Reference: Talan et al. Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. NEJM March 2016
Guest Skeptic: Chip Lange is an Emergency Medicine Physician Assistant working primarily in rural Missouri in community hospitals. He has international experience in critical care and emergency medicine. He has a new blog called TOTAL EM, which stands for Tools Of the Trade and Academic Learning in Emergency Medicine. He has recently started podcasting and is always looking to expand this new project. He cares about providing TOTAL care everywhere and wants us all to be excellent when we see and treat out patients.
Case: A 40 year-old male with a history of MRSA presents complaining of an area of redness and swelling consistent with an abscess developing on his arm. He says that he has heard that antibiotics may not be necessary after his friend had an incision and drainage (I&D) and they did not give her any antibiotics. He denies any allergies to antibiotics and has taken Sulfa drugs in the past without complication.
Background: Cutaneous abscesses are a very common complaint in the emergency department and we have discussed the management of these before on the SGEM.
One issue was whether or not to pack after I&D? Our bottom line in 2012 was that routine packing of simple cutaneous abscesses might not be necessary (SGEM#13: Better Out than In).
We recently looked at whether irrigation of a cutaneous abscess after I&D reduces the need for further intervention. The SGEM bottom line from that review was that irrigation is probably not necessary (SGEM #156: Working at the Abscess Wash).
Another issue that has been debated over the years is if antibiotics should be routinely prescribed after I&D. We covered a review by Hankin and Everett from 2007 on SGEM#13. It identified that there was very little high quality evidence available on the subject.
They stated: “A conclusive, multicenter, double-blind, randomized, placebo-controlled clinical trial is lacking and sorely needed.”
The SGEM conclusion at that time was that the evidence did not support using antibiotics routinely in simple cutaneous abscesses even in the era of MRSA.
Now we have a multicenter, double-blind, randomized, placebo-controlled clinical trial to address this issue.
Clinical Question: Does TMP/SMX offer a higher clinical cure rate than placebo in patients with a drained uncomplicated cutaneous abscess?
Reference: Talan et al. Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. NEJM March 2016
Population: All emergency department patients greater than 12 years of age with cutaneous abscess that presented less than one week after onset and that measured at least 2 cm in diameter (whether by borders of induration if the lesion was fluctuant or by ultrasound of the cavity if not fluctuant).
Exclusion Criteria: Indwelling device; suspected osteomyelitis or septic arthritis; diabetic foot, decubitis, or ischemic ulcer; mammalian bite; wound with organic foreign body; infection or another organ system/site; perirectal, perineal or paronychial location; intravenous drug use within previous month and fever; underlying skin condition; long-term care residence; incarceration; immunodeficiency (e.g., absolute neutrophil count <500/mm3, immunosuppressive drugs, active chemotherapy, or known AIDS assessed by subject history); creatinine clearance <50mL/min; cardiac condition with risk of endocarditis; allergy or intolerance to TMP/SMX; taking warfarin, phenytoin, or methotrexate; known G-6-PD or folic acid deficiency; pregnant or lactating; TMP/SMX treatment within 24 hours; concurrent treatment with topical or systemic antibiotic; or enrolled in the study within 12 weeks. Laboratory testing was done at the discretion of the treating clinician.
Intervention: Incision and drainage and treatment with TMP/SMX (7 days of 4 single strength pills taken twice a day)
Comparison: Incision and drainage and treatment with placebo
Primary: Clinical cure of abscess lesion at the test-of-cure visit, which was 7-14 days after the end of the treatment period. Clinical cure was considered if they did not meet the criteria for clinical failure at or before the test-of cure visit.
Secondary: Composite cure (no additional antibiotic therapy or surgical drainage procedure was necessary), surgical drainage procedures, changes in erythema size, the presence of swelling or induration and tenderness, invasive infection, skin infections at the same site and at a different side, hospitalizations, similar infections in household contacts, days missed from normal activities, days missed from school or work, and days that analgesics were used.
Clinical failure was defined as the following: fever (attributable to the infection), an increase in the maximal dimension of erythema by >25% from baseline, or worsening of wound swelling and tenderness by the visit during the treatment period (day 3 or 4); fever, no decrease in the maximal dimension of erythema from baseline, or no decrease in swelling or tenderness by the visit at the end of the treatment period (day 8–10); fever or more than minimal erythema, swelling, or tenderness by the test-of-cure visit (day 14–21). Participants who withdrew from the trial, were lost to follow- up before final classification, or had missing or unassigned outcomes were classified as having had clinical failure.
Author’s Conclusions:In settings in which MRSA was prevalent, TMP/SMX treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo.
Quality Checklist for Randomized Clinical Trials:
The study population included or focused on those in the ED. Yes
The patients were adequately randomized. Yes
The randomization process was concealed. Yes
The patients were analyzed in the groups to which they were randomized. Yes, by modified intention-to-treat analysis
The study patients were recruited consecutively (i.e. no selection bias). Unsure
The patients in both groups were similar with respect to prognostic factors. Yes
All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
All groups were treated equally except for the intervention. Yes
Follow-up was complete (i.e. at least 80% for both groups). Yes
All patient-important outcomes were considered. Yes
The treatment effect was large enough and precise enough to be clinically significant. Unsure
Key Results: 1,265 patients underwent randomization. The median age was 35, 57% male and 45% had wound cultures positive for MRSA.
Adverse Events: These were similar between TMP/SMX and placebo with most being mild. The most common adverse event reported was GI issues (43% TMP/SMX vs. 36% placebo group). No cases of Clostridium difficile– associated diarrhea, no treatment-associated serious or life-threatening adverse events and the discontinuation rate was similar in both groups. There were two deaths in total with one in each group.
We have a surprise for the SGEMers. Dr. David Talan the lead author of this NEJM paper has agreed to come on the show and answer some questions.
Dr. David Talan
Dr. Talan is considered an authority in the area of acute infections that result in severe morbidity and death. He is currently on the faculty of the Department of Emergency Medicine, and Department of Medicine, Division of Infectious Diseases at Olive View-UCLA Medical Center. Dr. Talan also serves on the editorial board of the Annals of Emergency Medicine.
Listen to the podcast to hear Dr. Talan’s responses to our questions.
Consecutive Recruitment: It was unclear to us if the recruitment of patients was consecutive?
Modified Intention to Treat (mITT): You did a mITT analysis and a per-protocol analysis. Why did you modify the ITT analysis and do you think that really mattered to your results?
Dose of TMP/SMX: You used four single strength pills of TMP/SMX twice a day based on the recommendation at the time from The Sanford Guide to Antimicrobial Therapy. The newer Sanford Guide does not recommend this higher dose except in obese patients (BMI>40). So do you think two single strength pills twice a day will work just as well?
Secondary Outcomes. These can be used as hypothesis generating. You had a number of secondary outcomes that demonstrated TMP/SMX superior to placebo in the per-protocol analysis. Was there an outcome in particular that you think is especially interesting and should be pursued?
MRSA Prevalence: You had a high rate of MRSA (45%). Do you think these results have external validity to populations without such high prevalence?
Proper Incision and Drainage: As part of this study, you trained everyone on how to do an incision and drainage properly. That included irrigating the abscess and packing the abscess. Both of these may not to be necessary for the successful treatment of a simple cutaneous abscess. As an expert in this area what are your thoughts on the standard treatment and do you irrigate and pack your abscesses?
Superiority Trial: This was designed as a superiority trial with a power of 90% to detect an absolute between-group difference of 7.5 percentage e points, assuming a cure rate of 90% in the trimethoprim–sulfamethoxazole group in the per-protocol population. You only found a 7.2% difference in the Per-Protocol Population?
Statistical vs. Clinical Significance: You found a statistical significant difference but do you think this represents a clinical significant difference?
What about the Harm? Adverse events were similar between the two groups with most being mild. Are you worried about C diff or resistance?
Advice to EM doctors? Based on this study and your expertise in the area, what would be your advice to EM doctors in treating uncomplicated cutaneous abscesses?
Comment on author’s conclusion compared to SGEM Conclusion: We generally agree with the authors’ conclusions.
SGEM Bottom Line: The addition of TMP/SMX to the treatment of uncomplicated cutaneous abscesses represents an opportunity for shared decision-making.
Case Resolution: You discuss with your patient that in the past there was some limited evidence suggesting that antibiotics may not be of benefit but that there were limitations due to the studies small size. However, a newer, larger study demonstrates that antibiotics are effective in increasing the cure rate for abscesses. After shared decision-making including the risks, benefits, and potential complications of antibiotics, the patient agrees to receive TMP/SMX for his abscess after the incision and drainage is complete.
Clinical Application: TMP/SMX should be considered as part of the treatment regimen for the management of cutaneous abscesses.
What do I tell my patient? You are right, until recently we did not have good evidence that antibiotics were helpful in treating abscesses. However a new well-done study has shown antibiotics can increase the cure rate by 7%. That means we need to treat 14 patients for one more patient to be cured. Antibiotics are not without risk though and there are certain populations that were not included in the study. We should consider TMP/SMX in the treatment of your abscess.
Keener Kontest: Last weeks’ winner was Lane Rathgeber from Regina, Saskatchewan. Lane knew streptokinase is the name of the fibrinolytic substance produced by Lancefield Group A beta-hemolytic streptococci.
Listen to the podcast for this weeks’ question. If you know the answer then send an email to TheSGEM@gmail.com with keener in the subject line. The first correct answer will receive a cool skeptical prize.
Other FOAMed Resources:
REBEL EM: Trimethoprim-Sulfamethoxazole for Uncomplicated Skin Abscesses?