Clinical equivalency of ciprofloxacin 750 mg enterally and 400 mg intravenously for patients receiving enteral feeding: Systematic review

Abstract

Background: Concomitant enteral administration of ciprofloxacin with products containing magnesium, aluminum, and calcium (e.g., as enteral feeds) decreases the oral bioavailability of this antibiotic. The manufacturer currently recommends holding enteral feeds for a total of 8 h after ciprofloxacin is given, but this is not feasible for patients who are receiving continuous enteral feeding. A previous study demonstrated that a higher dose of oral ciprofloxacin (750 mg BID) may compensate for the reduced bioavailability associated with this drug-food interaction, allowing adequate concentrations for effective bactericidal activity. Objective: To evaluate whether ciprofloxacin 750 mg administered enterally is a clinically feasible alternative to ciprofloxacin 400 mg administered intravenously for adults receiving enteral feeds. Methods: A literature search was conducted in EMBASE (January 1980 to April 2008) and MEDLINE (January 1949 to April 2008), with no language restrictions, using the key words "ciprofloxacin", "fluoroquinolone", "tube feed", and "enteral". For trials that remained after screening of the abstract, the full text was reviewed and the reference lists were hand-searched to identify additional trials. The following outcomes were prespecified: death, serious adverse events, clinical cure, microbiological cure, re-infection, total adverse events, ratio of area under the curve (AUC, in microgram-hours per millilitre) to minimum inhibitory concentration (MIC, in micrograms per millilitre), ratio of maximum serum concentration (Cmax, in micrograms per millilitre) to MIC, and Cmax. Results: The search identified 121 potentially eligible studies, which were screened on the basis of information provided in the abstract. From this initial screening, it was clear that 113 studies did not meet the inclusion criteria. The remaining 8 studies were subjected to a full-text review, which revealed that only 1 study met the inclusion criteria. In that study, ciprofloxacin 750 mg given enterally yielded an AUC similar to that achieved with 400 mg given parentally, but the Cmax was lower. No clinical outcomes were reported. Conclusions: There is insufficient evidence from this systematic review to determine whether patients receiving enteral feeds concomitantly with enteral ciprofloxacin 750 mg BID will achieve clinical outcomes similar to those receiving parenteral ciprofloxacin 400 mg BID.