J. Paediatr. Child Health (1991) 27, 113-1 15
Haemophilus influenzae septicaemia in the neonate: Report of two cases and review of the English literature S-N. WONG and T-L. NG Deparfmenf of Paediatrics, Queen Mary Hospital, Hong Kong
Abstract Two neonates with early onset respiratory illness were found to have Haemophilus influenzae septicaemia. One of them died. A review of the English literature showed that Haemophilus influenzae septicaemia is increasing in incidence. Almost all cases presented with respiratory distress in the first 2 days. Other associated features included meningitis, arthritis, conjunctivitis and cellulitis. The mortality, which averaged 52%, was high, especially in premature babies. The septicaemia was caused by ascending infection from the colonized maternal birth canal, and most cases were caused by nontypable strains of Haemophilus influenzae. Because of the occurrence of ampicillin or chloramphenicol resistance, a third generation cephalosporin is the treatment of choice for known cases of serious infection.
Key words: Haemophilus influenzae; neonates; septicaemia.
Haemophilus influenzae is a major cause of meningitis in infants and children less than 5 years of age. In septicaemia in the neonatal period, Group B Streptococcus and Gram-negative coliforms are the commonest isolates, while Haemophilus influenzae is considered an uncommon cause. In our institution, there was no case of Haemophilus influenzae isolates from the blood or cerebrospinal fluid in neonates from 1980 to 1988. From June to December 1989, however, we have encountered two cases of Haemophilus influenzae septicaemia. We report these two interesting cases, and review the English literature concerning this uncommon infection.
CASE REPORT 1
This 1200 g male baby was born at a gestational age of 30 weeks to a gravida 2 para 2 Pakistani mother after spontaneous onset of premature labour and failure of tocolytic therapy. There was no maternal fever or offensive vaginal discharge. Fetal membranes were ruptured just before vaginal delivery. However, thick turbid meconium-stained liquor was noted at birth. He was cyanotic, flaccid and bradycardiac at birth, and responded to immediate intubation and ventilation. The Apgar score was 2 at 1 min, 5 at 5 min, and 7 at 10 min. On admission to the Neonatal Intensive Care Unit he had a temperature of 375°C and breath sounds were decreased in both lungs. The other systems were normal. The assessed maturity was appropriate for a gestational age of 30 weeks. His chest radiograph showed complete opacity of both lungs and an air-bronchogram. His initial Hb was 14.7 g/dL; the white blood cell count was 2.8x109/L with 15%
Correspondence: Dr S-N. Wong, Department of Paediatrics, Queen Mary Hospital, Pokfulam Rd, Hong Kong. S-N. Wong. MB. BS. MRCP. T-L. Ng, MB, BS, MRCP. Accepted for publication 19 October 1990.
polymorphs. Penicillin and cefuroxime were given after cultures of blood, tracheal and gastric aspirate, ear, nose, umbilical and rectal swabs were taken. His respiratory illness deteriorated progessively. At 9 h of life, he required ventilation with Fio, of 1.O. pressure of 3915 cmH,O, and a rate of 60 per rnin, but he remained hypoxaemic with Pao, ranging from 4 to 6 kPa, and Paco, of 6 kPa. In view of the possibility of persistent fetal circulation, a tolazoline infusion was tried without improvement. His blood pressure was low despite adequate volume loading and inotropic infusions. Terminally, he developed acute renal failure, intraventricular haemorrhage and metabolic acidosis, and finally succumbed at 27 h of age. His blood culture was subsequently positive for Haemophilus influenzae. However, the specific serotype was not determined. The organism was susceptible to cefuroxime, ampicillin, erythromycin, chloramphenicol and co-trirnoxazole. His mother's high vaginal swab, placental swab, and the other cultures taken from the baby did not lead to isolation of any recognized pathogen. The placental histology demonstrated acute chorio-amnionitis.
CASE REPORT 2
This baby was born at a gestational age of 36 weeks to a primigravida Vietnamese mother. Her birthweight was 1435 g. There had been intrauterine growth retardation from 25 weeks gestation. Spontaneous labour occurred without any evidence of maternal fever, vaginitis, or prolonged rupture of membranes. The baby was born on a police ferry and the umbilical cord was clamped by the accompanying nurse. On arriving at the hospital 40 min later, the baby was cyanotic with apnoea and bradycardia. She responded well to intubation and ventilation. On admission to the Neonatal Intensive Care Unit, her condition was fair with
114
S-N. Wong and T-L. Ng
respiratory distress. She was active with good sucking and grasp reflexes. The other systems were normal and the assessed maturity was 32-34 weeks. She was rapidly weaned to CPAP at 12 h of age, at which time she developed two episodes of apnoea. Her physical examination was unremarkable. Her white blood cell count was 15.7x109/L with 60% polymorphs, and 10% band forms. The cerebrospinal fluid was blood stained due to a traumatic tap but no white blood cells were seen. The CSF glucose concentration was 1.8 mmol/L (50% of blood glucose) and the protein concentration was 3 g/L. Cultures of blood, cerebrospinal fluid, tracheal aspirate, nasal, eye, ear, throat, umbilical swabs were taken. She was given penicillin and cefuroxime afterwards. There was a good clinical response. She was extubated after 2 days. Subsequently, the cultures of all specimens, with the exception of the CSF, were positive for a nontypable strain of Haemophilus influenzae, which was sensitive to cefamandole and co-trimoxazole; but resistant to ampicillin, erythromycin and chloramphenicol. She was treated with cefuroxime for 3 weeks. Her subsequent recovery was uneventful apart from one episode of suspected sepsis on day 22 of life. She was discharged well on day 43 of life with a bodyweight of 2340 g. No recognized pathogens were isolated from the maternal vaginal swab. However, the placenta was not sent for histological examination.
DISCUSSION Though Haernophilus influenzae as a cause of neonatal septicaemia was almost unheard of before the 1970s, an increasing incidence has been reported in the past 2 decades. Freedman et a/.' at Yale reported no cases from 1928 to 1957, one case out of 73 neonates with septicaemia (1.4%)from 1958 to 1965, and nine out of 239 cases (3.8%)from 1966 to 1978. At present, the reported incidence ranged from 2.6% of all neonatal septicaemias from Wallace et a/.' at Houston, to 7.9% from Campognone et at Providence, Ireland. In Oxford, Milne et a14 reported Haernophilus influenzae infections in 0.23 babies per 1000 live births from January 1985 to March 1987. A total of 116 cases (including the present two) have been reported in the English literature since 1965.'-25.28 A major proportion of the victims were premature or low birthweight babies. As shown in Tables 1 and 2, 45% were less than 30 weeks gestation, 87% were less than 37 weeks; and 43% and 85% were less than 1.5 kg and 2.5 kg, respectively. It was remarkable how similar these cases were in their clinical features. One hundred and one presented with early onset of respiratory distress. Of the 88 cases where the data were available, 92% presented in the first 48 h, and 4.5% presented in Table 1 Gestational ages of all reported cases of Haemophflus fnflu-
enzae septicaemia in neonates* Gestational age (weeks)
Cases ~
37 Total
33 12 9 10 10 74
Cumulative % __ 44 6 60 8 73 0 86 5 100 0 1000
*Data derived from references 2-1 5,17-20,22-25, and present report
Birthweights of all reported cases of Haemophilus influenzae septicaemia in neonates*
Table 2
Birthweight (9)
< 1500 1500-1 749 1750-1 999 2000-2499 2500-2999 >3000 Total
Cases
Cumulative %
31 6 9 15 6 5 72
43.1 51.4 63.9 84.7 93.1 100.0 100.0
*Data derived from references 2-8, 10-20, 22-25, and present report. Table 3 Clinical features of Haemophilus influenzae septicaemia ( n = 114)*
Clinical features Respiratory distress Meningitis Conjunctivitis Arthritis Cellulitis Abscess (scalp) Mastoiditis Pericarditis infected circumcision site
Number (Vo) 101 (89.0) 11 (9.7) 5 (4.4) 4 (3.5) 3 (2.6) 2 (1.8) 1 (0.9) 1 (0.9) 1 (0.9)
Reference no 1-5. 7-13, 15, 19, 20, 22-25, present report 1-3, 9. 10, 12, 13, 16, 18, 25, 28 3. 4, 7 13, 17, 28 2, 14 2, 7 16 12 17
*Clinical features not reported in two cases in reference 21
the third and fourth days of life. Only three cases presented beyond 5 days: one had a scalp abscess? one had an infected circumcision site17 and the third had generalized septicaemia, meningitis and pericarditis.'' Other associated features are listed in Table 3 and included meningitis, arthritis, cellulitis and conjunctivitis. Maternal genitourinary infection and prolonged rupture of membranes (for more than 24 h) before delivery are frequent associations, occurring in 27.4% and 21.6%, re~pectively.~ This suggests vertical transmission due to ascending infection during labour or delivery. In utero infection causing septic abortion also has been reported.6 Among the neonates with Haemophilus influenzae septicaemia, Khuri-Bulos and Mclntosh7 reported all maternal cultures to be positive, and Campognone3 reported 42% positive cultures from the maternal cervix, and 69% positive cultures from the placenta. Unlike Group B Streptococcus, which colonizes roughly 10-50% of pregnant women, Haernophilus influenzae is an uncommon organism in the maternal genitourinary tract. Khuri-Bulos and Mclntosh' in 1983 screened 455 women and found only two to be harbouring the organism ( < l % ) ,However, the chance of neonatal infection is high if the mother has the organism. The risk of neonatal infection for maternal colonization was reported as 50% for Haernophilus influenzae septicaemia'~' but only about 1% for Group B ~treptococcus.~~~6~2~ Of the 101 cases in which typing was performed, 74 of the isolates were nontypable, 19 were type b, and eight were encapsulated organisms other than type b. Wallace et a/.' speculated that biotype IV was more common (47% of their series) and might have particular pathogenicity for newborns.
115
Haernophilus influenzae septicaemia
Table 4 Mortality in relation to gestational age in neonatal Haemophilus influenzae septicaemia
Gestational age (weeks)
37 Overall
No. dead/total cases
Mortality rate (%)
23/30 10/20 2/11 2/10 37/71
77.0 50.0 18.2 20.0 52.1
However, later reports2' did not confirm this finding. The lack of a polysaccharide capsule makes the nontypable Haemophilus influenzae susceptible to phagocytosis, so it is an uncommon cause of septicaemia or meningitis outside the neonatal age group. However, it may be particularly virulent in the newborn baby, especially the premature baby, who has immature immune defences against infection. The relative infrequency of Haemophilus influenzae type b is explained by the presence of protective maternal antibody, the level of which declines after 2 months.29 From the available data (Table 4), the mortality rate from this infection is high, with a mean of 52%. Most deaths occurred in the premature babies. Haemophilus influenzae is usually susceptible to ampicillin and chloramphenicol, and is almost always susceptible to the second or third generation cephalosporins. In our community, as in most other parts of the world, 20% of the Haemophilus influenzae isolates were resistant to ampicillin and 14% were resistant to chloramphenico13° For serious infections, a thirdgeneration cephalosporin is the treatment of choice, especially since about 10%of cases were associated with meningitis. This infection is still uncommon at present. Nevertheless, the empirical antibiotic regimen for neonatal sepsis may need to be modified to include agents against this organism should this infection increase in incidence. Thus a more complete epidemiological study should be undertaken, first to define the incidence of neonatal Haemophilus influenzae colonization or infection, and second to define the antibiotic resistance pattern of the organism in the local community.
REFERENCES 1 Freedman R. M., lngram D. L.. Gross I., Ehrenkranz R. A,, Warshaw J. B., Baltimore R. S. A half-century of neonatal sepsis at Yale: 1928 to 1978. Amer. J. Dis. Child. 1981; 135: 140-4. 2 Wallace R. J. Jr, Baker C. J.. Quinones F. J., Hollis D. G., Weaver R. E.. Wiss K. Nontypable Haemophilus influenzae (biotype 4) as a neonatal, maternal, and genital pathogen. Rev. Infect. Dis. 1983; 5: 123-36. 3 Campognone P., Singer D. B. Neonatal sepsis due to nontypable Haemophilus influenzae. Amer. J. Dis. Child. 1986; 140: 117-21. 4 Milne L. M., lsaacs D., Crook P. J. Neonatal infections with Haemophilus species. Arch. Dis. Child. 1988; 63: 83-5. 5 Friesen C. A., Cho C. T. Characteristic features of neonatal sepsis due to Haemophilus influenzae. Rev. Infect. Dis. 1986; 8: 777-80.
6 Berczy J., Fernlund K.. Kamme C. Haemophilus influenzae in septic abortion. Lancet 1973; i: 1197. 7 Khuri-Bulos N., Mclntosh K. Neonatal Hemophilus influenzae infection: Report of eight cases and review of the literature. Amer. J. Dis. Child. 1975; 129: 57-62. 8 Nicholls S..Yuille T. D., Mitchell R. G. Perinatal infections caused by Haemophilus influenzae. Arch. Dis. Child. 1975; 50: 739-41. 9 Courtney S. E., Hall R. T. Haemophilus influenzae sepsis in the premature infant. Amer. J. Dis. Child. 1978; 132: 1039-40. 10 Lilien L. D., Yeh T. F., Novak G. M., Jacobs N. M. Early-onset Haemophilus sepsis in newborn infants: Clinical, roentgenographic, and pathologic features. Pediatrics 1978; 62; 299-303. 11 Bale J. F. Jr, Watkins M. Fulminant neonatal Hemophilus influenzae pneumonia and sepsis. J. Pediatr. 1978; 92: 233-4. 12 Collier A. M.. Connor J. D.. Nyhan W. L. Systemic infection with Hemophilus influenzae in very young infants. J. Pediatr. 1967; 70: 539-47. 13 Granoff D. M., Nankervis G. A. Infectious arthritis in the neonate caused by Hemophilus influenzae. Amer. J. Dis. Child. 7975; 129: 730-3. 14 Halal F., Delorme L., Brazeau M., Ahronheim G. Congenital vesicular eruption caused by Hemophilus influenzae type b. Pediatrics 1978; 62: 494-6. 15 lngram M. J. Neonatal Hemophilus influenzae septicemia originating from maternal amnionitis. Amer. J. Dis. Child. 1970; 119: 66-7. 16 Lee T. 8.. Stingle W. H., Ombres P.. Lewis J. S., Cooper L. 2. Neonatal meningitis and mastoiditis caused by Hemophilus influenzae. J. Amer. Med. Assoc. 1976; 235: 407-9. 17 Marston G.. Wald E. R. Hemophilus influenzae type b sepsis in infant and mother. Pediatrics 1976: 58: 863-4. 18 Mathies A. W. Jr, Hodgman J., lvler D. Hemophilus influenzae meningitis in a premature infant. Pediatrics 1965; 35: 791-2. 19 Murphy J. F., Minchom P. Hemophilus influenzae infection in the newborn (Letter). Arch. Dis. Child. 1983; 58: 477. 20 Pickering L. K., Simon F. A. Re-evaluation of neonatal Hemophilus influenzae infections. South. Med. J. 1977; 70: 205-7. 21 Placzek M. M., Whitelaw A. Early and late neonatal septicaemia. Arch. Dis. Child. 1983; 58: 728-31. 22 Speer M., Rosan R. C.. Rudolph A. J. Hemophilus influenzae infection in the neonate mimicking respiratory distress syndrome. J. Pediatr. 1978; 93: 295-6. 23 Wilschanski M. A,, Schimmel M. S.. lsacsohn M.. Eidelman A. I. Haemophilus influenzae neonatal sepsis-what is appropriate initial therapy? Acta Paediatr. Scand. 1988; 77: 916-7. 24 Gilsdorf J. R. Haemophilus influenzae non-type b infections in children. Amer. J. Dis. Child. 1987; 141: 1063-5. 25 Chattopadhyay B. Fatal neonatal septicaemia and meningitis due to Haemophilus influenzae acquired from the mother. Postgrad. Med. J. 1984; 60: 707-8. 26 McCracken G. H. Jr, Shinefield H. R. Changes in the pattern of neonatal septicaemia and meningitis. Amer. J. Dis. Child. 1966; 112: 33-9. 27 Baker C. Summary of the workshop on perinatal infections due to Group B Streptococcus. J. Infect. Dis. 1977; 136: 137-52. 28 Kleiman M. B., Reynolds J. K., Schreiner R. L., Smith J. W. Failure to demonstrate special virulence of nontypable Haemophilus influenzae biotype 4 in neonatal sepsis. J. Infect. Dis. 1983; 148: 615. 29 Coulehan J. L., Michaels R. H., Hallowell C.. Schults R., Welty T. K., Kuo J. S. C. Epidemiology of Haemophilus influenzae type b disease among Navajo Indians. Public Health Reports 1984; 99: 404-9. 30 Ling J. M., Khin-Thi-Oo H.. Hui Y. W., French G. L. Antimicrobial susceptibilities of Haemophilus species in Hong Kong. J. Infect. (England) 1989; 19: 135-42.
Haemophilus influenzae septicaemia in the neonate: Report of two cases and review of the English literature S-N. WONG and T-L. NG Deparfmenf of Paediatrics, Queen Mary Hospital, Hong Kong
Abstract Two neonates with early onset respiratory illness were found to have Haemophilus influenzae septicaemia. One of them died. A review of the English literature showed that Haemophilus influenzae septicaemia is increasing in incidence. Almost all cases presented with respiratory distress in the first 2 days. Other associated features included meningitis, arthritis, conjunctivitis and cellulitis. The mortality, which averaged 52%, was high, especially in premature babies. The septicaemia was caused by ascending infection from the colonized maternal birth canal, and most cases were caused by nontypable strains of Haemophilus influenzae. Because of the occurrence of ampicillin or chloramphenicol resistance, a third generation cephalosporin is the treatment of choice for known cases of serious infection.
Key words: Haemophilus influenzae; neonates; septicaemia.
Haemophilus influenzae is a major cause of meningitis in infants and children less than 5 years of age. In septicaemia in the neonatal period, Group B Streptococcus and Gram-negative coliforms are the commonest isolates, while Haemophilus influenzae is considered an uncommon cause. In our institution, there was no case of Haemophilus influenzae isolates from the blood or cerebrospinal fluid in neonates from 1980 to 1988. From June to December 1989, however, we have encountered two cases of Haemophilus influenzae septicaemia. We report these two interesting cases, and review the English literature concerning this uncommon infection.
CASE REPORT 1
This 1200 g male baby was born at a gestational age of 30 weeks to a gravida 2 para 2 Pakistani mother after spontaneous onset of premature labour and failure of tocolytic therapy. There was no maternal fever or offensive vaginal discharge. Fetal membranes were ruptured just before vaginal delivery. However, thick turbid meconium-stained liquor was noted at birth. He was cyanotic, flaccid and bradycardiac at birth, and responded to immediate intubation and ventilation. The Apgar score was 2 at 1 min, 5 at 5 min, and 7 at 10 min. On admission to the Neonatal Intensive Care Unit he had a temperature of 375°C and breath sounds were decreased in both lungs. The other systems were normal. The assessed maturity was appropriate for a gestational age of 30 weeks. His chest radiograph showed complete opacity of both lungs and an air-bronchogram. His initial Hb was 14.7 g/dL; the white blood cell count was 2.8x109/L with 15%
Correspondence: Dr S-N. Wong, Department of Paediatrics, Queen Mary Hospital, Pokfulam Rd, Hong Kong. S-N. Wong. MB. BS. MRCP. T-L. Ng, MB, BS, MRCP. Accepted for publication 19 October 1990.
polymorphs. Penicillin and cefuroxime were given after cultures of blood, tracheal and gastric aspirate, ear, nose, umbilical and rectal swabs were taken. His respiratory illness deteriorated progessively. At 9 h of life, he required ventilation with Fio, of 1.O. pressure of 3915 cmH,O, and a rate of 60 per rnin, but he remained hypoxaemic with Pao, ranging from 4 to 6 kPa, and Paco, of 6 kPa. In view of the possibility of persistent fetal circulation, a tolazoline infusion was tried without improvement. His blood pressure was low despite adequate volume loading and inotropic infusions. Terminally, he developed acute renal failure, intraventricular haemorrhage and metabolic acidosis, and finally succumbed at 27 h of age. His blood culture was subsequently positive for Haemophilus influenzae. However, the specific serotype was not determined. The organism was susceptible to cefuroxime, ampicillin, erythromycin, chloramphenicol and co-trirnoxazole. His mother's high vaginal swab, placental swab, and the other cultures taken from the baby did not lead to isolation of any recognized pathogen. The placental histology demonstrated acute chorio-amnionitis.
CASE REPORT 2
This baby was born at a gestational age of 36 weeks to a primigravida Vietnamese mother. Her birthweight was 1435 g. There had been intrauterine growth retardation from 25 weeks gestation. Spontaneous labour occurred without any evidence of maternal fever, vaginitis, or prolonged rupture of membranes. The baby was born on a police ferry and the umbilical cord was clamped by the accompanying nurse. On arriving at the hospital 40 min later, the baby was cyanotic with apnoea and bradycardia. She responded well to intubation and ventilation. On admission to the Neonatal Intensive Care Unit, her condition was fair with
114
S-N. Wong and T-L. Ng
respiratory distress. She was active with good sucking and grasp reflexes. The other systems were normal and the assessed maturity was 32-34 weeks. She was rapidly weaned to CPAP at 12 h of age, at which time she developed two episodes of apnoea. Her physical examination was unremarkable. Her white blood cell count was 15.7x109/L with 60% polymorphs, and 10% band forms. The cerebrospinal fluid was blood stained due to a traumatic tap but no white blood cells were seen. The CSF glucose concentration was 1.8 mmol/L (50% of blood glucose) and the protein concentration was 3 g/L. Cultures of blood, cerebrospinal fluid, tracheal aspirate, nasal, eye, ear, throat, umbilical swabs were taken. She was given penicillin and cefuroxime afterwards. There was a good clinical response. She was extubated after 2 days. Subsequently, the cultures of all specimens, with the exception of the CSF, were positive for a nontypable strain of Haemophilus influenzae, which was sensitive to cefamandole and co-trimoxazole; but resistant to ampicillin, erythromycin and chloramphenicol. She was treated with cefuroxime for 3 weeks. Her subsequent recovery was uneventful apart from one episode of suspected sepsis on day 22 of life. She was discharged well on day 43 of life with a bodyweight of 2340 g. No recognized pathogens were isolated from the maternal vaginal swab. However, the placenta was not sent for histological examination.
DISCUSSION Though Haernophilus influenzae as a cause of neonatal septicaemia was almost unheard of before the 1970s, an increasing incidence has been reported in the past 2 decades. Freedman et a/.' at Yale reported no cases from 1928 to 1957, one case out of 73 neonates with septicaemia (1.4%)from 1958 to 1965, and nine out of 239 cases (3.8%)from 1966 to 1978. At present, the reported incidence ranged from 2.6% of all neonatal septicaemias from Wallace et a/.' at Houston, to 7.9% from Campognone et at Providence, Ireland. In Oxford, Milne et a14 reported Haernophilus influenzae infections in 0.23 babies per 1000 live births from January 1985 to March 1987. A total of 116 cases (including the present two) have been reported in the English literature since 1965.'-25.28 A major proportion of the victims were premature or low birthweight babies. As shown in Tables 1 and 2, 45% were less than 30 weeks gestation, 87% were less than 37 weeks; and 43% and 85% were less than 1.5 kg and 2.5 kg, respectively. It was remarkable how similar these cases were in their clinical features. One hundred and one presented with early onset of respiratory distress. Of the 88 cases where the data were available, 92% presented in the first 48 h, and 4.5% presented in Table 1 Gestational ages of all reported cases of Haemophflus fnflu-
enzae septicaemia in neonates* Gestational age (weeks)
Cases ~
37 Total
33 12 9 10 10 74
Cumulative % __ 44 6 60 8 73 0 86 5 100 0 1000
*Data derived from references 2-1 5,17-20,22-25, and present report
Birthweights of all reported cases of Haemophilus influenzae septicaemia in neonates*
Table 2
Birthweight (9)
< 1500 1500-1 749 1750-1 999 2000-2499 2500-2999 >3000 Total
Cases
Cumulative %
31 6 9 15 6 5 72
43.1 51.4 63.9 84.7 93.1 100.0 100.0
*Data derived from references 2-8, 10-20, 22-25, and present report. Table 3 Clinical features of Haemophilus influenzae septicaemia ( n = 114)*
Clinical features Respiratory distress Meningitis Conjunctivitis Arthritis Cellulitis Abscess (scalp) Mastoiditis Pericarditis infected circumcision site
Number (Vo) 101 (89.0) 11 (9.7) 5 (4.4) 4 (3.5) 3 (2.6) 2 (1.8) 1 (0.9) 1 (0.9) 1 (0.9)
Reference no 1-5. 7-13, 15, 19, 20, 22-25, present report 1-3, 9. 10, 12, 13, 16, 18, 25, 28 3. 4, 7 13, 17, 28 2, 14 2, 7 16 12 17
*Clinical features not reported in two cases in reference 21
the third and fourth days of life. Only three cases presented beyond 5 days: one had a scalp abscess? one had an infected circumcision site17 and the third had generalized septicaemia, meningitis and pericarditis.'' Other associated features are listed in Table 3 and included meningitis, arthritis, cellulitis and conjunctivitis. Maternal genitourinary infection and prolonged rupture of membranes (for more than 24 h) before delivery are frequent associations, occurring in 27.4% and 21.6%, re~pectively.~ This suggests vertical transmission due to ascending infection during labour or delivery. In utero infection causing septic abortion also has been reported.6 Among the neonates with Haemophilus influenzae septicaemia, Khuri-Bulos and Mclntosh7 reported all maternal cultures to be positive, and Campognone3 reported 42% positive cultures from the maternal cervix, and 69% positive cultures from the placenta. Unlike Group B Streptococcus, which colonizes roughly 10-50% of pregnant women, Haernophilus influenzae is an uncommon organism in the maternal genitourinary tract. Khuri-Bulos and Mclntosh' in 1983 screened 455 women and found only two to be harbouring the organism ( < l % ) ,However, the chance of neonatal infection is high if the mother has the organism. The risk of neonatal infection for maternal colonization was reported as 50% for Haernophilus influenzae septicaemia'~' but only about 1% for Group B ~treptococcus.~~~6~2~ Of the 101 cases in which typing was performed, 74 of the isolates were nontypable, 19 were type b, and eight were encapsulated organisms other than type b. Wallace et a/.' speculated that biotype IV was more common (47% of their series) and might have particular pathogenicity for newborns.
115
Haernophilus influenzae septicaemia
Table 4 Mortality in relation to gestational age in neonatal Haemophilus influenzae septicaemia
Gestational age (weeks)
37 Overall
No. dead/total cases
Mortality rate (%)
23/30 10/20 2/11 2/10 37/71
77.0 50.0 18.2 20.0 52.1
However, later reports2' did not confirm this finding. The lack of a polysaccharide capsule makes the nontypable Haemophilus influenzae susceptible to phagocytosis, so it is an uncommon cause of septicaemia or meningitis outside the neonatal age group. However, it may be particularly virulent in the newborn baby, especially the premature baby, who has immature immune defences against infection. The relative infrequency of Haemophilus influenzae type b is explained by the presence of protective maternal antibody, the level of which declines after 2 months.29 From the available data (Table 4), the mortality rate from this infection is high, with a mean of 52%. Most deaths occurred in the premature babies. Haemophilus influenzae is usually susceptible to ampicillin and chloramphenicol, and is almost always susceptible to the second or third generation cephalosporins. In our community, as in most other parts of the world, 20% of the Haemophilus influenzae isolates were resistant to ampicillin and 14% were resistant to chloramphenico13° For serious infections, a thirdgeneration cephalosporin is the treatment of choice, especially since about 10%of cases were associated with meningitis. This infection is still uncommon at present. Nevertheless, the empirical antibiotic regimen for neonatal sepsis may need to be modified to include agents against this organism should this infection increase in incidence. Thus a more complete epidemiological study should be undertaken, first to define the incidence of neonatal Haemophilus influenzae colonization or infection, and second to define the antibiotic resistance pattern of the organism in the local community.
REFERENCES 1 Freedman R. M., lngram D. L.. Gross I., Ehrenkranz R. A,, Warshaw J. B., Baltimore R. S. A half-century of neonatal sepsis at Yale: 1928 to 1978. Amer. J. Dis. Child. 1981; 135: 140-4. 2 Wallace R. J. Jr, Baker C. J.. Quinones F. J., Hollis D. G., Weaver R. E.. Wiss K. Nontypable Haemophilus influenzae (biotype 4) as a neonatal, maternal, and genital pathogen. Rev. Infect. Dis. 1983; 5: 123-36. 3 Campognone P., Singer D. B. Neonatal sepsis due to nontypable Haemophilus influenzae. Amer. J. Dis. Child. 1986; 140: 117-21. 4 Milne L. M., lsaacs D., Crook P. J. Neonatal infections with Haemophilus species. Arch. Dis. Child. 1988; 63: 83-5. 5 Friesen C. A., Cho C. T. Characteristic features of neonatal sepsis due to Haemophilus influenzae. Rev. Infect. Dis. 1986; 8: 777-80.
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