This study compared a commonly used beta-lactam antibiotic, cephalexin, to placebo for the treatment of uncomplicated skin and soft tissue abscesses after incision and drainage in a population with high rates of community-acquired MRSA. Our findings of high clinical cure rates (84 to 90%) and no difference in clinical cure rates for cephalexin compared to placebo indicate that beta-lactam antibiotics probably do not provide an additional benefit over that afforded by incision and drainage in the treatment of cutaneous abscesses. Even though more than 90% of MRSA clinical isolates were positive for PVL genes, this had no apparent effect on outcome.
A possible criticism of the study design is that no active treatment arm was included (assuming that beta-lactams have no clinically useful antimicrobial activity against MRSA). However, given the high cure rates in both the cephalexin and placebo arms—rates which are consistent with those of four recently published studies of SSTIs (88 to 96%) (1
)—it is doubtful that an active agent would have performed any better. The one previous placebo-controlled study of cephradine for soft tissue infections, including abscesses, was conducted in 1985 and included 50 subjects (17
). That study found no difference in cure rates between the antibiotic and placebo groups; to our knowledge, microbiologic susceptibility was not reported. Observational, retrospective studies have found no difference in outcomes of patients treated with beta-lactam antibiotics for SSTIs caused by MRSA compared to those given an antibiotic to which the isolate was susceptible (11
). Our trial is the first interventional study that directly supports this finding. These observational studies in conjunction with our results strongly suggest that antibiotics may not be necessary for treating some SSTIs, including those caused by MRSA.
Clinicians have been reluctant to change the current standard of care, citing the lack of evidence from well-designed randomized control trials and the increasing prevalence of MRSA (7
). Even clinicians knowledgeable about antibiotic overuse continue to prescribe beta-lactam antibiotics for soft tissue infections (14
). The two main arguments in support of this practice are (i) that these infections may be polymicrobial, containing some streptococcal species sensitive to beta-lactam antibiotics (2
), and (ii) that killing the sensitive organisms in the soft tissue infection may tip the balance in favor of host defenses against the organisms that are resistant to the antibiotic given (11
The strengths of this study include its randomized, double-blind, placebo-controlled design; a well-defined study population; and a 91.6% follow-up rate (97.6% if the additional 10 patients whose follow-up consisted of chart review are included). Nevertheless, our study does have some limitations. Clinical outcomes were assessed at end of treatment, but 10 patients (6%) had their clinical outcomes determined by chart review. Two antibiotic treatment failures were found in emergency department records. When we analyzed the data excluding these 10 patients, it had no effect on study conclusions. Recurrence rates also were not determined, and whether antimicrobial therapy might have a beneficial effect by preventing recurrent infections some weeks or months later is an important question that merits further study. Data on treatment adherence were based on self-report and were not available for all patients. Adherence, therefore, could have been lower than reported. However, given the high cure rate for the placebo alone, this likely had no impact on results.
Our subjects were adults who were recruited from a single clinic, and they may not be representative of the general population. The MRSA rate of 87.8% in our study is higher than what was previously reported at the same clinic (30
) and is higher than rates reported from other study sites (26
). In a recent survey of MRSA isolates from this clinic, 91% belonged to the PVL-positive epidemic community clone MRSA USA300 (F. Perdreau-Remington, unpublished data), the most prominent community MRSA clone type in the United States and Canada (4
) and one that has been implicated as a cause of very severe infection (19
). Thus, all or almost all of the PVL-positive clinical isolates probably were USA300. We also had a high rate of injection drug users (48%). Thus, our findings may not be generalizable to children or to patient populations in which MRSA (and USA300 in particular) or injection drug use is not highly prevalent. Although our study criteria permitted enrollment of febrile patients, because only 1 out of the 166 was febrile these study results may not be generalizable to febrile patients. In addition, incision and drainage procedures were performed by attending surgeons; outcomes may not necessarily be the same in clinics run by other health care providers.
We included patients with medical comorbidities such as HIV infection, hepatitis, diabetes, and folliculitis, populations for whom clinicians often prescribe antibiotics (28
), but sample sizes were too small to determine whether or not these subgroups might benefit from antibiotics. This area merits further research because clinicians commonly feel compelled to prescribe antibiotics for infections in these populations.
Another population generally thought to require antibiotics is patients with larger abscesses. A previous study cited an abscess greater than 5 cm in diameter as a significant predictor of hospitalization (10
). We included patients with abscesses greater than 5 cm in length (n
= 28), width (n
= 34), or depth (including those down to the muscle) (n
= 24). Although the subgroup sample sizes were too small to make definitive conclusions, our overall findings suggest that even patients with large abscesses may not need antibiotics.
In summary, the 90.5% cure rate observed in the placebo arm of this study and good outcomes in cephalexin recipients despite an overall MRSA prevalence of >50% indicate that antibiotics may be unnecessary after surgical drainage of skin and soft tissue abscesses for populations with high rates of MRSA. Perhaps even more important, this study demonstrates that that a placebo control can be safely used in trials of uncomplicated SSTIs and should be considered in future studies of this type. The results of future placebo-controlled trials of SSTIs could have a significant impact on management of community-acquired MRSA infections.