Double Coverage for Anaerobes

26 Nov

One of our intensivists asked the following:

Is there a need to add metronidazole to cover anaerobes when using Piperacillin/Tazobactam  or meropenem?

Another great question and one frequently encountered with antimicrobial stewardship programs .(1)

The short answer is no.

Before we proceed Dr. Dan wrote this and provided the primary literature to back this up. I’m just posting it on his behalf.   Thanks D.

Treatment failure with anaerobic infections is most likely related to inadequate source control.

There is a classic study from 1975 by Weinstein et al. (2) of a rat model of fecal peritonitis that ID docs love to quote when discussing antimicrobial therapy for intra-abdominal sepsis. They injected fecal material into the peritoneal cavity of rats to cause peritonitis. They then treated with either gentamicin (gram-negative coverage) or clindamycin (anaerobic coverage), or both. The clindamycin treated mice died of sepsis. The gentamicin treated mice survived, but developed intra-abdominal abscesses. The combo treatment prevented abscess and death. This confirmed the role of anaerobes in abscess formation. It’s obviously not that “simple” when it comes to humans, but “covering” anaerobes is important to prevent/treat abscesses, although the first line for treatment of established abscesses is to drain them. (3) The reason for drainage is that it works. Antibiotics in general have difficulty penetrating the walls of established abscesses and are not happy in the low pH environment. There is a trend that I have observed towards treating smaller (<5 cm) abscesses with antibiotics alone, which may work, but I think is probably associated with a higher failure rate and increased exposure to antibiotics. Although resistance to antibiotics (pip-tazo; carbapenems; metronidazole) in Bacteroides spp is rare, the more we use and antibiotic, the more likely resistance will emerge (including metronidazole resistance, which has been described) (4). There probably isn’t much of a difference between drainage via interventional radiology or surgery for accessible abscesses.

Rates of resistance of carbapenems and B-lactam/B-lactamase combinations are very low for Bacteroides spp. A recent paper from Snydman et al. (5) reveals the rates of resistance of Bacteroides spp. for pip-tazo were on average 1% and for meropenem 2.5%. This is US data (in general the US has more resistance than Canada, this might hold true for anaerobes as well).

Unnecessary “Double-coverage” of anaerobes is considered an important target for antimicrobial stewardship programs.  A study by Curtis Donskey’s group showed that 30% of all antimicrobials prescribed were unnecessary and inappropriate. Antianaerobic therapy made up 35% of the overall number. 10% of the time, this was because of “redundant” treatment.

The more antibiotics we use, the higher the risk of resistance and adverse events, so eliminating redundant anti-anaerobic use is one of our ASP targets as well.

1)Double Anaerobic Coverage: What is the role in clinical practice?  http://www.nebraskamed.com/App_Files/pdf/careers/education-programs/asp/DoubleAnaerobicCoverage.pdf.

2)Weinstein WM, Onderdonk AB, Bartlett JG, Louie TJ, Gorbach SL. (1975) Antimicrobial therapy of experimental intraabdominal sepsis. J Infect Dis. 1975 Sep;132(3):282-6. http://www.ncbi.nlm.nih.gov/pubmed/1159331

3) Solomkin, J. S., Mazuski, J. E., Bradley, J. S., Rodvold, K. A., Goldstein, E. J. C., Baron, E. J., OʼNeill, P. J., et al. (2010). 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. Surgical Infections, 11(1), 79-109. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20034345

4)Steffens, L. S., Nicholson, S., Paul, L. V., Nord, C. E., Patrick, S., & Abratt, V. R. (2010). Bacteroides fragilis RecA protein overexpression causes resistance to metronidazole. Research in Microbiology, 161(5-3), 346-354. Elsevier. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20445272

5) Snydman, D. R., Jacobus, N. V., McDermott, L. A., Golan, Y., Goldstein, E. J. C., Harrell, L., Jenkins, S., et al. (2011). Update on resistance of Bacteroides fragilis group and related species with special attention to carbapenems 2006-2009. Anaerobe, 17(4), 147-151. http://www.ncbi.nlm.nih.gov/pubmed/21664469

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