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SCREENING SERIES

Group B Streptococcus: A Culture-based Prevention Strategy

Mara J. Dinsmoor, MD, MPH


In 1996, the Centers for Disease Control and Prevention (CDC) published guidelines for the prevention of perinatal transmission of Group B streptococcus (GBS).1 In those initial guidelines, the CDC recommended adopting one of two "separate but equal" protocols—one culture-based and one based on the presence or absence of risk factors. The experience gained in the ensuing years has built a strong case for the adoption of the culture-based strategy. This culminated in the publication of revised CDC guidelines in August 2002, suggesting that the culture-based strategy be implemented universally.2 These recommendations have been endorsed by the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists.3,4

TIMING OF CULTURES

In their initial reports on the efficacy of intrapartum antibiotic prophylaxis, Boyer et al5 performed cultures during a prenatal visit to determine which patients were colonized with GBS. They noted that 67% of patients with positive prenatal cultures actually had GBS colonization at the time of labor and delivery, while 9% of patients with negative prenatal cultures were GBS-positive at the time of delivery. Of note, only 20% of these cultures were performed in the third trimester, whereas most (67%) were collected in the second trimester. In 1994, Yancey et al6 reported that late intrapartum (35 to 37 weeks’ gestation) GBS cultures are very predictive of colonization status at delivery (Table 1). If the interval between antepartum and intrapartum cultures were less than 6 weeks, the antepartum cultures had a positive predictive value of 87% and a negative predictive value of 96%. If the interval were 6 weeks or longer, the positive predictive value dropped to 50% and the negative predictive value fell to 81%.

In terms of the risk of neonatal sepsis in culture-positive and culture-negative patients with and without risk factors, culture-positive women are the ones at highest risk (Figure 1). Boyer and Gotoff7 may have actually underestimated the risk in culture-positive women, as the prenatal visit at which the cultures were obtained was not specified. In prior studies by this group, the majority of cultures were performed at 15 to 28 weeks.5 As a result, many of the patients who had a positive prenatal culture may have been GBS-negative at delivery, thus falsely lowering the risk of neonatal sepsis in the "culture-positive" group.


View this table

Table1. Predictive Value of Third-trimester GBS Cultures for Intrapartum Colonization6

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 Figure1. Maternal colonization status/risk factors and risk of neonatal GBS sepsis7


DECISION ANALYSIS

Approaches to preventing GBS sepsis must balance the effectiveness of a preventive protocol with the number of women who require antibiotics and the costs of various protocols. In 1994, Rouse et al8 published a decision analysis of the theoretical implementation of 19 different GBS protocols based on a number of assumptions (Figure 2). This analysis revealed that the most effective and least expensive protocol for reducing the incidence of early-onset GBS sepsis would be one in which all women received antibiotics during labor—an option that is untenable for many reasons. By contrast, it was estimated that a risk-based protocol would lower the rate of GBS sepsis by 69% while treating 18% of mothers. A culture-based protocol would reduce neonatal sepsis rates by 86%, with 27% of mothers receiving treatment. The estimated costs of the two protocols were similar.


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 Figure2. Decision analysis for GBS prevention strategies8


RISK-BASED Versus culture-based protocols

No randomized trial has been performed comparing the two approaches to GBS prevention, as it has been estimated that a sample size of approximately 100,000 in each arm would be required.9 This leaves only the evidence provided by retrospective studies, with their inherent faults and biases. Boyer and Gotoff’s7 original work estimated that the use of risk factors would identify 74% of infected infants. Subsequent studies have reported that 40% to 60% of neonates with early-onset GBS sepsis have no risk factors for infection.10-12

Hafner et al13 reported that changing from a risk-based approach to a culture-based approach resulted in a significant reduction in neonatal GBS infections. In 3,623 deliveries from September 1992 to November 1994, antibiotics were administered to women with risk factors including premature rupture of the membranes (at less than 37 weeks), rupture of the membranes for more than 8 hours, labor for 18 hours or longer, maternal fever or diabetes, or a history of an infant with a GBS infection. A total of 432 women (11.9%) were treated, and 20 neonates (0.5%) were infected with GBS. From December 1994 to January 1997, antibiotics were administered in labor to women with positive vaginal/rectal cultures performed at 34 weeks. A total of 3,569 women delivered during this period, of whom 520 (14.6%) had GBS colonization. Only four neonates (0.1%) developed GBS sepsis. Two of these infants were born prior to 34 weeks’ gestation, and only one received intrapartum antibiotics. The other two infants were born at term to mothers with negative antepartum cultures.

Locksmith et al10 reported the results of three different GBS prophylaxis approaches, each practiced at different periods in the same hospital. These strategies included a selective screening protocol, a risk-based protocol, and a universal screening protocol. They found that the rates of both chorioamnionitis and postpartum endometritis were significantly reduced using the universal screening protocol compared with the other two protocols (Figure 3). Although neonatal GBS sepsis rates were lower with both the risk-based protocol and the universal screening protocol, neither reached statistical significance. In another study comparing early-onset GBS sepsis rates using different protocols, Main and Slagle11 reported that the rate of sepsis was 1.1 cases per 1,000 births during the 3-year period when a risk-based protocol was used. In the same hospital, subsequent use of a culture-based protocol over a 2-year period resulted in no cases of GBS sepsis. Although neither study was prospective or randomized, they represent the only comparisons of the two protocols that are currently available (Figure 4).


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 Figure3. Maternal and neonatal infection rates with three different protocols10

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 Figure4. GBS EONS rates in the United States with different management protocols10,11


Most recently, Schrag et al14 performed a population-based comparison of risk-based and culture-based protocols. They studied a stratified, random sample of births in eight geographic areas where the CDC performs active surveillance for GBS. All 312 deliveries resulting in the birth of a neonate with GBS were included, as well as 5,144 randomly selected deliveries (representing 629,912 live births) without neonatal GBS sepsis. Women with no documentation of prenatal GBS cultures were assumed to have been managed using a risk-based protocol. The risk of early-onset GBS sepsis was significantly lower among infants born to screened women compared with those in the risk-based group (adjusted relative risk, 0.46; 95% confidence interval, 0.36-0.60).

The culture-based protocol also appears to be easier for most practitioners to use. For example, Locksmith et al10 reported that 27% of cases of GBS sepsis occurring with a risk-based approach were due to protocol violations, compared with only 17% of cases occurring with a culture-based protocol. In another study, 94% of culture-positive patients received intrapartum antibiotics, while 71% of patients with unknown GBS status and prolonged rupture of membranes received intrapartum antibiotics.11 Other authors have reported compliance rates of 50% to 79% using the risk-based approach versus 80% to 90% using the culture-based approach (Figure 5).2,12,14


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 Figure5. Proportion of women receiving appropriate intrapartum antibiotics14


Although some have raised concerns that using a culture-based approach would lead to a large number of women requiring treatment, this has not proved to be the case. Antibiotic treatment rates in culture-based protocols average around 14%.2 Hafner et al12 reported that 11.9% of patients were treated using a risk-based approach, while 14.6% of patients were treated using a culture-based approach. In Main’s study,11 13.6% of patients had a positive culture, with 26.3% of women ultimately receiving antibiotics in labor. Schrag et al14 noted that 31% of patients received antibiotics when the culture-based approach was used, compared with 29% in the risk-based group. Others have reported treating up to 42% of patients using the risk-based approach.12

ANTIBIOTIC RESISTANCE

In recent years, increasing numbers of GBS strains have been reported that are resistant to erythromycin and clindamycin.15-17 Resistance rates vary from 6% to 21% for erythromycin and 3% to 15% for clindamycin. To date, no strains have been found that are resistant to penicillin or ampicillin. Following a culture-based strategy allows the clinician to request susceptibility testing in patients who are allergic to penicillin, permitting administration of reliable, effective intrapartum antibiotic prophylaxis. Although a polymerase chain reaction method for rapid detection of GBS (within 30 to 45 minutes) in the intrapartum period has proved highly sensitive (97%) and specific (100%) in a research setting, this technology is expensive and not yet widely available.18

CONCLUSION

The practitioner must weigh the available evidence in selecting the optimum GBS-prevention protocol to follow in pregnant women. Choosing culture-positive women to receive intrapartum antibiotic prophylaxis certainly makes sense. In the author’s experience, the bulk of evidence currently supports utilizing a culture-based protocol for prevention of neonatal GBS sepsis as the most effective strategy (Table 2).


View this table

Table2. Culture-based Protocol for Preventing Neonatal GBS Sepsis


Mara J. Dinsmoor, MD, MPH, is director of research, Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, Ill; and associate professor, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Ill.

References

  1. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: a public health perspective. Morb Mort Wkly Rpt. 1996;45(31):1-24.
  2. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: revised guidelines from the CDC. Morb Mort Wkly Rpt. 2002;51(RR-11):1-22.
  3. American Academy of Pediatrics Practice Guideline Endorsement. Prevention of perinatal group b streptococcal disease: revised guidelines from CDC. Available at: http://www.aap. org/policy/groupb.html. Accessed January 12, 2004.
  4. American Academy of Obstetricians and Gynecologists News Release, November 29, 2002. ACOG Advises Screening All Pregnant Women for Group B Strep. Available at: http://www.acog.org/from_home/publications/press_releases/nr11-29-02-1. cfm. Accessed January 12, 2004.
  5. Boyer KM, Gadzala CA, Kelly PD, et al. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease, II. Predictive value of prenatal cultures. J Infect Dis. 1983;148(5):802-809.
  6. Yancey MK, Schuchat A, Brown LK, et al. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol. 1996;88(5):811-815.
  7. Boyer KM, Gotoff SP. Strategies for chemoprophylaxis of GBS early-onset infections. Antibiot Chemother. 1985;35:267-280.
  8. Rouse DJ, Goldenberg RL, Cliver SP, et al. Strategies for the prevention of early-onset neonatal group B streptococcal sepsis: a decision analysis. Obstet Gynecol. 1994;83(4):483-494.
  9. Landon MB, Harger J, McNellis D, Mercer B, Thom EA. Prevention of neonatal group B streptococcal infection. Obstet Gynecol. 1994;84(3):460-462.
  10. Locksmith GJ, Clark P, Duff P. Maternal and neonatal infection rates with three different protocols for prevention of group B streptococcal disease. Am J Obstet Gynecol. 1999;18(2 pt 1):416-422.
  11. Main EK, Slagle T. Prevention of early-onset invasive neonatal group B streptococcal disease in a private hospital setting: The superiority of culture-based protocols. Am J Obstet Gynecol. 2000;182(6):1344-1354.
  12. Factor SH, Levin OS, Nassar A, et al. Impact of a risk-based prevention policy on neonatal group B streptococcal disease. Am J Obstet Gynecol. 1998;179(6 pt 1):1568-1571.
  13. Hafner E, Sterniste W, Rosen A, et al. Group B streptococci during pregnancy: a comparison of two screening and treatment protocols. Am J Obstet Gynecol. 1998;179(3 pt 1):677-681.
  14. Schrag SJ, Zell ER, Lynfild R et al for the Active Bacterial Core Surveillance Team. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med. 2002;347(4):233-239.
  15. Rouse DJ, Andrews WW, Lin FC, et al. Antibiotic susceptibility profile of group B streptococcus acquired vertically. Obstet Gynecol. 1998;92(6):931-934.
  16. Pearlman MD, Pierson CL, Faix RG. Frequent resistance of clinical group B streptococci isolates to clindamycin and erythromycin. Obstet Gynecol. 1998;92(2):258-261.
  17. Bland ML, Vermillion ST, Soper DE, Austin M. Antibiotic resistance patterns of group B streptococci in late third-trimester rectovaginal cultures. Am J Obstet Gynecol. 2001;184(6):1125-1126.
  18. Bergeron MG, Ke D, Menard C, et al. Rapid detection of group B streptococci in pregnant women at delivery. N Engl J Med. 2000;343(3):175-179.

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