The Journal of Pediatrics
Volume 151, Issue 6 , Pages 561-563, December 2007

Staphylococcus Aureus: A Moving Target

  • Arthur L. Frank, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Arthur L. Frank, MD, Department of Pediatrics MC 856, University of Illinois at Chicago, 840 S Wood St, Chicago IL 60612.

Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois

Article Outline

 

In this issue of The Journal, Faden et al1 present an analysis of 49 staphylococcal skin abscesses in children from Buffalo, NY. The clinical characteristics of these infections are in the range of current experience as extensively reported previously and summarized in a recent review.2 The authors emphasize, instead, characterization of the infecting organisms by relevant microbiologic and molecular testing. They report that 27% of the isolates are methicillin-susceptible Staphylococcus aureus (MSSA), not obviously different from any isolate since the emergence of penicillin resistance in S. aureus about 40 years ago.3 The other 73% of isolates provoke clinical and molecular interest because they are community-associated methicillin-resistant S. aureus (CA-MRSA), present in epidemiologically significant numbers in U.S. children only since the mid-1990s.4, 5 Molecular techniques developed for all bacteria, especially hospital-associated MRSA, have been applied in an attempt to understand the pathogen side of this new epidemiologic situation and staphylococcal disease in general.

See related article, p 700

The key feature of CA-MRSA is changed antibiotic susceptibility. All of the CA-MRSA organisms in the Buffalo study contain the SCCmecA type IV gene cassette, which confers resistance to all antistaphylococcal beta lactam antibiotics but not to other antibiotics. They also were susceptible to clindamycin, mupirocin, and, by implication from the reported therapy, trimethoprim-sulfamethoxazole. Resistance to these antibiotics is determined by different genetic mechanisms. Hospital-associated MRSA have different SCCmecA types and are resistant to more antibiotic groups. They are included in the Centers for Disease Control national MRSA database report referenced.6 Despite the clinical importance of antibiotic susceptibilities for treatment of CA-MRSA infections,2 Faden et al1 go beyond this in characterizing the organisms in their study.

One striking finding in this article is that almost all the isolates, with or without the SCCmecA IV (ie, MSSA or CA-MRSA), were in the same USA300 “family”6 by pulsed-field gel electrophoresis (PFGE) and multilocus sequence testing. These tests look at the overall genome according to where specific enzymes break the DNA (PFGE) or by DNA sequence changes in 7 neutral (“housekeeping”) loci. Furthermore, almost all isolates contained the putative virulence factor Panton-Valentine leukocidin (PVL) but not exotoxin (et) genes eta, etb, or staphylococcal toxic shock toxin 1. If this genetic background and particular factors have some relevance, we would expect to see similar clinical syndromes with these organisms whether CA-MRSA or MSSA. This does seem to be the case in this small group of patients with 1 type of infection.

There is also a difference between CA-MRSA and MSSA in these Buffalo isolates, besides the presence or absence of SCCmecA. Only the CA-MRSA have the lipo phospholipase gene, part of the arginine catabolic mobile element complex (ACME) identified in fully sequenced USA 300.7 Faden et al1 suggest that this gene could be a marker for the CA-MRSA in their community, as compared with MSSA. The authors who identified ACME in CA-MRSA7 theorize that it could be a factor enhancing skin colonization. This could then lead to the rapid, wide geographic clonal expansion with little genomic diversification that has been observed by their group and others. Clinical infection frequency could be increased secondarily and a gene in the ACME complex could allow for energy production in low oxygen wound environments. They also postulate clinical associations with other features seen in the sequence.

The detailed characterization of this small group of bacteria by Faden et al,1 combined with many similar analyses in the literature, points to a complex and unpredictable evolutionary pattern. The earliest recognized pediatric CA-MRSA outbreaks in the U.S. upper Midwest in the mid-1990s4, 5 occurred with PFGE type USA400. Starting about 2001, the USA300 PFGE type replaced USA400 in many locations, although documentation is sometimes with partial characterization or selected populations.8, 9, 10 Other U.S. regions recognized CA-MRSA some years later and may have had USA300 from the beginning. Almost all studies show a dominant CA-MRSA type over short periods of time, but most have substantial minority populations, and the mix of strains varies with time and geography. For example, a recent study documents the MRSA pattern changed from 2000-2002 in 2 hospitals in the San Francisco Bay area.11 One had 3 types of CA-MRSA at the start (USA500, 1000, and 1100; no USA300) but 50% USA300 by 2002, and the other had mostly hospital-associated MRSA initially, with USA300 just appearing in 2002. The MSSA and CA-MRSA have not always been from the same genetic background as was the case in Buffalo.12, 13 The reappearance of the historically important phage type 40/41 penicillin-resistant S. aureus from the 1950s and 1960s, now with new gene groups redefining itself as a PVL-positive CA-MRSA,14 is noted by Faden et al.1 The evolutionary reconstructions in that article and others demonstrate how various “base” MSSA can acquire SCCmec and other new virulence and resistance factors.

Data are far from complete on historical isolates in the literature, but the presence of PVL may not have been as universal as in the Buffalo specimens, especially if MSSA are included. The LCL gene is believed to have been in USA 300 CA-MRSA for some time. It was found in USA300 in other populations15, 16 but not in those without type-IVa SCCmec,15 and multiple testing in more collections may reveal additional variation. There are also ongoing changes in antibiotic susceptibility of CA-MRSA. One striking example from Boston is a high frequency of clindamycin, tetracycline, levofloxacin, and mupirocin resistance in some USA300 from 2004 to 2005.17 The authors reference previous similar observations and note that the resistance in their isolates derives from plasmids likely transferred from other bacterial reservoirs. The source of putative virulence or colonization factors is also often postulated or known to be from other bacteria; the ACME complex probably came from coagulase-negative staphylococci.7 In fact, almost all the virulence and antibiotic resistance factors identified in CA-MRSA research have features indicating transmissibility. The staphylococcus seems to have access to genetic change via a large number of components from many other organisms.

The sampling of selected, mostly recent, mostly U.S. literature above can guide the reader to many other similar studies indicating variation and complexity; experience in other countries adds even more.6, 14 CA-MRSA recently has been highlighted as a complication of influenza in children.18 This juxtaposition brings up a provocative similarity to that very different but famously successful pathogen, influenza A. The molecular evolution of the 2 pathogens may be different in detail but analogous in the final effect on human beings. It appears that S. aureus, like influenza A, is a moving target for clinicians and researchers that is revealed to be more complex the more it is studied. Predictable patterns of change or limitations of repertoire may become apparent over time, but current knowledge does not suggest that this will occur.

Clinicians and researchers will agree that the more that is known about the staphylococcus, the more likely new prevention and treatment methods will be developed. Understanding the mechanisms of illnesses and their manifestations is often satisfying to physicians and their patients even without an immediate opportunity for intervention. Genetic elements that cannot be controlled or predicted can be used in epidemiologic studies. These may enable interventions in nosocomial, community, or widespread outbreaks. One clinical solution to change and complexity of the pathogen could be to find an intervention that works for all variant staphylococci. A well-designed vaccine might qualify. The approach taken so far has been to adjust therapies to the changing pathogen, most obviously in the development of new or re-application of older antibiotics.2 It seems possible that supportive therapies on the basis of counteraction of known pathogenic and virulence factors will become part of the clinician’s armamentarium; immunoglobulin intravenously is already considered in therapy of staphylococcal toxic shock syndrome,19 and other treatments may result from current or future research.20 Detailed characterization of the infecting organisms in the community or even in the infected individual, as was demonstrated by Faden et al,1 may become routinely available in the future and could be used in choosing both public health measures and individual therapies.

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References 

  1. Faden H, Rose R, Lesse A, Hollands C, Dryja D, Glick PL. Clinical and molecular characteristics of staphylococcal skin abscesses in children. J Pediatr. 2007;151:700–703
  2. Daum RS. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med. 2007;357:380–390
  3. Chambers HF. The changing epidemiology of Staphylococcus aureus?. Emerg Infect Dis. 2001;7:178–182
  4. Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle-Vavra S, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998;279:593–598
  5. Centers for Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus— Minnesota and North Dakota, 1997-1999. MMWR. 1999;48:707–710
  6. McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol. 2003;41:5113–5120
  7. Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, et al. Complete genome sequence of USA300, an epidemic clone of community-acquired methicillin-resistant Staphylococcus aureus. Lancet. 2006;367:731–739
  8. Chavez-Bueno S, Bozdogan B, Katz K, Bowlware KL, Cushion N, Cavuoti D, et al. Inducible clindamycin resistance and molecular epidemiologic trends of pediatric community-acquired methicillin-resistant Staphylococcus aureus in Dallas, Texas. Antimicrob Agents Chemo. 2005;49:2283–2288
  9. Stemper ME, Brady JM, Qutaishat SS, Borlaug G, Reed J, Reed KD, et al. Shift in Staphylococcus aureus clone linked to an infected tattoo. Emerg Infect Dis. 2006;12:1444–1446
  10. Jungk J, Como-Sabetti K, Stinchfield P, Ackerman P, Harriman K. Epidemiology of methicillin-resistant Staphylococcus aureus at a pediatric healthcare system, 1991-2003. Pediatr Infect Dis J. 2007;26:339–344
  11. Bhattacharya D, Carleton H, Tsai CJ, Baron EJ, Perdreau-Remington F. Differences in clinical and molecular characteristics of skin and soft tissue methicillin-resistant Staphylococcus aureus isolates between two hospitals in northern California. J Clin Micro. 2007;45:1798–1803
  12. Hultén KG, Kaplan SL, Gonzalez BE, Hammerman WA, Lamberth LB, Versalovic J, et al. Three-year surveillance of community onset health care-associated Staphylococcus aureus infections in children. Pediatr Infect Dis J. 2006;25:349–353
  13. Jaggi P, Paule SM, Peterson LR, Tan TQ. Characteristics of Staphylococcus aureus infections, Chicago pediatric hospital. Emerg Infect Dis. 2007;13:311–314
  14. Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann H, Edwards G, et al. Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone. Lancet. 2005;365:1256–1258
  15. Goering RV, McDougal LK, Fosheim GE, Bonstetter KK, Wolter DJ, Tenover FC. Epidemiologic distribution of the arginine catabolic mobile element among selected methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates. J Clin Microbiol. 2007;45:1981–1984
  16. Johnson JK, Khoie T, Shurland S, Kreisel K, Stine OC, Roghmann MC. Skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus USA300 clone. Emerg Infect Dis. 2007;13:1195–1200
  17. Han LH, McDougal LK, Gorwitz RJ, Mayer KH, Patel JB, Sennot JM, et al. High frequencies of clindamycin and tetracycline resistance in methicillin-resistant Staphylococcus aureus pulsed-field type USA300 isolates collected at a Boston ambulatory health center. J Clin Microbiol. 2007;45:1350–1352
  18. Centers for Disease Control and Prevention. Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza—Louisiana and Georgia, December 2006-January 2007. MMWR. 2007;56:325–329
  19. Chuang YY, Huang YC, Lin TY. Toxic shock syndrome in children; epidemiology pathogenesis and management. Pediatr Drugs. 2005;7:11–25
  20. Buonpane RA, Churchill HRO, Moza B, Sundberg EJ, Peterson ML, Schlievert PM, et al. Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists. Nat Med. 2007;13:725–729

PII: S0022-3476(07)00889-X

doi:10.1016/j.jpeds.2007.09.030

Refers to article:

  • Clinical and Molecular Characteristics of Staphylococcal Skin Abscesses in Children , 29 October 2007

    Howard Faden, Rebecca Rose, Alan Lesse, Celeste Hollands, Diane Dryja, Philip L. Glick
    The Journal of Pediatrics December 2007 (Vol. 151, Issue 6, Pages 700-703)

The Journal of Pediatrics
Volume 151, Issue 6 , Pages 561-563, December 2007

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