title: In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.
abstract: We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants.
authors.affiliation: Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Clark
authors.forename: Klaudia
authors.initials: K
authors.lastname: Kosowska
authors.forename: Bülent
authors.initials: B
authors.lastname: Bozdogan
authors.forename: Kim
authors.initials: K
authors.lastname: Credito
authors.forename: Bonifacio
authors.initials: B
authors.lastname: Dewasse
authors.forename: Pamela
authors.initials: P
authors.lastname: McGhee
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: Peter C
authors.initials: PC
authors.lastname: Appelbaum
mesh_terms: D024881:Drug Resistance, Bacterial; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D015363:Quinolones; D047090:beta-Lactams