Dissociation of Pharmacokinetic-Pharmacodynamic Success and Clinical Failure of Tazobactam/Piperacillin in Escherichia coli Bacteremia: A Case Report

Abstract

An 84-year-old woman presenting with fever and the right lower guardant pain was found to have ischemic colitis and left renal abscess on CT scan findings, and started on empiric antimicrobial therapy with intravenous tazobactam/piperacillin (TAZ/PIPC) 4.5 g q8h. The blood culture prior to TAZ/PIPC grew Escherichia coli (E. coli) with MIC of 2 g/mL. The patients fever still continued; however, the follow-up blood cultures on another three occasions all demonstrated intermittent E. coli bacteremia despite continuation of TAZ/PIPC (MIC ranging from ? 2 to 16 g/mL). To make sure proper distribution of the drug, the pharmacokinetic parameters were quantitated after 18 dosing based on the serum concentration of TAZ/PIPC applied to the Sawchuk-Zaske equation: the serum peak/trough levels for PIPC and TAZ were 269/11 g/mL and 41/5 g/mL, with the time above MIC (T > MIC) of PIPC ranging from 70% to 100%. The volume of distribution of PIPC was 13.82 L, total clearance 98.89 mL/min, elimination rate constant (kel) 0.43 h^-1, and resultant plasma half-life (0.693/kel) 1.6 h. Although T > MIC thus reflected optimal pharmacokinetics of TAZ/PIPC against Gram-negative blood stream infection, since blood cultures remained positive, the antimicrobial regimen was switched to intravenous pazufloxacin and tobramycin. The altered therapeutic regimen resulted in sterilization of the blood culture and gradual disappearance of the renal abscess. To the best of our literature search, this case report is the first to demonstrate on the basis of patients pharmacokinetic profile that the maximal attainment of pharmacological target of beta-lactam (T > MIC) does not always provide reassurance of successful treatment of blood stream infections.




J Med Cases. 2013;4(12):820-824
doi: https://doi.org/10.4021/jmc1494w