Methicillin-resistant Staphylococcus aureus pneumonia in children: a call for increased vigilance.

During the past two decades in the United States, Staphylococcus aureus pneumonia has been infrequently encountered in healthy children. However, that trend may be changing, given the emerging reports from several parts of the country. (1-3) These reports suggest that the organism may be playing an increasing role, not only as a cause of pneumonia in children but also of complicated pneumonia. Schultz et al (1) recently published a 10-year (1993 to 2002) retrospective chart review of all pediatric discharges with a diagnosis of empyema and community-acquired pneumonia from a children's hospital in Texas. Although the number of children admitted with empyema decreased over the study period, S aureus emerged as the most common isolated etiologic agent, accounting for 60% of all isolates in 2001 to 2002 (versus 18% in 1993 to 1994), with an increase in the absolute number of cases over the period. Although the reported change in the relative frequency of S aureus isolates could be partially explained by the effectiveness of the seven-valent pneumococcal vaccine as evidenced by the attendant decrease in invasive Streptococcus pneumoniae infections in the series by Schultz et al, (1) the worrisome fact from that study is that 78% of the S aureus isolates were resistant to methicillin. In an earlier but similar study from another children's hospital in the country, Buckingham et al (2) reported that the proportion of cases of complicated parapneumonic effusions caused by S aureus increased from 6% in the period 1996 to 2000 (all of which were methicillin susceptible) to 30% in 2001 (all methicillin resistant).

It is of historic interest that Chartrand and McCracken, (4) on review of their experience in 79 children with S aureus pneumonia between 1965 and 1978, found no single methicillin-resistant S aureus (MRSA) isolate. Besides pneumonia, the increasing trend of community-acquired MRSA (CA-MRSA) infections has been reported in all age groups throughout the United States (5-8) and the rest of the world. (9-12) In one study from rural parts of the western United States, 75% of CA-MRSA isolates were from patients with no coexisting factors that could predispose them to MRSA infection. (13) In 2001, drawing from parallels in the evolution of the epidemiology of penicillinase-producing S aureus in the 1940s through the 1970s, Chambers (14) noted the ominous rising trend in the prevalence of hospital-associated S aureus (HA-MRSA) and predicted the inevitability of the emergence of high rates of MRSA in the community if the trend was maintained. The fulfillment of that prediction may be on the horizon. Although skin and soft tissue infections remain the most common infection caused by CA-MRSA, (8) the healthcare community should anticipate increasing cases of complicated pneumonia due to this organism, especially in children.

In the Journal, Stallworth et al (15) report a case of CA-MRSA empyema necessitatis in an 8-month-old infant. This report is relevant to the public health discussion of the current evolving epidemiology of CA-MRSA infections. Although not critical to this discussion, the child was reported to be previously healthy but it is uncertain if the authors excluded any underlying immunodeficiency that could have predisposed the child to bacterial infections, particularly by catalase-positive organisms such as Staphylococci.

It remains unclear whether CA-MRSA pneumonia in children is more likely to be complicated compared with methicillin-susceptible S aureus (MSSA) pneumonia. Of 30 children with community-acquired S aureus pneumonia admitted between 2000 and 2003 to Memorial Hermann Children's Hospital in Houston, Texas, Ochoa et al (16) found that 12 of 17 cases caused by CA-MRSA were complicated, compared with 2 of 13 caused by MSSA. Relative to HA-MRSA isolates, CA-MRSA isolates are more likely to carry the Panton-Valentine leukocidin (PVL) gene, (14) an exotoxin that induces lysis of host macrophages, thus impairing host response and facilitating tissue necrosis. This exotoxin is also frequently found in necrotizing lesions caused by MSSA. The staphylococcal isolates in the report by Stallworth et al (15) were not assayed for PVL.

Most epidemiologic studies (6, 7, 17) suggest clusters of clonal expansion of the CA-MRSA with lineage to the CDC-designated USA 300 clone but do not account for the entire genotypic variability of the strains. The exact origin and modality of spread of CA-MRSA is yet to be fully elucidated. The recent identification of cassette chromosome recombinase genes A and B (ccrAB) may provide the clue. It is believed that ccrAB genes encode enzymes that can precisely excise and integrate the methicillin resistance encoding gene mec, thereby facilitating entry into the S aureus chromosome to form the mobile genetic element, staphylococcal chromosome cassette mec (SCCmec). (14, 18, 19) Based on genetic polymorphism of both mec and ccr complexes, 5 types (types I through V) of SCCmec are recognized. A unique distinction between HA-MRSA and CA-MRSA is that the former predominantly carry types I, II, and III SCCmec, whereas the latter mostly contain types IV and V SCCmec.

In addition, unlike HA-MRSA, which tends to be multiresistant, CA-MRSA isolates remain susceptible to a wide range of antibiotics including clindamycin, gentamicin, trimethoprim-sulfamethoxazole, tetracycline, and some fluoroquinolones. How long that phenotypic CA-MRSA antibiotic susceptibility pattern will persist is currently conjectural. In the face of increasing drug resistance by the common respiratory pathogens and with limited alternatives, empirical treatment of childhood pneumonia could become challenging, particularly in the outpatient setting. In this regard, given the trend toward an increase in clindamycin-resistant MRSA, it is not altogether reassuring from the recent finding that most S aureus from military facilities in the northeast region of the United States are still susceptible to clindamycin and do not appear to have inducible resistance. (20) One can only hope that the report by Stallworth et al (15) and the trends that appear to be emerging will further underscore the need for judicious use of antimicrobials in all healthcare settings.

References

1. Schultz KD, Fan LL, Pinsky J, et al. The changing face of pleural empyemasin children: epidemiology and management. Pediatrics 2004;113:1735-1740.

2. Buckingham SC, King MD, Miller ML. Incidence and etiologies of complicated parapneumonic effusions in children, 1996 to 2001. Pediatr Infect Dis J 2003;22:499-504.

3. Alfaro C, Fergie J, Purcell K. Emergence of community-acquired methicillin-resistant Staphylococcus aureus in complicated parapneumonic effusions. Pediatr Infect Dis J 2005;24:274-276.

4. Chartrand SA, McCracken GH Jr. Staphylococcal pneumonia in infants and children. Pediatr Infect Dis 1982;1:19-23.

5. Kuehnert MJ, Hill HA, Kupronis BA, et al. Methicillin-resistant Staphylococcus aureus Hospitalizations, United States. Emerg Infect Dis [serial on the Internet]. 2005 June. Available at: http://www.cdc.gov/ncidod/EID/vol 11 no 06/04-0831.htm. Accessed July 11, 2005.

6. Moran GJ, Amii RN, Abrahamian FM, et al. Methicillin-resistant Staphylococcus aureus in community-acquired skin infections. Emerg Infect Dis [serial on the Internet]. 2005 June. Available at: http://www.cdc.gov/ncidod/EID/vol 11 no 06/04-064.htm. Accessed July 11, 2005.

7. Bratu S, Eramo A, Kopec R, et al. Community-associated methicillin-resistant Staphylococcus aureus in hospital nursery and maternity units. Emerg Infect Dis [serial on the Internet]. 2005 June. Available at: http://www.cdc.gov/ncidod/EID/vol 11 no 06/04-0885.htm. Accessed July 11, 2005.

8. Fridkin SK, Hageman JC, Morrison M, et al. Active bacterial core surveillance program of the Emerging Infections Program Network: Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med 2005;352:1436-1444.

9. Harbarth S, Francois P, Schrenzel J, et al. Community-associated methicillin-resistant Staphylococcus aureus, Switzerland. Emerg Infect Dis [serial on the Internet] 2005 June. Available at: http://www.cdc.gov/ncidod/EID/vol 11 no 06/04-1308.htm. Accessed July 11, 2005.

10. Mulvey MR, MacDougall L, Cholin B, et al. Community-associated methicillin-resistant Staphylococcus aureus, Canada. Emerg Infect Dis [serial on the Internet]. 2005 June. Available at: http://www.cdc.gov/ncidod/EID/vol 11 no 06/04-1146.htm. Accessed July 11, 2005.

11. Ma XX, Galiana A, Pedreira W, et al. Community-acquired methicillin-resistant Staphylococcus aureus, Uruguay. Emerg Infect Dis [serial on the Internet]. 2005 June. Available at: http://www.cdc.gov/ncidod/EID/vol 11 no 06/04-1059.htm. Accessed July 11, 2005.

12. Chen CJ, Huang YC, Chiu CH, et al. Clinical features and genotyping analysis of community-acquired methicillin-resistant Staphylococcus aureus infections in Taiwanese children. Pediatr Infect Dis J 2005;24:40-45.

13. Stephenson KB, Searle K, Stoddard GJ, et al. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci in rural communities, Western United States. Emerg Infect Dis [serial on the Internet]. 2005 June. Available at: http://www.cdc.gov/ncidod/EID/vol 11 no 06/05-0156.htm. Accessed July 11, 2005.

14. Chambers HF. The changing epidemiology of Staphylococcus aureus? Emerg Infect Dis 2001;7:178-182.

15. Stallworth J, Mack E, Ozimek C. Methicillin-resistant staphylococcus aureus empyema necessitatis in an eight-month-old child. South Med J 2005;98:1130-1131.

16. Ochoa TJ, Mohr J, Wanger A, et al. Community-associated methicillin-resistant Staphylococcus aureus in pediatric patients. Emerg Infect Dis [serial on the Internet]. 2005 June. Available at: Available from http://www.cdc.gov/ncidod/EID/vol 11 no 06/05-0142.htm. Accessed July 11, 2005.

17. Mishaan AM, Mason EO, Martinez-Aguilar G, et al. Emergence of a predominant clone of community-acquired Staphylococcus aureus among children in Houston, Texas. Pediatr Infect Dis J 2005;24:201-206.

18. Chambers HF. Community-associated MRSA: resistance and virulence converge. N Engl J Med 2005;352:1485-1487.

19. Crawford SE, Daum RS. Epidemic community-associated methicillin-resistant Staphylococcus aureus: modern times for an ancient pathogen. Pediatr Infect Dis J 2005;24:459-460.

20. Braun L, Craft D, Williams R, et al. Increasing clindamycin resistance among methicillin-resistant Staphylococcus aureus in 57 Northeast United States military treatment facilities. Pediatr Infect Dis J 2005;24:622-626.

Ekopimo Ibia, MD, MPH

From Merck Research Laboratories, Blue Bell, PA.

Reprint requests to Dr. E. Ibia, Merck Research Laboratories, BL A-33, 10 Sentry Parkway, Blue Bell, PA 19422. Email: [e-mail]

Accepted August 15, 2005.