Early neonatal streptococcal infection
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《美国医学杂志》
1 Department of Neonatology, National University Hospital, Singapore,2 Department of Pediatrics, National University of Singapore, Singapore,
Abstract
Objective. To determine the incidence of early onset Group B Streptococcal (GBS) infection in infants born over a two year period and to determine the outcome of sepsis evaluation in infants born to mothers with GBS colonization. Methods. The charts of infants born to mothers with GBS colonization were reviewed for details of sepsis evaluation and management. The microbiology records were used to identify proven cases of GBS septicemia and meningitis in neonates born during the study period. Results. Out of a total of 4636 live births in 2 years, there was one infant with culture-proven GBS septicemia, an incidence of 0.2 per 1000 live births. During the study period 83 infants were born to mothers who were known to have GBS carriage at the time of delivery. 73 out of these 83 infants (88%) had sepsis evaluation and received empirical parenteral penicillin for at least 5 days. There were no cases of blood culture-proven GBS sepsis among these 83 infants. However, there were 2 cases of probable sepsis giving an attack rate of 2.4%. All the three infants with definite or probable sepsis were preterm; there were no deaths among these affected infants. Conclusion. The overall incidence of early onset GBS sepsis was found to be low when compared to previous reported studies. The strategy of sepsis evaluation and management was found to be effective in preventing death and definite GBS septicemia in infants born to GBS colonized mothers.
Keywords: Group B Streptococcus; Sepsis; Newborn
Group B Streptococcus is the commonest organism causing early onset bacterial sepsis in the newborn in many parts of the world, especially the developed countries. The incidence of GBS infections (per 1000 live births), however, has shown variation between different countries such as India (0.17), Finland (0.76), Saudi Arabia (0.2-1.2), USA (1.4) and New Mexico (1.5) and at different time periods within the same country.[1],[2],[3],[4],[5] Hospital strategies to reduce early onset GBS sepsis in neonates should take into account the current incidence, morbidity and mortality in addition to the financial and emotional burden involved in its prevention and management. In our institution, at the time of this study, the protocol for the management of infants born to mothers with genital carriage of GBS included in-patient observation of these infants along with parenteral administration of penicillin for at least 5 days, irrespective of whether they were symptomatic at birth or not. As a result many asymptomatic term neonates had to stay in the hospital for extended periods causing parental anxiety besides increasing the hospital costs. To determine whether such a cautious approach was needed in the management of these infants at risk, knowledge on the current burden of GBS sepsis and the outcome of postnatal management of these infants was necessary. The present study was, therefore, undertaken to determine the incidence of early onset GBS sepsis in infants born at our institution and to determine the outcome of sepsis evaluation in infants born to mothers with GBS colonization during the same period.
Materials and Methods
This was a retrospective study conducted on neonates born in National University Hospital, Singapore between January 1999 and December 2000. During the study period, infants born to mother with genital carriage of GBS had sepsis evaluation at birth that included full blood count, C-reactive protein and blood culture. Infants received parenteral penicillin for at least 5 days irrespective of whether they were symptomatic or not. The charts of infants born to mothers who were detected to have GBS colonization during pregnancy were reviewed for details of sepsis evaluation, management and outcome. In particular, the type and doses of intrapartum antibiotics used, condition of the infant at birth, presence or absence of any clinical symptoms, results of full blood count, C-reactive protein and blood culture, and the postnatal management of these infants were reviewed.
At the time of the study, routine antenatal screening of pregnant women for genital carriage of GBS was not practiced in our institution. In order to identify those infants with GBS sepsis, whose mothers were not screened during pregnancy for GBS colonization, the microbiology records of the hospital during the same period were reviewed for any blood culture and/or CSF culture proven cases of GBS sepsis. These records had documented all the culture proven cases of GBS sepsis that occurred in the hospital during the study period.
Definition of early onset GBS sepsis : Early onset sepsis was defined as GBS sepsis presenting within the first 7 days of life. Cases of GBS sepsis were classified either as definite or probable based on the clinical symptoms and the results of laboratory investigations and culture results. Definite GBS sepsis was diagnosed when there was isolation of the organism either from the blood or CSF in a symptomatic neonate. The infection was categorized as probable when there was isolation of GBS from surface swabs in a symptomatic infant with laboratory evidence of infection (white cell count <4000/cmm or thrombocytopenia <150,000/cmm or raised C-reactive protein >1mg/dl) or radiological evidence of pneumonia.
Results
GBS colonization in mothers: During the period there were a total of 4636 live births among 4553 pregnant women. Out of these, 81 mothers (1.8%) were detected to have GBS colonization during pregnancy. The usual indications to send a vaginal swab for bacterial culture in these mothers were vaginal discharge, preterm labor, premature rupture of membranes and suspected chorioamnionitis.
Intrapartum antibiotics: Fifty five of 81 mothers (68%) with GBS colonization received at least one dose of an antibiotic during labor. Intravenous ampicillin was the commonest antibiotic used (48 out of 55) with erythromycin (3/55), ceftriaxone (2/55) or amoxicillin (2/55) in the remaining mothers. However, when intravenous ampicillin was used the dose was lower than that recommended by the American Academy of Pediatrics for the prevention of GBS sepsis in newborn.[11]
Postnatal management of infants: All the 83 infants born (including two pairs of twins) to 81 mothers with GBS colonization were observed in the hospital for signs and symptoms of sepsis. Sixteen infants (19%) were preterm (gestational age less than 37 weeks). Seventy three of these 83 infants (88%) had sepsis evaluation (full blood counts, C-reactive protein and blood culture) and received empirical parenteral penicillin for at least 5 days. Ten infants (12%) were not evaluated for sepsis at birth because the positive result of the mother's vaginal swab sent during labor was available only after the second postnatal day. All these 10 infants remained well with no signs or symptoms of sepsis. Among the cohort of 83 infants 2 preterm infants (2.4%) were diagnosed to have probable GBS sepsis and received intravenous penicillin for 10 days.
Incidence of early onset GBS sepsis
During the period of the study there was one infant who was born in our institution who had blood culture proven GBS sepsis presenting on the first day of life. This infant's mother was not tested antenatally for GBS carriage and hence the mother had not received any intrapartum antibiotics. This was the only case of definite early onset GBS sepsis (blood culture proven) among 4636 live births during the study period, giving an incidence of 0.2 per 1000 live births. If the two cases of probable GBS sepsis (blood culture negative) mentioned previously were also included, the incidence would be 0.6 per 1000 live births. All the three infants were born preterm. The clinical profiles of these three infants are shown in the table1.
Discussion
Group B Streptococcus is an important pathogen responsible for early onset bacterial sepsis in the newborn. The incidence of early onset GBS infection, however, varies in different parts of the world from 0.17 to 1.5 per 1000 live births. A low incidence has been reported from many Asian countries. The reasons for the low incidence in the Asian population are unclear but may be partly due to low rates of colonization and high prevalence of protective antibodies in the mother.[1] In the present study, the incidence of culture proven early onset GBS infection was 0.2 per 1000 live births, which is similar to the incidence in other Asian populations.
The incidence of GBS colonization in mothers has been reported to be 14.1% in a previous study in our institution,[7] which is within the often-quoted range of 5% -25% in different parts of the world. Assuming an attack rate of 1-2% invasive GBS disease in infants born to colonized mothers, an incidence of at least 1.4 per 1000 GBS sepsis is expected to occur in our institution in the absence of routine screening and preventive measures. The lower incidence of invasive GBS disease in newborns, therefore, may be due to other reasons.
First, there may be a difference in the incidence of colonization rates of invasive and non-invasive GBS strains. Many neonates who are colonized with the non-invasive strains may not become ill or septic. However, identifying the invasive strains of GBS before delivery may be difficult, as there are no reliable laboratory tests that differentiate invasive from non-invasive strains. Recently, Berner and colleagues[8] reported different cytokine expression in-vitro in cord blood mono-nuclear cells after stimulation with sepsis or colonizing strains of GBS. If further studies confirm this, it might become possible to screen GBS isolates from maternal swabs for their pathogenic properties.
The second reason for the lower incidence of GBS infection in the present study may be the intrapartum antibiotics administered to mothers with other risk factors for sepsis such as premature rupture of membranes, preterm labor or suspected chorioamnionitis. However, since the GBS status of these mothers may not be known during labor, the type, duration and dose of antibiotic used are subject to variation. In fact, during the study period there was a wide variation in the type and doses of antibiotic used even in those mothers who were detected to have GBS colonization. Most mothers received ampicillin in doses lower than those recommended by the American Academy of Pediatrics for the prevention of perinatal transmission of GBS disease.[6]
Thirdly, the postnatal penicillin treatment of infants born to GBS colonized mothers also may have contributed to the low incidence of invasive disease. During the study period, majority of the infants (88%) born to colonized mothers received parenteral penicillin soon after birth. Although there were 2 cases of probable GBS sepsis in this group, there were no deaths or cases of blood culture proven sepsis. Previous studies have reported the efficacy of postnatal penicillin prophylaxis in the prevention of early onset GBS sepsis.[9], [10] However, the dose of penicillin and duration of prophylaxis required are not well established. Also, the hospital stay will increase for at least some newborns who may not be colonized or, even if colonized will not become ill or septic. Also, concern has been raised regarding the partial treatment of neonates who may be already infected in-utero.[11]
Currently routine screening of all pregnant women for GBS colonization is not practiced in our institution. Hence the carriage rate of 1.8% found in the present study is clearly an underestimate. Testing of all pregnant women for GBS carriage is ideal to standardize intrapartum antibiotic prophylaxis and to further reduce the incidence of this serious but preventable disease of newborn. This may also reduce the need for sepsis evaluation in infants born to colonized mothers thus reducing their hospital stay and its associated cost.
Conclusion
In the present study, the overall incidence of early onset GBS sepsis was lower than the reported incidence in Western countries. Although the strategy of postnatal management was effective in preventing death and definite GBS septicemia in infants, in light of current knowledge and recommendation from Western countries,[6] further refinement of the protocol is likely to achieve similar results with shorter hospital stay and reduced costs. Adequate and standardized intrapartum antibiotic prophylaxis in colonized mothers will decrease the need for sepsis evaluation and postnatal penicillin therapy for their infants if they appear well at birth.
Acknowledgement
The authors are grateful to Dr. Gamini Kumarasinghe, chief of Microbiology department, National University Hospital, Singapore for providing us the data on blood and CSF cultures during the study period.
References
1. Kuruvilla KA, Thomas N, Jesudasan MV, Jana AK. Neonatal Group B Streptococcal bacteraemia in India: ten years experience. Acta Paediatr 1999; 88(9): 1031-1032
2. Kalliola S, Varkila JV, Takala AK, Eskola J. Neonatal group B streptococcal disease in Finland: a ten-year nationwide study. Pediatr Infect Dis J 1999; 18: 806-810.
3. Almuneef M, Alalola S, Ahmed S, Memish Z, Khan MY, Alshaalan M. The changing spectrum of Group B streptococcal infection in infants of Saudi Arabia. J Chemother 2000; 12(1): 48-52.
4. Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, O'Sullivan MJ et al. Risk factors and opportunities for prevention of early onset neonatal sepsis: a multicenter case-control study. Pediatrics 2000; 105: 21-26.
5. Gilson GJ, Christensen F, Romero H, Bekes K, Silva L, Qualls CR. 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 than37 weeks' gestation. J Perinatol 2000 Dec; 20(8 Pt 1): 491-495.
6. Committee on Infectious Diseases and Committee on Fetus and Newborn. American Academy of Pediatrics. Revised guidelines for prevention of early-onset group B streptococcal infection. Pediatrics. 1997; 99:489-496.
7. Chua S, Arulkumaran S, Chow C, Kumarasinghe G, Selamat N, Kuah BG, Ratnam SS. Genital group B streptococcus carriage in the antenatal period: Its role in PROM and preterm labour. Singapore Med J 1995; 36: 383-385.
8. Berner R, Csorba J, Brandis M. Different cytokine expression in cord blood mononuclear cells after stimulation with neonatal sepsis or colonizing strains of streptococcus agalactiae. Pediatric Research 2001; 49 : 691-697.
9. Patel DM, Rhodes PG, LeBlanc MH, Graves GR, Glick C, Morrison J. Role of postnatal penicillin prophylaxis in prevention of neonatal group B streptococcus infection. Acta Paediatr 1999; 88(8): 874-879.
10. Seigel JD, Cushion NB. Prevention of Early-Onset Group B Streptococcal Disease: Another Look at Single-Dose Penicillin at Birth. Obstet Gynecol 1996; 87: 692-698.
11. Pyati SP, Pildes RS, Jacobs NM, Ramamurthy RS, Yeh TF, Raval DS et al. Penicillin in Infants weighing two kilograms or less with early-onset group B streptococcal disease. NEJM 1983; 308: 1383-1389.(Niduvaje Krishnamoorthy, )
Abstract
Objective. To determine the incidence of early onset Group B Streptococcal (GBS) infection in infants born over a two year period and to determine the outcome of sepsis evaluation in infants born to mothers with GBS colonization. Methods. The charts of infants born to mothers with GBS colonization were reviewed for details of sepsis evaluation and management. The microbiology records were used to identify proven cases of GBS septicemia and meningitis in neonates born during the study period. Results. Out of a total of 4636 live births in 2 years, there was one infant with culture-proven GBS septicemia, an incidence of 0.2 per 1000 live births. During the study period 83 infants were born to mothers who were known to have GBS carriage at the time of delivery. 73 out of these 83 infants (88%) had sepsis evaluation and received empirical parenteral penicillin for at least 5 days. There were no cases of blood culture-proven GBS sepsis among these 83 infants. However, there were 2 cases of probable sepsis giving an attack rate of 2.4%. All the three infants with definite or probable sepsis were preterm; there were no deaths among these affected infants. Conclusion. The overall incidence of early onset GBS sepsis was found to be low when compared to previous reported studies. The strategy of sepsis evaluation and management was found to be effective in preventing death and definite GBS septicemia in infants born to GBS colonized mothers.
Keywords: Group B Streptococcus; Sepsis; Newborn
Group B Streptococcus is the commonest organism causing early onset bacterial sepsis in the newborn in many parts of the world, especially the developed countries. The incidence of GBS infections (per 1000 live births), however, has shown variation between different countries such as India (0.17), Finland (0.76), Saudi Arabia (0.2-1.2), USA (1.4) and New Mexico (1.5) and at different time periods within the same country.[1],[2],[3],[4],[5] Hospital strategies to reduce early onset GBS sepsis in neonates should take into account the current incidence, morbidity and mortality in addition to the financial and emotional burden involved in its prevention and management. In our institution, at the time of this study, the protocol for the management of infants born to mothers with genital carriage of GBS included in-patient observation of these infants along with parenteral administration of penicillin for at least 5 days, irrespective of whether they were symptomatic at birth or not. As a result many asymptomatic term neonates had to stay in the hospital for extended periods causing parental anxiety besides increasing the hospital costs. To determine whether such a cautious approach was needed in the management of these infants at risk, knowledge on the current burden of GBS sepsis and the outcome of postnatal management of these infants was necessary. The present study was, therefore, undertaken to determine the incidence of early onset GBS sepsis in infants born at our institution and to determine the outcome of sepsis evaluation in infants born to mothers with GBS colonization during the same period.
Materials and Methods
This was a retrospective study conducted on neonates born in National University Hospital, Singapore between January 1999 and December 2000. During the study period, infants born to mother with genital carriage of GBS had sepsis evaluation at birth that included full blood count, C-reactive protein and blood culture. Infants received parenteral penicillin for at least 5 days irrespective of whether they were symptomatic or not. The charts of infants born to mothers who were detected to have GBS colonization during pregnancy were reviewed for details of sepsis evaluation, management and outcome. In particular, the type and doses of intrapartum antibiotics used, condition of the infant at birth, presence or absence of any clinical symptoms, results of full blood count, C-reactive protein and blood culture, and the postnatal management of these infants were reviewed.
At the time of the study, routine antenatal screening of pregnant women for genital carriage of GBS was not practiced in our institution. In order to identify those infants with GBS sepsis, whose mothers were not screened during pregnancy for GBS colonization, the microbiology records of the hospital during the same period were reviewed for any blood culture and/or CSF culture proven cases of GBS sepsis. These records had documented all the culture proven cases of GBS sepsis that occurred in the hospital during the study period.
Definition of early onset GBS sepsis : Early onset sepsis was defined as GBS sepsis presenting within the first 7 days of life. Cases of GBS sepsis were classified either as definite or probable based on the clinical symptoms and the results of laboratory investigations and culture results. Definite GBS sepsis was diagnosed when there was isolation of the organism either from the blood or CSF in a symptomatic neonate. The infection was categorized as probable when there was isolation of GBS from surface swabs in a symptomatic infant with laboratory evidence of infection (white cell count <4000/cmm or thrombocytopenia <150,000/cmm or raised C-reactive protein >1mg/dl) or radiological evidence of pneumonia.
Results
GBS colonization in mothers: During the period there were a total of 4636 live births among 4553 pregnant women. Out of these, 81 mothers (1.8%) were detected to have GBS colonization during pregnancy. The usual indications to send a vaginal swab for bacterial culture in these mothers were vaginal discharge, preterm labor, premature rupture of membranes and suspected chorioamnionitis.
Intrapartum antibiotics: Fifty five of 81 mothers (68%) with GBS colonization received at least one dose of an antibiotic during labor. Intravenous ampicillin was the commonest antibiotic used (48 out of 55) with erythromycin (3/55), ceftriaxone (2/55) or amoxicillin (2/55) in the remaining mothers. However, when intravenous ampicillin was used the dose was lower than that recommended by the American Academy of Pediatrics for the prevention of GBS sepsis in newborn.[11]
Postnatal management of infants: All the 83 infants born (including two pairs of twins) to 81 mothers with GBS colonization were observed in the hospital for signs and symptoms of sepsis. Sixteen infants (19%) were preterm (gestational age less than 37 weeks). Seventy three of these 83 infants (88%) had sepsis evaluation (full blood counts, C-reactive protein and blood culture) and received empirical parenteral penicillin for at least 5 days. Ten infants (12%) were not evaluated for sepsis at birth because the positive result of the mother's vaginal swab sent during labor was available only after the second postnatal day. All these 10 infants remained well with no signs or symptoms of sepsis. Among the cohort of 83 infants 2 preterm infants (2.4%) were diagnosed to have probable GBS sepsis and received intravenous penicillin for 10 days.
Incidence of early onset GBS sepsis
During the period of the study there was one infant who was born in our institution who had blood culture proven GBS sepsis presenting on the first day of life. This infant's mother was not tested antenatally for GBS carriage and hence the mother had not received any intrapartum antibiotics. This was the only case of definite early onset GBS sepsis (blood culture proven) among 4636 live births during the study period, giving an incidence of 0.2 per 1000 live births. If the two cases of probable GBS sepsis (blood culture negative) mentioned previously were also included, the incidence would be 0.6 per 1000 live births. All the three infants were born preterm. The clinical profiles of these three infants are shown in the table1.
Discussion
Group B Streptococcus is an important pathogen responsible for early onset bacterial sepsis in the newborn. The incidence of early onset GBS infection, however, varies in different parts of the world from 0.17 to 1.5 per 1000 live births. A low incidence has been reported from many Asian countries. The reasons for the low incidence in the Asian population are unclear but may be partly due to low rates of colonization and high prevalence of protective antibodies in the mother.[1] In the present study, the incidence of culture proven early onset GBS infection was 0.2 per 1000 live births, which is similar to the incidence in other Asian populations.
The incidence of GBS colonization in mothers has been reported to be 14.1% in a previous study in our institution,[7] which is within the often-quoted range of 5% -25% in different parts of the world. Assuming an attack rate of 1-2% invasive GBS disease in infants born to colonized mothers, an incidence of at least 1.4 per 1000 GBS sepsis is expected to occur in our institution in the absence of routine screening and preventive measures. The lower incidence of invasive GBS disease in newborns, therefore, may be due to other reasons.
First, there may be a difference in the incidence of colonization rates of invasive and non-invasive GBS strains. Many neonates who are colonized with the non-invasive strains may not become ill or septic. However, identifying the invasive strains of GBS before delivery may be difficult, as there are no reliable laboratory tests that differentiate invasive from non-invasive strains. Recently, Berner and colleagues[8] reported different cytokine expression in-vitro in cord blood mono-nuclear cells after stimulation with sepsis or colonizing strains of GBS. If further studies confirm this, it might become possible to screen GBS isolates from maternal swabs for their pathogenic properties.
The second reason for the lower incidence of GBS infection in the present study may be the intrapartum antibiotics administered to mothers with other risk factors for sepsis such as premature rupture of membranes, preterm labor or suspected chorioamnionitis. However, since the GBS status of these mothers may not be known during labor, the type, duration and dose of antibiotic used are subject to variation. In fact, during the study period there was a wide variation in the type and doses of antibiotic used even in those mothers who were detected to have GBS colonization. Most mothers received ampicillin in doses lower than those recommended by the American Academy of Pediatrics for the prevention of perinatal transmission of GBS disease.[6]
Thirdly, the postnatal penicillin treatment of infants born to GBS colonized mothers also may have contributed to the low incidence of invasive disease. During the study period, majority of the infants (88%) born to colonized mothers received parenteral penicillin soon after birth. Although there were 2 cases of probable GBS sepsis in this group, there were no deaths or cases of blood culture proven sepsis. Previous studies have reported the efficacy of postnatal penicillin prophylaxis in the prevention of early onset GBS sepsis.[9], [10] However, the dose of penicillin and duration of prophylaxis required are not well established. Also, the hospital stay will increase for at least some newborns who may not be colonized or, even if colonized will not become ill or septic. Also, concern has been raised regarding the partial treatment of neonates who may be already infected in-utero.[11]
Currently routine screening of all pregnant women for GBS colonization is not practiced in our institution. Hence the carriage rate of 1.8% found in the present study is clearly an underestimate. Testing of all pregnant women for GBS carriage is ideal to standardize intrapartum antibiotic prophylaxis and to further reduce the incidence of this serious but preventable disease of newborn. This may also reduce the need for sepsis evaluation in infants born to colonized mothers thus reducing their hospital stay and its associated cost.
Conclusion
In the present study, the overall incidence of early onset GBS sepsis was lower than the reported incidence in Western countries. Although the strategy of postnatal management was effective in preventing death and definite GBS septicemia in infants, in light of current knowledge and recommendation from Western countries,[6] further refinement of the protocol is likely to achieve similar results with shorter hospital stay and reduced costs. Adequate and standardized intrapartum antibiotic prophylaxis in colonized mothers will decrease the need for sepsis evaluation and postnatal penicillin therapy for their infants if they appear well at birth.
Acknowledgement
The authors are grateful to Dr. Gamini Kumarasinghe, chief of Microbiology department, National University Hospital, Singapore for providing us the data on blood and CSF cultures during the study period.
References
1. Kuruvilla KA, Thomas N, Jesudasan MV, Jana AK. Neonatal Group B Streptococcal bacteraemia in India: ten years experience. Acta Paediatr 1999; 88(9): 1031-1032
2. Kalliola S, Varkila JV, Takala AK, Eskola J. Neonatal group B streptococcal disease in Finland: a ten-year nationwide study. Pediatr Infect Dis J 1999; 18: 806-810.
3. Almuneef M, Alalola S, Ahmed S, Memish Z, Khan MY, Alshaalan M. The changing spectrum of Group B streptococcal infection in infants of Saudi Arabia. J Chemother 2000; 12(1): 48-52.
4. Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, O'Sullivan MJ et al. Risk factors and opportunities for prevention of early onset neonatal sepsis: a multicenter case-control study. Pediatrics 2000; 105: 21-26.
5. Gilson GJ, Christensen F, Romero H, Bekes K, Silva L, Qualls CR. 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 than37 weeks' gestation. J Perinatol 2000 Dec; 20(8 Pt 1): 491-495.
6. Committee on Infectious Diseases and Committee on Fetus and Newborn. American Academy of Pediatrics. Revised guidelines for prevention of early-onset group B streptococcal infection. Pediatrics. 1997; 99:489-496.
7. Chua S, Arulkumaran S, Chow C, Kumarasinghe G, Selamat N, Kuah BG, Ratnam SS. Genital group B streptococcus carriage in the antenatal period: Its role in PROM and preterm labour. Singapore Med J 1995; 36: 383-385.
8. Berner R, Csorba J, Brandis M. Different cytokine expression in cord blood mononuclear cells after stimulation with neonatal sepsis or colonizing strains of streptococcus agalactiae. Pediatric Research 2001; 49 : 691-697.
9. Patel DM, Rhodes PG, LeBlanc MH, Graves GR, Glick C, Morrison J. Role of postnatal penicillin prophylaxis in prevention of neonatal group B streptococcus infection. Acta Paediatr 1999; 88(8): 874-879.
10. Seigel JD, Cushion NB. Prevention of Early-Onset Group B Streptococcal Disease: Another Look at Single-Dose Penicillin at Birth. Obstet Gynecol 1996; 87: 692-698.
11. Pyati SP, Pildes RS, Jacobs NM, Ramamurthy RS, Yeh TF, Raval DS et al. Penicillin in Infants weighing two kilograms or less with early-onset group B streptococcal disease. NEJM 1983; 308: 1383-1389.(Niduvaje Krishnamoorthy, )