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Journal of Antimicrobial Chemotherapy (2002) 50, 421-424
© 2002 The British Society for Antimicrobial Chemotherapy

Significance of low-level resistance to ciprofloxacin in Klebsiella pneumoniae and the effect of increased dosage of ciprofloxacin in vivo using the rat granuloma pouch model

Kurt Fuursted1,* and Helga Schumacher2

1 Department of Clinical Microbiology, Aarhus University Hospital, Aarhus Kommunehospital, DK-8000 Aarhus C; 2 Department of Clinical Microbiology, Viborg Sygehus, DK-8800, Viborg, Denmark

Received 21 November 2001; returned 3 April 2002; revised 24 May 2002; accepted 17 June 2002

This study was designed to compare the killing effect of ciprofloxacin on strains of Klebsiella pneumoniae with different MICs of ciprofloxacin in vivo using the rat granuloma pouch infection model. Five different strains were used: one ciprofloxacin-susceptible strain (MIC 0.06 mg/L); one strain highly resistant to ciprofloxacin (MIC 8 mg/L); and three nalidixic acid-resistant strains with low-level resistance to ciprofloxacin (MIC 0.25–0.5 mg/L). The efficacy of ciprofloxacin was evaluated 3 h after bacterial challenge (treating an acute infection) or after 3 days (treating a late infection) with a single intraperitoneal injection of ciprofloxacin (40 and 200 mg/kg). Ciprofloxacin was bactericidal against both growing K. pneumoniae (acute infection model) and non-growing K. pneumoniae (late infection model), but the extent of killing was significantly higher on growing bacteria and against ciprofloxacin-susceptible K. pneumoniae. A peak concentration of ciprofloxacin, at the infection site, <3 x MIC was not sufficient for optimal bacterial elimination. However, it was possible to compensate for the lower killing in low-level ciprofloxacin-resistant K. pneumoniae by increasing the dosage of ciprofloxacin from 40 to 200 mg/kg, consistent with the higher MIC.

* Corresponding author. Tel: +45-89-49-35-25; Fax: +45-89-49-35-50; E-mail: fuursted{at}rocketmail.com


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