Trends in Fluoroquinolone (Ciprofloxacin) Resistance in Enterobacteriaceae from Bacteremias, England and Wales, 1990-1999

David M. Livermore, Dorothy James, Mark Reacher, Catriona Graham, Thomas Nichols, Peter Stephens, Alan P. Johnson, and Robert C. George


Emerging Infectious Diseases. 2002;8(5) 

In This Article

Abstract and Introduction

The Public Health Laboratory Service receives antibiotic susceptibility data for bacteria from bloodstream infections from most hospitals in England and Wales. These data were used to ascertain resistance trends to ciprofloxacin from 1990 through 1999 for the most prevalent gram-negative agents: Escherichia coli, Klebsiella spp., Enterobacter spp., and Proteus mirabilis. Significant increases in resistance were observed for all four species groups. For E. coli, ciprofloxacin resistance rose from 0.8% in 1990 to 3.7% in 1999 and became widely scattered among reporting hospitals. The prevalence of resistance in Klebsiella spp. rose from 3.5% in 1990, to 9.5% in 1996 and 7.1% in 1999, while that in Enterobacter spp. rose from 2.1% in 1990 to 10.5% in 1996 and 10.9% in 1999. For both Klebsiella and Enterobacter spp., most resistance was localized in a few centers. Resistance was infrequent and scattered in P. mirabilis, but reached a prevalence of 3.3% in 1999.

Fluoroquinolone antimicrobial drugs were a major therapeutic advance of the 1980s because they have 100-fold greater activity than their parent compound, nalidixic acid[1]. Unlike nalidixic acid, which is used only for urinary infections and occasionally shigellosis, the fluoroquinolones have a broad range of therapeutic indications and are given as prophylaxis, e.g., for neutropenic patients. In veterinary medicine fluoroquinolones are used as treatment and metaphylaxis but not as growth promoters. Early researchers thought that fluoroquinolone resistance was unlikely to evolve, largely because resistant Escherichia coli mutants are exceptionally difficult to select in vitro[2] and because plasmid-mediated quinolone resistance remained unknown even after 30 years of nalidixic acid usage. Nevertheless, mutational fluoroquinolone resistance emerged readily in staphylococci and pseudomonads, which are inherently less susceptible than E. coli. More recently, fluoroquinolone resistance has emerged in E. coli and other Enterobacteriaceae, contingent on multiple mutations that diminish the affinity of its topoisomerase II and IV targets in varying ways, reduce permeability, and upregulate efflux[3]. Plasmid-mediated quinolone resistance has been reported, but it is exceptional[4].

We report here resistance trends to ciprofloxacin, the most widely used fluoroquinolone in the United Kingdom, in the prevalent Enterobacteriaceae species from bacteremias in England and Wales during the 1990s.


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