Dataset Information

Piperacillin-Tazobactam (TZP) Resistance in Escherichia coli Due to Hyperproduction of TEM-1 ?-Lactamase Mediated by the Promoter Pa/Pb.

ABSTRACT: TEM-1, mediated by plasmid and transposon, is the most commonly encountered ?-lactamase in Gram-negative bacteria. Four different promoters upstream of bla TEM-related genes have been identified: the weak P3 promoter, and the strong promoters Pa/Pb, P4, and P5. In this study, we investigated the genetic basis of a clinical strain of Escherichia coli (RJ904), which was found to be resistant to BLBLIs (?-lactam/?-lactamase inhibitors), including amoxicillin-clavulanate, ticarcillin-clavulanate (TCC), and piperacillin-tazobactam (TZP) but sensitive to third-generation cephalosporins. The conjugation test and S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) demonstrated that transfer of this resistance was mediated by a ca. 100 kb plasmid. The transformant with TZP resistance was screened out with the shortgun cloning. Sequence analysis revealed that the recombinant plasmid contained a bla TEM-1b gene with the strong promoter Pa/Pb. Different plasmids were cloned based on the clone vector pACYC184 with the insertion of the bla TEM-1b gene with promoters Pa/Pb or P3. Susceptibility to TZP was determined by the E-test, agar dilution, and broth microdilution. The level of bla TEM-1b-specific transcription was determined by quantitative real-time PCR. Substitution of Pa/Pb for P3 resulted in a 128-fold decline of the MIC value of TZP, from >1024 mg/L to 8 mg/L, and a significantly lower bla TEM-1b expression level. Hyperproduction of TEM-1 ?-lactamase mediated by the promoter Pa/Pb was responsible for high resistance to TZP in E. coli. Our data show possible risks of resistance development in association with the clinical use of TZP. The bla TEM promoter modifications should be considered for whole genome whole-genome sequencing-inferred bacterial antimicrobial susceptibility testing.

SUBMITTER: Zhou K

PROVIDER: S-EPMC6476967 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Piperacillin-Tazobactam (TZP) Resistance in Escherichia coli Due to Hyperproduction of TEM-1 β-Lactamase Mediated by the Promoter Pa/Pb.

Zhou Kaixin K Tao Ying Y Han Lizhong L Ni Yuxing Y Sun Jingyong J

Frontiers in microbiology 20190416

TEM-1, mediated by plasmid and transposon, is the most commonly encountered β-lactamase in Gram-negative bacteria. Four different promoters upstream of bla TEM-related genes have been identified: the weak P3 promoter, and the strong promoters Pa/Pb, P4, and P5. In this study, we investigated the genetic basis of a clinical strain of Escherichia coli (RJ904), which was found to be resistant to BLBLIs (β-lactam/β-lactamase inhibitors), including ...[more]

PMID: 31040841

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Project description:ObjectivesPiperacillin/tazobactam combined with vancomycin has been associated with a decline in renal function when compared with monotherapy. Teicoplanin is a glycopeptide similar to vancomycin. We investigated whether piperacillin/tazobactam combined with teicoplanin is associated with a decline in renal function as well.MethodsWe conducted a single-centre retrospective cohort study with data from our electronic health records from 9 August 2013 to 15 November 2019, including all adult patients that received either piperacillin/tazobactam, teicoplanin or piperacillin/tazobactam + teicoplanin. The incidence of acute kidney injury (AKI) at 48-72 h served as the primary outcome, whereas change in serum creatinine served as a secondary outcome.ResultsOf the 4202 included patients, 3188 (75.9%) received piperacillin/tazobactam, 791 (18.8%) received teicoplanin and 223 (5.3%) received piperacillin/tazobactam + teicoplanin. The incidence of AKI at 48-72 h after commencement of antibiotic therapy was 5.4% for piperacillin/tazobactam, 3.4% for teicoplanin and 11.7% for piperacillin/tazobactam + teicoplanin (P < 0.001). However, mean serum creatinine at 48-72 h was slightly higher in the piperacillin/tazobactam + teicoplanin group therapy compared with baseline [+1.61% (95% CI -2.25 to 5.70)], indicating a slight decrease in renal function, and decreased for piperacillin/tazobactam [-1.98% (95% CI -2.73 to -1.22)] and teicoplanin [-8.01% (95% CI -9.54 to -6.45)]. After correcting for significant confounders in a multivariate linear regression analysis, these patterns remained.ConclusionsOur study suggests that piperacillin/tazobactam + teicoplanin is associated with a higher prevalence of AKI compared with monotherapy. However, as the overall decline in renal function with piperacillin/tazobactam + teicoplanin is very small, its clinical relevance is likely limited. Therefore, piperacillin/tazobactam + teicoplanin can probably be safely combined.

Dataset Information

Piperacillin-Tazobactam (TZP) Resistance in Escherichia coli Due to Hyperproduction of TEM-1 ?-Lactamase Mediated by the Promoter Pa/Pb.

Publications

Piperacillin-Tazobactam (TZP) Resistance in <i>Escherichia coli</i> Due to Hyperproduction of TEM-1 β-Lactamase Mediated by the Promoter <i>Pa/Pb</i>.

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