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Official reprint from UpToDate www.uptodate.com ©2015 UpToDate

AuthorCarol J Baker, MD

Section EditorsSusan M Ramin, MDDaniel J Sexton, MD

Deputy EditorVanessa A Barss, MD, FACOG

Neonatal group B streptococcal disease: Prevention

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jul 2015. | This topic last updated: Mar 11, 2015.

INTRODUCTION — Group B streptococcus (GBS or Streptococcus agalactiae) is an encapsulated gram­positivecoccus that colonizes the gastrointestinal and genital tracts of 15 to 40 percent of pregnant women [1]. AlthoughGBS colonization usually remains asymptomatic in these women, maternal colonization is the critical determinantof infection in neonates and young infants (less than 90 days of age), in whom GBS is the most common cause ofbacterial infection [2,3]. Vertical (mother­to­child) transmission primarily occurs when GBS ascends from thevagina to the amniotic fluid after onset of labor or rupture of membranes, but can occur with intact membranes[4,5].

In the mid­1980s, randomized and controlled clinical trials demonstrated that intrapartum administration ofintravenous penicillin or ampicillin to GBS carriers protected their newborns from developing early­onset disease(ie, GBS infection at 0 to 6 days of age) [6­8]. Based upon this evidence, the Centers for Disease Control andPrevention (CDC) published guidelines for prevention of neonatal GBS disease in 2002 [4] and 2010 [3]. The keyintervention of these guidelines is intrapartum parenteral antibiotic prophylaxis of women whose infants are at highrisk of developing early­onset GBS infection because a maternal GBS culture was positive in the weeks beforedelivery or because of maternal characteristics that increase the risk of early­onset GBS disease in their offspring.

The 2010 CDC guidelines for prevention of early­onset GBS disease will be reviewed here. These guidelines havebeen endorsed by the American College of Obstetricians and Gynecologists [9] and the American Academy ofPediatrics [10]. The microbiology, epidemiology, clinical manifestations, and treatment of perinatal and adult GBSinfections, and the status of GBS vaccines are discussed separately:

IDENTIFICATION OF COLONIZED GRAVIDAS — Identification of women colonized with GBS plays the majorrole in the prevention of early­onset neonatal disease since GBS infection results from vertical transmission.Colonized women can be identified directly by culture or indirectly by the presence of specific maternalcharacteristics.

Culture versus risk factor­based screening — The first CDC guidelines published in 1996 for use of intrapartumchemoprophylaxis to prevent early­onset GBS infant disease allowed either culture­based or risk­based strategies.The culture­based approach involved performing routine antepartum GBS cultures on all pregnant women, with afew exceptions for women at very high risk of having an infected infant; all colonized women received intrapartumantibiotic prophylaxis. The risk factor­based approach administered intrapartum antibiotic prophylaxis to womenwith intrapartum risk factors for infant infection (see 'Risk factor­based approach' below). Although randomizedtrials directly comparing these two strategies had not been performed at the time these guidelines were written, thebulk of evidence supported culture­based screening followed by intrapartum chemoprophylaxis of women withpositive results since the majority of cases of early­onset disease occur in infants of women who have noidentifiable risk factors or in whom risk factors are not identified in time to provide effective chemoprophylaxis.

The value of routine cultures, rather than assessment of risk factors, was best demonstrated in a retrospective

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(See "Group B streptococcal infection in pregnant women".)(See "Management of the infant whose mother has received group B streptococcal chemoprophylaxis".)(See "Group B streptococcal infection in neonates and young infants".)(See "Group B streptococcus: Virulence factors and pathogenic mechanisms".)

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cohort study of deliveries in the United States from 1998 to 1999 [11]. Performing lower vaginal and rectalscreening cultures at 35 to 37 weeks of gestation and administering antibiotic prophylaxis to GBS carriers wasassociated with fewer cases of early­onset GBS disease in neonates than prophylaxis based upon the presence ofone or more maternal risk factors (adjusted RR 0.46, 95% CI 0.36­0.60). In fact, almost one in five culture­positivewomen did not have maternal risk factors for early­onset neonatal infection and would not have receivedintrapartum antibiotic prophylaxis. Based primarily on this study, but also on results from other controlled studies,major organizations in the United States, including the CDC, American College of Obstetricians andGynecologists, and American Academy of Pediatrics, have recommended screening cultures over risk­basedscreening for GBS [3,12].

Culture­based approach — The CDC recommends GBS rectovaginal screening cultures for all pregnantwomen at 35 to 37 weeks of gestation, with the following two exceptions: (1) women with GBS bacteriuria (≥10colonies in pure culture or mixed with a second microorganism [3]) during the current pregnancy and (2) womenwho previously gave birth to an infant with invasive GBS disease (see 'Exceptions' below). Cultures are performednear term because many women have transient or intermittent disease, thus GBS colonization status in earlypregnancy may not be predictive of status late in pregnancy [5,13,14]. Cultures are performed at 35 to 37 weeks ofgestation because the results will be available before most women go into labor and are reasonably predictive ofGBS status for about five weeks. The negative predictive value of GBS cultures performed ≤5 weeks beforedelivery is 95 to 98 percent, but declines after five weeks [14].

Exceptions

Performance of GBS cultures — Swabs for culture should be obtained, ideally before digital examination or useof lubricants, from both the lower vagina (vaginal introitus) and rectum (insert swab through the anal sphincter) toachieve maximum sensitivity [27­29]. Either two swabs (one for each site) or a single swab can be used; oneswab is more cost saving. The swabs may be obtained by either the healthcare provider or by the patient herselfafter appropriate instruction as studies have shown equivalent sensitivity [30­32]. A speculum should not be used

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GBS bacteriuria in current pregnancy — Women with GBS bacteriuria (any colony count) anytime in thecurrent pregnancy should routinely receive prophylactic intrapartum antibiotics, even if bacteriuria is treatedand a repeat urine culture is negative; therefore, they can be excluded from culture­based screening. Therationale for this recommendation is that GBS bacteriuria is a marker of heavy vaginal and rectal colonization(the source of GBS bacteriuria in these women), oral treatment of bacteriuria during pregnancy does notachieve long­term eradication of anogenital colonization, and the neonates of women with GBS bacteriuriaare at higher risk for early­onset GBS disease [13,15­17].

There is expert consensus that symptomatic or asymptomatic women with GBS bacteriuria ≥10 cfu/mLduring pregnancy should be treated according to current standards for treating bacteriuria during pregnancy.The utility of treating GBS bacteriuria at colony counts <10 cfu/mL is uncertain; some favor treatment toprevent urinary tract and other sequelae [18], while others do not treat patients with low levels of bacteriuria[19]. (See "Group B streptococcal infection in pregnant women" and "Urinary tract infections andasymptomatic bacteriuria in pregnancy".)

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Delivery of an infant with early­onset GBS disease in a previous pregnancy — There is also goodevidence that previous delivery of an infant with early­onset GBS disease is associated with a higher risk ofearly­onset disease in subsequent deliveries [11,20­22]. For this reason, women with this history shouldroutinely receive prophylactic intrapartum antibiotics, and therefore can be excluded from culture­basedscreening.

Women with a history of a positive GBS culture in one or more previous pregnancies but no infant with early­onset GBS disease should be cultured in every pregnancy. Although a history of GBS colonization in a priorpregnancy is a risk factor for colonization in subsequent pregnancies [23­25], 50 to 60 percent of thesewomen are not colonized in the subsequent pregnancy [25,26].

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to obtain the vaginal swab specimen. Sites other than the vagina and rectum (ie, cervical, perianal, perirectal orperineal) should not be sampled as they are less sensitive for detection of GBS, and add to the cost.

Both swabs, or a single swab of each site, should be placed promptly into non­nutrient transport media (eg, Amiesor Stuart's without charcoal) and transported at room temperature (in temperate climates) or refrigerated [33]. Theswab or swabs are then transferred to a selective enrichment broth at a laboratory experienced in the isolation ofGBS, incubated overnight at 37ºC, and subcultured onto blood agar plates (algorithm 1). Use of selectiveenrichment media substantially improves detection of GBS by enhancing GBS growth and preventing overgrowthof other organisms that may mask growth of GBS [3]. The CDC guidelines include detailed steps for isolation andproper identification of the organism [3]. Cultures require 24 to 48 hours to show positive results. It takes 48 hoursto definitively exclude GBS.

Susceptibility testing is not necessary in most cases because GBS isolates with confirmed resistance to penicillinor ampicillin have not been observed [34]. In patients with positive GBS cultures who have a serious allergy topenicillin (history of anaphylaxis, angioedema, respiratory distress, or urticaria), testing for sensitivity toerythromycin and clindamycin should be performed if one of these antibiotics is used for intrapartum antibioticprophylaxis [3]. (See 'Patients with penicillin allergy' below.)

Incidental findings — Some laboratories report non­GBS streptococcal organisms identified during GBSscreening cultures. In the only available study, group A Streptococcus (GAS) was present in 0.03 percent ofrectovaginal cultures from pregnant women [35]. Reporting GAS colonization identified during GBS screeningshould be discouraged because the maternal­fetal­neonatal attack rate of GAS in this setting is unknown(described in case reports [36]), opinions about management of these pregnancies vary widely among infectiousdisease experts, and few guidelines are available [37].

Rapid diagnostic tests — Nucleic acid amplification test (NAAT) methodology amplifies DNA or RNAsequences using various techniques, such as polymerase chain reaction (PCR). NAATs for GBS arecommercially available and provide results in less than two hours from the time the specimen is received by thelaboratory. These tests have not been universally adopted because of factors such as cost, inability to runsusceptibility testing, and lower sensitivity than standard culture using selective enriched broth media. Comparedto standard culture with selective broth media, the sensitivity of NAATs performed on non­enriched samplesranges from 62.5 to 98.5 percent, and 92.5 to 100 percent when performed on enriched samples (but use ofenriched samples takes more time, reducing the major advantage of NAAT) [3].

We agree with the CDC that the benefits and limitations of currently available NAATs do not support their use toreplace antenatal culture or risk­based assessment of intrapartum women with unknown GBS status. The majorbenefit of NAAT over standard culture is the rapidity of obtaining results; this is much less relevant in theantepartum period. Intrapartum, the sensitivity of NAAT performed directly on vaginal/rectal swabs without anenrichment step was less than that of culture in some studies; therefore, the presence of intrapartum risk factorsfor GBS colonization rather than NAAT results should guide administration of intrapartum antibiotic prophylaxis.

Where available, NAAT is an option for women at term with unknown antepartum GBS colonization status and nointrapartum risk factors for GBS colonization at the time of testing (risk factors: gestational age <37 weeks, GBSbacteriuria in current pregnancy, previous infant with GBS disease, temperature ≥100.4ºF [≥38.0ºC], or rupture ofamniotic membranes ≥18 hours) [3]. Women at term with unknown antepartum GBS colonization status, nointrapartum risk factors for GBS colonization, and positive NAAT results should receive intrapartum antibioticprophylaxis. Women who test negative on admission NAAT but subsequently develop fever or prolonged rupture ofmembranes should receive intrapartum prophylaxis. (See 'Indications for antibiotic prophylaxis' below.)

Other rapid diagnostic tests have been developed, including optical immunoassays and enzyme immunoassays,but none is sufficiently sensitive when used on a direct specimen to detect GBS colonization reliably in theintrapartum setting [3,38].

Risk factor­based approach — The presence of certain characteristics is an indirect means of identifying women

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whose infants are at increased risk of developing early­onset disease [4]. These risk factors can be used insteadof cultures to identify women who should receive antibiotic prophylaxis in labor to reduce the risk of having anaffected infant [39­44]:

Mathematical modeling suggests that these risk factors classify 25 to 30 percent of intrapartum women as at riskof GBS colonization, a prevalence similar to that predicted by a culture­based approach [45,46]. However, a studythat compared the risk­based approach to a culture­based approach for identifying women for intrapartum antibioticprophylaxis found that nearly 50 percent of women who delivered infants with early­onset GBS disease had noneof these listed risk factors [11].

The presence of prolonged rupture of membranes does not override a negative GBS culture within the previous fiveweeks; GBS prophylaxis is not indicted in this setting. Antibiotics would be indicated if the patient developsclinical signs of infection, such as intrapartum fever.

INTRAPARTUM ANTIBIOTIC PROPHYLAXIS — Antibiotics are given intrapartum rather than at the time of apositive culture because antibiotic administration remote from delivery does not eradicate GBS colonization at thetime of delivery, which is when the infant is at risk of vertical transmission [47­49]. The intravenous route isrequired to achieve rapid high concentrations both in maternal serum for placental transfer to the fetal systemiccirculation and in the amniotic fluid, which is inhaled and swallowed by the fetus.

Women with GBS colonization can enter labor spontaneously or be induced; cesarean delivery should be reservedfor standard obstetrical indications.

Indications for antibiotic prophylaxis — Intrapartum antibiotic prophylaxis is given in the following settings,which can be identified by laboratory testing, obstetrical history, or physical examination and are predictive of anincreased risk of early­onset GBS infection [3]: (See 'Identification of colonized gravidas' above.)

Antibiotic prophylaxis for GBS is not indicated — Intrapartum antibiotic prophylaxis is not recommended forwomen with [3]:

Intrapartum fever ≥100.4ºF [≥38ºC]Delivery before 37 weeks of gestation 0/7ths

Rupture of membranes ≥18 hoursPrevious delivery of an infant affected by GBS diseaseGBS bacteriuria (≥10 cfu/mL) in the current pregnancy 4

Positive screening culture for GBS from either vagina or rectum [5]

Positive history of birth of an infant with early­onset GBS disease [20­22]

GBS bacteriuria during the current pregnancy [15,16]

Unknown antepartum culture status (culture not performed or result not available) and:

Intrapartum fever (≥100.4ºF, ≥38ºC) or•

Preterm labor (<37 weeks of gestation) or•

Prolonged rupture of membranes (≥18 hours) [45] or•

Intrapartum NAAT positive for GBS (see 'Rapid diagnostic tests' above)•

A positive GBS rectovaginal culture or GBS bacteriuria in a previous pregnancy and none of the indicationsfor prophylaxis listed above. Cultures remote from delivery are not predictive of culture status at delivery[11,14].

Women with a positive GBS culture who undergo planned cesarean delivery (at any gestational age) withoutlabor or rupture of membranes, as the risk of GBS transmission is much lower in this setting [3,50].

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Antibiotic regimen — Penicillin G 5 million units intravenously initial dose, then 2.5 to 3 million unitsintravenously every four hours until delivery is recommended for intrapartum antibiotic prophylaxis; the range of 2.5to 3 million units allows for the various formulations of penicillin that are available in pharmacies [3]. GBS isolateswith confirmed resistance to penicillin or ampicillin have not been observed [34]. Ampicillin 2 g intravenously initialdose, then 1 g intravenously every four hours until delivery can be used, but penicillin is preferred based upon itsnarrower spectrum of activity, which theoretically reduces the opportunity for development of ampicillin­resistantorganisms (see 'Development of antibiotic resistance' below).

GBS is susceptible to penicillin G, ampicillin, extended­spectrum penicillins, cephalosporins, and vancomycin, butpenicillin G is the most active agent in vitro. Approximately 30 percent of GBS isolates are resistant toerythromycin and 20 percent are resistant to clindamycin, and these rates appear to be increasing [51­55].Erythromycin is no longer recommended for prophylaxis, while clindamycin use depends on results of multiplesusceptibility tests (see 'Patients with penicillin allergy' below). Almost all isolates are resistant to trimethoprim­sulfamethoxazole [56].

Oral treatment is not recommended, although randomized trials comparing oral versus parenteral therapy have notbeen performed. In laboring women, absorption from the gastrointestinal tract is not reliable because of delayedtransit time and vomiting. The intravenous route is required to achieve rapid high concentrations both in maternalserum for placental transfer to the fetal systemic circulation and in the amniotic fluid, which is inhaled andswallowed by the fetus. Also, the high dose of antibiotics required to rapidly reduce the number of organisms in thegenital secretions and amniotic fluid (if colonized) to prevent neonatal infection cannot be tolerated orally. In non­laboring women, prospective studies found that oral therapy did not substantially reduce rectovaginal colonization[49,57].

Patients with penicillin allergy — If the patient's history suggests a "low risk" for anaphylaxis (eg, isolatedmaculopapular rash without urticaria or pruritus), then cefazolin 2 g initial dose, then 1 g every eight hours untildelivery is recommended for intrapartum antibiotic prophylaxis (algorithm 2) [3]. (See "Penicillin allergy: Immediatereactions".) This recommendation is based on the ability of cefazolin to reach bactericidal concentrations in theamniotic fluid three hours after an intravenous dose.

If the patient's history suggests a "high risk" for anaphylaxis (eg, anaphylaxis, angioedema, respiratory distress,urticaria, particularly if these symptoms occurred within 30 minutes of drug administration), then antibioticsusceptibility testing of GBS isolates must be performed to verify susceptibility to clindamycin. If laboratoryfacilities are adequate, clindamycin and erythromycin susceptibility testing is recommended on prenatal GBSisolates from penicillin­allergic women at high risk for anaphylaxis. Resistance to erythromycin is often associatedwith clindamycin resistance. If an isolate is resistant to erythromycin, it may have inducible resistance toclindamycin, even if it appears susceptible to clindamycin by standard in vitro testing methods. If a GBS isolate issusceptible to clindamycin, resistant to erythromycin, and D­zone testing for inducible resistance is negative (noinducible resistance), then clindamycin 900 mg intravenously every eight hours until delivery can be used for GBSintrapartum prophylaxis [3].

If the GBS isolate is resistant to clindamycin or susceptibility results are not available, 2010 CDC guidelinesrecommend use of vancomycin 1 g every 12 hours in patients with normal renal function until delivery of the infant

However, patients planning cesarean delivery should undergo routine vaginal and rectal screening for GBS at35 to 37 weeks because onset of labor or rupture of membranes may occur before the planned cesareandelivery and either of these events increases the risk of GBS transmission and therefore would be anindication for antibiotic prophylaxis.

Pregnant women with negative GBS cultures at 35 to 37 weeks of gestation, even if they have one or moreof the following intrapartum risk factors: intrapartum fever (≥100.4ºF, ≥38ºC), preterm labor (<37 weeks ofgestation), or prolonged rupture of membranes (≥18 hours) [4]. However, the use of broad­spectrumintrapartum antibiotics for the treatment (not prophylaxis) is indicated for febrile women in labor if they haveclinical evidence of chorioamnionitis.

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[3]. Infectious disease guidelines advocate weight­based dosing of vancomycin (15 to 20 mg/kg) because of thehigh prevalence of overweight and obese American women. We agree with weight­based vancomycin dosing (20mg/kg maximum dose 2 g). This approach is supported by a study of vancomycin levels in neonatal cord bloodthat noted therapeutic neonatal levels were usually achieved in neonates exposed to a maternal vancomycinregimen of 20 mg/kg every 8 hours (maximum individual dose 2 g) but infrequently achieved in neonates exposedto standard maternal dosing of 1 g every 12 hours (therapeutic levels: >80 percent versus 9 percent) [58].However, vancomycin has not been evaluated for effectiveness in preventing early­onset GBS and itspharmacokinetic profile is not favorable to achieving bactericidal concentrations in the amniotic fluid. In addition,vancomycin­resistant GBS isolates have been reported [59]. (See "Vancomycin dosing and serum concentrationmonitoring in adults".)

An alternative approach is to perform penicillin skin testing in a woman with a history of penicillin allergy todetermine her allergy status [60]. Patients with negative skin tests could then receive intrapartum antibioticprophylaxis with penicillin. However, patients with negative skin tests should avoid taking a penicillin­based druguntil it is administered for intrapartum antibiotic prophylaxis, due to a small potential risk of re­sensitization from asubsequent course. (See "Penicillin allergy: Immediate reactions".)

In 2008, 76 percent of GBS­positive women who were allergic to penicillin in one large hospital received anappropriate antibiotic compared with 16 percent in 2004 to 2006 [61]. The improvement in antibiotic selection wasthe result of educating providers through lectures, publicizing the CDC guidelines on posters throughout thehospital, and adding a field for “PCN allergy” to the laboratory ordering systems so that, if filled out properly, thelaboratory could be reflexively prompted to perform GBS sensitivity testing.

Timing and duration of prophylaxis — Intrapartum antibiotic prophylaxis with penicillin, ampicillin, or cefazolin ismost effective if administered at least four hours before delivery [56,62­64]. Although fetal serum penicillin levelswith these agents are high within 30 minutes of a maternal intravenous infusion [65,66] and maternal vaginal GBScolony counts begin to fall promptly after beginning intravenous antibiotics, the nadir in GBS colony counts in theamniotic and vaginal fluid is not reached until approximately three hours after the first antibiotic dose [67].

Since the time of delivery cannot be predicted, prophylaxis is begun at hospital admission for labor or rupture ofmembranes and continued every four hours until the infant is delivered. Few studies examining the optimumduration of intrapartum antibiotic prophylaxis have been reported, but cases of early­onset neonatal disease arerare if appropriate doses of penicillin or ampicillin are given, if four or more hours have passed between the firstdose and delivery, and if no maternal infection (eg, chorioamnionitis or bacteremia) is present. In an observationalstudy of 33 GBS carriers with preterm premature rupture of membranes receiving penicillin prophylaxis, dailygenital tract cultures for GBS were negative in 29/33 patients (88 percent) by day 1, in 32/33 patients by day 2,and in all 33 patients by day 3 [68].

Medically necessary procedures should not be delayed in order to provide four hours between antibioticadministration and the procedure.

Recolonization can occur after cessation of therapy.

APPROACH TO THREATENED PRETERM DELIVERY

Preterm labor — Women with a known positive GBS culture within the previous five weeks should be given GBSprophylaxis if admitted in preterm labor.

The colonization status of women admitted with preterm labor or preterm rupture of membranes generally is notknown since screening is performed at 35 to 37 weeks of gestation to maximize agreement between antepartumculture results and maternal GBS status at delivery. If colonization status is unknown, GBS cultures are obtainedat time of presentation and then antibiotic prophylaxis is administered if the birth is potentially viable. If the patientis in true preterm labor, GBS prophylaxis is continued until she delivers. If after a period of observation the patientis not felt to be in true labor, GBS prophylaxis should be discontinued (algorithm 3) [3].

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Management of subsequent episodes of preterm labor depends on final culture results at 48 hours. If the cultureresult is negative, no GBS prophylaxis is needed if preterm labor recurs within the next five weeks. Culture resultsare not predictive of GBS status for more than five weeks [14], so if preterm labor occurs more than five weeksafter the negative culture, the approach is the same as that for a woman with unknown colonization status.

If the patient is undelivered at 35 to 37 weeks of gestation, a vaginal­rectal culture should be repeated to predictGBS status and guide management at term.

Preterm premature rupture of membranes — Women with chorioamnionitis typically receive broad­spectrumantibiotic therapy. This therapy should include an agent known to be active against GBS to replace GBSprophylaxis.

Women with preterm premature rupture of membranes undergoing expectant management and given antibiotics forlatency should receive a regimen that includes prophylaxis for GBS, after GBS cultures have been obtained(algorithm 4). GBS prophylaxis is discontinued if the cultures are negative for GBS. The management of thesepatients is discussed separately. (See "Preterm premature (prelabor) rupture of membranes", section on'Chemoprophylaxis for GBS'.)

OUTCOME — Maternal intrapartum GBS chemoprophylaxis has resulted in a significant reduction in early­onsetGBS disease (>80 percent of cases) and neonatal death [4,69­71]. Late­onset GBS disease has remained stableor decreased [72,73].

Early­onset GBS — A 2014 Cochrane review of randomized trials of intrapartum antibiotic treatment of womencolonized with GBS found that intrapartum antibiotic prophylaxis resulted in a significant reduction in early­onsetneonatal GBS infection (OR 0.17, 95% CI 0.04­0.74), and a nonstatistical reduction in neonatal mortality (all causemortality RR 0.19, 95% CI 0.01­3.92; mortality from early onset GBS RR 0.31, 95% CI 0.01­7.50) [71].

In the United States, widespread use of GBS screening and intrapartum antibiotic prophylaxis has resulted in asubstantial decrease in early­onset GBS infections (ie, diagnosis of neonatal GBS infection within six days afterbirth). This was illustrated in a report from the CDC showing that, in 1993, before active efforts at prevention, theincidence of early­onset GBS infection was 1.5 per 1000 live births [4]. After publication of the initialrecommendations in the 1990s (risk factor­based approach), the incidence of early­onset disease fell to 0.52 per1000 live births (in 2000). Revision of these recommendations in 2002 (universal screening) was associated with afurther drop in incidence to 0.31 cases per 1000 live births (in 2003), a rise to 0.40 cases per 1000 live births in2006, and then a fall to 0.24 cases per 1000 live births in 2010 [3,69,73]. This was mostly due to a significantincrease in early­onset disease from 2003 to 2006 among term black infants (from 0.33 to 0.70 cases per 1000 livebirths).

Late­onset GBS — In the United States, the incidence of late­onset GBS infection (7 to 89 days after birth)has remained stable at an average 0.35 cases/1000 live births [73]. The incidence of late­onset GBS infection inEurope appears to be similar to or slightly lower than that in the United States, but is less well­defined becausemost European studies have not performed population­based active surveillance of culture­confirmed invasiveinfection [72].

Missed cases — Some women colonized at delivery are not identified, despite screening. About 4 percent ofwomen who test negative at 35 to 37 weeks have a false negative result, and about 60 percent of early­onset GBSoccurs in these women [14,74­76].

In a retrospective review of 25 neonates with early­onset GBS, maternal GBS cultures at 35 to 37 weeks ofgestation were presumably falsely negative in 16 (64 percent); the mothers in 19 of these 25 pregnancies hadone or more risk factors for early­onset GBS infection (delivery at <37 weeks, intrapartum fever >100.4ºF,clinical chorioamnionitis, or GBS colonization) [74].

Another retrospective review included 254 cases of early­onset GBS among 7691 live births from a multi­state GBS surveillance system [75]. About 75 percent of GBS cases (189/254) occurred in term infants, but

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The methods used for processing screening cultures in these studies were not described, and may have affectedthe results. These findings suggest that more sensitive methods of detection would be useful.

In the United States, some missed cases are due to nonadherence to the CDC’s prenatal screening andintrapartum prophylaxis guidelines [77,78].

Development of antibiotic resistance — There is a theoretical possibility that extensive use of intrapartumprophylaxis could result in increased antibiotic resistance among GBS isolates and/or an increased incidence ofinfections due to other pathogens. Thus far, no consistent trends have been identified [79­88]. A population­basedGBS surveillance program in 10 states tested 4882 GBS isolates and found that 100 percent were sensitive topenicillin, ampicillin, and vancomycin, but 32 percent were resistant to erythromycin and 15 percent were resistantto clindamycin [89]. Susceptibility to first generation cephalosporins was not assessed; however, a similarpopulation­based surveillance study reported all GBS isolates were sensitive to cefazolin [90].

Exposure to broad­spectrum intrapartum antibiotic prophylaxis has been associated with an increased risk of late­onset serious bacterial infections and infection with resistant organisms [84,91,92]. These findings support therecommendation to use penicillin as the preferred agent for GBS prophylaxis, rather than broader spectrumantibiotics, such as ampicillin.

GBS PROPHYLAXIS FOR OBSTETRICAL PROCEDURES

Antepartum procedures — There are no high quality data about the usefulness of antibiotic prophylaxis ofantepartum obstetrical procedures in women colonized with GBS or in those in whom GBS status is unknown [4].Such procedures include vaginal examination, mechanical and pharmacologic cervical ripening, and membranestripping/sweeping. In the absence of such data, we suggest not administering prophylactic antibiotics.

Low quality indirect support for avoiding chemoprophylaxis was provided by a meta­analysis of 19 trials ofmembrane stripping for induction of labor in women of undetermined GBS status [93]. The prevalence of neonatalinfection among neonates exposed and unexposed to this procedure was similar.

Intrapartum procedures — There is no evidence that intrapartum vaginal examinations and other clinicallyindicated invasive procedures (eg, placement of a fetal scalp electrode, amniotomy) increase the risk of early­onset GBS infection in infants of women who are known to be colonized, although data on transmission risk inthese settings are limited [94]. Ideally, amniotomy and other invasive procedures are performed at least four hoursafter intrapartum antibiotic prophylaxis has been initiated; however, these procedures should not be delayed toachieve an optimal antibiotic concentration when there is medically/obstetrically urgent need for them.

Cesarean delivery — As discussed above, GBS colonization is not an indication for cesarean delivery;cesarean delivery should be performed for standard medical/obstetrical indications. Women with a positive GBSculture who undergo planned cesarean delivery without labor or rupture of membranes do not require GBSprophylaxis, as the risk of GBS transmission to the fetus/neonate is much lower in this setting [3,50]. However,onset of labor or rupture of membranes may occur before the planned cesarean delivery and either of these eventsincreases the risk of GBS transmission; in these cases, GBS prophylaxis is indicated and should be initiated assoon as possible. An urgent cesarean delivery should not be delayed to achieve ≥4 hours of intrapartum antibioticprophylaxis before the procedure.

NEWBORNS

Preventive strategies after birth — The efficacy of prevention strategies targeting newborns, rather than maternalcolonization, is controversial. Large observational studies have suggested that administration of intramuscularpenicillin to the newborn immediately after delivery may reduce early­onset GBS disease [95,96]. However, a

only about one­fifth of these cases (37/189) occurred in women whose screen results were positive; 116cases (61.4 percent) occurred in women whose screen results were negative, 34 cases (13.4 percent) wereattributed to missed screening, and two cases occurred in women whose screen results were not known.

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nonblinded randomized trial involving 1187 infants failed to identify a benefit in outcome of GBS disease orneonatal mortality [97].

The discrepancy between the results of the observational studies and the randomized trial may be explained bymethodologic issues [98]. The randomized trial may not have included sufficient numbers of patients to detect adifference in outcome between treated and control infants. In addition, the participants in the randomized trial werepreterm low birth­weight infants who were transferred to a neonatal intensive care unit. Twenty of 24 infectedbabies became symptomatic within the first hour of life, suggesting that infection may have been present at thetime of delivery. Finally, there were differences in general management that may have contributed to thediscrepant findings. Unless high quality evidence becomes available, the standard for prevention of early­onsetGBS disease is maternal rather than newborn chemoprophylaxis.

Management of newborns — Management of newborns is discussed separately.

GUIDELINES FROM NATIONAL ORGANIZATIONS

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and“Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 to 6 gradereading level, and they answer the four or five key questions a patient might have about a given condition. Thesearticles are best for patients who want a general overview and who prefer short, easy­to­read materials. Beyondthe Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are writtenat the 10 to 12 grade reading level and are best for patients who want in­depth information and are comfortablewith some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e­mail thesetopics to your patients. (You can also locate patient education articles on a variety of subjects by searching on“patient info” and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

(See "Management of the infant whose mother has received group B streptococcal chemoprophylaxis".)

(See "Group B streptococcal infection in neonates and young infants".)

Royal College of Obstetricians and Gynecologists. The Prevention of Early­onset neonatal Group BStreptococcal Disease. Green­top guideline No. 36 July 2012.

Society of Obstetricians and Gynaecologists of Canada. The Prevention of Early­Onset Neonatal Group BStreptococcal Disease. October 2013.

Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Screening and Treatmentfor Group B Streptococcus in Pregnancy. November 2012.

Centers for Disease Control and Prevention. 2010 Guidelines for the Prevention of Perinatal Group BStreptococcal Disease (endorsed by the American Academy of Family Physicians, American Academy ofPediatrics, American College of Obstetricians and Gynecologists, American College of Nurse­Midwives).

th th

th th

Basics topics (see "Patient information: Group B streptococcal disease (The Basics)")

Beyond the Basics topics (see "Patient information: Group B streptococcus and pregnancy (Beyond theBasics)")

Maternal Group B streptococcal (GBS) colonization occurs in 10 to 40 percent of women and is the criticaldeterminant of early­onset GBS infection in neonates less than 7 days of age. (See 'Introduction' above.)

We recommend universal screening of pregnant women to identify those at risk for having a newborn withearly­onset GBS disease (Grade 1A). Colonized women can transmit GBS to offspring, resulting in early­onset disease in neonates, and some of these cases will be missed if a selective risk factor based approach

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is taken. (See 'Identification of colonized gravidas' above and 'Outcome' above.)

We recommend obtaining GBS cultures at 35 to 37 weeks of gestation, rather than a risk factor­basedapproach. Women with GBS bacteriuria anytime in pregnancy (Grade 2B) or an infant with early­onset GBSinfection in a previous pregnancy (Grade 2C) should routinely receive prophylactic intrapartum antibiotics;therefore, they can be excluded from culture­based screening. (See 'Culture­based approach' above and'Exceptions' above.)

Swabs for GBS culture should be obtained from both the lower vagina (not cervix) and rectum (not the analorifice) to achieve maximum sensitivity; these should be placed in transport media, sent to the laboratory andinoculated into selective media for incubation and further processing. (See 'Performance of GBS cultures'above.)

In women with positive GBS cultures from either the vagina or rectum, we recommend intrapartum antibioticprophylaxis at the onset of labor, with administration until delivery (Grade 1A). (See 'Intrapartum antibioticprophylaxis' above.)

In women with positive GBS vaginal­rectal cultures undergoing a planned cesarean delivery in the absence oflabor or rupture of membranes, we recommend not administering intrapartum antibiotic prophylaxis, given thelow risk of early­onset disease (Grade 1B). (See 'Intrapartum antibiotic prophylaxis' above and 'Outcome'above.)

Women with intrapartum fever (≥100.4ºF, ≥38ºC) whose culture status is unknown (culture not performed orresult not available) should receive intrapartum antibiotic treatment (not prophylaxis) that includes an agentactive against GBS. (See 'Intrapartum antibiotic prophylaxis' above and 'Outcome' above.)

The colonization status of women who present with threatened preterm delivery generally is not known. Inthese women, we suggest obtaining a GBS rectovaginal culture and giving antibiotic prophylaxis (Grade 2B).Continuation of therapy is then guided by culture results and uterine activity. Antibiotic therapy is continueduntil delivery or until the threat of imminent preterm delivery has passed. (See 'Approach to threatenedpreterm delivery' above.)

For women in labor with unknown culture status, we recommend intrapartum antibiotic prophylaxis if thegestational age is less than 37 weeks or the duration of membrane rupture is ≥18 hours (Grade 1B). Maternaltemperature ≥100.4º F (≥38.0ºC) is suggestive of infection and should be treated with antibiotics that provideactivity against GBS. (See 'Intrapartum antibiotic prophylaxis' above.)

Intrapartum antibiotic prophylaxis is most effective if penicillin, ampicillin, or cefazolin are administered atleast four hours before delivery. (See 'Timing and duration of prophylaxis' above.)

In women without penicillin allergy, penicillin G is the preferred drug for prophylaxis, given its low cost, lowincidence of side effects, and uniform GBS susceptibility. The Centers for Disease Control recommend adose of 5 million units intravenously initially, then 2.5 to 3 million units intravenously every four hours untildelivery. Ampicillin 2 g intravenously initial dose then 1 g every four hours until delivery is an acceptablealternative. (See 'Antibiotic regimen' above.)

In patients with a non­serious penicillin allergy, cefazolin is recommended in place of penicillin G. (See'Patients with penicillin allergy' above.)

In patients with penicillin allergy at risk for anaphylaxis, clindamycin is recommended if susceptibility testinghas been performed and sensitivity to clindamycin is documented. If the GBS isolate is resistant toclindamycin or susceptibility results are not available, we suggest vancomycin 20 mg/kg every 12 hours,maximum 2 grams per dose rather than vancomycin 1 gram every 12 hours (Grade 2C). Neither clindamycinnor vancomycin has been evaluated for effectiveness in preventing early­onset GBS infant disease. (See'Patients with penicillin allergy' above.)

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REFERENCES

1. Regan JA, Klebanoff MA, Nugent RP. The epidemiology of group B streptococcal colonization in pregnancy.Vaginal Infections and Prematurity Study Group. Obstet Gynecol 1991; 77:604.

2. Baker CJ, Barrett FF. Transmission of group B streptococci among parturient women and their neonates. JPediatr 1973; 83:919.

3. Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases, National Center for Immunization andRespiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group Bstreptococcal disease­­revised guidelines from CDC, 2010. MMWR Recomm Rep 2010; 59:1.

4. Schrag S, Gorwitz R, Fultz­Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease.Revised guidelines from CDC. MMWR Recomm Rep 2002; 51:1.

5. Boyer KM, Gadzala CA, Kelly PD, et al. Selective intrapartum chemoprophylaxis of neonatal group Bstreptococcal early­onset disease. II. Predictive value of prenatal cultures. J Infect Dis 1983; 148:802.

6. Boyer KM, Gotoff SP. Prevention of early­onset neonatal group B streptococcal disease with selectiveintrapartum chemoprophylaxis. N Engl J Med 1986; 314:1665.

7. Easmon CS, Hastings MJ, Deeley J, et al. The effect of intrapartum chemoprophylaxis on the verticaltransmission of group B streptococci. Br J Obstet Gynaecol 1983; 90:633.

8. Boyer KM, Gadzala CA, Kelly PD, Gotoff SP. Selective intrapartum chemoprophylaxis of neonatal group Bstreptococcal early­onset disease. III. Interruption of mother­to­infant transmission. J Infect Dis 1983;148:810.

9. American College of Obstetricians and Gynecologists. ACOG Committee Opinion: number 279, December2002. Prevention of early­onset group B streptococcal disease in newborns. Obstet Gynecol 2002; 100:1405.

10. Committee on Infectious Diseases, Committee on Fetus and Newborn, Baker CJ, et al. Policy statement—Recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics 2011;128:611.

11. Schrag SJ, Zell ER, Lynfield R, et al. A population­based comparison of strategies to prevent early­onsetgroup B streptococcal disease in neonates. N Engl J Med 2002; 347:233.

12. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG CommitteeOpinion No. 485: Prevention of early­onset group B streptococcal disease in newborns. Obstet Gynecol2011; 117:1019.

13. Regan JA, Klebanoff MA, Nugent RP, et al. Colonization with group B streptococci in pregnancy andadverse outcome. VIP Study Group. Am J Obstet Gynecol 1996; 174:1354.

14. Yancey MK, Schuchat A, Brown LK, et al. The accuracy of late antenatal screening cultures in predictinggenital group B streptococcal colonization at delivery. Obstet Gynecol 1996; 88:811.

15. Persson K, Christensen KK, Christensen P, et al. Asymptomatic bacteriuria during pregnancy with specialreference to group B streptococci. Scand J Infect Dis 1985; 17:195.

16. Wood EG, Dillon HC Jr. A prospective study of group B streptococcal bacteriuria in pregnancy. Am J ObstetGynecol 1981; 140:515.

17. Yancey MK, Duff P, Kubilis P, et al. Risk factors for neonatal sepsis. Obstet Gynecol 1996; 87:188.18. Aungst M, King J, Steele A, Gordon M. Low colony counts of asymptomatic group B streptococcus

bacteriuria: a survey of practice patterns. Am J Perinatol 2004; 21:403.

Antepartum antibiotic treatment of GBS colonization remote from delivery does not reduce the incidence ofGBS colonization at the time of delivery, and should be avoided. (See 'Intrapartum antibiotic prophylaxis'above.)

Women with unknown culture status at term and no risk factors for early­onset GBS disease who testpositive for GBS with intrapartum NAAT should receive intrapartum antibiotic prophylaxis. (See 'Rapiddiagnostic tests' above.)

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19. Allen VM, Yudin MH, Bouchard C, et al. Management of group B streptococcal bacteriuria in pregnancy. JObstet Gynaecol Can 2012; 34:482.

20. Christensen KK, Dahlander K, Lindén V, et al. Obstetrical care in future pregnancies after fetal loss in groupB streptococcal septicemia. A prevention program based on bacteriological and immunological follow­up. EurJ Obstet Gynecol Reprod Biol 1981; 12:143.

21. Faxelius G, Bremme K, Kvist­Christensen K, et al. Neonatal septicemia due to group B streptococci­­perinatal risk factors and outcome of subsequent pregnancies. J Perinat Med 1988; 16:423.

22. Carstensen H, Christensen KK, Grennert L, et al. Early­onset neonatal group B streptococcal septicaemia insiblings. J Infect 1988; 17:201.

23. Turrentine MA, Ramirez MM. Recurrence of group B streptococci colonization in subsequent pregnancy.Obstet Gynecol 2008; 112:259.

24. Page­Ramsey SM, Johnstone SK, Kim D, Ramsey PS. Prevalence of group B Streptococcus colonizationin subsequent pregnancies of group B Streptococcus­colonized versus noncolonized women. Am J Perinatol2013; 30:383.

25. Cheng PJ, Chueh HY, Liu CM, et al. Risk factors for recurrence of group B streptococcus colonization in asubsequent pregnancy. Obstet Gynecol 2008; 111:704.

26. Colicchia LC, Lauderdale DS, Du H, et al. Recurrence of group B streptococcus colonization in successivepregnancies. J Perinatol 2015; 35:173.

27. Badri MS, Zawaneh S, Cruz AC, et al. Rectal colonization with group B streptococcus: relation to vaginalcolonization of pregnant women. J Infect Dis 1977; 135:308.

28. Knudtson EJ, Lorenz LB, Skaggs VJ, et al. The effect of digital cervical examination on group Bstreptococcal culture. Am J Obstet Gynecol 2010; 202:58.e1.

29. Schwope OI, Chen KT, Mehta I, et al. The effect of a chlorhexidine­based surgical lubricant during pelvicexamination on the detection of group B Streptococcus. Am J Obstet Gynecol 2010; 202:276.e1.

30. Price D, Shaw E, Howard M, et al. Self­sampling for group B streptococcus in women 35 to 37 weekspregnant is accurate and acceptable: a randomized cross­over trial. J Obstet Gynaecol Can 2006; 28:1083.

31. Hicks P, Diaz­Perez MJ. Patient self­collection of group B streptococcal specimens during pregnancy. J AmBoard Fam Med 2009; 22:136.

32. Arya A, Cryan B, O'Sullivan K, et al. Self­collected versus health professional­collected genital swabs toidentify the prevalence of group B streptococcus: a comparison of patient preference and efficacy. Eur JObstet Gynecol Reprod Biol 2008; 139:43.

33. Larsen JW, Sever JL. Group B Streptococcus and pregnancy: a review. Am J Obstet Gynecol 2008;198:440.

34. Andrews JI, Diekema DJ, Hunter SK, et al. Group B streptococci causing neonatal bloodstream infection:antimicrobial susceptibility and serotyping results from SENTRY centers in the Western Hemisphere. Am JObstet Gynecol 2000; 183:859.

35. Mead PB, Winn WC. Vaginal­rectal colonization with group A streptococci in late pregnancy. Infect DisObstet Gynecol 2000; 8:217.

36. Stefonek KR, Maerz LL, Nielsen MP, et al. Group A streptococcal puerperal sepsis preceded by positivesurveillance cultures. Obstet Gynecol 2001; 98:846.

37. Steer JA, Lamagni T, Healy B, et al. Guidelines for prevention and control of group A streptococcal infectionin acute healthcare and maternity settings in the UK. J Infect 2012; 64:1.

38. Honest H, Sharma S, Khan KS. Rapid tests for group B Streptococcus colonization in laboring women: asystematic review. Pediatrics 2006; 117:1055.

39. Adair CE, Kowalsky L, Quon H, et al. Risk factors for early­onset group B streptococcal disease inneonates: a population­based case­control study. CMAJ 2003; 169:198.

40. Oddie S, Embleton ND. Risk factors for early onset neonatal group B streptococcal sepsis: case­controlstudy. BMJ 2002; 325:308.

41. Zaleznik DF, Rench MA, Hillier S, et al. Invasive disease due to group B Streptococcus in pregnant womenand neonates from diverse population groups. Clin Infect Dis 2000; 30:276.

42. Schuchat A, Zywicki SS, Dinsmoor MJ, et al. Risk factors and opportunities for prevention of early­onset

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neonatal sepsis: a multicenter case­control study. Pediatrics 2000; 105:21.43. Schuchat A, Deaver­Robinson K, Plikaytis BD, et al. Multistate case­control study of maternal risk factors

for neonatal group B streptococcal disease. The Active Surveillance Study Group. Pediatr Infect Dis J 1994;13:623.

44. Boyer KM, Gadzala CA, Burd LI, et al. Selective intrapartum chemoprophylaxis of neonatal group Bstreptococcal early­onset disease. I. Epidemiologic rationale. J Infect Dis 1983; 148:795.

45. Boyer KM, Gotoff SP. Strategies for chemoprophylaxis of GBS early­onset infections. Antibiot Chemother(1971) 1985; 35:267.

46. Rouse DJ, Goldenberg RL, Cliver SP, et al. Strategies for the prevention of early­onset neonatal group Bstreptococcal sepsis: a decision analysis. Obstet Gynecol 1994; 83:483.

47. Centers for Disease Control and Prevention (CDC). Laboratory practices for prenatal Group B streptococcalscreening and reporting­­Connecticut, Georgia, and Minnesota, 1997­1998. MMWR Morb Mortal Wkly Rep1999; 48:426.

48. Klebanoff MA, Regan JA, Rao AV, et al. Outcome of the Vaginal Infections and Prematurity Study: resultsof a clinical trial of erythromycin among pregnant women colonized with group B streptococci. Am J ObstetGynecol 1995; 172:1540.

49. Gardner SE, Yow MD, Leeds LJ, et al. Failure of penicillin to eradicate group B streptococcal colonization inthe pregnant woman. A couple study. Am J Obstet Gynecol 1979; 135:1062.

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

51. Pearlman MD, Pierson CL, Faix RG. Frequent resistance of clinical group B streptococci isolates toclindamycin and erythromycin. Obstet Gynecol 1998; 92:258.

52. Biedenbach DJ, Stephen JM, Jones RN. Antimicrobial susceptibility profile among beta­haemolyticStreptococcus spp. collected in the SENTRY Antimicrobial Surveillance Program­­North America, 2001.Diagn Microbiol Infect Dis 2003; 46:291.

53. Manning SD, Foxman B, Pierson CL, et al. Correlates of antibiotic­resistant group B streptococcus isolatedfrom pregnant women. Obstet Gynecol 2003; 101:74.

54. Manning SD, Pearlman MD, Tallman P, et al. Frequency of antibiotic resistance among group BStreptococcus isolated from healthy college students. Clin Infect Dis 2001; 33:E137.

55. de Azavedo JC, McGavin M, Duncan C, et al. Prevalence and mechanisms of macrolide resistance ininvasive and noninvasive group B streptococcus isolates from Ontario, Canada. Antimicrob AgentsChemother 2001; 45:3504.

56. Edwards MS, Nizet V, Baker CJ. Group B Streptococcal Infections. In: Infectious Diseases of the Fetusand Newborn Infant, 7th ed, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders,Philadelphia 2011. p.419.

57. Baecher L, Grobman W. Prenatal antibiotic treatment does not decrease group B streptococcus colonizationat delivery. Int J Gynaecol Obstet 2008; 101:125.

58. Onwuchuruba CN, Towers CV, Howard BC, et al. Transplacental passage of vancomycin from mother toneonate. Am J Obstet Gynecol 2014; 210:352.e1.

59. Park C, Nichols M, Schrag SJ. Two cases of invasive vancomycin­resistant group B streptococcusinfection. N Engl J Med 2014; 370:885.

60. Macy E. Penicillin skin testing in pregnant women with a history of penicillin allergy and group Bstreptococcus colonization. Ann Allergy Asthma Immunol 2006; 97:164.

61. Critchfield AS, Lievense SP, Raker CA, Matteson KA. Group B Streptococcus prophylaxis in patients whoreport a penicillin allergy: a follow­up study. Am J Obstet Gynecol 2011; 204:150.e1.

62. de Cueto M, Sanchez MJ, Sampedro A, et al. Timing of intrapartum ampicillin and prevention of verticaltransmission of group B streptococcus. Obstet Gynecol 1998; 91:112.

63. Fairlie T, Zell ER, Schrag S. Effectiveness of intrapartum antibiotic prophylaxis for prevention of early­onsetgroup B streptococcal disease. Obstet Gynecol 2013; 121:570.

64. Turrentine MA, Greisinger AJ, Brown KS, et al. Duration of intrapartum antibiotics for group B streptococcuson the diagnosis of clinical neonatal sepsis. Infect Dis Obstet Gynecol 2013; 2013:525878.

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65. Barber EL, Zhao G, Buhimschi IA, Illuzzi JL. Duration of intrapartum prophylaxis and concentration ofpenicillin G in fetal serum at delivery. Obstet Gynecol 2008; 112:265.

66. Pacifici GM. Placental transfer of antibiotics administered to the mother: a review. Int J Clin Pharmacol Ther2006; 44:57.

67. McNanley AR, Glantz JC, Hardy DJ, Vicino D. The effect of intrapartum penicillin on vaginal group Bstreptococcus colony counts. Am J Obstet Gynecol 2007; 197:583.e1.

68. Alvarez JR, Williams SF, Ganesh VL, Apuzzio JJ. Duration of antimicrobial prophylaxis for group Bstreptococcus in patients with preterm premature rupture of membranes who are not in labor. Am J ObstetGynecol 2007; 197:390.e1.

69. Centers for Disease Control and Prevention (CDC). Trends in perinatal group B streptococcal disease ­United States, 2000­2006. MMWR Morb Mortal Wkly Rep 2009; 58:109.

70. Edmond KM, Kortsalioudaki C, Scott S, et al. Group B streptococcal disease in infants aged younger than 3months: systematic review and meta­analysis. Lancet 2012; 379:547.

71. Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization.Cochrane Database Syst Rev 2014; 6:CD007467.

72. Didier C, Streicher MP, Chognot D, et al. Late­onset neonatal infections: incidences and pathogens in theera of antenatal antibiotics. Eur J Pediatr 2012; 171:681.

73. Centers for Disease Control and Prevention (2008) Active Bacterial Core Surveillance Report, EmergingInfections Program Network, Group B Streptococcus, 2007. http://www.cdc.gov/abcs/reports­findings/survreports/gbs07.pdf (Accessed on March 21, 2012).

74. Puopolo KM, Madoff LC, Eichenwald EC. Early­onset group B streptococcal disease in the era of maternalscreening. Pediatrics 2005; 115:1240.

75. Van Dyke MK, Phares CR, Lynfield R, et al. Evaluation of universal antenatal screening for group Bstreptococcus. N Engl J Med 2009; 360:2626.

76. Lin FY, Weisman LE, Azimi P, et al. Assessment of intrapartum antibiotic prophylaxis for the prevention ofearly­onset group B Streptococcal disease. Pediatr Infect Dis J 2011; 30:759.

77. Stoll BJ, Hansen NI, Sánchez PJ, et al. Early onset neonatal sepsis: the burden of group B Streptococcaland E. coli disease continues. Pediatrics 2011; 127:817.

78. Verani JR, Spina NL, Lynfield R, et al. Early­onset group B streptococcal disease in the United States:potential for further reduction. Obstet Gynecol 2014; 123:828.

79. Sutkin G, Krohn MA, Heine RP, Sweet RL. Antibiotic prophylaxis and non­group B streptococcal neonatalsepsis. Obstet Gynecol 2005; 105:581.

80. Chen KT, Puopolo KM, Eichenwald EC, et al. No increase in rates of early­onset neonatal sepsis byantibiotic­resistant group B Streptococcus in the era of intrapartum antibiotic prophylaxis. Am J ObstetGynecol 2005; 192:1167.

81. Towers CV, Carr MH, Padilla G, Asrat T. Potential consequences of widespread antepartal use of ampicillin.Am J Obstet Gynecol 1998; 179:879.

82. Towers CV, Briggs GG. Antepartum use of antibiotics and early­onset neonatal sepsis: the next 4 years. AmJ Obstet Gynecol 2002; 187:495.

83. Mercer BM, Carr TL, Beazley DD, et al. Antibiotic use in pregnancy and drug­resistant infant sepsis. Am JObstet Gynecol 1999; 181:816.

84. Glasgow TS, Young PC, Wallin J, et al. Association of intrapartum antibiotic exposure and late­onsetserious bacterial infections in infants. Pediatrics 2005; 116:696.

85. Rentz AC, Samore MH, Stoddard GJ, et al. Risk factors associated with ampicillin­resistant infection innewborns in the era of group B streptococcal prophylaxis. Arch Pediatr Adolesc Med 2004; 158:556.

86. Sinha A, Yokoe D, Platt R. Intrapartum antibiotics and neonatal invasive infections caused by organismsother than group B streptococcus. J Pediatr 2003; 142:492.

87. Schrag SJ, Hadler JL, Arnold KE, et al. Risk factors for invasive, early­onset Escherichia coli infections inthe era of widespread intrapartum antibiotic use. Pediatrics 2006; 118:570.

88. Puopolo KM, Eichenwald EC. No change in the incidence of ampicillin­resistant, neonatal, early­onsetsepsis over 18 years. Pediatrics 2010; 125:e1031.

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89. Phares CR, Lynfield R, Farley MM, et al. Epidemiology of invasive group B streptococcal disease in theUnited States, 1999­2005. JAMA 2008; 299:2056.

90. Castor ML, Whitney CG, Como­Sabetti K, et al. Antibiotic resistance patterns in invasive group Bstreptococcal isolates. Infect Dis Obstet Gynecol 2008; 2008:727505.

91. Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG. Changing patterns in neonatal Escherichia colisepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics 2008; 121:689.

92. Ecker KL, Donohue PK, Kim KS, et al. The impact of group B streptococcus prophylaxis on late­onsetneonatal infections. J Perinatol 2013; 33:206.

93. Boulvain M, Stan C, Irion O. Membrane sweeping for induction of labour. Cochrane Database Syst Rev2005; :CD000451.

94. Gibbs RS, Schrag S, Schuchat A. Perinatal infections due to group B streptococci. Obstet Gynecol 2004;104:1062.

95. Siegel JD, McCracken GH Jr, Threlkeld N, et al. Single­dose penicillin prophylaxis of neonatal group­B­streptococcal disease. Lancet 1982; 1:1426.

96. Patel DM, Rhodes PG, LeBlanc MH, et al. Role of postnatal penicillin prophylaxis in prevention of neonatalgroup B streptococcus infection. Acta Paediatr 1999; 88:874.

97. Pyati SP, Pildes RS, Jacobs NM, et al. Penicillin in infants weighing two kilograms or less with early­onsetGroup B streptococcal disease. N Engl J Med 1983; 308:1383.

98. Woodgate P, Flenady V, Steer P. Intramuscular penicillin for the prevention of early onset group Bstreptococcal infection in newborn infants. Cochrane Database Syst Rev 2004; :CD003667.

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GRAPHICS

Algorithm for recommended laboratory testing for prenatalscreening for group B streptococcal (GBS) colonization

* Direct plating with appropriate media may be done in addition to enriched culture. Direct platingshould not be used as the sole means to identify GBS.

Reproduced from: Verani JR, McGee L, Schrag SJ. Division of Bacterial Diseases, National Center forImmunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Preventionof perinatal group B streptococcal disease­­revised guidelines from CDC, 2010. MMWR Recomm Rep2010; 59:1.

Graphic 57194 Version 2.0

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CDC algorithm for GBS prophylaxis in penicillin allergy*

IV: intravenously.* Broader spectrum agents, including an agent active against GBS, might be necessary for treatmentof chorioamnionitis.• Doses ranging from 2.5 to 3.0 million units are acceptable for the doses administered every 4hours following the initial dose. The choice of dose within that range should be guided by whichformulations of penicillin G are readily available to reduce the need for pharmacies to speciallyprepare doses.Δ Penicillin­allergic patients with a history of anaphylaxis, angioedema, respiratory distress, orurticaria following administration of penicillin or a cephalosporin are considered to be at high risk foranaphylaxis and should not receive penicillin, ampicillin, or cefazolin for GBS intrapartum prophylaxis.For penicillin­allergic patients who do not have a history of those reactions, cefazolin is the preferredagent because pharmacologic data suggest it achieves effective intraamniotic concentrations.Vancomycin and clindamycin should be reserved for penicillin­allergic women at high risk foranaphylaxis.◊ If laboratory facilities are adequate, clindamycin and erythromycin susceptibility testing should beperformed on prenatal GBS isolates from penicillin­allergic women at high risk for anaphylaxis. If nosusceptibility testing is performed, or the results are not available at the time of labor, vancomycin isthe preferred agent for GBS intrapartum prophylaxis for penicillin­allergic women at high risk foranaphylaxis.§ Resistance to erythromycin is often but not always associated with clindamycin resistance. If anisolate is resistant to erythromycin, it might have inducible resistance to clindamycin, even if itappears susceptible to clindamycin. If a GBS isolate is susceptible to clindamycin, resistant toerythromycin, and testing for inducible clindamycin resistance has been performed and is negative(no inducible resistance), then clindamycin can be used for GBS intrapartum prophylaxis instead ofvancomycin.

Reproduced from: Verani JR, McGee L, Schrag SJ. Division of Bacterial Diseases, National Center forImmunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC).Prevention of perinatal group B streptococcal disease­­revised guidelines from CDC, 2010. MMWRRecomm Rep 2010; 59:1.

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CDC algorithm for screening for GBS in pretermlabor before 37 weeks

CDC: Centers for Disease Control and Prevention; GBS: Group B streptococcus.* If patient has undergone vaginal­rectal GBS culture within the preceding 5weeks, the results of that culture should guide management. GBS­colonizedwomen should receive intrapartum antibiotic prophylaxis. No antibiotics areindicated for GBS prophylaxis if a vaginal­rectal screen within 5 weeks wasnegative.• Patient should be regularly assessed for progression to true labor; if thepatient is considered not to be in true labor, discontinue GBS prophylaxis.Δ If GBS culture results become available prior to delivery and are negative,then discontinue GBS prophylaxis.◊ Unless subsequent GBS culture prior to delivery is positive.§ A negative GBS screen is considered valid for 5 weeks. If a patient with ahistory of PTL is re­admitted with signs and symptoms of preterm labor and hada negative GBS screen >5 weeks prior, she should be rescreened and managedaccording to this algorithm at that time.

Reproduced from: Centers for Disease Control and Prevention. Prevention ofPerinatal Group B Streptococcal Disease. Revised Guidelines from CDC, 2010.MMWR 2010; 59:No. RR­10.

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CDC algorithm for screening for GBS in PROMbefore 37 weeks of gestation

CDC: Centers for Disease Control and Prevention; GBS: Group Bstreptococcus; PROM: premature rupture of membranes.* If patient has undergone vaginal­rectal GBS culture within the preceding 5weeks, the results of that culture should guide management. GBS­colonizedwomen should receive intrapartum antibiotic prophylaxis. No antibiotics areindicated for GBS prophylaxis if a vaginal­rectal screen within 5 weeks wasnegative.• Antibiotics given for latency in the setting of pPROM that include ampicillin 2g intravenously (IV) once, followed by 1 g IV every 6 hours for at least 48hours are adequate for GBS prophylaxis. If other regimens are used, GBSprophylaxis should be initiated in addition.Δ GBS prophylaxis should be discontinued at 48 hours for women with pPROMwho are not in labor. If results from a GBS screen performed on admissionbecome available during the 48­hour period and are negative, GBS prophylaxisshould be discontinued at that time.◊ Unless subsequent GBS culture prior to delivery is positive.§ A negative GBS screen is considered valid for 5 weeks. If a patient withpPROM is entering labor and had a negative GBS screen >5 weeks prior, sheshould be rescreened and managed according to this algorithm at that time.

Reproduced from: Centers for Disease Control and Prevention. Prevention ofPerinatal Group B Streptococcal Disease. Revised Guidelines from CDC, 2010.MMWR 2010; 59:No. RR­10.

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Disclosures: Carol J Baker, MD Consultant/Advisory Boards: Pfizer (vaccines­no product); Novartis Vaccines (vaccines­no product).Susan M Ramin, MD Nothing to disclose. Daniel J Sexton, MD Grant/Research/Clinical Trail Support: Cubist [C. difficile infection(Fidaxomycin)]. Consultant/Advisory Boards: Johnson & Johnson [Pelvic mesh­related infection]; Sterilis [Medical waste disposalsystems]; Magnolia Medical Technologies [Intravenous devices]. Other Financial Interest: National Football League [Infection controlprogram]. Equity Ownership/Stock Options: Magnolia Medical Technologies [Intravenous devices]. Vanessa A Barss, MD, FACOGNothing to disclose.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through amulti­level review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

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