Cotrimoxazole
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Development of drug resistance: case report A woman in her 70’s [exact age not stated] developed resistance to cotrimoxazole while being treated for cystitis. The woman, who had recurrent cystitis, received oral cotrimoxazole [sulfamethoxazole/trimethoprim] daily comprised of 160 mg/day trimethoprim and 800 mg/day sulfamethoxazole intermittently. She had been receiving treatment with cotrimoxazole every time, when she had symptoms of cystitis. She had received treatment with cotrimoxazole for 4 days in March 2017, for 7 days in April 2017, for 11 days in January 2018, for 4 days in February 2018, for 3 days in October 2018, and for 3 days in December 2018. The urine culture in December 2018, revealed thymidine-dependent small-colony variant (TD-SCV) of Escherichia (E) coli producing extended-spectrum β-lactamase (ESBL). Broth dilution method using frozen plates had determined the minimum inhibitory concentrations (MICs) of the TD-SCV and wild-type (WT) E. coli isolates. Both the TD-SCV and WT isolates were resistant to quinolones, penicillins and cephalosporins (except for cefmetazole), and susceptible to carbapenems. Different patterns were detected in the susceptibilities of both cotrimoxazole and aminoglycosidic agents. The woman’s treatment with cotrimoxazole was discontinued, as the TD-SCV isolate was resistant to cotrimoxazole. Subsequently, she recovered from cystitis. A sequencing analysis to detect a mutation in the thyA gene was performed to clarify the mechanism of thymidine-dependency. The ORF of the thyA gene (795bp) of the SCV isolate was amplified and sequenced using primers Ec thyA-R (50-AAGGYGTCTCGAAGAATTTAAC-30) and Ec thyA-F (50-TTCCATCCCGATGATTGTC-30), which were designed based on the thyA sequences of E. coli ATCC 8739 (accession number CP000946) and E. coli ATCC 25922 (accession number CP009072). In the SCV isolate, the deletion c.681_682delGC was identified in the thyA gene. Based on these findings and clinical presentation it was concluded that the deletion in thyA gene had occurred during the course of cotrimoxazole, which might undergone mutational alteration from WT E. coli to the TD-SCV and resulted in the development of resistance to cotrimoxazole. Nagano N, et al. Isolation of thymidine-dependent and extended-spectrum-beta-lactamase-producing Escherichia coli small-colony variant from urine of a septuagenarian female patient with recurrent cystitis: A case report with genetic investigation. Journal of Infection and Chemotherapy 26: 1066-1069, No. 10, Oct 2020. Available from: 803502380 URL: http://doi.org/10.1016/j.jiac.2020.05.013
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Reactions 26 Sep 2020 No. 1823
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