Increasing Skin Infections and Staphylococcus aureus Complications in Children, England, 1997–2006

During 1997–2006, general practitioner consultations for skin conditions for children <18 years of age in England increased 19%, from 128.5 to 152.9/1,000 child-years, and antistaphylococcal drug prescription rates increased 64%, from 17.8 to 29.1/1,000 child-years. During the same time period, hospital admissions for Staphylococcus aureus infections rose 49% from 53.4 to 79.3/100,000 child-years.

S taphylococcus aureus infection is a leading cause of staphylococcal bacteremia in adults (1) and children (2) in hospitals in the United Kingdom, and recent reports suggest invasive staphylococci are emerging from the community (3). Flucloxacillin is the antimicrobial drug recommended for treating S. aureus skin infection in UK primary care centers (4). Therefore, its use provides a proxy marker of S. aureus skin infection in children. Flucloxacillin prescribing in children has increased over the past 15 years (5), despite well-documented reductions in prescribing rates for other commonly prescribed antibacterial drugs during 1995-2000 (6), which suggests that S. aureus skin infections in the community may be increasing.
We examined the incidence of local complications of S. aureus disease in children over a 10-year period using nationally representative data from primary care clinicians in England. Ethics approval for this study was obtained from the Independent Scientifi c and Ethical Advisory Commit-tee, application no. 2006/ISEAC/012.

The Study
The MediPlus UK database contains anonymized longitudinal data from >500 UK general practitioners who contribute clinical data on >1 million patients (7) that have been used widely for research (8). Consultations are coded by using the International Classifi cation of Diseases, Tenth Revision (ICD-10), and antimicrobial drug prescriptions are coded by using the British National Formulary for children, Chapters 5.1.1-5.1.3 (9). Using Mediplus UK, we extracted data on all skin conditions (ICD-10 code) and atopic dermatitis (ICD-10 code L20) as an index condition in children <18 years of age who saw general practitioners in England from January 1, 1997, through December 31, 2006. We counted prescriptions for all oral and topical antibacterial drugs prescribed for skin infections, and used all oral preparations containing fl ucloxacillin prescribed for skin conditions as a proxy measure of unresolved S. aureus skin infection. We calculated age-sex adjusted annual consulting and prescribing rates by totaling the number of consultations or prescriptions and dividing by the number of person-years contributed by each child in the registered population for each calendar year. We then directly standardized these rates by using the age-sex distribution for the reference year 2000.
The Hospital Episode Statistics (HES) database has recorded all inpatient hospital activity in National Health Service hospitals across England since 1989 and is used widely to monitor disease trends in England (www.hesonline.nhs.uk) (10). The main reason for admission, i.e., primary diagnosis, is recorded by using ICD-10 codes. We used HES data to calculate age-sex adjusted admission rates per 100,000 resident population for children <18 years of age for each calendar year from January 1, 1997, through December 31, 2006, for conditions commonly caused by S. aureus, including septic arthritis (ICD-10 codes M00.0 for staphylococcal arthritis and M00.9 for pyogenic arthritis), osteomyelitis (M86), and locally invasive skin infections (L02, cutaneous abscesses and boils; L03, cellulitis). Rates were calculated as the total number of admissions per year divided by the mid-year estimate of the number of children residing in England (using the 2000 population in England as the reference population) (11). Confi dence intervals (CIs) were generated with a Poisson approximation. We used linear regression to test for linear trends in age-sex adjusted admission rates across the period. We used Stata version 9 software (Stata Corp., College Park, TX, USA) for all statistical analysis.

Conclusions
The increasing incidence of childhood skin infections and prescribing of the major antistaphylococcal drug fl ucloxacillin seen in UK primary care, coupled with concurrent increases in childhood hospital admissions for skin bone and joint infections caused by S. aureus in hospitals in England, suggests an increase in community-onset S. aureus disease in England over the past 10 years. The time frame, a large nationally representative population, use of prospectively collected data, and consistency of patterns make it unlikely our fi ndings arose by chance. Because HES data records primary diagnosis when patients are admitted, most infections will be community-, not hospital-, acquired. Flucloxacillin has remained the treatment of choice for S. aureus skin infections in UK primary care for decades (9), and its increased use is not explained by treatment drift from other groups of antibacterial drugs used to treat skin infections or by increasing antibacterial drug treatment of atopic eczema colonized with staphylococci. Total unplanned admission rates in children <19 years of age have increased by 13% during 1997-2006 (12), but these increases are modest compared with the 49% increase in S. aureus complications seen over the same time frame in our study.
Limitations of our study include the use of clinically coded proxy measures for S. aureus infections that are subject to recording bias. Because of the lack of microbiologic surveillance, we could not differentiate whether increases in S. aureus disease were caused by methicillin-sensitive S. aureus or methicillin-resistant S. aureus. Antimicrobial drugs for skin infections are available only by prescription in the UK but not exclusively from GPs. Thus, our prescribing data excluded prescriptions issued from other healthcare settings. Our fi ndings that admission rates for osteomyelitis, boils, and cellulitis increased but septic arthritis rates were stable might be because septic arthritis is also caused by pneumococci, β-hemolytic streptococci, and gram negative organisms (13).
A growing body of evidence supports our fi ndings of increases in community-onset S. aureus disease in children.   .0, or pyogenic arthritis, M00.9). All of these codes were included in the category "all skin, bone, and joint infections." CI, confidence interval. †p value for test for linear trend across years.