CME Author: Vicki Brower
Study Authors: Srinivas Acharya Nanduri, Susan Petit, et al.; and Sagori Mukhopadhyay and Karen Puopolo.
Target Audience and Goal Statement:
Infectious disease specialists, obstetricians/gynecologists, pediatricians, neonatal physicians and nurses, epidemiologists
The goal was to describe the incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of early onset disease (EOD) group B Streptococcus (GBS) and late-onset disease (LOD) in the U.S. during the years 2006 to 2015 to inform intrapartum antibiotics prophylaxis (IAP) and vaccine development.
- What are the recent trends in GBS EOD (i.e., birth to 7 days old) and LOD (7 to 89 days old) in neonates from 2006 to 2015 in the U.S.?
- What are the pertinent facts regarding case characteristics, antimicrobial resistance, and serotype distribution of EOD and LOD, and how do they pertain to IAP guidelines and vaccine development?
- What are potential solutions to the problems found?
Study Synopsis and Perspective:
From 2006 to 2015, there was a substantial decline in GBS EOD in infants, while the incidence of LOD remained relatively stable, reported CDC researcher Srinivas Acharya Nanduri, MBBS, MD, MPH, and colleagues. However, a little over 20% of infants with EOD did not receive intrapartum antibiotic prophylaxis despite having indications for it, thus indicating potential gaps in treatment, the authors wrote in JAMA Pediatrics. In addition, beginning in 2008, the annual rate of LOD has been higher than that of EOD.
GBS is “a leading infectious cause of morbidity and mortality among infants in the United States,” Nanduri and co-authors wrote, noting that infection may be preventable by improved implementation of intrapartum antibiotic prophylaxis guidelines.
These call for “routine screening of pregnant women for vaginal/rectal colonization with GBS with intrapartum antibiotic prophylaxis (IAP) to reduce vertical GBS transmission and subsequent invasive disease in the infant,” noted Sagori Mukhopadhyay, MD, and Karen M. Puopolo, MD, both of Children’s Hospital of Philadelphia, writing in an accompanying editorial. One potential outcome of LOD is meningitis, which can be fatal, they added.
Since LOD is not preventable by IAP, one way to reduce the incidence (and the risk of EOD) would be a preventive vaccine, especially in light of concerns about the emergence of antibiotic resistance, Nanduri and colleagues wrote, noting that several experimental vaccines are currently in development in phase I and phase II testing.
For their study, Nanduri and colleagues used active population-based and laboratory-based surveillance for invasive GBS disease, the Active Bacterial Core Surveillance, which conducts surveillance in selected counties in 10 states.
The team found 1,277 cases of EOD and 1,387 of LOD from 2006 to 2015 across the surveillance areas. Nearly all cases of EOD occurred within 48 hours of birth, and a little over a quarter of cases occurred in preterm infants. Median patient age for a positive culture for LOD was 34 days.
The incidence of EOD declined during the study period, from 0.37 to 0.23 per 1,000 live births (P<0.001), with a case-fatality rate of 6.9% in full-term infants. Annual rates of EOD are higher in preterm infants compared with full-term infants, and in black infants compared with white infants. There was also a statistically significant decline in EOD among both white infants and black infants during this time period. Two serotypes (Ia and III) were most common in EOD neonates.
A little under half of mothers of infants with EOD had no indication for IAP, and thus did not receive it, while 21.8% did not receive intrapartum antibiotics despite an indication of need, the authors found.
In their editorial, Mukhopadhyay and Puopolo characterized this finding as “frustrating,” specifically citing the fact that 48% of cases of EOD GBS occurred in infants born to women who did not meet the criteria for IAP, either because of a negative GBS screening result or an unknown GBS status without clinical risk factors.
“Improvements in obstetric practice, aided by electronic health records and decision support tools, may improve the timing and antibiotic choice for IAP,” Mukhopadhyay and Puopolo wrote. “Rescreening women with negative antenatal GBS testing results on presentation for delivery with polymerase chain reaction-based point-of-care tests could improve the identification of colonized women.”
However, the logistics and cost of the latter approach may be significant barriers for most birthing centers, the editorial stated.
Nanduri and colleagues found that the incidence of LOD remained stable during the study period (mean 0.31 per 1,000 live births), with a case-fatality rate of 5.4% in full-term infants. Annual rates of LOD were also higher among preterm infants versus term infants and for black versus white infants.
Serotype III was most common in LOD, and increased from 2006 to 2015 for 0.12 to 0.20 cases per 1,000 live births (P<.001). The six other most common serotypes were Ia, Ib, II, IV, and V. While no β-lactam resistance was identified, about 20% of isolates showed "constitutive clindamycin resistance," the researchers found, adding that six serotypes caused 99.3% of all EOD, and 99.7% of LOD.
In 2015, there were an estimated 840 EOD cases and 1,265 LOD cases nationally. In addition, over the period of the study, resistance to numerous antibiotics was found. Serotype-specific incidence varied more in LOD than EOD, the authors wrote, noting that a hexavalent vaccine would cover most cases.
“Despite reductions in EOD, a significant burden of invasive GBS disease among infants remains; an effective multivalent maternal vaccine could reduce disease burden,” the researchers concluded.
JAMA Pediatrics, Jan. 14, 2019; DOI:10.1001/jamapediatrics.2018.4826
Editorial: JAMA Pediatrics, Jan. 14, 2019; DOI:10.1001/jamapediatrics.2018.4824
Study Highlights: Explanation of Findings
Disease caused by EOD GBS has declined among infants, and the rates of LOD GBS are now higher than EOD among U.S. infants, the new study found. In 2015, there were an estimated 840 EOD cases of GBS and 1,265 LOD cases nationally. “Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there are no current public health interventions,” the researcher concluded.
They recommended revisions in IAP guidelines to improve adherence and sustain low levels of EOD. But with LOD rates higher than EOD rates, “greater than half of all infant GBS disease in the U.S. currently is not preventable by any currently available strategy,” the team pointed out. “To address persistent areas of challenge, an alternative strategy, such as prevention through vaccines, will likely be necessary for further significant declines in disease rates.”
Mukhopadhyay and Puopolo emphasized in their editorial that prevention of GBS disease remains incomplete, noting “missed opportunities and biologic limitations that contribute to residual GBS EOD” as one of two major issues that drive GBS IAP policies. The second issue comes from “discomfort with the high rates of perinatal antibiotic exposure,” and the concern that widespread perinatal exposure to antibiotics may contribute to the emergence and expansion of antibiotic-resistant GBS.
Whether a vaccine will obviate screening is an open question, but it can certainly be a first step to eliminate neonatal GBS in the U.S. and address the international issue of GBS-associated stillbirth, preterm birth, and neonatal disease and mortality, the editorialists wrote.
One downside to vaccines, Nanduri and co-authors noted, is that in both EOD and LOD, 20.4% and 49.6% of cases, respectively, occurred in infants who were born prematurely at less than 35 weeks of gestation and/or had disease onset at more than 42 days old, meaning that maternal vaccines might not be as effective in these cases in prevention.
One limitation to the data, the team said, was that the surveillance system represents only 10% of U.S. live births and thus may not represent “the full variation within the country.”