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Pharmacokinetics of Ceftazidime‐Avibactam in Two Patients With KPC ‐Producing Klebsiella pneumoniae Bacteremia and Renal Impairment
Author(s) -
Veillette John J.,
Truong James,
Forland Steven C.
Publication year - 2016
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1840
Subject(s) - ceftazidime/avibactam , medicine , avibactam , pharmacokinetics , klebsiella pneumoniae , ceftazidime , dosing , volume of distribution , bacteremia , renal function , gastroenterology , antibiotics , microbiology and biotechnology , biology , pseudomonas aeruginosa , biochemistry , genetics , escherichia coli , bacteria , gene
Limited data exist regarding optimal dosing of ceftazidime/avibactam (C/A) in patients with unique physiology, who were excluded from published clinical trials. Data are also lacking regarding clinical efficacy of C/A in patients with infections due to multidrug‐resistant gram‐negative pathogens. To expand knowledge in these areas, we present pharmacokinetic data from two patients with Klebsiella pneumoniae carbapenemase (KPC) ‐producing K. pneumoniae bloodstream infections, both of whom had renal impairment, and one of whom was morbidly obese. C/A was initiated in both patients at higher doses than those recommended in the package insert. To assess adequacy of dosing at steady state, a trough was drawn before and consecutive levels were drawn after a C/A dose such that half‐life and volume of distribution for ceftazidime and avibactam could be calculated using the Sawchuk–Zaske method. Both patients cleared their bloodstream infection without evidence of toxicity. Patient 1 and patient 2 had prolonged half‐lives for ceftazidime (22.8 and 14.5 hours, respectively) and avibactam (19.6 and 11.3 hours, respectively). Both patients had volumes of distribution significantly larger than those listed in the package insert: ceftazidime 47.1 L and 24.7 L and avibactam 50.3 L and 38.7 L for patients 1 and 2, respectively. Considering the larger volumes of distribution and levels observed in our patients, recommended doses and intervals may not be sufficient for obese patients with renal failure, especially for those infected with KPC ‐producing organisms. Additional efficacy and pharmacokinetic data are still needed for this agent to define optimal dosing strategies in patients commonly encountered in clinical practice.