Case of the Month

April 2012

A 23 year old HIV-seronegative mother (G2 P2 -1), gave birth to monochorionic, diamniotic twin infants.

The mother had a history of miscarriage at 23 weeks (unknown cause). She was HIV seronegative. She had booked late and was 24 weeks by late ultrasound. The twin pregnancy was treated as an inevitable miscarriage when she went into preterm labour. The mother did not receive intrapartum antibiotics and there was no fetal monitoring.

Twin A was born with Apgars of 8,9 and 9. No resuscitation was necessary. Birth weight was 700g. Liquor was clear. She was assessed as being 27 weeks according to Ballard score and commenced on CPAP. No surfactant was given. Penicillin and gentamicin were commenced according to the protocol for preterm infants. Initial blood tests revealed:

WCC = 5.18 x 109/L; Hb = 15.1 g/dl; plt = 266 x 109/L
C- reactive protein (CRP) = 12 on day 1 and repeat after 12 hours was < 4.
Blood culture was negative after 5 days - Antibiotics were stopped after 3 days.

On day 20 she received ibuprofen to close a patent ductus arteriosus.

On day 22 (gestational age 30 weeks and 1 day) she developed recurrent apnoea.

WCC= 4.27 x 109/L
Neutrophils were 12% with absolute count of 0.51 per mm3
Hb = 11.6 g/dl, nucleated RBCs 18 x 109/L
Plt = 436 x 109 /L
CRP was 114.

She was started on meropenem and vancomycin but was too unstable for lumbar puncture.

Within 6 hours the blood culture grew Gram positive cocci in chains, sensitive to penicillin, ampicillin and erythromycin.

Twin A demised on day 24.

X ray of Twin A

Twin B had Apgar scores of 3, 5 and 8. Birth weight was 820g.
She was estimated to be 29 weeks by Ballard score.
After initial resuscitation she was started on CPAP.

First 2 weeks of life were uneventful. She also received penicillin and gentamicin for the first 3 days. These were stopped after CRP was < 4 and initial blood culture was negative.

On day 17 Twin B started to desaturate.

WCC = 13.8 x 10 9/L
Hb = 13.8 g/dl; platelets =323 x 109/L.
CRP was < 4

Meropenem was started, but stopped after 4 days when the blood culture came back negative.

3 days later a repeat crp was < 4.

On day 25 Twin B developed persistent tachycardia. Penicillin was started. This was just after Twin A had demised.

Penicillin stopped after 2 days as the infant was asymptomatic, CRP was < 4 and blood culture was negative.

On day 33 Twin B again developed desaturations and was admitted to NICU.

WCC= 3.6 x 109/L, neutrophil count = 64%
Hb = 9.2g/dl; Plt = 300 x 109 /L
Blood culture grew Gram positive cocci in chains after 9 hours sensitive to penicillin, ampicillin and erythromycin.
Lumbar puncture : CSF was yellow. P=0; L = 5; RBC= 0. No growth.

Twin B was treated for 14 days with Penicillin. On day 51 Twin B deteriorated again (5 days after stopping penicillin) and was started on meropenem and vancomycin. Blood culture again grew Gram positive cocci in chains sensitive to penicillin, ampicillin and erythromycin. The culture was positive within 4.5 hours suggesting a high bacterial load.

Additional investigations and information: Maternal breast milk was sent twice for culture and was negative. Maternal and Twin B throat swabs were negative for group B streptococcus Mother did not have mastitis.

Xray of Twin B

Both infants had Group B Streptococcus on blood culture.

Question 1: What are the different clinical presentations of Group B Streptococcal infection in infants?

Answer to Q1

Group B Streptococcus or Streptococcus agalactiae can present as early onset disease (EOD) between 0-6 days or as late onset disease (LOD) in young infants between 7-90 days.

EOD is caused by ascending infection; the infant usually aspirates infected amniotic fluid and develops symptoms of pneumonia shortly after birth. Other common presentations are septicaemia and meningitis. GBS can also present with a focal pathology such as cellulitis, adenitis, osteomyelitis or arthritis. Infants with LOD GBS have similar clinical presentations.

Although EOD has a higher mortality, LOD often results in long term sequelae such as cognitive defects, deafness and blindness.

In America and Europe EOD has been reduced by the introduction maternal screening for GBS and intrapartum antibiotic prophylaxis (IAP), but incidence of LOD remains unchanged (1).

African data is limited as GBS is often under reported but is nevertheless a major cause of morbidity and mortality.

Common serotypes reported in South Africa are Ia, Ib and III with serotype III reported as being the most pathogenic strain.(2). A recent systematic review and meta-analysis of GBS found that in low- and high-income countries, the main serotypes are Ia, Ib, II, III and V, thus a vaccine including these serotypes could prevent invasive GBS (3).

Question 2: What are the risk factors and modes of transmission for late onset invasive Group B Streptococcus?

Answer to Q2

Mode of transmission

While EOD GBS is always transmitted vertically, LOD GBS can be acquired from other sources. Infection from maternal colonization with GBS is one mode of transmission; one study showed that 50% of infants that developed LOD GBS were colonized at birth and their mothers were colonized with the identical serotype (4). In infants whose mothers are not colonized, it is often difficult to establish the route of infection. Nosocomial transmission has been reported (5,6). Case reports have identified breast milk as a source of infection and horizontal transmission after the perinatal period may occur (7-10).

Risk factors

Prematurity is the major risk factor for LOD GBS (11).

Although maternal colonization is a risk factor for LOD GBS as described above (11), it is not as strongly associated with risk as is EOD. In the United States African Americans have higher risk of LOD, with black infants having a three times higher incidence of late onset GBS (12). A recent paper showed a high incidence of GBS in HIV-exposed but un-infected infants with more LOD than in unexposed infants (5 out of 6 episodes were LOD compared with 2 out of 16 episodes in unexposed infants)(13). However other studies from Brazil, Zimbabwe and Malawi suggest that maternal colonization by GBS is not increased in those that are HIV-infected(14 - 17). The Brazilian study found no cases of LOD GBS in HIV-infected women, but there was no comparator group, limiting interpretation of the findings (17).

Question 3: What are the possible causes of recurrent invasive Group B streptococcus infection and what can be done to prevent it?

Answer to Q3

Recurrence of GBS disease was first reported in the mid seventies (18,19,20). DNA restriction enzyme analysis has allowed differentiation between infection with a ‘new’ GBS strain and the same strain. In a previous case series it was found that 5 out of 6 infants infected with the same serotypes had genetically identical GBS isolates suggesting persistent mucosal colonization may be more common than infection with a new strain (21).

Rifampicin has been used to clear persistent mucosal colonization but has limited efficacy (22) As seen in our case report penicillin also fails to eradicate persistent colonization (23).

Question 4: Is there evidence that twins are at greater risk of invasive GBS?

Answer to Q4

Twin pregnancy has been reported as an uncommon risk factor for invasive GBS disease (24,25,26) despite vaginal GBS rates having been shown to be similar in twin and singleton pregnancies (25). Some guidelines recommend investigation of the other twin and commencement of empiric antibiotics until cultures become available (27). The relative risk of a twin having invasive GBS if the other twin is infected has been calculated as being as high a 25 times that of an infant without an infected twin (28). Twins are likely to share predisposing factors for LOD such as a low concentration of maternal IgG specific antibody for capsular polysaccharide that is available for placental transport, decreased placental transport of maternal IgG if they are born before 34 weeks gestation and the same bacterial virulence of a particular strain of GBS (if they are infected with the same strain)(29).


  1. Jordan HT, Farley MM, Craig A et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, population-based analysis. Pediatr Infect Dis J (2008); 27: 1057-64
  2. Madzivhandila M, Adrian PV, Cutland CL, Kuwanda L, Schrag SJ, et al. (2011) Serotype Distribution and Invasive Potential of Group B Streptococcus Isolates Causing Disease in Infants and Colonizing Maternal-Newborn Dyads. PLoS ONE 6(3): e17861. doi:10.1371/journal.pone.0017861
  3. Edmond KM, Kortsalioudaki C, Scott S, et al. Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta- analysis. Lancet 2012; published online Jan 5. DOI:10.1016/S0140- 6736(11)61651-6.
  4. Dillon HC Jr, Khare S, Gray BM. Group B streptococcal carriage and disease:a 6-year prospective study. J Pediatr 1987;110(1):31–6.
  5. Easmon CS, Hastings MJ, Clare AJ, et al. Nosocomial transmission of group B streptococci. Br Med J 1981;283(6289):459–61.
  6. Anthony BF, Okada DM, Hobel CJ. Epidemiology of the group B streptococcus: maternal and nosocomial sources for infant acquisitions. J Pediatr 1979;95(3): 431–6.
  7. Olver WJ, Bond DW, Boswell TC, et al. Neonatal group B streptococcal disease associated with infected breast milk. Arch Dis Child 2000;83(1):F48–9.
  8. Dinger J, Muller D, Pargac N, et al. Breast milk transmission of group B strepto- coccal infection. Pediatr Infect Dis J 2002;21(6):567–8.
  9. Godambe S, Shah PS, Shah V. Breast milk as a source of late onset neonatal sepsis. Pediatr Infect Dis J 2005;24(4):381–2.
  10. Wang LY, Chen CT, Liu WH, et al. Recurrent neonatal group B streptococcal disease associated with infected breast milk. Clin Pediatr (Phila) 2007;46(6): 547–9.
  11. Lin FY, Weisman LE, Troendle J, et al. Prematurity is the major risk factor for late- onset group B Streptococcus disease. J Infect Dis 2003;188(2):267–71
  12. Schuchat A, Oxtoby M, Cochi S, et al. Population-based risk factors for neonatal group B streptococcal disease: results of a cohort study in metropolitan Atlanta. J Infect Dis 1990;162(3):672–7
  13. Epalza C, Goetghebuer T, Hainaut M, Prayez F, Barlow P, Dediste A, et al. High incidence of invasive group B streptococcal infections in HIV-exposed uninfected infants. Pediatrics 2010;126:e631–8
  14. El Beitune P, Duarte G, Maffei CM, Quintana SM, De Sa Rosa ES, Nogueira AA. Group B Streptococcus carriers among HIV-1 infected pregnant women: prevalence and risk factors. Eur J Obstet Gynecol Reprod Biol 2006;128:54–8.
  15. Mavenyengwa RT, Moyo SR, Nordbo SA. Streptococcus agalactiae colonization and correlation with HIV-1 and HBV seroprevalence in pregnant women from Zimbabwe. Eur J Obstet Gynecol Reprod Biol 2010;150:34–8
  16. Joao EC, Gouvêa MI, Menezes JA, Matos HJ, Cruz ML, Rodrigues CA, de Souza MJ, Fracalanzza SE, Botelho AC, Calvet GA, Grinsztejn BG. Group B Streptococcus in a cohort of HIV-infected pregnant women: prevalence of colonization, identification and antimicrobial susceptibility profile.Scand J Infect Dis. 2011 Sep;43(9):742-6. Epub 2011 Jun 15. Gray KJ, Kafulafula G, Matemba M, Kamdolozi M, Membe G, French N, Streptococcus and HIV infection in pregnant women, Malawi, 2008–2010. Emerg Infect Dis. 2011;17:1932–5
  17. Broughton DD, Mitchell WG, Grossman M, Hadley WK, Cohen MS. Re- currence of group B streptococcal infection. J Pediatr 1976;89:182–5.
  18. Walker SH, Santos AQ, Quintero BA. Recurrence of group B III strepto- coccal meningitis. J Pediatr 1976;89:187–8.
  19. Ruiz-Gomez D, Tarpay MM, Riley HD. Recurrent group B streptococcal infections: report of three cases. Scand J Infect Dis 1979;11:35–8
  20. Green PA, Singh KV, Murray BE, Baker CJ. Recurrent group B streptococcal infections in infants: clinical and microbiologic aspects. J Pediatr 1994; 125:931–8.
  21. Fernandez M, Rench MA, Albanyan EA. Failure of rifampin to eradicate Group B streptococcal colonization in infants. Pediatr Infect Dis J. 2001;20:371-6.
  22. Paredes A, Wong P, Yow MD. Failure of penicillin to eradicate the carrier state of Group B streptococcus in infants. J Pediatr. 1976;89:191-3.
  23. Edwards MS, Jackson CV, Baker CJ. Increased risk of group B streptococcal disease in twins. JAMA 1981;245:2044–6.
  24. Pass MA, Khare S, Dillon HC Jr. Twin pregnancies: incidence of group B streptococcal colonization and disease. J Pediatr 1980;97:635–7.
  25. Christensen KK, Christensen P, Gro ̈gaard J, Hjalt CA. Fatal streptococcus group B meningitis in newborn twins. Scand J Infect Dis 1974;6:361–3.
  26. American Academy of Pediatrics. Group B streptococcal infections. In: Peter G, ed. 1997 Red book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997: 494–501.
  27. Edwards MS, Baker CJ. Group B streptococcal infections. In: Remington J, Klein JO, editors Infectious Diseases of the Fetus and Newborn Infant, 5th ed Philadelphia: WB Saunders, 2001, p 1091-156.
  28. Doran KS, Benoit VM, Gertz RE, Beall B, Nizet V. Late-onset group B streptococcal infection in identical twins: insight to disease pathogenesis.J Perinatol. 2002 Jun;22(4):326-30
Outcome of the case:

GBS can be recurrent and can occur soon after a full course of penicillin. Twins have increased risk of GBS. Prematurity is the major risk factor for LOD.

Earn CPD Points


FIDSSA Members can earn CPD points by logging into the secure section of the website and visiting the MyCPD section.