Usefulness of a hub and spoke TDM-guided expert clinical pharmacological advice program of dalbavancin for optimizing very long-term curative or suppressive treatment of chronic staphylococcal infections

Abstract

A hub and spoke model for optimizing long-term treatment of chronic staphylococcal infections with dalbavancin based on therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) was implemented. This multicentric retrospective cohort study included patients receiving dalbavancin monotherapy lasting >6 weeks at different spoke hospitals having treatment optimized by means of a TDM-guided ECPA program at a hub hospital. Optimal pharmacokinetic/pharmacodynamic target against staphylococci with an MIC up to 0.125 mg/L was defined as dalbavancin concentrations >8.04 mg/L. Patients received dalbavancin therapy for curative (curative group) or suppressive (suppressive group) purposes. Clinical outcome was assessed by means of repeated ambulatory visits. A total of 12 spoke hospitals applied for 414 TDM-based ECPA for 101 patients, of whom 64.4% (65/101) were treated for curative and 35.6% (36/101) were for suppressive purposes. In the curative and suppressive groups, TDM-based ECPA optimized treatment for up to 14 and 28 months, respectively, and ensured median optimal exposure of 95.7% and 100%, respectively. In the curative group, having <70% of treatment time with concentrations above the optimal target increased failure risk [odds ratio (OR), 6.71; confidence interval (CI), 0.97-43.3; P = 0.05]. In the suppressive group, infective endocarditis was associated with an increased risk of ineffective treatment (OR, 8.65; CI, 1.29-57.62; P = 0.046). Mild adverse events were reported in 4.5% (5/101) of cases. A hub and spoke TDM-guided ECPA program of dalbavancin may be cost-effective for optimizing long-term treatment of chronic staphylococcal infections and for patients admitted to hospitals lacking in-house MD clinical pharmacologists.

Keywords: dalbavancin; long-term treatment; model-informed precision dosing; therapeutic drug monitoring.

Fig 1

Connection map of the hub and spoke model showing Italian hospitals joining the TDM-guided expert clinical pharmacological advice program for optimizing dalbavancin long-term therapy. The map was created using the libraries “maps” and “geosphere” of R software.

Fig 2

Flowchart of patient inclusion criteria in the study.

Fig 3

Spaghetti graph representing C-RP values overt time in each patient of the suppressive group (n = 36) having normal baseline C-RP value (<5 mg/dL, upper panel) or elevated baseline C-RP value (≥5 mg/dL, lower panel) in relation to clinical outcome (green = effective treatment, red = ineffective treatment).

Fig 4

Pathway of each patient of the curative group (n = 65) in terms of timing and amount of administered dalbavancin doses, of provided TDM-guided expert clinical pharmacological advice (ECPA), and of clinical outcome. Dark blue, blue, sky blue, and turquoise dots represent dalbavancin dose amount of 1,500, 1,000, 800, and 500 mg, respectively; fuchsia crosses represent TDM-guided ECPA assessment; green or red + represents test of cure (TOC) positive or negative, respectively; green or red − represents a clinical successful or unsuccessful 6-month follow-up, respectively.

Fig 5

Pathway of each patient of the suppressive group (n = 36) in terms of timing and amount of administered dalbavancin doses, of provided TDM-guided expert clinical pharmacological advice (ECPA), and of clinical outcome. Dark blue, blue, cyan, and turquoise dots represent dalbavancin dose amount of 1,500, 1,000, 750, and 500 mg, respectively; fuchsia crosses represent TDM-guided ECPA assessment; green or red + represents dalbavancin treatment efficacy or inefficacy, respectively.

Fig 6

Circular barplots of the individual proportion of time with optimal PK/PD target attainment of dalbavancin during the overall treatment duration in relation to the number of dalbavancin doses and the clinical outcome in the curative group (left panel) and in the suppressive group (right panel). Green and red columns represent, respectively, test of cure (TOC) positive or negative in the curative group, effective or ineffective treatment in the suppressive group.