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ORIGINAL RESEARCH |
From the University of Florida College of Medicine, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Gainesville, Florida.
Address reprint requests to: Rodney K. Edwards, MD, MS, University of Florida College of Medicine, Department of Obstetrics and Gynecology, PO Box 100294, Gainesville, FL 32610-0294; E-mail: edwardsr{at}obgyn.ufl.edu.
| ABSTRACT |
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METHODS: We performed a prospective cohort study of women identified as carriers of group B streptococci by current pregnancy genital tract (group 1) or urine cultures (group 2), or a positive culture in a prior pregnancy (group 3). Intrapartum culture specimens were obtained, and isolates were tested for susceptibility to six antibiotics using the agar disk diffusion technique.
RESULTS: Intrapartum cultures were positive for 68% (62, 73), 61% (49, 72), and 48% (36, 60) of groups 1 (n = 249), 2 (n = 69), and 3 (n = 59), respectively. Cultures were positive in 67% (61, 73) of women in group 1 whose cultures were done 42 days or less before delivery (n = 218). The proportion of isolates (n = 239) susceptible to penicillin, ampicillin, cefazolin, and vancomycin was 100% (98, 100). The proportion susceptible to clindamycin and erythromycin was 91% (87, 94) and 79% (73, 84), respectively.
CONCLUSION: The positive predictive value of antenatal group B streptococci cultures is lower than was previously reported. Clindamycin and erythromycin are not optimal agents for prophylaxis against early-onset neonatal group B streptococcal infection in patients who are allergic to penicillin.
Streptococcus agalactiae, commonly known as group B streptococci, are gram-positive aerobic coccoid bacteria that can be isolated from the vagina and rectum of 1535% of pregnant women when using selective broth media.1,2 Without intervention, the organism causes early-onset (within the first 7 days of life) neonatal infection in one to two per 1000 live births in the general obstetric population.3
Administration of intravenous intrapartum antibiotic prophylaxis substantially reduces the incidence of early-onset neonatal group B streptococcal infection.46 The Centers for Disease Control and Prevention (CDC) recommends that intrapartum antibiotic prophylaxis with penicillin G, or alternatively ampicillin, should be given to women in labor who either have been shown to carry group B streptococci by culture or who develop risk factors for transmission of the organism.7
To date, no penicillin-resistant or ampicillin-resistant isolates of group B streptococci have been reported. However, resistance of group B streptococcal isolates to erythromycin and clindamycin, the agents recommended for intrapartum antibiotic prophylaxis in penicillin-allergic women, has increased. Recent studies from this country report that 315% of isolates are resistant to clindamycin and 718% of isolates are resistant to erythromycin.811
Initially, acceptance of the screening-based approach was limited because serial cultures from pregnant women had suggested that women might carry group B streptococci intermittently.12 This concern was the reason that the CDC recommended culture at 3537 weeks gestation, rather than earlier in pregnancy. The reliability of these 3537 week cultures has been evaluated in at least one study. Yancey et al13 found that 87% of women with positive anogenital cultures performed within 6 weeks of delivery had positive intrapartum cultures (positive predictive value 87%). One scenario that is omitted by the CDC recommendations is the management of a current pregnancy in a woman who had a positive screening culture for group B streptococci in a previous pregnancy. The principal objective of this study was to estimate the positive predictive values of various methods of identifying carriers of group B streptococciprior pregnancy colonization, current pregnancy urine culture, and current pregnancy anogenital culture. In addition, we estimated the proportion of group B streptococci isolates susceptible to six antibiotics.
| MATERIALS AND METHODS |
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In our prenatal clinics, all women undergo a screening urine culture at the first prenatal visit. Women having group B streptococci isolated from this urine culture and women with a history of group B streptococcal colonization in a prior pregnancy are considered to be colonized in the current pregnancy. Women admitted for preterm labor or preterm premature rupture of the membranes are screened for group B streptococcal colonization with combined vaginal and anal cultures. All other women undergo screening anovaginal cultures at 3537 weeks gestation.
After women gave written informed consent, and before they received any dose of antibiotics, culture specimens were taken from the lower vagina, perineum, and perianal skin of these subjects. The swabs used to obtain these culture specimens were commercially available dual rayon-tipped swabs with modified Stuart bacterial transport medium (Culturette II, Becton Dickinson, Sparks, MD). One of these swabs was used for this prospective cohort study, and the other swab was used for culture of Enterobacteriaceae for a concurrent randomized clinical trial.
Within 24 hours of collection, swabs were inoculated into selective Todd-Hewitt broth containing polymixin B (10 µg/mL), nalidixic acid (15 µg/mL), and crystal violet (0.1 µg/mL), and incubated at 37C for 1824 hours.14 Broth subculture, identification, and storage of group B streptococci isolates were performed according to standard techniques described previously.15 A single investigator (RKE) performed all of these cultures.
Susceptibility of group B streptococci isolates to penicillin, ampicillin, cefazolin, vancomycin, clindamycin, and erythromycin was determined by the agar disk diffusion method described by Bauer et al,16 using interpretation zones established by the National Committee for Clinical Laboratory Standards. Staphylococcus aureus American Type Culture Collection 25923 was used as a reference standard.
The medical records of subjects and their infants were reviewed. Demographic and outcome data were entered into a relational database (Access, Microsoft Corp., Redmond, WA). Also entered into the database were the group B streptococci culture results and the results of antibiotic susceptibility testing. All data management and analysis was done using SAS 8.0 (SAS Institute, Cary, NC). All tests of statistical significance were two-tailed and used an
level of 0.05.
Groups were determined by method of identification as a group B streptococcus carrier (current pregnancy-positive genital tract culture [group 1], current pregnancy-positive urine culture [group 2], or positive urine or genital tract culture in a prior pregnancy [group 3]). For demographic data from these three groups, analysis of variance was performed on continuous variables using the Duncan test for multiple comparisons, and the
2 test was performed on nominal variables to detect differences between groups. The proportions of women in each group with positive intrapartum group B streptococci cultures and 95% confidence intervals around these proportions were calculated. These proportions represent the positive predictive value of each method of carrier identification. The proportions of collective isolates susceptible, of intermediate susceptibility, and resistant to the six antibiotics were also calculated.
| RESULTS |
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There were 249 women in group 1, 69 women in group 2, and 59 women in group 3. Demographic data for these three groups are shown in Table 1
. In group 1, 218 women had their genital tract cultures performed 42 days or less before delivery. This subset of group 1 did not differ from the rest of the group regarding any of the demographic variables presented in Table 1
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In the entire cohort, only one neonatal death occurred. That infant had hypoplastic left heart syndrome, and the death was unrelated to infection. There were three cases of neonatal infections in the cohorttwo cases of pneumonia and one case of bacteremia caused by Bacteroides fragilis. There were no cases of culture-confirmed neonatal group B streptococcal infection in the cohort.
| DISCUSSION |
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Deciding whether to give intrapartum antibiotic prophylaxis to a woman who was colonized in a prior pregnancy is particularly difficult. Unfortunately, the CDC recommendations do not address this situation.7 Fully one-half of the small group of women in our study who were given intrapartum antibiotic prophylaxis because they were identified as a group B streptococcus carrier in a previous pregnancy did not have evidence of group B streptococci in their genital tracts at the time of the current labor. Therefore, their infants were at significantly decreased risk for developing early-onset group B streptococcal infections.
Because there is a growing body of literature that describes the potential for intrapartum antibiotic prophylaxis to have untoward effects, it is important that we strive to limit the administration of antibiotics for this purpose to those patients who stand to benefit from it. Until a reliable rapid detection method or effective vaccine for group B streptococci becomes widely available, further research aimed at specifically targeting those fetuses at risk of group B streptococcal infection should be a priority.
Other groups have reported on the susceptibility patterns of group B streptococci isolates to various antibiotics.811 Our results are in keeping with those of others. Fortunately, we found no isolates that were resistant to penicillin or ampicillin. However, the finding that only 91% and 79% of isolates were susceptible to clindamycin and erythromycin, respectively, is of concern when treating women who have a history of allergy to penicillins. The proportion of isolates susceptible to erythromycin makes this antibiotic unsuitable for use as the agent of intrapartum antibiotic prophylaxis for penicillin-allergic women in our obstetric population. Although the proportion of group B streptococci isolates susceptible to clindamycin was higher, using an agent for prophylaxis to which one in 11 isolates is resistant is far from ideal.
The incidence of a history of penicillin allergy, specifically in an obstetric population, has been reported to be 12%.8 However, in the same study, only 30% of patients reporting such an allergy could describe their reaction. Furthermore, when assessed by skin testing, only 1020% of patients reporting a history of penicillin allergy are truly allergic to this antibiotic.17 The remainder of these patients (with negative skin tests) could take penicillin without sequelae. Introduction of skin testing for those women requiring intrapartum antibiotic prophylaxis who have a history of penicillin allergy would decrease the likelihood of using a drug to which the strain of group B streptococcus carried was resistant. However, the logistics involved in implementing skin testing in this group of women makes this option less attractive.
Short of skin testing, the use of cefazolin for intrapartum antibiotic prophylaxis might be a reasonable option in penicillin-allergic women without a history of anaphylaxis. All of the isolates we tested were susceptible to this first-generation cephalosporin. Although up to 8% of patients with true penicillin allergies have been reported to have hypersensitivity reactions to cephalosporins,18 some of these data are complicated by the fact that early cephalosporins were contaminated with trace amounts of penicillin.19 The authors of future recommendations regarding intrapartum antibiotic prophylaxis in penicillin-allergic women will need to carefully consider these issues.
| Footnotes |
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Received December 28, 2001. Received in revised form March 22, 2002. Accepted April 11, 2002.
| REFERENCES |
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