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Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. CSL and TZP-nonsusceptible Enterobacteriaceae are typically resistant to extended-spectrum cephalosporins such as ceftriaxone (CRO). However, 11 nonrepetitive Enterobacteriaceae strains, which were resistant to CSL and TZP yet susceptible to CRO, were collected from January to December 2020. Antibiotic susceptibility tests and whole-genome sequencing were conducted to elucidate the mechanism for this rare phenotype. Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla  SHV-1 only, and four harbored bla  SHV-1 and bla  TEM-1B . Two Escherichia coli strains carried bla  TEM-1B only, while two Klebsiella oxytoca isolates harbored bla  OXY-1-3 and bla  OXY-1-1 , respectively. No mutation in the β-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae . Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum β-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae . Antibiotic susceptibility tests Antibiotics Breakpoint, (μg/ml) Klebsiella pneumoniae  Escherichia cou Klebriehd axyoca E1 E3 E4 E7 E9 E10 E11 E6 E8 E2 E5 CRO  ≤1≥4  ≤0.5  ≤0.5  ≤0.5  ≤0.5 1  ≤0.5  1  ≤0.5  ≤0.5  1  1  CAZ  4 ≥16  1  2  1  4  4  4  4  2  4  1 1  FEP  ≤2 216 1  1  0.25  1  2  2  2  0.5  2  1 1  AMC  ≤8 ≥32  ≥128  ≥128  ≥128  ≥128  ≥128  ≥128  ≥128  ≥128  ≥128  ≥128  ≥128  CSL  ≤16 ≥64  64  64  64  64  ≥128  128  ≥128  64  128  128  ≥128  TZP  ≤16 ≥128  ≥256  ≥256  ≥256  ≥256  2256  2256  ≥256  ≥256  ≥256  ≥256  ≥256  FPT  ≤2 ≥16  1  0.5  0.06  0.125  2  1  2  0.25  1  0.125  0.25  FPZ  ≤2 216  0.25  0.25  0.06  0.125  0.25  0.25 1  0.125  0.25  0.125  0.125  CZA  ≤8 216 1  0.5  0.25  0.25  1  0.25  1  0.5  0.5  0.5  0.25  CZT  ≤2 28  2  1  0.5 1  2  2  2 1  1  2  2 CROceftriaxone, CAZceftazidime, FEPcefepime, AMC:amoxicillin clavulanic-acid, CSLcefoperazone/sulbactam, TZP:piperadllin/tazobactam, FPT:cefepime tazobactam, FPZ:cefepime/zidebactam, CZA:ceftazidime/avibactam, CZTceftolozane/tazobactam Gene sequencing results Number Strain ST p-Lactamase gene Promoter sequence mutation Omp mutation El  Kpn  45  blaSHV-1, blaTEM-lB  none  OmpK36, OmpK3 7  E3  Kpn  45  blaSHV-1, blaTEM-lB  none  OmpK36. OmpK3 7  E4  Kpn  2854  blaSHV-1  none  OmpK36, OmpK3 7  E7  Kpn  2358  blaSHV-1 - blaTEM-lB  none  OmpK36, OmpK3 7  E9  Kpn  2358  blaSHV-1. blaTEM-lB  none  OmpK36. OmpK3 7  E10  Kpn 18  9  blaSHV-1  none  OmpK36. OmpK3 7  Ell  Kpn  45  blaSHV-1  none  OmpK36, OmpK3 7  E6  Eco  88  blaTEM-lB  none  none  ES  Eco  409  blaTEM-1B  none  none  E2  Kox  194  blaOXY-1-3  none  OmpK36 mutations. OmpK35 and OmpK 37 deficiency  E5  Kox 11  blaOXY-1-1  none  no OmpK (OmpK3 5, OmpK36 and OmpK37) gene found .

polish journal of microbiology

Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in <i>Enterobacteriaceae</i> Due to Narrow-Spectrum β-Lactamases as Well as Omp Mutation

Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in Enterobacteriaceae Due to Narrow-Spectrum β-Lactamases as Well as Omp Mutation