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Antibiotic treatment of parturient women colonized with group B streptococci
Antibiotic treatment of parturient women colonized with group B streptococci ROBERT
T.
WILLIAM L.
HALL,
M.D.
PH.D.*
BARNES,
KRISHNAN.
M.D.
DAVID
J.
HARRIS,
PHILIP
G.
RHODES,
JAMIL
FAYEZ,
GERALD
L.
M.D. M.D. M.D.
MILLER,
M.D.
Kansas Ci@, Missourz A prospective study was conducted among third-trimester parturient women with cervical or urethral colonization with group B streptococci to determine the injuence of antibiotic treatment on subsequent colonizations among their infants. Cultures were obtained from dm sulabs inoculated directly onto selective blood agar media containing neomycin and naladixic acid. Seventy-four women were found to be colonized among 1,098 cultured (7 per cent). A signa$cant reduction in colonization was noted among mothers treated with ampicillin within three weeks of completion of therapy. This difference was no longer apparent at delivery. There was likewise no daff erence in the colonization rate of infants in the treatment and no-treatment groups. The data suggest that additional measures must be undertaken to prevent maternal recolonization.
THE GROUP B STREPTOCOCCUS hasemergedas a significant pathogen in neonatal sepsis and meningitis in recent years.im6 Two distinct clinical forms of the disease have been described.4-7 An early form is characterized by rapid onset of respiratory distress, rate is sepsis, and shock. A very high mortality associated with this form of the disease. In nearly all reported cases, the source of colonization of the infant has been the birth canal of the pregnant mother.4* ‘-lo Serologic subtyping of the group B streptococci has been identical in infant and maternal vaginal cultures.‘, g, *O From the Kansas City General Hosp&al, Departments Obstetrics-Gynecology and Pathology, and the Children’s Mercy Hospital, Department of Pediatrics. Received
for publication
Revised
March
Accepted
March
December
of
4, 1974.
20, 1975. 20, 1975.
Reprint requests: Dr. Robert T. Hall, Children’s Mercy Hospital, 24th and Gillhorn Rd., KansaF City, Missouri 64108. *Present address: Veterans Administration Ho+tal, Kansas City, Missouri, and Department of Pathology, University of Kansas Medical Center, Kansas City, Kansas 66103.
Late-onset disease characteristically occurs between three and six weeks and has been termed a “meningitis form.“4* ii The vast majority of reported cases have been associated with meningitis; however, mortality rates have been considerably lower than in the early-onset diseases. 6* ’ The source of colonization of these infants has not been determined. Franciosi and associates4 describe the early-onset disease as being associated primarily with B-I subtypes, although Baker and colleagues’ have found Type III to be responsible for 75 per cent of early-onset disease in their experience. Late-onset disease has been primarily associated with Type III strains.4a 7-g There are no convincing data which indicate that colonization rates of pregnant women have increased in recent years. Hood and co-workers’ reported a colonization rate of 5 per cent from New Orleans, in 1961, which is similar to the incidence in the parturient population from the Denver area reported in 1973.” Notable exceptions are the 23 per cent vaginal colonization rate reported by Baker and Barrett” using a selective antibiotic broth media and a 29 per cent colonization rate of third-trimester women noted in Palm Beach County, Florida, where multiple cultures
Antibiotic treatment of group B streptococci
Volume Number
124 6
Table
I. Effect of ampicillin
treatment
on maternal Treatment
Positive
Mothers, follow-up Mothers, Infants, N.S.
3 wk.
at delivery at delivery
= Not
4 8 6
and infant
colonization
(2 7)
with group
No treatment
Negative 23 15 (4 unknown) 21
B streptococci
(34) Negative
Positive 14 13 10
631
Sign$cance
20 16 (5 unknown) 24
x2 = 3.84: N.S. N.S
p = 0.05
significant.
were obtained.” The high colonization rates in the latter two studies may be a reflection of different methods used for isolation and identification of group B streptococci. Based upon an attack rate of two to three per 1,000 parturient women, whose infants had a very high mortality rate, Franciosi and associates have suggested the antepartum treatment of pregnant women harboring vaginal group B streptococci in an attempt to eradicate the organism before delivery and prevent colonization of infants.4 Successful eradication was demonstrated in 13 of 14 pregnant women treated with penicillin in an initial preliminary study. This approach is supported by McCracken” who feels that pregnant women with proved colonization should be treated routinely. This point of view is not shared by Baker and Barrett” who feel that the high incidence of colonization among parturients with a relatively low attack rate makes antibiotic prophylaxis of gravid female carriers impractical. Eickhoff and associates13 have expressed similar disagreement with the routine treatment of pregnant women because of lack of data which support the successful eradication of the streptococcal flora from the birth canal and subsequent colonization of their infants and the potential risk of adverse reactions to antibiotic treatment. In an attempt to determine the efficacy of antibiotic treatment of group B streptococcal colonization of parturient women and their infants, a prospective study was undertaken at the Kansas City General Hospital.
Patients and methods Maternal cervical and urethral cultures were obtained in the third trimester of pregnancy from sterile dry swabs inoculated directly onto selective blood agar media containing naladixic acid (15 mcg. per milliliter) and neomycin (30 mcg. per milliliter). Identification of group B streptococci was made by colony morphology, a typical zone of hemolysis, resistance to bacitracin, and the ability of the organism to hydrolyze hippurate.14 Subtyping was performed with the slide agglutination method of Cropp and colleagues.‘5 Antisera were sup-
plied by the Streptococcal Disease Section of the Center for Disease Control in Fort Collins, Colorado. Test strains were obtained from Dr. Rebecca Lancefield. Third-trimester pregnant women were divided into two groups by random assignment dictated by the last number of the chart. Treatment mothers received oral ampicillin, 500 mg. four times daily for seven days. The control group received no medication. Repeat cultures were obtained of the cervix and urethra at the end of antibiotic therapy in the treatment group and at the same time in the control group. No attempt was made to determine the compliance of the treatment group to ensure adherence to the antibiotic regimen. Attempts were made to obtain urethral cultures of the male sexual partner; however, because of a lack of identification and compliance of these partners, this was not possible, and this phase of the study was abandoned. Repeat cervical and urethral cultures were obtained in
both
groups
at the
time
of
delivery.
Immediately
following admission of the infant to the nursery, cultures were obtained of the infants’ nares, oropharynx, umbilicus, ear canal, and rectum. These culture swabs were processed in the same way as maternal cultures. Antibiotic therapy of infants was dictated by the clinical course and was not controlled by the results of infant culture data. Blood, urine, and cerebrospinal fluid cultures were obtained prior to antibiotic therapy when utilized. Data collection sheets were prepared which gave detailed pertinent maJerna1 and infant clinical data.
Results In the third trimester of pregnancy, 1,098 women were cultured and 74 patients (7 per cent) with cervical and/or urethral colonization were identified. Sixteen patients had positive urethral cultures alone. Five had positive cervical cultures alone, and the remainder were culture-positive in both sites. Sixty-one patients returned within three weeks of completing the treatment or no-treatment regimen and constitute the study population. Culture results are shown in Table I. The initial follow-up cultures
632
Hall et al.
Table
II. Infant
March Am. J. Obstet.
colonization
with Group Treatment
Maternal colonization
8 Positive 15 Negative 4 Unknown 5
Positzve
5 1 0
6
Negative
B streptococci
in relation
to maternal
(27)
at delivery
No treatment Maternal coloniratioz
Not done
Positive
3 13
0 1
13 Positive 16 Negative
-3
1
2
19
colonization
2
revealed a significant difference between the treatment and no-treatment groups. Of the 27 treated with ampicillin, cultures of four patients remained positive, whereas 14 of the 34 patients who received no treatment had positive cultures. However, at the time of delivery, this difference was no longer apparent. There were eight positive, fifteen negative, and four unknown cultures in the treatment group. There were 13 positive, 16 negative, and five unknown cultures in the no-treatment group. There was likewise no difference in colonization of infants in the two groups at the time of delivery. Infant culture data suggest that multiple sites should be obtained since the umbilicus was the only positive culture in two infants and the nose or throat alone in two infants. Multiple sites were colonized in the remaining 12 patients. Table II depicts the group B streptococci flora of infants in relation to their mothers’ cultures. In the treatment group , five of the six culture-positive infants had mothers whose cultures were positive. In the no treatment group, six of the 11 culture-positive infants had culture-positive mothers. The five infants born to culture-negative women probably reflect an inadequate identification technique of positive maternal colonization. It. is interesting to note that seven infants born to mothers who initially had positive cultures, but whose cultures were unknown at the time of delivery, had e cultures. This could readily be explained by chance alone; however, negative cultures were also obtained from 11 of the 13 mothers who were initially known to be colonized with group B streptococci but who failed to have follow-up cultures during pregnancy and were deleted from the study group. Over all, the entire group of 18 infants born to mothers who were initially colonized in the third trimester of pregnancy but whose colonization status at the time of delivery was unknown had negative cultures of multiple sites at birth. We have no explanation for this phenomenon. Serologic subtypes of group B streptococci are
Table
III.
,‘Vot done
7 12
0 0 1 (Stillborn) 1
0
4
la
23
Subtypes
Subtype Ia
Ib II III Unknown
of group Mothers
[34)
Negative
6 4
U&own
34
15, 1976 Gynecol.
B streptococci (61)
6 I3 16 3 Mixed 20 9 (I*) 64
Infants
(16)
3 36 2 Mixed 4 2 (I*) 18
*Could not be typed.
shown in Table III. There was 100 per cent correlation between maternal and infant subtypes. Type B-Ic reactions were agglutinated by Ia antisera and reported as Type Ia. Approximately 30 per cent of the strains which could be typed were Type III which is consistent with the experience of Franciosi and associates,4 Baker and Barrett,” and Wilkinson and colleagues.g Three maternal and two infant cultures agglutinated both Ib and II antisera and probably represent mixed flora rather than true cross-reactions. No cross-reactions occurred with test strains. There were very few strains which could not be typed. There were too few infants with clinical disease to correlate the occurrence of illness with the serotype. Table IV depicts clinical information regarding the perinatal period. The mean birth weight and gestational age were consistent with those of term infants, and only two were born prematurely. There was a paucity of perinatal complications. Three infants in the no-treatment group had premature rupture of the membranes more than one hour prior to the onset of labor; however, none had prolonged rupture of membranes. None of the sixteen infants had abnormally low Apgar scores. One infant from each group developed radiographic and clinical evidence of pneumonia. The serotypes of streptococci in these two infants were Ia and Ib, respectively. Both were treated with systemic penicillin and gentamicin and both survived. Blood cultures were obtained from 14 infants and all were negative. Seven infants in addition to the two with pneumonia received antibiotics primarily
Volume Number
Table
Antibiotic treatment of group 6 streptococci
124 6
IV. Clinical
data associated
with group
B streptococcal
I Birth weight Gestational aee Duration of &pture Premature rupture Perinatal asphyxia >5 Polymorphonuclear Pneumonia Antibiotic therapy Sepsis or meningitis
of membranes of membranes leukocytes
(hr.)
in gastric
aspirate
because of the knowledge of the maternal colonization and concern on the part of the house officer of the potential
danger
of
sepsis.
No
statement
can
be made
regarding the routine treatment of culture-positive infants from the data in this study. Maternal complications were limited to one case of postpartum endometritis for which antibiotics were administered and two antepartum urinary tract infections from which group B streptococci were isolated from mixed flora of “clean-voided” specimens. The data from the present study indicate that antibiotic therapy with oral ampicillin in the third trimester of pregnancy cannot be utilized by the methods employed to decrease maternal colonization of the genitourinary tract or the infant colonization rate at the time of birth. However, the data do indicate that a significant reduction in cervical and urethral colonization can be obtained within three weeks of completion of therapy. This suggests that recolonization occurs, probably through venereal transmission or through re-emergence of an undetectably low population of streptococci following antibiotic treatment. These data should not be construed as evidence that antibiotic treatment has no place in the management of the pregnant woman. Rather it points out the difficulties encountered with such a regimen. It would appear that antibiotic therapy must be continued until the time of delivery and that further study of the male sexual partner is essential. Unfortunately, the latter problem was not possible in this study. It is encouraging to note that 11 of the 16 colonized infants were delivered of mothers who were shown to be culture positive. The five infants delivered of mothers with negative cultures probably represent a failure of the maternal culture technique. Since completion of this study, there are published data available which demonstrate that utilization of broth media and repeated cultures will significantly improve the culture yield and reduce false negative results to a minimum.lO~ I2
633
colonization Treatment
(6)
3248 Cm. ? 328 (SD.) 39.1 wk. + 1.3 (SD.) \ I o-4 None None 315 1 3 None
I
No treatment
(IO)
3014 Cm. ? 543 (SD.) 39.1 wk. + 2.0 (SD.) o-15 ~ ’ 3 None 216 1 6 None
We cannot, on the basis of our data, recommend routine culturing of mothers during pregnancy as a standard clinical procedure. Additional data are clearly needed to determine whether successful eradication can be obtained by the methods suggested above. Benzathine penicillin was used successfully to eradicate streptococci from the vaginal flora of 13 women studied by Franciosi and associates.4 There are no data on follow-up cultures from that population; however, this would seem to be a logical approach in a continued investigation. Ampicillin was chosen for the present study because of data from Bergquist and co-workers which suggested that a significant number of strains of streptococci were partially resistant to penicillin. All of the strains encountered in the present study were sensitive to penicillin. There are no published reports of penicillin-resistant group B streptococci in the United States. Although group B streptococcal colonization of infants was not found to be influenced by maternal antibiotic treatment with ampicillin, temporary eradication of the flora in the birth canal was demonstrated. Streptococcal sepsis continues to grow as a significant cause of neonatal death and morbidity. Data from our institution and those of others have not shown that antibiotic treatment of the infant at the onset of symptoms is successful. Routine prophylactic treatment of colonized infants is unlikely to be satisfactory because of the frequent rapid onset of the disease in the first 48 hours of life prior to the availability of culture results. Therefore, continued efforts at maternal identification of group B streptococcal carriers and an additional trial of antibiotic therapy in controlled conditions are indicated.
The authors would like to express their appreciation to the house staff and nursing personnel of the Kansas City General Hospital for their participation in the studv.
634
March
Hall et al
Am. .I. Obstet.
REFERENCES
9.
1. Hoof,
2.
3.
4.
5.
6.
7.
8.
M., Janney, A., and Dameron, G.: Beta hemolytic streptococcus group B associated with problems of the perinatal period, AM. J. OBSTET. GYNECOL. 82: 809, 1961, Eickhoff, T. C., Klein, J. O., Daly, A. K., Ingall, D.. and Finland, M.: Neonatal sepsis and other infections due to group B beta-hemolytic streptococci, N. Engl. J. Med. 271: 1221, 1964. Bergquist, G., Hurvell, B., Molmborg, A. S., Rylander, M., and Tunnell, R.: Neonatal infections caused by group B streptococci, Stand. J. Infect. Dis. 3: 157, 1971, Franciosi, R. A., Knostman, J. D., and Zimmerman, R. A.: Group B streptococcal neonatal and infant infections, J, Pediatr. 82: 707, 1973. Hey, D. J., Hall, R. T., Burry, V. F., and Thurn, A. N.: Neonatal infections caused by group B streptococci, AM. J. OBSTET. GYNECOL. 116: 43, 1973. Barton, L. L., Feigen, R. D., and Lins, R.: Group B beta hemolytic streptococcal meningitis in infants, J. Pediatr. 82: 719, 1973. Baker, C. I., Barrett, F. F., Gordon, R. C., and You, M. D.: Suppurative meningitis due to streptococci of Lancefield group B: A study of 33 infants, J. Pediatr. 82: 724, 1973. Bergquist, G., Hurvell, B., Thal, E., and Vaclavinkova, V.: Neonatal infections caused by group B streptococci: Relation between the occurrence in vaginal flora of term pregnant women and infection in the newborn infant, Stand. J. Infect. Dis. 3: 209, 1973.
10.
11. 12.
13.
14.
15.
15, 1976 Gynecol.
Wilkinson, H. W.. Facklam, R. R., and Wortham, E. C.: Distribution by serological type of group B streptococci isolated from a variety of clinical material over a five-year period (with special reference to neonatal sepsis and meningitis), Infect. Immun. 8: 228, 1973. Baker, C. J., and Barrett, F. F.: Transmission of group B streptococci among parturient women and their neonates, J. Pediatr. 83: 919, 1973. McCracken, G. A.: Group B streptococci: The new challenge in neonatal infections, J. Pediatr. 82: 703, 1973. Aher. R. C., Facklam. R., Wilkinson, H.. and Bennett, J. V.: Nosocomial group B streptococcal infection in neonates, Thirteenth Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, D. C., September 19, 1973. Eickhoff, 7‘. C., Fleirt, J. O., Mortimer. E. A., and Wehrle. P. F.: The issue of prophylaxis of neonatal group B streptococcal infections, J. Pediatr. 83: 1097, 1973. Ayers, S. H., and Rupp, P.: Differentiation of hemolytic streptococci from human and bovine sources by hydrolysis of sodium hippurate,J. Infect. Dis. 30: 388, 1922. Cropp, C. B., Zimmerman, R. A., Jelinkova, J., Auernheimer, A. H., Bolin, R. A., and Wyrick, B. D.: Serotyping of Group B streptococci by slide agglutination, fluorescence, microscopy. and microimmunodiffusion, J. Lab. Clin. Med. 84: 594, 1974.
T.
WILLIAM L.
HALL,
M.D.
PH.D.*
BARNES,
KRISHNAN.
M.D.
DAVID
J.
HARRIS,
PHILIP
G.
RHODES,
JAMIL
FAYEZ,
GERALD
L.
M.D. M.D. M.D.
MILLER,
M.D.
Kansas Ci@, Missourz A prospective study was conducted among third-trimester parturient women with cervical or urethral colonization with group B streptococci to determine the injuence of antibiotic treatment on subsequent colonizations among their infants. Cultures were obtained from dm sulabs inoculated directly onto selective blood agar media containing neomycin and naladixic acid. Seventy-four women were found to be colonized among 1,098 cultured (7 per cent). A signa$cant reduction in colonization was noted among mothers treated with ampicillin within three weeks of completion of therapy. This difference was no longer apparent at delivery. There was likewise no daff erence in the colonization rate of infants in the treatment and no-treatment groups. The data suggest that additional measures must be undertaken to prevent maternal recolonization.
THE GROUP B STREPTOCOCCUS hasemergedas a significant pathogen in neonatal sepsis and meningitis in recent years.im6 Two distinct clinical forms of the disease have been described.4-7 An early form is characterized by rapid onset of respiratory distress, rate is sepsis, and shock. A very high mortality associated with this form of the disease. In nearly all reported cases, the source of colonization of the infant has been the birth canal of the pregnant mother.4* ‘-lo Serologic subtyping of the group B streptococci has been identical in infant and maternal vaginal cultures.‘, g, *O From the Kansas City General Hosp&al, Departments Obstetrics-Gynecology and Pathology, and the Children’s Mercy Hospital, Department of Pediatrics. Received
for publication
Revised
March
Accepted
March
December
of
4, 1974.
20, 1975. 20, 1975.
Reprint requests: Dr. Robert T. Hall, Children’s Mercy Hospital, 24th and Gillhorn Rd., KansaF City, Missouri 64108. *Present address: Veterans Administration Ho+tal, Kansas City, Missouri, and Department of Pathology, University of Kansas Medical Center, Kansas City, Kansas 66103.
Late-onset disease characteristically occurs between three and six weeks and has been termed a “meningitis form.“4* ii The vast majority of reported cases have been associated with meningitis; however, mortality rates have been considerably lower than in the early-onset diseases. 6* ’ The source of colonization of these infants has not been determined. Franciosi and associates4 describe the early-onset disease as being associated primarily with B-I subtypes, although Baker and colleagues’ have found Type III to be responsible for 75 per cent of early-onset disease in their experience. Late-onset disease has been primarily associated with Type III strains.4a 7-g There are no convincing data which indicate that colonization rates of pregnant women have increased in recent years. Hood and co-workers’ reported a colonization rate of 5 per cent from New Orleans, in 1961, which is similar to the incidence in the parturient population from the Denver area reported in 1973.” Notable exceptions are the 23 per cent vaginal colonization rate reported by Baker and Barrett” using a selective antibiotic broth media and a 29 per cent colonization rate of third-trimester women noted in Palm Beach County, Florida, where multiple cultures
Antibiotic treatment of group B streptococci
Volume Number
124 6
Table
I. Effect of ampicillin
treatment
on maternal Treatment
Positive
Mothers, follow-up Mothers, Infants, N.S.
3 wk.
at delivery at delivery
= Not
4 8 6
and infant
colonization
(2 7)
with group
No treatment
Negative 23 15 (4 unknown) 21
B streptococci
(34) Negative
Positive 14 13 10
631
Sign$cance
20 16 (5 unknown) 24
x2 = 3.84: N.S. N.S
p = 0.05
significant.
were obtained.” The high colonization rates in the latter two studies may be a reflection of different methods used for isolation and identification of group B streptococci. Based upon an attack rate of two to three per 1,000 parturient women, whose infants had a very high mortality rate, Franciosi and associates have suggested the antepartum treatment of pregnant women harboring vaginal group B streptococci in an attempt to eradicate the organism before delivery and prevent colonization of infants.4 Successful eradication was demonstrated in 13 of 14 pregnant women treated with penicillin in an initial preliminary study. This approach is supported by McCracken” who feels that pregnant women with proved colonization should be treated routinely. This point of view is not shared by Baker and Barrett” who feel that the high incidence of colonization among parturients with a relatively low attack rate makes antibiotic prophylaxis of gravid female carriers impractical. Eickhoff and associates13 have expressed similar disagreement with the routine treatment of pregnant women because of lack of data which support the successful eradication of the streptococcal flora from the birth canal and subsequent colonization of their infants and the potential risk of adverse reactions to antibiotic treatment. In an attempt to determine the efficacy of antibiotic treatment of group B streptococcal colonization of parturient women and their infants, a prospective study was undertaken at the Kansas City General Hospital.
Patients and methods Maternal cervical and urethral cultures were obtained in the third trimester of pregnancy from sterile dry swabs inoculated directly onto selective blood agar media containing naladixic acid (15 mcg. per milliliter) and neomycin (30 mcg. per milliliter). Identification of group B streptococci was made by colony morphology, a typical zone of hemolysis, resistance to bacitracin, and the ability of the organism to hydrolyze hippurate.14 Subtyping was performed with the slide agglutination method of Cropp and colleagues.‘5 Antisera were sup-
plied by the Streptococcal Disease Section of the Center for Disease Control in Fort Collins, Colorado. Test strains were obtained from Dr. Rebecca Lancefield. Third-trimester pregnant women were divided into two groups by random assignment dictated by the last number of the chart. Treatment mothers received oral ampicillin, 500 mg. four times daily for seven days. The control group received no medication. Repeat cultures were obtained of the cervix and urethra at the end of antibiotic therapy in the treatment group and at the same time in the control group. No attempt was made to determine the compliance of the treatment group to ensure adherence to the antibiotic regimen. Attempts were made to obtain urethral cultures of the male sexual partner; however, because of a lack of identification and compliance of these partners, this was not possible, and this phase of the study was abandoned. Repeat cervical and urethral cultures were obtained in
both
groups
at the
time
of
delivery.
Immediately
following admission of the infant to the nursery, cultures were obtained of the infants’ nares, oropharynx, umbilicus, ear canal, and rectum. These culture swabs were processed in the same way as maternal cultures. Antibiotic therapy of infants was dictated by the clinical course and was not controlled by the results of infant culture data. Blood, urine, and cerebrospinal fluid cultures were obtained prior to antibiotic therapy when utilized. Data collection sheets were prepared which gave detailed pertinent maJerna1 and infant clinical data.
Results In the third trimester of pregnancy, 1,098 women were cultured and 74 patients (7 per cent) with cervical and/or urethral colonization were identified. Sixteen patients had positive urethral cultures alone. Five had positive cervical cultures alone, and the remainder were culture-positive in both sites. Sixty-one patients returned within three weeks of completing the treatment or no-treatment regimen and constitute the study population. Culture results are shown in Table I. The initial follow-up cultures
632
Hall et al.
Table
II. Infant
March Am. J. Obstet.
colonization
with Group Treatment
Maternal colonization
8 Positive 15 Negative 4 Unknown 5
Positzve
5 1 0
6
Negative
B streptococci
in relation
to maternal
(27)
at delivery
No treatment Maternal coloniratioz
Not done
Positive
3 13
0 1
13 Positive 16 Negative
-3
1
2
19
colonization
2
revealed a significant difference between the treatment and no-treatment groups. Of the 27 treated with ampicillin, cultures of four patients remained positive, whereas 14 of the 34 patients who received no treatment had positive cultures. However, at the time of delivery, this difference was no longer apparent. There were eight positive, fifteen negative, and four unknown cultures in the treatment group. There were 13 positive, 16 negative, and five unknown cultures in the no-treatment group. There was likewise no difference in colonization of infants in the two groups at the time of delivery. Infant culture data suggest that multiple sites should be obtained since the umbilicus was the only positive culture in two infants and the nose or throat alone in two infants. Multiple sites were colonized in the remaining 12 patients. Table II depicts the group B streptococci flora of infants in relation to their mothers’ cultures. In the treatment group , five of the six culture-positive infants had mothers whose cultures were positive. In the no treatment group, six of the 11 culture-positive infants had culture-positive mothers. The five infants born to culture-negative women probably reflect an inadequate identification technique of positive maternal colonization. It. is interesting to note that seven infants born to mothers who initially had positive cultures, but whose cultures were unknown at the time of delivery, had e cultures. This could readily be explained by chance alone; however, negative cultures were also obtained from 11 of the 13 mothers who were initially known to be colonized with group B streptococci but who failed to have follow-up cultures during pregnancy and were deleted from the study group. Over all, the entire group of 18 infants born to mothers who were initially colonized in the third trimester of pregnancy but whose colonization status at the time of delivery was unknown had negative cultures of multiple sites at birth. We have no explanation for this phenomenon. Serologic subtypes of group B streptococci are
Table
III.
,‘Vot done
7 12
0 0 1 (Stillborn) 1
0
4
la
23
Subtypes
Subtype Ia
Ib II III Unknown
of group Mothers
[34)
Negative
6 4
U&own
34
15, 1976 Gynecol.
B streptococci (61)
6 I3 16 3 Mixed 20 9 (I*) 64
Infants
(16)
3 36 2 Mixed 4 2 (I*) 18
*Could not be typed.
shown in Table III. There was 100 per cent correlation between maternal and infant subtypes. Type B-Ic reactions were agglutinated by Ia antisera and reported as Type Ia. Approximately 30 per cent of the strains which could be typed were Type III which is consistent with the experience of Franciosi and associates,4 Baker and Barrett,” and Wilkinson and colleagues.g Three maternal and two infant cultures agglutinated both Ib and II antisera and probably represent mixed flora rather than true cross-reactions. No cross-reactions occurred with test strains. There were very few strains which could not be typed. There were too few infants with clinical disease to correlate the occurrence of illness with the serotype. Table IV depicts clinical information regarding the perinatal period. The mean birth weight and gestational age were consistent with those of term infants, and only two were born prematurely. There was a paucity of perinatal complications. Three infants in the no-treatment group had premature rupture of the membranes more than one hour prior to the onset of labor; however, none had prolonged rupture of membranes. None of the sixteen infants had abnormally low Apgar scores. One infant from each group developed radiographic and clinical evidence of pneumonia. The serotypes of streptococci in these two infants were Ia and Ib, respectively. Both were treated with systemic penicillin and gentamicin and both survived. Blood cultures were obtained from 14 infants and all were negative. Seven infants in addition to the two with pneumonia received antibiotics primarily
Volume Number
Table
Antibiotic treatment of group 6 streptococci
124 6
IV. Clinical
data associated
with group
B streptococcal
I Birth weight Gestational aee Duration of &pture Premature rupture Perinatal asphyxia >5 Polymorphonuclear Pneumonia Antibiotic therapy Sepsis or meningitis
of membranes of membranes leukocytes
(hr.)
in gastric
aspirate
because of the knowledge of the maternal colonization and concern on the part of the house officer of the potential
danger
of
sepsis.
No
statement
can
be made
regarding the routine treatment of culture-positive infants from the data in this study. Maternal complications were limited to one case of postpartum endometritis for which antibiotics were administered and two antepartum urinary tract infections from which group B streptococci were isolated from mixed flora of “clean-voided” specimens. The data from the present study indicate that antibiotic therapy with oral ampicillin in the third trimester of pregnancy cannot be utilized by the methods employed to decrease maternal colonization of the genitourinary tract or the infant colonization rate at the time of birth. However, the data do indicate that a significant reduction in cervical and urethral colonization can be obtained within three weeks of completion of therapy. This suggests that recolonization occurs, probably through venereal transmission or through re-emergence of an undetectably low population of streptococci following antibiotic treatment. These data should not be construed as evidence that antibiotic treatment has no place in the management of the pregnant woman. Rather it points out the difficulties encountered with such a regimen. It would appear that antibiotic therapy must be continued until the time of delivery and that further study of the male sexual partner is essential. Unfortunately, the latter problem was not possible in this study. It is encouraging to note that 11 of the 16 colonized infants were delivered of mothers who were shown to be culture positive. The five infants delivered of mothers with negative cultures probably represent a failure of the maternal culture technique. Since completion of this study, there are published data available which demonstrate that utilization of broth media and repeated cultures will significantly improve the culture yield and reduce false negative results to a minimum.lO~ I2
633
colonization Treatment
(6)
3248 Cm. ? 328 (SD.) 39.1 wk. + 1.3 (SD.) \ I o-4 None None 315 1 3 None
I
No treatment
(IO)
3014 Cm. ? 543 (SD.) 39.1 wk. + 2.0 (SD.) o-15 ~ ’ 3 None 216 1 6 None
We cannot, on the basis of our data, recommend routine culturing of mothers during pregnancy as a standard clinical procedure. Additional data are clearly needed to determine whether successful eradication can be obtained by the methods suggested above. Benzathine penicillin was used successfully to eradicate streptococci from the vaginal flora of 13 women studied by Franciosi and associates.4 There are no data on follow-up cultures from that population; however, this would seem to be a logical approach in a continued investigation. Ampicillin was chosen for the present study because of data from Bergquist and co-workers which suggested that a significant number of strains of streptococci were partially resistant to penicillin. All of the strains encountered in the present study were sensitive to penicillin. There are no published reports of penicillin-resistant group B streptococci in the United States. Although group B streptococcal colonization of infants was not found to be influenced by maternal antibiotic treatment with ampicillin, temporary eradication of the flora in the birth canal was demonstrated. Streptococcal sepsis continues to grow as a significant cause of neonatal death and morbidity. Data from our institution and those of others have not shown that antibiotic treatment of the infant at the onset of symptoms is successful. Routine prophylactic treatment of colonized infants is unlikely to be satisfactory because of the frequent rapid onset of the disease in the first 48 hours of life prior to the availability of culture results. Therefore, continued efforts at maternal identification of group B streptococcal carriers and an additional trial of antibiotic therapy in controlled conditions are indicated.
The authors would like to express their appreciation to the house staff and nursing personnel of the Kansas City General Hospital for their participation in the studv.
634
March
Hall et al
Am. .I. Obstet.
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