Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use.

OBJECTIVES: The worldwide rapid increase in antibiotic-resistant bacteria has made efforts to prolong the lifespan of existing antibiotics very important. Antibiotic resistance often confers a fitness cost in the bacterium. Resistance may thus be reversible if antibiotic use is discontinued or reduced. To examine this concept, we performed a 24 month voluntary restriction on the use of trimethoprim-containing drugs in Kronoberg County, Sweden. METHODS: The intervention was performed on a 14 year baseline of monthly data on trimethoprim resistance and consumption. A three-parameter mathematical model was used to analyse the intervention effect. The prerequisites for reversion of resistance (i.e. fitness cost, associated resistance and clonal composition) were studied on subsets of consecutively collected Escherichia coli from urinary tract infections. RESULTS: The use of trimethoprim-containing drugs decreased by 85% during the intervention. A marginal but statistically significant effect on the increase in trimethoprim resistance was registered. There was no change in the clonal composition of E. coli and there was no measurable fitness cost associated with trimethoprim resistance in clinical isolates. The frequency of associated antibiotic resistances in trimethoprim-resistant isolates was high. CONCLUSIONS: A lack of detectable fitness cost of trimethoprim resistance in vitro together with a strong co-selection of other antibiotics could explain the rather disappointing effect of the intervention. The result emphasizes the low possibility of reverting antibiotic resistance once established and the urgent need for the development of new antibacterial agents.

Antimicrobial resistance in Escherichia coli in urine samples from children and adults: a 12 year analysis.

AIM: To investigate the distribution and antimicrobial resistance in urinary tract pathogens, primarily Escherichia coli, in two age groups, children < or = 2 y and adults 18-50 y, over a period of 12 y. METHODS: From the database of the microbiological laboratory all urinary tract culture data were extracted and structured according to date, patient age, bacteriological findings, antimicrobial susceptibility results and sample type. Statistical longitudinal analysis of bacteriological findings and antimicrobial resistance trends in the two age groups were performed. RESULTS: Statistical significance was obtained for the following results. Escherichia coli was the most common pathogen in both age groups and irrespective of sample type. In E. coli resistance to ampicillin and trimethoprim was higher in children than in adults and increased over time in both age groups. Resistance to fluoroquinolones was higher in adults than in children and increased over time in both groups. Resistance to pivmecillinam, cefadroxil and nitrofurantoin was below 2% in 2001 in both age groups. CONCLUSION: The steadily increasing and now high E. coli resistance levels in children to ampicillin and trimethoprim render empirical therapy with these drugs doubtful. The stable and low levels of resistance to pivmecillinam, cefadroxil and nitrofurantoin (< 2% in 2001) make these drugs reasonable alternatives in uncomplicated lower urinary tract infections.