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.

Keywords: Haematological malignancy; Nephrotoxicity; Pharmacokinetics; Teicoplanin; Therapeutic drug monitoring.