title: Effectiveness of fosfomycin combined with other antimicrobial agents against multidrug-resistant Pseudomonas aeruginosa isolates using the efficacy time index assay.
abstract: We investigated the effectiveness of fosfomycin combined with other antibiotics, such as piperacillin, cefepime, ceftazidime, imipenem, meropenem, aztreonam, gentamicin, or levofloxacin, against 30 Pseudomonas aeruginosa strains, including multidrug-resistant strains, isolated from clinical specimens, using the efficacy time index (ETI) assay. The assay refers to the result of pharmacokinetics obtained from adult men volunteers, and yields an ETI to evaluate the effect of a combination of antimicrobial agents. With the ETI, based on serum concentration 3 h after the administration of two antimicrobial agents, the effectiveness of antimicrobial combinations was evaluated as follows: poor, ETI < 0.5; fair, 0.5 < or = ETI < 1; good, 1 < or = ETI < 8; and excellent, ETI > or = 8. The combination of fosfomycin and cefepime (efficacy rate [excellent plus good], 76.7%) and fosfomycin/aztreonam (efficacy rate, 76.7%) appeared to be the most effective, followed by fosfomycin/meropenem (efficacy rate, 76.6%), fosfomycin/imipenem (efficacy rate, 73.3%), fosfomycin/ceftazidime (efficacy rate, 70%), fosfomycin/gentamicin (efficacy rate, 70%), fosfomycin/piperacillin (efficacy rate, 66.7%), and fosfomycin/levofloxacin (efficacy rate, 66.7%). Fosfomycin/cefepime, fosfomycin/aztreonam, and fosfomycin/meropenem may be clinically useful in selected patients, particularly for P. aeruginosa. The ETI assay provided information on the minimum inhibitory concentration (MIC) of many pairs of combined antimicrobial agents simultaneously. The ETI assay may be a useful technique with which to investigate the effect of combinations of antimicrobial agents against P. aeruginosa, including multidrug-resistant strains.
authors.affiliation: Department of Clinical Laboratory, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. okazaki-kyr@umin.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okazaki
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Noriko
authors.initials: N
authors.lastname: Asano
authors.forename: Koji
authors.initials: K
authors.lastname: Araki
authors.forename: Naoko
authors.initials: N
authors.lastname: Shukuya
authors.forename: Teruo
authors.initials: T
authors.lastname: Egami
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Higurashi
authors.forename: Koji
authors.initials: K
authors.lastname: Morita
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Uchimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D005578:Fosfomycin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D005578:Fosfomycin