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.     

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.     

An obstetric approach to the prevention of early-onset group B beta-hemolytic streptococcal sepsis

Group B beta-hemolytic streptococcus is one of the most common causes of neonatal sepsis. Despite its relationship to neonatal morbidity and mortality, no consensus exists for an approach to its prevention. Several characteristics of the organism such as high maternal carriage rates, the intermittent nature of this carriage, and the failure of antibiotics to permanently eliminate carriage have limited the success of proposed intervention protocols. In this clinical opinion we review characteristics of the organism and previously suggested intervention protocols. Then, based on this review and an analysis of recently published data, a protocol focusing on preterm births is presented. This proposal favors intrapartum treatment of all mothers who are delivered of preterm infants and who are either carriers of group B beta-hemolytic streptococci or whose carriage status is unknown. A comparison of the costs and benefits of this and other approaches is made.     

Effect of a screening-based prevention policy on prevalence of early-onset group B streptococcal sepsis

OBJECTIVE: To assess the effectiveness and feasibility of implementing the Centers for Disease Control and Prevention (CDC) screening-based guidelines for preventing early-onset group B streptococcal sepsis. METHODS: We compared prevalence of early-onset group B streptococcal sepsis after institution of the CDC screening-based protocol (October 1, 1995 through August 31, 1999) with that of historical controls (January 1, 1992 through June 30, 1995). We reviewed medical records for a cohort of deliveries of at least 23 weeks' gestation (January 1, 1996 through December 31, 1996) for group B streptococcal colonization status, risk factors, and intrapartum antibiotic prophylaxis. RESULTS: The prevalence of early-onset group B streptococcal sepsis was 1.16 per 1000 (36 of 31, 133) live births before and 0.14 per 1000 (four of 28,733) live births after institution of the CDC protocol (P <.001). Maternal colonization was known for 95.3% of the 7168 women who delivered (January 1, 1996 through December 31, 1996) at or after 37 weeks' gestation. Of 2174 women who qualified for intrapartum antibiotic prophylaxis, 1871 (86.1%) received it before delivery. There was 93. 8% compliance with intrapartum antibiotic prophylaxis for women who delivered vaginally and 53.2% compliance for women who delivered by cesarean. CONCLUSION: Institution of the CDC screening-based protocol was accomplished at a specialty women's hospital, staffed by full-time faculty and community physicians, with 93.8% compliance for vaginal deliveries, and was associated with an 88% reduction in early-onset group B streptococcal sepsis.     

Purpura fulminans in three cases of early-onset neonatal group B streptococcal meningitis

The diagnosis of purpura fulminans was associated with three cases of early-onset group B beta-hemolytic streptococcal (GBS) disease. All three infants had confirmed bacterial disease, extensive purpuric lesions involving the extremities, and laboratory evidence of a consumptive coagulopathy. All three children survived but had markedly compromised neurologic outcomes. Purpura fulminans has not been previously reported with early-onset GBS disease.     

"Real World" compliance with strategies to prevent early-onset group B streptococcal disease.

OBJECTIVE: To assess the "real-world" compliance with risk- and culture-based strategies to prevent early-onset group B streptococcal disease. STUDY DESIGN: We retrospectively reviewed the medical records of consecutive term pregnancies delivered at three institutions (a subset of practices at an academic hospital using the culture-based strategy, an academic hospital using the risk-based strategy, and a community hospital using both) between January and March 1998. We abstracted demographic data and risk factors for group B streptococcus, group B streptococcal culture information, documentation of intrapartum antibiotic prophylaxis, and adverse drug reactions. We compared intrapartum compliance with the intended strategy. RESULTS: There were a total of 505 women managed with the risk-based strategy. Of those, 79 had a risk factor for group B streptococcal disease and 72/79 (91.1%) received intrapartum antibiotic prophylaxis. There were a total of 428 women managed with the culture-based strategy. Of those, 70 had positive cultures and 67 (95.7%) received intrapartum antibiotic prophylaxis. An additional 39 women in the culture-based group had no documentation that cultures had been done. Of those, eight (20.5%) had risk factors and all eight received intrapartum antibiotic prophylaxis. Compliance with the risk-based strategy was 91.1 versus 96.2% with the culture-based strategy (p=0.3). Among women managed using the risk-based strategy, 5/426 (1.2%) received intrapartum antibiotic prophylaxis without an identifiable risk factor. Among women in the culture-based strategy, 5/359 (1.4%) received intrapartum antibiotic prophylaxis with documented negative group B streptococcal cultures (p=0.5). When examined by site, compliance with the intended strategy was 91.2% at the academic hospital using the risk-based strategy, 100% at the academic hospital using the culture-based strategy, 90.9% at the community practices using the risk-based strategy, and 82.4% at the community practices using the culture-based strategy. CONCLUSION: Overall, intrapartum compliance with the risk-based approach was similar to the culture-based approach. However, there were more cultures not done and cultures done at inappropriate gestations at the community hospital practice.     

Dizygotic twins discordant for early-onset Citrobacter koseri and group B streptococcal sepsis.

Early-onset neonatal sepsis is usually a multisystem fulminant illness with prominent respiratory symptoms, and typically the infant has acquired the organism from the maternal genital tract during the intrapartum period. In this article, we report a rare case of dizygotic twins where each individual suffered early-onset sepsis caused by a different pathogen. Group B streptococcal (GBS) sepsis was diagnosed in twin A 1 day after birth; sepsis and meningitis caused by Citrobacter koseri was diagnosed in twin B at the age of the 4 days. The mother developed pre-eclampsia and fever and the twins were delivered via cesarean section at 35 week's gestation. Twin A received ampicillin treatment for 14 days and recovered fully. Twin B was treated with ceftriaxone for 4 weeks and follow-up brain ultrasound revealed persistent enlargement of the bilateral-lateral ventricles. When empiric antibiotic is considered for the symptomatic twin of a sibling with early-onset GBS infection, samples of blood and cerebrospinal fluid (CSF) should be obtained for culture study before treatment. Adjustment of antibiotic treatment based on the results of cultures and CSF Gram stain and antibiotic susceptibility test is essential.     

Cost-effectiveness of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal disease

OBJECTIVE: To estimate the costs and effects of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal (GBS) disease in the Netherlands. The treatment strategies include a risk-based strategy, a screening-based strategy, a combined screening/risk-based strategy and the current Dutch guideline. DESIGN: Cost-effectiveness analysis based on decision model. SETTING: Obstetric care system in the Netherlands. POPULATION/SAMPLE: Hypothetical cohort of 200,000 neonates. METHODS: A decision analysis model was used to compare the costs and effects of different treatment strategies with no treatment. Baseline estimates were derived from literature and a survey among parents of children affected by GBS disease. The analysis was performed from a societal perspective, and costs and effects were discounted at a percentage of 3%. Main outcome measures Cost per quality adjusted of life-year (QALY). RESULT: The risk-based strategy will prevent 352 cases of early-onset GBS for 5.0 million Euros, indicating a cost-effectiveness ratio of 7600 Euros per QALY gained. The combined screening risk-based strategy has comparable results. The current Dutch guideline resulted in lower effects for higher costs. The screening-based strategy shows the highest reduction in cases of early-onset GBS, however, at a cost-effectiveness ratio of 59,300 Euros per QALY gained. Introducing the polymerase chain reaction (PCR) test may lead to a more favourable cost-effectiveness ratio. CONCLUSION: In the Dutch system, the combined screening/risk-based strategy and the risk-based strategy have reasonable cost-effectiveness ratios. If it becomes feasible to add the PCR test, the cost-effectiveness of the combined screening/risk-based strategy may even be more favourable.     

Endotoxin enhancement as a possible etiology of early-onset group B beta-hemolytic streptococcal sepsis in the newborn

Group B streptococcal cells, either viable or heat-killed, contain a substance that induced fever in rabbits with maximal responses occurring four hours after intravenous injection. In contrast, supernatant fluids failed to induce significant fever. Group B streptococcal cells also enhanced host susceptibility to lethal shock by endotoxin as much as 40,000-fold. A graph of log streptococcal cell dose used for pretreatment versus log LD50 endotoxin gave a straight line with a slope of approximately -1. Rabbits that received both streptococcal cells and endotoxin showed initial fever followed by hypothermia, labored breathing, watery diarrhea, evidence of vascular collapse, and finally death. Animals that received streptococcal cells or endotoxin alone showed only fevers and mild diarrhea. A possible theory for the cause of death in the neonate infected with group B streptococci is presented.     

Liberal diagnosis and treatment of intrauterine infection reduces early-onset neonatal group B streptococcal infection but not sepsis by other pathogens

OBJECTIVE: Comparison of the incidence and case fatality of early-onset group B streptococcus sepsis and sepsis caused by other pathogens in neonates after change of management of intrauterine infection. METHODS: All infants delivered from 1988 through 1997 at a gestational age > or = 24 weeks with a birth weight > or = 500 gram without lethal congenital abnormalities were eligible for inclusion. Infants delivered by cesarean section before the onset of labor or rupture of membranes were excluded. During the first period (1988-1991) intrauterine infection was diagnosed by a temperature > 38 degrees C, during the second period (1992-1997) this diagnosis was made at a lower temperature (> or = 37.8 degrees C) or by fetal tachycardia > or = 160/min. Treatment of intrauterine infection was similar during both periods with 3 x 2 gram amoxicillin and 1 x 240 mg gentamicin every 24 hours intravenously during labor. Prophylactic treatment during labor was only given to women with a history of an earlier infant with early-onset group B streptococcus sepsis. RESULTS: During the first period 6,103 infants were included, during the second period 8,504. Intrauterine infection was diagnosed and treated more often in the second period (7.1% vs. 2.6%). The incidence of early-onset group B streptococcus sepsis was significantly lower in the second period than in the first period [0.2% vs. 0.4%; OR 0.5 (0.3-0.9)] and survival without disability higher [80% vs. 52%; OR 4.5 (1.4-16.5)]. However, in both periods the overall incidence of neonatal sepsis (3.6% vs. 3.5%) and overall mortality because of sepsis (14.3% vs.13.1%) were similar. CONCLUSIONS: Although the early detection of clinical signs of intrauterine infection might have been effective for the prevention of serious sequelae of early-onset group B streptococcus sepsis the overall incidence and mortality from neonatal sepsis remained unchanged. Evaluation of preventive measures for early-onset group B streptococcus sepsis should always take the incidence of neonatal sepsis caused by other pathogens into account.     

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.     

Use of extracorporeal membrane oxygenation to rescue a newborn with early-onset group B streptococcal sepsis and cardiopulmonary failure.

Group B streptococcal (GBS) infection is an important cause of perinatal morbidity and mortality. We report the use of extracorporeal membrane oxygenation (ECMO) to rescue a newborn with refractory GBS sepsis and meningitis who developed cardiopulmonary failure. This 2-day-old infant weighed 2640 g and was born to a healthy mother at full term. Respiratory distress, hypotension, and persistent pulmonary hypertension developed on the second day of life. The clinical condition deteriorated rapidly despite conventional treatment, and venoarterial ECMO was established to rescue this moribund newborn. During ECMO, the patient regained stable hemodynamics and good oxygenation, and infection was controlled. ECMO was used for 90 hours and the baby was weaned smoothly. Neurologic assessment after ECMO revealed hydrocephalus, abnormal electroencephalogram, and increased brain auditory evoked potential threshold. This report emphasizes that ECMO may be considered to rescue neonatal patients with cardiopulmonary failure due to GBS sepsis. Possible neurologic complications after ECMO should be carefully monitored.     

Maternal group B streptococcal (GBS) genital tract colonization at term in women who have asymptomatic GBS bacteriuria

OBJECTIVE: To determine the rate of positive group B streptococcus (GBS) cultures at 35-37 weeks gestation in women who have first trimester asymptomatic GBS bacteriuria. METHODS: Pregnant women with asymptomatic first trimester GBS bacteriuria had genital cultures for GBS performed at 35-37 weeks gestational age. Serotyping was performed by the standard Lancefield capillary precipitin method. RESULTS: Fifty-three women with positive urine cultures had genital cultures performed at 35-37 weeks. Sixteen of the 53 (30.2%; 95% confidence interval: 18.4-44.3%) third trimester vaginal cultures were positive for GBS. Five of eight (63%) of the women with typable urine serotypes had the same typable serotype in the third trimester genital culture. CONCLUSION: Genital tract cultures at 35-37 weeks for GBS correlate poorly with first trimester asymptomatic GBS bacteriuria. Recommendations for GBS prophylaxis in labor in women who have first trimester asymptomatic GBS bacteriuria should be investigated further and reconsidered.     

Transient increase of early-onset group B streptococcal septicemia

Since 1976, all cases of neonatal group B streptococcal (GBS) septicemia/meningitis have been registered at two Swedish University Hospitals. A significant increase in the number of infants contracting early-onset GBS-septicemia was noticed at one clinic in 1981, from 1-3 cases per yr to 8 cases. Six months prior to this increase the number of deliveries increased from about 1500 per yr to nearly 3000 per yr. It is suggested that external factors, e.g., subtle changes in the nursing combined with an extended disadvantage at the ward might influence the development of early-onset GBS septicemia.     

Intrapartum chemoprophylaxis of early-onset group B streptococcal disease

A randomized study in 121 pregnant women carrier of group B streptococci is undertaken in order to assess the administration of 500 mg of intrapartum ampicillin intravenously to interrupt mother-to-fetus group B streptococcal transmission. In the prophylaxis group there was a significant reduction in neonatal colonization (3.7 vs. 42.9%) and in severe neonatal colonization (0 vs. 25%). There was no case of group B streptococcal sepsis in the prophylaxis group compared to 4.6% (3 cases) in the control group (P greater than 0.05). Clinically infected newborns represented 3.3% in the prophylaxis group vs. 13.8% in the control group. When the organism was isolated during delivery in the vagina or amniotic fluid, prophylaxis was quickly followed by second negative cultures. Ampicillin levels in the amniotic fluid were detected early, and they increased significantly till the third hour. Bactericidal levels in the umbilical cord were detected in 60% of newborns. All these findings support the usefulness of ampicillin prophylaxis in the prevention of early-onset group B streptococcal sepsis.     

Comparison of early-onset neonatal sepsis caused by Escherichia coli and group B Streptococcus

OBJECTIVE: The purpose of this study was to compare maternal characteristics and neonatal morbidity and mortality rates that are associated with early-onset neonatal sepsis that is caused by group B Streptococcus and Escherichia coli. STUDY DESIGN: This was a retrospective review of newborn infants with a positive blood culture (and/or cerebrospinal fluid) that was positive for either E coli or group B Streptococcus during the first week of life. Data were abstracted from maternal and neonatal medical records. RESULTS: Among 28,659 deliveries during the study period, 102 episodes of early-onset neonatal sepsis were identified, 61 of which were caused by group B Streptococcus and 41 of which were caused by E coli. E coli sepsis cases had a lower birth weight, a higher percentage with 5-minute Apgar score <7, and a longer stay in the hospital neonatal intensive care unit and required mechanical ventilation more frequently. Death after early-onset neonatal sepsis with E coli was also more frequent. CONCLUSION: Early-onset sepsis with E coli is associated with more morbidity and a higher mortality rate compared with early-onset group B Streptococcus.