Monthly dalbavancin dosing for suppressive therapy: a pharmacokinetic estimation analysis and case series

Retained hardware/prosthetic infections frequently require antimicrobial suppression therapy. Treatment options are often limited by resistance, allergies, and dosing frequencies. Dalbavancin (DAL) is a potentially attractive option for suppression of gram-positive infections given its potential for infrequent dosing. However, optimal DAL suppression dosing is unknown. An in silico pharmacokinetic/pharmacodynamic simulation was performed to assess the predicted dalbavancin concentration resulting from suppressive regimens. Serum levels were deemed adequate if the fAUC₂₄/MIC was above the PK target of 27.1. Patients at a U.S. medical center receiving DAL as suppressive therapy were reviewed. PK simulation of DAL dosed 1,500 mg monthly resulted in free serum concentrations above the PK target. Because many clinicians opt to initiate these regimens with two doses given 1 week apart, the next modeled regimen included this load, before initiating 1,500 mg monthly. This initial load did not significantly alter total drug exposure. The final simulated regimen was 1,000 mg monthly. With this simulation, the lower 95% CI fAUC₂₄/MIC fell just below the PK target for an isolate at the breakpoint. Nine patients who received dalbavancin 1,500 mg monthly as suppressive therapy were reviewed. All had retained hardware and received DAL for a median 591 days, with 7 patients still receiving treatment and no reported suppressive therapy failure. Monthly 1500 mg dalbavancin dosing for suppressive therapy is supported by this case series and PK simulation data. An initial weekly loading dose appears unnecessary. Reducing the monthly dose to 1000 mg may also be appropriate for certain patients, though clinical data is needed to support this practice.