Pharmacokinetics of Ceftolozane-Tazobactam during Prolonged Intermittent Renal Replacement Therapy

Chemotherapy. 2018;63(4):203-206. doi: 10.1159/000493196. Epub 2018 Oct 10.

Abstract

Background: Prolonged intermittent renal replacement therapy (PIRRT) eliminates many drugs, and without dosing data, for new antibiotics like ceftolozane/tazobactam, suboptimal concentrations and treatment failure are likely.

Objectives: Herein, we describe the effect of PIRRT on the plasma pharmacokinetics of ceftolozane/tazobactam ad-ministered in a critically ill 55-year-old patient with a polymicrobial sternal wound osteomyelitis, including a multiresistant Pseudomonas aeruginosa.

Method: Blood samples were taken over 4 days where the patient received a 7.5-h PIRRT treatment. One- and 2-compartment models were tested for ceftolozane and tazobactam separately, and the log-likelihood ratio and goodness-of-fit plots were used to select the final model.

Results: Two-compartment models were developed for ceftolozane and tazobactam separately and described significant differences in clearance of ceftolozane and tazobactam with and without PIRRT (8.273 vs. 0.393 and 8.020 vs. 0.767 L/h, respectively).

Conclusions: A ceftolozane/tazobactam dose of 500 mg/250 mg appears to be sufficient to attain pharmacokinetic/pharmacodynamic targets during PIRRT while the manufacturer's recommended dosing of 100 mg/50 mg every 8 h was sufficient during non-PIRRT periods.

Keywords: Antibiotics; Dosing; Extended daily dialysis; Renal replacement therapy; Sustained low efficiency dialysis.

Publication types

  • Case Reports

MeSH terms

  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Cephalosporins / blood
  • Cephalosporins / pharmacokinetics
  • Cephalosporins / therapeutic use*
  • Female
  • Half-Life
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / pathology
  • Middle Aged
  • Osteomyelitis / complications
  • Osteomyelitis / drug therapy*
  • Osteomyelitis / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / isolation & purification
  • Renal Replacement Therapy
  • Tazobactam / blood
  • Tazobactam / pharmacokinetics
  • Tazobactam / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • ceftolozane
  • Tazobactam