Topic Article
Staphylococcus aureus in Dermatology Outpatients with Special Emphasis on Community-Associated Methicillin-Resistant Strains
Uta Jappe, Dagmar Heuck, Birgit Strommenger, Constanze Wendt, Guido Werner, Doris Altmann and Wolfgang Witte
Journal of Investigative Dermatology (2008), 128, 2655-2664; doi: 10.1038/jid.2008.133

MRSA in Dermatology

Brian R. Keegan ¹, Yvonne Romagosa ¹ and Robert S. Kirsner ¹

Journal of Investigative Dermatology (2008) 128, 2566. doi:10.1038/jid.2008.301

Methicillin-resistant Staphylococcus aureus (MRSA), first described in hospital settings (hospital-acquired or health care–associated MRSA; HA-MRSA), has garnered a tremendous amount of interest from both health-care workers and the general public since its discovery in 1961 (Barber, 1961). This interest stems from a number of factors, including the magnitude of the infections, the broader concern of antibiotic resistance, and media sensationalism of selected cases. Genetic resistance patterns as well as the initial locations of infection have recently shifted, with a trend toward affecting the nonhospitalized population. Community-associated MRSA (CA-MRSA) (Saravolatz et al., 1982) is even more intriguing to lay and professional groups. CA-MRSA is distinguished from HA-MRSA by its more limited antibiotic-resistance profile, differences in the toxins it produces, the population susceptible to it, and its propensity for outbreaks (Naimi et al., 2003). Of interest to dermatologists, CA-MRSA has a stronger predilection for skin involvement compared with HA-MRSA.

The emergence of MRSA in the community has led many physicians to wonder how prevalent these infections are and how they should be treated in the outpatient setting. These questions have been at least partly answered by the EMERGEncy ID Net Study Group, which reported that 59% of adult patients with acute purulent skin and soft-tissue infections who presented to their emergency rooms were infected with MRSA (Moran et al., 2006). This study also demonstrated that the most effective treatment in this population was incision and drainage of the infection. Such studies provide tremendous insight into MRSA, yet they have also raised critical questions for practitioners in dermatology. Jappe et al. analyze the frequency, antibiotic resistance, and molecular profiles of cutaneous infections from S. aureus in the outpatient dermatology clinic at the University of Heidelberg in Germany.

Over a 6-year period, the authors isolated S. aureus in 52% of their infected study population; 14% of these isolates were MRSA. Thus, only 7% of their total study population had MRSA. Additionally, via strict definitions as well as extensive genotyping and resistance profiling, Jappe et al. (2008) concluded that 22% of the total MRSA isolates were caused by CA-MRSA and the remainder due to HA-MRSA. These observations are intriguing because, contrary to many clinicians’ prior impressions, MRSA infections were relatively uncommon in this study population, with CA-MRSA accounting for only 1.4% of the total isolates.

Through the following questions, we examine this paper in greater detail.

QUESTIONS

1. What are the differences between CA-MRSA and HA-MRSA?
2. How does the study sample influence the study results?
3. How are S. aureus infections categorized?
4. What are the major findings of this study?
5. What may be the clinical implications of this article?
6. What further studies could be performed?

ANSWERS

1. Interest in methicillin-resistant Staphylococcus aureus (MRSA), first discovered in 1961 (Barber, 1961), stems from a number of factors, including the magnitude of the infections, concern over the development of antibiotic resistance, and media sensationalism of selected cases. It has drawn greater attention since a variant, community associated MRSA (CA-MRSA) (Saravolatz et al., 1982), was first described. The original description and subsequent studies have noted that CA-MRSA is distinguished from health-care associated MRSA (HA-MRSA) by a more limited antibiotic-resistance profile, differences in toxins produced, the susceptible populations, and a propensity for outbreaks (Naimi et al., 2003).

Since antibiotics were first identified, they have been a mainstay for treating bacterial infections. Their widespread use has enabled the proliferation of bacteria that are resistant to various antibiotics (Hawkey, 2008). A retrospective analysis of antibiotic resistance demonstrates that S. aureus is one of the most versatile bacteria, often developing resistance patterns that emerge only 2–5 years after the introduction of a new class of antibiotics. Furthermore, a 2007 report on emerging infectious diseases published by the Centers for Disease Control and Prevention estimated that the number of MRSA cases requiring hospitalization rose from 127,000 in 1999 to 278,000 in 2005; over the same period, the number of deaths increased from 11,000 to more than 17,000 (Klein, 2007). These figures suggest that MRSA infections are responsible for more deaths in the United States each year than AIDS. Increased awareness of antibiotic resistance by both physicians and the general public has led to discussions about their proper use. It is important to study CA-MRSA and HA-MRSA in order to improve our patient care and to limit further development of antibiotic resistance.

Studies have shown that HA-MRSA most often affects older patients in nursing homes and hospitals, whereas CA-MRSA usually affects younger, nonhospitalized patients. In addition, these bacteria exhibit different antibiotic-resistance profiles. HA-MRSA generally responds to vancomyocin, daptomyosin, and linazolid; CA-MRSA is usually susceptible to these antibiotics as well as bactrim, doxycyclin, and clindamycin (this is thought to be secondary to their different staphylococcal cassette chromosome mec (SCC_mec_) cassettes (see below)). Furthermore, HA-MRSA is more often systemic, whereas CA-MRSA infections are usually limited to the skin and soft tissues. Finally, although study results are not conclusive, HA-MRSA and CA-MRSA appear to express different toxin profiles (Naimi et al., 2003).

2. Both research and clinical populations are expected to be influenced by a number of factors, including patients’ age, referral patterns, socioeconomic status, residential status, and local antibiotic usage (Carmeli, 2008). Since patients with more serious infections and individuals without access to clinics are more likely to go to an emergency room, it is not surprising that the EMERGEncy ID Net Study Group noted that 59% of the infections in its database were caused by MRSA (Moran et al., 2006). In contrast, it would be expected that patients with less serious infections would present to the outpatient dermatology clinic; it is therefore also not surprising that in the University of Heidelberg clinic study only 14% of infections were from MRSA (Jappe et al., 2008). Furthermore, it is important to know the definitions that are used by the researchers, as well as the inclusion, exclusion, and follow-up criteria. For instance, the 248 infections noted by Jappe et al. during the 27-month study period could have been influenced by the number of clinic visits, the exclusion of patients, or the limited incidence of infection in this population.

3. Pathogens can be subclassified by antibiotic profile, location of infection, genetic profile (expression of antibiotic resistance genes, toxins, or virulence factors) and isotype/genetic variance. CA-MRSA typically has a limited resistance profile, showing resistance to penicillin and its derivatives (oxacillin, methicillin, etc.), but is often susceptible to clindamycin, chloramphenicol, trimethoprim/sulfamethoxazole, and tetracyclines (Naimi et al., 2003). HA-MRSA may be susceptible to some antibiotics but often requires treatment with vancomycin, linezolid, or daptomycin; occasionally it is resistant to these antibiotics as well (Kaul et al., 2008). CA-MRSA and HA-MRSA differ in their predominant location of infection; HA-MRSA infections are usually systemic, whereas CA-MRSA is often found on skin and is accessible to drainage(Naimi et al., 2003). Some of these differences are thought to arise from the different virulence factors of these bacteria. For instance, methicillin resistance is encoded by the mec_A gene, which is inserted in the SCC_mec cassette/operon that codes for an altered penicillin-binding protein (PBP2a or PBP2’) that has a lower affinity for binding β-lactams (penicillins, cephalosporins, and carbapenems). This cassette is a mobile genetic element consisting of five types and several subtypes. HA-MRSA incorporates the SCC_mec_ types I–III and CA-MRSA types IV and V (Deurenberg et al., 2007). Oxacillin-resistant strains are detected by phenotypic and genotypic methods, including restriction mapping, gene sequencing, and dendrograms (tree diagrams%28graphtheory%29 used to illustrate the origin and phylogenic arrangement of organisms).

4. Several important conclusions can be drawn from this study. First, the prevalence of MRSA infections in the German outpatient clinic (14%) is not as high as that found in the previously studied ER population (59%) (Moran et al., 2006). Second, the PLV virulence factor is not exclusive to CA-MRSA, since it was found in some HA-MRSA infections. Third, traveling or contact with travelers is a risk factor for CA-MRSA (all four cases of CA-MRSA in this study were associated with traveling in the previous 12 months). Finally, CA-MRSA infections tend to be deeper infections, with one case of an abscess and two cases of furuncles noted in this study. However, there were deep infections caused by HA-MRSA and the population numbers in the study are limited; conclusions should therefore be tempered.

5. The results from this study demonstrate that MRSA infections made up a small but significant portion of the total number of infections treated in this clinic during the 27-month study period. The findings suggest that deep infections and travel contact are risk factors for CA-MRSA. However, to apply this information in practice, one should consider a patient’s demographics, including age, referral patterns, socioeconomic status, residential status, local antibiotic usage, and comorbidities. Ultimately, when faced with an HA-MRSA or CA-MRSA infection, a clinician must decide whether to perform an invasive procedure and whether to start antibiotics or observe the course while collecting culture data.

6. This study provides valuable information about infections and antibiotic resistance in an outpatient clinic. It also raises many new questions. First, only S. aureus infections were discussed—what other types of infections were noted? Second, some information was gathered on MRSA in the nares, but collection was not uniform and the clinical significance of this information was unclear. Third, little information was given concerning the outcomes, including interventional procedures and the need for hospital admission. Finally, given the apparently low prevalence of MRSA infections in outpatient clinics, these results should be validated in a larger study population.

REFERENCES

Barber M (1961) Methicillin-resistant staphylococci. J Clin Pathol 14:385–93

Carmeli Y (2008) Strategies for managing today’s infections. Clin Microbiol Infect 14(Suppl 3):22–31

Deurenberg RH, Vink C, Kalenic S, Friedrich AW, Bruggeman CA, Stobberingh EE (2007) The molecular evolution of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect 13:222–35

Hawkey PM (2008) The growing burden of antimicrobial resistance. J Antimicrob Chemother 62(Suppl 1):i1–9

Jappe U, Heuck D, Strommenger B, Wendt C, Werner G, Altmann D et al. (2008) Staphylococcus aureus in dermatology outpatients with special emphasis on community-associated methicillin-resistant strains. J Invest Dermatol 128:2655–64

Kaul DR, Collins CD, Hyzy RC (2008) New developments in antimicrobial use in sepsis. Curr Pharm Des 14:1912–20

Klein E, Smith DL, Laxminarayan R (2007) Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999–2005. Emerg Infect Dis 13:1840–6

Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB et al. (2006) Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 355:666–74

Naimi TS, LeDell KH, Como-Sabetti K et al. (2003) Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. J Am Med Assoc 290:2976–84

Saravolatz LD, Pohlod DJ, Arking LM (1982) Community-acquired methicillin-resistant Staphylococcus aureus infections: a new source for nosocomial outbreaks. Ann Intern Med 97:325–9

¹ Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA