Group B streptococcal infection overview

# Overview
Despite substantial progress in prevention of perinatal Group B Streptococal (GBS) disease since the 1990s, GBS remains the leading cause of early-onset neonatal sepsis in the United States.  Universal screening at 35--37 weeks' gestation for maternal GBS colonization and use of intrapartum antibiotic prophylaxis has resulted in substantial reductions in the burden of early-onset GBS disease among newborns. Although early-onset GBS disease has become relatively uncommon in recent years, the rates of maternal GBS colonization (and therefore the risk for early-onset GBS disease in the absence of intrapartum antibiotic prophylaxis) remain unchanged since the 1970s. Continued efforts are needed to sustain and improve on the progress achieved in the prevention of GBS disease. There also is a need to monitor for potential adverse consequences of intrapartum antibiotic prophylaxis (e.g., emergence of bacterial antimicrobial resistance or increased incidence or severity of non-GBS neonatal pathogens). In the absence of a licensed GBS vaccine, universal screening and intrapartum antibiotic prophylaxis continue to be the cornerstones of early-onset GBS disease prevention.

# Historical Perspective
In the 1970s, the bacterium GBS emerged as the leading infectious cause of early neonatal morbidity and mortality in the United States.  Beginning in the mid 1980s, clinical trials and well-designed observational studies demonstrated that administering intravenous antibiotics during labor to women at risk for transmitting GBS to their newborns could prevent invasive disease in the first week of life (i.e., early-onset disease).  As a result of the collaborative efforts of clinicians, researchers, professional organizations, parent advocacy groups, and the public health community in the 1990s, recommendations for intrapartum prophylaxis to prevent perinatal GBS disease were issued in 1996 by the American College of Obstetricians and Gynecologists (ACOG) and CDC and in 1997 by the American Academy of Pediatrics (AAP). Revised guidelines for the prevention of early-onset GBS disease issued in 2002 recommended universal culture-based screening of all pregnant women at 35-37 weeks gestation to optimize the identification of women who should receive intrapartum antibiotic prophylaxis.  The most recent CDC guidelines were published in 2010.

# Classification
GBS infection can be classified into three main categories depending on the type of affected subjects.  GBS infection can occur in pregnant women, neonates, or non-pregnant adults mainly the elderly.  Neonatal GBS infection can be further classified into early-onset or late-onset depending on the timing of the onset of the symptoms.  Infections in newborns occurring within the first week of life are designated as early-onset disease, whereas late-onset infections occur in infants aged >1 week, with most infections evident during the first 3 months of life. 

# Pathophysiology
The gastrointestinal tract serves as the primary reservoir for GBS and is the likely source of vaginal colonization.  Early-onset neonatal infections are acquired vertically through exposure to GBS from the vagina of a colonized woman.  GBS is characterized by its ability to adhere to epithelial surfaces, such as the vagina, placental membranes, blood brain barrier, and respiratory tract.  GBS can penetrate the host cell barriers and evade the host's immune response.  The polysaccharide antiphagocytic capsule is this bacterium's main virulence factor.

# Causes
GBS disease is caused by the infection with the bacterium GBS which is a beta hemolytic gram-positive streptococcus characterized by the presence of group B Lancefield antigen. GBS displays beta-hemolysis when cultured on a blood agar plate and produces zones of hemolysis that are only slightly larger than the colonies themselves. The species other name S. agalactiae, where "agalactiae" means "no milk", alludes to this.  GBS hydrolyzes sodium hippurate and gives a positive response in the CAMP test. GBS is also sensitive to bile and will lyse in its presence.  GBS is a species of the normal flora of the gut and female urogenital tract.  The polysaccharide antiphagocytic capsule is this bacterium's main virulence factor.

# Differential Diagnosis
GBS infection causes a wide variety of clinical presentations depending on the type of the affected subjects; therefore, the differential diagnosis of GBS infection varies based on the age of the patient and their health condition.  Early-onset GBS infection in neonates might lead to pneumonia, meningitis, or sepsis and it must be differentiated from other types of infectious agents in this category of patients.

# Epidemiology and Demographics
GBS causes invasive disease primarily in infants, pregnant or postpartum women, and older adults, with the highest incidence among young infants.  Before active prevention was initiated, an estimated 7,500 cases of neonatal GBS disease occurred annually in the United States. Striking declines in disease incidence coincided with increased prevention activities in the 1990s, and a further reduction occurred following the issuance of the recommendation for universal screening in 2002.  However, GBS disease remains the leading infectious cause of morbidity and mortality among newborns in the United States.  The continued burden of disease and newly available data relevant to early-onset GBS disease prevention from the fields of epidemiology, obstetrics, neonatology, microbiology, molecular biology, and pharmacology prompted revision of the guidelines for early-onset GBS disease prevention.

# Risk Factors
Maternal intrapartum GBS colonization is the primary risk factor for early-onset disease in infants.  Additional risk factors for early-onset disease in infants include gestational age < 37 completed weeks, longer duration of membrane rupture, intra-amniotic infection, young maternal age, and black race.

# Screening
The Center of Disease Control and Prevention (CDC)'s screening guidelines for GBS infection recommend universal culture-based screening for all pregnant women for vaginal and rectal GBS colonization in order to determine which women should receive intrapartum GBS chemoprophylaxis. CDC recommended that women with unknown GBS colonization status at the time of delivery be managed according to the presence of intrapartum risk factors.  CDC's guidelines recommend screening for vaginal and rectal GBS colonization at 35-37 weeks' gestation.  Swabbing both the lower vagina and rectum (through the anal sphincter) increases the culture yield substantially compared with sampling the cervix or the vagina without also swabbing the rectum.  Routine screening for asymptomatic bacteriuria is recommended in pregnant women, and laboratories should screen urine culture specimens for the presence of GBS in concentrations of 104 colony-forming units (cfu)/ml or greater.

# Natural History, Complications and Prognosis
GBS is the leading infectious cause of morbidity and mortality among infants in the United States, particularly among preterm neonates. Most newborns with early-onset disease have symptoms on the day of birth. Babies who develop late-onset disease may appear healthy at birth and develop symptoms of GBS disease after the first week of life.

# Diagnosis

## History and Symptoms
Symptoms of GBS infection in neonates include apnea, bluish color to skin, cold skin, difficulty breathing, difficulty feeding, and irritability. GBS infection in pregnancy is most commonly asymptomatic.  If the adult patient is symptomatic, the constellation of symptoms depends on the type of infection GBS is causing.

## Physical Examination
The physical examination of neonates with GBS infection reveals lethargy, cyanosis, an unstable temperature that can be either high or low, tachycardia, and breathing difficulty.  The breathing difficulty is manifested by flaring of the nostrils, grunting, and tachypnea with short periods of apnea.  Hypotension might also be present.  In case of early-onset GBS infection, the 5 minutes apgar score of the newborn may be low.

## Laboratory Findings
Any newborn with signs of sepsis should receive a full diagnostic evaluation and receive antibiotic therapy pending the results of the evaluation, regardless of the maternal GBS colonization status.  Well-appearing newborns whose mothers had suspected chorioamnionitis should undergo a limited diagnostic evaluation and receive antibiotic therapy pending culture results.  No routine diagnostic testing for GBS is recommended among well-looking infants unless either the gestational age is <37 weeks or the duration of membrane rupture before delivery was 18 hours.  The diagnosis of GBS infection is confirmed by the isolation of the organism in either the blood or the cerebrospinal fluid (CSF).

# Treatment

## Medical Therapy
GBS infection should be suspected as a causative agent for bacterial meningitis in infants less than two years of age, among whom empirical antibiotic therapy should be initiated immediately.  Ampicillin or penicillin are recommended for the treatment of confirmed neonatal GBS meningitis.  Intrapartum antibiotic treatment should be administered to asymptomatic pregnant women who are carriers of GBS because it provides prophylaxis against the transmission of the infection to the neonate.  Penicillin remains the agent of choice for intrapartum antibiotic prophylaxis, with ampicillin as an acceptable alternative.  Penicillin and ampicillin are generally effective for the treatment of GBS infection in non-pregnant adults.

## Primary Prevention
Penicillin remains the agent of choice for intrapartum antibiotic prophylaxis for the primary prevention of early-onset GBS infection, with ampicillin as an acceptable alternative.  Penicillin-allergic women who do not have a history of anaphylaxis, angioedema, respiratory distress, or urticaria following the administration of a penicillin or a cephalosporin should receive cefazolin.  Antimicrobial susceptibility testing should be ordered for antenatal GBS cultures performed on penicillin-allergic women at high risk for anaphylaxis because of a history of anaphylaxis, angioedema, respiratory distress, or urticaria following the administration of a penicillin or a cephalosporin.  Penicillin-allergic women at high risk for anaphylaxis should receive clindamycin if their GBS isolate is susceptible to clindamycin and erythromycin, as determined by antimicrobial susceptibility testing; if the isolate is sensitive to clindamycin but resistant to erythromycin, clindamycin may be used if testing for inducible clindamycin resistance is negative. Penicillin-allergic women at high risk for anaphylaxis should receive vancomycin if their isolate is intrinsically resistant to clindamycin as determined by antimicrobial susceptibility testing, if the isolate demonstrates inducible resistance to clindamycin, or if susceptibility to both agents is unknown.  GBS vaccines have been investigated as a tool for reducing maternal colonization and preventing transmission to neonates; however, no licensed vaccine is available currently. The measures used to prevent early-onset GBS disease also might prevent some perinatal maternal infections; however, they do not prevent late-onset infant disease.

## Secondary Prevention
Currently available GBS infection prevention strategies will not prevent all cases of early-onset disease. Rapid detection of neonatal infections and initiation of appropriate treatment is needed to minimize morbidity and mortality among the cases that continue to occur.  Any newborn with signs of sepsis should receive a full diagnostic evaluation and receive antibiotic therapy pending the results of the evaluation, regardless of the maternal colonization status.  Well-appearing newborns whose mothers had suspected chorioamnionitis should undergo a limited evaluation and receive antibiotic therapy pending culture results.  Well-appearing infants whose mothers had no chorioamnionitis and no indication for GBS prophylaxis should be managed according to routine clinical care.  Well-appearing infants of any gestational age whose mother received adequate intrapartum GBS prophylaxis (4 hours of penicillin, ampicillin, or cefazolin before delivery) should be observed for 48 hours, and no routine diagnostic testing is recommended.  For well-appearing infants born to mothers who had an indication for GBS prophylaxis but received no or inadequate prophylaxis, if the infant is well-appearing and 37 weeks and 0 days' gestational age and the duration of membrane rupture before delivery was <18 hours, then the infant should be observed for 48 hours, and no routine diagnostic testing is recommended. If the infant is well-appearing and either <37 weeks and 0 days' gestational age or the duration of membrane rupture before delivery was 18 hours, then the infant should undergo a limited evaluation and observation for 48 hours.

## Future or Investigational Therapies
GBS vaccines have been investigated as a tool for reducing maternal colonization and preventing transmission to neonates; however, no licensed vaccine is available currently.  Phase I and II clinical trials among healthy, non-pregnant adults of monovalent polysaccharide-protein conjugate vaccines of GBS disease-associated types have shown these vaccines to be well tolerated and immunogenic.  A recent, double-blind randomized trial of a conjugate vaccine against GBS serotype III among non-pregnant women of reproductive age found a significant delay in acquisition of colonization with the vaccine-serotype among vaccine recipients.