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Neonatal group B streptococcal infection
Current Paedlatrzcs (1996)6. 34-37 © 1996PearsonProfessionalLtd
Mini-symposium: Infections
Neonatal group B streptococcal infection
R.M. Blumberg, R.G. Feldman
The group B streptococcus (GBS) is the commonest .bacterial infection in the first days of life in most centres in Europe, North America and Australia. The incidence of infection varies significantly between 0.3 per 1000 births in Britain and up to 5 per 1000 births in Southern USA. The immunological shortcomings of the newborn, accentuated in prematurity, and the virulence of the organism conspire to make the infant particularly vulnerable to this infection.
Table 1 Bacteriological identification characteristics of group B streptococcus
13-haemolysis CAMP factor* Growth on 40% bile agar Growth in 6.5% NaC1 broth Orange pigment when grown on Islam's medium Hydrolysis of arginine and hippurate Acid from glucose, maltose, sucrose, trehalose and glycerol *The CAMP factor is a soluble protein produced by GBS which enhances the action of staphylococcal [3-haemolysin on sheep erythrocytes.
Bacteriology GBS, also called Streptococcus agalactiae belongs to the genus Streptococcus. They are Gram-positive non-motile facultatively anaerobic cocci normally growing in chains and are often slightly elongated. The typical morphology in horse blood agar is a grey mucoid colony surrounded by a zone of ~-haemolysis of up to 2 mm. Table 1 lists the associated characteristics which can be used to identify GBS. The bacterium also possesses a unique carbohydrate which was first detected serologically by Lancefield in 1933. Lancefield showed that the ~haemolytic streptococci could be separated into a number of distinct serological groups and she classified S. agalaetiae as belonging to group B. The derivative of this serological investigation, now performed as a latex agglutination test, is the most common way in which group B streptococci are identified in diagnostic bacteriology laboratories. GBS also possess a polysaccharide capsule. This capsule coats the organism and has been shown to be of key importance in the pathogenesis of infection. There are several different capsular types of GBS; at
present eight varieties have been described, but the more common ones are Ia, Ib, II, III and V. Antibodies to the capsule, when present, protect against infection. Unfortunately, most adults do not possess protective levels of anti-capsular antibody. For example, 90% of women of child bearing age have sub-protective levels of antibody to the type III capsule. Little is known about the surface proteins of GBS. Most strains appear to possess one of a number of proteins which give the appearance of ladders when examined on an acrylamide gel. These include the 'CC and 'Rib' proteins. Some strains also possess an IgA binding protein. Many strains have bound and soluble forms of a C5a peptidase which inhibits macrophage recruitment.
Carriage The primary reservoir is the gastrointestinal tract but the vagina is also frequently colonised. The carriage rate varies to a limited degree geographically but differences are somewhat difficult to assess as methods of culture vary. In order to best assess carriage at the time of delivery, culture should be taken from the vagina and rectum and cultured in an enrichment medium before being plated out onto an agar plate. Most diagnostic laboratories in Britain do not routinely provide
Raoul M. Blumberg, MRCP Research Fellow, Department of Paediatrics and Neonatal Medicine Robert G. Feldman Phi), MRC Path, Senior Lecturer, Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School. Hammersmith Hospital, Du Cane Road, London, W12 ONN, Correspondence and requests for offprints to RGE
34
Neonatal group B streptococcal infection
35
Table 2 Climcaland epidemiologicaldifferencesbetweenearly and late onset group B streptococcalinfection Early sepsis
Late sepsis
Usual age of onset Maternal obstetriccomplications Prematurity Transmission Respiratory and cardiovascularsigns Neurologicalinvolvement Mortality Culture sites
<24 hours Common Common Vertical 90% 15% 20% Mucocutaneous, blood, CSF
Serotype
All serotypes
>7 days Uncommon Uncommon Horizontal/vertical 30% 85% 10% Infrequent isolation of organisms from sites other than blood and CSF PredominantlyserotypeIII
Table 3 Presentingfeatures of group B streptococcalinfection.
Table 4 Risk factors and obstetric comphcations
Early
Late
Respiratorydistress Cyanosis Apnoea Hypotension/poorperfusion Lethargy
Impaired consciousness Seizures Bulging fontanelle Extensorrigidity Focal signs
• • • • • • • • •
a culture method sensitive enough to reliably predict GBS carriage. When using sensitive culture techniques, the GBS carriage rate is 25-30% in both the U K and USA. Geographic variation in carriage therefore does not explain the differences in incidence in different countries. There are some racial differences and it appears that individuals of Afro-Caribbean descent have a slightly higher GBS carriage rate than Caucasians. The definitive explanation for the variation in incidence of GBS infection could be related to geographical strain differences or variation in the immune response to GBS antigens. Transmission to neonate
Historically the disease has been classified into early and late sepsis. Rather, it is a continuum, separated by time and mode of colonisation and immediate or delayed invasion of host defenses. Some of the clinical and epidemiological differences are listed in Tables 2 and 3. The pathogenesis o f early GBS sepsis is related to acquisition of the organism prior to or during birth. It is either carried on body surfaces and orifices during delivery or the amniotic fluid is infected from the ascending vaginal route in the presence of ruptured or apparently intact membranes. The organisms are aspirated into the bronchial tree in utero, initiating a pneumonia and bacteraemia. Of approximately 25% of mothers colonised at the time of delivery, transmission to the neonate occurs in about 50% of whom 0.2-2% become infected. Infants born to women who are heavily colonised are at a greater risk of infection. In late or delayed GBS infection, the organism may be transmitted at the time of delivery but is more likely to be acquired horizontally following birth from a colonised mother or other contacts, including nursery personnel. The nasopharynx is colonised before mucosal invasion and haematogenous dissemination.
Premature rupture of membranes Prolongedrupture of membranes (>18 hours) Chorioamnionitis Mat.ernatfever Fetaltachycardia Fetaldistress Prematurity Placentalabruption GBS colonisation
Early onset disease
Early onset disease usually manifests within the first 24 hours of life and has fulminating course with a high mortality. Greater that 50% of infection is clinically apparent at birth. There is a setting of obstetric complications and the risk factors in 70% of cases are shown in Table 4. The remaining cases occur in term infants in the absence of any risk factors, including infants delivered by caesarean section. The most frequent clinical presentation is of a newborn infant who develops respiratory distress a few hours following birth with tachypnoea, grunting and recession. Severe disease may resemble birth asphyxia, with a poor response to resuscitation, or manifest by respiratory failure, apnoea and shock soon after delivery. If not aggressively treated, hypotension is followed by poor perfusion and metabolic acidosis which has a poor prognosis. Initially the differential diagnosis includes respiratory distress syndrome, transient tachypnoea of the newborn, cyanotic heart disease or persistent pulmonary hypertension (PPHN) which may occur as a complication of the septicaemia in its own right. In 35% of cases the X-ray will show features of congenital pneumonia but in 50% it is indistinguishable from hyaline membrane disease. Features assisting the diagnosis include a background of obstetric complications, poor condition at birth with a low apgar score, neutropaenia, normal echocardiography, a pleural effusion and relatively compliant lungs with ventilation. Meningitis complicates early sepsis in proportion of cases and in the event of survival the sequelae of early-onset GBS meningitis comprise a similar spectrum to the late onset variety (see below).
36
Current Paediatrics
Management of acute sepsis
Septicaemia is a neonatal emergency demanding urgent and effective management with frequent reassessment and evaluation of response to therapy. Culture of blood, skin surfaces, and suprapubic urine should be followed by prompt IV antibiotic therapy. Lumbar puncture should be delayed until the infant is stable but should be performed at the earliest opportunity. Continuous monitoring of ECG, respiration, as well as invasive blood pressure monitoring and oxygen saturation are mandatory. Septicaemia is frequently complicated by shock which requires volume expansion with whole blood or fresh frozen plasma (FFP) followed by inotropic support. Ventilatory assistance is usually required. Fluid balance and administration must include measurement of urinary output, and take into account skin losses due to pyrexia or fluid retention due to renal failure and syndrome of inappropriate ADH. Metabolic acidosis should be partially corrected with sodium bicarbonate or THAM and disseminated intravascular coagulation treated with FFP and platelets. Therapy may be augmented with IV immunoglobulin or whole blood exchange but the results of studies for these interventions remain small equivocal. Trials are presently being undertaken to ascertain whether the white cell growth factors, G-CSF and GM-CSF are beneficial in cases where infants are neutropenic. Late onset disease
Late onset GBS sepsis usually presents as a neurological syndrome after the first week and up to 3 months of age. General features of poor feeding, fever and impaired consciousness with or without irritability are seen in the majority of cases. Neurological signs are secondary to cerebral oedema, meningeal inflammation, and ischaemic vascular injury. They include seizures, bulging fontanelle, extensor rigidity and focal signs, e.g. ophthalmoplegia, hemiparesis and cranial nerve palsy. Diagnosis is confirmed on lumbar puncture and blood culture. Principles of management are as for early onset disease with particular care to early detection of the specific neurologic complications. These relate to raised intracranial pressure, ventriculitis with localisation of infection, acute hydrocephalus and intracerebral mass, e.g. an abscess, infarct or subdural effusion. They may result in deterioration in the level of consciousness, failure to respond to antibiotic therapy and increase in head size. Table 5 Neurologicalsequelae
• • • • • • •
neurodevelopmentaldelay deafness hydrocephalus seizuredisorders spasticmono/quadraparesis corticalblindness microcephaly
Cerebral ultrasonography is valuable for serial non-invasive assessment, however neuroimaging using CT and MRI will yield greater anatomic detail. Electroencephalogram (EEG) and brain stem auditory evoked responses (BAER) may assist in assessment and prognosis. The mortality rate is approximately 10%. Of the survivors 50% are normal; 30% suffer mild to moderate neurological sequelae and 20% severe (Table 5). Features associated with poor prognosis are severe depression of consciousness, leucopaenia < 5 x 109/1 and neutropaenia <1 x 109/1. All survivors should receive regular neurodevelopmental follow-up, early hearing testing and if indicated, further imaging. Spectrum of neonatal GBS infection
Apart from the frequently described clinical syndromes, less frequent forms of GBS pathology have been described: asymptomatic bacteraemia, septic arthritis, osteomyelitis, ethmoiditis, orbital and facial cellulitis, empyema, and conjunctivitis.
Antibiotic treatment
Despite several decades of penicillin use, the group B streptococcus remains uniformly sensitive to penicillin. However, it should be noted that the minimum inhibitory concentrations (MIC) of penicillin for GBS (0.02-0.4 ~tg/ml) is higher than that for group A streptococci. GBS has also remained universally sensitive to cephalosporins, chloramphenicol and semi-synthetic penicillins such as amoxycillin. Less than 10% of isolated strains are erthyromycin resistant but the majority are now tetracycline resistant. GBS is resistant to aminoglycosides but when these agents are given in combination with a [3-1actam antimicrobial the combination is synergistic and leads to accelerated killing of GBS. There are few trials in the literature comparing different treatment regimens and any recommendation is therefore conjectural to some degree. Three important factors must be taken into account when proposing a treatment regimen: 1. GBS causes severe and potentially fatal infections. 2. Relapses, especially with focal infections have been well documented; 3. Very high bacterial colony counts in CSF are recognised (10 7 to 108 per ml) and these presumably require higher levels of antimicrobial than MIC tests might suggest. In practice, this means that GBS infections should be treated aggressively, high doses should be administered and therapy should not be stopped prematurely. The treatment of choice, especially when treating empirically immediately after birth should be penicillin or amoxycillin and an aminoglycoside such as gentamicin. Any of the cephalosporins used to treat newborn
Neonatal group B streptococcal infection infants such as cefotaxime and ceftazidime are also appropriate alternatives. Sepsis not involving any focal site should be treated for 10 days: therapy should be prolonged for 2-3 weeks in the case of meningitis and to 4 weeks in the presence of osteomyelitis. Prevention of infection
There has been considerable attention given to the possibility of preventing early onset GBS sepsis over the last decade by administering antimicrobial prophylaxis during labour. It is now certain that this approach can significantly reduce the number of cases of infection but this subject remains confused and controversial and as a result there is rarely a rational protocol in operation in hospitals. In countries such as the USA where the incidence of GBS infection is relatively high, the choice of a protocol to prevent GBS infections is easier than in countries such as Britain where the infection is relatively uncommon. Many of the protocols require the universal screening of all pregnant women for GBS carriage and this is an expensive approach as it is difficult to justify the cost in low-incidence areas. In addition, screening, when performed, is often done suboptimally, as explained above. There has also been some recent interest in rapid antigen screening tests for detecting GBS carriage at the oneset of labour. These tests are quick to perform and highly selective but are not sufficiently sensitive to reliably detect all carriage. However, onset of GBS sepsis is related to heaviness of carriage so it may be that these tests would be a satisfactory screening method but this has yet to be adequately tested in a trial. The rapid tests are also relatively expensive but probably no more than the true cost of conventional culture. What is important is that a standard protocol is adopted within every hospital. A number of options are given below in Table 6.
37
GBS adult infection
GBS colonisation of the female gastrointestinal and genital tracts is asymptomatic. However in pregnancy it may initiate disease; chorioamnionitis, stillbirth, post-partum endometritis, puerperal sepsis and urinary tract infection. Adult GBS infection unassociated with pregnancy is seen generally in the elderly or immunocompromised, particularly diabetes mellitus and involving the genitourinary tract. Infection may also occur in normal adults with significant morbidity and mortality; and includes endocarditis, pneumonia, soft tissue infections, septic arthritis, osteomyelitis, endophthalmitis and meningitis. Infections have a high incidence of bacteraemia but unlike neonates hypotension or shock are rare. FURTHER READING
Baker CJ. Group B Streptococcal Infections In: Stollerman GH, ed Advances in Internal Medicine, Vol.25. New York: Year Book Medical Publishers, Inc, 1980:475-501. Baker CJ. Group B streptococcal infections in newborn. Prevention at last? N Engl J Med 1986:314:1702 1704 Boyer KM, Gotoff SR Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chcmoprophylaxis. N Engl J Med 1986; 314(26):1665 1669. Easmon CSF, Hastings MJG. GBS colonisation in mothers and babies. Antibiot Chemother 1985; 35:28-39. Edwards MS, Rench MA, Haffar AA, Murphy MA, Desmond MM, Baker CJ. Long-term sequelae of group B streptococcal meningitis in infants. J Pediatr 1985; 106:717 722. Feldman RG, Fleer A. The immune response to the group B streptococcus. Rev Med Microbiol 1992; 3:52-58. Glvner LB, Nagaraj SK. Hyperimmune hmnan IgG or recombinant human granulocyte-macrophage colony-stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats. J Pediatr. 1993" 122:774-779. Gotoff SP, Boyer KM. Cellular and humoral aspects of host defence mechanisms against GBS. Antibiot Chemother. 1985; 35:142-156. Van Oppen C, Feldman R. Antibiotic prophylaxis of neonatal group B streptococcal refections [editorial]. BMJ. 1993; 306'411~412. Volpe JJ. Bacterial and Fungal Intracramal Infections. In: Neurology of the Newborn. United States; W.B. Saunders Company, 1995; Ch 21 73~766.
Table 6 Some alternatwe protocols for reducing the incidence of neonatal GBS infections. Protocol
Advantages
Disadvantages
Screen by culture during pregnancy. Administer amoxycillin to identified GBS carriers who also have an additional risk factor*
Well researched
Expensive Some cases still occur
AntlmicroNal prophylaxis to all women m labour
All cases are effectively covered
Excessive antibiotics administered
Antlmicrobial prophylaxis given to all women with risk factors
Cheap
Relatively large amounts of antibiotics prescribed Not tested in a trial
Screen by culture during pregnancy. Administer amoxycillin to all women who are identified as carriers
More potential cases covered rather than restricting prophylaxis to women with risk factors
Relatively large amounts of antibiotics prescribed. Expensive
Screen women with a risk factor with a rapid screening test at onset of labour. Administer antibiotic prophylaxis only to those women where the rapid test is positive
Targeted prophylaxis leading to restricted antibiotic usage
Not tested in a trim Relatively expenswe. Will miss some cases Not tested in trial
*Risk factors are maternal pyrexla, prolonged rupture of membranes and premature labour.
Mini-symposium: Infections
Neonatal group B streptococcal infection
R.M. Blumberg, R.G. Feldman
The group B streptococcus (GBS) is the commonest .bacterial infection in the first days of life in most centres in Europe, North America and Australia. The incidence of infection varies significantly between 0.3 per 1000 births in Britain and up to 5 per 1000 births in Southern USA. The immunological shortcomings of the newborn, accentuated in prematurity, and the virulence of the organism conspire to make the infant particularly vulnerable to this infection.
Table 1 Bacteriological identification characteristics of group B streptococcus
13-haemolysis CAMP factor* Growth on 40% bile agar Growth in 6.5% NaC1 broth Orange pigment when grown on Islam's medium Hydrolysis of arginine and hippurate Acid from glucose, maltose, sucrose, trehalose and glycerol *The CAMP factor is a soluble protein produced by GBS which enhances the action of staphylococcal [3-haemolysin on sheep erythrocytes.
Bacteriology GBS, also called Streptococcus agalactiae belongs to the genus Streptococcus. They are Gram-positive non-motile facultatively anaerobic cocci normally growing in chains and are often slightly elongated. The typical morphology in horse blood agar is a grey mucoid colony surrounded by a zone of ~-haemolysis of up to 2 mm. Table 1 lists the associated characteristics which can be used to identify GBS. The bacterium also possesses a unique carbohydrate which was first detected serologically by Lancefield in 1933. Lancefield showed that the ~haemolytic streptococci could be separated into a number of distinct serological groups and she classified S. agalaetiae as belonging to group B. The derivative of this serological investigation, now performed as a latex agglutination test, is the most common way in which group B streptococci are identified in diagnostic bacteriology laboratories. GBS also possess a polysaccharide capsule. This capsule coats the organism and has been shown to be of key importance in the pathogenesis of infection. There are several different capsular types of GBS; at
present eight varieties have been described, but the more common ones are Ia, Ib, II, III and V. Antibodies to the capsule, when present, protect against infection. Unfortunately, most adults do not possess protective levels of anti-capsular antibody. For example, 90% of women of child bearing age have sub-protective levels of antibody to the type III capsule. Little is known about the surface proteins of GBS. Most strains appear to possess one of a number of proteins which give the appearance of ladders when examined on an acrylamide gel. These include the 'CC and 'Rib' proteins. Some strains also possess an IgA binding protein. Many strains have bound and soluble forms of a C5a peptidase which inhibits macrophage recruitment.
Carriage The primary reservoir is the gastrointestinal tract but the vagina is also frequently colonised. The carriage rate varies to a limited degree geographically but differences are somewhat difficult to assess as methods of culture vary. In order to best assess carriage at the time of delivery, culture should be taken from the vagina and rectum and cultured in an enrichment medium before being plated out onto an agar plate. Most diagnostic laboratories in Britain do not routinely provide
Raoul M. Blumberg, MRCP Research Fellow, Department of Paediatrics and Neonatal Medicine Robert G. Feldman Phi), MRC Path, Senior Lecturer, Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School. Hammersmith Hospital, Du Cane Road, London, W12 ONN, Correspondence and requests for offprints to RGE
34
Neonatal group B streptococcal infection
35
Table 2 Climcaland epidemiologicaldifferencesbetweenearly and late onset group B streptococcalinfection Early sepsis
Late sepsis
Usual age of onset Maternal obstetriccomplications Prematurity Transmission Respiratory and cardiovascularsigns Neurologicalinvolvement Mortality Culture sites
<24 hours Common Common Vertical 90% 15% 20% Mucocutaneous, blood, CSF
Serotype
All serotypes
>7 days Uncommon Uncommon Horizontal/vertical 30% 85% 10% Infrequent isolation of organisms from sites other than blood and CSF PredominantlyserotypeIII
Table 3 Presentingfeatures of group B streptococcalinfection.
Table 4 Risk factors and obstetric comphcations
Early
Late
Respiratorydistress Cyanosis Apnoea Hypotension/poorperfusion Lethargy
Impaired consciousness Seizures Bulging fontanelle Extensorrigidity Focal signs
• • • • • • • • •
a culture method sensitive enough to reliably predict GBS carriage. When using sensitive culture techniques, the GBS carriage rate is 25-30% in both the U K and USA. Geographic variation in carriage therefore does not explain the differences in incidence in different countries. There are some racial differences and it appears that individuals of Afro-Caribbean descent have a slightly higher GBS carriage rate than Caucasians. The definitive explanation for the variation in incidence of GBS infection could be related to geographical strain differences or variation in the immune response to GBS antigens. Transmission to neonate
Historically the disease has been classified into early and late sepsis. Rather, it is a continuum, separated by time and mode of colonisation and immediate or delayed invasion of host defenses. Some of the clinical and epidemiological differences are listed in Tables 2 and 3. The pathogenesis o f early GBS sepsis is related to acquisition of the organism prior to or during birth. It is either carried on body surfaces and orifices during delivery or the amniotic fluid is infected from the ascending vaginal route in the presence of ruptured or apparently intact membranes. The organisms are aspirated into the bronchial tree in utero, initiating a pneumonia and bacteraemia. Of approximately 25% of mothers colonised at the time of delivery, transmission to the neonate occurs in about 50% of whom 0.2-2% become infected. Infants born to women who are heavily colonised are at a greater risk of infection. In late or delayed GBS infection, the organism may be transmitted at the time of delivery but is more likely to be acquired horizontally following birth from a colonised mother or other contacts, including nursery personnel. The nasopharynx is colonised before mucosal invasion and haematogenous dissemination.
Premature rupture of membranes Prolongedrupture of membranes (>18 hours) Chorioamnionitis Mat.ernatfever Fetaltachycardia Fetaldistress Prematurity Placentalabruption GBS colonisation
Early onset disease
Early onset disease usually manifests within the first 24 hours of life and has fulminating course with a high mortality. Greater that 50% of infection is clinically apparent at birth. There is a setting of obstetric complications and the risk factors in 70% of cases are shown in Table 4. The remaining cases occur in term infants in the absence of any risk factors, including infants delivered by caesarean section. The most frequent clinical presentation is of a newborn infant who develops respiratory distress a few hours following birth with tachypnoea, grunting and recession. Severe disease may resemble birth asphyxia, with a poor response to resuscitation, or manifest by respiratory failure, apnoea and shock soon after delivery. If not aggressively treated, hypotension is followed by poor perfusion and metabolic acidosis which has a poor prognosis. Initially the differential diagnosis includes respiratory distress syndrome, transient tachypnoea of the newborn, cyanotic heart disease or persistent pulmonary hypertension (PPHN) which may occur as a complication of the septicaemia in its own right. In 35% of cases the X-ray will show features of congenital pneumonia but in 50% it is indistinguishable from hyaline membrane disease. Features assisting the diagnosis include a background of obstetric complications, poor condition at birth with a low apgar score, neutropaenia, normal echocardiography, a pleural effusion and relatively compliant lungs with ventilation. Meningitis complicates early sepsis in proportion of cases and in the event of survival the sequelae of early-onset GBS meningitis comprise a similar spectrum to the late onset variety (see below).
36
Current Paediatrics
Management of acute sepsis
Septicaemia is a neonatal emergency demanding urgent and effective management with frequent reassessment and evaluation of response to therapy. Culture of blood, skin surfaces, and suprapubic urine should be followed by prompt IV antibiotic therapy. Lumbar puncture should be delayed until the infant is stable but should be performed at the earliest opportunity. Continuous monitoring of ECG, respiration, as well as invasive blood pressure monitoring and oxygen saturation are mandatory. Septicaemia is frequently complicated by shock which requires volume expansion with whole blood or fresh frozen plasma (FFP) followed by inotropic support. Ventilatory assistance is usually required. Fluid balance and administration must include measurement of urinary output, and take into account skin losses due to pyrexia or fluid retention due to renal failure and syndrome of inappropriate ADH. Metabolic acidosis should be partially corrected with sodium bicarbonate or THAM and disseminated intravascular coagulation treated with FFP and platelets. Therapy may be augmented with IV immunoglobulin or whole blood exchange but the results of studies for these interventions remain small equivocal. Trials are presently being undertaken to ascertain whether the white cell growth factors, G-CSF and GM-CSF are beneficial in cases where infants are neutropenic. Late onset disease
Late onset GBS sepsis usually presents as a neurological syndrome after the first week and up to 3 months of age. General features of poor feeding, fever and impaired consciousness with or without irritability are seen in the majority of cases. Neurological signs are secondary to cerebral oedema, meningeal inflammation, and ischaemic vascular injury. They include seizures, bulging fontanelle, extensor rigidity and focal signs, e.g. ophthalmoplegia, hemiparesis and cranial nerve palsy. Diagnosis is confirmed on lumbar puncture and blood culture. Principles of management are as for early onset disease with particular care to early detection of the specific neurologic complications. These relate to raised intracranial pressure, ventriculitis with localisation of infection, acute hydrocephalus and intracerebral mass, e.g. an abscess, infarct or subdural effusion. They may result in deterioration in the level of consciousness, failure to respond to antibiotic therapy and increase in head size. Table 5 Neurologicalsequelae
• • • • • • •
neurodevelopmentaldelay deafness hydrocephalus seizuredisorders spasticmono/quadraparesis corticalblindness microcephaly
Cerebral ultrasonography is valuable for serial non-invasive assessment, however neuroimaging using CT and MRI will yield greater anatomic detail. Electroencephalogram (EEG) and brain stem auditory evoked responses (BAER) may assist in assessment and prognosis. The mortality rate is approximately 10%. Of the survivors 50% are normal; 30% suffer mild to moderate neurological sequelae and 20% severe (Table 5). Features associated with poor prognosis are severe depression of consciousness, leucopaenia < 5 x 109/1 and neutropaenia <1 x 109/1. All survivors should receive regular neurodevelopmental follow-up, early hearing testing and if indicated, further imaging. Spectrum of neonatal GBS infection
Apart from the frequently described clinical syndromes, less frequent forms of GBS pathology have been described: asymptomatic bacteraemia, septic arthritis, osteomyelitis, ethmoiditis, orbital and facial cellulitis, empyema, and conjunctivitis.
Antibiotic treatment
Despite several decades of penicillin use, the group B streptococcus remains uniformly sensitive to penicillin. However, it should be noted that the minimum inhibitory concentrations (MIC) of penicillin for GBS (0.02-0.4 ~tg/ml) is higher than that for group A streptococci. GBS has also remained universally sensitive to cephalosporins, chloramphenicol and semi-synthetic penicillins such as amoxycillin. Less than 10% of isolated strains are erthyromycin resistant but the majority are now tetracycline resistant. GBS is resistant to aminoglycosides but when these agents are given in combination with a [3-1actam antimicrobial the combination is synergistic and leads to accelerated killing of GBS. There are few trials in the literature comparing different treatment regimens and any recommendation is therefore conjectural to some degree. Three important factors must be taken into account when proposing a treatment regimen: 1. GBS causes severe and potentially fatal infections. 2. Relapses, especially with focal infections have been well documented; 3. Very high bacterial colony counts in CSF are recognised (10 7 to 108 per ml) and these presumably require higher levels of antimicrobial than MIC tests might suggest. In practice, this means that GBS infections should be treated aggressively, high doses should be administered and therapy should not be stopped prematurely. The treatment of choice, especially when treating empirically immediately after birth should be penicillin or amoxycillin and an aminoglycoside such as gentamicin. Any of the cephalosporins used to treat newborn
Neonatal group B streptococcal infection infants such as cefotaxime and ceftazidime are also appropriate alternatives. Sepsis not involving any focal site should be treated for 10 days: therapy should be prolonged for 2-3 weeks in the case of meningitis and to 4 weeks in the presence of osteomyelitis. Prevention of infection
There has been considerable attention given to the possibility of preventing early onset GBS sepsis over the last decade by administering antimicrobial prophylaxis during labour. It is now certain that this approach can significantly reduce the number of cases of infection but this subject remains confused and controversial and as a result there is rarely a rational protocol in operation in hospitals. In countries such as the USA where the incidence of GBS infection is relatively high, the choice of a protocol to prevent GBS infections is easier than in countries such as Britain where the infection is relatively uncommon. Many of the protocols require the universal screening of all pregnant women for GBS carriage and this is an expensive approach as it is difficult to justify the cost in low-incidence areas. In addition, screening, when performed, is often done suboptimally, as explained above. There has also been some recent interest in rapid antigen screening tests for detecting GBS carriage at the oneset of labour. These tests are quick to perform and highly selective but are not sufficiently sensitive to reliably detect all carriage. However, onset of GBS sepsis is related to heaviness of carriage so it may be that these tests would be a satisfactory screening method but this has yet to be adequately tested in a trial. The rapid tests are also relatively expensive but probably no more than the true cost of conventional culture. What is important is that a standard protocol is adopted within every hospital. A number of options are given below in Table 6.
37
GBS adult infection
GBS colonisation of the female gastrointestinal and genital tracts is asymptomatic. However in pregnancy it may initiate disease; chorioamnionitis, stillbirth, post-partum endometritis, puerperal sepsis and urinary tract infection. Adult GBS infection unassociated with pregnancy is seen generally in the elderly or immunocompromised, particularly diabetes mellitus and involving the genitourinary tract. Infection may also occur in normal adults with significant morbidity and mortality; and includes endocarditis, pneumonia, soft tissue infections, septic arthritis, osteomyelitis, endophthalmitis and meningitis. Infections have a high incidence of bacteraemia but unlike neonates hypotension or shock are rare. FURTHER READING
Baker CJ. Group B Streptococcal Infections In: Stollerman GH, ed Advances in Internal Medicine, Vol.25. New York: Year Book Medical Publishers, Inc, 1980:475-501. Baker CJ. Group B streptococcal infections in newborn. Prevention at last? N Engl J Med 1986:314:1702 1704 Boyer KM, Gotoff SR Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chcmoprophylaxis. N Engl J Med 1986; 314(26):1665 1669. Easmon CSF, Hastings MJG. GBS colonisation in mothers and babies. Antibiot Chemother 1985; 35:28-39. Edwards MS, Rench MA, Haffar AA, Murphy MA, Desmond MM, Baker CJ. Long-term sequelae of group B streptococcal meningitis in infants. J Pediatr 1985; 106:717 722. Feldman RG, Fleer A. The immune response to the group B streptococcus. Rev Med Microbiol 1992; 3:52-58. Glvner LB, Nagaraj SK. Hyperimmune hmnan IgG or recombinant human granulocyte-macrophage colony-stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats. J Pediatr. 1993" 122:774-779. Gotoff SP, Boyer KM. Cellular and humoral aspects of host defence mechanisms against GBS. Antibiot Chemother. 1985; 35:142-156. Van Oppen C, Feldman R. Antibiotic prophylaxis of neonatal group B streptococcal refections [editorial]. BMJ. 1993; 306'411~412. Volpe JJ. Bacterial and Fungal Intracramal Infections. In: Neurology of the Newborn. United States; W.B. Saunders Company, 1995; Ch 21 73~766.
Table 6 Some alternatwe protocols for reducing the incidence of neonatal GBS infections. Protocol
Advantages
Disadvantages
Screen by culture during pregnancy. Administer amoxycillin to identified GBS carriers who also have an additional risk factor*
Well researched
Expensive Some cases still occur
AntlmicroNal prophylaxis to all women m labour
All cases are effectively covered
Excessive antibiotics administered
Antlmicrobial prophylaxis given to all women with risk factors
Cheap
Relatively large amounts of antibiotics prescribed Not tested in a trial
Screen by culture during pregnancy. Administer amoxycillin to all women who are identified as carriers
More potential cases covered rather than restricting prophylaxis to women with risk factors
Relatively large amounts of antibiotics prescribed. Expensive
Screen women with a risk factor with a rapid screening test at onset of labour. Administer antibiotic prophylaxis only to those women where the rapid test is positive
Targeted prophylaxis leading to restricted antibiotic usage
Not tested in a trim Relatively expenswe. Will miss some cases Not tested in trial
*Risk factors are maternal pyrexla, prolonged rupture of membranes and premature labour.