Ciprofloxacin : Use and resistance in Community, Nursing Home and Hospital

Abstract

The aim of the studies described in this thesis was to analyze some aspects of ciprofloxacin use and clinical and (molecular) epidemiology of ciprofloxacin resistance in different settings, both within hospitals (chapter 3,4 and 6), community and nursing homes (chapter 2 and 5). With its broad spectrum against gram negative organisms and favorable pharmacokinetics, ciprofloxacin use has increased over the last two decades, as did resistance against ciprofloxacin. Chapter 2 describes a nation-wide epidemiological analysis of culture-proven Campylobacter infections in the Netherlands over the years 2000-2004 and the effect of region, degree of urbanization and season on the incidence of campylobacteriosis and development of resistance. High stable rates of resistance to fluoroquinolones (35%) were observed and resistance was higher in travel related infections (54%) than in endemic infections (33%). The high resistance rates to fluoroquinolones warrants reconsideration of its use as drug of first choice in the empiric treatment of gastrointestinal infections in the Netherlands. In chapter 3 the effects of intervention to reduce and improve ciprofloxacin use in a hospital have been described. Despite relatively low baseline ciprofloxacin consumption, intervention led to 3-4 fold sustained reduction in the use of ciprofloxacin and significant improvement in quality of ciprofloxacin prescription. Close collaboration within a hospital between medical microbiologists and clinicians is an important condition to reduce liberal and inappropriate use of antibiotics. Chapter 4 describes our randomized double-blind placebo-controlled trial where ciprofloxacin use appeared not beneficial at all in reducing occurrence of significant bacteriuria and urinary tract infection after catheter removal. We determined the prevalence and molecular epidemiology of ESBL-producing and of ciprofloxacin-resistant Enterobacteriaceae in a teaching hospital and nursing homes in its immediate catchment area in a point prevalence and retrospective analysis in chapter 5. Our findings demonstrate a persistently high prevalence of ciprofloxacin-resistant (26%) and ESBL-producing (7%) Enterobacteriaceae in nursing home residents. In chapter 6 we investigated the evolution of ciprofloxacin resistance and molecular epidemiology of clinical E. coli isolates in haematology patients receiving ciprofloxacin prophylaxis on the population and individual patient level. We provide evidence for cross-transmission of ciprofloxacin resistant E. coli and in vivo mutation to a resistant phenotype of previously sensitive E. coli strains (in 7% of patients). In our study we observe that in 27% of patients ciprofloxacin-resistant E. coli strains can be demonstrated. Resistance to antibiotics is becoming an increasingly important worldwide problem. Inappropriate use of antibiotics is considered to be the most important reason for development of antibiotic resistance. Antibiotic pressure in the community, hospitals and nursing homes, should be reduced by a shift to treatment based on results of microbiologic investigation rather than empiric treatment. Given large quantities of antibiotics currently use in veterinary medicine, judicious and targeted use of antibiotics in clinical medicine alone will not be enough to prevent ever increasing levels of resistance. The use of veterinary antimicrobial drugs associated with induction of resistance to antibiotics in humans should be limited, preferably by government regulations