Abstract
To the Editor:
We read with interest the new guidelines for the diagnosis and management of complicated intra-abdominal infections [1]. Several empiric antimicrobial regimens are advocated by the authors. Among the agents listed, the authors seem to recommend that metronidazole be included in combination therapy with broad-spectrum beta-lactams such as piperacillin-tazobactam and the carbapenems (i.e., imipenem-cilastatin, meropenem, and doripenem). We do not believe this recommendation is supported by meaningful data.
Piperacillin-tazobactam and the carbapenems have excellent activity against anaerobic bacteria, comparable to that of metronidazole. In a recent review of anaerobic bacterial susceptibility to antimicrobial agents, the National Survey for the Susceptibility of Bacteroides fragilis Group described < 1% resistance rates to piperacillin-tazobactam and imipenem-cilastatin in Bacteroides isolates, a figure unchanged since 1981 [2].
Table 3 of the guidelines recommends metronidazole for severe biliary tract infections or if an enteric anastomosis is present (recommendation 61). We are not aware of any evidence supporting the addition of metronidazole to the therapy of severe biliary tract infections when adequate anaerobic activity is already provided by an accompanying broad-spectrum beta-lactam antibiotic such as piperacillin-tazobactam or one of the carbapenems listed in the table.
Furthermore, the recommendations for health care-associated infections are misleading. Recommended drugs include “meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, ceftazidime or cefepime plus metronidazole” (recommendation 46). The addition of metronidazole to a drug that lacks anaerobic coverage is reasonable and appropriate in intra-abdominal and some biliary infections, but it is unnecessary when surgeons and infectious disease specialists are using a drug such as piperacillin-tazobactam with adequate anaerobic coverage.
Metronidazole is generally well-tolerated but is not free of toxicity [3]. Significant synergy between metronidazole and other drugs in the treatment of Bacteroides has not been described. In an era of constrained resources, the addition of therapies with little apparent benefit is difficult to justify.
Footnotes
Author Disclosure Statement
None of the authors has any financial conflicts of interest to report concerning the content of this letter.
The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, Department of Veterans Affairs, or the U.S. Government.
Dr. Maves and Dr. Halsey are employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 USC §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 USC §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties.