Clinically significant borderline resistance of sequential clinical isolates of Klebsiella pneumoniae

Wagenlehner, F. M. E. and Heisig, P. and Irtenkauf, C. and Notka, F. and Decker, J. and Lehn, N. and Linde, H. (2003) Clinically significant borderline resistance of sequential clinical isolates of Klebsiella pneumoniae. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 22 (4). pp. 367-373. ISSN 0924-8579

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Abstract

Two sequential clinical isolates of Klebsiella pneumoniae (Kpn) were isolated from bronchoalveolar lavage fluid (Kpn#1) and sputum (Kpn#2) of a patient with pneumonia, complicated by anatomical and immunosuppressive problems due to Wegener's granulomatosis. Despite 4 weeks of systemic treatment with ciprofloxacin (CIP) Kpn#2 was isolated thereafter. A fluoroquinolone-resistant mutant (Kpn#1-SEL) was derived from Kpn#1 in vitro by selecting on agar plates supplemented with ofloxacin. Kpn#1, Kpn#1-SEL and Kpn#2 had an identical pattern in PFGE. CIP MICs were 0.25, 2 and 4 mg/l for Kpn#1, Kpn#2 and Kpn#1-SEL, respectively. Kpn ATCC 10031 (CIP MIC 0.002 mg/l) served as control. We analyzed mechanisms of fluoroquinolone resistance by deter-mining antibiotic susceptibility, organic solvent tolerance, accumulation of fluoroquinolones, dominance testing with wild-type topoisomerase genes (gyrA/B, parC/E), sequencing of the quinolone resistance determining regions of gyrA/B, parC/E and marR and Northern blotting of marR and acrAB genes. Compared with Kpn ATCC 10031, elevated MICs to fluoroquinolones and unrelated antibiotics in Kpn#1 was presumably due to a primary efflux pump other than AcrAB and increased the CIP MIC 125-fold. Although Kpn#1 tested sensitive according to NCCLS breakpoints, the elevated CIP MIC of 0.25 mg/l presumably rendered this isolate clinically resistant and lead to therapeutic failure in this case. Further increase of MIC to fluoroquinolones in vivo and in vitro was distinct. Kpn#1-SEL, selected in vitro, acquired a GyrA target mutation, whereas in Kpn#2 no known resistance mechanism could be detected. (C) 2003 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Item Type: Article
Uncontrolled Keywords: MULTIPLE-ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; FLUOROQUINOLONE RESISTANCE; CIPROFLOXACIN; OVEREXPRESSION; MUTATIONS; STRAINS; MUTANTS; GENE; fluoroquinolone resistance; clinical aspects; efflux; Klebsiella pneumoniae
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 Aug 2021 10:26
Last Modified: 04 Aug 2021 10:26
URI: https://pred.uni-regensburg.de/id/eprint/38556

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