Utility of Adjunct Antibiotics After I+D – Systematic Review + Meta-Analysis

Background

Skin and soft tissue abscesses are a common emergency department (ED) presentation. The approach to management has changed little in recent decades: incision and drainage (I+D) and then discharge home with follow up. However, increasing rates of methicillin-resistant staph aureus (MRSA) over the last decade have led to further consideration of adjunct therapy with oral antibiotics to improve cure rates. Two recent studies (Talan 2016, Daum 2017) have shown a modest but consistent benefit to oral antibiotics.

Primary Results

Primary Results:

• Search yielded 2,772 references of which, 15 had full-text review
• Four studies (with 2,406 patients) included in the systematic review and meta-analysis
  • Three studies performed in the ED only
  • One study performed in ED and outpatient setting
• Anti-MRSA antibiotics used: TMP-SMX (3 studies) TMP-SMX or Clindamycin (1 study)

Critical Findings

• Treatment failures (primary outcome)
  • Anti-MRSA antibiotics 7.7% vs Placebo 16.1%
  • Absolute difference: 7.4% (NNT = 13.5)
  • OR = 2.32 (95% CI: 1.75 – 3.08)
  • Statistical Heterogeneity (I²) = 0%
  • Loss to follow up: 6.1%
• New lesions at different sites (secondary outcome)
  • Anti-MRSA antibiotics 6.2% vs. Placebo 15.3%
  • Absolute difference: 9.1% (NNT = 11)
  • OR = 0.32 (95% CI: 0.23 – 0.44)
• Adverse events
  • Anti-MRSA antibiotics 24.8% vs. Placebo 22.2%
  • NNH = 23

Strengths

• Largest meta-analysis/systematic review to date
• PRISMA guidelines used for systematic review and meta-analysis
• Multiple databases searched for relevant articles
• Two investigators independently extracted data from the studies included in the systematic review
• Quality of studies was assessed using the Cochrane Risk of Bias tool
• Risk of bias was determined to be low in all studies (a meta-analysis is only as good as the studies that go into it)
• Included studies were multicenter increasing external validity
• Primary endpoint is patient centered
• Statistical heterogeneity was absent for the primary outcome

Limitations

• Results are heavily weighted by two of the four included studies
• All studies conducted in US. Unclear if this affects generalizability
• Studies did not all use the same antibiotic (Daum et al used clindamycin or TMP-SMX) and did not all use the same dose of antibiotic
• Clinical cure (the primary endpoint) was defined differently in the different studies
• I+D technique was not standardized in all studies. Inadequate drainage would skew the results
• Only one study (Daum 2017) included children < 12 years of age
• In the two largest studies (Talan 2016, Daum 2017) patients had significant overlying cellulitis
• Compliance with treatment assignment low in Talan article which may reduce adverse event rate

Other Issues

• Though the serious adverse event rate was low, it should be noted widespread use of antibiotics for abscesses (particularly the use of TMP-SMX) may reveal a higher rate of adverse events

Author's Conclusions

“The use of systemic antibiotics for skin and soft tissue abscesses after incision and drainage resulted in an increased rate of clinical cure. Providers should consider the use of antibiotics while balancing the risk of adverse events.”

Our Conclusions

We agree with the authors. The available evidence demonstrates a modest but consistent benefit to adjunct, anti-MRSA antibiotics after I+D of simple abscesses in terms of clinical cure and occurrence of new lesions without a significant increase in adverse events.

However, four issues deserve to be stressed:

1. Many of the patients included in the recent studies by Talan and Daum had significant overlying cellulitis. This clouds the issue of whether we are treating the abscess or the cellulitis with the antibiotics.
2. Expanded use of anti-MRSA antibiotics will increase the rate of serious adverse events (C. diff diarrhea, hyperkalemia, Steven’s Johnson Syndrome, hypersensitivity reactions etc) in comparison to standard care with no antibiotics
3. The clinical cure rate without antibiotics is high: 84%. Most patients will improve without antibiotics and, thus, delayed use or addition at follow up may be a superior strategy
4. Widespread antibiotic use will likely change the resistance patterns of staphylococcus aureus

Potential Impact To Current Practice

The findings of this systematic review and meta-analysis show strong evidence that antibiotic therapy, in addition to I&D, leads to higher cure rates for small abscesses with overlying cellulitis. These findings should not be taken to mean that all patients with abscesses who are I&D’d in the ED will need antibiotics as the majority of abscesses (84%) will resolve with I&D alone. The increased clinical cure rate must be weighed against the potential risks associated with increase antibiotic use such as adverse medication-related events and increasing antibiotic resistance.

Bottom Line

ED providers should consider adjunctive therapy with oral antibiotics with MRSA coverage after I&D of simple, small (<5cm) abscesses with overlying cellulitis in healthy individuals to increase short-term cure rates. The presence of significant overlying cellulitis continues to warrant adjunctive therapy with antibiotics.

Read More

• REBEL EM: Trimethoprim-Sulfamethoxazole for Uncomplicated Skin Abscesses
• Bryan Hayes at ALiEM: Sulfamethoxazole-Trimethoprim for Skin and Soft Tissue Infections: 1 or 2 Tablets BID?
• The SGEM: SGEM#164: Cuts Like a Knife
• Core EM: Antibiotics in the Treatment of Smaller Abscesses
• EM Nerd: The Case of the Pragmatic Wound

References

1. Talan DA et al. Trimethoprim–Sulfamethoxazole versus placebo for uncomplicated skin abscess. NEJM 2016; 374(9): 823-32. PMID: 26962903
2. Daum RS et al. A placebo-controlled trial of antibiotics for smaller skin abscesses. NEJM 2017; 376(26): 2545-55. PMID: 28657870
3. Schmitz GR 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(3): 283-7. PMID: 20346539