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

Abstract

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.

Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

“…These plasmids have rapidly spread resistance to third-generation cephalosporins and other antibiotics [ 162 , 164 , 165 , 167 , 169 ]. Several studies have reported that UPEC isolates are resistant to ampicillin [ 166 ], oral first-generation cephalosporins, TMP-SMX [ 156 ], cefuroxime [ 170 ], cotrimoxazole [ 171 ], amoxicillin-clavulanate [ 169 ], nalidixic acid [ 172 ], cefradine [ 173 ], and aminopenicillins [ 174 ]. Figure 7 depicts the representative antibiotic structural formulations whose resistance to UPEC has been demonstrated (orange background) and those showing susceptibility to UPEC (purple background).…”

“…Sci. 2023, 24, x 1 cefuroxime [170], cotrimoxazole [171], amoxicillin-clavulanate [169], nalidixic acid cefradine [173], and aminopenicillins [174]. Figure 7 depicts the representative ant structural formulations whose resistance to UPEC has been demonstrated (orange ground) and those showing susceptibility to UPEC (purple background).…”

Clinical and epidemiological characteristics and frequent symptomatology of patients with urinary tract infections in a General Hospital in Paraguay during the year 2022

“…La prevalencia de infecciones urinarias por E. coli es muy frecuente según numerosos estudios. (15,16,17,18,19) En cuanto a los síntomas, los vómitos fueron el síntoma más frecuente, esta alta incidencia de vómitos podría sugerir que es un síntoma comúnmente asociado con la condición clínica estudiada. (20) Otra manifestación clínica relevante fue la disminución de la micción.…”

Uropathogenic Escherichia coli (UPEC)-Associated Urinary Tract Infections: The Molecular Basis for Challenges to Effective Treatment

“…Additionally, biofilm formation was significantly correlated with the pap adhesion gene [ 30 ].A study from Iran reported statistically higher levels of papEF in strong biofilm formers, and the adhesion genes fimH , focG , sfaS , set-1 , and cvaC were more common in weaker biofilm formers [ 31 ]. We have previously shown that the biofilm forming tendencies of UPEC isolates are variable and not apparent from colony morphology, and that sub-inhibitory concentrations of ciprofloxacin and trimethoprim can, in some cases induce UPEC isolates to form stronger biofilms in vitro, even when resistant to antibiotics [ 119 , 120 ].…”