Effect of Sub-Inhibitory Concentrations of Nitrofurantoin, Ciprofloxacin, and Trimethoprim on In Vitro Biofilm Formation in Uropathogenic Escherichia coli (UPEC).

The purpose of this study was to determine the effect of sublethal concentrations of nitrofurantoin, ciprofloxacin, and trimethoprim on biofilm formation in 57 uropathogenic Escherichia coli strains (UPEC). The minimum inhibitory concentration of nitrofurantoin, ciprofloxacin, and trimethoprim was determined and the biofilm formation for each isolate with and without sub-lethal concentrations of each antibiotic was then quantified. The statistical significance of changes in biofilm formation was ascertained by way of a Dunnett's test. A total of 22.8% of strains were induced to form stronger biofilms by nitrofurantoin, 12% by ciprofloxacin, and 19% by trimethoprim; conversely 36.8% of strains had inhibited biofilm formation with nitrofurantoin, 52.6% with ciprofloxacin, and 38.5% with trimethoprim. A key finding was that even in cases where the isolate was resistant to an antibiotic as defined by EUCAST, many were induced to form a stronger biofilm when grown with sub-MIC concentrations of antibiotics, especially trimethoprim, where six of the 22 trimethoprim resistant strains were induced to form stronger biofilms. These findings suggest that the use of empirical treatment with trimethoprim without first establishing susceptibility may in fact potentiate infection in cases where a patient who is suffering from a urinary tract infection (UTI) caused by trimethoprim resistant UPEC is administered trimethoprim. This emphasizes the need for laboratory-guided treatment of UTI.

Uropathogenic Escherichia coli Biofilm-Forming Capabilities are not Predictable from Clinical Details or from Colonial Morphology.

Antibiotic resistance is increasing to an extent where efficacy is not guaranteed when treating infection. Biofilm formation has been shown to complicate treatment, whereby the formation of biofilm is associated with higher minimum inhibitory concentration values of antibiotic. The objective of the current paper was to determine whether biofilm formation is variable among uropathogenic Escherichia coli isolates and whether formation is associated with recurrent urinary tract infection (UTI), and whether it can be predicted by phenotypic appearance on culture medium A total of 62 E. coli isolates that were reported as the causative agent of UTI were studied (33 from patients denoted as having recurrent UTI and 29 from patients not specified as having recurrent UTI). The biofilm forming capability was determined using a standard microtitre plate method, using E. coli ATCC 25922 as the positive control. The majority of isolates (93.6%) were found to be biofilm formers, whereby 81% were denoted as strong or very strong producers of biofilm when compared to the positive control. Through the use of a Wilcox test, the difference in biofilm forming propensity between the two patient populations was found to not be statistically significant (p = 0.5). Furthermore, it was noted that colony morphology was not a reliable predictor of biofilm-forming propensity. The findings of this study indicate that biofilm formation is very common among uropathogens, and they suggest that the biofilm-forming capability might be considered when treating UTI. Clinical details indicating a recurrent infection were not predictors of biofilm formation.

Empirical treatment of urinary tract infections: how rational are our guidelines?

Objectives: This study considers susceptibility test results obtained over a 6 month period for Enterobacteriaceae that caused urinary tract infections (UTIs) in the Cork region of Ireland and uses these results to examine the suitability of Irish empirical treatment guidelines. Patients and methods: UTI-causing Enterobacteriaceae isolates were analysed using EUCAST guidelines to determine resistance to a set of commonly prescribed antimicrobial agents, i.e. ampicillin, amoxicillin/clavulanate, cefalexin, ciprofloxacin, nitrofurantoin and trimethoprim. Patients were categorized by age and patient type, based on origin (hospital inpatients, patients in long-term care facilities and all other non-hospitalized patients). In total, 8999 test results were analysed using the IBM Cognos Analytics Series 7 interrogation tool and Microsoft Office Excel. Results: A variety of resistance patterns were observed. Only one antimicrobial agent, nitrofurantoin, demonstrated a resistance rate of less than 20% for all patient categories considered. Conclusions: Previous studies determined that a resistance rate of >20% renders an antimicrobial agent unsuitable for use as an empirical treatment option. This study demonstrated that this resistance rate is exceeded in many cases, potentially rendering some antimicrobial agents unsuitable for use as empirical treatment. We suggest that the focus on susceptibility when producing surveillance data to create empirical treatment guidelines may inadvertently camouflage resistance rates. The findings of this study highlight the need for laboratory-guided treatment of UTIs and ideally a pre-emptive sample should be obtained for laboratory investigation prior to commencement of antimicrobial therapy.