Timing of Symptoms of Early-Onset Sepsis after Intrapartum Antibiotic Prophylaxis: Can It Inform the Neonatal Management?

Abstract

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003-2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Keywords: Escherichia coli; early-onset sepsis; group B streptococcus; intrapartum antibiotic prophylaxis; newborn; prevention.

Figure 1

Hours of life at the onset of symptoms among 191 GBS cases according to IAP-exposure with different antibiotics. Bar graphs are presented as percentages. The number of cases for each different antibiotic and time interval is: beta-lactams, <4 h prior to delivery (0 h, n = 17; 7–24 h, n = 1; no symptoms, n = 6); beta-lactams, ≥4 h prior to delivery (0 h, n = 17; 7–24 h, n = 1); beta-lactams, timing undetermined (0 h, n = 2; 1–6 h, n = 1; no symptoms, n = 6); non beta-lactams (0 h, n = 6; 1–6 h, n = 2; no symptoms, n = 5); no IAP exposure (0 h, n = 42; 1–6 h, n = 31; 7–24 h, n = 33; >24 h, n = 16; no symptoms, n = 21).

Figure 2

Hours of life at the onset of symptoms among 72 E. coli cases according to IAP-exposure with different antibiotics. Bar graphs are presented as percentages. The number of cases for each different antibiotic and time interval is: beta-lactams, susceptible, <4 h prior to delivery (0 h, n = 2); beta-lactams, susceptible, ≥4 h prior to delivery (1–6 h, n = 2); beta-lactams, susceptible, timing unknown (0 h, n = 1; no symptoms, n = 1); beta-lactams, unsusceptible (0 h, n = 20; 1–6 h, n = 1; 7–24 h, n = 3; >24 h, n = 6; no symptoms, n = 3); non beta-lactams, unsusceptible (0 h, n = 1; 7–24 h, n = 2; >24 h, n = 1); no IAP exposure (0 h, n = 20; 1–6 h, n = 3; 7–24 h, n = 1; >24 h, n = 3; no symptoms, n = 2).