Group B strep (GBS) in pregnancy which can lead to early onset GBS (EOGBS) infection in neonates
1. What every clinician should know
Clinical features
Group B streptococcus (GBS), a gram positive bacteria, causes invasive disease in pregnant women and their newborns. GBS colonizes the GI and GU tracts of 10-30% of pregnant women. The organism can be transmitted to the neonate primarily through exposure to infected secretions in the course of vaginal delivery.
Pregnant women can become infected with GBS, resulting in urinary tract infections, pyelonephritis, pneumonia, sepsis and postpartum endometritis.
Newborns may become ill within the first 7 days of life, resulting in early onset GBS (EOGBS) versus late onset infection, which occurs after the first 7 days up until 3 months of age.
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EOGBS generally presents with signs of sepsis or pneumonia (respiratory symptoms) within the first 24-48 hours. Effective prevention strategies instituted during delivery have significantly decreased the incidence of EOGBS from 1.7 cases/1000 live births in the early 1990s to 0.34-.37 cases/1000 live births in 2010.
Risk factors
Risk factors for EOGBS include maternal colonization with GBS, gestational age less than 37 weeks, prolonged rupture of membranes (More than 18 hours), intraamaniotic infection, Black race, young maternal age, low maternal GBS-specific anticapsular antibody, previous delivery of a baby with invasive GBS disease and GBS bacteriuria.
2. Diagnosis and differential diagnosis
Urine cultures should be obtained from all pregnant women at the initial visit. If GBS is identified in the initial urine specimen but is less than 105, this should be recorded in the maternal record and requires intrapartum antibiotic prophylaxis(IAP) in labor. If GBS identified in the urine is greater than 105, the mother should be treated for asymptomatic bacteriuria. This occurs in 2-7% of pregnant women and is a sign of heavy colonization. Following a 7 day course of antibiotics, obtain a test of cure and record GBS colonization in the medical record because this woman requires IAP.
Diagnosis of GBS colonization is also made by GBS cultures obtained by swabbing the lower vagina and rectum (through the anal sphincter). Swabs obtained by the provider or the patient yield similar colonization rates. Once swabs are obtained, an enrichment broth should be used to maximize identification of beta hemolytic GBS.
Rapid GBS tests are commercially available PCR-based tests and are highly sensitive and specific. However, their real world performance in labor has been limited. The advantage of these tests is that they eliminate the need for antepartum cultures and allow treatment of those babies at greatest risk for disease, i.e. those whose mothers are colonized in labor. Note: Colonization is intermittent and some small percentage of women will be GBS negative at 35 weeks but positive at delivery at 40 weeks.
The strategy to prevent EOGBS relies on screening pregnant women and giving IAP to those who are GBS positive. If screening is not done prior to labor, women should receive IAP based upon risk factors alone: rupture of membranes after 18 hours, gestational age greater than 37 0/7 weeks, fever in labor above100.4.
3. Management
Antepartum
Preterm labor.Women who present with preterm labor should have a GBS culture obtained on admission. If tocolysis is utilized, IAP should be given while GBS status is unknown because preterm babies are at the greatest risk for infection. If labor does not progress, discontinue IAP until labor begins. If the initial culture is positive, record in the chart and give IAP in labor. If the culture is negative and the patient goes into labor within 5 weeks, no IAP is indicated. If the patient reaches 35-37 weeks and more than 5 weeks have passed since the initial culture, another GBS rectovaginal culture should be obtained.
Preterm premature rupture of membranes.Women with pPROM should have a GBS culture obtained on admission. Antibiotics given for latency should include an antibiotic such as ampicillin to cover GBS. If labor does not ensue after the latency antibiotics have been completed and the GBS culture is positive, give IAP in labor. A negative culture does not require IAP in labor despite preterm gestation and prolonged rupture of membranes.
Term.Routine screening should be done at 35-37 weeks gestation on all women except those with GBS bacteriuria during the index pregnancy, those whose previous baby had invasive GBS disease or those who have had a culture within the 5 weeks prior due to preterm labor or premature rupture of the membranes. If the GBS culture is positive, IAP is given in labor.
Intrapartum
GBS status should be known on admission. Information from prenatal records should be sent to the birth hospital with this critical information. In addition, pregnant women should be informed of their GBS status to allow them to prompt providers in labor. IAP should be given to all GBS positive women except those who have a cesarean delivery prior to labor or rupture of membranes.
If GBS status is unknown in labor, give IAP if rupture of membranes is greater than 18 hours, gestational age is less than 37 0/7 weeks, fever is above 100.4 in labor. Note: T.100.5 may indicate intraamniotic infection that should be treated with broad spectrum antibiotics to cover GBS and other vaginal pathogens.
IAP.Give ampicillin or penicillin. If If penicillin allergy, determine allergy. If rash, give Cefazolin. If hives, give vancomycin unless GBS isolate is known to be sensitive to clindamycin (45% if GBS isolates are clindamycin resistant). Resistance to erythromycin is also common and there is data suggesting that erythromycin does not penetrate the amniotic sac.
Postpartum
IAP should be discontinued at the time of delivery.
Postpartum maternal disease may occur as GBS can cause urinary tract infection, pyelonephritis, endometritis and sepsis. It should be noted that because GBS can be a significant factor in postpartum infection, antibiotic coverage that includes coverage for gram positive organisms is appropriate empiric therapy. Include penicillin, cephalosporin or clindamycin in the antibiotic regimen. Duration of antibiotics and route of delivery depends on the process treated; for instance, oral cephalosporins for 7 days for uncomplicated UTI is reasonable. However, 3-5 days of broad spectrum IV antibiotics may be more appropriate for post-cesarean endometritis even when GBS is the only organism that grows from blood cultures.
4. Complications
Neonatal complications
Neonatal complications of GBS infection include sepsis, pneumonia and meningitis, with variable and sometimes devastating longterm sequelae. Maternal intrapartum antibiotic prophylaxis is the best intervention to minimized early onset GBS disease in the neonate. IAP does not affect the occurrence or severity of late onset GBS disease.
Maternal complications
Maternal complications of GBS infection that happen prior to delivery can rarely be associated with maternal sepsis leading to fetal death or preterm delivery. Despite this rare devastating outcome, prolonged antibiotics for colonized women is not recommended. It is not possible to sterilize the GI tract, which is the primary source of GBS colonization.
The utility of widespread IAP initially led to fears that antibiotic resistance to GBS isolates would increase dramatically and change the patterns of neonatal sepsis. There have been no GBS isolates reported to be resistant to PCN or cephazolin. Presently, studies show increasing incidence of GBS isolates that are resistant to clindamycin (as high as 45%). In one study of very preterm infants, there was an increase in penicillin resistant E. coli sepsis, although this was likely attributable to prolonged antibiotics used for PROM latency.
5. Prognosis and outcome
In general, pregnancy outcome is excellent where maternal illness is rare and neonatal disease is unlikely if adequate IAP is admisistered. If IAP is less than 4 hours prior to delivery, evaluation by pediatrics is indicated to determine if a neonate needs additional laboratory evaluation to determine the presence of infection and/or the need for antibiotics. CDC has specific guidelines for the evaluation of these neonates at risk; however, the extent of evaluation does vary from institution to institution.
There is no apparent impact on longterm health for GBS colonized women. It is important to inform women that GBS colonization is intermittent. Therefore, colonization may or may not occur in subsequent pregnancies. Women whose infants do have invasive GBS infection are at risk for all future pregnancies and IAP should be given. These women do not need to be recultured with each pregnancy.
6. What is the evidence for specific management and treatment recommendations
Verani, JR, McGee, L, Schrag, SJ. “Prevention of perinatal GBS disease-revised guidelines from CDC 2010”. MMWR Recomm Rep. vol. 59. 2010 Nov 19. pp. 1-36. (These are the updated guidelines that were revised from the 2006 guidelines which reaffirm the 35-37 week culture recommendation and IAP for colonized women. Clearer recommendations for GBS cultures and prophylaxis with preterm labor and pPROM along with guidelines for neonatal assessment were incorporated in this publication.)
Koenig, JM, Keenan, WJ. “Group B Streptococcus and early onset sepsis in the era of maternal prophylaxis”. Pediatr Clin North Am. vol. 56. 2009 Jun. pp. 689-708. (This review highlights some of the cases where neonatal sepsis still occurs despite maternal prophylaxis and demonstrates the need for continued improved testing mechanisms for maternal colonization and the benefits of maternal immunization.)
Goins, NP, Talbot, TR, Schaffner, W, Edwards, KM. “Adherence to perinatal Group B streptococcal prevention guidelines”. Obstet Gynecol. vol. 115. 2010 Jun. pp. 1217-24. (This retrospective study of active surveillance for neonatal sepsis focuses on the lapses in the published guidelines. Areas of poorest compliance included women with allergy to PCN and preterm deliveries. Among 40 cases of early onset GBS identified, 25% were born to women known to be colonized at 35 weeks who also received adequate IAP suggesting that the present strategy is not perfect.)
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