Clinical Context

Resistance of Staphylococcus aureus to methicillin is not only prevalent in hospitals, but it is also on the rise in the community. Compared with methicillin-resistant S aureus (MRSA) acquired in healthcare settings, community-associated MRSA (Ca-MRSA) typically affects younger and healthier individuals, including children. Most Ca-MRSA infections involve only the skin and soft tissue, but invasive infections can be life threatening and even fatal.

Use of antibacterial agents may be a factor predisposing to Ca-MRSA. The investigators of the present study by Schneider-Lindner and colleagues previously reported a dose-dependent association of antibacterial drug prescriptions among adults in primary care with subsequent diagnoses of Ca-MRSA. In children, however, evidence is limited regarding the association of antibiotics with the development of Ca-MRSA.

Therefore, the objective of this study was to investigate the association of antibacterial agents with a later diagnosis of Ca-MRSA in children, considering the number and class of antibacterial drug prescriptions.

Study Synopsis and Perspective

Antibiotic use in children is associated with a dose-dependent, increased risk of acquiring MRSA in the community, according to the results of a population-based, case-control study reported online August 1 in the Archives of Pediatrics & Adolescent Medicine.

"Antibacterial agents have been suggested to play a role in the emergence of [community-associated (Ca)]-MRSA, and we have recently shown, in adults, a dose-dependent association of antibacterial drug prescriptions in primary care with later diagnoses of Ca-MRSA," write Verena Schneider-Lindner, MD, MSc, from the Centre for Clinical Epidemiology at Sir Mortimer B. Davis–Jewish General Hospital in Montreal, Quebec, Canada, and colleagues. "However, there are only sparse data from children in support of this conceptual model, currently precluding its extension to children.... In this study we therefore investigated the association of antibacterial agents with a later diagnosis of Ca-MRSA in children, considering the number and class of antibacterial drug prescriptions."

Using data from children 1 to 19 years old in the UK General Practice Research Database from 1994-2007, the investigators identified children diagnosed with MRSA as outpatients. Using the case's diagnosis date as the index date, control participants (n = 9357) were individually matched to case patients (n = 297) based on age and practice.

The main exposure of interest was prescription of antibiotics 180 to 30 days before the index date. To prevent protopathic bias, prescriptions written 30 days before the index date were excluded. Conditional logistic regression allowed estimation of rate ratios (RRs) from the odds ratios of exposure for case patients vs control participants, after adjustment for comorbid conditions, use of other prescription drugs, and hospitalization.

The annual rate of MRSA was 4.5 per 100,000 children. During the 150-day window of exposure, 52.5% of case patients and 13.6% of control participants received prescriptions for antibiotics. For a prescription of any antibiotic, the adjusted RR was 3.5 (95% confidence interval [CI], 2.6 - 4.8). Increasing number of antibiotic prescriptions was associated with increasing RRs. The RR was 2.2 for 1 prescription (95% CI, 1.5 - 3.20), 3.3 for 2 prescriptions (95% CI, 1.9 - 5.6), 11.0 for 3 prescriptions (95% CI, 5.6 - 21.6), and 18.2 for 4 prescriptions (95% CI, 9.4 - 35.4). Antibacterial classes varied widely in RR, with the highest RR observed for quinolones (14.8; 95% CI, 3.9 - 55.8).

"While close to half of children were diagnosed as having MRSA in the community without prior antibacterial drugs, such agents are associated with a dose-dependent increased risk, concordant with findings in adults," the study authors write.

Limitations of this study include inability to differentiate asymptomatic carriers from children with clinically significant infections, lack of microbiological test results confirming the medical diagnosis, and measurement of exposure based on prescriptions issued rather than on records of prescriptions dispensed from pharmacies or actual drug ingestion.

"[A]ntibacterial agents are not a necessary precondition for MRSA, but there is a robust association of antibacterial drug prescriptions with a subsequent diagnosis of MRSA for children in the community," the study authors conclude. "Although we could not establish causality of the association, our results support efforts to minimize unnecessary antibacterial drug prescribing, particularly of second-line agents, to children in the community. Given limitations in case ascertainment, our Ca-MRSA incidence estimates should be cautiously interpreted."

Dr. Schneider-Lindner received a fellowship from the Canadian Institutes of Health Research. The other study authors have disclosed no relevant financial relationships.

Arch Pediatr Adolesc Med. Published online August 1, 2011.

Clinical Implications

• In a UK population-based case-control study, close to half of children diagnosed with Ca-MRSA had no prior antibacterial drug exposure. However, prescription of these drugs is associated with an increased risk for Ca-MRSA, similar to the findings in adults.
• The increased risk for Ca-MRSA with antibiotic use in children was dose dependent and varied widely among different classes of antibacterial agents.

CME Test