Antibacterial Drugs and MRSA in Children

Although methicillin resistance is common in Staphylococcus aureus in hospitals, the presence of such resistance in the community is also increasingly reported. It is commonly referred to as community-associated methicillin-resistant Staphylococcus aureus (Ca-MRSA). This emergent resistant organism is more likely to affect younger, healthier individuals, such as children, compared with the hospital-based version. In this population-based case-control study [Arch Pediatr Adolesc Med. 2011;165(12):1107-1114], the authors sought 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. To conduct the study, the investigators analyzed the General Practice Research Database of the United Kingdom (England, Northern Ireland, Scotland, and Wales), which contains demographic information, medical diagnoses, laboratory data, referral information, vaccinations, and prescriptions from >400 general practices representing >4 million active patients (approximately 7% of the population of the United Kingdom). The data are representative of the population of the United Kingdom and are widely used in research on prescription drug use and safety, antibacterial drug use, and infectious diseases. The authors studied data from all children 1 to 19 years of age from January 1, 1993, to December 31, 2007. Cases were cohort members with a diagnostic code indicative of Ca-MRSA during the study period from January 1, 1994, to December 31, 2007. For each case, controls were individually matched on practice and month and year of birth, and their corresponding case’s diagnosis date was designated as the index date. Cases and controls had to have at least 1 year of follow-up in the database prior to the index date. The primary outcome measure was rate ratios (RRs) estimated from the odds ratios of exposure in cases compared with controls using conditional logistic regression, adjusted for comorbid conditions, other prescription drug use, and hospitalization. A total of 525 children with diagnostic codes indicative of MRSA were identified; 514 with correct diagnosis dates from 248 individual general practices were considered. During the study period, the annual number of children diagnosed as having MRSA generally increased, and the largest number of cases was diagnosed in 2006. Based on cohort follow-up time, the average annual incidence was 4.5 cases per 100,000 person-years for children of all ages. In children <1 year of age, the rate was 31.5 cases per 100,000 person-years. A total of 297 cases and 9357 matched controls were included in the analysis. Most cases were boys (60.6%), and their median age was 8.0 years (interquartile range, 3.6-14.5 years). About half of the cases (52.5%) and substantially fewer controls (13.6%) had received ≥1 antibacterial drug prescription in the 150-day exposure window. Accounting for differences in sex and comorbid conditions, as well as hospitalizations, this difference translated to a >3 times higher risk of MRSA diagnosis in children with any prior antibacterial drug prescription compared with those without (adjusted RR, 3.5; 95% confidence interval [CI], 2.6-4.8). The risk of being diagnosed as having MRSA increased by about 2-fold with each antibacterial drug prescription (unadjusted RR, 2.2; 95% CI, 2.0-2.4), which remained similar after adjustment (adjusted RR, 1.8; 95% CI, 1.6-2.0). MRSA diagnoses were nonlinearly associated with increasing numbers of antibacterial drug prescriptions. Compared with no prescription, children with 3 prescriptions had a 10-fold greater risk of MRSA (adjusted RR, 11.0; 95% CI, 5.6-21.6), whereas those with ≥4 prescriptions had close to a 20-fold increase in risk (adjusted RR, 18.2; 95% CI, 9.4-35.4). After accounting for potential confounders and prescriptions from other antibacterial drug classes in the exposure time window, both penicillinase-resistant penicillins and broad-spectrum penicillins were associated with a later diagnosis of MRSA, and the association was particularly strong for macrolides (RR, 5.2; 95% CI, 3.3-8.4) and quinolones (RR, 14.8; 95% CI, 3.9-55.8).