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Revista chilena de infectología

versión impresa ISSN 0716-1018

Rev. chil. infectol. v.26 n.5 Santiago oct. 2009

http://dx.doi.org/10.4067/S0716-10182009000600001 

Rev Chil Infect 2009; 26 (5): 403-404

EDITORIAL

 

Staphylococcus aureus: Old bug with new tricks

 

Staphylococcus aureus: Now 120 years after it was first discovered, Staphylococcus aureus continúes KJ to elude clinicians, perhaps raising more questions than ever before. The bacterium's pathogenicity stems in part from its repertoire of virulence factors, proclivity for tissue and endovascular invasión, and its malleability in integrating genetic elements that confer virulence and antimicrobial resistance, while simultaneously evading the host's immune response1-3. The successful evolutionary history of methicillin-resistant S. aureus (MRSA) is perhaps a forewarning of our current global epidemic and future challenges4-6. Though MRSA was a well-known cause of health care-associated (HCA) infections, it was not until reports of infection with unique clones of MRSA in otherwise healthy subjects without typical HCA risk factors, that the escalating prevalence of community-associated (CA) MRSA began to be recognized7-11. The Centers forDisease Control and Prevention (CDC) of the United States has identified MRSA as a major public health problem in a population-based surveillance study, estimating the incidence rate for invasive MRSA infections in the United States to be 31.8 per 100,000 persons, leading to 18,650 deaths in 2005 alone12. Since first reported in children, CA-MRSA infections continué to disproportionately affect the pediatric population9,12,13 with frequencies varying geographically from 30 to 70% across pediatric hospitals in the US14,46. Data suggest that CA-MRSA isolates and risk factors for infection may be different in children than adults17. The versatility of CA-MRSA has allowed it to emerge as a major bacterial pathogen causing a diverse spectrum of clinical illnesses ranging from the more common skin and soft-tissue infections, toxin-mediated diseases to invasive, suppurative infections, with the highest mortality seen in those patients with sepsis and disseminated disease18. It is not surprising that during the last decade, the increasing magnitude of CA-MRSA disease burden, virulence, and its changing epidemiology has now been reported worldwide19.

In tbis issue of the Revista Chilena de Infectología, authors highlight the evolving clinical epidemiology of CA-MRSA infections in Argentina and Uruguay, along with corresponding antimicrobial usage and emerging resistance patterns. Both studies demónstrate that greater than 60%o of S. aureus isolates are methicillin-resistant and skin and soft-tissue abscesses are the most common clinical presentations. Paganini et al, performed a multi-center, prospective observational study in children over 1 month of age seeking medical attention, comparing CA-MRSA infections in previously healthy subjects to children with known underlying medical conditions or HCArisk factors.

Similar to other studies assessing the impact of CA-MRSA in children with health care exposures20-21, the majority of cases in both groups were skin and soft-tissue infections, though the rates were highest children without HCA risk factors. The rates of bacteremia, sepsis, and overall mortality were also similar in both groups. Interestingly, previously healthy children required more surgical procedures than children with underlying medical conditions or HCArisk factors. Children with HCArisk factors had higher levéis of rifampin, trimethoprim/sulfamethoxazole, and clindamycin resistance. Although CA-MRSA strains were thought to be similar in both groups, no molecular analyses were performed on the isolates to confirm this observation and may explain some of the differences observed. There was a high discordance (> 50%>) in both groups between empiric antibiotic therapy and the pathogen isolated and delay of 72-96 hours before appropriate antimicrobial therapy was started. These observations underscore not only the importance of empiric antibiotic choices, but the need for improved, rapid diagnostic methodologies. Telechea and colleagues performed a retrospective observational study to assess antimicrobial usage in hospitalized children at a pediatric hospital in Uruguay from 2001-2006. They evaluated the in vitro susceptibilities of the S. aureus isolates obtained from sterile body sites and skin/soft tissue abscesses during the same study period. The authors comment that new national empiric antibiotic guidelines were established in 2004 in response to the increasing rates of MRSA, howe-ver the empiric antibiotics recommended depending on the clinical syndrome are unclear and any epidemiologic differences that may have been noted before or after the guidelines were implemented are lacking. As expected, the use of clindamycin, vancomycin, and trimethoprim/ sulfamethoxazole increased during the study period. Although oxacillin susceptibility of S. aureus isolates decreased, use of ceftriaxone and cefotaxime increased. The increased use of clindamycin during the study period coincided with an increase in both erythromycin and clindamycin susceptibility. From 2004-6, there was a decrease in inducible clindamycin resistance, as evaluated by D-zone testing, although the overall rate was still high at 21%o. Though the actual impact of inducible clindamycin resistance is not well described, most experts would not recommend empiric clindamycin therapy in áreas where local microbiology laboratory results demónstrate that the proportion of CA-MRSAisolates resistant to clindamycin are greater than 10%.

Continued surveillance of CA-MRSA infections locally, including clinical epidemiology and disease syndromes, MRSAmicrobiology cultures and molecular genotypic information, and antimicrobial susceptibility testing are even more important as the definition of what is considered a CA-MRSA infection becomes more contentious22,23. CA-MRSAinfections have been defined by the US Centers for Disease Control and Prevention as the isolation of MRSA from a subject in the outpatient setting or within 48 hours of admission in hospitalized patients with no indwelling catheters, prior hospitalization, or known history of previous MRSA infection or colonization9,24. Molecular characteristics have also been used to classify an MRSA isolate as acquired in the community. Pulse-field gel electrophoresis types USA 300 and 400, corresponding to multilocus sequence types 8 and 1, respectively, have been the predominant MRSA types associated with community transmission25. MRSA strains carrying the mecA gene on the staphylococcal cassette chromosome mee (SCCmec) gene complex or isolates containing certain virulence genes such as PVL or genetic elements such as arginine catabolic mobile element (ACME) have also been used to define CA-MRSA isolates25-29. Lastly, unhke HCA-MRSA, CA-MRSA strains have typically demonstrated susceptibility to most classes of antimicrobial agents (other than ß-lactams and macrolides) such as clindamyein, trimethoprim/sulfame-thoxazole, fluoroquinolones, and tetraeyelines.

However, differences between what were considered 'typical' HCA and CA-MRSA isolates are becoming less distinct. Growing exceptions to the epidemiologic, antimicrobial susceptibility, and molecular definitions of CA-MRSA infections, make it less likely that a single, comprehensive definition is achievable. Discovery of new virulence determinants30-32, findings of CA-MRSA isolates in hospital settings33-36, and changing antimicrobial susceptibilities to vancomyein and clindamyein14,37,38 and newer anti-staphylococcal antibiotics39-41 continué to challenge clinicians and researchers alike. Many key clinical questions also remain unanswered and highlight the urgent need for studies to provide data needed to guide the optimal treatment of invasive disease, management of sknd soft-tissue infections, and performance of successful prevention and surveillance strategies, as well as stimu-lating antimicrobial new drug and vaccine development. In the interim, in an effort to help guide clinicians, the CDC has published a summary of strategies for clinical management of MRSA in the community (http://www.cdc.gov/ncidod/dhqp/ar_mr-sa_ca_04meeting.html) and the AmericanAcademy of Pediatrics has also formulated a suggested algorithm for managing children with suspected CA-MRSA infections.

 

Monica I. Ardura, DO


Assistant Professor of Pediatrics,
Division of Pediatric Infectious Diseases
University ofTexas Southwestern Medical Center,
Dallas, Texas, USA

 

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