Community-associated Methicillin-resistant Staphylococcus Aureus Skin Research Articles

Home Environmental Contamination Is Associated with Community-associated Methicillin-resistant Staphylococcus aureus Re-colonization in Treated Patients

BackgroundStrategies to interrupt household transmission of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) that target human colonization show mixed results. Our aim was to determine whether home environmental contamination and pet carriage with MRSA were associated with re-colonization or persistent colonization of index patients diagnosed with CA-MRSA skin or soft-tissue infection (SSTI).MethodsIndex patients from a randomized controlled trial (NCT00966446) that tested household-wide decolonization of people were eligible to participate in this substudy. Before randomization, eight environmental sites and all pets were sampled in the home. Patients were treated by their physician for the initial SSTI between diagnosis (visit 0) and the home visit (visit 1). They provided swabs every 2 weeks for 3 months (7 visits). After broth-enrichment culture, MRSA isolates were PCR-confirmed and spa-typed.ResultsOf 88 index patients recruited from the main trial, 64 (73%) provided swabs for ≥3 visits and were included in this analysis. At visit 1, 41 (64%) households were MRSA contaminated and 6 (9%) had MRSA-positive pet(s). All MRSA-positive pets lived in homes with MRSA environmental contamination. After visit 1, 42 (66%) index patients and their household members were block-randomized to nasal mupirocin and chlorhexidine body wash decolonization. Thirty-seven (58%) index patients had two consecutive negative swabs (de-colonized); 13 (35%) of these later were MRSA-positive (re-colonized). Patients with home contamination had higher rates of re-colonization than those without (Cox proportional hazard ratio 6.0 [95% CI: 1.2, 30.6], P < 0.03). Persistent colonization (all or all but one swab positive) was identified in 6 (9%) of index patients and was associated with identification of matching spa-types in environmental and subsequent human MRSA isolates (P < 0.05).ConclusionIn patients with MRSA SSTI, MRSA-contaminated homes, and potentially MRSA-positive pets, are associated with re-colonization and persistent colonization. Future studies are needed to determine whether environmental decontamination can improve the success of household decolonization interventions.Disclosures All authors: No reported disclosures.

Role of Antibodies in Protection Elicited by Active Vaccination with Genetically Inactivated Alpha Hemolysin in a Mouse Model of Staphylococcus aureus Skin and Soft Tissue Infections

Due to the emergence of highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, S. aureus has become a major threat to public health. A majority of CA-MRSA skin and soft tissue infections in the United States are caused by S. aureus USA300 strains that are known to produce high levels of alpha hemolysin (Hla). Therefore, vaccines that contain inactivated forms of this toxin are currently being developed. In this study, we sought to determine the immune mechanisms of protection for this antigen using a vaccine composed of a genetically inactivated form of Hla (HlaH35L). Using a murine model of skin and soft tissue infections (SSTI), we found that BALB/c mice were protected by vaccination with HlaH35L; however, Jh mice, which are deficient in mature B lymphocytes and lack IgM and IgG in their serum, were not protected. Passive immunization with anti-HlaH35L antibodies conferred protection against bacterial colonization. Moreover, we found a positive correlation between the total antibody concentration induced by active vaccination and reduced bacterial levels. Animals that developed detectable neutralizing antibody titers after active vaccination were significantly protected from infection. These data demonstrate that antibodies to Hla represent the major mechanism of protection afforded by active vaccination with inactivated Hla in this murine model of SSTI, and in this disease model, antibody levels correlate with protection. These results provide important information for the future development and evaluation of S. aureus vaccines.

Detection of Epidemic USA300 Community-Associated Methicillin-Resistant Staphylococcus aureus Strains by Use of a Single Allele-Specific PCR Assay Targeting a Novel Polymorphism of Staphylococcus aureus pbp3

In recent years, the dramatic increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections has become a significant health care challenge. Early detection of CA-MRSA is important because of its increased virulence associated with the arginine catabolic mobile element (ACME), Panton-Valentine leukocidin (PVL), and other toxins that may contribute to disease severity. In particular, the USA300 epidemic clone has emerged and now represents the cause of as much as 98% of CA-MRSA skin and soft tissue infections in the United States. Current diagnostic assays used to identify CA-MRSA strains are based on complex multiplex PCRs targeting the staphylococcal cassette chromosome mec (SCCmec) DNA junction, a multitude of genes, and noncoding DNA fragments or on a number of lengthy sequence-typing methods. Here, two nucleotide polymorphisms, G88A and G2047A, that were found to be in strict linkage disequilibrium in the S. aureus penicillin-binding protein 3 (pbp3) gene were also found to be highly associated with the USA300 clone of CA-MRSA. Clinical isolates that contained this pbp3 allele were also positive for the presence of SCCmec type IV, the ACME, and the PVL toxin gene and matched the t008 or t121 molecular spa types, which are associated specifically with the USA300 CA-MRSA clone. A single allele-specific PCR targeting the G88A polymorphism was developed and was found to be 100% sensitive and specific for the detection of USA300 CA-MRSA and 91.5% sensitive and 100% specific for the detection of all CA-MRSA isolates in this study.

Prospective Investigation of Nasal Mupirocin, Hexachlorophene Body Wash, and Systemic Antibiotics for Prevention of Recurrent Community-Associated Methicillin-Resistant Staphylococcus aureus Infections

Recurrent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections are an increasingly common problem. However, there are no data on the efficacy of decolonization regimens. We prospectively evaluated 31 patients with recurrent CA-MRSA skin infections who received nasal mupirocin, topical hexachlorophene body wash, and an oral anti-MRSA antibiotic. The mean number of MRSA infections after the intervention decreased significantly from baseline (0.03 versus 0.84 infections/month, P = <0.0001). This regimen appears promising at preventing recurrent CA-MRSA infections.

Severe Myelosuppression and MRSA Infection as the Presentation of Perinatal HIV Infection

Severe Myelosuppression and MRSA Infection as the Presentation of Perinatal HIV Infection

Host Chemokines Bind to Staphylococcus aureus and Stimulate Protein A Release

There are few examples of host signals that are beneficial to bacteria during infection. Here we found that 31 out of 42 host immunoregulatory chemokines were able to induce release of the virulence factor protein A (SPA) from a strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Detailed study of chemokine CXCL9 revealed that SPA release occurred through a post-translational mechanism and was inversely proportional to bacterial density. CXCL9 bound specifically to the cell membrane of CA-MRSA, and the related SPA-releasing chemokine CXCL10 bound to both cell wall and cell membrane. Clinical samples from patients infected with S. aureus and samples from a mouse model of CA-MRSA skin abscess all contained extracellular SPA. Further, SPA-releasing chemokines were present in mouse skin lesions infected with CA-MRSA. Our data identify a potential new mode of immune evasion, in which the pathogen exploits a host defense factor to release a virulence factor; moreover, chemokine binding may serve a scavenging function in immune evasion by S. aureus.

Comparative Analysis of Virulence and Toxin Expression of Global Community‐Associated Methicillin‐ResistantStaphylococcus aureusStrains

The current pandemic of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections is caused by several genetically unrelated clones. Here, we analyzed virulence of globally occurring CA-MRSA strains in a rabbit skin infection model. We used rabbits because neutrophils from this animal species have relatively high sensitivity to Panton-Valentine leukocidin (PVL), a toxin epidemiologically correlated with many CA-MRSA infections. Virulence in the rabbit model correlated with in vitro neutrophil lysis and transcript levels of phenol-soluble modulin α and α-toxin, but not PVL genes. Furthermore, abscesses caused by USA300 and its PVL-negative progenitor USA500 were comparatively large and similar in size, suggesting that PVL has played a limited role in the evolution of USA300 virulence in the context of skin infections. Our study indicates a major but not exclusive impact of virulence on the epidemiological success of USA300 and other CA-MRSA strains and emphasizes the importance of core genome-encoded toxins in CA-MRSA skin infections.

Targeting of Alpha‐Hemolysin by Active or Passive Immunization Decreases Severity of USA300 Skin Infection in a Mouse Model

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are predominantly those affecting skin and soft tissues. Although progress has been made, our knowledge of the molecules that contribute to the pathogenesis of CA-MRSA skin infections is incomplete. We tested the hypothesis that alpha-hemolysin (Hla) contributes to the severity of USA300 skin infections in mice and determined whether vaccination against Hla reduces disease severity. Isogenic hla-negative (Deltahla) strains caused skin lesions in a mouse infection model that were significantly smaller than those caused by wild-type USA300 and Newman strains. Moreover, infection due to wild-type strains produced dermonecrotic skin lesions, whereas there was little or no dermonecrosis in mice infected with Deltahla strains. Passive immunization with Hla-specific antisera or active immunization with a nontoxigenic form of Hla significantly reduced the size of skin lesions caused by USA300 and prevented dermonecrosis. We conclude that Hla is a potential target for therapeutics or vaccines designed to moderate severe S. aureus skin infections.

Ceftaroline for complicated skin and skin-structure infections

Importance of the field: A dramatic increase in infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has been observed, in part as a result of the epidemic of community-associated MRSA skin and skin-structure infections (SSSIs). Simultaneously, decreasing sensitivities of S. aureus to vancomycin have been reported and invasive infections caused by these strains have been associated with worse clinical outcomes. Clearly, new agents active against MRSA are needed. Ceftaroline is a new cephalosporin active against MRSA and many Gram-negative bacteria, though it is not active against Pseudomonas spp. and extended spectrum β-lactamase producers (ESBL).Areas covered in this review: In this review we focus on the properties of ceftaroline such as in vitro activity, the pharmacokinetic and pharmacodynamic characteristics, and its efficacy and safety observed in the clinical trials of patients with SSSI. Finally, we provide an overview of the possible future role of ceftaroline and other compounds in development for the treatment of SSSIs. The literature search was based on PubMed articles plus review of the abstracts presented in the most important international conferences in the field.What the reader will gain: The reader will gain clear concepts to understand the value that ceftaroline might have in the treatment of SSSIs, including those caused by MRSA.Take home message: Ceftaroline has shown bactericidal activity against common pathogens associated with SSSIs including MRSA, noninferiority in clinical trials of patients with complicated SSSI (cSSSI), and a favorable safety profile.

A Case of Community-Associated Methicillin-Resistant Staphylococcus Aureus Infections in a Community Hospital

Infections caused by methicillin-resistant Staphylococcus Aureus (MRSA) have recently occurred in communities in people lacking known healthcare risk factors. This MRSA infection is referred to as community-associated MRSA (CA-MRSA) infection, and is distinct from hospital-associated MRSA infection, which occurs in people with risk factors. We experienced a patient diagnosed with CA-MRSA cellulitis, as culture of pus revealed MRSA and he had not been exposed to healthcare environments for the past year. The patient was a previously healthy 38-year-old man with suppurative cellulitis in his right index finger following injury to the finger at his worksite. The cellulitis was successfully managed with incision and drainage (I&D), followed by cefazolin during a 10-day clinical course, although the patient’s MRSA strain was resistant to cefazolin. There are several reports that suggest that I&D followed by antibiotic treatment for CA-MRSA skin infection produces equivalent clinical outcomes, whether the antibiotic prescribed was effective or not. Given that MRSA emerged in an outpatient setting, CA-MRSA should be considered a possible etiology of skin infection in healthy individuals with no classical risk factors for acquisition of MRSA.

Revision of a Treatment Algorithm for Community-Associated Methicillin-Resistant Staphylococcus Aureus Skin Infections

Purpose Describe the need for a revision to a treatment algorithm for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections 3 years after implementation. Methods Medical records for patients seen in the emergency department (ED) for CA-MRSA skin infections from October 2005 through August 2007 were compared with records for patients seen from September 2002 through September 2004. Results Most patients with CA-MRSA initially were seen in the ED; however, by mid-2007 an increasing number of patients were coming to primary care clinics, particularly with recurrent episodes, and treatment for CA-MRSA was suboptimal in this setting. In addition, approximately 14% of CA-MRSA cases were not considered high risk based on the algorithm risk assessment. When the algorithm was implemented, the risk assessment classified less than 5% of CA-MRSA cases as low risk. Furthermore, newly published data suggested that incision and drainage (I&amp;D) was sufficient for small abscesses. Therefore, a revised algorithm that provided for treatment in all ambulatory settings, encouraged I&amp;D for small abscesses, and facilitated empiric treatment for CA-MRSA in all cases of suspected staphylococcal infection was developed. Initial feedback from providers has been positive, and a post implementation review has been planned. Conclusion A treatment algorithm that initially facilitated the care of patients with CA-MRSA skin infections in the ED only required revision because changes in the epidemiology of this disease had been observed. The new algorithm provides for empiric treatment for CA-MRSA in all cases of suspected staphylococcal skin infection, regardless of perceived risk or setting.

Community-associated methicillin-resistant Staphylococcus aureus skin infections: advances toward identifying the key virulence factors

In recent years there has been an increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in healthy individuals, the cause of which is largely unknown. CA-MRSA primarily causes skin and soft-tissue infections but certain strains are also associated with unusually severe pathology. The purpose of this review is to provide a critical analysis of our current knowledge of virulence factors contributing to skin and soft-tissue infections caused by CA-MRSA. Isolates classified as pulsed-field gel electrophoresis type USA300 have emerged as the predominant CA-MRSA genotype and in most geographic areas account for 97% or more of CA-MRSA infections. Recent key studies, such as those reporting the complete genome sequence of USA300, and the discovery of cytolytic peptides that contribute significantly to CA-MRSA virulence, lead the way for future investigations. Although we have only a cursory understanding of the molecular mechanisms of CA-MRSA virulence, studies using clinically relevant CA-MRSA isolates are beginning to identify virulence determinants specific to this pathogen. Identifying CA-MRSA virulence determinants and the concerted regulation of these factors will foster development of vaccines and therapeutics designed to control CA-MRSA skin infections.

Bag and Mask Ventilation

To the Editor: In his review of skin and softtissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA), Daum (July 26 issue)1 cites a study2 indicating that intravenous trimethoprim–sulfamethoxazole (TMP-SMX) is significantly less effective than vancomycin for the treatment of serious S. aureus infections. However, in this randomized, double-blind, comparative trial of TMP-SMX and vancomycin, therapeutic failures occurred only in patients with methicillin-susceptible S. aureus (MSSA) infections. TMP-SMX was successful in treating all MRSA infections, including tricuspid-valve endocarditis. Clinical failures commonly occurred with MSSA tricuspid-valve endocarditis; otherwise, the cure rates with TMPSMX and with vancomycin were similar. On the basis of the results of this study, vancomycin may be superior for MSSA infections; however, the same cannot be concluded for MRSA infections. Although the currently available clinical data for community-associated MRSA skin infections are sparse, in this era of an increasing incidence of MRSA infection and concern about the variable efficacy of vancomycin, TMP-SMX may be a useful alternative in selected cases.

Community-Associated Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections at a Public Hospital

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have emerged among patients without health care-associated risk factors. Understanding the epidemiology of CA-MRSA is critical for developing control measures. At a 464-bed public hospital in Chicago and its more than 100 associated clinics, surveillance of soft tissue, abscess fluid, joint fluid, and bone cultures for S aureus was performed. We estimated rates of infection and geographic and other risks for CA-MRSA through laboratory-based surveillance and a case-control study. The incidence of CA-MRSA skin and soft tissue infections increased from 24.0 cases per 100,000 people in 2000 to 164.2 cases per 100,000 people in 2005 (relative risk, 6.84 [2005 vs 2000]). Risk factors were incarceration (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.00-3.67), African American race/ethnicity (OR, 1.91; 95% CI, 1.28-2.87), and residence at a group of geographically proximate public housing complexes (OR, 2.50; 95% CI, 1.25-4.98); older age was inversely related (OR, 0.89; 95% CI, 0.82-0.96 [for each decade increase]). Of 73 strains tested, 79% were pulsed-field gel electrophoresis type USA300. Clonal CA-MRSA infection has emerged among Chicago's urban poor. It has occurred in addition to, not in place of, methicillin-susceptible S aureus infection. Epidemiological analysis suggests that control measures could focus initially on core groups that have contributed disproportionately to risk, although CA-MRSA becomes endemic as it disseminates within communities.

Evolving Epidemiology of Pediatric Staphylococcus aureus Cutaneous Infections in a Baltimore Hospital

To examine the epidemiology, antibiotic susceptibility profiles, and outcomes in pediatric Staphylococcus aureus (SA) cutaneous infections at a time when community-associated (CA) methicillin-resistant SA (CA-MRSA) infections seemed to be increasing in our community. The hospital microbiology database was searched for unique skin and wound SA isolates among pediatric patients between November 2002 and October 2003. Demographic and clinical data were abstracted from medical records. Cases were classified as either health care-associated (HA) or CA. Among 181 pediatric SA cutaneous infections, 81 (45%) were caused by MRSA. Most (84%) of these MRSA were CA. Between the first 6 months and second 6 months of the study period, CA-MRSA increased from 15% to 45% (P < 0.001) of all SA cutaneous infections. Ninety-eight percent and 94% of CA-MRSA were susceptible to trimethoprim/sulfamethoxazole and clindamycin (confirmed by D test), respectively. Hospitalization occurred for 25% of CA-MRSA and 75% of HA-MRSA (P = 0.004). Drainage procedures were performed for 70% of CA-MRSA. No cases of CA-MRSA skin infections were accompanied by bacteremia. The CA-MRSA cutaneous infections increased in children in our urban Baltimore hospital in 2003. These CA-MRSA were erythromycin resistant, clindamycin susceptible, and trimethoprim/sulfamethoxazole susceptible. The CA-MRSA cutaneous infections frequently required drainage and were not associated with bacteremia. Children with cutaneous MRSA infections were less likely to have traditional health care risk factors than children with cutaneous methicillin-sensitive SA infections--an inversion of past patterns of MRSA infections--but were equally likely to be hospitalized when other factors were considered. These CA-MRSA cutaneous infections can be managed with abscess drainage and culture, careful follow-up, and empirical clindamycin therapy when clinically indicated.

Risk Factors for Community-Associated Methicillin-Resistant Staphylococcus aureus Skin Infections among HIV-Positive Men Who Have Sex with Men

We investigated community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections among HIV-positive men who have sex with men. We performed a matched case-control study of 35 case patients and 76 control subjects. CA-MRSA skin infections were associated with high-risk sex and drug-using behaviors and with environmental exposures but not with immune status.