Group B Strep & Antibiotic Prophyllaxis

Strep bacteria

Streptococcus is a genus of spherical (coccus) bacteria that, because of the way they divide, grow in chains, from pairs to long chains of multiple organisms. There are over 50 different species that have been identified. Some of them cause health problems in humans ranging from dental caries (S. mutans typically) to pneumonia (S. pneumoniae). One species in particular, S. pyogenes, is implicated in a wide variety of severe disease from toxic shock syndrome, to necrotizing fasciitis, impetigo, pneumonia, sepsis, and the common "strep throat".

Many Streptococcus species are harmless to humans and some even beneficial. A number of Streptococcus species colonize the human body and form part of the human microbiome. Long thought to be largely commensual (benefitting from the human body while causing no harm), science is now beginning to understand that some and perhaps many of these species have in fact mutualistic relationship with the human body. Both organisms derive benefit.

Group B Strep

S. agalactiae is a variety of Streptococcus bacteria that colonizes vaginas and the lower intestinal tract of females (and the genitourinary and lower intestinal tract of males) (Bliss, 2002). It is the only known member of a subgroup termed Lancefield Group B and hence is commonly referred to as Group B strep or GBS. The population prevalence is around 15% - 25% of women in the US. That is, at any given time between 15% and 25% of women will be colonized with GBS.

GBS generally doesn't cause disease in healthy adult women but has been implicated in invasive disease in nursing home residents, an immune compromised population. A typical colonization in otherwise healthy pregnant women is thought to persist for less than six weeks but may be highly variable.

The situation becomes more complicated for women during labor and delivery.

Microbiome

Humans are colonized by many types of bacteria as well fungi and viruses. Indeed there are ten times more microbial cells than human cells in the average human body. These organisms are as important for human health as our own cells. They play a vital role in absorbing, digesting and utilizing food, and in preventing or allowing a wide range of diseases including diabetes, autoimmune disorders, obesity, allergies, and likely some cancers. As the baby passes through the birth canal, it picks up many bacterial, fungal, and probably viral species which provide the founding species of the baby's own microbiome.

The establishment of this microbiome plays a very significant role in training the immune system of the newborn about what species to attack and, importantly, what species to ignore. The various microorganisms also keep each other in check and help to establish a healthy, stable, and necessary microbiome. (See my blog post, We Are Not Alone)

Group B Strep during birth

If, however, GBS is one of those species the baby is exposed to in the birth process, it can cause infections which may be serious, even causing death of the newborn. Prior to the widespread use of antibiotics in labor, between 1.5 and 3 out of every 1000 newborns developed invasive GBS disease (Zangwell, et al, 1992; Baker et al, 1990). That means approximately 1 of every 100 babies who are exposed to GBS will develop significant disease.

A smaller proportion will develop GBS sepsis or pneumonia, or more rarely menningitis, and a proportion of those babies will die as a result. A further known complication is that GBS can cross the placental barrier and cause GBS sepsis in utero and even fetal demise. Fortunately this event is thought to be extremely rare (Ramus, et al, 1999).

The policy

In response to the accumulation of information beginning in the 1970s, the American College of Obstetrics and Gynecology began to formulate a policy, finalized and implemented by a consensus group from ACOG and the US Centers for Disease Control in 1996, to obtain recto-vaginal cultures on pregnant women at 36 weeks gestation and provide antibiotics during labor to those who screened positive. As a result of this initiative the incidence of invasive GBS disease declined from approximately 1.5 per 1000 live births to 0.5 per 1000 live births. (These results applied to early onset GBS disease of the newborn. Another category, late onset GBS disease, was not impacted by the introduction of antibiotics) (Schrag et al, 2000).Since then universal screening of pregnant women at 36 weeks gestation and the prophyllactic administration of antibiotics during labor for those who have positive screens has become the standard of care in the US. Though this sounds like a pretty cut and dried success story, a closer look at the literature reveals some significant concerns.

The results

First, the studies results that were used to justify the prophylactic administration of antibiotics all focused on the incidence of GBS disease in newborns, but when researchers went looking for evidence that giving prophylactic antibiotics in labor was saving newborn lives, it simply wasn't there. While the Intrapartum Antibiotic Protocol (IAP) did indeed cut the number of cases of early onset GBS disease in newborns, no study has ever demonstrated that IAP results in fewer neonatal deaths from GBS. In other words, providing antibiotics only to newborns who had GBS disease produced exactly the same number of newborn deaths as providing prophylactic antibiotics to every pregnant woman who had a positive screen for recto-vaginal GBS (WHO Reproductive Health Library Summary, 2014).

The data suggest that prophylactc antibiotics must be given to 25 women (and thus 25 in utero babies) to prevent one case of early onset GBS disease (Ohlsson and Shah, 2014). Therefore, giving antibiotics to 25 women and their in utero babies will prevent one newborn from getting GBS disease but doesn't prevent any newborn deaths.

Second, there were few IAP studies done and those that were done, weren't done very well.

The Cochrane Reviews are systematic reviews of primary research in human health care and health policy, and are internationally recognized as the highest standard in evidence-based health care. A Cochrane Review published 10 June, 2014 was able to identify only three studies, all over 20 years old, that compared treatment of GBS positive women with no treatment (Ohlsson and Shah, 2014). There was inadequate randomization of subjects to treatment arms and there was no placebo control group in any study. Further the researchers were not blinded to the treatment arms - that is, they knew which babies' mothers had received IAP and which hadn't. In the Cochrane Review authors' words:

"We found a high risk of bias for one or more key domains in the study methodology and execution... There is lack of evidence from well designed and conducted trials to recommend IAP to reduce neonatal EOGBSD (GBS disease). The opportunity to conduct such trials has likely been lost, as practice guidelines (albeit without good evidence) have been introduced in many jurisdictions. This review finds that giving antibiotics is not supported by conclusive evidence."

Finally, a recent study published in the infectious disease edition of the flagship British medical journal, Lancet, reports that the introduction of IAP in the Netherlands actually increased the rate of early onset GBS disease (and late onset GBS disease). IAP was introduced in the Netherlands in 1999 following its introduction three years earlier in the US. In a study of the entire population of the Netherlands from 1987 through 2011, researchers found that the incidence of early onset GBS disease nearly doubled from 0.11 per 1000 live births to 0.19 per 1000 live births, prompting nationwide calls for the guidelines to be reassessed and alternative prevention methods considered (Bekker, et al, 2014). No similiar study has been undertaken in the US.

Clearly the jury is still out on IAP. No mother wants her newborn to be ill and require hospitalization with IV antibiotics. But what about the 25 mothers who receive antibiotics and did not need them? Even more importantly, what about the 24 newborns who receive antibiotics but would not have gotten sick even without them? It is true that providing antibiotics to fifty people, 25 moms and 25 soon to be born babies, may prevent one case of GBS disease (at least in the US), but there is no evidence it will save any lives.

The 25 women who received unneeded antibiotics may experience side effects ranging from mild to severe, but the evidence is accumulating that the 24 babies who received unneeded antibiotics, and even the offspring of the female newborns when they have children, may suffer from long term, debilitating, and possibly fatal sequelae.

This information is not being provided to women when they consent to receive IAP, which is inconsistent with the principle and the legal obligation of informed consent. Pregnant women are under tremendous pressure to give consent without adequate information and to accept interventions that have demonstrated dubious benefit and significant potential harm.

This is no small ethical issue for a profession whose prime directive is primum non nocere - first do no harm. At the very least it should be clear that it is neither an irrational nor unrealistic position for a pregnant women to question or refuse prophylactic antibiotics for a positive GBS screen.

Works Cited:

Bliss SJ, Manning SD, Tallman P, et al: Group B streptococcus colonization in male and nonpregnant female university students: A cross-sectional prevalence study. Clin Infect Dis 2002; 34:184-190.

Ramus RM, McIntire DD, Wendel GD, Jr. Antibiotic chemoprophylaxis for group B strep is not necessary with elective cesarean section at term [Abstract]. Am J Obstet Gynecol 1999;180:S85.

Zangwill KM, Schuchat A, Wenger JD. Group B streptococcal disease in the United States, 1990: report from a multistate active surveillance system. MMWR 1992;41(SS-6):25--32.

Baker CJ, Edwards MS. Group B streptococcal infections. In: Remington J, Klein JO, eds. Infectious diseases of the fetus and newborn infant. Philadelphia: W.B. Saunders, 1990:742--811.

Schrag SJ, Zywicki S, Farley MM, et al. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000;342:15--20.

WHO, Reproductive Health Library Summary. Intrapartum antibiotics for known maternal Group B streptococcal colonization, 22 September, 2014.

Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database of Systematic Reviews 2014, Issue 6.

Bekker V, Bijlsma MW, van de Beek D, Kuijpers TW, van der Ende A. Incidence of invasive group B streptococcal disease and pathogen genotype distribution in newborn babies in the Netherlands over 25 years: a nationwide surveillance study. Lancet Infect. Dis. Volume 14, No. 11, 1083–1089, November 2014

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