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J Antimicrob Chemother. 1991 Aug;28(2):185-98.
Phenotypic characterization of quinolone-resistant mutants of Enterobacteriaceae selected from wild type, gyrA type and multiply-resistant (marA) type strains.

Piddock LJ, Hall MC, Walters RN.

Medical School, University of Birmingham, UK.

The NCTC type strains of Escherichia coli, Enterobacter cloacae, Serratia marcescens and Klebsiella pneumoniae were exposed to 3, 5 and 10 x MIC of nalidixic acid, enoxacin, ciprofloxacin, PD 117596 and PD 127391. From each strain a mutant with a high MIC of quinolones alone (gyrA) and a mutant with intermediate resistance to quinolones, some beta-lactams, chloramphenicol and tetracycline (multiply resistant, m-r) were selected on agar containing antibiotics. The gyrA mutants required a higher concentration of quinolone to inhibit DNA synthesis by 50% but quinolone uptake kinetics and outer membrane profile were the same as the wild type. The m-r mutants had similar DNA synthesis IC50 as the wild type, decreased quinolone uptake kinetics and had decreased expression of an OMP of approximately 40 kD. The gyrA and m-r mutants were then exposed to 3, 5 and 10 x MIC of the same quinolones and new mutants (F2) selected. The F2 mutants from the gyrA mutants displayed a further increase in quinolone MIC; the F2 mutants from the m-r mutants had several phenotypes: high quinolone MICs with cross resistance to other agents, high quinolone resistance alone, or intermediate quinolone resistance alone. Most F2 mutants had MICs above the recommended breakpoint concentrations for quinolones. The F2 mutants often had altered biochemical profiles (API 20E), however, only in the case of E. cloacae did this affect speciation with the strains being identified as Rhanella aquatalis.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1663926&dopt=Abstract




Med J Aust. 1992 Jan 6;156(1):20-4.
Resistance to ciprofloxacin of respiratory pathogens in patients with cystic fibrosis.

Dostal RE, Seale JP, Yan BJ.

Department of Pharmacology, University of Sydney, NSW.

OBJECTIVE: To determine the incidence of resistance to ciprofloxacin in respiratory pathogens isolated from patients with cystic fibrosis (CF) compared with that of isolates from patients without CF. The hypothesis was that repeated exposure of these respiratory pathogens to ciprofloxacin would reduce their sensitivity. DESIGN: Isolates of Pseudomonas aeruginosa and Staphylococcus aureus were obtained prospectively from sputa of patients with CF, as part of their routine care. The sensitivities of these isolates to ciprofloxacin were determined by standard agar dilution techniques. SETTING AND PATIENTS: The study was carried out in patients who attended the outpatient clinic or were treated as inpatients of a tertiary referral hospital. Sputa were obtained from 71 patients with CF (age range, 2-31 years) and isolates of P. aeruginosa and S. aureus were compared with those from 54 hospital patients who did not have CF. OUTCOME MEASURES: Sensitivities to ciprofloxacin, expressed as the minimal concentrations required to inhibit growth of the organisms (MIC), were used to make comparisons between different isolates and the same isolates within patients at different times. RESULTS: A higher incidence of ciprofloxacin resistance was displayed by isolates of P. aeruginosa from CF patients who had been previously prescribed ciprofloxacin (MIC50 of 2.0 mg/L and 4.0 mg/L for mucoid and non-mucoid strains respectively). The MIC of individual organisms tended to rise after a course of ciprofloxacin had been given to their host. A much lower incidence of resistance was displayed by isolates of P. aeruginosa from patients without CF (MIC50, 0.25 mg/L). Similarly, S. aureus isolates from patients with CF exhibited greater resistance to ciprofloxacin (MIC50, 32 mg/L) than isolates from other patients (MIC50, 0.75 mg/L). CONCLUSION: The resistance of P. aeruginosa appears to be related to ciprofloxacin exposure, so further development of resistance may be diminished by restricting the frequency of ciprofloxacin administration to individual patients.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1734188&dopt=Abstract




Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):168-71.
Antistaphylococcal activity of the fluoroquinolones CI-960, PD 131628, sparfloxacin, ofloxacin and ciprofloxacin.

Barry AL, Fuchs PC.

Clinical Microbiology Institute, Tualatin, Oregon 97062.

Five fluoroquinolones were tested against 300 staphylococci from a wide variety of US medical centers including 150 strains resistant to penicillinase-resistant penicillins (PRP-resistant). Ten ciprofloxacin-resistant strains of PRP-resistant Staphylococcus aureus were relatively resistant to the other fluoroquinolones, but the remaining 290 isolates were susceptible to all five drugs at established or anticipated breakpoint concentrations. The relative potency of the study drugs could be ranked as follows: CI-960 greater than PD 131628 greater than sparfloxacin greater than ciprofloxacin greater than ofloxacin. All five drugs were bactericidal against PRP-resistant and PRP-susceptible staphylococci.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2060518&dopt=Abstract












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