Background Beta-lactam antibiotics (βLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide guidelines on the optimization of beta-lactam treatment in ICU patients. Methods A consensus committee of 18 experts from the two societies had the mission of producing these guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only “optional” recommendations. Results After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding βLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of βLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement. Conclusions The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering βLA in critically ill patients. Electronic supplementary material The online version of this article (10.1186/s13054-019-2378-9) contains supplementary material, which is available to authorized users.

The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV and FTC breast milk doses represented 0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for TFV but between the half-maximal inhibitory concentration and the adult minimal expected concentration for FTC. The rare children who will acquire HIV despite TDF-FTC therapy will need to be monitored for viral resistance acquisition.For prevention of mother-to-child transmission (PMTCT) of HIV in resource-limited settings, single-dose nevirapine (sd-NVP) has been commonly administered at the start of labor up to now according to previous World Health Organization (WHO) guidelines. However, the use of sdNVP results in resistance mutations in 15 to 70% of women, at 4 to 6 weeks postpartum, compromising the success of subsequent treatments with NVP in mothers and children (1, 7). Adding a single dose of tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) reduced these resistance mutations by half (2, 10). TDF and FTC placental transfer has already been studied (4, 5), but no data were reported so far on the transfer of these drugs after birth through breast-feeding. Breast-feeding cessation or replacement feeding introduced under routine circumstances is no longer recommended by WHO, as these interventions are often associated with increased mortality and morbidity (13). Thus, it is important to assess to what extent maternal TDF and FTC are transmitted through breast milk to infants. Furthermore, TDF-FTC-based fully suppressive antiretroviral regimens represent now a recommended approach for PMTCT in pregnant, delivering, and breast-feeding women (14).Five Ivorian mothers included in the ANRS 12109 TEmAA (Tenofovir/Emtricitabine in Africa and Asia) study and who chose to exclusively breast-feed their infant were administered one tablet of NVP (200 mg) plus two tablets of TDF (300 mg)-FTC (200 mg) at the start of labor and one TDF-FTC daily tablet for 7 days postpartum. The protocol was approved by the Ethics Committee of the country (Cote d'Ivoire). The women and the children's fathers were asked to sign an informed consent form. Maternal blood and milk samples were collected concomitantly after drug administration on days 1, 2, 3, and 7 after delivery. A liquid-liquid extraction procedure was performed using 300 l of methanol-dichloromethane (10/16, vol/vol) containing 0.1% hydrochloric acid added to 100 l of milk samples. After vortexing and centrifugation at 20,000 ϫ g at ϩ4°C for 20 min, the upper phase was withdrawn and evaporated under nitrogen to dryness. The sample was then reconstituted with 100 l of mobile phase, and 40 l of the extract was injected in the analytical system. TFV and FTC concentrations were measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method previously described (9) and adapted for FTC. Limits of quantitation were 4.9 and 9.5 ng/ml for TFV and FTC, respectively. Maximal and minim...