title: Time-kill effect of levofloxacin on multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: synergism with imipenem and colistin.
abstract: In the present study, we challenged the concept that levofloxacin should not be used for the management of ventilator-associated pneumonia (VAP) when minimum inhibitory concentrations (MICs) exceed 2 μg/ml. Multidrug-resistant (MDR) and genetically distinct isolates of Pseudomonas aeruginosa (n = 49) and Acinetobacter baumannii (n = 29) from patients with VAP were exposed over time to levofloxacin, imipenem, colistin and their combinations. Synergy between levofloxacin and imipenem was found in 55.3 % and between levofloxacin and colistin in 90.9 % of isolates of P. aeruginosa within the first 4 h of growth. Synergy with imipenem but not with colistin was dependent of the MIC. Synergy between levofloxacin and imipenem was found in 58.6 % of isolates of A. baumannii after 24 h of growth. Considerable synergy was found between levofloxacin and colistin, reaching 84.8 % of isolates of A.baumannii after 6 h of growth. Synergy was independent from the MIC. These results create hopes that levofloxacin can be used as combination therapy for infections by MDR bacteria.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Safarika
authors.forename: I
authors.initials: I
authors.lastname: Galani
authors.forename: A
authors.initials: A
authors.lastname: Pistiki
authors.forename: E J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D064704:Levofloxacin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015378:Imipenem; D003091:Colistin