To the Editor
Schmitz et al1 reported the results of a prospective study of adjunctive antibacterial therapy for the treatment of uncomplicated cutaneous abscesses. They concluded that “[a]fter the incision and drainage of uncomplicated abscesses in adults, treatment with trimethoprim-sulfamethoxazole does not reduce treatment failure but may decrease the formation of subsequent lesions.” However, given the point estimate and wide 95% confidence interval (CI) of the difference in treatment failures with and without antibiotics (9%; −2% to +21%), conclusions should not be drawn from this study about the efficacy of antibacterial agents for therapy of uncomplicated abscesses. Indeed, the clear trend to a reduction in treatment failures and the significant reduction in recurrent lesions with antibacterial therapy despite the small sample size underscore the possibility that antibacterial therapy is of substantial benefit for uncomplicated cutaneous abscesses. Unfortunately, this study is but the latest in a string of underpowered investigations into this important clinical issue (Table).
Table.
Studies comparing active antibacterial therapy versus inactive therapy/placebo for uncomplicated cutaneous abscesses.
| First Author, Year | Results | Difference, % (95% CI*) | P Value |
|---|---|---|---|
| Randomized controlled trials | |||
| Schmitz,1 2010 | Treatment failure: 15/88 (17% TMP-SMX) vs 27/102 (26% placebo) | 9 (–2.2 to 21.1) | .1 |
| Recurrence: 4/46 (9% TMP-SMX) vs 14/50 (28% placebo) | 19 (4.4 to 34.2) | .02 | |
| Duong,3 2009 | Treatment failure: 3/73 (4% TMP-SMX) vs 4/76 (5% placebo) | 1 (–7.0 to 9.3) | .5 |
| Recurrence: 9/70 (13% TMP-SMX) vs 19/72 (26% placebo) | 13 (–0.7 to 27.8) | .04 | |
| Llera,4 1985 | Treatment failure: 1/27 (3.7% cephradine) vs 1/23 (4.3% placebo) | 0.6 (–14.4 to 15.6) | .9 |
| Macfie,5 1977† | Recurrence: 0/57 (0% clindamycin) vs 3/41 (7% placebo) | 7 (–2.8 to 17.4) | .07 |
| Observational studies | |||
| Ruhe,6 2007 | Treatment failure: 16/312 (5% active antibiotics) vs 29/219 (13% discordant antibiotics) | 8 (2.6 to 13.6) | .001 |
| Paydar,7 2006‡ | Treatment failure (intention to treat): 2/178 (1% active antibiotics) vs 22/263 (8% discordant antibiotics)‡ | 7 (3.8 to 11.4) | .001 |
| Lee,8 2004 | Treatment failure: 0/26 (0% active antibiotics)§ vs 4/37 (11% discordant antibiotics) | 11 (–2.5 to 24.1) | .1 |
TMP-SMX, Trimethoprim-sulfamethoxazole.
The 95% CI in the study by Schmitz et al1 is reported as it was in the article, without continuity correction; all other CIs in this table were recalculated with continuity correction.
Two study arms in which abscess cavities were sutured shut are not included; clindamycin given at very low dose (150 mg orally every 6 hours).
When patients lost to follow-up were excluded, failure rates were 2 of 166 (antibiotics) vs 1 of 242 (no antibiotics), but the “failure” in the no-antibiotic arm was subsequent development of necrotizing fasciitis requiring leg amputation.
Includes 5 patients who were treated initially with active antibiotics and 21 patients who initially received discordant antibiotics but who began receiving active antibiotics instead after culture results became available.
We are unaware of any previously published discussion about what difference in treatment failure or abscess recurrence rate is clinically meaningful when studies of uncomplicated abscesses are evaluated. However, an estimated 1.8 million Staphylococcus aureus infections occur per year in the United States, of which greater than 90% are skin and soft tissue infections.2 Hence, a failure rate of 9%, which was the point estimate for excess failures in the placebo arm of the study by Schmitz et al,1 would result in 145,000 excess treatment failures per year in the United States. Even a difference of 5% would be clinically meaningful, with an excess of greater than 80,000 treatment failures per year in the United States. These failures may lead to inpatient hospitalization, the need for repeated procedures, loss of work time, and other morbidity. Failure of treatment associated with development of bloodstream infection or deep tissue infection, though rare, is of grave concern. Therefore, studies should be powered to rule out a difference in treatment failure rates of less than 5% between patients treated with and without antibiotics.
A review of previously published studies suggests that there may be a 5% to 10% excess failure rate when an active antibiotic is withheld after incision and drainage of an uncomplicated abscess (Table). The 95% CI for outcomes in previous underpowered, smaller studies all included differences of this magnitude. Meta-analysis of the reviewed studies is not likely to elucidate the issue, given the mixture of observational and randomized trials, the discordant types of antibiotics and doses used, and the clear heterogeneity of results. Rather, we hope that the 2 ongoing National Institutes of Health–funded placebo-controlled trials (NCT00730028 and NCT00729937) of uncomplicated abscesses will finally clarify the issue by providing an adequately powered comparison of an active antibacterial agent versus placebo. Until such time as adequately powered studies are available, we urge caution in interpreting available data and recommend against concluding that adjunctive antibacterial therapy is of no benefit in the treatment of incised and drained, uncomplicated abscesses. Finally, close monitoring is warranted for patients from whom antibacterial therapy is withheld after incision and drainage.
Guidelines for Letters to the Editor.
Annals welcomes letters to the editor, including observations, opinions, corrections, very brief reports, and comments on published articles. Letters to the editor should not exceed 500 words and 5 references. They should be submitted using Annals’ Web-based peer review system, Editorial Manager™ (http://www.editorialmanager.com/annemergmed). Annals no longer accepts submissions by mail.
Letters should not contain abbreviations. A Manuscript Submission Agreement (MSA), signed by all authors, must be faxed to the Annals office at the time of submission. Financial association or other possible conflicts of interest should always be disclosed, as documented on the MSA, and their presence or absence will be published with the correspondence. Letters discussing an Annals article must be received within 8 weeks of the article's publication.
Published letters will be edited and may be shortened. Authors of articles for which comments are received will be given the opportunity to reply. If those authors wish to respond, their reply will not be shared with the author of the letter before publication.
Neither Annals of Emergency Medicine nor the Publisher accepts responsibility for statements made by contributors or advertisers.
Funding and support
By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. BS has received grant support from Gilead, Astellas, Novartis, and has consulted for Merck, Pfizer, Arpida, Theravance, Advanced Life Sciences, Basilea, The Medicines Company, Achaogen, Novartis, Cerexa, Wyeth, and Trius. HB has served as an advisor/consultant in the last 12 months to Astellas/Theravance, Basilea, Cerexa, Cubist, Durata, Johnson & Johnson, Merck (adjudication committee), Methylgene, Nabriva, Optimer, Rib-X, Targanta/TMC, and Wyeth (DSMB). JB's employer, the University of California, has service contracts with Johnson & Johnson, Cerexa, Trius, Nabriva, and Dow Pharmaceuticals and research grant support from Johnson & Johnson, Cubist, Wyeth, and Roche. AD, through her company, Axistat, has served as a consultant to the following pharmaceutical companies in the last 12 months; Achaogen, Arcion (DSMB), Calixa, Cempra, Cerexa, Cubist, Corthera, Hologic, Durata, Poniard and Trius. GHT, through his company, Talbot Advisors LLC, has served as an advisor to the following pharmaceutical companies in the last 12 months: Actelion, Calixa, Cempra, Cerexa, Cubist, Durata, MMM, Rib-X, Wyeth (DSMB); he is a shareholder in Calixa, Cerexa, Durata, Mpex, and Nabriva, and sits on the Board of Directors of Nabriva.
Contributor Information
Brad Spellberg, Division of General Internal Medicine Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center David Geffen School of Medicine at UCLA Los Angeles, CA.
Helen Boucher, Division of Geographic Medicine and Infectious Diseases Tufts University School of Medicine and Tufts Medical Center Boston, MA.
John Bradley, Division of Infectious Diseases Rady Children's Hospital San Diego University of California at San Diego San Diego, CA.
Anita Das, AxiStat Inc San Francisco, CA.
George Talbot, Talbot Advisors LLC Wayne, PA.
References
- 1.Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection. Ann Emerg Med. 2010;56:283–287. doi: 10.1016/j.annemergmed.2010.03.002. [DOI] [PubMed] [Google Scholar]
- 2.Chambers HF. Community-associated MRSA: resistance and virulence converge. N Engl J Med. 2005;352:1485–1487. doi: 10.1056/NEJMe058023. [DOI] [PubMed] [Google Scholar]
- 3.Duong M, Markwell S, Peter J, et al. Randomized, controlled trial of antibiotics in the management of community-acquired skin abscesses in the pediatric patient. Ann Emerg Med. 2010;55:401–407. doi: 10.1016/j.annemergmed.2009.03.014. [DOI] [PubMed] [Google Scholar]
- 4.Llera JL, Levy RC. Treatment of cutaneous abscess: a double-blind clinical study. Ann Emerg Med. 1985;14:15–19. doi: 10.1016/s0196-0644(85)80727-7. [DOI] [PubMed] [Google Scholar]
- 5.Macfie J, Harvey J. The treatment of acute superficial abscesses: a prospective clinical trial. Br J Surg. 1977;64:264–266. doi: 10.1002/bjs.1800640410. [DOI] [PubMed] [Google Scholar]
- 6.Ruhe JJ, Smith N, Bradsher RW, et al. Community-onset methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: impact of antimicrobial therapy on outcome. Clin Infect Dis. 2007;44:777–784. doi: 10.1086/511872. [DOI] [PubMed] [Google Scholar]
- 7.Paydar KZ, Hansen SL, Charlebois ED, et al. Inappropriate antibiotic use in soft tissue infections. Arch Surg. 2006;141:850–854. doi: 10.1001/archsurg.141.9.850. discussion 855-856. [DOI] [PubMed] [Google Scholar]
- 8.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. 2004;23:123–127. doi: 10.1097/01.inf.0000109288.06912.21. [DOI] [PubMed] [Google Scholar]