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Objectives Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Reference anti-CMV treatment is valganciclovir/ganciclovir, which is contraindicated in pregnancy given questions about teratogenicity. Methods We analysed reports from VigiBase, the world’s largest safety database, and performed a disproportionality analysis of adverse pregnancy outcomes associated with (val)ganciclovir compared with any other drugs or with (val)aciclovir as comparators. Results Among 3 104 984 reports related to childbearing-age women or to pregnancy topics, 6186 were exposed to (val)ganciclovir or (val)aciclovir including 251 adverse pregnancy outcomes with (val)ganciclovir (n = 34) or (val)aciclovir (n = 217). We did not evidence any increased reporting of any adverse pregnancy outcome [miscarriage, stillbirth, small weight for gestational age, preterm birth ( Conclusions These preliminary results require confirmation but suggest the possibility for trial evaluation of val(ganciclovir) in severe maternal or fetal CMV infections.

Objectives This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). Methods From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). Results One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). Conclusions Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.

Background Excess of acute kidney injury (AKI) secondary to the association of vancomycin plus piperacillin is debated. Objectives To detect a signal for an increased risk of AKI with the vancomycin and piperacillin combination compared with other vancomycin-based regimens. Methods Using VigiBase, the WHO global database of individual case safety reports (ICSR) from 1997 to 2019, we conducted a disproportionality analysis comparing the reporting of AKI cases between different vancomycin-based regimens (vancomycin plus piperacillin, cefepime or meropenem). To take into account a possible notoriety bias, we secondarily restricted the study period to before 2014, the date of the first publication of AKI in patients receiving vancomycin plus piperacillin. Results are expressed using the reporting OR (ROR) and its 95% CI. Results From 1997 to 2019, 53 701 ICSR concerning vancomycin have been registered in the database, including 6016 reports of AKI (11.2%), among which 925 (15.4%) were reported with vancomycin/piperacillin, 339 (5.6%) with vancomycin/cefepime and 197 (3.7%) with vancomycin/meropenem. ROR (95% CI) for AKI was 2.6 (2.4–2.8) for vancomycin/piperacillin, 2.5 (2.2–2.9) for vancomycin/cefepime and 0.5 (0.4–0.6) for vancomycin/meropenem versus other vancomycin-containing regimens. After restriction of the study period to 1997–2013, the ROR for AKI remains significant only for vancomycin/piperacillin [ROR (95% CI) = 2.1 (1.8–2.4)]. Conclusions We found a disproportionality in reports of AKI in patients receiving vancomycin plus piperacillin compared with vancomycin in other regimens. This suggests a drug–drug interaction between these two antibiotics resulting in an increased risk of AKI.