Elsevier

Vaccine

Volume 31, Supplement 4, 28 August 2013, Pages D20-D26
Vaccine

Review
Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: Experience in the United States and implications for a potential group B streptococcal vaccine

https://doi.org/10.1016/j.vaccine.2012.11.056Get rights and content

Abstract

Group B Streptococcus (GBS) emerged as the leading cause of newborn infection in the United States in the 1970s. In the 1980s clinical trials demonstrated that giving intrapartum intravenous ampicillin or penicillin to mothers at risk was highly effective at preventing invasive GBS disease in the first week of life (early-onset). In 1996, the first national guidelines for the prevention of perinatal GBS disease were issued; these recommended either antenatal screening for GBS colonization and intrapartum antimicrobial prophylaxis (IAP) to colonized women, or targeting IAP to women with certain obstetric risk factors during labor. In 2002, revised guidelines recommended universal antenatal GBS screening. A multistate population-based review of labor and delivery records in 2003–2004 found 85% of women had documented antenatal GBS screening; 98% of screened women had a colonization result available at labor. However, missed opportunities for prevention were identified among women delivering preterm and among those with penicillin allergy, and more false negative GBS screening results were observed than expected. The incidence of invasive early-onset GBS disease decreased by more than 80% from 1.8 cases/1000 live births in the early 1990s to 0.26 cases/1000 live births in 2010; from 1994 to 2010 we estimate that over 70,000 cases of EOGBS invasive disease were prevented in the United States. IAP effectiveness is similar and high among term (91%) and preterm (86%) infants when first line therapy is received for at least 4 h. However, early-onset disease incidence among preterm infants remains twice that of term infants; moreover disease among infants after the first week of life (late-onset disease) has not been impacted by IAP. The US experience demonstrates that universal screening and IAP for GBS-colonized women comprise a highly effective strategy against early-onset GBS infections. Maximizing adherence to recommended practices holds promise to further reduce the burden of early-onset GBS disease. Yet there are also inherent limitations to universal screening and IAP. Some of these could potentially be addressed by an efficacious maternal GBS vaccine.

Highlights

► We reviewed intrapartum prophylaxis impact on newborn group B streptococcal disease. ► US uptake of prenatal screening and intrapartum antibiotics was rapid and widespread. ► The incidence of invasive early-onset GBS disease decreased by more than 80%. ► From 1994 to 2010 over 70,000 cases of newborn invasive GBS disease were prevented. ► Current prevention limitations might be addressed by a maternal GBS vaccine.

Section snippets

History of group B streptococcal disease and prevention interventions

The bacteria group B Streptococcus (GBS) emerged as the leading cause of infection in newborns in the United States in the 1970s. Case series reported fatality rates as high as 50%, with pneumonia and meningitis the leading clinical syndromes. Early-onset GBS infections (onset within the first week of life) result predominantly from vertical transmission of GBS from colonized mothers during the intrapartum period whereas infections from one week to 90 days of age (late-onset infections) result

Development and evolution of GBS prevention policy

Prevention of early-onset GBS disease crosses clinical specialty boundaries because a maternal intervention is needed to protect newborns from disease. In 1992 the American Academy of Pediatrics promoted an IAP strategy that focused on maternal screening for GBS colonization, with an emphasis on colonized women with either preterm delivery or prolonged membrane rupture [4]. During the same time period the American College of Obstetricians and Gynecologists advocated an approach that did not

Implementation of prevention, 1996–2002

Successful implementation of an intrapartum prophylaxis strategy is complex and requires strong collaboration between obstetric, clinical laboratory and newborn care providers. Implementation involves two key steps: (1) ascertainment of whether a woman has an indication for IAP; (2) administration of appropriate IAP to women with indications.

Shortly after issuance of the first consensus guidelines, having a newly established hospital policy for GBS prevention was associated with stronger

Implementation of prevention in the era of universal screening

The key steps to successful prevention under a universal screening strategy include reaching a high proportion of women for antenatal screens; correct specimen collection and processing; and implementation of appropriate IAP to women with indications. A large, multistate review of births in 2003 and 2004, shortly after issuance of the first universal screening recommendations, documented rapid, widespread uptake of screening [16]: 85% of women had documented antenatal GBS screening, and 98% of

Impact of IAP and universal screening on perinatal GBS disease

Despite the high incidence of early-onset GBS disease in the pre-prevention era, monitoring disease trends was complicated by the fact that even large hospitals had only a small number of invasive cases annually. This necessitated surveillance in a large catchment area. To this end, in 1990 the Centers for Disease Control and Prevention in collaboration with state partners launched multistate invasive group B streptococcal disease surveillance as part of the Active Bacterial Core surveillance

IAP effectiveness

Direct IAP effectiveness estimates are helpful as a complement to disease trend data, and also provide a context for comparing IAP to other possible prevention strategies such as a GBS vaccine. A case-control analysis of the effectiveness of IAP among mother with obstetric risk factors reported an adjusted effectiveness of 86% (95% confidence interval, 66–94%) against invasive early-onset GBS disease, with slightly lower point estimates for the subgroup of mothers with intrapartum fever and

Maximizing the impact of IAP in the United States

From a review of ABCs invasive early-onset GBS cases that occurred in 2008–2009, we estimated that optimal implementation of prenatal screening and intrapartum prophylaxis could have prevented 31–43% of cases, suggesting that further reduction of the burden of early-onset GBS disease is achievable under current prevention strategies [19]. While the evaluation of laboratory practices for the processing and testing of prenatal screening specimens from the mothers of the cases in that study is

Global experience with IAP

Beyond the US, several industrialized countries have implemented IAP policies. Some (e.g., Spain, Canada, Australia) have adopted indications for prophylaxis similar to the US, and have documented declines similar to the United States [31], [32]. Countries and single hospitals that have adopted risk-based approaches have also documented declines [24]. A recent systematic review of neonatal GBS disease globally found that early-onset GBS disease incidence in countries that used IAP (0.23.1000

GBS vaccine considerations in the setting of widespread IAP

With a trivalent (serotypes 1a, 1b and III) GBS conjugate vaccine currently undergoing Phase II trials in pregnant women (clinicaltrials.gov identifiers NCT01446289, NCT01412801, NCT01193920) it is reasonable to consider factors that might influence the decision to introduce maternal GBS vaccination in a country such as the US where widespread IAP is already in place.

Compared to a serotype-specific maternal vaccine, IAP has certain advantages. First, it is effective against all GBS serotypes;

Conclusions

The experience in the United States has shown that universal screening and IAP for GBS-colonized women comprise a highly effective strategy against early-onset GBS infections that has been very well implemented at the population level. There are shortcomings, however, with the current GBS prevention efforts. Some of the limitations can be overcome by maximizing adherence to recommended practices, and there is room to further reduce the burden of early-onset GBS disease through improved

Acknowledgements

We acknowledge the hard work and contributions of all the members of the Active Bacterial Core surveillance GBS team over the years.

Conflicts of interest statement: None declared.

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    This work was funded solely by the Centers for Disease Control and Prevention.

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