Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Int J Antimicrob Agents. 2005 Jun;25(6):514-22. doi: 10.1016/j.ijantimicag.2005.02.008.

Abstract

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of beta-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Infections / drug therapy*
  • Clavulanic Acids / administration & dosage
  • Clavulanic Acids / adverse effects
  • Clavulanic Acids / pharmacokinetics
  • Clavulanic Acids / pharmacology
  • Female
  • Home Infusion Therapy / methods*
  • Humans
  • Male
  • Middle Aged
  • Ticarcillin / administration & dosage
  • Ticarcillin / adverse effects
  • Ticarcillin / pharmacokinetics
  • Ticarcillin / pharmacology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Clavulanic Acids
  • ticarcillin-clavulanic acid
  • Ticarcillin