title: Teicoplanin use in adult patients with haematological malignancy: Exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity.
abstract: In 2010, our hospital introduced a higher target teicoplanin trough concentration of ≥20 mg/L by Day 3 for haematological malignancy patients. This study aimed to explore whether target trough concentrations were achieved, to identify factors associated with trough concentrations attained, and to assess clinical efficacy with teicoplanin treatments and nephrotoxicity. This was a retrospective, single-centre, cohort study of 172 teicoplanin treatments in 104 adults with haematological malignancy. Mixed-effects regression was used to evaluate factors affecting trough concentrations, and logistic regression was used to assess the relationship between trough concentrations and treatment outcomes. Nephrotoxicity was assessed using the RIFLE criteria. Considerable variability in trough concentrations was observed, with trough concentrations ≥20 mg/L rarely achieved early in therapy. A mixed-effects regression model explaining 52% of the variation in trough concentrations was developed. Dose and day of therapy were positively associated with trough concentration, whilst estimated renal function and, interestingly, acute myeloid leukaemia diagnosis were negatively associated (P<0.05). Results suggested a positive relationship between trough concentration and the likelihood of a favourable outcome for coagulase-negative staphylococcal central line-associated bloodstream infections. Elucidation of a specific target concentration requires further investigation. Teicoplanin was well tolerated renally. Findings suggest a risk of underexposure if conventional teicoplanin doses are used in haematological malignancy patients. Given the variability in trough concentrations observed, the identified factors affecting trough concentrations attained and the suggested link with clinical outcome, individualised initial dosing followed by therapeutic drug monitoring is recommended to ensure early adequate exposure in this vulnerable patient group.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Byrne
authors.affiliation: Department of Pharmacy, Tallaght Hospital, Dublin 24, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Egan
authors.affiliation: Department of Microbiology, Tallaght Hospital, Dublin 24, Ireland.
authors.forename: Jérôme P
authors.initials: JP
authors.lastname: Fennell
authors.affiliation: Department of Pharmacy, Tallaght Hospital, Dublin 24, Ireland.
authors.forename: Philomena
authors.initials: P
authors.lastname: O'Byrne
authors.affiliation: Department of Haematology, Tallaght Hospital, Dublin 24, Ireland.
authors.forename: Helen
authors.initials: H
authors.lastname: Enright
authors.affiliation: Department of Pharmacy, Tallaght Hospital, Dublin 24, Ireland.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Deasy
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Ryder
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland. Electronic address: ddarcy@tcd.ie.
authors.forename: Deirdre M
authors.initials: DM
authors.lastname: D'Arcy
authors.affiliation: Department of Haematology, Tallaght Hospital, Dublin 24, Ireland.
authors.forename: Johnny
authors.initials: J
authors.lastname: McHugh
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy*; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017334:Teicoplanin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin
keywords: Haematological malignancy; Nephrotoxicity; Pharmacokinetics; Teicoplanin; Therapeutic drug monitoring