A meropenem pharmacokinetics model in patients with haematological malignancies.

BACKGROUND: Optimal dosing of antibiotics is critical in immunocompromised patients suspected to have an infection. Data on pharmacokinetics (PK) of meropenem in patients with haematological malignancies are scarce. OBJECTIVES: To optimize dosing regimens, we aimed to develop a PK population model for meropenem in this population. METHODS: Patients aged ≥18 years, hospitalized in the haematology department of our 1500 bed university hospital for a malignant haematological disease and who had received at least one dose of meropenem were eligible. Meropenem was quantified by HPLC. PK were described using a non-linear mixed-effect model and external validation performed on a distinct database. Monte Carlo simulations estimated the PTA, depending on renal function, duration of infusion and MIC. Target for free trough concentration was set at >4× MIC. RESULTS: Overall, 88 patients (181 samples) were included, 66 patients (75%) were in aplasia and median Modification of Diet in Renal Disease (MDRD) CLCR was 117 mL/min/1.73 m2 (range: 35-359). Initial meropenem dosing regimen ranged from 1 g q8h to 2 g q8h over 30 to 60 min. A one-compartment model with first-order elimination adequately described the data. Only MDRD CLCR was found to be significantly associated with CL. Only continuous infusion achieved a PTA of 100% whatever the MIC and MDRD CLCR. Short duration of infusion (<60 min) failed to reach an acceptable PTA, except for bacteria with MIC < 0.25 mg/L in patients with MDRD CLCR below 90 mL/min/1.73 m2. CONCLUSIONS: In patients with malignant haematological diseases, meropenem should be administered at high dose (6 g/day) and on continuous infusion to reach acceptable trough concentrations.

Barriers to implementation of the new targeted BCG vaccination in France: a cross sectional study.

The aim of the study was to assess factors influencing BCG vaccination among targeted children after the end of universal and mandatory BCG vaccination in France. A cross-sectional study was conducted in 2009 among general practitioners (GPs) of the French Sentinel Network. With the participation of 358 physician-investigators, 920 children were included. Of the 261 children (31%) identified to be at risk of tuberculosis, only 113 (44%) were vaccinated. The median number of French criteria for BCG vaccination correctly cited by the GPs was 3 of the existing 6. Of the 10 proposed, a median number of 5 regions in the world according to their level of tuberculosis risk were correctly classified by GPs. After adjustment using an alternating logistic model, 7 variables were found to be associated with the immunisation status of the target population. Six of these increased the probability of being vaccinated: children older than 6 months (OR=3.4 (CI 95% [1.4-8.6])), residents in central Paris or its suburbs (OR=14.7 [4.4-49.5]), children expected to travel to highly endemic regions (OR=3.5 [1.4-8.6]), those living in unfavourable conditions (OR=19.9 [6.2-63.9]), the GP's good knowledge of vaccination guidelines (OR=1.4 [1.1-1.9]) and the GP's perception of tuberculosis as a common disease (OR=2.2 [1.1-4.5]). Surprisingly, GPs with university training on infectious diseases tended to be more reluctant to follow vaccination guidelines (OR=0.14 [0.1-0.4]). Actions targeted at these factors could contribute to improving BCG immunisation coverage.