title: Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics.
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.
authors.affiliation: Infection Management Services, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102, Australia. wendy_munckhof@health.qld.gov.au
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Munckhof
authors.forename: John
authors.initials: J
authors.lastname: Carney
authors.forename: Gail
authors.initials: G
authors.lastname: Neilson
authors.forename: John
authors.initials: J
authors.lastname: Neilson
authors.forename: Julia
authors.initials: J
authors.lastname: Carroll
authors.forename: Brett
authors.initials: B
authors.lastname: McWhinney
authors.forename: Michael
authors.initials: M
authors.lastname: Whitby
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy*; D002969:Clavulanic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D018718:Home Infusion Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013982:Ticarcillin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; C043215:ticarcillin-clavulanic acid; D013982:Ticarcillin