Antimicrobial prophylaxis of neonatal group B streptococcal sepsis

This article reviews available studies on prevention of neonatal group B streptococcal infections with antimicrobial prophylaxis. The data show that short-term administration of ampicillin to parturients with prenatal streptococcal colonization and perinatal risk factors effectively prevents these serious infections. A strong case can be made for prenatal screening for group B streptococcal carriage to identify mothers whose babies are at risk.     

Early-onset neonatal group B streptococcal sepsis: intrapartum antibiotic prophylaxis in the clinical setting.

OBJECTIVE: To evaluate how guidelines for the use of intrapartum antibiotics for the prevention of early-onset Group B streptococcal infection are utilized in a clinical setting. STUDY DESIGN: Review of maternal/infant records for the year 1993 in a perinatal center. RESULTS: Intrapartum antibiotics were administered to 77.8% of 443 Group B streptococcus (GBS)-colonized women. There were 452 infants born to these mothers, of which four developed GBS infection. During the same period, an additional 11 infants with GBS infection were born to women with "negative" or "unknown" GBS status (the women did not receive intrapartum antibiotics). Infants of GBS-colonized women who had not receive antibiotics were more likely to develop infection than GBS negative or unknown status, odds ratio 9.0, 95% confidence interval (2.8-29.1). CONCLUSION: This study supports the use of intrapartum antibiotics as an important means of preventing early-onset neonatal GBS infection but demonstrates problems that may be encountered in the clinical application of guidelines for intrapartum antibiotic prophylaxis.     

No increase in rates of early-onset neonatal sepsis by non-group B Streptococcus or ampicillin-resistant organisms

OBJECTIVE: We assessed the impact of a risk-based approach to group B Streptococcus (GBS) prophylaxis on the rates of early-onset neonatal sepsis (EONS). STUDY DESIGN: A retrospective cohort study of neonates born at a tertiary-care hospital from 1990 to 1996 was performed. Cases of EONS were identified among neonates born in a period without GBS prophylaxis (1990-1992) and compared with those born in a period with GBS prophylaxis (1993-1996). The antibiotic susceptibility data on each organism isolated in the blood culture were obtained. RESULTS: In the period without prophylaxis, 99 cases of EONS were identified among 25,934 neonates for a rate of 3.8 per 1000 births. In the period with prophylaxis, 90 cases of EONS occurred among 34,262 neonates for a rate of 2.6 per 1000. The rate of GBS-EONS significantly decreased between the 2 periods (from 1.9 to 1.1, P =.01). There was a trend toward a decrease in the rate of EONS caused by non-GBS gram-positive organisms (from 1.2 to 0.7, P =.06). There was no significant increase in the rate of EONS caused by gram-negative or ampicillin-resistant organisms. CONCLUSIONS: A risk-based approach to GBS prophylaxis reduced the incidence of GBS-EONS at a tertiary-care hospital. This decrease was not accompanied by an increase in the incidence of EONS by non-GBS or ampicillin-resistant organisms.     

Compliance with a protocol for intrapartum antibiotic prophylaxis against neonatal group B streptococcal sepsis in women with clinical risk factors

OBJECTIVE: The aim of this study was to determine the prevalence of clinical risk factors (CRF) for neonatal sepsis in laboring women and to evaluate clinician compliance with a CRF-based protocol for intrapartum antibiotic prophylaxis (IAP). METHODS: A retrospective chart audit was undertaken at a district hospital (A) and a tertiary obstetric hospital (B) in Sydney, Australia between 1996 and 1998, to determine compliance with IAP in women with defined CRF. RESULTS: Eighty-five (12%) women at Hospital A and 117 (19%) at Hospital B had one or more CRF. Overall compliance rates with the IAP protocols were 65 and 50% at Hospitals A and B respectively, but varied according to maternal, obstetric and sepsis-related risk factors. We postulate that differences between the hospitals were related to protocol implementation. CONCLUSIONS: Compliance with a CRF-based protocol was lower than previously reported. Improvements in protocol development, implementation and maintenance are required to enhance compliance with IAP based on CRF.     

Epidemiology and predictive values of risk factors for neonatal group B streptococcal sepsis

OBJECTIVES: To determine the incidence of and factors affecting risk factors for neonatal group B streptococcal (GBS) sepsis and their predictive values for intrapartum GBS carriage; to calculate the proportions of women eligible for intrapartum antibiotic prophylaxis (IAP) using different selection protocols. DESIGN: Cohort study. SETTING: Antenatal clinics and labour wards of a community hospital and a tertiary referral centre in western Sydney POPULATION: Women attending antenatal clinics during the study periods were invited to participate. METHODS: Approximately 500 women attending antenatal clinics were screened for GBS carriage at 26-32 weeks gestation and at delivery, using several screening methods. Clinical risk factors for neonatal sepsis were recorded during labour. MAIN OUTCOME MEASURES: Incidence of antenatal anovaginal GBS carriage and clinical risk factors during labour, their predictive values for intra-partum GBS carriage and their relationship, if any, to demographic and obstetric factors. RESULTS: Antenatal and intra-partum GBS carriage rates were similar but varied from 18% to 27%, depending on screening methods. The best positive and negative predictive values of antenatal GBS culture, for intra-partum carriage, were 69% (95% confidence interval (CI) 64-74) and 92% (95% CI 50-94) respectively Clinical risk factors occurred in similar proportions of GBS carriers and non-carriers. CONCLUSIONS: Neither early antenatal screening nor clinical risk factors are reliable predictors of intra-partum GBS carriage. Intra-partum antibiotic prophylaxis based on GBS carriage or risk factors when carrier status is unknown would involve approximately 35% of women, compared with approximately 16% if based on risk factors only Both strategies would prevent similar proportions of neonatal deaths from GBS sepsis. Compliance with a preventive protocol is the most likely determinant of its overall effectiveness.     

Antibiotic prophylaxis for presumptive group B streptococcal infection in preterm premature rupture of the membranes: effect on neonatal and maternal infectious morbidity

Objective: The purpose of this study was to determine if the prevalence of neonatal and maternal infectious morbidity in patients with preterm premature rupture of membranes (PROM) who received ampicillin prophylaxis for presemptive group B streptococcal colonization is increased compared to those who received no prophylaxis.Methods: The charts of all patients with preterm PROM who delivered between January 1988 and December 1993 were retrospectively reviewed. The routine use of ampicillin prophylaxis was initiated in January 1991. Patients with singleton gestations were included in the analysis only if chorioamnionitis was excluded on admission. Variables used in the final analysis included gestational age at the time of preterm PROM, gestational age at delivery, duration of rupture of membranes, birth weight, method of delivery, use of steroids, tocolytics, or antibiotics for group B streptococcus prophylaxis, neonatal sepsis, neonatal mortality, and postpartum endomyometritis. Data were analyzed using Student's t-test, chi-square test, Fisher's exact test, and stepwise logistic regression analysis to evaluate the effect of chemoprophylaxis for group B streptococcus on the incidence of neonatal sepsis and maternal postpartum endomyometritis. A two-tailed P < 0.05 was used to denote statistical significance.Results: The charts of 206 patients were reviewed; 146 patients received ampicillin for group B streptococcal prophylaxis and 60 patients did not. There was a significantly higher incidence of postpartum endomyometritis among the patients who received ampicillin (62% vs. 22%; P < 0.01). The association between postpartum endomyometritis and chemoprophylaxis remained significant even after controlling for other confounding variables. There was no significant difference in the incidence of neonatal sepsis (5% vs. 7%; P = 0.7) or death (5% vs. 3%; P = 0.9) between both groups.Conclusions: Group B streptococcal prophylaxis with a short course of intravenous ampicillin increases the risk of postpartum endomyometritis in patients with premature PROM.     

Intrapartum antibiotic prophylaxis and early-onset neonatal sepsis patterns

OBJECTIVE: To compare the relative effects of intrapartum antibiotic prophylaxis regimens on patterns of early-onset neonatal sepsis. METHODS: We performed an historical cohort study of 17187 infants born at our center from September 1993 to February 2000. A risk-based strategy was employed prior to July 1996 and a screening-based strategy was utilized thereafter. Ampicillin was utilized prior to March 1995 and penicillin was used thereafter. RESULTS: There were 75 cases of neonatal sepsis, 34 (4. 10/1000) in the risk-based era and 41 (4.63/1000) in the screening-based era (p = 0.62). There were fewer ampicillin-resistant isolates during the risk-based than the screening-based era (32 versus 61%; p = 0.014). The only significant change in organism-specific sepsis rates was an increase in the rate of infection caused by coagulase-negative staphylococci in the screening-based era (0.36 versus 1.46/1000; p = 0.018), but 75% of infants infected with these organisms were not exposed to beta-lactam antibiotics within 72 h prior to delivery. For the risk- and screening-based eras, respectively, the rates of Gram-negative sepsis (1.21 versus 1.46/1000; p = 0.65) and the proportions of Gram-negative pathogens that were ampicillin-resistant (70 versus 77%; p = 1.0) were similar. The drug employed for prophylaxis did not appear to affect the pattern of sepsis cases. CONCLUSION: In our patient population, coagulase-negative staphylococci have become the most common cause of early-onset neonatal sepsis. The cause of this shift in pathogen prevalence is uncertain and seemingly unrelated to intrapartum antibiotic exposure.     

Compliance with a risk factor-based intrapartum prophylaxis program for neonatal group B streptococcal disease

AIM: The US Centre for Disease Control (CDC) recently amended their guidelines for the prevention of early-onset group B streptococcal disease (EOGBSD) of the newborn to recommend bacteriological screening, rather than risk factor-based screening, as the preferred method of identifying 'at risk' mother-infant pairs. This recommendation was derived from population data suggesting that the effectiveness of bacteriological screening was superior to a risk-factor approach because antibiotic compliance was better with the former. Whether poor compliance and therefore impaired prevention is inherent in risk-factor screening has not been widely tested. METHODS: For a 6-month period we audited compliance with an established risk-factor EOGBSD prophylaxis program. RESULTS: During the audit period, 1243 women delivered, of whom 287 (23%) had at least one risk factor. Of these women, 193 (67%), representing 15% of all women giving birth, received antibiotics. Thus, there were 94 women who were eligible for antibiotics but did not receive prophylaxis. There were sound clinical reasons for withholding antibiotics in 68 of these. Therefore, the corrected compliance rate within our program was 73%. CONCLUSION: This compares favourably with published compliance rates with bacteriological-based programs, but we have suggested mechanisms to improve compliance further.     

Duration of intrapartum prophylaxis for neonatal group B streptococcal disease: a systematic review

OBJECTIVE: To examine published evidence regarding duration of intrapartum antibiotic prophylaxis administered to pregnant women colonized with group B Streptococcus (GBS) to reduce infant colonization with GBS and to prevent early-onset GBS sepsis. DATA SOURCES: A search was conducted in The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2006), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to January 2006), and in protocols and guidelines of the Centers for Disease Control and Prevention, American Academy of Pediatrics, and American College of Obstetrics and Gynecology. METHODS OF STUDY SELECTION: All randomized controlled trials and observational studies in which duration of intrapartum antibiotic prophylaxis is reported relative to subsequent neonatal GBS colonization or sepsis were considered. Case series and study designs using historical cohorts or controls for comparison were excluded. TABULATION, INTEGRATION, AND RESULTS: Three prospective cohort studies and one case-control study met inclusion criteria. Heterogeneity of study design and assembly of cohorts precluded meta-analysis. A systematic review of the individual studies was performed. All studies were rated as fair or poor validity with regard to their ability to evaluate duration of intrapartum prophylaxis and transmission of GBS to the newborn. All 4 studies were largely composed of women with existing risk factors for GBS disease of the newborn. One study supported more than 1 hour of prophylaxis, two studies supported more than 2 hours of prophylaxis, and one was inconclusive. CONCLUSION: Despite unequivocal clinical guidelines recommending at least 4 hours of intrapartum antibiotic prophylaxis, there are no well-designed studies examining duration of intrapartum antibiotic prophylaxis for prevention of early-onset GBS disease of the newborn. We recommend continuing to initiate intrapartum prophylaxis according to the American College of Obstetricians and Gynecologists guidelines; however, the transmission of GBS to neonates exposed to less than 4 hours of intrapartum prophylaxis and their subsequent management require further study.     

Compliance with protocols for prevention of neonatal group B streptococcal sepsis: practicalities and limitations

OBJECTIVE: To compare two protocols for intrapartum antibiotic prophylaxis (IAP) against neonatal group B streptococcal (GBS) sepsis, with respect to staff compliance, in a prospective cohort study in the obstetric units of a community hospital (A) and a university teaching hospital (B). METHODS: Cohorts comprised about 500 women attending antenatal clinics at each hospital (total 1096). Women identified as GBS carriers at 26-32 weeks' gestation and those who had intrapartum clinical risk factors (CRF) were eligible for IAP. Compliance was defined as the proportion of women eligible for IAP who received it according to protocol - as determined by audit of case records - and compared between hospitals and according to indication. RESULTS: Overall, 39% of women were eligible for IAP. Indications were GBS carriage alone (21%), CRF alone (13%) and both (5%). Compliance was similar for GBS carriers at both hospitals: 78% at Hospital A and 76% at Hospital B. However, because of the poor predictive value of screening before 32 weeks, only 65% of intrapartum GBS carriers actually received IAP. For women with CRF only, compliance was significantly lower at Hospital B than Hospital A (56 vs. 75%; p = 0.03). CONCLUSIONS: According to currently recommended protocols, about one-third of healthy women are eligible for intrapartum antibiotics to prevent neonatal GBS sepsis. In practice, antibiotics are often used inefficiently because of poor compliance with protocols and poor predictive values of selection criteria. Better implementation strategies should improve compliance, but GBS vaccines are needed to replace prophylactic antibiotic use, with its associated disadvantages.     

Compliance with a risk-factor-based guideline for the prevention of neonatal group B streptococcal sepsis

Objective: The purpose of this study was to determine the compliance rate with a maternal risk-factor-based guideline for the prevention of neonatal group B streptococcal (GBS) sepsis.Methods: In August 1994, a risk-factor-based guideline for selective intrapartum prophylaxis against neonatal GBS was adopted by a group model health maintenance organization. This guideline identified the following maternal risk factors for neonatal GBS sepsis: preterm delivery, rupture of membranes for >18 h, fever/chorioamnionitis, and history of a previous GBS-affected child. Patients with one or more risk factors were to receive intrapartum antibiotic prophylaxis consisting of either ampicillin, erythromycin, or clindamycin. We conducted a retrospective chart review to record risk factors and use of antibiotics. We hypothesized that >90% of patients with risk factors would receive intrapartum chemoprophylaxis.Results: A total of 805 maternal charts were reviewed. Of these, 105 (13%) were candidates for intrapartum prophylaxis. We found an overall compliance rate of 65%. Compliance rates by risk factor were preterm delivery (51%), prolonged rupture of membranes (73%), fever/chorioamnionitis (87%), and previous affected child (100%).Conclusions: Our results show unexpectedly low compliance rates with a risk-factor-based guideline for the prevention of neonatal GBS sepsis. Only 65% of women with any risk factor for neonatal GBS sepsis received intrapartum antibiotic prophylaxis appropriately. Educational efforts to improve compliance with a risk-factor-based guideline should specifically address mothers delivering at 34-36 weeks gestation and mothers with prolonged rupture of membranes.     

Choosing a strategy to prevent neonatal early-onset group B streptococcal sepsis: economic evaluation

Objective To determine the most appropriate strategy to prevent neonatal streptococcal sepsis in a setting with a low incidence of the disease.
Design Decision analysis and economic evaluation.
Setting Geneva University Hospitals, Switzerland.
Population Pregnant women at 35-37 weeks of gestation and in labour.
Methods Local data and data from the literature were used in a decision analysis to compare the current policy of antibiotic administration at Geneva University Hospitals with the recommended preventive strategies.
Main outcome measures Number of episodes of sepsis averted; cost and number needed to treat to prevent one episode of sepsis; and proportion of women receiving antibiotics during labour.
Results Compared with the current policy, the risk factors strategy would prevent 69 streptococcal sepsis per million deliveries and the screening strategy would prevent 102 cases of sepsis per million deliveries. Cost per averted sepsis case would be £60, 700 and £473, 600, respectively. The number needed to treat to prevent one sepsis would be 1087 with a risk factors strategy and 1029 with a screening strategy. Preventive strategies would increase the proportion of women receiving antibiotics during labour from 6% with the current policy, to 13.5% and 16.5% respectively.
Conclusions Preventive strategies are more effective than the current policy, but imply increased hospital costs and a notable increase in the proportion of women receiving antibiotics during labour, which may be unjustified in a low incidence setting.     

Efficacy of a strategy to prevent neonatal early-onset group B streptococcal (GBS) sepsis

BACKGROUND: Existing guidelines recommend different strategies to prevent early-onset neonatal GBS sepsis. In 1997, using our own data on incidence and risk factors, we established a new prevention strategy which includes GBS screening at 36 weeks' gestation and intrapartum antibiotic prophylaxis (IAP) in women with positive or unknown GBS colonization with at least one risk factor. The present study evaluates the efficacy of the new prevention strategy. METHODS: Retrospective study of the incidence of early-onset GBS sepsis among all live births at the University Women's Hospital Basel between 1997 and 2002. Additional analysis of delivery and post partum period of all GBS sepsis cases, including GBS screening, risk factors during labor (prematurity, rupture of membranes (ROM) <12 h, intrapartum signs of infection), and IAP. Comparison of this group's characteristics G2 (9,385 live births, using the new strategy) with the previous group, G1 (1984-1993, 16,126 live births, without GBS screening or routine IAP) was performed. RESULTS: The incidence of early-onset GBS sepsis was reduced from 1/1000 (G1) to 0.53/1000 (G2). We observed a significant reduction of overall intrapartum risk factors in cases of GBS sepsis. CONCLUSION: This study suggests that our new prevention strategy is effective in reducing the incidence of early-onset GBS sepsis in neonates. In comparison, implementation of the CDC's prevention strategy might have prevented 2 additional cases in 9385 live births. However, this would have required treating a much larger number of pregnant women with IAP with consequential increasing costs, side effects and complications.     

Randomized, placebo-controlled trial of transplacental antibiotic prophylaxis of neonatal group B streptococcal colonization and bacteremia in rabbits

Objective: We evaluated the effect of maternal administration of ampicillin/sulbactam on colonization and bacteremia in newborn rabbits after intracervical inoculation of mothers with group B streptococci (GBS).Methods: New Zealand white rabbits on day 30 of a 31-day gestation were inoculated intracervically with 10(4)-10(5) colony forming units (cfu) GBS. Two hours after inoculation mothers received ampicillin/sulbactam (50 mg/kg) or saline (control) intramuscularly as a single dose, in a randomized double-blinded manner. We induced labor 4 h later with intramuscular oxytocin. At delivery, cultures for GBS were taken from neonatal oropharynx. Thereafter, cultures were taken from neonatal oropharynx and anorectum daily and from neonatal heart at death or after 96 h. Sample size analysis showed a need for 17 pups in each group.Results: In the control group, induction failed in one animal that was excluded from analysis. At birth, 0 of 39 pups of treated does had positive oropharyngeal cultures compared to 26 of 27 (96%) pups of saline-treated does (P < 0.0001). Pups treated with antibiotic in utero were also significantly less likely to have positive oropharyngeal cultures at 24, 48, and 72 h after birth compared to controls (24 h, 0% vs. 100%, P < 0.0001; 48 h, 8% vs. 100%, P < 0.0001; 72 h, 16% vs. 100%, P < 0.0001). Treated pups were significantly less likely to have positive anorectal cultures at 24, 48, and 72 h after birth compared to control animals (24 h, 0% vs. 100%, P < 0.0001; 48 h, 0% vs. 95%, P < 0.0001; 72 h, 0% vs. 92%, P < 0.0001). Treated pups were significantly less likely to have positive heart cultures at 72 h after birth compared to controls (11% vs. 92%, P < 0.0002). Cumulative neonatal survival was higher in treated pups compared to controls at 72 and 96 h after birth (72 h, 32% vs. 0%, P = 0.0003; 96 h, 26% vs. 0%, P = 0.015).Conclusions: Single dose transplacental prophylaxis given 4 h before delivery resulted in decreased neonatal GBS colonization and bacteremia and improved neonatal survival in rabbits.     

Antibiotic resistance patterns of group B streptococcal clinical isolates

OBJECTIVES: To determine the in vitro resistance of group B streptococcus (GBS) to 12 antibiotics. To determine if there has been any decrease in sensitivity to the penicillins or other antibiotics currently used for GBS chemoprophylaxis in pregnant women. Find suitable alternative antibiotics to penicillin. Find an antibiotic that will have minimal selective pressure for resistance among the endogenous resident vaginal microflora. METHODS: The antibiotic susceptibility profiles of 52 clinical isolates of GBS were evaluated to 12 antibiotics: ampicillin, azithromycin, cefamandole, cefazolin, ceftriaxone, ciprofloxacin, clindamycin, erythromycin, nitrofurantoin, ofloxacin, penicillin and vancomycin. Antibiotic sensitivities were determined using disk diffusion and microdilution methods according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: All isolates were sensitive to vancomycin, ofloxacin, ampicillin, ciprofloxacin, nitrofurantoin and penicillin. However, the following number of clinical isolates exhibited intermediate or decreased sensitivity, nine (17%) to ampicillin, eight (15%) to penicillin, 14 (32%) to ciprofloxacin and one (2%) to nitrofurantoin. Thirty-one percent of the isolates were resistant to azithromycin and ceftriaxone, 19% to clindamycin, 15% to cefazolin and 13% to cefamandole. Eighteen (35%) of the clinical isolates tested were resistant to 6 of the 12 antibiotics tested. CONCLUSIONS: The relatively high rates of resistance for 6 of the 12 antibiotics tested suggest that for women allergic to penicillin and colonized with GBS, antibiotic sensitivities to their isolates should be determined. The antibiotic selected for intrapartum chemoprophylaxis should be guided by the organism's antibiotic sensitivity pattern. Patients with GBS bacteriuria should be treated with nitrofurantoin.