TABLE 1

K. pneumoniae isolates recovered from patients treated with ceftazidime-avibactama

Patient-isolate IDDays from admission to culture (source)Ceftazidime-avibactam exposure at time of culture (days)Ceftazidime-avibactamMIC (μg/ml)bKPC-3 variantcRelative fold change in blaKPC expression by qRT-PCRd
CeftazidimeMeropenemErtapenemPiperacillin-tazobactamCefepimeCeftriaxoneAztreonam
1-A6 (sputum)02 (S)512128256>512>128>128>256Wild-typeReference
1-B20 (sputum)10256>5120.5 (S)1>51216328D179Y, T243 M↓ 2.64-fold
1-C42 (sputum)24256>5120.25 (S)2>512163216D179Y, T243 MNPe
2-A7 (abscess)04 (S)256328>512>128>128>256Wild-typeReference
2-B48 (urine)1932>51288>512>128>128>256V240G<2-fold
2-C48 (urine)19>256>512416>5121648D179Y↓ 10.45-fold
2-D78 (urine)194 (S)25648>512>128>128>256T243A<2-fold
3-A6 (BALF)02 (S)256328>512>128>128>256Wild-typeReference
3-B64 (BALF)151285120.25 (S)12564164 (S)D179Y↓ 2.05-fold
3-C82 (BALF)15645120.125 (S)0.52568164 (S)D179YNP
  • a BALF, bronchoalveolar lavage fluid; S, susceptible, based on CLSI interpretive criteria (susceptibility breakpoints: ceftazidime-avibactam, ≤8 μg/ml; ceftazidime, ≤4 μg/ml; meropenem, ≤1 μg/ml; piperacillin-tazobactam, ≤16 μg/ml; cefepime, ≤2 μg/ml; ceftriaxone, ≤1 μg/ml; aztreonam, ≤4 μg/ml). Boldface rows represent baseline isolate from each patient.

  • b MICs within the susceptible range are indicated by “(S)”; all other MICs indicated resistance.

  • c When relevant, amino acid substitutions within KPC-3 are listed.

  • d RT-PCR was performed for a representative isolate from each patient that expressed a given KPC-3 variant. Data show differences in gene expression relative to the corresponding baseline isolate (reference).

  • e NP, RT-PCR not performed.