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Incidence of late-onset GBS cases are higher than early-onset disease

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IAP is “the best we have” to prevent GBS despite its controversy

Perinatal group B Streptococcus (GBS) disease prevention guidelines are credited for the low rate of early-onset disease (EOD) cases of GBS in the United States, but the practice of intrapartum antibiotic prophylaxis (IAP) remains controversial in places like the United Kingdom where the National Health Service does not recommend screening-based IAP for GBS, Sagori Mukhopadhyay, MD, MMSc, and Karen M. Puopolo, MD, PhD, wrote in a related editorial.

One reason for concern about GBS IAP policies is that, despite the decreased number of EOD cases after implementation of IAP, the rate of late-onset disease (LOD) cases remain the same, the authors wrote. And implementation of IAP is not perfect: In some cases IAP was used for less than the recommended duration, used less effective drugs, or given too late so fetal infections were already established.

In addition, some may be uncomfortable with increased perinatal exposure to antibiotics – “a long-held concern about the extent to which widespread perinatal antibiotic use may contribute to the emergence and expansion of antibiotic-resistant GBS,” they added. However, despite the concern, the fatality ratio for EOD was 7% in the study by Nanduri et al., and one complication of GBS in survivors is neurodevelopmental impairment, according to a meta-analysis of 18 studies.

One solution that could address both EOD and LOD cases of GBS is the development of a GBS vaccine. Although there is reluctance to vaccinate pregnant women, recent studies have shown success in vaccinating women for influenza, tetanus, diphtheria, and pertussis; these recent efforts have “reinvigorated” academia’s interest in vaccine research for this population.

“Vaccination certainly could be a first step to eliminating neonatal GBS disease in the United States and may be the only available approach to addressing the substantial international burden of GBS-associated stillbirth, preterm birth, and neonatal disease morbidity and mortality,” the authors wrote. “But for now, while GBS IAP may be imperfect, it is the success we have.”

Dr. Mukhopadhyay and Dr. Puopolo are from the division of neonatology at the Children’s Hospital of Philadelphia. Dr. Mukhopadhyay and Dr. Puopolo commented on the study by Nanduri et al. in an accompanying editorial (Mukhopadhyay et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2018.4824). They reported no relevant conflicts of interest.



Incidence of late-onset disease for group B streptococcus is higher than early-onset disease for infants under 90 days old in the United States, according to a multistate study of invasive group B streptococcal disease published in JAMA Pediatrics.

Group B strep Janice Haney Carr/CDC

Using data from the Active Bacterial Core surveillance (ABCs) program, Srinivas Acharya Nanduri, MD, MPH, at the Centers for Disease Control and Prevention, and colleagues performed an analysis of early-onset disease (EOD) and late-onset disease (LOD) cases of group B Streptococcus (GBS) in infants from 10 different states between 2006 and 2015, and whether mothers of infants with EOD received intrapartum antibiotic prophylaxis (IAP). EOD was defined as between 0 and 6 days old, while LOD occurred between 7 days and 89 days old.

They found 1,277 cases of EOD and 1,387 cases of LOD in total, with a decrease in incidence of EOD from 0.37 per 1,000 live births in 2006 to 0.23 per 1,000 live births in 2015 (P less than .001); LOD incidence remained stable at a mean 0.31 per 1,000 live births during the same time period.

In 2015, the national burden for EOD and LOD was estimated at 840 and 1,265 cases, respectively. Mothers of infants with EOD did not have indications for and did not receive IAP in 617 cases (48%) and did not receive IAP despite indications in 278 (22%) cases.

“While the current culture-based screening strategy has been highly successful in reducing EOD burden, our data show that almost half of remaining infants with EOD were born to mothers with no indication for receiving IAP,” Dr. Nanduri and colleagues wrote.

Because there currently is no effective prevention strategy against LOS GBS, the investigators wrote that a maternal vaccine against the most common serotypes “holds promise to prevent a substantial portion of this remaining burden,” and noted several GBS candidate vaccines were in advanced stages of development.

The researchers also looked at GBS serotype data in 1,743 patients from seven different centers. The most commonly found serotype isolates of 887 EOD cases were Ia (242 cases, 27%) and III (242 cases, 27%) overall. Serotype III was most common for LOD cases (481 cases, 56%) and increased in incidence from 0.12 per 1,000 live births to 0.20 per 1,000 live births during the study period (P less than .001), while serotype IV was responsible for 53 cases (6%) of both EOD and LOD.

Dr. Nanduri and associates wrote that over 99% of the serotyped EOD (881 cases) and serotyped LOD (853 cases) cases were caused by serotypes Ia, Ib, II, III, IV, and V. With regard to antimicrobial resistance, there were no cases of beta-lactam resistance, but there was constitutive clindamycin resistance in 359 isolate test results (21%).

The researchers noted that they were limited in the study by 1 year of whole-genome sequencing data, the ABCs capturing only 10% of live birth data in the United States, and conclusions on EOD prevention restricted to data from labor and delivery records.

This study was funded in part by the CDC. Paula S. Vagnone received grants from the CDC, while William S. Schaffner, MD, received grants from the CDC and personal fees from Pfizer, Merck, SutroVax, Shionogi, Dynavax, and Seqirus outside of the study. The other authors reported no relevant disclosures.

SOURCE: Nanduri SA et al. JAMA Pediatr. 2019 Jan 14. doi: 10.1001/jamapediatrics.2018.4826.

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