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Key Paper Evaluation 10.1586/14787210.6.1.9 © 2008 Future Drugs Ltd ISSN 1478-7210 9 www.future-drugs.com Is antimicrobial therapy needed to manage uncomplicated skin and soft-tissue abscesses? Expert Rev. Anti Infect. Ther. 6(1), 9–13 (2008) Michael W Ellis Infectious Disease Service, MCHE-MDI, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234-6200, USA Tel.: +1 210 916 4355 Fax: +1 210 916 0388 michael.ellis2@amedd. army.mil Evaluation of: Rajendran PM, Young D, Maurer T et al. Randomized, double-blind, placebo- controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob. Agents Chemother. 51, 4044–4048 (2007). Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections occur across a wide spectrum of epidemiologic groups, which range from medically underserved urban dwellers to professional athletes. CA-MRSA primarily causes skin and soft- tissue infections but it can also cause severe invasive disease, including necrotizing pneumonia and necrotizing fasciitis. In light of CA-MRSA’s proclivity to cause skin and soft-tissue abscesses and its capacity to inflict severe illness, investigators have been prompted to revisit the question of whether adjunctive antimicrobial therapy is necessary in the management of uncomplicated abscesses. This article evaluates the findings of a recently published randomized, double-blind, placebo-controlled trial that aims to determine whether ‘standard- of-care’ antimicrobial therapy is needed after adequate surgical incision and drainage of uncomplicated skin and soft-tissue abscesses. KEYWORDS: abscess • community-associated methicillin-resistant Staphylococcus aureus • methicillin resistance • methicillin-resistant Staphylococcus aureus • skin and soft tissue • Staphylococcus aureus This article addresses the findings reported by Rajendran et al. and whether incision and drain- age alone are adequate therapy in a population at high risk for abscesses caused by community- associated methicillin-resistant Staphylococcus aureus (CA-MRSA) [1]. Incision and drainage have long been considered to form the corner- stone of therapy for skin and soft-tissue abscesses [2]. Current evidence-based literature and expert opinion suggest that even in the setting of CA-MRSA, adjunctive antimicro- bial therapy may be unnecessary for effective management of uncomplicated abscesses [2–5]. Recently, CA-MRSA has emerged as an important pathogen, especially within certain high-risk groups, such as children in daycare, soldiers, prisoners and athletes [6]. Despite numerous reports of severe disease that includes necrotizing pneumonia [7], severe sepsis [8], and necrotizing fasciitis [9], CA-MRSA primarily manifests as uncomplicated skin and soft-tissue infections (SSTIs) [5,10,11]. Indeed, invasive infection represents less than 6% of disease attributed to CA-MRSA [5,10]. Current evidence suggests that even in com- munities at risk for CA-MRSA skin and soft-tis- sue abscesses, effective adjunctive antimicrobial therapy may be unnecessary [4,5,12], although a recent report contradicts this prevailing notion [13]. The randomized, double-blind, placebo- controlled trial conducted by Rajendran et al. in a population known to have a high incidence of CA-MRSA abscesses represents an important step in further delineating the most effective treatment strategy for CA-MRSA abscesses [1]. Methods The authors conducted this randomized, dou- ble-blind, placebo-controlled trial at the Inte- grated Soft Tissue Infection Services (ISIS) Clinic, at the San Francisco General Hospital

Is antimicrobial therapy needed to manage uncomplicated skin and soft-tissue abscesses?

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Page 1: Is antimicrobial therapy needed to manage uncomplicated skin and soft-tissue abscesses?

Key Paper Evaluation

10.1586/14787210.6.1.9 © 2008 Future Drugs Ltd ISSN 1478-7210 9www.future-drugs.com

Is antimicrobial therapy needed to manage uncomplicated skin and soft-tissue abscesses?Expert Rev. Anti Infect. Ther. 6(1), 9–13 (2008)

Michael W EllisInfectious Disease Service, MCHE-MDI, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234-6200, USATel.: +1 210 916 4355Fax: +1 210 916 [email protected]

Evaluation of: Rajendran PM, Young D, Maurer T et al. Randomized, double-blind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population atrisk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob.Agents Chemother. 51, 4044–4048 (2007).

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infectionsoccur across a wide spectrum of epidemiologic groups, which range from medicallyunderserved urban dwellers to professional athletes. CA-MRSA primarily causes skin and soft-tissue infections but it can also cause severe invasive disease, including necrotizing pneumoniaand necrotizing fasciitis. In light of CA-MRSA’s proclivity to cause skin and soft-tissue abscessesand its capacity to inflict severe illness, investigators have been prompted to revisit thequestion of whether adjunctive antimicrobial therapy is necessary in the management ofuncomplicated abscesses. This article evaluates the findings of a recently publishedrandomized, double-blind, placebo-controlled trial that aims to determine whether ‘standard-of-care’ antimicrobial therapy is needed after adequate surgical incision and drainage ofuncomplicated skin and soft-tissue abscesses.

KEYWORDS: abscess • community-associated methicillin-resistant Staphylococcus aureus • methicillin resistance • methicillin-resistant Staphylococcus aureus • skin and soft tissue • Staphylococcus aureus

This article addresses the findings reported byRajendran et al. and whether incision and drain-age alone are adequate therapy in a population athigh risk for abscesses caused by community-associated methicillin-resistant Staphylococcusaureus (CA-MRSA) [1]. Incision and drainagehave long been considered to form the corner-stone of therapy for skin and soft-tissueabscesses [2]. Current evidence-based literatureand expert opinion suggest that even in thesetting of CA-MRSA, adjunctive antimicro-bial therapy may be unnecessary for effectivemanagement of uncomplicated abscesses [2–5].

Recently, CA-MRSA has emerged as animportant pathogen, especially within certainhigh-risk groups, such as children in daycare,soldiers, prisoners and athletes [6]. Despitenumerous reports of severe disease that includesnecrotizing pneumonia [7], severe sepsis [8], andnecrotizing fasciitis [9], CA-MRSA primarilymanifests as uncomplicated skin and soft-tissue

infections (SSTIs) [5,10,11]. Indeed, invasiveinfection represents less than 6% of diseaseattributed to CA-MRSA [5,10].

Current evidence suggests that even in com-munities at risk for CA-MRSA skin and soft-tis-sue abscesses, effective adjunctive antimicrobialtherapy may be unnecessary [4,5,12], although arecent report contradicts this prevailing notion[13]. The randomized, double-blind, placebo-controlled trial conducted by Rajendran et al. ina population known to have a high incidence ofCA-MRSA abscesses represents an importantstep in further delineating the most effectivetreatment strategy for CA-MRSA abscesses [1].

MethodsThe authors conducted this randomized, dou-ble-blind, placebo-controlled trial at the Inte-grated Soft Tissue Infection Services (ISIS)Clinic, at the San Francisco General Hospital

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from November 2004 to March 2005. The ISIS Clinic is acenter designed specifically to treat underserved urban patientswith soft-tissue infections [14].

In this investigation, the authors’ principal objective was tocompare ‘standard-of-care’ antimicrobial treatment withcephalexin with placebo after surgical incision and drainage ofuncomplicated skin and soft-tissue abscesses. Other objectiveswere to establish the prevalence of CA-MRSA in the studypopulation and to determine whether discordance betweentherapy and isolate susceptibility affected clinical outcomes.After randomization, patients received either cephalexin500 mg four-times daily for 7 days, or the same regimen withidentical-appearing capsules.

Patients were eligible to participate in this study if they wereat least 18 years of age and were determined by an ISIS Clinicsurgeon to have a surgically drainable abscess that was alsosevere enough to receive at least 5 days of antimicrobial ther-apy. The authors used the following as diagnostic criteria foran abscess: acute onset within 7 days prior to enrollment;purulent drainage or purulent aspirate; erythema, induration(greater than or equal to 2 cm), or tenderness; and evidence ofloculated fluid at the time of enrollment. The clinical stand-ard-of-care cited by the authors for the ISIS Clinic is to pre-scribe an antibiotic if two or more of these criteria are met.Febrile patients were included; however, patients with evidenceof complicated or severe SSTIs were excluded (e.g., toxic shocksyndrome, hypotension, suspected osteomyelitis or septicarthritis). Patients with allergy to penicillin or cephalexin, orwith dose-altering renal insufficiency were also excluded.

At the initial presentation to the ISIS Clinic, patients withuncomplicated abscesses underwent a directed history andphysical exam. After measuring the abscess, cleansing it with10% povidone–iodine solution and injecting local anesthetic,investigators incised the lesion (No. 11 blade), completelydrained it of pus, probed it and packed from deep to superfi-cial with plain gauze for healing by secondary intention. ADacron swab of the abscess cavity was sent for culture and sus-ceptibility testing, specifically for staphylococci and strepto-cocci. Isolates identified as CA-MRSA were also tested forPanton–Valentine leukocidin (PVL).

After incision and drainage, participants were randomizedto either arm by the pharmacist using a block randomizationscheme to generate a 1:1 ratio of subjects in each group. Allparticipants were seen daily for 7 days in the ISIS Clinic inorder to change dressings and assess wound healing (absenceof purulence, rubor, calor, dolor and edema/induration).Clinical response (cure or failure) was the primary study out-come measured. The assessment of clinical cure was made atthe 7-day-follow-up visit by one of the investigators or one offive trained study nurses. Treatment adherence was measuredby self-reporting.

This was an intent-to-treat (ITT) analysis with the primarycomparison being the proportion of participants whosewounds were considered to be clinically cured. The authors

calculated the sample size to provide 80% power to detect adifference of 10% or more between groups. A one-tailedFisher exact test with a 5% level of significance was used forthe primary comparison.

ResultsThe investigators screened 713 patients who were seen in theISIS Clinic during the study period; and of these, 187 were eli-gible for enrollment. Of the 187 eligible patients, 166 wereenrolled and randomized, 82 to the cephalexin arm and 84 tothe placebo arm. A total of 21 declined enrollment.

The majority of subjects were middle-aged and the overallbaseline characteristics of the two study groups were similar.Notable baseline characteristics were that approximately half ofthe patients were Caucasian; more than a third were homeless;approximately a third had chronic hepatitis B; and 15.9 and7.1% were HIV positive in the cephalexin and placebo arms,respectively. Approximately 40% had a history of folliculitis.Importantly, the mean abscess surface area was approximately19 cm2 (1–150 cm2). With regard to pertinent abscess charac-teristics, approximately two-thirds were confined to the subcu-taneous tissue; however, the remainder extended to fascia ormuscle. Compliance was 72.2% in the cephalexin group and78% in the placebo group.

All 166 randomized subjects were included in the ITT analy-sis, with two in each arm having been lost to follow-up. Therewas no statistical difference in the clinical cure rates betweengroups; 90.5% (95% confidence interval [CI]: 0.82–0.96) inthe placebo group, and 84.1% (95% CI: 0.74–0.91) in thecephalexin group (p = 0.25). Participants who were cured andthose who were not did not differ in terms of baseline demo-graphics or abscess characteristics. No adverse events werenoted during the investigation and no participants developeddisseminated disease or pneumonia.

There was no statistically significant difference found betweenthe cultured pathogens in each group. Of the 162 participantswho were cultured, 114 isolates (70.4%) revealed S. aureus. Ofthose S. aureus isolates that underwent antimicrobial susceptibil-ity testing, 88% (87 out of 99) were MRSA, and of these 93%were PVL positive. Antimicrobial susceptibility patterns weresimilar in both groups. There was no statistically significantdifference in the cultured pathogens between groups.

Discussion & significanceThis investigation demonstrated in a prospective manner thatstandard-of-care therapy with cephalexin for the treatment ofuncomplicated skin and soft-tissue abscesses that had beenincised and drained by a surgeon conferred no added benefitover placebo, even in a population where CA-MRSA was highlyendemic [1]. These findings support what has been observed inrecent retrospective studies: adding antimicrobial therapy toincised and drained abscesses (even MRSA abscesses) may be

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unnecessary [4,5,12]. Additionally, the results from this study sug-gest that in future clinical trials examining the treatment ofuncomplicated MRSA skin and soft-tissue abscesses, a placebocontrol could be safely employed.

Another interesting finding from this study was that abscesssize or depth did not appear to affect clinical outcome. Thisimportant finding is augmented by the fact that this investiga-tion involved sizeable abscesses with approximately a thirdreaching fascia or muscle. These results differ from a report ofCA-MRSA SSTI in children, which demonstrated thatabscesses greater than 5 cm were associated with a greater riskfor hospitalization [12]. Rajendran et al. point out that theirstudy was not powered to adequately address this question.

The authors note that the chief criticism of their investigationis that no antimicrobial agent with activity against CA-MRSAwas given to the participants despite the fact that this popula-tion was anticipated to have a high prevalence of CA-MRSA(59%) [15]. They suggest, however, that given their high clinicalcure rates (90.5% in the placebo group) that an active agentwould have been unlikely to confer added therapeutic benefit.They add that their high clinical cure rates, 90.5 and 84.1% inthe placebo and cephalexin arms, respectively, fall within thealready described rates in SSTI trials [16,17].

Rajendran et al. point out several strengths and limitations totheir investigation. They highlight that, unlike other recentinvestigations that have all been retrospective, this was a rand-omized, double-blind, placebo-controlled trial. The authors alsonote that they achieved excellent subject follow-up (91.6%).The first limitation they describe is that they did not examinerecurrent infection rates. One observation with CA-MRSASSTI is that some patients subsequently develop recurrentfurunculosis [6]. The authors note that it is possible that recur-rence or re-infection could be prevented with effective antimi-crobial therapy. Other limitations of the study pertain to its gen-eralizability. First, the authors point out that as a single-centerinvestigation with high rates of CA-MRSA abscesses, theirresults may not pertain to other sites with lower CA-MRSArates or sites with different predominant CA-MRSA strains. Sec-ond, their results are not applicable to children with uncompli-cated skin and soft-tissue abscesses. Third, although fever wasnot an exclusion criterion, only one out of the 166 enrolled sub-jects was noted to have fever. As such, their findings may notpertain to febrile patients or patients with other evidence of sys-temic disease. Finally, incision and drainage procedures in thisstudy were carried out by attending surgeons. Although thisadds strength to the study overall, these results may not bereproducible by other healthcare providers, especially those lessaccustomed to aggressive abscess management.

Expert commentaryIn many ways, CA-MRSA is no longer an emerging pathogen,but rather it is a common pathogen causing primarily skin andsoft-tissue abscesses in many communities. Indeed, in some

communities, it is the leading cause of skin and soft-tissueabscesses [4,5,11]. The general understanding of what geneticfactors contribute to CA-MRSA’s virulence continues toincrease; however, the evidence-based knowledge of how tobest clinically manage these infections lags. The investigationconducted by Rajendran et al. is an important step toward abetter understanding of effective treatment for CA-MRSA skinand soft-tissue abscesses.

The findings of Rajendran et al. that adjunctive antimicro-bial therapy may be unnecessary for uncomplicated abscessesare consistent with older studies and more recent retrospectivestudies [3–5,12,18]. However, a recently published large retro-spective observational study by Ruhe et al. contradicts thesefindings [13]. In this investigation, of 492 patients comprising531 uncomplicated CA-MRSA SSTIs (abscesses and cellul-itis), Ruhe found that patients who received effective anti-microbial therapy (an agent to which the isolate was suscepti-ble) were more likely to have treatment success [13]. Therapywas successful for 95% (296 out of 312) of patients whoreceived effective antimicrobial therapy compared with 87%(190 out of 219) of patients who received ineffective antimi-crobial therapy (adjusted odds ratio, 2.80; 95% CI:1.26–6.22; p = 0.01) [13]. Although methodologically sound,this investigation is nevertheless limited by its retrospectivenature and consequently the authors temper the strength oftheir findings by describing them as only having a moderateimpact on clinical outcome. Taken together with the existingliterature, the contradicting work of Ruhe et al. suggests thatthere is a hole in the understanding of how to best manageuncomplicated CA-MRSA skin and soft-tissue abscesses.

When assessing the recent retrospective investigations[4,5,12,13], as well as the work by Rajendran et al. [1], it is impor-tant to point out that ineffective therapy based on in vitroantimicrobial susceptibilities should not necessarily be consid-ered completely inert or placebo like. It is possible that evenantimicrobials to which the isolate is resistant may exert aneffect, whether good or bad, on the clinical outcome [19,20].For example, Stevens et al. recently demonstrated that subin-hibitory concentration of the β-lactam nafcillin induced andenhanced toxin production (e.g., PVL) in virulent CA-MRSAstrains [20]. It is possible that some of the ineffective antimicro-bials prescribed to patients with CA-MRSA abscesses actuallyactively worsen their infection by increasing toxin production.

Abounding are other CA-MRSA management questions thathave not been prospectively addressed in adequately poweredstudies:

• What therapy to use in the case of concomitant cellulitis?

• What is the importance of abscess size in therapeutic decisionmaking?

• What is the role of adjunctive antibiotics in the case of thefebrile or systemically ill patient?

• Does adjunctive therapy prevent the rare case of severe orinvasive disease?

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• Does adjunctive antimicrobial therapy prevent additionalinfections within at risk groups (e.g., family members)?

• What therapy would prevent recurrence or reinfection?

There is a need for large randomized, controlled trials toaddress these questions. To achieve statistical significance,these trials may prove unwieldy in terms of numbers and fol-low-up duration. For example, with an estimated recurrencerate of 10% for furunculosis [6], accumulating a sample sizelarge enough to address this issue might require thousands ofpatients. An important legacy of the Rajendran et al. study isthat it will serve as a building block for future investigationsas investigators will be able to use these data while designingtreatment trials.

As Rajendran’s work illustrates, with a placebo cure rate of90.3%, the cornerstone of effective management of skin andsoft-tissue abscesses remains adequate incision and drainage.Currently, clinicians must rely on sound judgment andexpert guidelines for the management of CA-MRSA disease[2,21]. The role of adjunctive antimicrobial therapy in themanagement of CA-MRSA disease remains incompletelyunderstood; however, despite its limitations, the work ofRajendran et al. augments the current understanding of thebest way to manage uncomplicated CA-MRSA skin andsoft-tissue abscesses.

Five-year viewThe struggle to determine what makes CA-MRSA so clinicallyvirulent on a molecular level has just begun and importantvirulent factors are certainly yet to be identified. In addition,what makes some individuals prone to disease from animmunologic perspective has still to be fully elucidated. Regard-less of results from future prospective randomized treatment

trials, an effective vaccine that matches the pathogen’s viru-lence with effective host immunity will prove the best solutionto skin and soft-tissue disease caused by CA-MRSA.

DisclaimerThe opinions or assertions contained herein are the private views of the authorand are not to be construed as official or reflecting the views of theDepartment of the Army, the Department of Defense or US Government. Theauthor is an employee of the US government. This work was prepared as partof his official duties and, as such, there is no copyright to be transferred.

Financial & competing interests disclosureThe author has no relevant affiliations or financial involvement with anyorganization or entity with a financial interest in or financial conflictwith the subject matter or materials discussed in the manuscript. Thisincludes employment, consultancies, honoraria, stock ownership or options,expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that may manifest across a spectrum that ranges from uncomplicated to severe disease. The majority of CA-MRSA infections are uncomplicated skin and soft-tissue infections.

• Adequate incision and drainage of CA-MRSA skin and soft-tissue abscesses is the cornerstone of effective management.

• Adjunctive antimicrobial therapy for the treatment of CA-MRSA skin and soft-tissue abscesses may be unnecessary.

• Large, randomized, placebo-controlled trials are needed to better define the role for adjunctive antimicrobial therapy in the management of CA-MRSA infections.

References1 Rajendran PM, Young D, Maurer T et al.

Randomized, double-blind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob. Agents Chemother. 51, 4044–4048 (2007).

2 Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin. Infect. Dis. 41, 1373–1406 (2005).

3 Llera JL, Levy RC. Treatment of cutaneous abscess: a double-blind clinical study. Ann. Emerg. Med. 14, 15–19 (1985).

4 Moran GJ, Krishnadasn A, Gorwitz RJ et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N. Engl. J. Med. 355, 666–674 (2006).

5 Fridkin SK, Hageman JC, Morrison M et al. Methicillin-resistant Staphylococcus aureus in three communities. N. Engl. J. Med. 352, 1436–1444 (2005).

6 Daum RS. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N. Engl. J. Med. 357, 380–390 (2007).

7 Francis JS, Doherty MC, Lopatin U et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton–Valentine leukocidin gene. Clin. Infect. Dis. 40, 100–107 (2005).

8 Adem PV, Montgomery CP, Husain AN et al. Staphylococcus aureus sepsis and the Waterhouse–Friderichsen syndrome in children. N. Engl. J. Med. 353, 1245–1251 (2005).

9 Miller LG, Perdreau-Remington F, Rieg G et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N. Engl. J. Med. 352, 1445–1453 (2005).

10 Kaplan SL, Hulten KG, Gonzalez BE et al. Three-year surveillance of community-acquired Staphylococcus aureus infections in children. Clin. Infect. Dis. 40, 1785–1791 (2005).

11 Ellis MW, Griffith ME, Dooley DP et al. Targeted intranasal mupirocin to prevent colonization and infection by community-associated methicillin-resistant Staphylococcus aureus strains soldiers: a

Page 5: Is antimicrobial therapy needed to manage uncomplicated skin and soft-tissue abscesses?

Antimicrobial therapy and uncomplicated skin and soft-tissue abscesses Key Paper Evaluation

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cluster randomized controlled trial. Antimicrob. Agents Chemother. 51, 3591–3598 (2007).

12 Lee MC, Rios AM, Aten MF et al. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatr. Infect. Dis. J. 23, 123–127 (2004).

13 Ruhe JJ, Smith N, Bradsher RW, Menon A. Community-onset methicillin-resistant Staphylococcus aureus skin and soft-tissue infection: impact of antimicrobial therapy on outcome. Clin. Infect. Dis. 44, 777–784 (2007).

14 Harris HW, Young DM. Care of injection drug users with soft tissue infections in San Francisco, California. Arch. Surg. 137, 1217–1222 (2002).

15 Young DM, Harris HW, Charlebois ED et al. An epidemic of methicillin-resistant Staphylococcus soft tissue infection among medically underserved patients. Arch. Surg. 139, 947–953 (2004).

16 Weigelt J, Itani K, Stevens D et al. Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections. Antimicrob. Agents Chemother. 49, 2260–2266 (2005).

17 Jauregui LE, Babazadeh S, Seltzer E et al. Randomized, double-blind comparison of once-weekly dalbavancin versus twice-daily linezolid therapy for the treatment of complicated skin and skin structure infections. Clin. Infect. Dis. 41, 1407–1415 (2005).

18 Macfie J, Harvey J. The treatment of acute superficial abscesses: a prospective clinical trial. Br. J. Surg. 64, 264–266 (1977).

19 Paydar KZ, Hansen SL, Charlebois ED, Harris HW, Young DM. Inappropriate antibiotic use in soft tissue infections. Arch. Surg. 141, 850–856 (2006).

20 Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus. J. Infect. Dis. 195, 202–211 (2007).

Website

101 Gorwitz RJ, Jernigan DB, Jernigan JA, Powers JH; and Participants in the CDC-convened experts’ meeting on management of MRSA in the community. Strategies for clinical management of MRSA in the community: summary of an expert’s meeting Convened by the Centers for Disease Control and Prevention. March 2006www.cdc.gov/ncidod/dhqpr/ar_mrsa_ ca.html.

Affiliation• Michael W Ellis, MD, MAJ, MC

Infectious Disease Service, MCHE-MDI, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234-6200, USATel.: +1 210 916 4355Fax: +1 210 916 [email protected]