Intrapartum Antibiotic Prophylaxis For Neonatal
Group B Streptococcal Disease
Ahmed Tarif A.A. Eltahawy, MD, Ph.D.
Group B streptococcus (GBS) was recognized as a major pathogen of neonatal disease in the 1970s. Vertical transmission of GBS during labour or delivery may result in early-onset GBS sepsis in the neonate, which constitutes 80% of the GBS disease among newborns. With a case-fatality rate of 5% to 20%, prevention of GBS neonatal disease has been an ongoing concern. Continued efforts to eradicate GBS-newborn disease require an understanding of the pathogen, colonization, and transmission, GBS sampling and detection methods, and maternal therapy.
Bacteriology and epidemiology
GBS are gram-positive organisms, arranged in diplococci or in chains. These bacteria are divided into eleven serotypes based on antigenic variation of capsular polysaccharides Ia, Ic, I b/c, II, IIc, III, IV, V, VI, VII, VIII. The serotypes accounting for the greatest percentage of neonatal and maternal infections are GBS capsular types, Ia, III, and V, serotypes Ib and II remain important but less frequent causes of invasive disease. Rates of GBS colonization of women can vary by race, geographic location, ethnic group, age, and socioeconomic status, but are similar between pregnant and non-pregnant women, with 10% - 30% of women colonized in either the gastrointestinal tract or the vagina. Vertical transmission of GBS to neonates occurs in 40% to 73% of culture-positive women, but only 1% to 2% of their infants develop early onset diseases. The presence or absence of maternal antibodies to GBS has been reported to be a risk factor for the disease. In one study, 76% of pregnant carriers with healthy neonates had detectable serum IgG to GBS whereas none of the seven women whose infants developed invasive GBS had detectable antibodies.
Risk factors for the development of GBS neonatal sepsis
Pregnant women with the following conditions are at high risk of having a baby with GBS disease:
q Diagnosis of GBS vaginal colonization or GBS bacteriuria in present or preceding pregnancy.
q Preterm labour (<37 weeks gestation)
q Prolonged rupture of membranes (>18 hours).
q Maternal fever (>38oC orally).
q Previous delivery of a newborn infant with GBS disease.
Treatment of GBS-carrier mothers with the above risk factors during labour will lead to 60% reduction in neonatal infection rate and 95% reduction in neonatal death due to this disease.
Maternal GBS colonization is transient and usually asymptomatic. However, GBS can cause disease at any age. Invasive GBS disease affects pregnant women and adults with underlying medical condition, such as diabetes mellitus, or other immunocompromising disorders. Symptomatic maternal infection often manifests as: urinary tract infections, chorioamnionitis, endometritis, post-partum wound infections, pyelonephritis, cystitis and sepsis. Factors that increase the likelihood of symptoms development in mothers are heavy colonization of the genitourinary tract, rupture of membranes for more than 12 hours and more than 6 vaginal examination during labour.
Infections in neonates and infants
predisposing maternal obstetric complications, and is directly related to the ascending spread of the pathogen from the vagina and cervix of colonized mothers. Early-onset infection is characterized by sepsis, respiratory distress, apnea, pneumonia, and less frequently meningitis
Long-term sequelae of both early- and late-onset invasive disease include hearing and vision impairment, mild learning disabilities, or severe mental retardation.
Different strategies have evolved over the past 3 decades such as decolonization attempts during pregnancy using oral antibiotics, post-partum chemoprophylaxis with intramuscular penicillin in all newborns and intrapartum prophylaxis. With the exception of intra-partum prophylaxis, other preventive approaches have been unsuccessful. Boyer and Gotoff demonstrated in a randomized clinical trial during the 1980s that antibiotic prophylaxis administered to GBS carriers during labour was very effective in preventing disease in newborns. Controversy remains as to the best method of identifying which women should receive intrapartum antibiotic prophylaxis. In collaboration with the American College of Obstetrics and Gynecology (ACOG), and the American Academy of Pediatrics, the Centers for Disease Control and Prevention (CDC) has developed two strategies for preventing perinatal GBS disease. The screening approach (culture-based protocol), which specifies that all pregnant women should be screened at 35-37 weeks’ gestation for GBS carriage. All identified carriers and women who deliver preterm before availability of a culture result should be offered intrapartum antimicrobial prophylaxis once they are in labour or have ruptured membranes. The non-screening approach (risk-based) specifies that intrapartum antimicrobial agents should be offered to women with risk factors (mentioned previously). Recommendations common to both strategies include the administration of intrapartum antibiotics to women with GBS bacteriuria, which is suggestive of heavy colonization, and to those who previously had an infant with GBS invasive disease. Re-analysis now shows that culture-based protocol provides greater reduction in early-onset neonatal disease than a risk-based protocol. The CDC replacement guidelines of August 2002 recommend culture-based GBS prevention; the risk-based strategy is no longer supported.
To optimize culture results a combined vaginal (lower lateral wall) and anorectal swabbing should be done. Collection of cultures between 35-37 weeks gestation is recommended to improve sensitivity and specificity of detection of women who remain colonized at the time of delivery. Collection of cervical specimens decreases the yield of GBS. The swabs should be placed for 18 to 24 hours in a selective broth medium that contains antibiotics that inhibit competitive organisms, and subcultured onto sheep blood agar plates. If no GBS are isolated, incubation should be repeated for an additional 24 hours. A limitation of rapid-screening methods which look for GBS antigens in the vaginal and rectal swabs such as coagglutination, enzyme immunoassay and latex particles agglutination is the lack of sensitivity in identifying mothers who are not heavily colonized. This may have significant implication, considering that neonatal infections often occur in infants born to mothers with light or moderate colonization. Polymerase chain reaction assay (PCR) is a promising new method with a sensitivity and specificity of 97% and 100% respectively. The length of time required to obtain the results is between 30 to 45 minutes.
Advantages of screening-based approach:
False-negative culture results are minimized, nearly all who are identified antenatally as carriers will still be colonized with the organism at delivery. This approach increases the likelihood of starting intrapartum prophylaxis earlier, before development of risk factors or symptoms, allowing time for adequate antibiotic levels to be reached in amniotic fluid.
Disadvantages of screening-based approach:
Lack of time to administer prophylaxis despite positive antenatal carrier state if there is a precipitous delivery. Missing infections in mothers who have no prenatal care. The possibility of obtaining negative culture prenatally but positive cultures at delivery.
Unresolved issues with culture-based protocol:
When caesarean delivery is done in early labour or with no labour before 37 weeks gestation is it better to wait for 3 to 4 hours to give antibiotics or to perform the caesarean delivery immediately? The treatment of women at 35 to 37 weeks gestation with a recent negative culture result, do they still need prophylaxis because they are at <37 weeks gestation?
Disadvantages of risk-based approach:
Inadequate time for prophylaxis when infants are delivered less than 4 hours following development of maternal risk factors. More than 50% of term newborns who develop GBS infection do not have maternal risk factors and therefore do not meet criteria for intrapartum prophylaxis based on the risk-based approach.
Intravenous penicillin G is generally used for intrapartum prophylaxis in a dose of 5 million unit as a loading dose, then 2.5 million unit intravenously every 4 hours until delivery. An alternative is ampicillin in a dose of 2 grams IV load, then one gram every four hours until delivery, this is also recommended when the patient becomes febrile during labour with a possibility of chorioamnionitis. For those with penicillin allergy, intravenous clindamycin is given in a dose of 900 mg every 8 hours until delivery. Vancomycin one gram IV every 12 hours until delivery is recommended when high rates of clindamycin resistance are prevalent.
Consequence of intrapartum antimicrobial prophylaxis
Intrapartum antimicrobial prophylaxis (IAP) has lowered the incidence of early-onset GBS sepsis by 50-80%. However, there are concerns that the use of IAP may select for infections caused by enterocbacteriaceae, including some strains resistant to antimicrobials especially in low-birth weight and premature neonates. Therefore rigorous surveillance for non-GBS early onset sepsis in combination with targeted research activities should be used to guide future prevention strategies.
It is anticipated that a multivalent vaccine containing the major serotypes could be effective against most invasive GBS disease. Several challenges remain before vaccine can be implemented such as the continued shift in GBS serotype prevalence, the optimal strategy for vaccine administration, and concerns regarding teratogenicity and other adverse effects, which would limit the evaluation of trial vaccines in pregnant women.