Principles of Anti-infective Dosing in Pregnancy

AbstractPurposeAnti-infectives are among the most commonly prescribed medications in pregnancy. However, detailed information on the pharmacokinetics and pharmacodynamics of these medications in pregnancy is limited, leading to uncertainty among clinicians regarding the tolerability and efficacy of treatments. The purposes of this review were to highlight key physiologic changes during pregnancy that influence drug behavior, and to discuss areas of active research related to anti-infective drugs in pregnancy.MethodsA review of literature in PubMed was performed for topics related to physiologic changes of pregnancy, postcesarean surgical site infections, vaccines in pregnancy, and intrauterine infections. The literature was reviewed and pertinent sources were utilized for this article.FindingsPhysiologic changes during pregnancy may impact drug disposition and efficacy. Cefazolin regimens are the current prophylactic treatment of choice for postcesarean surgical site infections. Vaccines are provided in pregnancy for both maternal and neonatal benefit. Broad-spectrum antibiotics continue to be used as first-line therapy for intrauterine infections.ImplicationsContinued efforts to broaden the knowledge base on anti-infective drug behavior in pregnancy will result in increased therapeutic options for this population

Birthweight Extremes and Neonatal and Childhood Outcomes after Preterm Premature Rupture of Membranes

Objective To determine the association between birthweight extremes and risk of adverse neonatal and childhood outcomes following preterm premature rupture of membranes (PPROM). Study Design This is a secondary analysis of data from the Beneficial Effects of Antenatal Magnesium Sulfate Trial. Women with nonanomalous singletons and PPROM delivering ≥24.0 weeks were included. Birthweight was classified as small for gestational age (SGA), appropriate for gestational age (AGA), or large for gestational age (LGA). Composite severe neonatal morbidity and childhood outcomes at age 2, were compared between these groups. Results One thousand five hundred and ninety-eight infants were included (58 SGA, 1,354 AGA, and 186 LGA). There was an inverse relationship between birthweight and rate of composite major neonatal morbidity (55.2% of SGA, 31.5% of AGA, 18.3% of LGA, p < 0.001). Former-SGA children were more likely to be diagnosed with major composite childhood morbidity at age 2 (25.9% of SGA, 8.3% of AGA, 5.9% of LGA, p < 0.001). In multivariate models, LGA infants had improved initial neonatal outcomes compared with AGA infants (adjusted odds ratio [aOR], 0.44; 95% confidence interval [CI], 0.28-0.71; p = 0.001). Conclusion Among infants delivered following PPROM, those who were LGA at delivery had improved composite adverse neonatal outcomes. SGA increases the risk of severe neonatal morbidity, early childhood death, and moderate/severe cerebral palsy at age 2

Factors Associated with Previable Delivery following Second Trimester Rupture of Membranes

Objective To identify factors associated with previable delivery in second trimester preterm rupture of membranes (PROM). Study Design We conducted a single-center retrospective cohort study of women with pregnancies complicated by second trimester PROM (14.0-21.9 weeks' gestation) from 2000 to 2015 who elected expectant pregnancy management and achieved at least 24 hours latency. Maternal characteristics and clinical factors were compared among pregnancies that reached viability (≥ 23.0 weeks) and pregnancies delivered before viability ( 1cm, Group B streptococcus carrier status, bacterial vaginosis, and chlamydial infection during pregnancy were similar between groups. Median time to delivery was significantly shorter in women who delivered < 23 weeks compared with those who reached ≥ 23 weeks (6 vs. 46 days, p < 0.01). Conclusion Previable delivery occurred in the majority of women with second trimester PROM. No maternal or clinical factors were associated with delivery prior to viability. Counseling women with second trimester PROM should include the inability to determine which pregnancies will reach viability