The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).

This study aims to investigate whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies at standard (105) and high (108) inocula. Combined therapy was compared with daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2g/4hiv, fosfomycin 2g/6h iv and daptomycin 6-10mg/kg/d iv were administered. The combination of daptomycin and fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four out of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 mcg/mL) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/d in terms of both the proportion of sterile vegetations (100% vs. 72%, P=.046) and the decrease in the density of bacteria within the vegetations (P=.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/d (100% vs. 93%, P=1.00) and had similar activity to daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/d (100% vs. 88%, P=0.48). Daptomycin non-susceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.Copyright © 2018 American Society for Microbiology

The association between SARS-CoV-2 infection and preterm delivery: a prospective study with a multivariable analysis.

To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity. We conducted a multicentre prospective study in pregnancy based on a universal antenatal screening program for SARS-CoV-2 infection. Throughout Spain 45 hospitals tested all women at admission on delivery ward using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020. The cohort of positive mothers and the concurrent sample of negative mothers was followed up until 6-weeks post-partum. Multivariable logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of SARS-CoV-2 infection and obstetric outcomes. Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions. Among 1009 screened pregnancies, 246 were SARS-CoV-2 positive. Compared to negative mothers (763 cases), SARS-CoV-2 infection increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32-3.36, p = 0.002); iatrogenic preterm delivery was more frequent in infected women (4.9% vs 1.3%, p = 0.001), while the occurrence of spontaneous preterm deliveries was statistically similar (6.1% vs 4.7%). An increased risk of premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11-2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43-8.94, p  This prospective multicentre study demonstrated that pregnant women infected with SARS-CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research