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Antimicrobial Agents and Chemotherapy, July 2005, p. 2959-2964, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2959-2964.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

In Vitro Synergy of Ciprofloxacin and Gatifloxacin against Ciprofloxacin-Resistant Pseudomonas aeruginosa

George A. Pankey* and Deborah S. Ashcraft

Ochsner Clinic Foundation, New Orleans, Louisiana

Received 9 July 2004/ Returned for modification 15 September 2004/ Accepted 15 March 2005

Multidrug-resistant Pseudomonas aeruginosa with combined decreased susceptibility to ceftazidime, ciprofloxacin, imipenem, and piperacillin is increasingly being found as a cause of nosocomial infections. It is important to look for combinations of drugs that might be synergistic. Ciprofloxacin resistance by P. aeruginosa is mediated in part by an efflux pump mechanism. Gatifloxacin, an 8-methoxyfluoroquinolone, inhibits a staphylococcal efflux pump. An earlier in vitro study using an Etest synergy method and time-kill assay suggested synergy of ciprofloxacin and gatifloxacin against P. aeruginosa. Synergy testing was performed by Etest and time-kill assay for 31 clinically unique, plasmid DNA distinct, U.S. P. aeruginosa isolates. Etest MICs for ciprofloxacin were 4 to >32 µg/ml, and for gatifloxacin they were >32 µg/ml. Ciprofloxacin plus gatifloxacin showed synergy by the Etest method for 6 (19%) of the 31 P. aeruginosa isolates using a summation fractional inhibitory concentration of ≤0.5 for synergy. Synergy was demonstrated for 13/31 (42%) of isolates by time-kill assay. No antagonism was detected. The remaining isolates were indifferent to the combination. The Etest method and time-kill assay were 65% (20/31) concordant. The mechanism of the in vitro synergy may include P. aeruginosa ciprofloxacin efflux pump inhibition by gatifloxacin.


* Corresponding author. Mailing address: Infectious Diseases Research, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121. Phone: (504) 842-4006. Fax: (504) 842-5433. E-mail: gpankey{at}ochsner.org.


Antimicrobial Agents and Chemotherapy, July 2005, p. 2959-2964, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2959-2964.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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