Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Streptococcus agalactiae (Group B Streptococcus )
The Pathogen and Pathogenicity
Streptococcus agalactiae is the species designation for Lancefield group B Streptococcus (GBS). Colonies appear on sheep blood agar as 3- to 4-mm, grey-white colonies typically with a narrow zone of β-hemolysis; organisms are gram-positive cocci. The group B–specific cell wall carbohydrate antigen is common to all strains, and a surface capsular polysaccharide (CPS) allows classification into serotypes Ia, Ib, II, III, IV, V, VI, VII, VIII, and IX. Surface proteins are numerous and include Alp-like proteins and Rib in addition to pilus islands (PI-1, PI-2a, PI-2b) that facilitate attachment to mucosal surfaces. GBS capsular types also can be characterized by whole genome sequencing into clonal complexes and sequence types.
Pilus island proteins are found in all GBS strains of human origin. Antibodies to pili and some Alps confer protection in experimental infection, suggesting that they play an important role in mediating invasion. , Some Alps mediate translocation across epithelial barriers; GBS also can use a paracellular route by transiently opening cell junctions. , The β-hemolysin/cytolysin forms pores that compromise epithelial and endothelial barrier function. ,
High-virulence clones of GBS have emerged. The hypervirulent clonal complex ST-17, almost always associated with type III strains, has a tropism for meninges and typically is found among invasive but not colonizing young infant isolates. CPSs allow the organism to evade ingestion by host phagocytic cells. GBS suppresses phagocyte function and promotes bacterial survival by engaging host sialic acid–recognizing immunoglobulin superfamily inhibitory lectins. , Antibodies to CPSs are protective in animal models, and the risk for invasive infection in neonates correlates with low concentrations of maternal antibodies to the infecting GBS CPS in clinical studies. ,
The presence of GBS in the maternal genital tract at delivery is critical to early-onset neonatal infection. Early-onset infection occurs in an estimated 1% of neonates born to mothers with GBS vaginal or rectal colonization at delivery who do not receive intrapartum antibiotic prophylaxis (IAP). Replication of organisms in association with maternal chorioamnionitis further enhances fetal/infant risk. The incidence of early-onset disease is influenced by a number of factors ( Table 119.1 ). The higher the genital inoculum, longer the duration of exposure, and shorter the gestation of the infant, the greater the risk of invasive neonatal infection.
TABLE 119.1
Pathogenesis of Early-Onset Group B Streptococcus Infection
| Feature | Comment |
|---|---|
| Strain virulence | Clonal virulence; capsule type (e.g., III), amount of capsule and hemolysin production, surface components (e.g., sialic acid, Alp proteins, hemolysin, pili, among others) enhance virulence by facilitating invasion and downregulating immune responsiveness |
| Inoculum size | Risk correlates with a high density of maternal vaginal colonization |
| Premature rupture of membranes | Risk of infection increases with rupture of membranes >1 hr before the onset of labor |
| Preterm delivery | Risk correlates inversely with gestational age |
| Prolonged rupture of membranes | Risk increases when membranes are ruptured ≥18 hr before delivery |
| Maternal bacteriuria (≥10 5 cfu/mL) due to group B Streptococcus during pregnancy | Risk increases because bacteriuria correlates with high density maternal genital colonization, premature rupture of placental membranes, and preterm delivery |
| Serum concentrations of immunoglobulin G to colonizing capsular polysaccharide type | Risk correlates inversely with levels of maternal serum immunoglobulin G to the capsular polysaccharide of the colonizing strain |
As in early-onset infection, low concentrations of antibody to type III CPS are found uniformly in sera obtained during the acute phase of illness from infants with late or very late-onset infection. A viral infection preceding development may alter epithelial surfaces in a way that promotes the entry of GBS into the bloodstream. Extended hospitalization, as is required by very low birth weight infants, enhances the risk of healthcare exposure to GBS if hand hygiene is not optimal.
Epidemiology
Depending on the culture method used, body site sampled and population studied, GBS can be isolated from the maternal genital or lower gastrointestinal tract in 18%–35% of pregnant women. When specimens are obtained from the rectum and lower vagina rather than the cervix, and when a selective antibiotic-containing broth medium is used rather than solid agar, colonization detection rates increase by 30%–50%. Culture specimens obtained within 5 weeks before term gestation optimize the sensitivity in predicting colonization at delivery.
Neonates acquire colonization with GBS vertically, either in utero by the ascending route shortly before birth or at delivery. Heavy maternal colonization, intrapartum fever, African American ethnicity, and lack of IAP are associated with transmission. Uninterrupted, the rate of vertical transmission of colonization from a mother colonized with GBS to an infant at delivery averages 50%. Infants born to mothers heavily colonized with GBS (≥10 5 colony-forming units per milliliter [CFUs/mL]) or who have characteristics listed in Table 119.1 are at enhanced risk for invasive infection. Acquisition of colonization by infants can occur from the mother or other household contacts after hospital discharge. Whether late-onset disease results from an exogenous source, such as breast milk, or from established colonization or both is controversial. The synchrony of recurrent disease in twins and the detection of GBS DNA in breast milk suggest that an enteral mode of acquisition can occur in some cases. The incidence of early-onset GBS disease (within the first 6 days of life) has declined by 80% compared with the pre-prevention era baseline rate in 1993. In 2018, the incidence was 0.25 cases per 1000 live births. Attack rates for early-onset disease are related inversely to birth weight and can exceed 20 per 1000 live births in infants weighing <1000 g. Because of the reduction in early-onset disease by IAP and the ineffectiveness of IAP for late-onset disease (7–89 days of age), the latter are equal to or slightly greater than early-onset cases. GBS infections in infants 3 months of age or older (very late-onset) occur primarily among those requiring prolonged hospitalization for complications of extreme prematurity.
The distribution of capsular types among isolates causing early-onset disease parallels that of organisms colonizing the maternal genital tract. The CPSs that most commonly cause early-onset cases, as reported by the Centers for Disease Control and Prevention (CDC) during 2006–2015, were Ia (27%), Ib (9%), II (16%), III (27%), IV (7%), and V (14%). For late-onset infections, CPS III accounted for 56% of cases; the remainder of cases were caused by Ia (20%), Ib (6%), II (3%), IV (6%), and V (8%). Infections occur occasionally in epidemic clusters; the associated GBS types are similar to those that cause late-onset disease. ,
Clinical Manifestations
Early-Onset Infection
Early-onset GBS infection is associated commonly with maternal obstetric complications ( Table 119.2 ). The presenting signs, such as lethargy, tachypnea or apnea, bradycardia, and poor feeding, are indistinguishable from the signs of infections caused by other bacteria. Irritability and hyperthermia are noted more often in term than preterm infants ( Table 119.3 ), and bacteremia without signs of infection occurs almost exclusively in term infants. Regardless of the age of onset and focus of infection, respiratory distress often occurs in infants with early-onset infection. Radiographic findings can be consistent with pneumonia, respiratory distress syndrome, transient tachypnea of the neonate, or meconium aspiration.
TABLE 119.2
Comparison of Early-, Late-, and Very Late-Onset Group B Streptococcus Infections
| Feature | Early-Onset | Late-Onset | Very Late-Onset |
|---|---|---|---|
| Age range | <7 days | 7–89 days | ≥3 mo |
| Median age at onset | 1 day | 37 days | Unknown |
| Maternal obstetric complications | Common | Preterm delivery | Preterm delivery |
| Frequency of gestation <37 wk | Frequent (∼20%) | Frequent (∼50%) | Almost always |
| Usual clinical presentations | Septicemia (80%–85%) Meningitis (5%–10%) Pneumonia (10%–15%) |
Meningitis (25%–35%) Bloodstream infection without focus (65%) Soft tissue, bone, joint infection, or pneumonia (5%–10%) |
Bloodstream infection without focus (common) with a focus (occasional) a |
| Common capsular types | Ia, II, III, V | III (>50%), Ia, V | III, Ia, V |
| Mortality rate | 2%–19% b | 3%–8% | Low |
Modified from Edwards MS, Nizet V, Baker CJ. Group B streptococcal infections. In: Wilson CB, Nizet V, Maldonado VY, et al. (eds). Infectious Diseases of the Fetus and Newborn Infant . 8th ed. Philadelphia, PA: Elsevier Saunders; 2016:411–456.
a Includes peritoneum, urinary tract, skin and soft tissue, and central nervous system.
TABLE 119.3
Clinical Features of Early-Onset Group B Streptococcus Infection
| Features | Term | Preterm |
|---|---|---|
| Respiratory distress | +++ | ++ |
| Lethargy or poor tone | ++ | +++ |
| Cyanosis | ++ | ++ |
| Poor feeding | ++ | ++ |
| Apnea or bradycardia | + | ++ |
| Poor perfusion | + | ++ |
| Hypotension | + | ++ |
| Irritability | + | – |
| Hyperthermia | + | – |
| Healthy appearing | + | – |
+++, most common; ++, commonly observed (25%–50%); +, occasionally observed (10%–25%); –, rarely observed.
The clinical syndromes commonly associated with early-onset infection are bloodstream infection (BSI) without a focus (with shock in about 25% of cases), pneumonia, and meningitis. , Payne and colleagues identified 6 features that predict a fatal outcome in early-onset disease: (1) birth weight <2500 g, (2) absolute neutrophil count <1500 cells/μL, (3) hypotension, (4) apnea, (5) initial pH <7.25, and (6) demonstration of pleural effusion on initial chest radiograph.
Late-Onset Infection
The median age of onset for late-onset disease is 37 days. Affected term infants usually have an unremarkable early neonatal course. BSI without a focus is the most common presentation, but meningitis occurs in about 30% of cases. Characteristic features are fever, poor feeding, and irritability; infants usually recover uneventfully with antimicrobial and supportive therapy. Infants with meningitis can have similar presenting features, but some have a fulminant onset and rapid progression. In these infants, the presenting features can include poor color, grunting, altered level of consciousness, apnea, or seizures. A number of presenting clinical or laboratory findings are associated with a fatal outcome or abnormal neurologic examination at hospital discharge for infants with GBS meningitis ( Table 119.4 ). Seizures at admission remains a significant risk factor for poor outcome in multivariate analysis.
TABLE 119.4
Features at Admission That Predict an Adverse Early Outcome for Infants With Group B Streptococcus Meningitis a
| Feature | Comment |
|---|---|
| Need for pressor therapy | Indicates advanced or overwhelming infection |
| Coma or semicoma | Indicates advanced or overwhelming infection |
| Seizures | Indicates cerebritis |
| Pallor | Surrogate for shock |
| Low CSF glucose | <20 mg/dL |
| Elevated CSF protein | ≥300 mg/dL |
CSF, cerebrospinal fluid.
Several other foci of infection can occur in late-onset disease, including osteomyelitis, arthritis, and cellulitis-adenitis syndrome. Osteomyelitis has an indolent presentation, with diminished mobility of an extremity or pain with motion that has been present for weeks before diagnosis. The proximal humerus is the most frequent site in osteomyelitis; less frequently, the long bones of the lower extremities and flat or small bones are involved. This focal manifestation has become rare in the era of maternal IAP.
The mean age at diagnosis of pyogenic arthritis is 20 days. The duration of signs of infection is usually several days, and the hip and knee joints are common sites of involvement. GBS cellulitis-adenitis syndrome usually is unilateral, involving facial or submandibular sites, although inguinal, scrotal, and prepatellar sites have been described. Presenting signs include poor feeding, irritability, and fever. Affected infants typically have a BSI (∼90% of cases), and aspiration of the involved soft tissue or lymph node often yields the organism. Abscesses can form, necessitating surgical drainage.
A number of less common or unusual foci of infection have been reported, including urinary tract infection with or without associated structural abnormalities, endocarditis, otitis media, necrotizing fasciitis, and others. Isolation of GBS from a normally sterile body site should be considered indicative of invasive infection.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here