Endocarditis caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae: emergence of resistance to ciprofloxacin and piperacillin-tazobactam during treatment despite initial susceptibility

Abstract

Three episodes of bacteremia occurred in the course of prosthetic valve endocarditis caused by an extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The second isolate developed resistance to ciprofloxacin and the third isolate to piperacillin-tazobactam (PIP-TZ) following sequential therapy with each agent. The first isolate was resistant to PIP-TZ only at high inocula, the second isolate acquired increased transcription of the acrA gene, and the third isolate became resistant to PIP-TZ due to loss of beta-lactamase inhibition by TZ. We question if and how PIP-TZ susceptibility should be reported for ESBL-producing Enterobacteriaceae.

FIG. 1.

Clinical course of treatment, including documentation of bacteremia and antimicrobial regimens used, for the patient described in the text. Cefepime was given at a dose of 2 g twice a day, ciprofloxacin at 400 mg twice a day, piperacillin-tazobactam at 4.5 g three times a day, amikacin at 500 mg twice a day, and meropenem at 1 g three times a day.

FIG. 2.

Determination of β-lactamase activity in cell-free crude extract by use of nitrocefin hydrolysis with and without tazobactam. β-Lactamase activity is expressed as units per milligram protein per minute.