Establishing the Role of Tigecycline in an era of Antimicrobial Resistance

Jason J. Schafer; Debra A. Goff

Disclosures

Expert Rev Anti Infect Ther. 2008;6(5):557-567. 

In This Article

Resistance

Although tigecycline is designed to overcome determinants of tetracycline resistance, including specific efflux pumps, it has been found to be a substrate for some multidrug-efflux pumps. These include the MexXY-OprM in P. aeruginosa and AcrAB in Proteus mirabilis,[35,36] both of which are efflux pumps within the resistance nodulation division (RND). As a result, tigecycline displays poor activity against these bacterial species.

Resistance to tigecycline has also been encountered clinically in isolates of A. baumannii.[37,38,39] In some instances, resistance to this pathogen has been reported to develop during tigecycline therapy. One report described the development of MDR A. baumannii bloodstream infections in two patients during tigecycline therapy for separate infections for 9 and 16 days, respectively.[37] The MIC values of these isolates to tigecycline were 4 and 16 µg/ml and one patient died as a result of an overwhelming A. baumannii infection. This report, in addition to subsequent reports of resistance developing during A. baumannii therapy, has raised concern for the role of this agent in treating these infections.[38,39]

The mechanism of resistance to tigecycline occurring in A. baumannii isolates has been investigated.[40] Previously, expression of the RND-type efflux pump AdeABC has been identified in A. baumannii as a mechanism that can confer resistance to multiple antimicrobial agents.[41,42] Upon investigation of A. baumannii isolates, one group has indicated that the AdeABC efflux pump may be, at least partially, implicated in conferring resistance to tigecycline.[40] Further investigation of tigecycline resistance mechanisms in A. baumannii is currently warranted.

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