Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has rapidly become a leading cause of skin and soft tissue infections (SSTIs) in the United States.1 The anterior nares are recognized as an important site of carriage of S. aureus and a potential source for spreading organisms to other people.2 Large population-based studies have estimated that the adult nasal carriage rate of S. aureus in the United States has decreased in recent years to around 29%, even though the rates of MRSA carriage have increased to 1.5% in adults and 0.9% in children.3
There is little information about the relationship of S. aureus nasal colonization and symptomatic skin infections in children. The purposes of this prospective study were to prospectively characterize S. aureus nasal carriage in a population of children presenting with skin and soft tissue infections, to determine concordance of nasal carriage with wound isolates, and to identify associations between nasal carriage with S. aureus and recurrent skin infections.
We are currently conducting an ongoing, randomized, double-blinded clinical trial comparing cephalexin and clindamycin for outpatient treatment of purulent SSTIs (eg, abscess, furuncle, carbuncle, cellulitis with suspected abscess) in children aged 6 months to 18 years old. This study was approved by the Institutional Review Board of the Johns Hopkins Medical Institutions. Children who met the inclusion criteria had clinical data collected during the initial encounter, and then by repeat visit or telephone follow-up at 2 to 3 days, 1 week, and 3 months. For the 3 month follow-up, if patients were unable to be contacted, the medical records were reviewed to capture any visits for repeat infections.
Specimens were obtained from anterior nares and wounds at entry and at the time of any recurrent infections using the BactiSwab II culturette with modified Stuart's medium (Remel, Lenexa, KS). Nasal swabs were plated onto BD-CHROMagar for S. aureus (BBL)4; after overnight incubation at 37°C, plates were read at 24 and 48 hours, and typical mauve colonies had confirmatory identification for S. aureus and susceptibility testing performed using the BD Phoenix Automated Microbiology System (BD Diagnostics, Sparks, MD).5 When methicillin-susceptible S. aureus (MSSA) was identified, isolates were plated onto CHROMagar-MRSA (BBL) to detect the coexistence of MRSA. Isolates were tested for susceptibility to a standard array of antimicrobial agents, including cotrimoxazole, clindamycin, erythromycin, tetracycline, moxifloxacin, and vancomycin. The d-test was used to detect inducible clindamycin resistance in erythromycin-resistant isolates.
All isolates were subjected to PFGE (pulsed field gel electropheresis) using standard extraction methods,6 and evaluated for strain-relatedness as described by Tenover et al.7 The first 20 isolates and all subsequent isolates that were not identical to the USA300 strain were tested by PCR for the presence of the genes encoding LukS-PV and LukF-PV, 2 proteins specific for the Panton-Valentine Leukocidin toxin.8
χ2 and Fisher exact test testing were used to compare proportions of events and characteristics, using Stata 8.0 (State Corp, College Station, TX).
We enrolled 95 children presenting with SSTIs into the antibiotic treatment trial between September 2006 and December 2007. Participants had an average age of 8.8 years (range, 8 months–18 years) and were mostly African American (88/95, 93%) and female (53/95, 56%). Thirty-five patients (37%) had a history of SSTI, and 30 patients (32%) had a history of recent antibiotic use in the last 6 months. In most cases, patients had a drainage procedure or had wounds that were spontaneously draining (92/95, 97%). Spontaneous wound drainage at the time of presentation occurred in 23 patients (24%). Wound cultures were successfully obtained in 98% of patients and nares cultures were obtained on all patients. By the 2–3 day follow-up, only 6 patients (6%) met criteria for treatment failures, and by the 1 week follow-up, all patients had either resolution or continued improvement in symptoms. Follow-up telephone contact and/or visits to determine SSTI recurrence frequency was achieved in 74% of participants.
Eighty-three of 95 (87%) wound cultures grew S. aureus; of the remaining, 2 patients did not have wound cultures, 4 patients had no growth of organisms, 2 patients had Proteus mirabilis, 1 patient had a coagulase-negative Staphylococcus, and 3 patients had polymicrobial skin or genital flora. Sixty-four (77%) of the S. aureus isolates were MRSA and 19 (23%) were MSSA. Sixty-three of 64 MRSA and 10 of 19 MSSA wound isolates were clonally related to the PFGE type USA300. Panton-Valentine Leukocidin was detected in all tested MRSA and USA300-related MSSA wound isolates. Antimicrobial susceptibility testing of wound isolates demonstrated high rates of susceptibility to clindamycin (91%), tetracyclines (92%), cotrimoxazole (97%), and vancomycin (100%) and lower susceptibility to erythromycin (15%) and moxifloxacin (32%) (Table 1, http://links.lww.com/A660). Inducible clindamycin resistance (as identified by the d-test) was not detected in any of the wound MRSA isolates.
Nasal Colonization and Concordance.
Forty of 95 patients (42%) grew S. aureus from anterior nares cultures, of which 22 isolates (23%) were MRSA and 18 isolates (19%) were MSSA. One patient had an anterior nares culture with S. aureus but did not have a successful wound culture sent. Nasal MRSA colonization was more common among patients with concomitant MRSA SSTI (20/64, 31%) than among those with MSSA SSTI (1/19, 5%) or SSTI not due to S. aureus (1/12, 8%; Fisher exact test P = 0.021) (Table 2). Of the 39 cases with S. aureus recovered from both nasal and wound cultures, 26 (67%) nasal and wound culture pairs were concordant by methicillin-susceptibility, but only 23 (59%) had identical methicillin susceptibility and PFGE type. Of the 16 cases (41%) with discordant methicillin susceptibility or PFGE type, 3 had identical methicillin susceptibility (all MSSA) but different PFGE type, 1 had different methicillin susceptibility but identical PFGE type, and 12 had different methicillin susceptibility and PFGE type.
Three month follow-up data were available for 94/95 patients, and of these, 21 (22%) had recurrent SSTI. Recurrent SSTI was more common after MRSA infection than after MSSA infection (28% vs. 5%, Fisher exact test, P = 0.059) (Table 3). Of 12 patients without any organism isolated from the initial wound infection, 2 (17%) had a recurrent SSTI within 3 months. Among patients with initial MRSA wound infections, recurrent SSTIs were less common in those with baseline nasal MRSA colonization compared with those without baseline nasal MRSA colonization (19% vs. 42%, Fisher exact test, P = 0.093).
Previous studies have found that both adults and children with MRSA SSTIs have high rates of MRSA nasal colonization.9,10 Alfaro et al9 reported that 29% of children hospitalized for MRSA SSTIs at their institution had nasal colonization with MRSA. In a study by Zafar et al10 examining the prevalence of nasal MRSA colonization in both adult patients presenting with SSTI and their household contacts, significantly increased MRSA nasal carriage rates were found in both patients (41% colonized) and their household contacts (20% colonized).
MRSA infections in colonized patients are typically caused by the same strain of S. aureus as found in the anterior nares.11–13 One study of patients presenting to an adult ED with SSTIs found that when MRSA was identified in both nose and wound, all of the isolates were identical by strain typing.13 Analysis of the nasal and wound isolates from our pediatric SSTI cohort, however, suggests that discordance between the infecting agent and the colonizing agent is common in children. A striking 33% of our patients either grew MRSA from their wound but MSSA from their nose or MSSA from their wound but MRSA from their nose. When analyzed by both methicillin-resistance status and PFGE type, only 59% of wound and nasal isolates were concordant. These findings suggest that MRSA nasal colonization in children may not be as strongly related to MRSA SSTIs in the context of CA-MRSA.
Previous studies have reported an increased risk of developing MRSA infections among patients with MRSA nasal colonization,14 but these studies have not included the present study population of children with incident MRSA SSTIs managed as outpatients. The problem of recurrent CA-MRSA SSTIs in adults and children is well known, though not well quantified. We found that the overall rate of SSTI recurrence within 3 months of an incident SSTI reached nearly 22%; the rate of recurrence after initial MRSA SSTI was 28%, substantially (though not statistically significant) higher than the 5% SSTI recurrence after MSSA SSTI. However, there was no evidence that baseline MRSA nasal colonization at the time of incident MRSA SSTI increased the risk of recurrence; in fact, there was an unexpected, though nonstatistically significant trend toward lower SSTI recurrence risk after initial MRSA SSTI if MRSA nasal colonization was present (19%) than if it was absent (42%). This finding suggests that baseline MRSA colonization status does not increase the risk of recurrent SSTI after incident SSTI. Taken together, these findings suggest that for community-acquired SSTIs, wound infection by MRSA—rather than nasal colonization with MRSA—may be a better predictor of children at higher risk of subsequent SSTI.
One of the major limitations of this study is that only the anterior nares was cultured to evaluate colonization. Other studies have identified carriage of S. aureus in the pharynx, axilla, perineum, and the skin. Nonetheless, the anterior nares is consistently the most common single site for detecting colonization1,15 and is the method most commonly used for detection of colonization status. Other limitations of this study include a small sample size; incomplete follow-up on some patients; incomplete information regarding infection and colonization in household members; and current lack of information about the antibiotic used for treatment in this blinded trial.
Children presenting with SSTIs have higher rates of S. aureus nasal colonization than healthy counterparts, but there is substantial discordance between wound and nasal strains. SSTI recurrence after incident MRSA infection was very common overall in our study, but baseline MRSA nasal colonization status did not help to predict children at risk for recurrent SSTIs. The utility of determining nasal colonization status in children with CA-MRSA infections remains uncertain.
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