Intrapartum Antimicrobial Prophylaxis Research Articles

Neonatal sepsis: Progress towards improved outcomes

Neonates are predisposed to infections during the perinatal period due to multiple exposures and a relatively compromised immune system. The burden of disease attributed to neonatal infections varies by geographic region and maternal and neonatal risk factors. Worldwide, it is estimated that more than 1.4 million neonatal deaths annually are the consequence of invasive infections. Risk factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic immaturity, maternal Group B streptococcal colonization, prolonged rupture of membranes, and maternal intra-amniotic infection. Intrapartum antimicrobial prophylaxis administered to GBS-colonized women has reduced the burden of disease associated with early onset GBS invasive infections. Active surveillance has identified Gram-negative pathogens as an emerging etiology of early-onset invasive infections. Late-onset neonatal sepsis (LOS) attributable to Gram-positive organisms, including coagulase negative Staphylococci and Staphylococcus aureus, is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of late-onset sepsis, especially among infants who receive broad spectrum antimicrobial agents. Prophylactic fluconazole administration to very low birthweight (VLBW) neonates during the first 6 weeks of life reduces invasive candidiasis in neonatal intensive care units with high rates of fungal infection. Prevention of healthcare associated infections through antimicrobial stewardship, limited steroid use, early enteral feeding, limited use of invasive devices and standardization of catheter care practices, and meticulous hand hygiene are important and cost-effective strategies for reducing the burden of late-onset neonatal sepsis.

Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics

Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of early-onset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p = 0.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure.

Colonization, serotypes and transmission rates of group B streptococci in pregnant women and their infants born at a single University Center in Germany

To evaluate colonization, transmission rate and serotype distribution of group B streptococci (GBS) in pregnant women and infants born in a single University Center in Germany. In a prospective study we collected cultures from pregnant women and ear cultures from newborns. We performed serotyping and susceptibility testing. Obstetrical factors associated with mother to infant transmission were analyzed using logistic regression. We evaluated cultures of 869 pregnant women and 845 neonates including 657 paired maternal-neonatal cultures. Maternal colonization occurred in 21.1% (183/869), transmission from mother to newborn in 11.2% (17/152). Intrapartum antimicrobial prophylaxis (IAP) and cesarean delivery were associated with reduction of transmission rate (P=0.014 and 0.019, respectively). The incidence for early-onset disease (EOD) was 1.71 per 1000 live births. Of GBS positive women IAP was administered in only 39% (59/152). Serotype III was the most prevalent isolate (28% maternal; 52% neonatal) and transmission occurred more frequently compared to other serotypes. The incidence of EOD and distribution of serotypes in Germany are similar to published data from the USA prior to 1996. Despite national guidelines with universal GBS screening, our study demonstrated a lack of adherence to this recommendation. There is a need for enhanced compliance.

Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics

In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance.

Invasive Early-Onset Neonatal Group B Streptococcal Cases – Alaska, 2000–2004

We conducted a review of invasive early-onset neonatal group B Streptococcus (GBS) infections that occurred during 2000-2004 in Alaska to determine the proportion of cases that might have been prevented by complete implementation of the 2002 Centers for Disease Control and Prevention (CDC) guidelines. Cases were identified from statewide laboratory-based surveillance conducted by the CDC Arctic Investigations Program, and from the Alaska Medicaid database using International Classification of Diseases 9 codes 038.0, 041.02, 320.2, and 482.3. Neonates were considered to have early-onset disease if clinical illness within 6 days after birth was accompanied by GBS isolation from a normally sterile site. Maternal and neonatal medical records were reviewed. Potentially preventable cases were those for whom the 2002 CDC GBS maternal screening and intrapartum antimicrobial prophylaxis (IAP) guidelines were not completely implemented. Preventability of events not related to clinician implementation of the guidelines were not considered. Twenty-one neonates with invasive early-onset GBS disease were identified (0.42/1,000 live births). Three of the eight mothers for whom IAP was indicated, did not receive adequate IAP. Nine of the 13 mothers for whom there was no indication for IAP, had not been screened appropriately. Therefore, a total of 12 neonates were determined to have had potentially preventable GBS disease. Over 50% of the invasive early-onset neonatal GBS cases in Alaska were potentially preventable. The majority of these cases may have been prevented by closer adherence to either specific IAP administration guidelines or to maternal screening guidelines.

Early-Onset and Late-Onset Neonatal Group B Streptococcal Disease—United States, 1996-2004

In 2002, CDC, the American College of Obstetricians and Gynecologists (ACOG), and the American Academy of Pediatrics (AAP) issued revised guidelines for prevention of perinatal invasive group B streptococcal (GBS) disease. These guidelines recommend universal screening of pregnant women for rectovaginal GBS colonization at 35-37 weeks' gestation and administering intrapartum antimicrobial prophylaxis to carriers. To assess the impact of the guidelines on multistate trends in neonatal GBS disease incidence, CDC analyzed data from the Active Bacterial Core surveillance (ABCs) system from 1996-2004. This report summarizes the results of that analysis, which determined that incidence of GBS disease in infants aged 0-6 days (i.e., early-onset disease) in 2004 had decreased by 31% from 2000-2001, the period immediately before universal screening was implemented. Incidence of GBS disease in infants aged 7-89 days (i.e., late-onset disease) remained unchanged during the 9-year period reviewed. Continued monitoring is needed to assess the impact of the 2002 guidelines on early-onset disease and the long-term effect of widespread intrapartum use of antimicrobial agents on neonatal GBS disease.

A trial of preventing early- and late-onset Group B streptococcal sepsis with combined intrapartum chemoprophylaxis and universal neonatal screening

Prevention of early-onset Group B Streptococcal (GBS) infection has been attempted by employing universal maternal screening for GBS, intrapartum chemoprophylaxis, and a single dose of penicillin given to neonates in the first hour of life. This strategy, however, does not seem to prevent the occurrence of late-onset neonatal group B streptococcal disease. We assessed early and late-onset GBS disease with the use of a before-after study designed to evaluate the implementation of intrapartum antimicrobial prophylaxis. Moreover, universal neonatal screening for colonization of GBS was carried out with swabs of the external ear canal. Newborns with GBS colonization received a preventive treatment with oral amoxicillin for 10 days. Early-onset GBS infection decreased from 0.5 per thousand at baseline period to 0.19 per thousand at the study period. The incidence of late-onset GBS disease decreased from 1:1348 (0.74 per thousand) to 1:20,710 (0.048 per thousand). The overall cost for universal neonatal screening paid for by the Italian Health System in the study period was 31,065 US dollars with an antibiotic prophylaxis cost of 2,399 US dollars. A combined strategy based on GBS culture screening and assessment of risk factors for perinatal GBS disease can significantly reduce the rate of both early and late-onset GBS infections.

Detection of group B streptococcal bacteremia in simulated intrapartum antimicrobial prophylaxis

The diagnostic value of negative blood cultures from neonates whose mothers receive intrapartum antimicrobial prophylaxis for prevention of perinatal group B streptococcal disease is uncertain. We investigated whether blood culture medium containing resin designed to adsorb antibiotic improved group B streptococcal detection following simulated intrapartum antimicrobial prophylaxis. Group B streptococcus ( Streptococcus agalactiae) was preincubated with varying antibiotic concentrations before inoculation into BACTEC Peds Plus resin-containing medium, BACTEC Standard, or Trek ESP 80A. In the presence of 10 mcg/mL ampicillin, detection of both low (<500 CFU/mL) and high (>500 CFU/mL) S. agalactiae inocula ranged between 75-100% of resin-containing medium bottles; detection rates in both non-resin-containing media were lower. When S. agalactiae was detected, it was detected sooner with resin-containing medium. The addition of gentamicin to ampicillin did not affect sensitivity of resin-containing medium for S. agalactiae. In our model, resin-containing medium more consistently and more rapidly detected S. agalactiae than did either of two non-resin-containing media, in the presence of antibiotic levels likely present in fetal sera following intrapartum antimicrobial prophylaxis.

Prevention of neonatal group B streptococcal disease: A combined intrapartum and neonatal protocol

Objective: We sought to assess the efficacy of a clinical protocol to reduce the incidence of early-onset neonatal group B Streptococcus (GBS) infection. Study design: We assessed neonatal sepsis from GBS and other organisms with use of a before-after study design to evaluate the effects of implementation of combined intrapartum antimicrobial prophylaxis given selectively to mothers with GBS risks and penicillin G given to all neonates. Results: In 1994, early-onset GBS infection developed in 31 of 13,887 live births (2.2/1000), 13 preterm and 18 term cases. After implementation of the prophylaxis protocol (1995), 6 of 13,527 live births had early-onset GBS (0.4/1000) (P < .001). There were no preterm (P = .0004) and 6 term GBS cases (P = .02). The efficacy continued through 1999 (0.5/1000) without an increase in neonatal infections from other bacteria. Conclusion: Combined maternal and infant antimicrobial prophylaxis can significantly and safely reduce rates of early-onset GBS infection in both preterm and term infants. (Am J Obstet Gynecol 2002;186:618-26.)

Prevention of group B streptococcus early-onset neonatal sepsis: comparison of the Center for Disease Control and prevention screening-based protocol to a risk-based protocol in infants at greater than 37 weeks' gestation.

To compare the Center for Disease Control consensus guidelines' screening-based strategy to a risk-based strategy as regards the incidence of early-onset group B streptococcus (GBS) infection among term infants. A cohort of university hospital prenatal clinic mother-infant pairs who were screened for GBS at 35 to 37 weeks' gestation were compared to a matched control group of unscreened mother-infant pairs from the outreach satellite prenatal clinics who delivered at the same institution during the same time period. GBS screening was carried out with rectovaginal cultures plated on selective media. GBS-positive women received antimicrobial prophylaxis in labor whereas women of unknown GBS status were only treated intrapartum if they had a risk factor for GBS infection. Principal outcome variables included incidence of cases of neonatal early-onset GBS sepsis (blood, urine, or cerebrospinal fluid positive for GBS), incidence of cases of strongly suspected GBS sepsis (culture negative), and incidence of neonatal sepsis with non-GBS organisms. There were 3164 screened mother-infant pairs who were compared to 2684 unscreened pairs. The incidence of GBS carriage was 13.3%. A random sample of 420 screened women were compared to a matched sample of 407 women of unknown GBS carrier status for characterization of demographics and risk factors. No cases of documented GBS sepsis occurred in the infants of the screened women, but four cases occurred among the infants of the women who did not undergo screening (incidence 1.5/1000) (p = 0.04), only one of whom had a risk factor for GBS infection. Cases of suspected but culture negative sepsis were not more common in the screened population when compared to the unscreened. There was one case of Escherichia coli sepsis in an infant of a mother in the unscreened group. GBS screening at 35 to 37 weeks, with intrapartum antimicrobial prophylaxis of carriers, decreased the incidence of neonatal early-onset GBS sepsis and appears to have advantages over treatment based on risk factors alone in term infants.

Early-onset neonatal group B streptococcal infection: Implications for practice

Group B streptococcus (GBS) is the leading bacterial infection associated with morbidity and mortality of newborns in the United States. Most neonatal infections can be prevented through the use of intrapartum antimicrobial prophylaxis in women who are at increased risk for transmitting infection to their newborns. However, prevention strategies have not been implemented widely or consistently, and the incidence of neonatal GBS disease has not declined. An understanding of GBS epidemiology, clinical presentation, and prevention strategies enhances the PNP's decision-making skills in the nursery and strengthens the PNP's ability to evaluate and compare new approaches to GBS prevention. J Pediatr Health Care. (2000). 14, 264-269.

Early-onset neonatal group B streptococcal infection: Implications for practice

<h2>Abstract</h2> Group B streptococcus (GBS) is the leading bacterial infection associated with morbidity and mortality of newborns in the United States. Most neonatal infections can be prevented through the use of intrapartum antimicrobial prophylaxis in women who are at increased risk for transmitting infection to their newborns. However, prevention strategies have not been implemented widely or consistently, and the incidence of neonatal GBS disease has not declined. An understanding of GBS epidemiology, clinical presentation, and prevention strategies enhances the PNP's decision-making skills in the nursery and strengthens the PNP's ability to evaluate and compare new approaches to GBS prevention. J Pediatr Health Care. (2000). <i>14,</i> 264-269.

Adoption of Perinatal Group B Streptococcal Disease Prevention Recommendations by Prenatal-Care Providers—Connecticut and Minnesota, 1998

Group B streptococcal (GBS) infections are the leading bacterial cause of serious neonatal disease in the United States (1). In 1996, in collaboration with the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists, CDC issued consensus guidelines for preventing perinatal GBS disease (2-4). These guidelines recommend using either a screening-based or a risk-based strategy to identify women who should receive intrapartum antimicrobial prophylaxis. To assess adoption of the GBS disease prevention guidelines, the Connecticut and Minnesota state health departments surveyed prenatal-care providers during January-April 1998. This report presents the survey findings, which indicate that most prenatal-care providers in Connecticut and Minnesota have adopted perinatal GBS disease prevention policies and that strategy choice may vary by state and provider type.

Antimicrobial prevention of early-onset group B streptococcal sepsis: estimates of risk reduction based on a critical literature review.

To identify interventions that reduce the attack rate for early-onset group B streptococcal (GBS) sepsis in neonates. Literature review and reanalysis of published data. The rate of early-onset GBS sepsis in high-risk neonates can be reduced by administration of antibiotics. Treatment during pregnancy (antepartum prophylaxis) fails to reduce maternal GBS colonization at delivery. With the administration of intravenous ampicillin, the risk of early-onset infection in infants born to women with preterm premature rupture of membranes is reduced by 56% and the risk of GBS infection is reduced by 36%; addition of gentamicin may increase the efficacy of ampicillin. Treatment of women with chorioamnionitis with ampicillin and gentamicin during labor reduces the likelihood of neonatal sepsis by 82% and reduces the likelihood of GBS infection by 86%. Universal administration of penicillin to neonates shortly after birth (postpartum prophylaxis) reduces the early-onset GBS attack rate by 68% but is associated with a 40% increase in overall mortality and therefore is contraindicated. Intrapartum prophylaxis, alone or combined with postnatal prophylaxis for the infants, reduces the early-onset GBS attack rate by 80% or 95%, respectively. Women with chorioamnionitis or premature rupture of membranes and their infants should be treated with intravenous ampicillin and gentamicin. Intrapartum antimicrobial prophylaxis may be appropriate for other women whose infants are at increased but less extreme risk, and supplemental postpartum prophylaxis may be indicated for some of their infants. Selection of appropriate candidates and prophylaxis strategies requires careful consideration of costs and benefits for each patient. group B streptococcus, neonatal sepsis, early-onset sepsis, prevention, prophylaxis.

Adoption of Hospital Policies for Prevention of Perinatal Group B Streptococcal Disease—United States, 1997

Group B streptococcal (GBS) infections are the leading bacterial cause of disease and deaths among newborns in the United States. In 1993, the annual cost of caring for newborns with sepsis caused by group B Streptococcus was an estimated $294 million. A survey of hospital GBS disease prevention practices in 1994 indicated that those hospitals with a prenatal screening policy had fewer neonatal GBS disease cases. In 1996, to promote a coordinated approach to prevention, CDC issued consensus guidelines about GBS disease prevention that were endorsed by the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics. These consensus guidelines recommend using either a screening-based strategy or a risk-based strategy for identifying women who should receive intrapartum antimicrobial prophylaxis. To evaluate adoption of the consensus guidelines, in 1997, hospitals in eight surveillance areas were surveyed, and the results were compared with findings of a similar survey conducted in 1994. The proportion of hospitals with prevention policies in each site was compared with the site's rate of early-onset disease to assess the impact of the prevention policies. This report presents the survey findings, which indicate that more hospitals have adopted GBS disease prevention policies since issuance of the consensus guidelines.

Frequent resistance of clinical group b streptococci isolates to clindamycin and erythromycin

Objective: To determine both the frequency of reported penicillin allergy in parturients and the frequency of resistance in vitro of clinical isolates of group B streptococci to clindamycin and erythromycin. Methods: One hundred clinical isolates of group B streptococci were tested to determine the frequency of resistance to clindamycin, erythromycin, penicillin G, vancomycin, and cefazolin. The frequency of beta-lactam allergy and reported allergic reaction also were recorded for all consecutive laboring women during the 4-month study. Results: The frequency of group B streptococcal resistance to clindamycin was 15% and to erythromycin was 16%. No isolates were resistant to penicillin G, vancomycin, or cefazolin. Twelve percent of the 963 women who delivered during the study reported a penicillin allergy, but only 30% of those could describe their allergic reaction. Conclusion: In vitro resistance of group B streptococci to clindamycin and erythromycin occurred frequently in this population. Whereas the importance of this finding in vivo is uncertain, it raises concern about the possibility of inadequate prophylaxis using currently recommended alternatives in penicillin-allergic patients. Artful questioning of women reporting penicillin allergy may lessen the likelihood of using these less desirable agents in the setting of intrapartum antimicrobial prophylaxis.

Prevention of group B streptococcal infection in neonates

Most publications on the subject of group B streptococcus since December 1996 have concentrated on supporting and to some degree extending our existing knowledge of the epidemiology of group B streptococcus and of intrapartum antimicrobial prophylaxis, which is the only approach available for reducing the incidence of group B streptococcal infection. Of greatest importance clinically are the reviews and studies on intrapartum antimicrobial prophylaxis, which continue to show that this is a worthwhile intervention as it significantly reduces the incidence of early onset group B streptococcal sepsis. The best approach to the detection of carriage is also covered, as is the changing epidemiology as a result of the implementation of intrapartum antimicrobial prophylaxis in some centres. Finally, the prospect of a vaccine is discussed.

Prevention of Early-onset Group B Streptococcal Sepsis (EOGBSS): Implementation of the CDC Guidelines † 1424

Background: CDC guidelines for prevention of EOGBSS which recommended intrapartum antimicrobial prophylaxis (IAP) for GBS positive (+) or GBS unknown (unk) women with risk factors (RF=fever >38°C, PROM≥18hrs or <37wks GA) were instituted 10/1/95 at Magee-Womens Hospital(MWH). The purpose of this study was to document the effectiveness of these guidelines.

Prophylaxis for neonatal group B streptococcus infections

For the past two decades, group B streptococcus (GBS) has been the pathogen most frequently isolated from neonates with invasive bacterial disease. This is a review of the relevant aspects of microbiology, epidemiology, and clinical manifestations and a summary of the major studies of prevention strategies that led to the development of the 1996 consensus guidelines for prevention of perinatal GBS disease. There is now sufficient experience to know that > or = 80% of cases of early onset GBS disease can be prevented when a protocol for intrapartum chemoprophylaxis with either penicillin or ampicillin is implemented consistently within a delivery population. Present controversies revolve around the choice between a universal screening-based strategy versus a risk factor-based strategy, optimal management of the neonate born to a mother who received intrapartum antimicrobial prophylaxis, and effective methods to ensure implementation. The present guidelines will likely be refined as additional experience is gained.

The Pediatric Costs of Strategies for Minimizing the Risk of Early-Onset Group B Streptococcal Disease

Objective: To estimate the pediatric costs associated with the Centers for Disease Control and Prevention (CDC) guidelines for the management of infants born to mothers receiving intrapartum antimicrobial prophylaxis for prevention of early-onset group B streptococcal disease.Methods: For an annual United States birth cohort of 3.95 million infants, we estimated the cost of pediatric care provided to full-term asymptomatic infants when pediatricians followed the CDC algorithm for the management of infants exposed to intrapartum antimicrobial prophylaxis under culture-based and risk factor–based maternal care approaches. We calculated the relative contribution of pediatric costs to the total costs of preventing a case of early-onset group B streptococcal sepsis.Results: Total pediatric costs were $41 million for a culture-based approach and $33 million for a risk factor–based approach. Hospital and physician costs accounted for more than 78% of this total. The majority (over 95%) of the pediatric costs were associated with vaginal deliveries. Incorporating pediatric costs into previous cost-effectiveness analyses increased the cost per sepsis case averted by as much as 51% for culture-based strategies and by as much as 112% for risk factor–based strategies. Pediatric costs varied with the average length of stay for full-term infants and with the average cost of a hospital day.Conclusion: Substantial pediatric costs are associated with the implementation of an obstetric strategy for minimizing the risk of early-onset group B streptococcal disease. Such costs should be included in future cost-effectiveness analyses of different strategies for minimizing the risk of group B streptococcal disease in newborns.