Quinolone resistance inPseudomonas aeruginosa andStaphylococcus aureus. Development during therapy and clinical significance

Abstract

This review focuses on published information on the experimental as well as clinical data on the emergence of quinolone resistant isolates. In the course of clinical use of fluoroquinolones, only a sporadic emergence of quinolone resistance has been noted. The resistant organisms emerged particularly in certain clinical settings where large numbers of organisms frequently causing chronic infections are present and/or in loci where quinolone concentrations may not be optimal. In terms of occurrence in individuals, quinolone resistance has emerged most frequently in hospitalized and nursing-home patients with identifiable risk factors. Epidemiological studies revealed that in nearly all the cases studied one or one predominating quinolone resistant clone was selected that was horizontally transmitted. Thus, the emergence of quinolone resistance is not due to an independent selection of resistant strains in a number of patients, but to the clonal spread of one strain once it has acquired quinolone resistance. Therefore, the rate of quinolone resistance is very likely to be lower than reported.

Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use

“…High rates of fluoroquinolone resistance were found in patients with HAUTIs evaluated in the emergency department [109, 110] and in nursing home residents [111]. Horizontal transmission of one, or few predominating clone(s) in nursing home residents is frequent [2]. …”

“…Especially in experimental endocarditis caused either by MSSA or MRSA fluoroquinolones proved effective and were not associated with the development of fluoroquinolone resistance in most of the models. In addition, their in vivo activity was equivalent or even superior to that of vancomycin or imipenem [2, 316, 317]. …”

“…Despite millions of prescriptions in the first two decades of their use, the emergence of quinolone resistance during treatment was uncommon except in Staphylococcus aureus particularly in methicillin-resistant S. aureus and P. aeruginosa . Resistance to fluoroquinolones emerged rapidly in these two species, predominantly due to clonal spread among nursing home residents and immunocompromised patients [2]. However, since the mid 1990s quinolone resistance started to increase in almost all Gram-positive and Gram-negative species and minimal concentrations (MICs) inhibiting 90% of the strains studied varied species specifically over a broad range from ≤0.015 up to ≥128 mg/L [3–5] thus indicating that resistant subpopulations were frequent already two decades ago but passed almost unnoticed.…”

Phenotypic Resistance of Staphylococcus aureus , Selected Enterobacteriaceae , and Pseudomonas aeruginosa after Single and Multiple In Vitro Exposures to Ciprofloxacin, Levofloxacin, and Trovafloxacin

“…Despite widespread use over 10 or more years, selection of resistant clones has been modest. Clinically significant resistance to ciprofloxacin has occurred for Staphylococcus aureus (especially methicillin-resistant S. aureus [MRSA]), Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Acinetobacter baumanii (1,3,12,19). Surprisingly, resistance of Enterobacteriaceae has been modest.…”

Design, synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

“…[2][3][4][5] One particularly alarming sign is the acquisition of resistance to vancomycin (VRE and vancomycin-resistant staphylococcal strains), an antibiotic generally regarded as the agent of last resort for hospital-acquired infections. 2,[4][5][6] In the field of quinolone antibacterial agents, various attempts have been made to obtain potent drugs for resistant Gram-positive bacteria, and trovafloxacin, 7 moxifloxacin, 8 gemifloxacin, 9 and gatifloxacin, 10 etc., have been developed and introduced into clinical use over the last few years.…”