Double Anaerobic Coverage—A Call for Antimicrobial Stewardship : Infectious Diseases in Clinical Practice

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Editorial Comment

Double Anaerobic Coverage—A Call for Antimicrobial Stewardship

Trienski, Tamara L. PharmD, BCIDP, FIDSA; Bhanot, Nitin MD, MPH, MMM, FIDSA∗†

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Infectious Diseases in Clinical Practice: November 2022 - Volume 30 - Issue 6 - e1244
doi: 10.1097/IPC.0000000000001244
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The use of double anaerobic coverage (DAC) has been associated with increased risks of drug resistance, adverse reactions, and hospital costs.1 Double anaerobic coverage for intra-abdominal infections (IAIs) is not recommended by society guidelines.2 This is pertinent as long as the antimicrobial agent used has reliable activity against the Bacteroides fragilis group, the predominant anaerobes implicated in IAIs. With increasing rates of antimicrobial resistance, some agents that were initially deemed to have effective anerobic activity, should not be used empirically to treat IAIs. These include moxifloxacin, clindamycin, and second-generation cephalosporins, such as cefoxitin and cefotetan.3,4 If these agents are used for targeted treatment of microbes other than anaerobes, then additional and reliable anaerobic coverage is warranted. Carbapenems, metronidazole, and β-lactam/β-lactamase inhibitors, on the other hand, have reliable anaerobic coverage, although some resistance has been reported among these agents as well.5 This level of resistance is not enough to warrant use of DAC empirically; however, one should note that there is variation in the anaerobic efficacy among the β-lactam/β-lactamase inhibitors. Particularly, resistance has been reported to ampicillin-sulbactam in different parts of the world.6 Therefore, a more effective empiric agent should be selected considering regional antimicrobial resistance patterns, especially for severe infections. Piperacillin-tazobactam has adequate empiric anaerobic coverage and may be relied as monotherapy for IAIs against B. fragilis group.7 Other appropriate empiric regimens for IAIs include ceftriaxone or cefepime in conjunction with metronidazole.

Use of 2 agents with anaerobic coverage should only be considered in select clinical circumstances, such as using clindamycin along with a β-lactam/β-lactamase inhibitor in necrotizing fasciitis for its antitoxin effects and not anaerobic activity.8

In this issue, Raymond and colleagues9 assessed DAC used postoperatively in patients with intra-abdominal infections. The authors used a cohort of 134 patients and matched them 1:1 between DAC and single anaerobic coverage (SAC). The primary outcomes were length of stay (LOS), in-hospital postoperative complications, and readmission within 30 days of discharge due to postoperative complications. Double anaerobic coverage was used more often for GI perforations (38.8% vs 16.4%, P = 0.004) and acute perforated appendicitis (23.9% vs 10.4%, P = 0.039). Single anaerobic coverage was used more often for acute cholecystitis (37.3% vs 9%, P = 0.039). The length of treatment with DAC was significantly longer than SAC (median, 9 days; interquartile range, 6–14 days vs 5 days; interquartile range, 3–7 days; P < 0.001). In a univariate analysis, DAC was shown to have a longer LOS (median, 9 days vs 5 days, odds ratio, 1.13; 95% confidence interval, 1.05–1.21; P < 0.001) and more in-hospital postoperative complications (25.4% vs 9%; odds ratio, 3.46; 95% confidence interval, 1.27–9.42; P = 0.015). The most common in-hospital postoperative complications in the DAC cohort were septic shock (16.4%), postoperative infection (6%), and surgical site infections (3%). Double anaerobic coverage was shown to have less readmissions within 30 days due to postoperative complications than SAC, but this was not statistically significant. In the SAC cohort, the most common in-hospital postoperative complications were postoperative infection (6%), septic shock (1.5%), and surgical site infections (1.5%). For secondary outcomes, patients receiving SAC did not have any reported in-hospital mortality or hospital-acquired Clostridioides difficle infections (HA-CDIs). However, in patients receiving DAC, the rate of in-hospital mortality was 6% and the rate of hospital-acquired C. difficle infections was 1.5%. This study demonstrated that DAC was associated with worse clinical outcomes than SAC.

Antimicrobial Stewardship is crucial to address the prescribing of DAC and can impact patient outcomes and associated costs. The Joint Commission medication management standard for antimicrobial stewardship has updated elements of performance effective January 1, 2023. One of required elements involves implementation of either preauthorization for specific antibiotics or prospective review and feedback regarding antibiotic prescribing practices.10 Reviewing patients that are receiving multiple antimicrobial agents that cover anaerobes would be an appropriate target for prospective audit and feedback. Education alone is not enough to reduce the use of DAC.11


1. Song YJ, Kim M, Huh S, et al. Impact of an antimicrobial stewardship program on unnecessary double anaerobic coverage prescription. Infect Chemother. 2015;47(2):111–116.
2. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:133–164.
3. Hecht DW. Prevalence of antibiotic resistance in anaerobic bacteria: worrisome developments. Clin Infect Dis. 2004;39(1):92–97.
4. Karlowsky JA, Walkty AJ, Adam HJ, et al. Prevalence of antimicrobial resistance among clinical isolates of Bacteroides fragilis group in Canada in 2010-2011: CANWARD surveillance study. Antimicrob Agents Chemother. 2012;56(3):1247–1252.
5. Fernández-Canigia L, Litterio M, Legaria MC, et al. First national survey of antibiotic susceptibility of the Bacteroides fragilis group: emerging resistance to carbapenems in Argentina. Antimicrob Agents Chemother. 2012;56(3):1309–1314.
6. Liu CY, Huang YT, Liao CH, et al. Increasing trends in antimicrobial resistance among clinically important anaerobes and Bacteroides fragilis isolates causing nosocomial infections: emerging resistance to carbapenems. Antimicrob Agents Chemother. 2008;52(9):3161–3168.
7. Snydman DR, Jacobus NV, McDermott LA, et al. National survey on the susceptibility of Bacteroides fragilis group: report and analysis of trends in the United States from 1997 to 2004. Antimicrob Agents Chemother. 2007;51(5):1649–1655.
8. Andreoni F, Zürcher C, Tarnutzer A, et al. Clindamycin affects group a Streptococcus virulence factors and improves clinical outcome. J Infect Dis. 2017;215(2):269–277.
9. Raymond L, Cani E, Zeana C, et al. Clinical outcomes of single versus double anaerobic coverage for intra-abdominal infections. Infect Dis Clin Pract. 2022. [needs completed].
10. The Joint Commission. Medication Management (MM) Chapter (MM.09.01.01). New and Revised Antibiotic Stewardship Requirements–Hospital (HAP) Accreditation Program. Available at: Accessed 20 September 2022.
11. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51–e77.
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