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Obstetrics & Gynecology 2002;100:540-544
© 2002 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Intrapartum Antibiotic Prophylaxis 2: Positive Predictive Value of Antenatal Group B Streptococci Cultures and Antibiotic Susceptibility of Clinical Isolates

Rodney K. Edwards, MD, MS, Penny Clark, PhD and Patrick Duff, MD

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
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: To estimate the probability of positive intrapartum group B streptococcus cultures among women previously identified as carriers of this organism, and to estimate the susceptibility of group B streptococci to six commonly used antibiotics.

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 15–35% 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.4–6 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 3–15% of isolates are resistant to clindamycin and 7–18% of isolates are resistant to erythromycin.8–11

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 35–37 weeks’ gestation, rather than earlier in pregnancy. The reliability of these 35–37 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 streptococci—prior 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
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
We performed a prospective cohort study evaluating the proportions of women with positive group B streptococci cultures at the time of labor. Women were eligible for the study if they were admitted to Shands Hospital at the University of Florida from February 26, 2000, to May 22, 2001, for spontaneous or induced labor, were at a gestational age of 36 weeks or more, and were culture-proven carriers of group B streptococci. Exclusion criteria included planned cesarean delivery, antibiotics taken within the preceding 7 days, multifetal gestation, or antepartum fetal death. Allergy to penicillins was not an exclusion criterion. The University of Florida Health Center Institutional Review Board approved the study.

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 35–37 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 18–24 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 {alpha} 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 {chi}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
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
During the study period, 2896 women delivered at our hospital. Of these women, 2304 delivered at 36 weeks’ gestation or more, and 428 women met the inclusion criteria for this study. A total of 390 women were actually enrolled. Of these women, 13 were excluded before processing the entry specimen because of failure to activate the transport media (seven), entry specimen sent inadvertently to the clinical laboratory (one), delivery before the entry specimen was obtained (one), or the subject having received antibiotics within the preceding week (four). With these exclusions, 377 women made up the cohort.

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 1Go. 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 1Go.


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Table 1. Demographic Data
 
Table 2Go displays the numbers of women in each group who had positive intrapartum group B streptococci culture results and the positive predictive values for each method of identification of group B streptococci carriers. In addition, we specifically evaluated the subset of group 1 whose cultures were obtained 42 days or less before delivery (n = 218).


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Table 2. Intrapartum Group B Streptococcal Culture Results
 
Susceptibility of group B streptococcus isolates (n = 239) to penicillin, ampicillin, cefazolin, and vancomycin was 100% (98, 100). Susceptibility to clindamycin was 91% (87, 94). All of the remaining isolates were resistant to this antibiotic. Susceptibility to erythromycin was 79% (73, 84). Eleven percent of isolates were resistant to erythromycin, and 10% of isolates showed intermediate susceptibility to this antibiotic.

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 cohort—two 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
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
To our knowledge, our cohort study is only the second one that has specifically evaluated the positive predictive value of late pregnancy genital tract cultures for group B streptococci. The study by Yancey et al13 found that 87% of women who had positive cultures within 6 weeks of delivery were still positive at the time of labor. In contrast, we found a positive predictive value of only 67% for such cultures. The implication of this result is that one-third of these women received antibiotics but were presumably at low risk of delivering an infant with early-onset group B streptococcal infection. Because our study included only women who were known to be colonized, we cannot evaluate how many women had undetected (and therefore untreated) colonization with group B streptococci at the time of labor. The negative predictive value in the study by Yancey et al was 96%.13

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.8–11 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 10–20% 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
 
This study was supported in part by a grant from the Children’s Miracle Network.

PII S0029-7844(02)02097-5

Received December 28, 2001. Received in revised form March 22, 2002. Accepted April 11, 2002.


    REFERENCES
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
1. Dillon HC, Gray E, Pass MA, Gray BM. Anorectal and vaginal carriage of group B streptococci during pregnancy. J Infect Dis 1982;145:794–9.[Medline]

2. Regan JA, Klebanoff MA, Nugent RP. The epidemiology of group B streptococcal colonization in pregnancy. Vaginal infections and prematurity study group. Obstet Gynecol 1991;77:604–10.[Abstract/Free Full Text]

3. McKenna DS, Iams JD. Group B streptococcal infections. Sem Perinatol 1998;22:267–76.

4. Yow MD, Mason EO, Leeds LJ, Thompson PK, Clark DJ, Gardner SE. Ampicillin prevents intrapartum transmission of group B streptococcus. JAMA 1979;241:1245–7.[Abstract]

5. Boyer KM, Gadzala CA, Kelly PD, Gotoff SP. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. III. Interruption of mother-to-infant transmission. J Infect Dis 1983;148:810–6.[Medline]

6. Boyer KM, Gotoff SP. Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis. N Engl J Med 1986;314: 1665–9.[Abstract]

7. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: A public health perspective. MMWR 1996;45:1–24.[Medline]

8. Pearlman MD, Pierson CL, Faix RG. Frequent resistance of clinical group B streptococci isolates to clindamycin and erythromycin. Obstet Gynecol 1998;92:258–61.[Abstract]

9. Fernandez M, Hickman ME, Baker CJ. Antimicrobial susceptibilities of group B streptococci isolated between 1992 and 1996 from patients with bacteremia or meningitis. Antimicrob Agents Chemother 1998;42:1517–9.[Abstract/Free Full Text]

10. Morales WJ, Dickey SS, Bornick P, Lim DV. Change in antibiotic resistance of group B streptococcus: Impact on intrapartum management. Am J Obstet Gynecol 1999; 181:310–4.[Medline]

11. Silverman NS, Morgan M, Nichols WS. Antibiotic resistance patterns of group B streptococcus in antenatal genital cultures. J Reprod Med 2000;45:979–82.[Medline]

12. Boyer KM, Gadzala CA, Kelly PD, Burd LI, Gotoff SP. Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. II. Predictive value of prenatal cultures. J Infect Dis 1983;148:802–9.[Medline]

13. Yancey MK, Schuchat A, Brown LK, Ventura VL, Markenson GR. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol 1996;88:811–5.[Abstract]

14. Gray BM, Pass MA, Dillon HC Jr. Laboratory and field evaluation of selective media for isolation of group B streptococci. J Clin Microbiol 1979;9:466–70.[Abstract/Free Full Text]

15. Lin FY, Philips JB 3rd, Azimi PH, Weisman LE, Clark P, Rhoads GG, et al. Level of maternal antibody required to protect neonates against early-onset disease caused by group B streptococcus type Ia: A multicenter, seroepidemiology study. J Infect Dis 2001;184:1022–8.[Medline]

16. Bauer AW, Kirby WMM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 1966;45:493–6.[Medline]

17. Salkind AR, Cuddy PG, Foxworth JW. Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. JAMA 2001;285: 2498–505.[Abstract/Free Full Text]

18. Petz LD. Immunologic cross-reactivity between penicillin and cephalosporins: A review. J Infect Dis 1978;137Suppl:S74–9.

19. Pedersen-Bjergaard J. Cephalothin in the treatment of penicillin sensitive patients. Act Allergol 1967;22: 299–306.




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