Timing of antimicrobial prophylaxis for cesarean section is critical for gut microbiome development in term born infants

Abstract

Animal models imply that the perinatal exposure to antibiotics has a substantial impact on microbiome establishment of the offspring. We aimed to evaluate the effect of timing of antimicrobial prophylaxis for cesarean section before versus after cord clamping on gut microbiome composition of term born infants. We performed an exploratory, single center randomized controlled clinical trial. We included forty pregnant women with elective cesarean section at term. The intervention group received single dose intravenous cefuroxime after cord clamping (n = 19), the control group single dose intravenous cefuroxime 30 minutes before skin incision (n = 21). The primary endpoint was microbiome signature of infants and metabolic prediction in the first days of life as determined in meconium samples by 16S rRNA gene sequencing. Secondary endpoints were microbiome composition at one month and 1 year of life. In meconium samples of the intervention group, the genus Staphylococcus pre-dominated. In the control group, the placental cross-over of cefuroxime was confirmed in cord blood. A higher amino acid and nitrogen metabolism as well as increased abundance of the genera Cutibacterium, Corynebacterium and Streptophyta were noted (indicator families: Cytophagaceae, Lactobacilaceae, Oxalobacteraceae). Predictive models of metabolic function revealed higher 2ʹfucosyllactose utilization in control group samples. In the follow-up visits, a higher abundance of the genus Clostridium was evident in the intervention group. Our exploratory randomized controlled trial suggests that timing of antimicrobial prophylaxis is critical for early microbiome engraftment but not antimicrobial resistance emergence in term born infants.

Application of a Physiologically Based Pharmacokinetic Model to Predict Cefazolin and Cefuroxime Disposition in Obese Pregnant Women Undergoing Caesarean Section

“…In other situations, cefuroxime 1500 mg dose is recommended if MIC 90 of ≥ 8 µg/g are desired for at least 95% of women at 2 h post dose; if the CS is delayed > 2 h post cefuroxime administration of 1500 mg in lean, obese, or morbidly obese pregnant women, a second dose might be required to maintain cefuroxime concentrations ≥ 8 µg/g or µg/mL (Tables S5 and S6). Balancing the benefit vs. the maternal/foetal safety should be considered [64].…”

Antibiotic Use During Pregnancy and Childbirth: Prospective Observational Study on Prevalence, Indications, and Prescribing Patterns in a German Tertiary Center

“…As large trials and meta-analyses revealed a lower risk for complications when antibiotics are given before skin incision 11 38 39 , guidelines changed and now recommend the administration of antibiotics 30 to 120 minutes before skin incision 40 41 42 . This, however, leads to an intrauterine exposure to antibiotics of all infants born by CS and there is evidence that even a single dose of antibiotics has an impact on early neonatal gut microbiome development 43 . A recent prospective multicenter study from Switzerland did not find an increased risk for infections in mothers who received the antibiotic after cord clamping.…”

Maternal-infant antibiotic resistance genes transference: what do we know?

“…Recently, it has been shown that the way an infant is born and the amount of antibiotics they are exposed to during the perinatal period can affect the development of the gut microbiome establishment and have long-term impacts on their health, such as increasing the risk of asthma, inflammation, and obesity 117 , 118 .…”