title: Pharmacokinetics of Ceftazidime-Avibactam in Two Patients With KPC-Producing Klebsiella pneumoniae Bacteremia and Renal Impairment.
abstract: 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.
authors.affiliation: Loma Linda University School of Pharmacy, Loma Linda, California.
authors.forename: John J
authors.initials: JJ
authors.lastname: Veillette
authors.affiliation: Loma Linda University School of Pharmacy, Loma Linda, California.
authors.forename: James
authors.initials: J
authors.lastname: Truong
authors.affiliation: Loma Linda University School of Pharmacy, Loma Linda, California.|Department of Pharmacy, Loma Linda University Medical Center, Loma Linda, California.|Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Forland
mesh_terms: D000328:Adult; D000368:Aged; D053961:Azabicyclo Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D001426:Bacterial Proteins / Q000378:metabolism; D002442:Ceftazidime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000302:isolation & purification; D008297:Male; D009767:Obesity, Morbid / Q000150:complications; D051437:Renal Insufficiency / Q000150:complications; D014018:Tissue Distribution; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D053961:Azabicyclo Compounds; D001426:Bacterial Proteins; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D065093:beta-Lactamase Inhibitors; D002442:Ceftazidime; D001618:beta-Lactamases; C063912:carbapenemase
keywords: 
  KPC
  ; 
  Klebsiella pneumoniae
  ; avibactam; ceftazidime; obesity; pharmacokinetics; renal impairment