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Preventing group B streptococcal infections in newborns

Porta, Kelly MS, PA-C; Rizzolo, Denise PA-C, PhD

Journal of the American Academy of PAs: March 2015 - Volume 28 - Issue 3 - p 24–29
doi: 10.1097/01.JAA.0000460915.52391.70
CME: Neonatology
Free
CME

Despite advances in intrapartum antibiotic prophylaxis (IAP), group B streptococcal infection continues to be a predominant cause of early-onset disease in neonates. About 2% of neonates exposed to group B Streptococcus develop clinical manifestations including sepsis, pneumonia, and meningitis. Screening in late pregnancy reduces the incidence of early-onset sepsis by more than 80%. Clinicians must be able to identify the risk factors and clinical manifestations of group B streptococcal infection and to understand management and prevention guidelines.

Kelly Porta is an assistant professor and academic coordinator in the PA program at Hofstra University in New York. She practices at the newborn nursery at Montefiore Medical Center and pediatric ICU at Jacobi Medical Center. Denise Rizzolo is an associate professor in the PA program at Seton Hall University in South Orange, N.J., an assistant clinical professor in the Pace completion program in New York City, and practices urgent care in Springfield, N.J. The authors have disclosed no potential conflicts of interest, financial or otherwise.

Earn Category I CME Credit by reading both CME articles in this issue, reviewing the post-test, then taking the online test at http://cme.aapa.org. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of March 2015.

Figure

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Box 1

Box 1

In the 1970s, researchers identified group B Streptococcus as the leading cause of morbidity and mortality in neonates.1,2 Before the initiation of intrapartum antibiotic prophylaxis (IAP) in the 1990s, early-onset group B streptococcal disease affected about 1.7 to 1.8 infants per 1,000 live births.1,3 In response to this significant burden of disease, in 1996 the CDC issued its first set of guidelines for the prevention of group B streptococcal infection.1 The CDC revised these guidelines in 2002 and again in 2010. Nevertheless, group B streptococcal infection continues to be a predominant cause of early-onset disease in neonates.4 Between 1% and 2% of neonates exposed to group B Streptococcus develop clinical manifestations of infection, including sepsis, pneumonia, and meningitis.1

Screening for group B Streptococcus in late pregnancy, and administering IAP for mothers who test positive and those who have risk factors, reduces the incidence of early-onset sepsis by more than 80%.3 However, even with medical advances and preventive measures, group B Streptococcus remains a significant cause of morbidity and mortality in neonates.5,6 Clinicians must be able to identify risk factors and clinical manifestations of group B Streptococcus infection and follow the CDC's latest management and prevention guidelines.

Box 2

Box 2

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ABOUT GROUP B STREPTOCOCCUS

Group B Streptococcus (also called Streptococcusagalactiae) is a gram-positive bacterium that takes the form of pairs or chains.2 It colonizes the gastrointestinal and genital tracts of 10% to 30% of pregnant women.1 Researchers find that neonates born to mothers who are positive for group B Streptococcus are 25 times more likely to develop early-onset group B streptococcal disease.1,7 Maternal group B Streptococcus colonization can be transient, intermittent, or persistent.1,8 Group B Streptococcus can cause early-onset disease within the first week of life, and late-onset disease, which occurs in neonates between 7 days and 3 months of life. The bacterium also can infect children, older adults, pregnant and postpartum women, and may result in stillbirth and preterm labor.1,6,9,10

Maternal colonization is the primary risk factor for developing group B streptococcal infection.1 Other risk factors are listed in Table 1.

Table 1

Table 1

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CLINICAL PRESENTATION

A neonate's age at the time he or she develops symptoms of group B streptococcal infection indicates whether the neonate has early-onset or late-onset disease.

Early-onset disease generally presents clinically during the first week of life, with most neonates becoming ill less than 24 hours postpartum. Although the disease is typically transmitted during vaginal labor and delivery, it also may occur before rupture of membranes.11,12 Neonates with early-onset disease commonly present with pneumonia (10%) and sepsis (83%); meningitis is less frequent (7%).1,6 Respiratory distress, grunting, retractions, hypoxemia, and tachypnea are typical clinical manifestations of pneumonia.10 Neonates may exhibit other signs and symptoms indicative of sepsis such as apnea, lethargy, poor feeding, temperature instability, hypotension, or irritability.5,10 Neonates rarely present with fever in the first day of life, although they may be febrile later.10 Neonates with early-onset group B streptococcal meningitis may present with nonspecific symptoms such as apnea or respiratory distress.10

Ten serotypes of group B Streptococcus have been identified (Ia, Ib, and II through IX). About 95% of early-onset disease is associated with serotypes Ia, Ib, II, III, and V.6,10

Late-onset disease occurs from 7 to 89 days postpartum and typically is contracted by household contacts.1,10 About 65% of patients with late-onset disease present with bacteremia of no known source. Symptoms may include fever (100.4° F [38° C] or higher), irritability, poor feeding, lethargy, grunting, and apnea.10 Meningitis, another sequela of late-onset disease, occurs in nearly 30% of patients.10 Symptoms of meningitis may range from irritability and lethargy to bulging fontanel and seizures.10 Additional manifestations of late-onset disease include urinary tract infections, respiratory illness, and cellulitis.1

Ninety percent of late-onset disease is associated with serotypes Ia, Ib, II, III, and V.6,10

Late-onset disease occurs in 0.32 per 1,000 births and its incidence is largely unaffected by IAP; therefore, this article will focus on the prevention of early-onset disease.13

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PREVENTION

The CDC first recommended IAP for the prevention of group B streptococcal infections in its 1996 guidelines.14 Before the introduction of IAP, early-onset disease occurred in 1.7 to 1.8 of every 1,000 live births.1,3 Following IAP introduction, the rate fell to 0.5 for every 1,000 live births from 1999 to 2001.15 The guidelines directed practitioners to initiate IAP for women with either a positive culture or risk factors including:

  • prolonged rupture of membranes (PROM), defined as rupture more than 18 hours before delivery
  • prematurity (gestational age less than 37 weeks)
  • intrapartum maternal fever (temperature of 100.4° F [38° C] or greater).1,14

In 2002, the CDC updated its guidelines to recommend universal group B Streptococcus screening for all pregnant women at between 35 and 37 weeks gestation, resulting in a further decrease in incidence of group B Streptococcus.1

The most recent update, in 2010, continues to recommend universal screening of pregnant women using vaginal and rectal cultures at 35 to 37 weeks gestation.1 The guidelines also recommend IAP for:

  • women who delivered a prior neonate with group B streptococcal disease (no culture is required for these women)
  • women with group B Streptococcus bacteriuria during the current pregnancy
  • women with positive cultures
  • women with known risk factors (PROM, prematurity, or intrapartum maternal fever) whose culture results are unknown.1

Women who are positive for group B Streptococcus and are scheduled for a cesarean section before rupture of membranes do not require IAP.1

The practitioner should introduce IAP and order a group B Streptococcus culture upon hospital admission for women with preterm labor and preterm premature rupture of membranes. IAP may be discontinued in these patients if labor ceases or culture results are negative. However, in women with positive cultures whose labor ceases, IAP should begin when labor resumes.

In some cases, patients who have preterm premature rupture of membranes but are not in labor receive antibiotics.1 If the antibiotics cover group B Streptococcus, no additional antibiotics are necessary. The CDC recommends IAP for 48 hours if a woman has preterm premature rupture of membranes, is not receiving antibiotics, and her group B Streptococcus status is unknown. The clinician may discontinue IAP if the culture results are negative.1

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LABORATORY RECOMMENDATIONS

To further decrease the incidence of early-onset disease, the CDC advocates for proper laboratory procedures and collection. This is especially important because studies confirm that many neonates who develop early-onset disease were born to group B Streptococcus-negative mothers (false negatives).16,17 Providers should obtain swabs of both the vagina and rectum and specifically request cultures for group B Streptococcus and request susceptibility testing if the woman has a history of anaphylaxis to a beta-lactam.1,16

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PRIMARY PROPHYLAXIS

IAP Penicillins are the primary antibiotics used for IAP because they have the narrowest spectrum and are less likely to cause bacterial resistance.18 Ampicillin is an acceptable alternative to penicillin G in preventing transmission of group B Streptococcus during vaginal labor and delivery.18 Both antibiotics achieve rapid therapeutic concentrations in the fetal circulation and amniotic fluid without evidence of neurotoxicity to the mother or fetus.1,15,18 For women with a history of penicillin allergy that still supports cephalosporin use, cefazolin is an alternative, since its pharmacokinetics are similar to penicillin.2

Because 20% of group B Streptococcus samples cultured are resistant to clindamycin, sensitivity testing should be performed on specimens before antibiotic administration. If sensitivity testing reveals clindamycin resistance, the CDC recommends using vancomycin.1,18 Because of increased bacterial resistance, the CDC no longer recommends erythromycin, which once was an acceptable alternative for IAP in women with a history of anaphylaxis to penicillin. See Table 2 for IAP prophylaxis guidelines.1

Table 2

Table 2

The CDC defines adequate prophylaxis as treatment with a beta-lactam for more than 4 hours before delivery.1 However, researchers found some benefit to IAP administered less than 4 hours before delivery. One study found transmission rates of group B Streptococcus to the neonate as follows:

  • IAP 1 hour before delivery, 46%
  • IAP 1 to 2 hours before delivery, 29%
  • IAP 2 to 4 hours before delivery, 2.9%
  • IAP more than 4 hours before delivery, 1.2%.19

Although the CDC recommends clindamycin and vancomycin for IAP in women who have demonstrated anaphylactic reactions to penicillin, minimal data support administration of these alternatives; therefore, alternative agents are recommended but not included in the definition of adequate prophylaxis.1,18

The introduction of IAP undoubtedly has reduced the incidence of early-onset disease; however, no treatment can be considered 100% effective in preventing group B streptococcal disease. False negatives or failure to receive appropriate antepartum testing may lead to early-onset disease in the neonate.

Secondary prophylaxis The 2010 CDC guidelines include directives regarding management of neonates born to group B Streptococcus-positive and group B Streptococcus-unknown mothers with risk factors.1 The American Academy of Pediatrics has since endorsed these guidelines and they are now part of neonatal hospital protocols. Additionally, the Committee on Fetus and Newborn (COFN) and the Committee on Infectious Disease support these guidelines, yet the COFN make further recommendations as described later.20

The CDC algorithm for secondary prophylaxis of group B Streptococcus is shown in Figure 1.

Figure 1

Figure 1

Symptomatic neonates When a neonate presents with signs of group B streptococcal disease, the practitioner should perform a complete sepsis evaluation, including a complete blood cell (CBC) count with white blood cell (WBC) differential and platelet count, along with a blood culture.1 If the neonate is clinically stable, the CDC recommends a lumbar puncture.1 This test is important for the diagnosis of meningitis because up to 38% of neonates with meningitis have negative blood cultures.20-22 If the neonate presents with respiratory distress, the CDC recommends a chest radiograph.1

The clinician should immediately start the neonate on empiric antibiotics that cover group B Streptococcus and other common pathogens such as Escherichia coli that cause early-onset sepsis.1,18 Clinicians often use ampicillin and gentamicin until culture and sensitivity results come back; however, consider possible resistant strains when choosing antibiotics.

Asymptomatic neonates with adequate maternal IAP Term and preterm neonates born to mothers who received adequate IAP do not need diagnostic testing. Instead, the CDC recommends that asymptomatic neonates be observed for 48 hours or more status-post delivery.1,18 Early discharge in term neonates may be appropriate only if the mother establishes early medical follow-up with a pediatric provider, all discharge criteria are met, and the mother or caregiver is reliable.1,18

Late-preterm neonates (35-36 weeks gestation) with adequate IAP Neonates of 35 to 36 weeks gestation who do not have signs of group B Streptococcus and whose mothers received adequate IAP do not require a diagnostic evaluation.1

Asymptomatic neonates with inadequate maternal IAP Before the 2010 guidelines, the CDC recommended partial sepsis evaluations (CBC count and blood culture) for all neonates with inadequate maternal IAP.11 Studies completed after the 2002 guidelines (but before the 2010 guidelines) indicated that a neonate's clinical presentation is a better indicator of sepsis than laboratory evaluation.1 The current guidelines suggest observation for 48 hours or more (without diagnostic evaluation) for asymptomatic term neonates born without prolonged rupture of membranes to group B Streptococcus-colonized mothers or mothers with risk factors who did not receive adequate IAP.1 However, if the neonate is preterm or the mother had prolonged rupture of membranes, the CDC recommends observation for 48 hours or more and a partial sepsis evaluation, including blood culture and a CBC count with differential and platelet count.1,14 In preterm neonates whose mothers had inadequate IAP, the COFN also recommends an evaluation but does not recommend drawing a blood culture unless antibiotics will be initiated.23 However, observation is recommended by the COFN in late-preterm neonates of 35 to 36 weeks gestation who do not show signs of early-onset disease and whose mothers had inadequate IAP.23

Asymptomatic neonates born to mothers with chorioamnionitis, regardless of group B Streptococcus status Pediatric and obstetric providers must coordinate with one another about maternal status and whether chorioamnionitis is suspected. At times, fever may be a mother's only presenting sign. The CDC recommends that neonates born to mothers diagnosed with chorioamnionitis receive a partial sepsis evaluation, including a blood culture and CBC count with differential and platelet count. The clinician should administer prophylactic antibiotics to cover for group B Streptococcus, E. coli, and gram-negative organisms pending results of the blood culture.1,18 According to Polin and colleagues, the timing of the CBC count is extremely important because the WBC count is more sensitive if drawn after 6 to 12 hours of life, rather than immediately following delivery.20 The COFN further suggests obtaining a C-reactive protein level at 6 to 12 hours of life, which may support the suspicion of infection.23

Asymptomatic term and preterm neonate with prolonged rupture of membranes (18 hours or more) regardless of group B Streptococcus status According to the CDC, any neonate born to a mother with prolonged rupture of membranes should have a blood culture and a CBC count with differential and platelet count at birth or 6 to 12 hours of life. Pediatric practitioners also should observe the neonate for 48 hours or more for clinical deterioration.18 The COFN supports close hospital observation without an evaluation; however, if close observation is not possible, a limited evaluation should be performed.23

Duration of antibiotics The CDC does not make recommendations for the duration of antibiotic treatment in neonates for secondary prophylaxis. The COFN suggests treating an asymptomatic term neonate for 48 hours or less (72 hours or less for preterm neonates) pending negative cultures.23

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SEEKING A VACCINE

Efforts are under way to develop a maternal vaccine to supplement IAP.1,3,4,24 Serotype-specific and simple protein vaccines have been studied.24 Administering vaccines to nonpregnant adolescent girls or pregnant women early in the third trimester can delay colonization and help strengthen immunity that may be passed on to the neonate.24 Such vaccinations might help reduce the number of patients with late-onset disease, stillbirths, and preterm labor related to group B Streptococcus, and would benefit:

  • neonates born to women with false-negative cultures resulting from group B Streptococcus transience or laboratory error
  • preterm neonates born before the completion of maternal group B Streptococcus cultures
  • neonates born via precipitous delivery with inadequate IAP.4,5

Although the FDA has not approved any vaccine, trials have confirmed that vaccination can reduce group B Streptococcus colonization.1,3

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CONCLUSION

For decades, group B Streptococcus has been a leading cause of morbidity and mortality in neonates. Although the incidence of infection declined significantly following the introduction of IAP in the late 1990s, group B Streptococcus remains the primary cause of sepsis in neonates. Obstetric and pediatric practitioners must identify patients at risk and follow the CDC's guidelines for preventing and treating this infection.

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REFERENCES

1. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010;59(RR-10):1-36.
2. Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev. 2013;1:CD007467.
3. Schrag SJ, Verani JR. 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. Vaccine. 2013;31(suppl 4):D20–D26.
4. Burns G, Plumb J. GBS public awareness, advocacy, and prevention—What's working, what's not and why we need a maternal GBS vaccine. Vaccine. 2013;31(suppl 4):D58–D65.
5. Mukhopadhyay S, Puopolo KM. Risk assessment in neonatal early onset sepsis. Semin Perinatol. 2012;36(6):408–415.
6. Phares CR, Lynfield R, Farley MM, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA. 2008;299(17):2056–2065.
7. Boyer KM, Gotoff SP. Strategies for chemoprophylaxis of GBS early-onset infections. Antibiot Chemother. 1985;35:267–280.
8. Oh W. Early onset neonatal group B streptococcal sepsis. Am J Perinatol. 2013;30(2):143–147.
9. Goldenberg RL, Thompson C. The infectious origins of stillbirth. Am J Obstet Gynecol. 2003;189(3):861–873.
10. Puopolo KM, Baker CJ. Group B streptococcal infections in neonates and young infants. UpToDate. Accessed January 1, 2015.
11. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep. 2002;51(RR-11):1–22.
12. Baker C. Chemoprophylaxis for the prevention of neonatal group B streptococcal disease. http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?21/16/21761?source=HISTORY. Accessed January 2, 2015.
13. Centers for Disease Control and Prevention. Active Bacterial core surveillance report. Emerging Infections Program Network. Group B Streptococcus, 2012. www.cdc.gov/abcs/reports-findings/survreports/gbs12.html. Accessed December 31, 2014.
14. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: a public health perspective. MMWR Recomm Rep. 1996;45(RR-7):1–24.
15. Schrag SJ, Zell ER, Lynfield R, et al. Active Bacterial Cora 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.
16. Centers for Disease Control and Prevention. Procedures for Laboratories. http://www.cdc.gov/groupbstrep/downloads/Lab-slideset.ppt. Accessed December 5, 2014.
17. Van Dyke MK, Phares CR, Lynfield R, et al.Evaluation of universal antenatal screening for group B Streptococcus. N Engl J Med. 2009;360(25):2626–2636.
18. Baker CJ, Byington CL, Polin RA.Committee on Infectious Diseases; Committee on Fetus and Newborn. Policy statement—recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics. 2011;128(3):611–616.
19. de Cueto M, Sanchez MJ, Sampedro A, et al. Timing of intrapartum ampicillin and prevention of vertical transmission of group B streptococcus. Obstet Gynecol. 1998;91(1):112–114.
20. Polin RA. Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129(5):1006–1015.
21. Stoll BJ, Hansen N, Fanaroff AA, et al. To tap or not to tap: high likelihood of meningitis without sepsis among very low birth weight infants. Pediatrics. 2004;113(5):1181–1186.
22. Garges HP, Moody MA, Cotten CM, et al. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters. Pediatrics. 2006;117(4):1094–1100.
23. Brady MT, Polin RA. Prevention and management of infants with suspected or proven neonatal sepsis. Pediatrics. 2013;132(1):166–168.
24. Jordan HT, Farley MM, Craig A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, population-based analysis. Pediatr Infect Dis J. 2008;27(12):1057–1064.
25. Tita ATN. Intraamniotic infection (chorioamnionitis). UpToDate. Accessed January 1, 2015.
    26. Benitz WE, Gould JB, Druzin ML. Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics. 1999;103(6):e77.
    Keywords:

    Group B Streptococcus; sepsis; neonates; pregnancy; intrapartum antibiotic prophylaxis (IAP); antibiotics

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