International Journal of Antimicrobial Agents 12 (1999) 33 – 39 Original article In vitro activity of clinafloxacin against fluoroquinolone resistant Spanish clinical isolates  Manuel Lo ´ pez-Brea *, Nuria Prieto, Diego Domingo, Carmen de las Cuevas, Isabel Sa ´nchez, Teresa Alarco ´n Department of Microbiology, Hospital Uniersitario de la Princesa, Diego de Leo ´n 62, 28006 Madrid, Spain Received 16 October 1998; revised manuscript accepted 8 December 1998 Abstract The in vitro activity of clinafloxacin against 162 ciprofloxacin-resistant clinical isolates was determined. Isolates were selected when their MIC to ciprofloxacin was 2 mg/l (intermediate) or 2 mg/l (resistant). The following strains were tested: 61 Escherichia coli, 12 Klebsiella pneumoniae,7 Proteus mirabilis, 21 Serratia marcescens,4 Enterobacter cloacae, 21 Pseudomonas aeruginosa, 21 Staphylococcus. aureus (resistant to methicillin) and 15 Enterococcus spp. Clinafloxacin, ciprofloxacin, ofloxacin and norfloxacin activities were evaluated by agar dilution using Mu ¨ eller – Hinton agar according to NCCLS recommendations. Of the 162 isolates, 16 (9.8%) were intermediate and 146 (90.1%) resistant to ciprofloxacin. 95 of the 162 strains (58.6%) were susceptible, 27 (16.7%) intermediately susceptible, and 40 strains (24.7%) were resistant to clinafloxacin. The percentage susceptible to clinafloxacin was 65.6% for E. coli, 75% for K. pneumoniae, 71.4% for P. mirabilis, 28.6% for S. marcescens, 75% for E. cloacae, 33.3% for P. aeruginosa, 90.5% for S. aureus and 40% for Enterococcus spp. Clinafloxacin was active against 58.6% of the ciprofloxacin-resistant clinical isolates tested. It was particularly active against S. aureus strains resistant to both ciprofloxacin and methicillin. © 1999 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. Keywords: Fluoroquinolones; Resistance; Clinafloxacin 1. Introduction Quinolones have become important over the last 10 years as a group of antibiotics available in both oral and parenteral formulations for the treatment of infec- tions caused by a wide range of bacterial pathogens. Typically, fluoroquinolones have potent antibacterial activities against gram-negative microorganisms, espe- cially against members of the Enterobacteriaceae [1], but remain only modestly active against some groups of bacteria, particularly gram-positive cocci and anaerobes. Recently, fluoroquinolone-resistant isolates have been recognised in many species, but mainly among Gram-positive cocci and Pseudomonas spp, rather than members of the Enterobacteriaceae [2]. However, clini- cal isolates of Serratia spp, Enterobacter spp, Proteus spp, Escherichia coli and Klebsiella pneumoniae resistant to fluoroquinolones have been reported [3]. Mutations in the gyr A and gyr B genes (encoding to the gyrase A and B subunit) and lack of outer mem- brane permeability have been described in clinical iso- lates of E. coli and K. pneumoniae [4] and have usually shown cross resistance to the older fluoroquinolone. New mechanisms such as efflux transport and muta-  This work was presented in part at the 37th Interscience Confer- ence on Antimicrobial Agents and Chemotherapy, Toronto 28 Sep- tember to 3 October 1997. * Corresponding author. Tel.: +34-91-309-0047; fax: +34-91-309- 0047. E-mail address: mlbrea@microb.net (M. Lo ´ pez-Brea) 0924-8579/99/$ - see front matter © 1999 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. PII:S0924-8579(99)00054-0