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Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55–13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection. [ABSTRACT FROM AUTHOR]

The emergence of carbapenemase resistant Gram-negative is designated as an 'urgent' priority of public health. Carbapenemase producing Klebsiella pneumoniae (CPKP) is linked with significant mortality. Conventionally used antibiotics (polymyxins, tigecycline, aminoglycosides, etc.) are associated with poor efficacy and toxicity profiles are quite worrisome. This article reviews mechanism of resistance and evidence regarding novel treatments of infections caused by CPKP, focusing mainly on currently approved new therapies and implications on future therapeutic strategies. A review of novel β-lactam/β-lactamase inhibitors (BLI) recently approved and in clinical development as well as cefiderocol, eravacycline and apramycin are discussed. Newly approved and forthcoming antimicrobial agents are promising to combat infections caused by CPKP. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam are novel agents with favorable outcome and associated with improved mortality in KPC-producing K.pneumoniae infections. However, are inactive against metallo-β-lactamases (MBL). Novel BLI in later stage of development, i.e. aztreonam-avibactam, cefepime-zidebactam, cefepime-taniborbactam, and meropenem-nacubactam as well as cefiderocol are active invitro against both KPC and MBL. Potential expectations of future therapeutic strategies are improved potency against CPKP, more tolerable safety profile, and capability of overcoming current resistance mechanism of multidrug-resistant K.pneumoniae. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) is the most common congenital viral infection and is regarded as the leading nongenetic cause of sensorineural hearing loss. Currently, international consensuses discourage prenatal screening of pregnant women. However, in few countries mainly in Southern Europe, screening of pregnant women for CMV infection is common practice. Management of women found with IgG+/IgM + and IgG avidity titers in the grey zone during first trimester causes significant stress to both families and health care workers.Patients and Methods: Pregnant women referred to our outpatient clinic with the diagnosis of acute CMV infection (IgM+/IgG+) during early pregnancy (gestational age ≤ 14 weeks) and IgG avidity in the grey zone were prospectively followed. The administration of CMV-HIG was offered and follow-up included fetal U/S, amniocentesis for CMV-DNA detection and MRI when appropriate. All neonates were examined by urine PCR and prospectively followed according to existing recommendations.Results: Ninety women (mean age 30.8 years) were retrospectively analyzed. Most (79.6%) received CMV-HIG. Four women terminated pregnancy (2 unrelated to CMV reasons and 2 because of CMV-positive amniotic fluid). Eighty-seven babies were born asymptomatic. Two newborns were diagnosed with congenital CMV infection. The overall transmission rate was 4.4%; 4.3 versus 5.6% for those receiving or not CMV-HIG. No adverse outcomes were detected during follow-up (median 24 months). Maternal age, parity, detection of maternal CMV-viremia upon diagnosis, delay between diagnosis and consultation, gestational week of first consultation, administration of CMV-HIG and number of doses were not associated with the risk of vertical CMV transmission.Discussions: Vertical transmission of CMV infection in pregnancies with acute CMV-infection and IgG avidity titers in the grey zone during first trimester was 4.4%, higher than that in infants born post nonprimary infection (NPI) during pregnancy. More powered studies are needed to prove a significant reduction in transmission using CMV-HIG. [ABSTRACT FROM AUTHOR]