The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community-acquired urinary tract infections (ca-UTIs) caused by ESBL-producing Escherichia coli. Eighty-nine ESBL-producing E. coli isolated from women suffering from ca-UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was performed on a MiSeq platform, and genome assembly was performed using SPAdes v3.11.0. Neither mecillinam MICs nor ESBL genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with ST131 were more likely to experience treatment failure compared to patients infected with non-ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with ST69 were more often successfully treated compared to patients infected with non-ST69 (p 0.04). Patients infected with blaCTX-M-15 ST131 strains were more likely to experience treatment failure than those infected with non-blaCTX-M-15 ST131 strains (p 0.02). The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results.

中文翻译：

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在生产ESBL的大肠杆菌引起的社区获得性尿路感染中吡维西南治疗失败的微生物危险因素。

这项研究的目的是确定在生产ESBL的大肠杆菌引起的社区获得性尿路感染（ca-UTIs）中吡维西南治疗失败的微生物危险因素。包括从患有ca-UTI的妇女中分离出的89个产生ESBL的大肠杆菌。使用MIC梯度试纸测定对美西林的敏感性。在MiSeq平台上进行全基因组测序，并使用SPAdes v3.11.0进行基因组组装。美西林MIC和ESBL基因型均与吡美西那治疗的患者的治疗结果无关。但是，特定的ST表现出治疗效果的显着差异。与非ST131感染的患者相比，经pivmecillinam剂量调整后，感染ST131的患者更有可能经历治疗失败，（p 0.02），美西林MIC和感染的严重程度。与非ST69感染的患者相比，ST69感染的患者更常被成功治疗（p = 0.04）。感染blaCTX-M-15 ST131菌株的患者比未感染blaCTX-M-15 ST131菌株的患者更有可能出现治疗失败（p 0.02）。结果表明，特定的STs与匹维西南的临床疗效有关。为了证实这些结果，需要对更多的菌株进行进一步的研究，包括更多的耐美西林的菌株。感染blaCTX-M-15 ST131菌株的患者比未感染blaCTX-M-15 ST131菌株的患者更有可能出现治疗失败（p 0.02）。结果表明，特定的STs与匹维西南的临床疗效有关。为了证实这些结果，需要对更多的菌株进行进一步的研究，包括更多的耐美西林的菌株。感染blaCTX-M-15 ST131菌株的患者比未感染blaCTX-M-15 ST131菌株的患者更有可能出现治疗失败（p 0.02）。结果表明，特定的STs与匹维西南的临床疗效相关。为了证实这些结果，需要对更多的菌株进行进一步的研究，包括更多的耐美西林的菌株。