentre study.

    PubMed

    Dündar, Devrim; Willke, Ayse; Sayan, Murat; Koc, Meliha Meric; Akan, Ozay Arıkan; Sumerkan, Bulent; Saltoglu, Nese; Yaman, Akgun; Ayaz, Celal; Koksal, Iftihar

    2016-09-01

    The aim of this study was to investigate the epidemiological and molecular features of clinical meticillin-resistant Staphylococcus aureus (MRSA) isolates in Turkey. MRSA isolates were collected from six regions of Turkey. The mecA and nuc genes were detected by PCR. Antimicrobial susceptibilities were determined by the disk diffusion method. Staphylococcal cassette chromosome mec (SCCmec) and staphylococcal protein A (spa) typing were performed by the sequencing method for 270 randomly selected MRSA isolates. The US Centers for Disease Control and Prevention (CDC) definition was used for epidemiological diagnosis of community-associated MRSA (CA-MRSA). Resistance rates of MRSA to ciprofloxacin, gentamicin, clindamycin, erythromycin, rifampicin, trimethoprim/sulfamethoxazole and tetracycline were 93.4%, 81.2%, 38.5%, 57.8%, 93.9%, 1.1% and 93.1%, respectively. The most frequent SCCmec type was SCCmec III (91.1%). SCCmec type IV was found in 5.2% of the isolates. The most frequent spa type was t030 (81.1%). Five isolates were CA-MRSA if only the epidemiological definition was used (5/725; 0.7%). Two isolates were defined as CA-MRSA both by epidemiological features and SCCmec typing (2/270; 0.7%). Of 14 SCCmec type IV isolates, 12 were not defined as CA-MRSA by epidemiological features. In conclusion, this is the most comprehensive multicentre study in Turkey investigating MRSA using both epidemiological and genotypic features. The CA-MRSA rate is low in Turkey. Combined use of epidemiological and genotypic methods is the most accurate approach for the diagnosis of CA-MRSA. PMID:27530838

  9. AraC-Type Regulator Rsp Adapts Staphylococcus aureus Gene Expression to Acute Infection.

    PubMed

    Li, Tianming; He, Lei; Song, Yan; Villaruz, Amer E; Joo, Hwang-Soo; Liu, Qian; Zhu, Yuanjun; Wang, Yanan; Qin, Juanxiu; Otto, Michael; Li, Min

    2016-03-01

    Staphylococcus aureus is an important human pathogen that can cause two categories of severe infections. Acute infections are characterized by pronounced toxin production, while chronic infections often involve biofilm formation. However, it is poorly understood how S. aureus controls the expression of genes associated with acute versus biofilm-associated virulence. We here identified an AraC-type transcriptional regulator, Rsp, that promotes the production of key toxins while repressing major biofilm-associated genes and biofilm formation. Genome-wide transcriptional analysis and modeling of regulatory networks indicated that upregulation of the accessory gene regulator (Agr) and downregulation of the ica operon coding for the biofilm exopolysaccharide polysaccharide intercellular adhesin (PIA) were central to the regulatory impact of Rsp on virulence. Notably, the Rsp protein directly bound to the agrP2 and icaADBC promoters, resulting in strongly increased levels of the Agr-controlled toxins phenol-soluble modulins (PSMs) and alpha-toxin and reduced production of PIA. Accordingly, Rsp was essential for the development of bacteremia and skin infection, representing major types of acute S. aureus infection. Our findings give important insight into how S. aureus adapts the expression of its broad arsenal of virulence genes to promote different types of disease manifestations and identify the Rsp regulator as a potential target for strategies to control acute S. aureus infection. PMID:26712209

  10. Clinical Characteristics of Methicillin-resistant Staphylococcus aureus Infection for Chronic Periprosthetic Hip and Knee Infection

    PubMed Central

    Ryu, Dong Jin; Moon, Kyoung Ho; Kim, Myung Ku; Kwon, Dae Gyu

    2014-01-01

    Purpose Deep infection after hip and knee arthroplasty is a serious complication and is difficult to treat due to its toxicity. The aims of our study were to find out the differences of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infection after hip and knee arthroplasty focusing on clinical course and laboratory findings. Materials and Methods We retrospectively reviewed 61 staphylococcal infection cases after hip and knee arthroplasty (MSSA in 25 patients, MRSA in 36 patients). Vital signs, laboratory tests, microbiology and clinical courses were analyzed. The average follow-up period was 3.8 years (range, 2 to 10.1 years). Results At initial visit, MRSA group showed significant higher erythrocyte sedimentation rate, C-reactive protein (CRP) and neutrophil percentage. The average duration for the normalization of CRP was longer in MRSA group (MRSA: 36.7±25.1 days, MSSA: 24.7±13.6 days; P=0.008). The mean interval between staging operation was longer in MRSA group (MRSA: mean 8.7 weeks [range, 6.4 to 21.4 weeks], MSSA: mean 6.8 weeks [range, 6 to 13.1 weeks]; P=0.012). MRSA group (13.9%) revealed higher recurrence rate than MSSA group (4%). Two patients (5.6%) from MRSA group expired by sepsis. One limb amputation (2.7%) was carried out in MRSA group. Conclusion MRSA infection after arthroplasty showed more toxic serologic parameter and poorer prognosis. Aggressive treatment should be considered for MRSA infection following arthroplasty.

  11. Efficacy of dicloxacillin-coated polyurethane catheters in preventing subcutaneous Staphylococcus aureus infection in mice.

    PubMed Central

    Sherertz, R J; Forman, D M; Solomon, D D

    1989-01-01

    In a mouse model, dicloxacillin-coated polyurethane catheters or control (uncoated) catheters were placed subcutaneously and then Staphylococcus aureus was inoculated at the time of insertion, 24 or 48 h later. The in vivo half-life of the antibiotic was 11 to 16 h. When 10(5) CFU of S. aureus were inoculated at the time of catheter insertion, dicloxacillin-coated catheters kept the number of S. aureus removed from catheters by sonication below 10(2) CFU at 12, 24, 48, and 96 h after inoculation compared with titers greater than 10(3.5) CFU for control catheters (P less than 0.05). When S. aureus was inoculated 24 h after catheter insertion, control catheters averaged greater than 10(2) CFU of S. aureus removed compared with less than 10(1.5) CFU for the dicloxacillin-coated catheters (P less than 0.05). No difference was found between coated and control catheters when S. aureus was inoculated 48 h after catheter insertion, but S. aureus titers averaged less than 10(2) CFU for all experimental groups. Our data suggest that in mice, regional prophylaxis of S. aureus subcutaneous space infection is feasible with catheters coated with dicloxacillin and that the presence of antibiotic is only necessary for the first 24 to 48 h. PMID:2802545

  12. High prevalence of hospital-associated methicillin-resistant Staphylococcus aureus in the community in Portugal: evidence for the blurring of community-hospital boundaries.

    PubMed

    Tavares, A; Miragaia, M; Rolo, J; Coelho, C; de Lencastre, H

    2013-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infection in the community (CA-MRSA), but in spite of its relevance, no data exist concerning its epidemiology in Portugal. In this study, we aimed to evaluate the prevalence, population structure, and origin of MRSA in the Portuguese community. A total of 527 isolates, both methicillin-susceptible S. aureus (MSSA) and MRSA, were collected from individuals with no healthcare-related risk factors attending 16 healthcare institutions in Portugal. Isolates were characterized for the presence of mecA, Panton-Valentine leukocidin (PVL), and arginine catabolic mobile element (ACME), and by staphylococcal cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), spa, and multilocus sequence typing (MLST). Susceptibility to a panel of 13 antibiotics was tested. Isolates relatedness was analyzed by goeBURST and BURP. We found a high frequency (21.6%) of MRSA in the community. However, only 11.4% of the isolates belonged to typical CA-MRSA epidemic clones (USA300, USA400, USA700, Southwest Pacific, European, and ST398). The remaining isolates, which constituted the great majority (88.6%), belonged to hospital-associated MRSA (HA-MRSA) epidemic clones, namely, to the EMRSA-15 clone (77.2%). PVL was rare and carried by 17 isolates only (five MRSA and 12 MSSA). In the whole collection, some MRSA and MSSA were highly related. The high frequency of MRSA in the community in Portugal seems to result mainly from dissemination from the hospital. They might also have emerged from an extant MSSA population, by SCCmec acquisition, or MRSA clonal introduction from abroad. PMID:23604782

  13. β-Lactams Interfering with PBP1 Induce Panton-Valentine Leukocidin Expression by Triggering sarA and rot Global Regulators of Staphylococcus aureus

    PubMed Central

    Dumitrescu, Oana; Choudhury, Priya; Boisset, Sandrine; Badiou, Cédric; Bes, Michele; Benito, Yvonne; Wolz, Christiane; Vandenesch, François; Etienne, Jerome; Cheung, Ambrose L.; Bowden, Maria Gabriela; Lina, Gerard

    2011-01-01

    Previous articles reported that beta-lactam antibiotics increase the expression of Staphylococcus aureus Panton-Valentine leukocidin (PVL) by activating its transcription. We investigated the mechanisms underlying the inductor effect of beta-lactams on PVL expression by determining targets and regulatory pathways possibly implicated in this process. We measured PVL production in the presence of oxacillin (nonselective), imipenem (penicillin-binding protein 1 [PBP1] selective), cefotaxime (PBP2 selective), cefaclore (PBP3 selective), and cefoxitin (PBP4 selective). In vitro, we observed increased PVL production consistent with luk-PV mRNA levels that were 20 to 25 times higher for community-acquired methicillin-resistant S. aureus (CA-MRSA) cultures treated with PBP1-binding oxacillin and imipenem than for cultures treated with other beta-lactams or no antibiotic at all. This effect was also observed in vivo, with increased PVL mRNA levels in lung tissues from CA-MRSA-infected mice treated with imipenem but not cefoxitin. To confirm the involvement of PBP1 inhibition in this pathway, PBP1 depletion by use of an inducible pbp1 antisense RNA showed a dose-dependent relationship between the level of pbp1 antisense RNA and the luk-PV mRNA level. Upon imipenem treatment of exponential-phase cultures, we observed an increased sarA mRNA level after 30 min of incubation followed by a decreased rot mRNA level after 1 to 4 h of incubation. Unlike the agr and saeRS positive regulators, which were nonessential for PVL induction by beta-lactams, the sarA (positive) and rot (negative) PVL regulators were necessary for PVL induction by imipenem. Our results suggest that antibiotics binding to PBP1 increase PVL expression by modulating sarA and rot, which are essential mediators of the inductor effect of beta-lactams on PVL expression. PMID:21502633

  14. A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model

    PubMed Central

    Prajsnar, Tomasz K; Hamilton, Ruth; Garcia-Lara, Jorge; McVicker, Gareth; Williams, Alexander; Boots, Michael; Foster, Simon J; Renshaw, Stephen A

    2012-01-01

    The innate immune system is the primary defence against the versatile pathogen, Staphylococcus aureus. How this organism is able to avoid immune killing and cause infections is poorly understood. Using an established larval zebrafish infection model, we have shown that overwhelming infection is due to subversion of phagocytes by staphylococci, allowing bacteria to evade killing and found foci of disease. Larval zebrafish coinfected with two S. aureus strains carrying different fluorescent reporter gene fusions (but otherwise isogenic) had bacterial lesions, at the time of host death, containing predominantly one strain. Quantitative data using two marked strains revealed that the strain ratios, during overwhelming infection, were often skewed towards the extremes, with one strain predominating. Infection with passaged bacterial clones revealed the phenomenon not to bedue to adventitious mutations acquired by the pathogen. After infection of the host, all bacteria are internalized by phagocytes and the skewing of population ratios is absolutely dependent on the presence of phagocytes. Mathematical modelling of pathogen population dynamics revealed the data patterns are consistent with the hypothesis that a small number of infected phagocytes serve as an intracellular reservoir for S. aureus, which upon release leads to disseminated infection. Strategies to specifically alter neutrophil/macrophage numbers were used to map the potential subpopulation of phagocytes acting as a pathogen reservoir, revealing neutrophils as the likely ‘niche’. Subsequently in a murine sepsis model, S. aureus abscesses in kidneys were also found to be predominantly clonal, therefore likely founded by an individual cell, suggesting a potential mechanism analogous to the zebrafish model with few protected niches. These findings add credence to the argument that S. aureus control regimes should recognize both the intracellular as well as extracellular facets of the S. aureus life cycle

  15. Biofilm formation by Staphylococcus aureus isolates from skin and soft tissue infections.

    PubMed

    Kwiecinski, Jakub; Kahlmeter, Gunnar; Jin, Tao

    2015-05-01

    Many diseases caused by Staphylococcus aureus are associated with biofilm formation. However, the ability of S. aureus isolates from skin and soft tissue infections to form biofilms has not yet been investigated. We tested 160 isolates from patients with various skin infections for biofilm-forming capacity in different growth media. All the isolates formed biofilms, the extent of which depended on the type of growth medium. The thickest biofilms were formed when both plasma and glucose were present in the broth; in this case, S. aureus incorporated host fibrin into the biofilm's matrix. There were no differences in the biofilm formation between isolates from different types of skin infections, except for a particularly good biofilm formation by isolates from diabetic wounds and a weaker biofilm formation by isolates from impetigo. In conclusion, biofilm formation is a universal behavior of S. aureus isolates from skin infections. In some cases, such as in diabetic wounds, a particularly strong biofilm formation most likely contributes to the chronic and recurrent character of the infection. Additionally, as S. aureus apparently uses host fibrin as part of the biofilm structure, we suggest that plasma should be included more frequently in in vitro biofilm studies. PMID:25586078

  16. Impacts of enterotoxin gene cluster-encoded superantigens on local and systemic experimental Staphylococcus aureus infections.

    PubMed

    Nowrouzian, F L; Ali, A; Badiou, C; Dauwalder, O; Lina, G; Josefsson, E

    2015-07-01

    Staphylococcus aureus is both a component of the normal skin flora and an important pathogen. It expresses a range of recognized and putative virulence factors, such as enterotoxins with superantigenic properties. Several superantigen genes, i.e., seg, sei, selm, seln, and selo, are encoded by the enterotoxin gene cluster (egc), which is found in the majority of S. aureus isolates. Carriage of egc is associated with fitness of S. aureus in the gut microbiota, but it is not known if it contributes to pathogenicity. We constructed egc+ (functional for the seg, selm, and selo genes) and isogenic egc- S. aureus mutants, and investigated their virulence profiles in murine infection models. No effect of egc was seen in a local skin and soft tissue infection model, but in an invasive infection model, increased weight loss was observed after infection with the egc+ as compared to the egc- mutant. Mortality and arthritis were not affected by egc status. Our data suggest that egc has limited effects on the virulence of S. aureus. It may primarily function as a colonization factor increasing commensal fitness, although it might have some aggravating effects on the infection when the bacteria reach the blood. PMID:25864191

  17. Infective endocarditis due to Staphylococcus aureus: 59 prospectively identified cases with follow-up.

    PubMed

    Fowler, V G; Sanders, L L; Kong, L K; McClelland, R S; Gottlieb, G S; Li, J; Ryan, T; Sexton, D J; Roussakis, G; Harrell, L J; Corey, G R

    1999-01-01

    Fifty-nine consecutive patients with definite Staphylococcus aureus infective endocarditis (IE) by the Duke criteria were prospectively identified at our hospital over a 3-year period. Twenty-seven (45.8%) of the 59 patients had hospital-acquired S. aureus bacteremia. The presumed source of infection was an intravascular device in 50.8% of patients. Transthoracic echocardiography (TTE) revealed evidence of IE in 20 patients (33.9%), whereas transesophageal echocardiography (TEE) revealed evidence of IE in 48 patients (81.4%). The outcome for patients was strongly associated with echocardiographic findings: 13 (68.4%) of 19 patients with vegetations visualized by TTE had an embolic event or died of their infection vs. five (16.7%) of 30 patients whose vegetations were visualized only by TEE (P < .01). Most patients with S. aureus IE developed their infection as a consequence of a nosocomial or intravascular device-related infection. TEE established the diagnosis of S. aureus IE in many instances when TTE was nondiagnostic. Visualization of vegetations by TTE may provide prognostic information for patients with S. aureus IE. PMID:10028079

  18. Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

    PubMed Central

    von Köckritz-Blickwede, Maren; Rohde, Manfred; Oehmcke, Sonja; Miller, Lloyd S.; Cheung, Ambrose L.; Herwald, Heiko; Foster, Simon; Medina, Eva

    2008-01-01

    Host genetic variations play a significant role in conferring predisposition to infection. In this study, we examined the immune mechanisms underlying the host genetic predisposition to severe Staphylococcus aureus infection in different mouse strains. Whereas C57BL/6 mice were the most resistant in terms of control of bacterial growth and survival, A/J, DBA/2, and BALB/c mice were highly susceptible and succumbed to infection shortly after bacterial inoculation. Other strains (C3H/HeN, CBA, and C57BL/10) exhibited intermediate susceptibility levels. Susceptibility of mice to S. aureus was associated with an inability to limit bacterial growth in the kidneys and development of pathology. Resistance to S. aureus in C57BL/6 mice was dependent on innate immune mechanisms because Rag2-IL2Rγ−/− C57BL/6 mice, which are deficient in B, T, and NK cells, were also resistant to infection. Indeed, neutrophil depletion or inhibition of neutrophil recruitment rendered C57BL/6 mice completely susceptible to S. aureus, indicating that neutrophils are essential for the observed resistance. Although neutrophil function is not inhibited in A/J mice, expression of neutrophil chemoattractants KC and MIP-2 peaked earlier in the kidneys of C57BL/6 mice than in A/J mice, indicating that a delay in neutrophil recruitment to the site of infection may underlie the increased susceptibility of A/J mice to S. aureus. PMID:18974303

  19. In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection

    PubMed Central

    Sadaka, Ama; Palmer, Kelli; Suzuki, Takashi; Gilmore, Michael S.

    2014-01-01

    Purpose To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model. Methods For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored. Results Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection. Conclusion Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity. PMID:25340474

  20. Predictive Factors for Metastatic Infection in Patients With Bacteremia Caused by Methicillin-Sensitive Staphylococcus aureus

    PubMed Central

    Sato, Fumiya; Hosaka, Yumiko; Hoshina, Tokio; Tamura, Kumi; Nakaharai, Kazuhiko; Kato, Tetsuro; Nakazawa, Yasushi; Yoshida, Masaki; Hori, Seiji

    2015-01-01

    Abstract: Background: Metastatic infections such as infective endocarditis and psoas abscess are serious complications of Staphylococcus aureus bacteremia because failure to identify these infections may result in bacteremia relapse or poor prognosis. In the present study, we determined the predictive factors for metastatic infection due to methicillin-sensitive S. aureus bacteremia. Methods: A retrospective cohort study was conducted among patients with methicillin-sensitive S. aureus bacteremia at the Jikei University Hospital between January 2008 and December 2012. Factors analyzed included the underlying disease, initial antimicrobial treatment and primary site of infection. Results: During the 5-year study period, 73 patients met the inclusion criteria and were assessed. The most common primary site of bacteremia was catheter-related bloodstream infection (25/73 [34.2%]). Metastatic infection occurred in 14 of 73 patients (19.2%) (infective endocarditis [3], septic pulmonary abscess [3], spondylitis [4], psoas abscess [4], epidural abscess [3] and septic arthritis [1]). Six patients had multiple metastatic infections. Multivariate analysis revealed that the predictive factors associated with the development of metastatic infection were a delay in appropriate antimicrobial treatment of >48 hours, persistent fever for >72 hours after starting antibiotic treatment and lowest C-reactive protein levels of >3 mg/dL during 2 weeks after the onset of bacteremia. Conclusions: This study demonstrated that additional diagnostic tests should be conducted to identify metastatic infection, particularly in patients with delayed antimicrobial treatment, persistent fever and persistently high C-reactive protein levels. PMID:25250988

  1. Practices and Procedures to Prevent the Transmission of Skin and Soft Tissue Infections in High School Athletes

    PubMed Central

    Fritz, Stephanie A.; Long, Marcus; Gaebelein, Claude J.; Martin, Madeline S.; Hogan, Patrick G.; Yetter, John

    2013-01-01

    Skin and soft tissue infections (SSTI) are frequent in student athletes and are often caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). We evaluated the awareness of CA-MRSA among high school coaches and athletic directors in Missouri (n = 4,408) and evaluated hygiene practices affecting SSTI transmission. Of 1,642 (37%) respondents, 61% received MRSA educational information during the past year and 32% indicated their school had written guidelines for managing SSTI in athletes. Coaches and athletic directors aware of written guidelines reported a lower incidence of SSTI in student athletes (26%) compared to those without written policies (34%, p=0.03). When confronted with SSTI, 49% of respondents referred student athletes to the school nurse or a physician. A relationship exists between school policies for SSTI management and lower incidence of SSTI. Educational initiatives by school nurses in conjunction with athletic staff may lead to practices that limit SSTI in this at-risk population. PMID:22472636

  2. Myeloid-derived suppressor cells (MDSCs) contribute to S. aureus orthopedic biofilm infection

    PubMed Central

    Heim, Cortney E.; Vidlak, Debbie; Scherr, Tyler D.; Kozel, Jessica A.; Holzapfel, Melissa; Muirhead, David E.; Kielian, Tammy

    2014-01-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes that are potent inhibitors of T cell activation. A role for MDSCs in bacterial infections has only recently emerged and nothing is known about MDSC function in the context of Staphylococcus aureus (S. aureus) infection. Since S. aureus biofilms are capable of subverting immune-mediated clearance, we examined whether MDSCs could play a role in this process. CD11b+Gr-1+ MDSCs represented the main cellular infiltrate during S. aureus orthopedic biofilm infection, accounting for over 75% of the CD45+ population. Biofilm-associated MDSCs inhibited T cell proliferation and cytokine production, which correlated with a paucity of T cell infiltrates at the infection site. Analysis of FACS-purified MDSCs recovered from S. aureus biofilms revealed increased Arg-1, iNOS, and IL-10 expression, key mediators of MDSC suppressive activity. Targeted depletion of MDSCs and neutrophils using the mAb 1A8 (anti-Ly6G) improved bacterial clearance by enhancing the intrinsic pro-inflammatory attributes of infiltrating monocytes and macrophages. Furthermore, the ability of monocytes/macrophages to promote biofilm clearance in the absence of MDSC action was revealed with RB6-C85 (anti-Gr-1 or anti-Ly6G/Ly6C) administration, which resulted in significantly increased S. aureus burdens both locally and in the periphery, since effector Ly-6C monocytes and by extension, mature macrophages, were also depleted. Collectively, these results are the first to demonstrate that MDSCs are key contributors to the chronicity of S. aureus biofilm infection, as their immunosuppressive function prevents monocyte/macrophage proinflammatory activity, which facilitates biofilm persistence. PMID:24646737

  3. Distinct Pathogenesis and Host Responses during Infection of C. elegans by P. aeruginosa and S. aureus

    PubMed Central

    Irazoqui, Javier E.; Troemel, Emily R.; Feinbaum, Rhonda L.; Luhachack, Lyly G.; Cezairliyan, Brent O.; Ausubel, Frederick M.

    2010-01-01

    The genetically tractable model host Caenorhabditis elegans provides a valuable tool to dissect host-microbe interactions in vivo. Pseudomonas aeruginosa and Staphylococcus aureus utilize virulence factors involved in human disease to infect and kill C. elegans. Despite much progress, virtually nothing is known regarding the cytopathology of infection and the proximate causes of nematode death. Using light and electron microscopy, we found that P. aeruginosa infection entails intestinal distention, accumulation of an unidentified extracellular matrix and P. aeruginosa-synthesized outer membrane vesicles in the gut lumen and on the apical surface of intestinal cells, the appearance of abnormal autophagosomes inside intestinal cells, and P. aeruginosa intracellular invasion of C. elegans. Importantly, heat-killed P. aeruginosa fails to elicit a significant host response, suggesting that the C. elegans response to P. aeruginosa is activated either by heat-labile signals or pathogen-induced damage. In contrast, S. aureus infection causes enterocyte effacement, intestinal epithelium destruction, and complete degradation of internal organs. S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. The C. elegans genes induced in response to S. aureus are mostly distinct from those induced by P. aeruginosa. In contrast to P. aeruginosa, heat-killed S. aureus activates a similar response as live S. aureus, which appears to be independent of the single C. elegans Toll-Like Receptor (TLR) protein. These data suggest that the host response to S. aureus is possibly mediated by pathogen-associated molecular patterns (PAMPs). Because our data suggest that neither the P. aeruginosa nor the S. aureus–triggered response requires canonical TLR signaling, they imply the existence of unidentified mechanisms for pathogen detection in C. elegans, with

  4. Staphylococcal Esx Proteins Modulate Apoptosis and Release of Intracellular Staphylococcus aureus during Infection in Epithelial Cells

    PubMed Central

    Korea, Charalampia G.; Balsamo, Giuliana; Pezzicoli, Alfredo; Merakou, Christina; Tavarini, Simona; Bagnoli, Fabio; Serruto, Davide

    2014-01-01

    The opportunistic pathogen Staphylococcus aureus is one of the major causes of health care-associated infections. S. aureus is primarily an extracellular pathogen, but it was recently reported to invade and replicate in several host cell types. The ability of S. aureus to persist within cells has been implicated in resistance to antimicrobials and recurrent infections. However, few staphylococcal proteins that mediate intracellular survival have been identified. Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system (Ess), are important during intracellular S. aureus infection. The Esx proteins are required for staphylococcal virulence, but their functions during infection are unclear. While isogenic S. aureus esxA and esxB mutants were not defective for epithelial cell invasion in vitro, a significant increase in early/late apoptosis was observed in esxA mutant-infected cells compared to wild-type-infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the protein also resulted in a significant increase of epithelial cell apoptosis. Furthermore, cells transfected with esxA showed an increased protection from apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced increased apoptosis but, remarkably, was unable to escape from cells as efficiently as the single mutants or the wild type. Thus, using in vitro models of intracellular staphylococcal infection, we demonstrate that EsxA interferes with host cell apoptotic pathways and, together with EsxB, mediates the release of S. aureus from the host cell. PMID:25047846

  5. Short Term, Low Dose Simvastatin Pretreatment Alters Memory Immune Function Following Secondary Staphylococcus aureus Infection.

    PubMed

    Smelser, Lisa K; Walker, Callum; Burns, Erin M; Curry, Michael; Black, Nathanael; Metzler, Jennifer A; McDowell, Susan A; Bruns, Heather A

    2016-01-01

    Statins are potent modulators of immune responses, resulting in their ability to enhance host survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial for survival following infection may also result in alterations in the generation of the immunologic memory response and subsequently affect immune responses mounted during secondary bacterial infection. In this study, we report that levels of total serum IgG2c, following primary infection, were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment, prior to primary infection, on immune responses activated during secondary S. aureus infection. A secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14 days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1 compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore, memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term, low dose simvastatin treatment to modulate memory immune function. PMID:26927218

  6. Novel characteristics of community-acquired methicillin-resistant Staphylococcus aureus strains belonging to multilocus sequence type 59 in Taiwan.

    PubMed

    Takano, Tomomi; Higuchi, Wataru; Zaraket, Hassan; Otsuka, Taketo; Baranovich, Tatiana; Enany, Shymaa; Saito, Kohei; Isobe, Hirokazu; Dohmae, Soshi; Ozaki, Kyoko; Takano, Misao; Iwao, Yasuhisa; Shibuya, Michiko; Okubo, Takeshi; Yabe, Shizuka; Shi, Da; Reva, Ivan; Teng, Lee-Jene; Yamamoto, Tatsuo

    2008-03-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains, which often produce Panton-Valentine leucocidin (PVL), are increasingly noted worldwide. In this study, we examined 42 MRSA strains (25 PVL-positive [PVL+] strains and 17 PVL-negative [PVL(-)] strains) isolated in Taiwan for their molecular characteristics. The PVL+ MRSA strains included CA-MRSA strains with multilocus sequence type (ST) 59 (major PVL+ MRSA in Taiwan), its variants, and worldwide CA-MRSA ST30 strains. The PVL(-) MRSA strains included the pandemic Hungarian MRSA ST239 strain, the Hungarian MRSA ST239 variant, MRSA ST59 (largely hospital-acquired MRSA strains) and its variants, the pandemic New York/Japan MRSA ST5 strain (Japanese type), and the MRSA ST8 strain. The major PVL+ CA-MRSA ST59 strain possessed a tetracycline resistance-conferring (tetK positive) penicillinase plasmid and a drug resistance gene cluster (a possible composite transposon) for multidrug resistance. Moreover, it carried a novel staphylococcal cassette chromosome mec (SCCmec) with two distinct ccrC genes (ccrC2-C8). This SCCmec (previously named SCCmec type V(T)) was tentatively designated SCCmec type VII. Sequencing of the PVL genes revealed the polymorphisms, and the PVL+ CA-MRSA ST59 strain possessed the ST59-specific PVL gene sequence. The data suggest that a significant amount of clonal spread is occurring in Taiwan and that the major PVL+ CA-MRSA ST59 Taiwan strain exhibits unique genetic characteristics, such as a novel SCCmec type and an ST59-specific PVL gene sequence. PMID:18086843

  7. Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue

    PubMed Central

    Schlecht, Lisa Marie; Peters, Brian M.; Krom, Bastiaan P.; Freiberg, Jeffrey A.; Hänsch, Gertrud M.; Filler, Scott G.

    2015-01-01

    Candida albicans and Staphylococcus aureus are often co-isolated in cases of biofilm-associated infections. C. albicans can cause systemic disease through morphological switch from the rounded yeast to the invasive hyphal form. Alternatively, systemic S. aureus infections arise from seeding through breaks in host epithelial layers although many patients have no documented portal of entry. We describe a novel strategy by which S. aureus is able to invade host tissue and disseminate via adherence to the invasive hyphal elements of Candida albicans. In vitro and ex vivo findings demonstrate a specific binding of the staphylococci to the candida hyphal elements. The C. albicans cell wall adhesin Als3p binds to multiple staphylococcal adhesins. Furthermore, Als3p is required for C. albicans to transport S. aureus into the tissue and cause a disseminated infection in an oral co-colonization model. These findings suggest that C. albicans can facilitate the invasion of S. aureus across mucosal barriers, leading to systemic infection in co-colonized patients. PMID:25332378

  8. Staphylococcus aureus infection induces protein A–mediated immune evasion in humans

    PubMed Central

    Pauli, Noel T.; Kim, Hwan Keun; Falugi, Fabiana; Huang, Min; Dulac, John; Henry Dunand, Carole; Zheng, Nai-Ying; Kaur, Kaval; Andrews, Sarah F.; Huang, Yunping; DeDent, Andrea; Frank, Karen M.; Charnot-Katsikas, Angella; Schneewind, Olaf

    2014-01-01

    Staphylococcus aureus bacterial infection commonly results in chronic or recurrent disease, suggesting that humoral memory responses are hampered. Understanding how S. aureus subverts the immune response is critical for the rescue of host natural humoral immunity and vaccine development. S. aureus expresses the virulence factor Protein A (SpA) on all clinical isolates, and SpA has been shown in mice to expand and ablate variable heavy 3 (VH3) idiotype B cells. The effects of SpA during natural infection, however, have not been addressed. Acutely activated B cells, or plasmablasts (PBs), were analyzed to dissect the ongoing immune response to infection through the production of monoclonal antibodies (mAbs). The B cells that were activated by infection had a highly limited response. When screened against multiple S. aureus antigens, only high-affinity binding to SpA was observed. Consistently, PBs underwent affinity maturation, but their B cell receptors demonstrated significant bias toward the VH3 idiotype. These data suggest that the superantigenic activity of SpA leads to immunodominance, limiting host responses to other S. aureus virulence factors that would be necessary for protection and memory formation. PMID:25348152

  9. Staphylococcus aureus infection induces protein A-mediated immune evasion in humans.

    PubMed

    Pauli, Noel T; Kim, Hwan Keun; Falugi, Fabiana; Huang, Min; Dulac, John; Henry Dunand, Carole; Zheng, Nai-Ying; Kaur, Kaval; Andrews, Sarah F; Huang, Yunping; DeDent, Andrea; Frank, Karen M; Charnot-Katsikas, Angella; Schneewind, Olaf; Wilson, Patrick C

    2014-11-17

    Staphylococcus aureus bacterial infection commonly results in chronic or recurrent disease, suggesting that humoral memory responses are hampered. Understanding how S. aureus subverts the immune response is critical for the rescue of host natural humoral immunity and vaccine development. S. aureus expresses the virulence factor Protein A (SpA) on all clinical isolates, and SpA has been shown in mice to expand and ablate variable heavy 3 (VH3) idiotype B cells. The effects of SpA during natural infection, however, have not been addressed. Acutely activated B cells, or plasmablasts (PBs), were analyzed to dissect the ongoing immune response to infection through the production of monoclonal antibodies (mAbs). The B cells that were activated by infection had a highly limited response. When screened against multiple S. aureus antigens, only high-affinity binding to SpA was observed. Consistently, PBs underwent affinity maturation, but their B cell receptors demonstrated significant bias toward the VH3 idiotype. These data suggest that the superantigenic activity of SpA leads to immunodominance, limiting host responses to other S. aureus virulence factors that would be necessary for protection and memory formation. PMID:25348152

  10. Infectious Dose Dictates the Host Response during Staphylococcus aureus Orthopedic-Implant Biofilm Infection.

    PubMed

    Vidlak, Debbie; Kielian, Tammy

    2016-07-01

    Staphylococcus aureus is a leading cause of prosthetic joint infections (PJIs) that are typified by biofilm formation. Given the diversity of S. aureus strains and their propensity to cause community- or hospital-acquired infections, we investigated whether the immune response and biofilm growth during PJI were conserved among distinct S. aureus clinical isolates. Three S. aureus strains representing USA200 (UAMS-1), USA300 (LAC), and USA400 (MW2) lineages were equally effective at biofilm formation in a mouse model of PJI and elicited similar leukocyte infiltrates and cytokine/chemokine profiles. Another factor that may influence the course of PJI is infectious dose. In particular, higher bacterial inocula could accelerate biofilm formation and alter the immune response, making it difficult to discern underlying pathophysiological mechanisms. To address this issue, we compared the effects of two bacterial doses (10(3) or 10(5) CFU) on inflammatory responses in interleukin-12p40 (IL-12p40) knockout mice that were previously shown to have reduced myeloid-derived suppressor cell recruitment concomitant with bacterial clearance after low-dose challenge (10(3) CFU). Increasing the infectious dose of LAC to 10(5) CFU negated these differences in IL-12p40 knockout animals, demonstrating the importance of bacterial inoculum on infection outcome. Collectively, these observations highlight the importance of considering infectious dose when assessing immune responsiveness, whereas biofilm formation during PJI is conserved among clinical isolates commonly used in mouse S. aureus infection models. PMID:27091926

  11. First report in South America of companion animal colonization by the USA1100 clone of community-acquired meticillin-resistant Staphylococcus aureus (ST30) and by the European clone of methicillin-resistant Staphylococcus pseudintermedius (ST71)

    PubMed Central

    2013-01-01

    Background Methicillin-resistant staphylococci can colonize and cause diseases in companion animals. Unfortunately, few molecular studies have been carried out in Brazil and other countries with the aim of characterizing these isolates. Consequently, little is known about the potential role of companion animals in transmitting these resistant bacteria to humans. In this work we searched for mecA gene among Staphylococcus isolates obtained from nasal microbiota of 130 healthy dogs and cats attended in a veterinary clinic located in the west region of Rio de Janeiro. The isolates recovered were identified to the species level and characterized using molecular tools. Results A community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate related to USA1100 (Southwest Pacific clone) and susceptible to all non-β-lactams was detected in a cat (1.7%, 1/60). Another coagulase-positive isolate harboring mecA was recovered from a dog (1.4%, 1/70) and identified as Staphylococcus pseudintermedius (MRSP) related to the European clone (ST71). The two isolates of Staphylococcus conhii subsp. urealyticus (1.4%, 1/70 dogs and 1.7%, 1/60 cats), similarly to the MRSP isolate, also presented high-level multiresistance. The majority of the methicillin-resistant coagulase-negative staphylococci recovered were Staphylococcus saprophyticus (5.7%, 4/70 dogs and 6.7%, 4/60 cats) and all clustered into the same PFGE type. Conclusions This work demonstrates that mecA-harboring Staphylococcus isolates are common members of the nasal microbiota of the healthy companion animals studied (9.2%, 12/130 animals), including some high-level multiresistant isolates of S. pseudintermedius and S. conhii subsp. urealyticus. The detection, for the first time in South America, of USA1100-related CA-MRSA and of ST71 MRSP (European clone), colonizing companion animals, is of concern. Both S. pseudintermedius and S. aureus are important agents of infections for animals. The USA1100 CA-MRSA

  12. Protective Role of Surfactant Protein D in Ocular Staphylococcus aureus Infection

    PubMed Central

    Zhang, Zhiyong; Abdel-Razek, Osama; Hawgood, Samuel; Wang, Guirong

    2015-01-01

    Staphylococcus aureus is one of the most common pathogens causing keratitis. Surfactant protein D (SP-D) plays a critical role in host defense and innate immunity. In order to investigate the role of SP-D in ocular S. aureus infection, the eyes of wild-type (WT) and SP-D knockout (SP-D KO) C57BL/6 mice were infected with S. aureus (107 CFU/eye) in the presence and absence of cysteine protease inhibitor(E64).Bacterial counts in the ocular surface were examined 3, 6, 12, 24 hrs after infection. Bacterial phagocytosis by neutrophils and bacterial invasion in ocular epithelial cells were evaluated quantitatively. S. aureus-induced ocular injury was determined with corneal fluorescein staining. The results demonstrated that SP-D is expressed in ocular surface epithelium and the lacrimal gland; WT mice had increased clearance of S. aureus from the ocular surface (p<0.05) and reduced ocular injury compared with SP-D KO mice. The protective effects of SP-D include increased bacterial phagocytosis by neutrophils (p<0.05) and decreased bacterial invasion into epithelial cells (p<0.05) in WT mice compared to in SP-D KO mice. In the presence of inhibitor (E64), WT mice showed enhanced bacterial clearance (p<0.05) and reduced ocular injury compared to absent E64 while SP-D KO mice did not. Collectively, we concluded that SP-D protects the ocular surface from S. aureus infection but cysteine protease impairs SP-D function in this murine model, and that cysteine protease inhibitor may be a potential therapeutic agent in S. aureus keratitis. PMID:26398197

  13. Evaluating efficacy of bacteriophage therapy against Staphylococcus aureus infections using a silkworm larval infection model.

    PubMed

    Takemura-Uchiyama, Iyo; Uchiyama, Jumpei; Kato, Shin-ichiro; Inoue, Tetsuyoshi; Ujihara, Takako; Ohara, Naoya; Daibata, Masanori; Matsuzaki, Shigenobu

    2013-10-01

    Silkworm larva has recently been recognized as an alternative model animal for higher mammals to evaluate the effects of antibiotics. In this study, we examined the efficacy of the bacteriophage (phage) therapy, which harnesses phages as antibacterial agents, against Staphylococcus aureus infections, using the silkworm larval infection model. Two newly isolated staphylococcal phages, S25-3 and S13', were used as therapeutic phage candidates. They were assigned to two different lytic phage genera, Twort-like and AHJD-like viruses, based on their morphologies and the N-terminal amino acid sequences of the major capsid proteins. Both had a broad host range and strong lytic activity and showed preservative quality. Administration of these phages alone caused no adverse effects in the silkworm larvae. Moreover, the viruses showed life-prolonging effects in the silkworm larval infection model 10 min, 6 h, 12 h, and 24 h following infection. Such phage effects in the silkworm larval model were almost paralleled to the therapeutic efficacies in mouse models. These results suggest that phages S25-3 and S13' are eligible as therapeutic candidates and that the silkworm larval model is valid for the evaluation of phage therapy as well as mouse models. PMID:23869440

  14. Increased infectivity of Staphylococcus aureus in an experimental model of snake venom-induced tissue damage.

    PubMed

    Saravia-Otten, Patricia; Gutierrez, Jose Maria; Arvidson, Staffan; Thelestam, Monica; Flock, Jan-Ingmar

    2007-09-01

    Soft-tissue infection is commonly found in patients bitten by Latin American Bothrops snakes. Staphylococcus aureus, which is not present in the mouth of the snake, is frequently isolated from these infections. The effects of B. asper venom on infection with S. aureus were analyzed in a model of infection in envenomated mouse gastrocnemius muscle. Inoculation of 50 colony-forming units (cfu) of S. aureus was enough to cause infection in envenomated muscle, compared with >5x104 cfu without venom. This effect was also achieved by injection of venom myotoxin III (an A(2) phospholipase). A sarA mutant strain in which production of extracellular toxins and enzymes is up-regulated and binding of fibronectin, fibrinogen, and other host proteins is down-regulated was much less virulent than the corresponding parental strain, indicating that the ability of S. aureus to mask itself with host molecules might be more important than the effects of secreted toxins and enzymes in this kind of infection. PMID:17674318

  15. Staphylococcus aureus epidemic in a neonatal nursery: a strategy of infection control.

    PubMed

    Bertini, Giovanna; Nicoletti, PierLuigi; Scopetti, Franca; Manoocher, Pourshaban; Dani, Carlo; Orefici, Graziella

    2006-08-01

    The risk of nosocomial infection due to Staphylococcus aureus in fullterm newborns is higher under hospital conditions where there are overcrowded nurseries and inadequate infection control techniques. We report on an outbreak of skin infection in a Maternity Nursery (May 21, 2000) and the measures undertaken to bring the epidemic under control. These measures included: separating neonates already present in the nursery on August 23, 2000 from ones newly arriving by creating two different cohorts, one of neonates born before this date and one of neonates born later; restricting healthcare workers caring for S. aureus- infected infants from working with non-infected infants; disallowing carrier healthcare workers from caring for patients; introducing contact and droplet precautions (including the routine use of gowns, gloves, and mask); ensuring appropriate disinfection of potential sources of contamination. A representative number of isolates were typed by genomic DNA restriction length polymorphism analysis by means of pulsed-field gel electrophoresis (PFGE). Among the 227 cases of skin lesions, microbiological laboratory analyses confirmed that 175 were staphylococcal infections. The outbreak showed a gradual reduction in magnitude when the overcrowding of the Nursery was reduced by separating the newborns into the two different Nurseries (two cohorts). The genotyping of the strains by PFGE confirmed the nurse-to-newborn transmission of S. aureus. The measures adopted for controlling the S. aureus outbreak can, in retrospect, be assessed to have been very effective. PMID:16602005

  16. Identification of Infantile Diarrhea Caused by Breast Milk-Transmitted Staphylococcus aureus Infection.

    PubMed

    Chen, Zhong; Pan, Wei-Guang; Xian, Wei-Yi; Cheng, Hang; Zheng, Jin-Xin; Hu, Qing-Hua; Yu, Zhi-Jian; Deng, Qi-Wen

    2016-10-01

    Staphylococcus aureus is a well-known organism which is responsible for a variety of human infectious diseases including skin infections, pneumonia, bacteremia, and endocarditis. Few of the microorganisms can be transmitted from mother to the newborn or infant by milk breastfeeding. This study aims to identify transmission of S. aureus from healthy, lactating mothers to their infants by breastfeeding. Stool specimens of diarrheal infants and breast milk of their mother (totally three pairs) were collected and six Staphylococcus aureus isolates were cultured positively. Homology and molecular characters of isolated strains were tested using pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing. Furthermore, toxin genes detection was also performed. Each pair of isolates has the same PFGE type and spa type. Four Sequence types (STs) were found among all the isolates; they are ST15, ST188, and ST59, respectively. Among the strains, seb, sec, and tst genes were found, and all were negative for pvl gene. The homology of the S. aureus strains isolated from the infants' stool and the mothers' milk was genetically demonstrated, which indicated that breastfeeding may be important in the transmission of S. aureus infection, and the character of S. aureus needed to be further evaluated. PMID:27344596

  17. Sternal and costochondral infections with gentamicin and methicillin resistant Staphylococcus aureus following thoracic surgery.

    PubMed

    Cafferkey, M T; Luke, D A; Keane, C T

    1983-01-01

    Six patients in a thoracic unit developed sternal osteomyelitis and costochondritis following median sternotomy. Five of the patients were operated on in another hospital. Gentamicin and methicillin resistant Staphylococcus aureus was isolated in pure culture in each case. The S. aureus isolate from 2 patients was of the same phage type suggesting cross-infection. Antibiotic prophylaxis administered in the perioperative period was ineffective. One patient, treated with amikacin (to which all of the strains were sensitive in vitro) and cefuroxime, died from overwhelming infection in spite of débridement and resuturing of the wound. The remaining 5 patients were cured with vancomycin therapy usually coupled with surgical intervention. PMID:6557667

  18. The herbal-derived honokiol and magnolol enhances immune response to infection with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA).

    PubMed

    Choi, Eun-Jin; Kim, Hyung-Ip; Kim, Ji-Ae; Jun, Soo Youn; Kang, Sang Hyeon; Park, Dong June; Son, Seok-Jun; Kim, Younghoon; Shin, Ok Sarah

    2015-05-01

    The emergence of antibiotic resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) reminds us an urgent need to develop a new immune-modulating agent for preventing S. aureus infection. In this study, we found that herbal medicines, honokiol and magnolol, caused a significant cellular immune modulatory effect during S. aureus infection. In mouse macrophages, these compounds drove upregulation of an antioxidant effect in response to S. aureus, resulting in a dampened total cellular reactive oxygen species (ROS) production and decreased production of inflammatory cytokines/chemokines, whereas honokiol induced increased types I and III interferon messenger RNA (mRNA) expression levels in response to MSSA infection. Moreover, the internalization of S. aureus by human alveolar epithelial cells was inhibited by these compounds. Furthermore, honokiol and magnolol treatment promoted a delay in killing during MSSA infection in Caenorhabditis elegans, suggesting antimicrobial function in vivo. In conclusion, honokiol and magnolol may be considered as attractive immune-modulating treatment for S. aureus infection. PMID:25586586

  19. Trends of Staphylococcus aureus bloodstream infections in a neonatal intensive care unit from 2000-2009

    PubMed Central

    2014-01-01

    Background Invasive methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections are major causes of numerous neonatal intensive care unit (NICU) outbreaks. There have been increasing reports of MRSA outbreaks in various neonatal intensive care units (NICUs) over the last decade. Our objective was to review the experience of Staphylococcus aureus sepsis in our NICU in the last decade and describe the trends in the incidence of Staphylococcus aureus blood stream infections from 2000 to 2009. Methods A retrospective perinatal database review of all neonates admitted to our NICU with blood cultures positive for Staphylococcus aureus from (Jan 1st 2000 to December 31st 2009) was conducted. Infants were identified from the database and data were collected regarding their clinical characteristics and co-morbidities, including shock with sepsis and mortality. Period A represents patients admitted in 2000-2003. Period B represents patients seen in 2004-2009. Results During the study period, 156/11111 infants were identified with Staphylococcus aureus blood stream infection: 41/4486 (0.91%) infants in Period A and 115/6625 (1.73%) in Period B (p < 0.0004). Mean gestation at birth was 26 weeks for infants in both periods. There were more MRSA infections in Period B (24% vs. 55% p < 0.05) and they were associated with more severe outcomes. In comparing the cases of MRSA infections observed in the two periods, infants in period B notably had significantly more pneumonia cases (2.4% vs. 27%, p = 0.0005) and a significantly higher mortality rate (0% vs. 15.7%, p = 0.0038). The incidences of skin and soft tissue infections and of necrotizing enterocolitis were not significantly changed in the two periods. Conclusion There was an increase in the incidence of Staphylococcus aureus infection among neonates after 2004. Although MSSA continues to be a problem in the NICU, MRSA infections were more prevalent in the

  20. Clindamycin-susceptibility Rates of Methicillin-resistant Staphylococcus aureus Varies by Infection Type in Pediatric Patients.

    PubMed

    Li, Amanda; Selvarangan, Rangaraj; Ogden, Richard; French, Brandon; Yu, Diana

    2016-08-01

    Hospital-wide antibiograms provide general susceptibility patterns. Specific antibiograms were created for methicillin-resistant Staphylococcus aureus isolates based on infection process and epidemiology. Using clinical microbiology laboratory data and patient profiles, high clindamycin resistance rates were seen for nonskin and soft tissue infections and noncommunity-associated methicillin-resistant S. aureus isolates. PMID:27164465

  1. Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection

    PubMed Central

    Li, Xue; Wang, Xiaogang; Thompson, Christopher D.; Park, Saeyoung; Park, Wan Beom

    2016-01-01

    ABSTRACT Treatment of Staphylococcus aureus infections has become increasingly difficult because of the emergence of multidrug-resistant isolates. Development of a vaccine to prevent staphylococcal infections remains a priority. To determine whether clumping factor A (ClfA) is a good target protein for inclusion in a multivalent vaccine, we evaluated its efficacy in a variety of relevant staphylococcal infection models, challenging with different S. aureus strains. ClfA adsorbed to Alhydrogel and mixed with Sigma Adjuvant System was more immunogenic and stimulated a more robust Th17 response than ClfA administered with alum alone. ClfA immunization induced the production of functional antibodies in rabbits and mice that blocked S. aureus binding to fibrinogen and were opsonic for S. aureus strains that produced little or no capsular polysaccharide. Mice immunized with ClfA showed a modest reduction in the bacterial burden recovered from subcutaneous abscesses provoked by S. aureus USA300 strain LAC. In addition, the ClfA vaccine reduced lethality in a sepsis model following challenge with strain Newman, but not ST80. Vaccination with ClfA did not protect against surgical wound infection, renal abscess formation, or bacteremia. Passive immunization with antibodies to ClfA did not protect against staphylococcal bacteremia in mice or catheter-induced endocarditis in rats. Some enhancement of bacteremia was observed by ClfA immunization or passive administration of ClfA antibodies when mice were challenged by the intraperitoneal route. Although rodent models of staphylococcal infection have their limitations, our data do not support the inclusion of ClfA in an S. aureus multivalent vaccine. PMID:26838725

  2. Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

    PubMed Central

    Gil, Carmen; Solano, Cristina; Burgui, Saioa; Latasa, Cristina; García, Begoña; Toledo-Arana, Alejandro

    2014-01-01

    The Staphylococcus aureus biofilm mode of growth is associated with several chronic infections that are very difficult to treat due to the recalcitrant nature of biofilms to clearance by antimicrobials. Accordingly, there is an increasing interest in preventing the formation of S. aureus biofilms and developing efficient antibiofilm vaccines. Given the fact that during a biofilm-associated infection, the first primary interface between the host and the bacteria is the self-produced extracellular matrix, in this study we analyzed the potential of extracellular proteins found in the biofilm matrix to induce a protective immune response against S. aureus infections. By using proteomic approaches, we characterized the exoproteomes of exopolysaccharide-based and protein-based biofilm matrices produced by two clinical S. aureus strains. Remarkably, results showed that independently of the nature of the biofilm matrix, a common core of secreted proteins is contained in both types of exoproteomes. Intradermal administration of an exoproteome extract of an exopolysaccharide-dependent biofilm induced a humoral immune response and elicited the production of interleukin 10 (IL-10) and IL-17 in mice. Antibodies against such an extract promoted opsonophagocytosis and killing of S. aureus. Immunization with the biofilm matrix exoproteome significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue, using an in vivo model of mesh-associated biofilm infection. Furthermore, immunized mice also showed limited organ colonization by bacteria released from the matrix at the dispersive stage of the biofilm cycle. Altogether, these data illustrate the potential of biofilm matrix exoproteins as a promising candidate multivalent vaccine against S. aureus biofilm-associated infections. PMID:24343648

  3. Non-invasive Imaging of Staphylococcus aureus Infections with a Nuclease-Activated Probe

    PubMed Central

    Hernandez, Frank J.; Huang, Lingyan; Olson, Michael E.; Powers, Kristy M.; Hernandez, Luiza I.; Meyerholz, David K.; Thedens, Daniel R.; Behlke, Mark A.; Horswill, Alexander R.; McNamara, James O.

    2013-01-01

    Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, non-invasive detection of S. aureus based on the activity of its secreted nuclease, micrococcal nuclease (MN). Several short, synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications, flanked with a fluorophore and quencher, were activated upon degradation by recombinant MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2′-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing bioluminescent S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This novel bacterial imaging approach has potential clinical applicability for S. aureus and several other medically significant pathogens. PMID:24487433

  4. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice

    PubMed Central

    Cho, John S.; Pietras, Eric M.; Garcia, Nairy C.; Ramos, Romela Irene; Farzam, David M.; Monroe, Holly R.; Magorien, Julie E.; Blauvelt, Andrew; Kolls, Jay K.; Cheung, Ambrose L.; Cheng, Genhong; Modlin, Robert L.; Miller, Lloyd S.

    2010-01-01

    Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in γδ but not αβ T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vγ5+ γδ T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R–deficient mice had a phenotype similar to that of γδ T cell–deficient mice. Importantly, γδ T cell–deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17–producing epidermal γδ T cells in innate immunity against S. aureus cutaneous infection. PMID:20364087

  5. Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation

    PubMed Central

    Kong, Cin; Tan, Man-Wah; Nathan, Sheila

    2014-01-01

    ABSTRACT Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans–S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host. PMID:24972867

  6. Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation.

    PubMed

    Kong, Cin; Tan, Man-Wah; Nathan, Sheila

    2014-01-01

    Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host. PMID:24972867

  7. Protective immunization against Staphylococcus aureus infection in a novel experimental wound model in mice.

    PubMed

    Schennings, Torgny; Farnebo, Filip; Szekely, Laszlo; Flock, Jan-Ingmar

    2012-10-01

    A novel murine experimental wound infection model was used to assess the efficacy of multi-component immunization against Staphylococcus aureus infection. Necrotic lesions were induced in mice with venom from Bothrops asper and infected with a low inoculum, 1 × 10(2) CFU. The wound infection model therefore more resembles a clinical case of S. aureus infection compared with conventional infection models where far more bacteria are required. Before infection, mice were immunized with four recombinant S.aureus proteins expressed from Escherichia coli: (i) domains 1-3 of Extracellular adherence protein (Eap), (ii) Efb - D (fusion protein combining Extracellular fibrinogen binding protein (Efb) and a fibronectin binding domain (D) of the fibronectin binding protein (FnBP) and (iii) clumping factor A (ClfA). In the immunized group, lower bacterial colonization, undisturbed crust formation and significantly faster wound healing were found compared with the unimmunized control group. Efb and Eap have previously been found to impair wound healing and neutralization of these proteins by antibodies restores a more natural wound healing process. This effect is further also enhanced by the proposed opsonic activity of antibodies against ClfA and FnBP. PMID:22958286

  8. Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin

    PubMed Central

    Chakraborty, Subhankari Prasad; Pramanik, Panchanan; Roy, Somenath

    2012-01-01

    Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5 × 106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils. PMID:22530141

  9. Emergence of Panton-Valentine leucocidin-positive ST8-methicillin-resistant Staphylococcus aureus (USA300 clone) in Korea causing healthcare-associated and hospital-acquired bacteraemia.

    PubMed

    Jung, J; Song, E H; Park, S Y; Lee, S-R; Park, S-J; Sung, H; Kim, M-N; Kim, S-H; Lee, S-O; Choi, S-H; Woo, J H; Kim, Y S; Chong, Y P

    2016-08-01

    Panton-Valentine leucocidin (PVL)-positive sequence type (ST)8-MRSA-SCCmec IVa (USA300) is the epidemic strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in North America. USA300 is extremely rare in South Korea, and PVL-negative ST72 SCCmec type IVc is the predominant CA-MRSA clone. In a multicentre, prospective cohort study of S. aureus bacteraemia, we identified PVL-positive ST8-MRSA isolates by performing multilocus sequence typing and PCR for PVL. We analyzed the clinical characteristics of patients with PVL-positive ST8-MRSA bacteraemia, and performed SCCmec, spa, and agr typing, PCR for arginine catabolic mobile element (ACME), virulence gene profiling, and pulsed-field gel electrophoresis (PFGE). Among a total of 818 MRSA isolates, we identified ten isolates of PVL-positive ST8-MRSA (USA300) (3 from Hospital D, 4 from Hospital G, and 3 from Hospital A), all of which involved exclusively healthcare-associated (5 isolates) and hospital-acquired bacteraemia (5 isolates). This strain accounted for 8~10 % of the hospital-acquired MRSA bacteraemia in Hospitals D and G. Bacteraemia of unknown origin was the most common type of infection followed by pneumonia. All the isolates were SCCmec type IVa, spa type t008, and agr group I. Eight of the isolates harboured ACME. In a PFGE analysis, four isolates were identical to the USA300 control strain, five differed by a single band, and the remaining one differed by two bands. All the isolates were pulsed-field type USA300. This is the first report of healthcare-associated and hospital-acquired bacteraemia caused by USA300 in South Korea. USA300 seems to be an emerging hospital clone in this country. PMID:27209287

  10. [Treatment with arbekacin of surgical infections by resistant strains of Staphylococcus aureus. Arbekacin Study Group].

    PubMed

    Morimoto, K; Nakatani, S; Kaji, M; Kinoshita, H; Fujimoto, M; Hirata, S; Ueda, T; Tamate, S; Yamazaki, O

    1994-06-01

    The frequency of infection by methicillin-resistant Staphylococcus aureus (MRSA) is high in Japan and control of such strains is urgently needed. Arbekacin (ABK), a semisynthetic aminoglycoside, has potent activity against S. aureus, including resistant strains, and against Gram-negative bacteria as well. For this reason, in surgical infections (which are often caused by more than one bacterium), this drug might be particularly effective. We calculated the MIC and the decrease in the MIC when cultures of 59 resistant strains of S. aureus isolated in our wards at Osaka City University Hospital, contained arbekacin in the medium. We also used the drug to treat 12 infections caused by resistant strains of S. aureus. The MICs of vancomycin had a single peak at 0.5 microgram/ml, and those for ABK had double peaks at 0.5 and 4.0 micrograms/ml. The effect of arbekacin in lowering the MIC of minocycline (MINO) was slight because of the low MIC of MINO. Effects on fosfomycin (FOM), ampicillin, clavulanic acid/ticarcillin, cefotiam, cefuzonam, flomoxef, and imipenem/cilastatin were strong; the peaks were lowered by 1/2(7)-1/2(11). When 1.0 micrograms/ml ABK was present in the medium, the efficacy of FOM was increased enough that, by prediction from the pharmacokinetics of FOM (blood level when given at the usual dose), all but one (2%) of the 47 resistant strains would be eradicated clinically. If 2.0 micrograms/ml ABK were in the medium, all strain would be eradicated, by our calculations. We treated 11 infections and one colonization by resistant strains of S. aureus with ABK and evaluated the response in these cases of infection. Four infections were treated with FOM as well. The clinical efficacy was good in four infections (three patients), fair in four, and poor in three, for an efficacy rate of 36%. All presumed causative bacteria were eradicated in two (18%) of the 11 infections and S. aureus strains were eradicated in three (27%) of the 11 infections. No symptoms of

  11. Antibody-Based Biologics and Their Promise to Combat Staphylococcus aureus Infections.

    PubMed

    Sause, William E; Buckley, Peter T; Strohl, William R; Lynch, A Simon; Torres, Victor J

    2016-03-01

    The growing incidence of serious infections mediated by methicillin-resistant Staphylococcus aureus (MRSA) strains poses a significant risk to public health. This risk is exacerbated by a prolonged void in the discovery and development of truly novel antibiotics and the absence of a vaccine. These gaps have created renewed interest in the use of biologics in the prevention and treatment of serious staphylococcal infections. In this review, we focus on efforts towards the discovery and development of antibody-based biologic agents and their potential as clinical agents in the management of serious S. aureus infections. Recent promising data for monoclonal antibodies (mAbs) targeting anthrax and Ebola highlight the potential of antibody-based biologics as therapeutic agents for serious infections. PMID:26719219

  12. An update on the epidemiology, pathogenesis and management of infective endocarditis with emphasis on Staphylococcus aureus.

    PubMed

    Tak, Tahir; Reed, Kurt D; Haselby, Ray C; McCauley, Charles S; Shukla, Sanjay K

    2002-01-01

    The incidence of infective endocarditis (IE) is thought to be around 4/100,000 person years in the general population, and 15/100,000 over the age of 50 years. The risk of acquiring IE is higher among patients with valvular heart disease (e.g., rheumatic valves, bicuspid aortic valves, myxomatous degeneration, etc.), congenital heart disease (e.g., coarctation, patent ductus arteriosus, ventricular septal defect, etc.), prosthetic cardiac valves, and among intravenous drug abusers. Staphylococcus aureus is one of the most common infective agents of IE, and most commonly originates from nosocomial sources, e.g., intravenous and arterial catheters, pacemaker leads, and prosthetic valves. Endocarditis caused by S aureus has a mortality rate of approximately 20% to 40%. In up to 40% of patients, IE caused by S aureus is associated with embolic complications. The risk of death increases with the development of complications. The epidemiology and microbiology of S aureus are changing rapidly, and resistance to antibiotics, especially methicillin, is becoming more widespread. In this review we will focus on the epidemiology, microbiology, and pathogenesis of S aureus IE, and also summarize the current guidelines for diagnosis, treatment, and prophylaxis of this clinical condition. PMID:12426917

  13. Clinical and Molecular Characterization of Invasive Heteroresistant Vancomycin-Intermediate Staphylococcus aureus Infections in Korean Hospitals.

    PubMed

    Kim, Eu Suk; Bae, In-Gyu; Cho, Jeong Eun; Choi, Yun Jung; Kim, Il-Hwan; Kang, Gi-Su; Sin, Hye-yun; Song, Kyoung-Ho; Park, Chulmin; Lee, Dong-Gun; Kim, Moonsuk; Park, Kyoung Un; Kim, Hong Bin

    2016-03-01

    Invasive heteroresistant vancomycin-intermediate Staphylococcus aureus (h-VISA) isolates were identified and characterized in 10 Korean hospitals from July 2009 to June 2011. The prevalence of h-VISA infections was 3.3% (42/1,289). Most (41/42) were health care-associated infections caused by strains belonging to sequence type 5. Cases of persistent bacteremia were frequent (17/42), and 30-day mortality was high (16/40). PMID:26677256

  14. The receptor for advanced glycation end products promotes bacterial growth at distant body sites in Staphylococcus aureus skin infection.

    PubMed

    Achouiti, Ahmed; Van't Veer, Cornelis; de Vos, Alex F; van der Poll, Tom

    2015-09-01

    The receptor for advanced glycation endproducts (RAGE) has been implicated in the regulation of skin inflammation. We here sought to study the role of RAGE in host defense during skin infection caused by Staphylococcus (S.) aureus, the most common pathogen in this condition. Wild-type (Wt) and RAGE deficient (rage(-/-)) mice were infected subcutaneously with S. aureus and bacterial loads and local inflammation were quantified at regular intervals up to 8 days after infection. While bacterial burdens were similar in both mouse strains at the primary site of infection, rage(-/-) mice had lower bacterial counts in lungs and liver. Skin cytokine and chemokine levels did not differ between groups. In accordance with the skin model, direct intravenous infection with S. aureus was associated with lower bacterial loads in lungs and liver of rage(-/-) mice. Together these data suggest that RAGE does not impact local host defense during S. aureus skin infection, but facilitates bacterial growth at distant body sites. PMID:26086798

  15. Metabolic Profiling for Detection of Staphylococcus aureus Infection and Antibiotic Resistance

    PubMed Central

    Näsström, Elin; Kouremenos, Konstantinos; Sundén-Cullberg, Jonas; Guo, YongZhi; Moritz, Thomas; Wolf-Watz, Hans; Johansson, Anders; Fallman, Maria

    2013-01-01

    Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) were used in vitro and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. In vitro experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe Escherichia coli sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, in vitro, and mice samples identified 25 metabolites indicative of effective treatment of S. aureus sepsis. Taken together, this study provides a

  16. Efficacy of Lantibiotic Treatment of Staphylococcus aureus-Induced Skin Infections, Monitored by In Vivo Bioluminescent Imaging.

    PubMed

    van Staden, Anton Du Preez; Heunis, Tiaan; Smith, Carine; Deane, Shelly; Dicks, Leon M T

    2016-07-01

    Staphylococcus aureus is a bacterial pathogen responsible for the majority of skin and soft tissue infections. Antibiotics are losing their efficacy as treatment for skin and soft tissue infections as a result of increased resistance in a variety of pathogens, including S. aureus It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options for skin and soft tissue infections. A select few lantibiotics, a group of natural defense peptides produced by bacteria, inhibit the growth of numerous clinical S. aureus isolates, including methicillin-resistant strains. In this study, the antimicrobial activities of nisin, clausin, and amyloliquecidin, separately administered, were compared to that of a mupirocin-based ointment, which is commonly used as treatment for S. aureus-induced skin infections. Full-thickness excisional wounds, generated on the dorsal surfaces of mice, were infected with a bioluminescent strain of S. aureus (strain Xen 36). The infections were monitored in real time using in vivo bioluminescent imaging. Lantibiotic treatments significantly reduced the bioluminescence of S. aureus Xen 36 to a level similar to that recorded with mupirocin treatment. Wound closure, however, was more pronounced during lantibiotic treatment. Lantibiotics thus have the potential to be used as an alternative treatment option for S. aureus-induced skin infections. PMID:27067340

  17. Risk factors and gene type for infections of MRSA in diabetic foot patients in Tianjin, China.

    PubMed

    Feng, Shu-Hong; Chu, Yue-Jie; Wang, Peng-Hua; Jun, Xu; Min, Ding; Li, Xue-Mei

    2013-06-01

    The objective was to study risk factors and gene type of DF patients infected with MRSA. A total of 429 DF patients were recruited. The patients with S aureus infections were divided into MRSA and MSSA groups. MRSA were genotyped by SCCmec. pvl and lukE-lukD were detected. A total of 559 pathogens were isolated from them, with G+ bacteria firstly(59.0%), followed G- bacilli (37.7%) and true fungi (3.3%). The 3 most frequently isolated pathogens were S aureus (35.2%), S epidermidis (12.3%), and Pseudomonas aeruginosa (11.2%). SCCmec III MRSA and SCCmec IVa MRSA had the same antibacterial spectrum. mecA positive rate was 100%. lukE-lukD and pvl positive rates were 100% and 0%, respectively. 28 strains belonged to SCCmec III and the others belonged to SCCmec IVa. The G+ cocci were the main pathogens, S aureus and S epidermidis were predominant among them. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis and hypoproteinemia are risk factors for MRSA. SCCmec IVa is high in proportion to MRSA isolates, suggesting that CA-MRSA has become major pathogen of DF infection. All the MRSA were harboring lukE-lukD, which has been reported to present poor leucotoxin compared to pvl, and may be a response to atypical local inflammatory reaction in DF infection. PMID:23771611

  18. Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis

    PubMed Central

    Stach, Christopher S.; Vu, Bao G.; Merriman, Joseph A.; Herrera, Alfa; Cahill, Michael P.; Schlievert, Patrick M.; Salgado-Pabón, Wilmara

    2016-01-01

    Background Superantigens are indispensable virulence factors for Staphylococcus aureus in disease causation. Superantigens stimulate massive immune cell activation, leading to toxic shock syndrome (TSS) and contributing to other illnesses. However, superantigens differ in their capacities to induce body-wide effects. For many, their production, at least as tested in vitro, is not high enough to reach the circulation, or the proteins are not efficient in crossing epithelial and endothelial barriers, thus remaining within tissues or localized on mucosal surfaces where they exert only local effects. In this study, we address the role of TSS toxin-1 (TSST-1) and most importantly the enterotoxin gene cluster (egc) in infective endocarditis and sepsis, gaining insights into the body-wide versus local effects of superantigens. Methods We examined S. aureus TSST-1 gene (tstH) and egc deletion strains in the rabbit model of infective endocarditis and sepsis. Importantly, we also assessed the ability of commercial human intravenous immunoglobulin (IVIG) plus vancomycin to alter the course of infective endocarditis and sepsis. Results TSST-1 contributed to infective endocarditis vegetations and lethal sepsis, while superantigens of the egc, a cluster with uncharacterized functions in S. aureus infections, promoted vegetation formation in infective endocarditis. IVIG plus vancomycin prevented lethality and stroke development in infective endocarditis and sepsis. Conclusions Our studies support the local tissue effects of egc superantigens for establishment and progression of infective endocarditis providing evidence for their role in life-threatening illnesses. In contrast, TSST-1 contributes to both infective endocarditis and lethal sepsis. IVIG may be a useful adjunct therapy for infective endocarditis and sepsis. PMID:27124393

  19. Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus

    PubMed Central

    Nash, Evelyn E.; Peters, Brian M.; Fidel, Paul L.

    2015-01-01

    Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An experimental mouse model of Candida albicans-Staphylococcus aureus intra-abdominal infection (IAI) results in 100% mortality by 48 to 72 h postinoculation, while monomicrobial infections are avirulent. Mortality is associated with robust local and systemic inflammation without a requirement for C. albicans morphogenesis. However, the contribution of virulence factors coregulated during the yeast-to-hypha transition is unknown. This also raised the question of whether other Candida species that are unable to form hyphae are as virulent as C. albicans during polymicrobial IAI. Therefore, the purpose of this study was to evaluate the ability of non-albicans Candida (NAC) species with various morphologies and C. albicans transcription factor mutants (efg1/efg1 and cph1/cph1) to induce synergistic mortality and the accompanying inflammation. Results showed that S. aureus coinoculated with C. krusei or C. tropicalis was highly lethal, similar to C. albicans, while S. aureus-C. dubliniensis, S. aureus-C. parapsilosis, and S. aureus-C. glabrata coinoculations resulted in little to no mortality. Local and systemic interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were significantly elevated during symptomatic and/or lethal coinfections, and hypothermia strongly correlated with mortality. Coinoculation with C. albicans strains deficient in the transcription factor Efg1 but not Cph1 reversed the lethal outcome. These results support previous findings and demonstrate that select Candida species, without reference to any morphological requirement, induce synergistic mortality, with IL-6 and PGE2 acting as key inflammatory factors. Mechanistically, signaling pathways controlled by Efg1 are critical for the ability of C. albicans to induce mortality from an intra-abdominal polymicrobial infection. PMID:26483410

  20. Noninvasive In Vivo Imaging to Evaluate Immune Responses and Antimicrobial Therapy against Staphylococcus aureus and USA300 MRSA Skin Infections

    PubMed Central

    Cho, John S.; Zussman, Jamie; Donegan, Niles P.; Irene Ramos, Romela; Garcia, Nairy C.; Uslan, Daniel Z.; Iwakura, Yoichiro; Simon, Scott I.; Cheung, Ambrose L.; Modlin, Robert L.; Kim, Jenny; Miller, Lloyd S.

    2011-01-01

    Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies. PMID:21191403

  1. Infections of diabetic foot ulcers with methicillin-resistant Staphylococcus aureus.

    PubMed

    Cervantes-García, Estrella; García-González, Rafael; Reséndiz-Albor, Aldo; Salazar-Schettino, Paz Maria

    2015-03-01

    Infected diabetic foot is the most common reason for hospitalization and complications in patients with type 2 diabetes mellitus (DM2). Methicillin-resistant Staphylococcus aureus (MRSA) is frequently isolated from such lesions, and its presence is growing, seriously deteriorating the infected patient's quality of life. The aim of this study was to assess the prevalence of MRSA as well as other microbiota in 100 patients diagnosed with (DM2) and with infected foot ulcers at the Hospital General de Mexico. The main results obtained show a prevalence of Staphylococcus aureus (42%), followed by Escherichia coli (36%) and, in lower percentages, other bacteria. MRSA was predominant (34%), and we conclude that the use of cefoxitin instead of oxacillin as the first-choice antibiotic has an advantage because it is a better inducer of methicillin-resistance expression. PMID:25573977

  2. The Impact of Infectious Disease Specialist Consultation for Staphylococcus aureus Bloodstream Infections: A Systematic Review.

    PubMed

    Paulsen, Julie; Solligård, Erik; Damås, Jan Kristian; DeWan, Andrew; Åsvold, Bjørn Olav; Bracken, Michael B

    2016-03-01

    Staphylococcus aureus is a common cause of severe bloodstream infection. We performed a systematic review to assess whether consultation with infectious disease specialists decreased all-cause mortality or rate of complications of S aureus bloodstream infections. The review also assessed parameters associated with the quality of management of the infection. We searched for eligible studies in PubMed, Embase, Scopus, and clinical trials.gov as well as the references of included studies. We identified 22 observational studies and 1 study protocol for a randomized trial. A meta-analysis was not performed because of the high risk of bias in the included studies. The outcomes are reported in a narrative review. Most included studies reported survival benefit, in the adjusted analysis. Recommended management strategies were carried out significantly more often among patients seen by an infectious disease specialist. Trials, such as cluster-randomized controlled trials, can more validly assess the studies at low risk of bias. PMID:27047985

  3. The Impact of Infectious Disease Specialist Consultation for Staphylococcus aureus Bloodstream Infections: A Systematic Review

    PubMed Central

    Paulsen, Julie; Solligård, Erik; Damås, Jan Kristian; DeWan, Andrew; Åsvold, Bjørn Olav; Bracken, Michael B.

    2016-01-01

    Staphylococcus aureus is a common cause of severe bloodstream infection. We performed a systematic review to assess whether consultation with infectious disease specialists decreased all-cause mortality or rate of complications of S aureus bloodstream infections. The review also assessed parameters associated with the quality of management of the infection. We searched for eligible studies in PubMed, Embase, Scopus, and clinical trials.gov as well as the references of included studies. We identified 22 observational studies and 1 study protocol for a randomized trial. A meta-analysis was not performed because of the high risk of bias in the included studies. The outcomes are reported in a narrative review. Most included studies reported survival benefit, in the adjusted analysis. Recommended management strategies were carried out significantly more often among patients seen by an infectious disease specialist. Trials, such as cluster-randomized controlled trials, can more validly assess the studies at low risk of bias. PMID:27047985

  4. Skin bacteriology and the role of Staphylococcus aureus in infection.

    PubMed

    Noble, W C

    1998-12-01

    Many of the staphylococci and coryneforms that inhabit normal human skin do not cause skin disease. Amongst the remainder the mechanisms of pathogenicity vary widely. For Proteus, Pseudomonas and Brevibacterium species proteolysis is a major determinant. The precise role of Corynebacterium minutissimum in erythrasma and the propionibacteria in acne is not known. Staphylococcus aureus, however, produces a wide range of non-specific agents, such as haemolysins and leucocidins as well as highly specific toxins such as the epidermolytic toxins involved in bullous impetigo and scalded skin syndrome. Most of the current attention, however, is devoted to the role of the enterotoxins and toxic shock toxin as superantigens, with emphasis on their role in atopic dermatitis. Molecularly similar toxins in the streptococci play a similar role and may also have a role in the aetiology of psoriasis. PMID:9990407

  5. Vaccination With a UV-Irradiated Genetically Attenuated Mutant of Staphylococcus aureus Provides Protection Against Subsequent Systemic Infection

    PubMed Central

    Burnside, Kellie; Lembo, Annalisa; Harrell, Maria Isabel; Klein, Jessica Abbey; Lopez-Guisa, Jesus; Siegesmund, Amy M.; Torgerson, Troy R.; Oukka, Mohamed; Molina, Douglas M.; Rajagopal, Lakshmi

    2012-01-01

    Staphylococcus aureus are gram-positive bacteria that cause clinically significant infections in humans. Severe S. aureus infections are particularly problematic in hospitalized patients and reoccur despite therapeutic measures. The absence of natural protective immune responses and the lack of high-throughput approaches to identify S. aureus antigens have imposed constraints in the development of effective vaccines. Here, we showed that vaccination with the genetically attenuated S. aureus mutant, inactivated using UV irradiation rather than heat, significantly increased survival and diminished bacterial burden and kidney abscesses when mice were challenged with virulent methicillin-sensitive or methicillin-resistant S. aureus. Protection conferred by immunization could be transferred to the naive host and was not observed in B-cell–deficient mice. Using a novel S. aureus whole-proteome microarray, we show that immunoglobulin G antibody responses to 83 proteins were observed in the immunized mice. These results suggest that protection against S. aureus infections requires antibody responses to the wide repertoire of antigens/virulence factors. Vaccination using UV-irradiated genetically attenuated S. aureus induces humoral immunity and provides a vaccine strategy for pathogens that fail to induce protective immunity. We also describe a novel, high-throughput technology to easily identify S. aureus antigens for vaccine development. PMID:22966130

  6. Methicillin-resistant Staphylococcus non-aureus Infection in an Irradiated Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Kolappaswamy, Krishnan; Shipley, Steven T; Tatarov, Ivan I; DeTolla, Louis J

    2008-01-01

    We describe a case of methicillin-resistant Staphylococcus non-aureus infection in a rhesus macaque (Macaca mulatta). The nonhuman primate described was part of a research project that involved whole-body gamma irradiation and subsequently developed acute generalized dermatitis with skin dryness, peeling, and erythema around the eyes. After initial evaluation, which included microbiologic culture and 6 d of medical treatment, the animal was euthanized due to concern regarding a possible outbreak of infectious or zoonotic disease. On the basis of skin culture, diagnosis of methicillin-resistant Staphylococcus non-aureus was confirmed. This report underscores the importance of the occupational risk of methicillin-resistant Staphylococcus non-aureus to research and animal care staff in a research animal facility setting. PMID:18459716

  7. DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?

    PubMed

    Blomfeldt, A; Aamot, H V; Eskesen, A N; Monecke, S; White, R A; Leegaard, T M; Bjørnholt, J V

    2016-08-01

    Providing evidence for microbial genetic determinants' impact on outcome in Staphylococcus aureus bloodstream infections (SABSI) is challenging due to the complex and dynamic microbe-host interaction. Our recent population-based prospective study reported an association between the S. aureus clonal complex (CC) 30 genotype and mortality in SABSI patients. This follow-up investigation aimed to examine the genetic profiles of the SABSI isolates and test the hypothesis that specific genetic characteristics in S. aureus are associated with mortality. SABSI isolates (n = 305) and S. aureus CC30 isolates from asymptomatic nasal carriers (n = 38) were characterised by DNA microarray analysis and spa typing. Fisher's exact test, least absolute shrinkage and selection operator (LASSO) and elastic net regressions were performed to discern within four groups defined by patient outcome and characteristics. No specific S. aureus genetic determinants were found to be associated with mortality in SABSI patients. By applying LASSO and elastic net regressions, we found evidence suggesting that agrIII and cna were positively and setC (=selX) and seh were negatively associated with S. aureus CC30 versus non-CC30 isolates. The genes chp and sak, encoding immune evasion molecules, were found in higher frequencies in CC30 SABSI isolates compared to CC30 carrier isolates, indicating a higher virulence potential. In conclusion, no specific S. aureus genes were found to be associated with mortality by DNA microarray analysis and state-of-the-art statistical analyses. The next natural step is to test the hypothesis in larger samples with higher resolution methods, like whole genome sequencing. PMID:27177754

  8. Active Immunization with an Octa-Valent Staphylococcus aureus Antigen Mixture in Models of S. aureus Bacteremia and Skin Infection in Mice

    PubMed Central

    van den Berg, Sanne; Koedijk, Dennis G. A. M.; Back, Jaap Willem; Neef, Jolanda; Dreisbach, Annette; van Dijl, Jan Maarten; Bakker-Woudenberg, Irma A. J. M.; Buist, Girbe

    2015-01-01

    Proteomic studies with different Staphylococcus aureus isolates have shown that the cell surface-exposed and secreted proteins IsaA, LytM, Nuc, the propeptide of Atl (pro-Atl) and four phenol-soluble modulins α (PSMα) are invariantly produced by this pathogen. Therefore the present study was aimed at investigating whether these proteins can be used for active immunization against S. aureus infection in mouse models of bacteremia and skin infection. To this end, recombinant His-tagged fusions of IsaA, LytM, Nuc and pro-Atl were isolated from Lactococcus lactis or Escherichia coli, while the PSMα1-4 peptides were chemically synthesized. Importantly, patients colonized by S. aureus showed significant immunoglobulin G (IgG) responses against all eight antigens. BALB/cBYJ mice were immunized subcutaneously with a mixture of the antigens at day one (5 μg each), and boosted twice (25 μg of each antigen) with 28 days interval. This resulted in high IgG responses against all antigens although the response against pro-Atl was around one log lower compared to the other antigens. Compared to placebo-immunized mice, immunization with the octa-valent antigen mixture did not reduce the S. aureus isolate P load in blood, lungs, spleen, liver, and kidneys in a bacteremia model in which the animals were challenged for 14 days with a primary load of 3 × 105 CFU. Discomfort scores and animal survival rates over 14 days did not differ between immunized mice and placebo-immunized mice upon bacteremia with S. aureus USA300 (6 × 105 CFU). In addition, this immunization did not reduce the S. aureus isolate P load in mice with skin infection. These results show that the target antigens are immunogenic in both humans and mice, but in the used animal models do not result in protection against S. aureus infection. PMID:25710376

  9. β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus USA300 Is Increased by Inactivation of the ClpXP Protease

    PubMed Central

    Bæk, Kristoffer T.; Gründling, Angelika; Mogensen, René G.; Thøgersen, Louise; Petersen, Andreas; Paulander, Wilhelm

    2014-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has acquired the mecA gene encoding a peptidoglycan transpeptidase, penicillin binding protein 2a (PBP2a), which has decreased affinity for β-lactams. Quickly spreading and highly virulent community-acquired (CA) MRSA strains recently emerged as a frequent cause of infection in individuals without exposure to the health care system. In this study, we found that the inactivation of the components of the ClpXP protease substantially increased the β-lactam resistance level of a CA-MRSA USA300 strain, suggesting that the proteolytic activity of ClpXP controls one or more pathways modulating β-lactam resistance. These pathways do not involve the control of mecA expression, as the cellular levels of PBP2a were unaltered in the clp mutants. An analysis of the cell envelope properties of the clpX and clpP mutants revealed a number of distinct phenotypes that may contribute to the enhanced β-lactam tolerance. Both mutants displayed significantly thicker cell walls, increased peptidoglycan cross-linking, and altered composition of monomeric muropeptide species compared to those of the wild types. Moreover, changes in Sle1-mediated peptidoglycan hydrolysis and altered processing of the major autolysin Atl were observed in the clp mutants. In conclusion, the results presented here point to an important role for the ClpXP protease in controlling cell wall metabolism and add novel insights into the molecular factors that determine strain-dependent β-lactam resistance. PMID:24867990

  10. Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

    PubMed Central

    Aguilar, Jorge L.; Varshney, Avanish K.; Wang, Xiaobo; Stanford, Lindsay; Scharff, Matthew

    2014-01-01

    Staphylococcal enterotoxin-like K (SEl-K) is a potent mitogen that elicits T-cell proliferation and cytokine production at very low concentrations. However, unlike the classical enterotoxins SEB and toxic shock syndrome toxin 1 (TSST-1), the gene for SEl-K is commonly present in more than half of all Staphylococcus aureus clinical isolates and is present in almost all USA300 community-acquired methicillin-resistant S. aureus (CA-MRSA) isolates. Sequencing of the sel-k gene in over 20 clinical isolates and comparative analysis with all 14 published sel-k sequences indicate that there are at least 6 variants of the sel-k gene, including one that is conserved among all examined USA300 strains. Additionally, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) that specifically detects and measures SEl-K protein in culture supernatants and biological fluids. Quantification of in vitro SEl-K secretion by various S. aureus isolates using this novel capture ELISA revealed detectable amounts of SEl-K secretion by all isolates, with the highest secretion levels being exhibited by MRSA strains that coexpress SEB. In vivo secretion was measured in a murine thigh abscess model, where similar levels of SEl-K accumulation were noted regardless of whether the infecting strain exhibited high or low secretion of SEl-K in vitro. We conclude that SEl-K is commonly expressed in the setting of staphylococcal infection, in significant amounts. SEl-K should be further explored as a target for passive immunotherapy against complicated S. aureus infection. PMID:24808237

  11. Polymorphisms in Fibronectin Binding Proteins A and B among Staphylococcus aureus Bloodstream Isolates Are Not Associated with Arthroplasty Infection

    PubMed Central

    Sharma-Kuinkel, Batu; Park, Lawrence P.; Rude, Thomas H.; Ruffin, Felicia; Hos, Nina J.; Seifert, Harald; Rieg, Siegbert; Kern, Winfried V.; Lower, Steven K.; Fowler, Vance G.; Kaasch, Achim J.

    2015-01-01

    Background Nonsynonymous single nucleotide polymorphisms (SNPs) in fibronectin binding protein A (fnbA) of Staphylococcus aureus are associated with cardiac device infections. However, the role of fnbA SNPs in S. aureus arthroplasty infection is unknown. Methods Bloodstream S. aureus isolates from a derivation cohort of patients at a single U.S. medical center with S. aureus bacteremia (SAB) and prosthetic hip or knee arthroplasties that were infected (PJI, n = 27) or uninfected (PJU, n = 43) underwent sequencing of fnbA and fnbB. A validation cohort of S. aureus bloodstream PJI (n = 12) and PJU (n = 58) isolates from Germany also underwent fnbA and fnbB sequencing. Results Overall, none of the individual fnbA or fnbB SNPs were significantly associated with the PJI or PJU clinical groups within the derivation cohort. Similarly, none of the individual fnbA or fnbB SNPs were associated with PJI or PJU when the analysis was restricted to patients with either early SAB (i.e., bacteremia occurring <1 year after placement or manipulation of prostheses) or late SAB (i.e., bacteremia >1 year after placement or manipulation of prostheses). Conclusions In contrast to cardiac device infections, there is no association between nonsynonymous SNPs in fnbA or fnbB of bloodstream S. aureus isolates and arthroplasty infection. These results suggest that initial steps leading to S. aureus infection of cardiovascular and orthopedic prostheses may arise by distinct processes. PMID:26606522

  12. SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections.

    PubMed

    Arya, Rekha; Ravikumar, R; Santhosh, R S; Princy, S Adline

    2015-01-01

    Staphylococcus aureus is a common pathogen seen in prosthetic vascular graft, leading to high morbidity and mortality. The virulence genes for severity of infections are under the control of global regulators. Staphylococcal accessory regulator A (SarA) a known master controller of biofilm formation is an attractive target for the drug development. A structure based screening of lead compounds was employed for the identification of novel small molecule inhibitors targeted to interact to the DNA binding domain of the transcriptional activator, SarA and hinder its response over the control of genes that up-regulate the phenotype, biofilm. The top-hit SarA selective inhibitor, 4-[(2,4-diflurobenzyl)amino] cyclohexanol (SarABI) was further validated in-vitro for its efficacy. The SarABI was found to have MBIC50value of 200 μg/ml and also down-regulated the expression of the RNA effector, (RNAIII), Hemolysin (hld), and fibronectin-binding protein (fnbA). The anti-adherence property of SarABI on S. aureus invasion to the host epithelial cell lines (Hep-2) was examined where no significant attachment of S. aureus was observed. The SarABI inhibits the colonization of MDR S. aureus in animal model experiment significantly cohere to the molecular docking studies and in vitro experiments. So, we propose that the SarABI could be a novel substitute to overcome a higher degree of MDR S. aureus colonization on vascular graft. PMID:26074884

  13. Prevention of Staphylococcus aureus Infections by Glycoprotein Vaccines Synthesized in Escherichia coli

    PubMed Central

    Wacker, Michael; Wang, Linhui; Kowarik, Michael; Dowd, Meghan; Lipowsky, Gerd; Faridmoayer, Amir; Shields, Kelly; Park, Saeyoung; Alaimo, Cristina; Kelley, Kathryn A.; Braun, Martin; Quebatte, Julien; Gambillara, Veronica; Carranza, Paula; Steffen, Michael; Lee, Jean C.

    2014-01-01

    Background. Staphylococcus aureus is a leading cause of superficial and invasive human disease that is often refractory to antimicrobial therapy. Vaccines have the potential to reduce the morbidity, mortality, and economic impact associated with staphylococcal infections. However, single-component vaccines targeting S. aureus have failed to show efficacy in clinical trials. Methods. A novel glycoengineering technology for creation of a multicomponent staphylococcal vaccine is described. Genes encoding S. aureus capsular polysaccharide (CP) biosynthesis, PglB (a Campylobacter oligosaccharyl transferase), and a protein carrier (detoxified Pseudomonas aeruginosa exoprotein A or S. aureus α toxin [Hla]) were coexpressed in Escherichia coli. Recombinant proteins N-glycosylated with S. aureus serotype 5 or 8 CPs were purified from E. coli. Results. Rabbits and mice immunized with the glycoprotein vaccines produced antibodies that were active in vitro in functional assays. Active and passive immunization strategies targeting the CPs protected mice against bacteremia, and vaccines targeting Hla protected against lethal pneumonia. The CP-Hla bioconjugate vaccine protected against both bacteremia and lethal pneumonia, providing broad-spectrum efficacy against staphylococcal invasive disease. Conclusions. Glycoengineering technology, whereby polysaccharide and protein antigens are enzymatically linked in a simple E. coli production system, has broad applicability for use in vaccine development against encapsulated microbial pathogens. PMID:24308931

  14. Sigma Factor SigB Is Crucial to Mediate Staphylococcus aureus Adaptation during Chronic Infections

    PubMed Central

    Tuchscherr, Lorena; Bischoff, Markus; Lattar, Santiago M.; Noto Llana, Mariangeles; Pförtner, Henrike; Niemann, Silke; Geraci, Jennifer; Van de Vyver, Hélène; Fraunholz, Martin J.; Cheung, Ambrose L.; Herrmann, Mathias; Völker, Uwe; Sordelli, Daniel O.; Peters, Georg; Löffler, Bettina

    2015-01-01

    Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs), which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, ΔsigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy-refractory infections. PMID

  15. Differential Role of Rapamycin and Torin/KU63794 in Inflammatory Response of 264.7 RAW Macrophages Stimulated by CA-MRSA

    PubMed Central

    Shappley, Rebekah K. H.

    2014-01-01

    Background. Rapamycin suppresses the RAW264.7 macrophage mediated inflammatory response but in lower doses induces it. In the present study, we tested the suppression of the inflammatory response in the presence of mTOR 1 and 2 inhibitors, Torin and KU63794. Methods. RAW264.7 cells were stimulated for 18 hrs with 106 to 107 CFU/mL inocula of community-acquired- (CA-) MRSA isolate, USA400 strain MW2, in the presence of Vancomycin. Then, in sequential experiments, we added Torin, KU63794, and Rapamycin alone and in various combinations. Supernatants were collected and assayed for TNF, IL-1, IL-6, INF, and NO. Results. Rapamycin induces 10–20% of the inflammatory cascade at dose of 0.1 ng/mL and suppresses it by 60% at dose of 10 ng/mL. The induction is abolished in the presence of Torin KU63794. Torin and KU63794 are consistently suppressing cytokine production 50–60%. Conclusions. There is a differential response between Rapamycin (mTOR-1 inhibitor) and Torin KU63794 (mTOR 1 and 2 inhibitors). Torin and KU63794 exhibit a dose related suppression. Rapamycin exhibits a significant induction-suppression biphasic response. Knowledge of such response may allow manipulation of the septic inflammatory cascade for clinical advantages. PMID:24800098

  16. [Directed therapeutic approach to Staphylococcus aureus infections. Clinical aspects of prescription].

    PubMed

    Carmona-Torre, F; Rua, M; Del Pozo, J L

    2016-09-01

    Infections caused by Staphylococcus aureus have had classically an important impact in morbidity and mortality in the nosocomial and community scene. The description of methicillin resistance among nosocomial isolates of S. aureus and his widespread diffusion has become methicillin-resistant S. aureus (MRSA) in one of the most common causes of bacterial nosocomial infections. In the last years MRSA strains have also emergence in the community. This together with a progressive increase in resistance to antibiotics used classically has become vancomycin in the treatment of choice in most cases according to clinical guidelines. As a result, a progressive rise in the minimum inhibitory concentration (MIC) to vancomycin has been reported. In this context strains with intermediate susceptibility to vancomycin (MIC 8-4 mg/L) and heteroresistance have been noted. These strains are associated with a higher risk of treatment failure when using vancomycin. Among isolates of S. aureus susceptible to vancomycin there has been described stains with elevated MICs (≥1.5 mg/L). It is controversial if the presence of these strains has an impact on clinical outcome if treatment with vancomycin or β-lactams is prescribed. The development of new antibiotics with activity against MRSA and exploring synergies offer a promising alternative to treatment with vancomycin. PMID:27608307

  17. Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion during Staphylococcus aureus infection

    PubMed Central

    Kim, Hwan Keun; Falugi, Fabiana; Missiakas, Dominique M.; Schneewind, Olaf

    2016-01-01

    A hallmark of Staphylococcus aureus disease in humans is persistent infections without development of protective immune responses. Infected patients generate VH3 plasmablast expansions and increased VH3 idiotype Ig; however, the mechanisms for staphylococcal modification of immune responses are not known. We report here that S. aureus-infected mice generate VH3 antibody expansions via a mechanism requiring MHC-restricted antigen presentation to CD4+ T cells and staphylococcal protein A (SpA), a cell wall-anchored surface molecule that binds Fcγ and VH3 variant heavy chains of Ig. VH3 expansion occurred with peptidoglycan-linked SpA from the bacterial envelope but not with recombinant SpA, and optimally required five tandem repeats of its Ig-binding domains. Signaling via receptor-interacting serine/threonine protein kinase 2 (RIPK2) was essential for implementing peptidoglycan-linked SpA superantigen activity. VH3 clan IgG from S. aureus-infected or SpA-treated animals was not pathogen-specific, suggesting that SpA cross-linking of VH3 idiotype B-cell receptors and activation via attached peptidoglycan are the determinants of staphylococcal escape from adaptive immune responses. PMID:27140614

  18. Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion during Staphylococcus aureus infection.

    PubMed

    Kim, Hwan Keun; Falugi, Fabiana; Missiakas, Dominique M; Schneewind, Olaf

    2016-05-17

    A hallmark of Staphylococcus aureus disease in humans is persistent infections without development of protective immune responses. Infected patients generate VH3 plasmablast expansions and increased VH3 idiotype Ig; however, the mechanisms for staphylococcal modification of immune responses are not known. We report here that S. aureus-infected mice generate VH3 antibody expansions via a mechanism requiring MHC-restricted antigen presentation to CD4(+) T cells and staphylococcal protein A (SpA), a cell wall-anchored surface molecule that binds Fcγ and VH3 variant heavy chains of Ig. VH3 expansion occurred with peptidoglycan-linked SpA from the bacterial envelope but not with recombinant SpA, and optimally required five tandem repeats of its Ig-binding domains. Signaling via receptor-interacting serine/threonine protein kinase 2 (RIPK2) was essential for implementing peptidoglycan-linked SpA superantigen activity. VH3 clan IgG from S. aureus-infected or SpA-treated animals was not pathogen-specific, suggesting that SpA cross-linking of VH3 idiotype B-cell receptors and activation via attached peptidoglycan are the determinants of staphylococcal escape from adaptive immune responses. PMID:27140614

  19. Comparison of Outcomes among Adult Patients with Nosocomial Bacteremia Caused by Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus: A Retrospective Cohort Study

    PubMed Central

    Wang, Jann-Tay; Hsu, Le-Yin; Lauderdale, Tsai-Ling; Fan, Wen-Chien; Wang, Fu-Der

    2015-01-01

    Several studies have shown that patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) have worse outcomes than those with bacteremia caused by methicillin-susceptible S. aureus (MSSA). However, only a limited number of studies have stratified the MRSA isolates into healthcare-associated (HA-) and community-associated (CA-) MRSA strains in such a comparison. This three-year retrospective cohort study, enrolling adult patients with nosocomial S. aureus bacteremia (SAB), was designed to investigate whether CA-MRSA and/or HA-MRSA strains were associated with different outcomes in comparison to MSSA in such a setting. The drug susceptibilities and staphylococcal cassette chromosome mec (SCCmec) types were determined for all of the causative isolates available. The MRSA bacteremia was further categorized into those caused by CA-MRSA strains (CA-MRSA-S bacteremia) when the causative isolates carried the type IV or V SCCmec element, those caused by HA-MRSA strains (HA-MRSA-S bacteremia) when the isolates carried the type I, II, or III SCCmec element, or unclassified MRSA bacteremia when the isolates were not available. The relevant demographic, clinical, and laboratory data were collected by reviewing the patients’ charts. The primary outcome was all-cause in-hospital mortality. A total of 353 patients were studied. The overall in-hospital mortality rate was 32.6%, with 23.3% in MSSA, 30.5% in CA-MRSA-S, 47.5% in HA-MRSA-S, and 35.3% in unclassified MRSA bacteremia, respectively. The multivariate analysis showed that HA-MRSA-S, but not CA-MRSA-S, bacteremia was associated with a significantly worse outcome compared with MSSA. The other risk factors independently associated with all-cause in-hospital mortality included the Charlson co-morbidity index, septic shock, thrombocytopenia, and persistent bacteremia. Resistance to linezolid and daptomycin was found among the MRSA isolates. The present study showed that bacteremia caused by HA

  20. Specific Behaviors Predict Staphylococcus aureus Colonization and Skin and Soft Tissue Infections Among Human Immunodeficiency Virus-Infected Persons.

    PubMed

    Crum-Cianflone, Nancy F; Wang, Xun; Weintrob, Amy; Lalani, Tahaniyat; Bavaro, Mary; Okulicz, Jason F; Mende, Katrin; Ellis, Michael; Agan, Brian K

    2015-04-01

    Background.  Few data exist on the incidence and risk factors of Staphylococcus aureus colonization and skin and soft tissue infections (SSTIs) among patients infected with human immunodeficiency virus (HIV). Methods.  Over a 2-year period, we prospectively evaluated adults infected with HIV for incident S aureus colonization at 5 body sites and SSTIs. Cox proportional hazard models using time-updated covariates were performed. Results.  Three hundred twenty-two participants had a median age of 42 years (interquartile range, 32-49), an HIV duration of 9.4 years (2.7-17.4), and 58% were on highly active antiretroviral therapy (HAART). Overall, 102 patients (32%) became colonized with S aureus with an incidence rate of 20.6 (95% confidence interval [CI], 16.8-25.0) per 100 person-years [PYs]. Predictors of colonization in the final multivariable model included illicit drug use (hazard ratios [HR], 4.26; 95% CI, 1.33-13.69) and public gym use (HR 1.66, 95% CI, 1.04-2.66), whereas antibacterial soap use was protective (HR, 0.50; 95% CI, 0.32-0.78). In a separate model, perigenital colonization was associated with recent syphilis infection (HR, 4.63; 95% CI, 1.01-21.42). Fifteen percent of participants developed an SSTI (incidence rate of 9.4 cases [95% CI, 6.8-12.7] per 100 PYs). Risk factors for an SSTI included incident S aureus colonization (HR 2.52; 95% CI, 1.35-4.69), public shower use (HR, 2.59; 95% CI, 1.48-4.56), and hospitalization (HR 3.54; 95% CI, 1.67-7.53). The perigenital location for S aureus colonization was predictive of SSTIs. Human immunodeficiency virus-related factors (CD4 count, HIV RNA level, and HAART) were not associated with colonization or SSTIs. Conclusions.  Specific behaviors, but not HIV-related factors, are predictors of colonization and SSTIs. Behavioral modifications may be the most important strategies in preventing S aureus colonization and SSTIs among persons infected with HIV. PMID:26380335

  1. Daily Bathing with Chlorhexidine-based Soap and the Prevention of Staphylococcus aureus Transmission and Infection

    PubMed Central

    Viray, Melissa A.; Morley, James C.; Coopersmith, Craig M; Kollef, Marin H.; Fraser, Victoria J.; Warren, David K.

    2014-01-01

    Objective Determine if daily bathing with chlorhexidine-based soap decreased methicillin-resistant Staphylococcus aureus (MRSA) transmission and ICU-acquired S. aureus infection among ICU patients. Design Prospective pre-post-intervention study with control unit Setting 1,250 bed tertiary-care teaching hospital Patients Medical and surgical intensive care unit (ICU) patients Methods Active surveillance for MRSA colonization was performed in both ICUs. In June 2005, a chlorhexidine bathing protocol was implemented in the surgical ICU. Changes in S. aureus transmission and infection rate before and after implementation were analyzed using time-series methodology. Results The intervention unit had a 20.68% decrease in MRSA acquisition after institution of the bathing protocol [pre-intervention 12.64 vs. post-intervention 10.03 cases/1000 patient-days-at-risk (95% CI: −5.19 – −0.04, p = 0.046)]. There was no significant change in MRSA acquisition in the control ICU during the study period [10.97 pre-June 2005 vs. 11.33/1000 patient-days at risk post-June 2005 (95% CI −37.40 – 15.19, p = 0.40)]. There was a 20.77% decrease in all S. aureus (including MRSA) acquisition in the intervention ICU from 2002-2007 [19.73 pre-intervention to 15.63 cases per 1000 patient-days at risk post-intervention (95% CI −7.25 – −0.95, p=0.012)]. The incidence of ICU-acquired MRSA infections decreased by 41.37% in the intervention ICU (1.96 pre-intervention vs. 1.15 infections per 1000 patient-days at risk post-intervention; p=0.001). Conclusions Institution of daily chlorhexidine bathing in an ICU resulted in a decrease in the transmission of S. aureus, including MRSA. These data support the use of routine daily chlorhexidine baths to decrease rates of S. aureus transmission and infections. PMID:24521588

  2. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE PAGESBeta

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.; Schneewind, Olaf

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host Bmore » cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  3. A β-lactone-based antivirulence drug ameliorates Staphylococcus aureus skin infections in mice.

    PubMed

    Weinandy, Franziska; Lorenz-Baath, Katrin; Korotkov, Vadim S; Böttcher, Thomas; Sethi, Shneh; Chakraborty, Trinad; Sieber, Stephan A

    2014-04-01

    Skin infections caused by Staphylococcus aureus are a major clinical concern, especially if they are caused by multi-resistant strains. In these cases, a spread into deeper soft tissues or the bloodstream results in life-threatening conditions that are difficult to treat by conventional antibiotics. Previous in vitro experiments with a small β-lactone-based molecule demonstrated that antibiotic-sensitive and -resistant S. aureus strains are effectively disarmed in their virulence and corresponding pathogenicity. In this work, in vivo mouse studies show that this methodology is effective for the treatment of skin abscesses in mice. A single dose of the β-lactone significantly decreased abscess size even when applied 6 h post-infection. Although the molecule requires pharmacological optimization (improved stability, for example), this study emphasizes the potential value of antivirulence therapies. PMID:24678014

  4. Montanide ISA 71 VG is Advantageous to Freund's Adjuvant in Immunization Against S. aureus Infection of Mice.

    PubMed

    Klimka, A; Michels, L; Glowalla, E; Tosetti, B; Krönke, M; Krut, O

    2015-05-01

    The enormous capacity of Staphylococcus aureus to acquire antibiotic resistance makes it a permanent task to search for and to develop new anti-infectives. One of the possible approaches is the early active immunization of risk patients and animal stocks to prevent S. aureus infections. Based on a S. aureus proteome screen with S. aureus-specific human antiserum, we have previously identified several anchorless cell wall proteins to be used as novel vaccine candidates. To develop an efficient anti-S. aureus vaccine, the supplemented adjuvants Montanide(™) ISA 71 VG and ISA 206 were compared to Freund's adjuvant in terms of handling, induction of cytokine profile, triggering antigen-specific immunoglobulin production of different IgG subclasses and provision of increased survival rates in our S. aureus sepsis mouse model. Immunization with ISA 71 VG in comparison with Freund's adjuvant induced slightly delayed but comparably strong increase of antigen-specific antibody titres and conferred protective effect against S. aureus challenge. In contrast using ISA 206 as adjuvant, significantly lower IgG titres and consequently, no protective effect against S. aureus infection were observed. Handling and tolerability of the Montanide is superior to Freund's adjuvant. Montanide(™) ISA 71 VG can serve as an effective adjuvant replacement for Freund's adjuvant in research with a prospective usage in animal and human vaccines against bacterial pathogens. PMID:25689117

  5. Prospective multicenter surveillance identifies Staphylococcus aureus infections caused by livestock-associated strains in an agricultural state.

    PubMed

    Nair, Rajeshwari; Wu, James; Carrel, Margaret; O'Brien, Ashley; Quick, Megan; Farina, Sarah; Wardyn, Shylo; Thapaliya, Dipendra; Grenier, Dylan; Smith, Tara C

    2016-07-01

    We conducted a surveillance study to investigate the epidemiology of Staphylococcus aureus infections in Iowa, using a convenience sample. Diagnostic laboratories submitted 20 S. aureus isolates per month for a 20-month period between 2011 and 2013. Of the 2226 isolates analyzed, 73.6% were methicillin-resistant S. aureus (MRSA) and 26.4% were methicillin-susceptible S. aureus (MSSA). S. aureus infections in 25 patients (1%) were caused by ST398- and ST9-associated strain types, and appeared to be a common occurrence in areas of the state with the highest numbers of hogs and hog farms. Twenty nine (5.1%) of MSSA isolates and 10 (40.0%) livestock-associated strains were multi-drug resistant. PMID:27198741

  6. Peripheral Intravenous Catheter Placement Is an Underrecognized Source of Staphylococcus aureus Bloodstream Infection

    PubMed Central

    Austin, Eloise D.; Sullivan, Sean B.; Whittier, Susan; Lowy, Franklin D.; Uhlemann, Anne-Catrin

    2016-01-01

    Few studies have focused on the risks of peripheral intravenous catheters (PIVs) as sources for Staphylococcus aureus bacteremia (SAB), a life-threatening complication. We identified 34 PIV-related infections (7.6%) in a cohort of 445 patients with SAB. Peripheral intravenous catheter-related SAB was associated with significantly longer bacteremia duration and thrombophlebitis at old PIV sites rather than current PIVs. PMID:27191005

  7. Clonal expansion during Staphylococcus aureus infection dynamics reveals the effect of antibiotic intervention.

    PubMed

    McVicker, Gareth; Prajsnar, Tomasz K; Williams, Alexander; Wagner, Nelly L; Boots, Michael; Renshaw, Stephen A; Foster, Simon J

    2014-02-01

    To slow the inexorable rise of antibiotic resistance we must understand how drugs impact on pathogenesis and influence the selection of resistant clones. Staphylococcus aureus is an important human pathogen with populations of antibiotic-resistant bacteria in hospitals and the community. Host phagocytes play a crucial role in controlling S. aureus infection, which can lead to a population "bottleneck" whereby clonal expansion of a small fraction of the initial inoculum founds a systemic infection. Such population dynamics may have important consequences on the effect of antibiotic intervention. Low doses of antibiotics have been shown to affect in vitro growth and the generation of resistant mutants over the long term, however whether this has any in vivo relevance is unknown. In this work, the population dynamics of S. aureus pathogenesis were studied in vivo using antibiotic-resistant strains constructed in an isogenic background, coupled with systemic models of infection in both the mouse and zebrafish embryo. Murine experiments revealed unexpected and complex bacterial population kinetics arising from clonal expansion during infection in particular organs. We subsequently elucidated the effect of antibiotic intervention within the host using mixed inocula of resistant and sensitive bacteria. Sub-curative tetracycline doses support the preferential expansion of resistant microorganisms, importantly unrelated to effects on growth rate or de novo resistance acquisition. This novel phenomenon is generic, occurring with methicillin-resistant S. aureus (MRSA) in the presence of β-lactams and with the unrelated human pathogen Pseudomonas aeruginosa. The selection of resistant clones at low antibiotic levels can result in a rapid increase in their prevalence under conditions that would previously not be thought to favor them. Our results have key implications for the design of effective treatment regimes to limit the spread of antimicrobial resistance, where

  8. Strain Specific Phage Treatment for Staphylococcus aureus Infection Is Influenced by Host Immunity and Site of Infection.

    PubMed

    Pincus, Nathan B; Reckhow, Jensen D; Saleem, Danial; Jammeh, Momodou L; Datta, Sandip K; Myles, Ian A

    2015-01-01

    The response to multi-drug resistant bacterial infections must be a global priority. While mounting resistance threatens to create what the World Health Organization has termed a "post-antibiotic era", the recent discovery that antibiotic use may adversely impact the microbiome adds further urgency to the need for new developmental approaches for anti-pathogen treatments. Methicillin-resistant Staphylococcus aureus (MRSA), in particular, has declared itself a serious threat within the United States and abroad. A potential solution to the problem of antibiotic resistance may not entail looking to the future for completely novel treatments, but instead looking into our history of bacteriophage therapy. This study aimed to test the efficacy, safety, and commercial viability of the use of phages to treat Staphylococcus aureus infections using the commercially available phage SATA-8505. We found that SATA-8505 effectively controls S. aureus growth and reduces bacterial viability both in vitro and in a skin infection mouse model. However, this killing effect was not observed when phage was cultured in the presence of human whole blood. SATA-8505 did not induce inflammatory responses in peripheral blood mononuclear cultures. However, phage did induce IFN gamma production in primary human keratinocyte cultures and induced inflammatory responses in our mouse models, particularly in a mouse model of chronic granulomatous disease. Our findings support the potential efficacy of phage therapy, although regulatory and market factors may limit its wider investigation and use. PMID:25909449

  9. Strain Specific Phage Treatment for Staphylococcus aureus Infection Is Influenced by Host Immunity and Site of Infection

    PubMed Central

    Pincus, Nathan B.; Jammeh, Momodou L.; Datta, Sandip K.; Myles, Ian A.

    2015-01-01

    The response to multi-drug resistant bacterial infections must be a global priority. While mounting resistance threatens to create what the World Health Organization has termed a “post-antibiotic era”, the recent discovery that antibiotic use may adversely impact the microbiome adds further urgency to the need for new developmental approaches for anti-pathogen treatments. Methicillin-resistant Staphylococcus aureus (MRSA), in particular, has declared itself a serious threat within the United States and abroad. A potential solution to the problem of antibiotic resistance may not entail looking to the future for completely novel treatments, but instead looking into our history of bacteriophage therapy. This study aimed to test the efficacy, safety, and commercial viability of the use of phages to treat Staphylococcus aureus infections using the commercially available phage SATA-8505. We found that SATA-8505 effectively controls S. aureus growth and reduces bacterial viability both in vitro and in a skin infection mouse model. However, this killing effect was not observed when phage was cultured in the presence of human whole blood. SATA-8505 did not induce inflammatory responses in peripheral blood mononuclear cultures. However, phage did induce IFN gamma production in primary human keratinocyte cultures and induced inflammatory responses in our mouse models, particularly in a mouse model of chronic granulomatous disease. Our findings support the potential efficacy of phage therapy, although regulatory and market factors may limit its wider investigation and use. PMID:25909449

  10. Clinical Effectiveness of Mupirocin for Preventing Staphylococcus aureus Infections in Nonsurgical Settings: A Meta-analysis.

    PubMed

    Nair, Rajeshwari; Perencevich, Eli N; Blevins, Amy E; Goto, Michihiko; Nelson, Richard E; Schweizer, Marin L

    2016-03-01

    A systematic literature review and meta-analysis was performed to identify effectiveness of mupirocin decolonization in prevention of Staphylococcus aureus infections, among nonsurgical settings. Of the 15 662 unique studies identified up to August 2015, 13 randomized controlled trials, 22 quasi-experimental studies, and 1 retrospective cohort study met the inclusion criteria. Studies were excluded if mupirocin was not used for decolonization, there was no control group, or the study was conducted in an outbreak setting. The crude risk ratios were pooled (cpRR) using a random-effects model. We observed substantial heterogeneity among included studies (I(2) = 80%). Mupirocin was observed to reduce the risk for S. aureus infections by 59% (cpRR, 0.41; 95% confidence interval [CI], .36-.48) and 40% (cpRR, 0.60; 95% CI, .46-.79) in both dialysis and nondialysis settings, respectively. Mupirocin decolonization was protective against S. aureus infections among both dialysis and adult intensive care patients. Future studies are needed in other settings such as long-term care and pediatrics. PMID:26503378