OVERVIEW: What every clinician needs to know

Pathogen name and classification

Streptococcus agalactiae or group B streptococcus (GBS)—a gram-positive, β-hemolytic organism in the Streptococcus genus that carries the Lancefield group B antigen. GBS are encapsulated organisms and ten antigenically distinct capsular serotypes have been described (1a, 1b, II–IX).

What is the best treatment?

What are the preferred anti-infective agent or agents and why?

GBS isolates are susceptible to penicillin, ampicillin, and other β-lactams, and penicillin/ampicillin remain the drugs of choice in non-penicillin allergic patients.

Are there issues of anti-infective resistance?

Recently, a small number of GBS isolates with reduced susceptibility to one or more β-lactam antibiotics have been described in the United States, Japan, and elsewhere. The prevalence of isolates with elevated minimum inhibitory concentrations (MICs) to penicillin or cephalosporins is currently extremely low, although recent increases have been documented, with the prevalence of penicillin resistance reported in Japan rising from 4.5% in 2007 to 6.6% in 2013. In the United States, incidence of reduced β-lactam susceptibility remains below 1% in surveys of both sterile and nonsterile site isolates, distributed among multiple capsular serotypes. The clinical relevance of GBS isolates with increased (but within the susceptible range) MICs is unclear.
The prevalence of erythromycin and clindamycin resistance in the United States is significant, ranging between 25 to 52% and 12 to 41%, respectively, in recent reports and resistance rates have been rising. Resistance to erythromycin and clindamycin has traditionally been associated with capsule serotype V, a serotype more commonly seen in GBS disease in nonpregnant adults, although increasing resistance among serotype IV isolates has recently been noted. The majority of GBS isolates are resistant to tetracycline. While fluoroquinolone resistance among isolates from invasive GBS disease in nonpregnant adults is low (1.2%) in the United States, fluoroquinolone resistant GBS (predominantly a highly clonal serotype 1b strain) accounted for approximately 24% of invasive isolates from a surveillance program in Japan and 33% in a study of invasive isolates in South Korea. The first two cases of GBS isolates with vancomycin resistance were reported in 2014, but vancomycin resistance remains extremely rare.

What are the mechanisms underlying resistance?

Resistance of GBS to erythromycin and clindamycin is mediated most commonly by two mechanisms:
Related Content

antibiotic target-site modification by 23S rRNA methylases encoded by erm genes (ermB, ermA, ermTR), resulting in either constitutively expressed or erythromycin-induced resistance to macrolides, lincosamides, and streptogramins—the MLS phenotype

a macrolide efflux pump encoded by the mefA/E genes, that confers only macrolide resistance (clindamycin susceptible)—the M phenotype
The erm-mediated target modification is the most common mechanism of resistance in GBS and results in significantly higher erythromycin MICs. Two mutations, one in the parC gene (producing amino acid substitution Ser₇₉Phe) and the other in gyrA (producing amino acid substitution Ser₈₁Leu) together mediate fluoroquinolone resistance in GBS.
Similar to penicillin-resistant S. pneumoniae (the pneumococcus), GBS isolates with reduced susceptibility to β-lactams demonstrate changes in penicillin binding proteins (PBPs) that are responsible for catalyzing the final steps of bacterial cell wall peptidoglycan synthesis. Alterations in the transpeptidase domain of the catalytic center result in reduced affinity for β-lactam antibiotics. A number of amino acid substitutions, particularly V405A and Q557E in PBP 2B, have been linked with reduced susceptibility to β-lactams in GBS and mutations within PBPs 2B, 2X, and 1A have been demonstrated within at least three distinct genetic lineages. Several of the PBP amino acid changes mirror alterations identified in the pneumococcus that have been linked to penicillin and cefotaxime resistance. However, in contrast to the mosaic pattern of PBP alterations in S. pneumoniae acquired by recombination events with other streptococcal species, PBP changes in GBS appear to result from single base substitutions. Although reduced β-lactam susceptibility is currently rare, ongoing accumulation of mutations, particularly additional mutations in the catalytic site of PBP 1A as seen with S. pneumoniae, may eventually lead to high level β-lactam resistance in GBS.
The recent occurrence of vancomycin resistance in two epidemiologically unrelated GBS isolates was due to the acquisition of vanG resistance genes that are typically found in Enterococcus faecalis. The vanG gene cluster encodes enzymes that synthesize peptidoglycan precursors with low-affinity for vancomycin by replacing the high-affinity C-terminal D-Ala residue with low-affinity D-serine (D-Ser), thus removing the vancomycin-binding target. The origin and mode of acquisition of the vanG resistance genes in GBS has yet to be determined.

What are the best methods for detecting resistance?

Disk diffusion (including E-test strips), broth microdilution techniques, or automated commercial systems approved for β-hemolytic streptococcal species, can be used for susceptibility testing of GBS isolates. Routine testing for penicillin or ampicillin susceptibility is not currently recommended by the Clinical Laboratory Standards Institute (CLSI), since beta-lactam nonsusceptible isolates remain rare in GBS. Although routine β-lactam susceptibility testing is not recommended, consideration should be given to testing in settings of suspected meningitis and possibly endocarditis. Erythromycin and clindamycin susceptibility should be confirmed prior to use of these agents for treatment of documented GBS infection (or for intrapartum antibiotic prophylaxis). The double-disk diffusion “D-zone” method is recommended to detect inducible clindamycin resistance (iMLS) in isolates that demonstrate erythromycin resistance and clindamycin susceptibility by standard testing.

What alternative therapies are available?

Cephalosporins (cefazolin for non-meningitis and ceftriaxone or cefotaxime for meningitis) can be used in penicillin-allergic individuals who are not at high risk for anaphylaxis. Vancomycin can be used for those at high risk for anaphylaxis. Due to rising and significant rates of resistance to erythromycin and clindamycin, these drugs should only be used after susceptibility has been confirmed with appropriate antimicrobial susceptibility testing. Aminoglycosides demonstrate synergistic killing of GBS with penicillin in vitro and the addition of aminoglycosides to penicillin or a cephalosporin is recommended by some experts for the first 2 weeks of the 4 to 6 week antibiotic course for GBS endocarditis.

How do patients contract this infection, and how do I prevent spread to other patients?

Epidemiology

Nonpregnant adults: In the era of intrapartum antibiotic prophylaxis for prevention of GBS infections in newborn infants, more than 80% of invasive GBS disease now occurs in nonpregnant adolescents and adults. Although invasive GBS disease can occur in adults of all ages, the median age is 62 years and nearly half of all disease occurs in those aged 65 years and older. Rates increase with advancing age and remain significantly higher in blacks than in whites in the United States. In most cases, adults with invasive GBS disease have one or more underlying diseases and require hospitalization for a median of 7 days. Nursing home residents account for about one-tenth of nonpregnant adult cases. The case fatality rate has improved from a rate of almost 25% in 1990 to less than 10% in recent years in the United States; case-fatality rates are highest in the elderly. GBS bacteremia may be polymicrobial in a subset of patients, most often in association with Staphylococcal species. Approximately 5% of invasive GBS infections in adults represent a recurrent episode of disease. Blood cultures are the most common site of isolation of GBS in invasive disease (>80%), followed by bone and joint fluid cultures. Urine cultures are the most common site of isolation of GBS from noninvasive adult disease. Capsule serotypes Ia and V are the predominant serotypes associated with nonpregnant adult GBS disease in the United States, with serotypes III, II, and Ib also common globally in various orders of frequency depending on the geographic location. A small proportion of nonpregnant adult disease in North America is attributable to serotype IV, but this appears to be increasing. Serotype IV represented approximately 6% of isolates from non-pregnant adults in U.S. in surveillance from 2005-2006, while 16% of isolates from early-onset neonatal infections in Minnesota in 2010 were serotype IV. In surveillance conducted in two Canadian provinces from 2010-2014, ~17% of adult invasive disease was due to serotype IV.
Pregnant women: GBS disease in pregnant women is associated with upper genital tract disease that results in fetal death in approximately 50% of cases. The median age is 28 years and most disease occurs in otherwise healthy pregnant women. Maternal death is rare. Blood cultures are the source of the GBS isolate in just over half of pregnancy-associated cases and most other cultures are from products of conception. The capsular serotypes in pregnancy-associated GBS disease in the United States and many European countries are similar to those seen most commonly in early-onset neonatal disease and include 1a, II, III, and V. Global variation in serotype distribution in pregnancy-associated and neonatal disease has been reported, most notably from Japan, where serotypes VI and VIII account for a greater proportion of colonization and disease.
Are there seasonal differences in the incidence of infection? Seasonal variability of invasive GBS infections in nonpregnant adults, with a late summer peak, has been noted in a recent report from active, population-based surveillance in 10 US sites participating in the Active Bacterial Core Surveillance/Emerging Infections Program Network.
Are there environmental conditions that predispose to this infection? Vaginal/rectal colonization with GBS contributes to increase risk of peripartum infection in pregnant women and early-onset GBS disease in the newborn due to exposure during labor and delivery. Reasons for the late summer peak of invasive GBS infections in nonpregnant adults are unclear but some possibilities include environmental conditions favorable to skin and soft tissue infections, and less likely, increased exposure to bovine S. agalactiae strains in summer months. GBS has been linked to bovine mastitis and can be isolated from milk samples obtained in mastitis control programs. However, distinct subtypes, clonal groups and host specificities among human and bovine strains of GBS suggest a very low likelihood for cross species transmission.
Are some individuals asymptomatic carriers of the organism? Asymptomatic colonization with GBS may occur in the gastrointestinal tract, the perineal area, vagina, cervix or urethra, and occasionally the skin and throat. Co-colonization with identical GBS isolates may occur in sexual partners. Male and female college students living in dormitories were frequently colonized (20-34%) with GBS; the anal orifice was the most common site followed by the vagina, urine, and throat. Up to a quarter of all pregnant women will have vaginal and/or rectal colonization with GBS, and when present late in pregnancy, colonization represents the most important risk factor for early-onset GBS disease in the newborn. Similarly, vaginal colonization near the time of delivery, particularly heavy colonization, is a risk factor for intra-amniotic infection and postpartum endometritis in pregnant women. GBS bacteriuria, present in a small but significant number (2-10%) of pregnant women, is a marker for heavy vaginal colonization, and has been identified as a risk factor for both early and late-onset disease in infants. In a study of 254 healthy adults ≥65 years of age, 22% had GBS colonization in the rectum, vagina, or urine and nearly half of the isolates were capsule serotype V, an important cause of invasive disease in the elderly.
Are there host factors that contribute to the risk of infection? Disruption of the integrity of skin and/or mucous membranes, and compromised blood flow or lymphatic drainage may predispose to GBS infection in nonpregnant adults. Examples include chronic foot ulcers in diabetes, pressure-related skin breakdown, postsurgical lymphatic disruption, and radiation damage. Unrecognized deep seated infections (e.g., osteomyelitis, endocarditis) may result in recurrent episodes of invasive GBS disease.
How prevalent is this infection and in what regions of the world is it most prevalent? GBS is well-established as an important pathogen in pregnancy-associated and neonatal disease from most regions of the world. It remains the most common cause of neonatal sepsis in the United States. Recognition of the significant burden of serious GBS infections among nonpregnant adults has increased in recent years as documented in reports from the United States, Canada, Spain, Sweden, Norway, Taiwan, Japan, South Korea, and elsewhere.
Is the incidence increasing, decreasing, or staying the same? Why? Substantial recent declines in early-onset neonatal disease in the United States have been attributed to implementation of guidelines for universal GBS screening of pregnant women at 35 to 37 weeks gestation and use of intrapartum antibiotic prophylaxis (IAP) as discussed in detail elsewhere. The use of IAP has also been associated with a significant decline in the rate of peripartum GBS infection in pregnant women, decreasing from 0.29 maternal invasive GBS cases per 1,000 live births in 1993 to a mean rate of 0.12 cases per 1,000 live births between 1999 and 2005 in the United States. In contrast, rates of invasive GBS disease in nonpregnant adults have been steadily increasing in recent years. Incidence rates more than doubled from 3.6 cases per 100,000 population during 1990 to 7.3 cases per 100,000 population in 2007, and then increased further to 8.7 cases per 100,000 population in 2014. The largest increases in incidence have been noted in those between 65 to 79 years of age. The proportion of adults with invasive GBS infection who have diabetes mellitus rose from 36% to 53% between 1998 and 2014. Although the reasons for increased rates of adult GBS disease are not fully understood, the increasing prevalence of predisposing conditions such as diabetes may be contributing.

Infection control issues

Should I use gloves, gowns, masks etc.? Isolation of nonpregnant adults with GBS infection is not recommended and person-to-person transmission of adult GBS disease in a healthcare setting is not well documented. However, transmission of the organism related to intimate contact is suggested by carriage studies of sexual partners. Nosocomial GBS disease may occur in nonpregnant adults and has been independently associated with the placement of a central venous catheter. Two cases of presumed catheter-associated GBS bacteremia that developed within several hours of each other were reported from a hemodialysis center and the subsequent investigation suggested that transmission may have occurred through the hands of healthcare personnel. While the origin of nosocomial transmission of GBS is not well established, the contribution of pre-existing skin or mucosal colonization is a plausible source. Good hand hygiene and adherence to universal precautions are essential.
Is vaccination recommended? Despite great interest in the development of a vaccine to prevent neonatal and serious non-pregnancy related GBS infections, no vaccine is currently available. Initial vaccine development efforts were focused on capsular polysaccharide (CPS) as the vaccine target and later on CPS-protein conjugate vaccines using tetanus toxoid or CRM197, a genetically detoxified form of diphtheria toxin, as carrier proteins to enhance immunogenicity. Prototypic monovalent conjugate vaccines with nine GBS capsule serotypes have been prepared and tested pre-clinically and some in Phase 1 and 2 human trials. Bivalent CPS-conjugate vaccines (e.g., CPS II and III) have been shown to be safe and immunogenic in human studies, but the lack of cross protection among capsular serotypes and variability of serotype distribution globally limits the broad application of a bivalent vaccine. More recently, a trivalent conjugate vaccine designed to protect against serotypes Ia, Ib, and III has been developed and tested in Phase 1/Phase 2 clinical trials, targeting pregnant women and women of childbearing age. In results published to date, GBS antibody responses to vaccine serotypes among vaccine recipients were statistically-significant, and antibody transfer to infants was documented, although more data are needed to determine the persistence of antibodies during the newborn period. Antibody responses in HIV-positive women were less robust than in HIV-negative women in a trial in Malawi and South Africa, however, which will merit further study. Reassuringly, none of these trials identified significant safety concerns. Early work is underway to develop vaccines that target conserved GBS surface proteins (Rib, alpha C, pilus proteins) that may elicit an effective immune response, with the potential of providing broad protection across capsular serotypes. Although the highest priority for GBS vaccine development is prevention of neonatal disease, targeting adult populations at high risk for GBS disease (e.g., adults with diabetes) may be an area of future investigation.
Is anti-infective prophylaxis recommended? Guidelines for the prevention of perinatal GBS disease have been developed and include recommendations for universal screening at 35 to 37 weeks gestation for maternal colonization and use of intrapartum antibiotic prophylaxis in all who test positive for GBS colonization. Antibiotic prophylaxis is not recommended for nonpregnant individuals colonized with GBS.

What host factors protect against this infection?

What key immune system factors protect against invasion by this pathogen? Once GBS organisms successfully penetrate skin or mucosal barriers to reach deep tissues or the bloodstream, neutrophils and macrophages become critical to clearance of the pathogen. Effective opsonophagocytic function is dependent upon adequate levels of type-specific antibodies and complement. GBS possess a number of mechanisms to subvert the immune response as shown in Table I below.
Which patients are at higher risk for contracting this infection? The majority of invasive GBS disease in nonpregnant adults occurs in individuals with significant underlying diseases including, most importantly, diabetes mellitus. Among patients with invasive GBS disease, those with diabetes were more likely to have skin, soft tissue, and bone infections compared with those without diabetes. Obesity also appears to have an association with both GBS colonization and GBS disease. A 2004-2008 retrospective analysis of pregnant women at an academic medical center found that those who were obese had a higher incidence of either vaginal or rectal GBS colonization when compared to those who were not. U.S. GBS surveillance in 2005 found that almost 88% of adults with invasive disease had at least one medical comorbidity, and obesity was commonly present. Additional pre-existing conditions associated with increased risk of serious GBS disease include: cirrhosis, history of stroke, breast cancer, decubitus ulcer, and neurogenic bladder. Nursing home residents are at significantly greater risk of invasive GBS infection than community-dwelling individuals of similar age.
Describe how the host defense responses to this pathogen explain the pathological changes. Release of tumor necrosis factor-α, interleukin (IL)-1, and IL-6 is elicited by peptidoglycan, and to a lesser extent by lipoteichoic acid and other bacterial cell wall components. The GBS β-hemolysin/cytolysin and cell wall components combine to stimulate inducible nitric oxide synthase in mouse macrophages. Cyclooxygenase COX2 is activated through the mitogen-activated protein kinase pathway. The combined activation of proinflammatory pathways triggered by GBS infection lead to pathologic changes typical of the sepsis syndrome, including the potential for end-organ damage.

Table I.

Adherence to host cells/tissue	Invasion of epithelial/endothelial barriers; spread	Immune evasion	Triggers of inflammation	Blood brain barrier penetration
FbsA/B (fibrinogen)ScpB (fibronectin)Srr1 (kerritin)Pili (epithelial cells)Alpha C protein (glycosaminoglycan)Lipoteichoic acidLmb (laminin)BibA (cervical/lung epithelial cells)LrrG (epithelial cells)Rib	Alpha C proteinβ-hemolysin/cytolysinFbsBScpBPiliLTAHyaluronate lyaseCAMP factorLrrG	Sialylated CPS (antiphagocytic)ScpB (cleaves C5a)BibA (binds C3bp)β-protein (binds Factor H)CspA (inhibits complement)SodA (neutralizes superoxide anions)PBP1a (resists cationic peptide killing)	PeptidoglycanLipoteichoic acidβ-hemolysin/cytolysinSurface lipoproteinsCell wall components	Pili/PilB (BMECs)IagA (anchors LTA)FbsA (fibrinogen)Lmb (laminin)β-hemolysin/cytolysin

*BMECs, brain microvascular endothelial cells; CPS, capsular polysaccharide; LTA, lipotechoic acid.

What are the clinical manifestations of infection with this organism?

What are the most common diseases associated with this pathogen?

Nonpregnant adults: One of the most common clinical presentations in nonpregnant adults with invasive GBS disease is bacteremia without an identified source of infection. Among those with a documented source, skin and soft tissue infections are the most important clinical syndromes associated with invasive GBS infections in adults, including cellulitis, infected decubitus ulcers, and diabetic foot ulcers. In 2007, skin and soft tissue infections accounted for ~25% of cases of invasive infection in the United States, pneumonia accounted for approximately 12% of cases, followed by osteomyelitis (9.4%) and septic arthritis (7.8%). More than half of the episodes of GBS septic arthritis are prosthetic joint infections. Osteomyelitis may result from contiguous spread from skin and soft tissue infections (e.g., diabetic foot infections) or by hematogenous spread, as is often the case with vertebral osteomyelitis. Pneumonia is more often seen in the elderly, particularly in residents of long-term care facilities. Peritonitis is uncommon and usually related to gastrointestinal pathology or, rarely, with peritoneal dialysis. Endocarditis (2-9%) and meningitis (1.6%) are uncommon but very serious clinical syndromes associated with high morbidity and mortality (discussed in detail below). Although more commonly associated with group A streptococcal infections, GBS has occasionally been associated with streptococcal toxic shock syndrome and necrotizing fasciitis. Among nonpregnant adults with invasive GBS disease, patients with diabetes are more likely to present with skin and soft tissue infections, osteomyelitis, and necrotizing fasciitis. GBS has been associated with intraabdominal and pelvic abscesses, including several in which an initial infection source was not identified, predominantly in diabetic patients. Infections associated with intravenous and arterial catheters and devices including pacemaker wires and vascular graft material have been reported. Urinary tract infections are the most common noninvasive form of GBS infection in adults, although skin and soft tissue infections without associated invasive disease (including cellulitis, erysipelas, and wound infections) and upper respiratory infections contribute to the noninvasive disease burden.
Pregnancy-associated disease: Pregnancy-associated GBS disease now represents less than 5% of all invasive GBS disease in adults in the United States. Chorioamnionitis, postpartum endometritis, and bacteremia are the most common manifestations of invasive GBS in pregnancy. Upper genital tract infection resulting in fetal death may occur in up to 50% of cases. Postpartum endometritis often follows caesarean delivery. Just as in nonpregnant adults, endocarditis and meningitis are rare but serious complications of pregnancy-associated GBS disease. A small number of endocarditis cases have been reported following elective abortions. Wound infections, cellulitis, fasciitis, pneumonia, infections of ventriculoperitoneal shunts, bone and joint infections, and deep abscess formation (including epidural abscess) may occur. Urinary tract infections are the most common manifestation of noninvasive, pregnancy-associated disease.

Additional details on clinical presentations

GBS endocarditis: Adult GBS endocarditis in the pre-antibiotic era was an almost exclusively pregnancy-associated disease in relatively young women, some of whom had pre-existing valvular heart disease. In more recent reviews, GBS endocarditis is a disease primarily of older adults with a number of underlying conditions, including diabetes, cirrhosis, urinary tract disease, malignancy, renal transplant, known valvular heart disease, and only rarely, pregnancy. The mean or median age of adults with GBS endocarditis is now over 55 years and men and women are more equally represented. GBS accounted for approximately 1.7-3% of adult infective endocarditis (IE) cases overall and 3% of all left-sided IE cases in Spain. Disease onset is most often acute and primarily effects left sided, native valves. Large vegetations (>1cm) are common, as are embolic events and intracardiac complications such as valve rupture and abscess formation. Although reported mortality has been as high as 34 to 56% in the antibiotic era, more recent estimates of case-fatality have improved and range between 10 to 13%.
GBS meningitis: In one case series, GBS was the reported etiology in 4-5% of acute bacterial meningitis episodes occurring in individuals over the age of 15 years. The mean age of adults presenting with GBS meningitis is 49 years (range 17-89) and 25% are older than 65 years of age. Gram stains of cerebrospinal fluid often (84%) demonstrate gram-positive cocci, and blood cultures may be positive in nearly 80% of cases. Most adults with GBS meningitis have significant underlying conditions, including diabetes (19%), autoimmune and/or immunocompromising conditions (17%), pregnancy (14%), cirrhosis (12.5%), and a communicating subarachnoid lesion in 11%. Recent endometritis was present in the majority of pregnancy-associated cases; endocarditis and concurrent upper or lower respiratory tract infection were the most common distant foci of infection in nonpregnant adults. Approximately one-third of adult GBS meningitis cases have a fatal outcome, and survivors may be left with permanent neurologic sequelae, such as deafness. Several cases of GBS meningitis have occurred in patients with indwelling ventriculoperitoneal shunts.
Prosthetic joint infections: The incidence of GBS infections after primary joint replacement has been estimated at 1 per 667 arthroplasties. Prosthetic hip infections appear to be slightly more common than knee infections based upon clinical reports. The average or median age at presentation ranges between 55 and 74 years and as many as 47% of patients have diabetes mellitus. GBS infections account for 6 to 12% of prosthetic joint infections overall, and serotypes Ia, III, and V are the most common serotypes associated with infection. There has been a report of a prosthetic knee infection occurring in a 65 year old man one week after undergoing a flexible sigmoidoscopy procedure without biopsy.

What common complications are associated with infection with this pathogen?

Sustained bacteremia may allow seeding of heart valves, joints, or meninges leading to endocarditis, septic arthritis, and meningitis. Endocarditis can be complicated by endophthalmitis, purulent pericarditis, myocardial abscess, and mycotic aneurysms. Local extension of bone and joint infections may result in deep tissue abscess formation including epidural abscesses complicating vertebral osteomyelitis.

How should I identify the organism?

What tissue samples will provide the highest diagnostic yield? Cultures should be obtained from appropriate body sites (e.g., blood, cerebrospinal fluid, urine, synovial fluid, sputum, etc.) depending on the clinical presentation. Swabs of the lower vagina and rectum should be obtained to screen for GBS colonization in pregnant women at 35 to 37 weeks gestation (as described in detail elsewhere).
What are the best staining techniques? What is the morphology by microscopy? Group B streptococci are gram-positive cocci that form pairs and short chains.
How should you culture the organism? What is the preferred media or tissue culture? Direct plating of specimens onto 5% sheep blood agar or use of standardized, commercial culture systems approved for isolation of streptococcal species can be used to isolate GBS from most infected body sites. Isolation of GBS from mucosal surfaces may, however, represent colonization. In order to maximize the yield in screening pregnant women for GBS colonization at vaginal/rectal sites that have mixed flora, incubation for 18 to 24 hours in antibiotic-containing selective broth media prior to definitive identification procedures is recommended. Todd-Hewitt broth supplemented with either a combination of gentamicin and nalidixic acid or colistin and nalidixic acid, with or without 5% sheep blood have been used. Commercially available chromogenic agar and broth media are available for detection of β-hemolytic GBS.
What is the expected colony morphology or cytopathic effect? GBS colonies are gray-white on blood agar plates and demonstrate narrow zones of β-hemolysis. A small (approximately 4%) proportion of GBS isolates are nonhemolytic. Therefore, typical whitish-gray colonies on blood agar plates that fail to demonstrate hemolysis should be further tested to exclude GBS
What biochemical and other assays are used for specific identification? The best way to definitively identify GBS is serologic determination of the presence of the Lancefield group B antigen on the surface of the bacteria. Latex slide agglutination using group B specific antisera is a commonly used technique. Hydrolysis of hippurate and a positive CAMP test are additional characteristics that serve to distinguish GBS from other Streptococci.
How fast does the organism grow? Growth of S. agalactiae can generally be detected within 24 to 48 hours using standard culture techniques.
How sensitive are the culture techniques? Standard culture techniques are sufficient for identification of GBS infection, particularly when the organism is present in pure or predominant culture. However, direct plating of vaginal/rectal swabs to screen for GBS colonization in pregnant women may fail to detect up to 50% of carriers, prompting the strong recommendation for incubation of screening specimens in selective enrichment broth for 18 to 24 hours prior to routine identification procedures.
Is a polymerase chain reaction (PCR) assay helpful? Is it commercially available? What is the sensitivity and specificity? Deoxyribonucleic acid probes and nucleic acid amplification tests such as PCR have been studied in the context of providing a more rapid and/or accurate assessment of GBS colonization in pregnancy and are discussed elsewhere. Current applications for use in the diagnosis of nonpregnancy related GBS disease are limited.

How does this organism cause disease?

What key virulence factors allow the pathogen to colonize, spread from person to person, invade tissue and cause tissue destruction?

Proposed GBS virulence mechanisms at key steps in disease pathogenesis are shown in Table I.

How do these virulence factors explain the clinical manifestations?

GBS possess an array of virulence factors that allow them to successfully invade mucosal/epithelial barriers, particularly in settings of impaired integrity of the skin or mucous membranes. Organisms can then penetrate and spread into subcutaneous tissue, fascia, bone, and joints leading to skin and soft tissue infections, fasciitis, osteomyelitis, and septic arthritis. The β-hemolysin/cytolysin is associated with lung epithelial cell injury and contributes to spread within the lungs in GBS pneumonia. Once in the bloodstream, the presence of the antiphagocytic, sialic-acid containing polysaccharide capsule and other complement-inhibitory factors allow S. agalactiae to survive in the bloodstream. Release of cell-wall components triggers a strong proinflammatory response that may produce a sepsis syndrome. Effective intravascular survival coupled with the capacity to cross the blood brain barrier, facilitates GBS infection of the subarachnoid space and the development of clinical meningitis.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Skoff, TH, Farley, MM, Petit, S. “Increasing burden of invasive group B streptococcal disease in nonpregnant adults, 1990-2007”. Clin Infect Dis. vol. 49. 2009. pp. 85-92. (Analysis of the epidemiology of over 19,000 cases of invasive GBS infections in nonpregnant adults collected over 18 years as part of the US Center for Disease Control and Prevention Active Bacterial Core surveillance (ABCs) population-based surveillance system)

Phares, CR, Lunfield, R, Farley, MM. “Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005”. JAMA. vol. 299. 2008. pp. 2056-65. (A comprehensive report from the ABCs group on the epidemiology of invasive GBS in all age groups [over 14,000 cases] in the era of intrapartum antibiotic prophylaxis guidelines. Includes serotype distribution by age groups and antimicrobial susceptibility data)

Farley, MM, Harvey, RC, Stull, T, Smith, JD, Schuchat, A, Wenger, JD, Stephens, DS. “A population-based assessment of invasive disease due to group B streptococcus in nonpregnant adults”. New Engl J Med. vol. 328. 1993. pp. 1807-11. (A more detailed clinical description of 140 cases of invasive GBS disease in nonpregnant adults from the Atlanta ABCs group)

Edwards, MS, Baker, CJ, Mandell, GL, Bennett, JE, Dolin, R. ” (group B streptococcus)”. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 2009. (Comprehensive overview of history, microbiology, pathogenesis, epidemiology, clinical disease in all ages, treatment, and prevention measures)

Schuchat, A, Wenger, JD. “Epidemiology of group B streptococcal disease—risk factors, prevention strategies, and vaccine development”. Epidemiol Rev. vol. 16. 1994. pp. 374-402. (An excellent review of the epidemiology of GBS disease prior to the publication of prevention guidelines for neonatal GBS disease)

Schuchat, A. “Epidemiology of group B streptococcal disease in the United States: shifting paradigms”. Clin Microbiol Rev. vol. 11. 1998. pp. 497-513. (An assessment of the epidemiology of GBS 25 years after its emergence as a significant infection in newborns and just after the publication of guidelines for use of IAP)

Schrag, SJ, Zywicki, S, Farley, MM. “Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis”. N Engl J Med. vol. 342. 2000. pp. 15-20. (An initial assessment of the impact of IAP on early-onset neonatal disease and disease in pregnant women based on over 7,000 cases of invasive GBS identified in active, population-based ABCs from 1993 to1998)

Schwartz, B, Schuchat, A, Oxtoby, MJ, Cochi, SL, Hightower, A, Broome, CV. “Invasive group B streptococcal disease in adults”. JAMA. vol. 266. 1991. pp. 1112-14. (One of the first population-based studies of invasive GBS disease in adults, allowing calculation of disease rates and the relative importance of adult disease)

Verani, JR, McGee, L, Schrag, SJ. “Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC, 2010”. MMWR Morbid Mortal Wkly Rept. vol. 59. 2010. pp. 1-32. (The most recent revision of the guidelines for prevention of perinatal GBS disease. Includes background material on neonatal and maternal infections, antibiotic resistance, nucleic acid diagnostic test performance, and vaccine development efforts. Also provides detailed description of selective culture methods, susceptibility testing, and IAP)

Farley, MM. “Group B streptococcal disease in nonpregnant adults”. Clin Infect Dis. vol. 33. 2001. pp. 556-61. (Review article highlighting clinical and epidemiologic features of serious GBS infections in nonpregnant adults.)

Munoz, P, Llancaqueo, A, Rodriguez-Créixems, M, Peláez, T, Martin, L, Bouza, E. “Group B streptococcus bacteremia in nonpregnant adults”. Arch Intern Med. vol. 157. 1997. pp. 213-16. (An analysis of 90 cases of GBS bacteremia in nonpregnant adults identified between 1985 and 1994 at a large teaching hospital in Spain)

Jackson, LA, Hilsdon, R, Farley, MM. “Risk factor for group B streptococcal disease”. Ann Intern Med. vol. 123. 1995. pp. 415-20. (A case–control study utilizing multiple conditional logistic regression analysis to identify risk factors for invasive GBS disease in nonpregnant adults.)

Blumberg, HM, Stephens, DS, Modansky, M. “Invasive group B streptococcal disease: the emergence of serotype V”. J Infect Dis. vol. 173. 1996. pp. 365-73. (Analysis of the serotype distribution and molecular epidemiologic characteristics of 179 invasive GBS isolates from a population-based isolate collection in Atlanta.)

Harrison, LH, Ali, A, Dwyer, DM. “Relapsing invasive group B streptococcal infection in adults”. Ann Intern Med. vol. 123. 1995. pp. 421-7. (Population-based identification of invasive GBS isolates; detailed molecular characterization of paired first and subsequent isolates; controls included in laboratory evaluation for comparison.)

Henning, KJ, Hall, EL, Dwyer, DM, Billmann, L, Schuchat, A, Johnson, JA, Harrison, LH. “Invasive group B streptococcal disease in Maryland nursing home residents”. J Infect Dis. vol. 183. 2001. pp. 1138-42. (A statistical comparison of nursing home and community dwelling residents with invasive GBS disease identified as part of a population-based surveillance system)

Kothari, NJ, Morin, CA, Glennen, A, Jackson, D, Harper, J, Schrag, SJ, Lynfield, R. “Invasive group B streptococcal disease in the elderly, Minnesota, USA, 2003-2007”. Emerg Infect Dis. vol. 15. 2009. pp. 1279-81. (A statistical comparison of elderly patients with invasive GBS disease residing in long-term care facilities to those who lived in the community. All cases were identified through population-based surveillance)

Sukhnanand, S, Dogan, B, Ayodele, MO. “Molecular subtyping and characterization of bovine and human isolates”. J Clin Microbiol. vol. 43. 2005. pp. 1177-86. (A comparison of 194 human invasive GBS isolates from upstate New York collected as part of population-based surveillance with 236 bovine GBS isolated obtained from the Cornell University Quality Milk Production Services mastitis control program. Detailed molecular characterizations and phylogenic comparisons performed)

Yancey, MK, Duff, P, Clark, P, Kurtzer, T, Frentzen, BH, Kubilis, P. “Peripartum infection associated with vaginal group B streptococcal colonization”. Obstet Gynecol. vol. 84. 1994. pp. 816-19. (Single institution-based study of 823 pregnant women screened for GBS colonization within 2 weeks of delivery. Risk for chorioamnionitis and endometritis was assessed using univariate and multivariate logistic regression.)

Manning, SD, Tallman, P, Baker, CJ, Gillespie, B, Marrs, CF, Foxman, B. “Determinants of co-colonization with group B among heterosexual college couples”. Epidemiology. vol. 13. 2002. pp. 533-9. (Single, large university-based study of 120 college student couples in which at least one partner was colonized with GBS. Associations for co-colonization were assessed using a logistic regression model)

Manning, SD, Neighbors, K, Tallman, PA. “Prevalence of group B colonization and potential for transmission by casual contact in healthy young men and women”. Clin Infect Dis. vol. 39. 2004. pp. 380-8. (First year dormitory residents (462) at a single large university in Michigan were sampled by dormitory floor for inclusion in a study to detect prevalence of GBS colonization and risk factors for colonization. A multinomial logit regression model was used to assess risk of colonization.)

Edwards, MS, Rench, MA, Palazzi, DL, Baker, CJ. “Group B streptococcal colonization and serotype-specific immunity in healthy elderly persons”. Clin Infect Dis. vol. 40. 2005. pp. 352-7. (A study of 254 predominantly white, healthy adults 65 years and older recruited from the community to a single institution in Houston for assessment of GBS colonization and serotype specific immunity)

Brooks, GF, Carroll, KC, Brooks, GF, Carroll, KC, Butel, JS, Morse, SA, Mietzner, TA. “The streptococci”. Jawtz, Melnick, and Adelberg’s Medical Microbiology. 2010. (Microbiology textbook chapter describing streptococcal classification)

Performance standard for antimicrobial susceptibility testing, M100-S20. vol. 30. 2010. (The latest guidelines for antimicrobial susceptibility testing of β-hemolytic streptococci, including guidance for testing group B streptococci)

Borchardt, SM, DeBusscher, JH, Tallman, PA, Manning, SD, Marrs, CF, Kurzynski, TA, Foxman, B. “Frequency of antimicrobial resistance among invasive and colonizing group B streptococcal insolates”. BMC Infect Dis. vol. 6. 2006. pp. 57-64. (Characterization of 482 GBS isolates collected through a Public Health Laboratory Surveillance program in Wisconsin)

Murayama, SY, Seki, C, Sakata, H. “Capsular type and antibiotic resistance in isolates from patients, ranging from newborns to the elderly, with invasive infections”. Antimicrob Agents Chemother. vol. 53. 2009. pp. 2650-3. (Characterization of 189 GBS sterile site isolates collected from 97 medical institutions participating in an Invasive Streptococcal Disease Working Group between 2006 and 2007 in Japan)

Lin F-Y, C, Azimi, PH, Weisman, LE. “Antibiotic susceptibility profiles for group B streptococci isolates from neonates, 1995-1998”. Clin Infect Dis. vol. 31. 2000. pp. 76-9. (Characterization of 119 invasive and 227 colonization isolates of GBS collected from 14 hospitals within six geographically dispersed academic centers in the United States)

Wang, Y-H, Su, L-H, Hou, J-N, Yank, T-H, Lin, T-Y, Chu, C, Chiu, C-H. “Group B streptococcal disease in nonpregnant patients: emergence of highly resistant strains of serotype Ib”. J Clin Microbiol. vol. 48. 2010. pp. 2571-4. (Systematic collection of 228 GBS isolates from nonpregnant adult patients with noninvasive and invasive infections admitted to a single institution in Taiwan between 2006 and 2008)

Seo, YS, Srinivasan, U, Oh, KY. “Changing molecular epidemiology of group B streptococcus in Korea”. J Korean Med Sci. vol. 25. 2010. pp. 817-23. (A collection of 196 colonizing and 234 clinical isolates collected from throughout Korea were evaluated for serotype, antibiotic resistance, and erythromycin and clindamycin resistance mechanisms)

Castor, ML, Whitney, CG, Como-Sabetti, K. “Antibiotic resistance patterns in invasive group B streptococcal isolates”. Infect Dis Obst Gyn. vol. 2008. 2008. pp. 727505(Analysis of a collection of 2,937 invasive GBS isolates from four US states doing population-based surveillance between 1996-2003. Isolates were serotyped, antimicrobial susceptibility testing performed, and erythromycin and clindamycin resistance mechanisms described.)

Pinheiro, S, Radhouani, H, Coelho, C. “Prevalence and mechanisms of erythromycin resistance in from healthy pregnant women”. Microbial Drug Resistance. vol. 15. 2009. pp. 121-4. (Characterization of 93 vaginal/rectal isolates collected from routine screening of 400 pregnant women in 2008 at a single institution in Portugal. Detailed phenotypic and genotypic description of erythromycin-resistant isolates.)

Schoening, TE, Wagner, J, Arvand, M. “Prevalence of erythromycin and clindamycin resistance among isolates in Germany”. Clin Microbiol Infect Dis. vol. 11. 2005. pp. 577-96. (A collection of 338 GBS isolates from two regions of Germany. Approximately 50% were vaginal/rectal carriage isolates and 22% invasive isolates.)

Persson, E, Berg, S, Bergseng, H, Bergh, K, Valsö-Lyng, R, Trollfors, B. “Antimicrobial susceptibility of invasive group B streptococcal isolates from south-west Sweden 1988-2001”. Scand J Infect Dis. vol. 40. 2008. pp. 308-13. (Analysis of 297 invasive GBS isolates collected during two time periods from multiple laboratories within south-west Sweden)

Gygax, SE, Schuyler, JA, Kimmel, LE, Trama, JP, Mordechai, E, Adelson, ME. “Erythromycin and clindamycin resistance in group B streptococcal clinical isolates”. Antimicrob Agents Chemother. vol. 50. 2006. pp. 1875-7. (A multiplex PCR assay was used to screen for the prevalence of erythromycin resistance genes and compared with resistance phenotypes in 222 cervicovagina-rectal swabs submitted from 20 states in the United States)

Kimura, K, Suzuki, S, Wachino, J. “First molecular characterization of group B streptococci with reduced penicillin susceptibility”. Antimicrob Agents Chemother. vol. 52. 2008. pp. 2890-7. (A report of 14 GBS sputum isolates collected between 1995 and 2005 in Japan with reduced susceptibility to penicillin. PBP mutations identified)

Dahesh, S, Hensler, ME, Van Sorge, NM, Gertz Jr, RE, Schrag, S, Nizet, V, Beall, BW. “Point mutation in the group B streptococcal gene conferring decreased susceptibility to β-lactam antibiotics”. Antimicrob Agents Chemother. vol. 52. 2008. pp. 2915-18. (Detailed characterization of PBPs from four serotype III GBS invasive isolates with elevated (but susceptible) MICs to penicillin/β-lactams. The four strains were selected from 22 with elevated MICs out of a population-based United States collection of 5,631 invasive isolates.)

Nagano, N, Nagano, Y, Kimura, K, Tamai, K, Yanagisawa, Arakawa Y. “Genetic heterogeneity in PBP genes among clinical isolates group B streptococci with reduced penicillin susceptibility”. Antimicrobial Agents Chemother. vol. 52. 2008. pp. 4258-67. (A comparison of PBP characteristics in eight GBS nonsterile site isolates with increased MICs to penicillin with those of four fully susceptible invasive and two mucosal GBS isolates in Japan.)

Chu, YW, Tse, C, Tsang, GK-L, So, DK-S, Fung, JT-L, Lo, JY-C. “Invasive group B isolates showing reduced susceptibility to penicillin in Hong Kong”. J Antimicrob Chemother. vol. 60. 2007. pp. 1407-9. (A report of two cases of bacteremia with GBS isolates with reduced susceptibility to penicillin in Hong Kong between 2005 and 2007.)

Kasahara, K, Baltus, AJ, Lee, S-H, Edelstein, MA, Edelstein, PH. “Prevalence of non-penicillin-susceptible group B streptococcus in Philadelphia and specificity of penicillin resistance screening methods”. J Clin Microbiol. vol. 48. 2010. pp. 1468-9. (Screening 1991 consecutive GBS isolates (mostly genitourinary) collected at a single institution in Philadelphia between 2008 and 2009 for evidence of elevated MICs to penicillin – none found.)

Nagao, N, Nagano, Y, Toyama, M. “Penicillin-Susceptible Group B Streptococcal Clinical Isolates with Reduced Cephalosporin Susceptibility”. Journal of Clinical Microbiology. vol. 52. 2014. pp. 3406-3410. (Study examined a small number of both penicillin-susceptible and penicillin-resistant GBS isolates that had decreased susceptibility to cephalosporins in order to evaluate resistance mechanisms.)

Berg, BR, Houseman,, JL, terSteeg, ZE, LeBar, WD, Newton, DW. “Antimicrobial Susceptibilities of Group B Strepcoccus Isolates from Prenatal Screening Samples”. Journal of Clinical Microbiology. vol. 52. 2014. pp. 3499-3500. (Brief report reviewing antimicrobial susceptibility testing for 387 Group B strep isolates identified during prenatal testing in Michigan in 2013. 45.2% of isolates were resistant to erythromycin, and 36.7% were resistant to clindamycin if isolates that had inducible resistance identified by D test were included.)

Capraro, GA, Rambin, ED, Vanchiere, JA, Bocchini, JA, Matthews-Greer, JM. “High Rates of Inducible Clindamycin Resistance among Prenatal Group B Streptococcal Isolates in One Northwest Louisiana Academic Medical Center”. Journal of Clinical Microbiology. vol. 51. 2013. pp. 2469(Brief report of antimicrobial susceptibility testing results from 544 prenatal screening GBS isolates at a single center in Louisiana from 2009-2010. 33% were resistant to clindamycin and 52% to erythromycin, which suggests increasing prevalence of resistance, particularly to erythromycin.)

Back, EE, O’Grady, EJ, Back, JD. “High Rates of Perinatal Group B Streptococcus Clindamycin and Erythromycin Resistance in an Upstate New York Hospital”. Antimicrobial Agents and Chemotherapy. vol. 56. 2012. pp. 739-742. (A report of susceptibility testing results for 688 prenatal GBS isolates from 2010-2011 at a single center in New York that also suggested increasing prevalence of clindamycin and erythromycin resistance, with 38.4% and 50.7% of isolates resistant, respectively.)

Park, C, Nichols, M, Schrag, SJ. “Two Cases of Invasive Vancomycin-Resistant Group B Streptococcus Infection”. New England Journal of Medicine. vol. 370. 2014. pp. 885-886. (Discusses two cases of invasive infection in which the GBS isolates were both found to have elevated MICs of 4 (g to vancomycin. One case was a GBS septic arthritis with associated bacteremia, and the other was a GBS bacteremia with chest wall cellulitis following a known GBS sacroiliitis.)

Ryu, H, Park, YJ, Kim, YK, Chang, J, Yu, JK. “Dominance of clonal complex 10 among the levofloxacin-resistant Streptococcus agalactiae isolated from bacteremic patients in a Korean hospital”. J Infect Chemother. vol. 20. 2014. pp. 509-511. (Description of the epidemiology of 49 invasive GBS isolates identified at a South Korean hospital from 2010-2013, 41 of which were from adult patients. The authors found that 32.7% of all of the isolates were levofloxacin-resistant, and 71.4% of the fourteen isolates belonging to one clonal complex (10) were resistant.)

Sendi, P, Johansson, L, Norrby-Teglund, A. “Invasive group B streptococcal disease in nonpregnant adults—a review with emphasis on skin and soft-tissue infections”. Infection. vol. 36. 2008. pp. 100-11. (Review of epidemiology, clinical disease, pathogenesis, drug resistance, and treatment.)

Blancas, D, Santin, M, Olmo, M, Alcaide, F, Carratala, J, Gudiol, F. “Group B streptococcal disease in nonpregnant adults: incidence, clinical characteristics, and outcome”. Eur J Clin Microbiol Infect Dis. vol. 23. 2004. pp. 168-73. (A retrospective chart review of 150 group B streptococcal infections (invasive, operative samples, or focal suppuration) in nonpregnant adults from 1993-2000 in a single tertiary care hospital in Spain showing a significant increase in the incidence over time.)

Tyrrell, GJ, Senzilet, LD, Spika, JS. “Invasive disease due to group B streptococcal infection in adults: result from a Canadian, population-based, active laboratory surveillance study—1996”. J infect Dis. vol. 182. 2000. pp. 168-73. (A 12-month population-based surveillance program for invasive GBS disease in adults covering nine public health units in Canada: 106 cases identified; clinical, epidemiology, serotyping, and antimicrobial susceptibility testing data included.)

Edwards, MS, Baker, CJ. “Group B streptococcal infections in elderly adults”. Clin Infect Dis. vol. 41. 2005. pp. 839-47. (A review article discussing the epidemiology, pathogenesis, and clinical features of invasive GBS infections in the elderly.)

“Group B Streptococcus”. 2014. (Publicly-available 2014 report of EIP surveillance data for GBS, including the rates of early and late-onset neonatal disease (both overall and broken down by race), and the number of cases and deaths reported broken down by age group.)

Diedrick, MJ, Flores, AE, Hillier, SL, Creti, R, Ferrieri, P. “Clonal Analysis of Colonizing Group B Streptococcus, Serotype IV, an Emerging Pathogen in the United States”. Journal of Clinical Microbiology. vol. 48. 2010. pp. 3100-3104. (Examination of 101 serotype IV GBS isolates to look at sequence typing and surface proteins. The authors reported that there seemed to be close associations between the surface proteins identified and the sequence type; this was also the first report of sequence type 459, which has subsequently been identified as a predominant sequence type for serotype IV isolates in Canada.)

Ferrieri, P, Lynfield, R, Creti, R, Flores, AE. “Serotype IV and Invasive Group B Streptococcus Disease in Neonates, Minnesota, USA, 2000-2010”. Emerging Infectious Diseases. vol. 19. 2013. pp. 551-558. (Describes the epidemiology of neonatal GBS isolates in Minnesota from 2000-2010. Researchers noted that ~16% of the 2010 isolates from cases of early-onset neonatal disease were serotype IV, which was a significant increase in incidence. They also identified significant clindamycin and erythromycin resistance in serotype IV isolates.)

Teatero, S, Athey, TBT, Caseseele, PV. “Emergence of Serotype IV Group B Streptococcus Adult Invasive Disease in Manitoba and Saskatchewan, Canada, Is Driven by Clonal Sequence Type 459 Strains”. Journal of Clinical Microbiology. vol. 53. 2015. pp. 2919-2926. (The authors reviewed 549 invasive GBS isolates in Saskatchewan and Manitoba from 2010-2014, and found that 93 (16.9%) were serotype IV. They studied 85 of those isolates to examine antimicrobial resistance patterns, and found that 89% belonged to one sequence type (459) and were resistant to clindamycin, erythromycin, and tetracycline.)

Murayama, SY, Seki, C, Sakata, H. “Capsular Type and Antibiotic Resistance in Streptococcus agalactiae Isolates from Patients, Ranging from Newborns to the Elderly, with Invasive Infections”. Antimicrobial Agents and Chemotherapy. vol. 53. 2009. pp. 2650-2653. (Review of 189 GBS isolates submitted from 97 institutions in Japan from 2005-2006 to examine antibiotic resistance patterns and serotyping. Overall, 124 of these isolates were from adult patients, with serotype Ib the most common, followed by V, II, III, and Ia. 28% were quinolone resistant.)

Le Doare, K, Heath, PT. “An overview of global GBS epidemiology”. Vaccine. 2013. pp. D7-D12. (Review of the GBS serotypes most commonly seen in non-pregnant adults, pregnant women, and both early- and late-onset neonatal disease.)

Ulett, KB, Benjamin, Jr, WH, Zhuo, F. “Diversity of Group B Streptococcus Serotypes Causing Urinary Tract Infection in Adults”. Journal of Clinical Microbiology. vol. 47. 2009. pp. 2055-2060. (Study in which culture were collected from 34,367 women who had an evaluation for urinary tract infection at the University of Alabama from 2007-2008; 387(1.1%) had cultures positive for GBS. These isolates were analyzed for serotype and antibiotic resistance.)

Lamagni, TL, Keshishian, C, Efstratious, A. “Emerging Trends in the Epidemiology of Invasive Group B Streptococcal Disease in England and Wales, 1991-2010”. Clinical Infectious Diseases. vol. 57. 2013. pp. 682-8. (Describes GBS surveillance trends, with an overall increase in case incidence seen over the time period in England and Wales, and a significant increase in the percentage of cases that were seen in adults. In adults, 50% of cases were either serotype III or serotype Ia, followed by V, II, and Ib in decreasing order of prevalence.)

Dangor, Z, Lala, SG, Cutland, CL. “Burden of Invasive Group B Streptococcus Disease and Early Neurological Sequelae in South African Infants”. PLoS ONE. vol. 10. 2015. pp. e0123014(Case-control study done in South Africa to examine risk factors for both early- and late-onset neonatal GBS disease. Infants with GBS disease were considered cases, and were matched to control infants based on the mother’s HIV status and age, gestational age at delivery, and time from delivery. Maternal GBS bacteriuria was a significant risk factor for early and late onset neonatal GBS disease in both univariable and multivariable analysis.)

Kessous, R, Weintraub, AY, Sergienko, R. “Bacteruria with group-B streptococcus: is it a risk factor for adverse pregnancy outcomes?”. The Journal of Maternal-Fetal and Neonatal Medicine. vol. 25. 2012. pp. 1983-1986. (Study done in Israel to examine whether pregnant women with group B strep bacteriuria had worse outcomes than those with vaginal GBS colonization and those with negative GBS cultures. Women with urinary GBS had an increased rate of chorioamnionitis compared to both other groups. They also had increased odds of premature rupture of membranes and preterm labor compared to women without GBS colonization.

Baker, CJ, Paoletti, LC, Wessels, MR, Guttormsen H-K, Rench, MA, Hickman, ME, Kasper, DL. “Safety and immunogenicity of capsular polysaccharide-tetanus toxoid conjugate vaccines for group B streptococcal types Ia and Ib”. J Infect Dis. vol. 179. 1999. pp. 142-50. (Report of preclinical and Phase 1 and 2 randomized, placebo-controlled human trials.)

Baker, CJ, Rench, MA, Fernandez, M. “Safety and immunogenicity of a bivalent group B streptococcal conjugate vaccine for serotypes II and III”. J infect Dis. vol. 188. 2003. pp. 66-73. (A safety and immunogenicity trial in 75 healthy adults combining two CPS-protein conjugates in single IM injection. Vaccines well-tolerated and immunogenic in most recipients.)

Maione, D, Margarit, I, Rinaudo, CD. “Identification of a universal group B vaccine by multiple genome screen”. Science. vol. 309. 2005. pp. 148-50. (Background science for future vaccine development.)

Meinke, AL, Senn, BM, Visram, Z. “Immunological fingerprinting of group B streptococci: from circulating human antibodies to protective antigens”. Vaccine. vol. 28. 2010. pp. 6997-7008. (Background science for future vaccine development.)

Donders, GG, Halperin, SA, Devlieger, R. “Maternal immunization with an investigational trivalent group B Streptococcal vaccine: a randomized controlled trial”. Obstetrics and Gynecology. vol. 127. 2016. pp. 213-221. (Phase 2 trial of a trivalent [serotypes Ia, Ib, and III] vaccine in 86 pregnant women in Canada and Belgium, 51 of whom received the vaccine. Women who received the vaccine developed antibodies against all three serotypes, although the response was better in those who had existing antibodies prior to the study. Antibodies were transferred to their infants, although the infant antibody response waned with time as expected. There were not serious safety concerns.)

Heath, PT. “Status of vaccine research and development of vaccines for GBS”. Vaccine.. vol. 34. 2016. pp. 2876-79. (Update on GBS vaccine development including CPS-protein conjugate and protein-based vaccines.)

Madhi, SA, Cutland, CL, Jose, L. “Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial”. Lancet Infectious Disease. vol. 16. 2016. pp. 923-34. (Results from a phase 1b/2 trial in South Africa in which a trivalent GBS vaccine [serotypes Ia, Ib, and III] was given to non-pregnant women to evaluate for safety and GBS antibody responses, and to pregnant women to evaluate optimal dosing. Women in both groups who received the vaccine had significant antibody responses to the included capsular serotypes, regardless of vaccine dose. There were not significant differences in reported adverse events between groups receiving the vaccine and those receiving placebo, and so no significant safety concerns were raised.)

Heyderman, RS, Madhi, SA, French, N. “Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial”. Lancet Infectious Disease. vol. 16. 2016. pp. 546-55. (The same trivalent GBS vaccine was tested in Malawi and South Africa in a phase 2 trial to compare antibody responses in women with and without HIV. It was similarly safe, but antibody responses in HIV-positive women were less robust than in HIV-negative women.)

Kleweis, SM, Cahill, AG, Odibo, AO, Tuuli, MG. “Maternal Obesity and Rectovaginal Group B Streptococcus Colonization at Term”. Infectious Diseases in Obstetrics and Gynecology. 2015. (Retrospective review of ~7700 pregnant women at Barnes-Jewish Hospital in Saint Louis from 2004-2008 to examine whether there was an association between obesity and colonization with GBS. 28.4% of obese women had either vaginal or rectal colonization, compared to 22.2% of non-obese women, which was statistically-significant. The researchers then adjusted for the presence of potential risk factors, including diabetes, race, and smoking, and an increased risk of GBS colonization in obese women remained significant. They additionally examined whether increasing BMI predicted increasing GBS risk, and found that it did appear to — 27.3% of women with a BMI between 30-40 were colonized, and 31.7% with a BMI (40 were colonized.)

Crum-Cianflone, NF. “An unusual case of a large, sporadic intraabdominal abscess due to group B Streptococcus and a review of the literature”. Infection. vol. 43. 2015. pp. 223-227. (Case report of an immunocompetent patient who developed a large intraabdominal abscess with only group B strep isolated, with no apparent inciting GI or urological infection. The authors reviewed 7 other cases of intraabdominal or pelvic abscesses secondary to group B strep, all of which had been seen in patients who were immunocompromised in some way, 5 of whom were diabetic.)

Sendi, P, Johansson, L, Norrby-Teglund. “Invasive Group B Streptococcal Disease in Non-pregnant Adults: A Review with Emphasis on Skin and Soft-tissue Infections”. Infection. vol. 36. 2008. pp. 100-111. (Review of studies of invasive GBS, including a compilation of results from 20 studies to look at common clinical presentations. Article focuses on skin/soft-tissue infections and associated complications, including cellulitis, erysipelas, ulcers, necrotizing fasciitis, and toxic shock syndrome.)

Tazi, A, Gueudet, T, Varon, E, Gilly, L, Trieu-Cuot, P, Poyart, C. “Fluoroquinolone-Resistant Group B Streptococci in Acute Exacerbation of Chronic Bronchitis”. Emerging Infectious Diseases. vol. 14. 2008. pp. 349-350. (Case report of a patient with bronchitis whose sputum culture was positive only for GBS, which was ultimately found to be the first quinolone-resistant isolate identified in France.)

Domingo, P, Barquet, N, Alvarez, M, Coll, P, Nava, J, Garau, J. “Group B streptococcal meningitis in adults: report of twelve cases and review”. Clin Infect Dis. vol. 25. 1997. pp. 1180-7. (A report of 12 cases of GBS meningitis in adults over a 15-year period from two hospitals in Barcelona and a literature review of 72 additional cases from 1942 to 1996.)

Georgieva, RI, García López, MV, Ruiz-Morales, J. ” left-sided infective endocarditis. Analysis of 27 cases from a multicentric cohort”. J Infection. vol. 61. 2010. pp. 54-9. (Prospective case collection of 27 cases of left-sided GBS endocarditis from seven hospitals, including cardiac surgery reference hospitals, in southern Spain between between 1984 and 2008.)

Sambola, A, Miro, JM, Tornos, MP. ” infective endocarditis: analysis of 30 cases and review of the literature, 1962-1998″. Clin Infect Dis. vol. 34. 2002. pp. 1576-84. (Report of 30 cases of GBS endocarditis identified between 1975 and 1998 from four major hospitals in Spain that serve as endocarditis referral centers, and literature review of 115 additional cases.)

Rollán, MJ, San Román, JA, Vilacosta, I, Sarriá, C, López, J, Acuna, M, Bratos, JL. “Clinical profile of native valve endocarditis”. Amer Heart J. vol. 146. 2003. pp. 1095-8. (A prospective study of all endocarditis diagnosed from a network of hospitals in Spain using Duke’s diagnostic criteria. Nine of 310 episodes were due to GBS.)

Baddour, LM. “Infective endocarditis caused by β-hemolytic streptococci”. Clin Infect Dis. vol. 26. 1998. pp. 66-71. (A survey of 271 Infectious Diseases Society of America members in the Emerging Infections network in 1996 soliciting information on patients treated with β-hemolytic streptococcal endocarditis. Response rate of 65%; reported 105 cases; 68% were GBS.)

Krohn, MA, Hillier, SL, Baker, CJ. “Maternal peripartum complications associated with vaginal group B streptococci colonization”. J Infect Dis. vol. 179. 1999. pp. 1410-15. (Cross-sectional, observational study using convenience sampling that enrolled over 8,000 participants at three geographically disperse clinical sites.)

Aharoni, A, Potasman, I, Levitan, Z, Golan, D, Sharf, M. “Postpartum maternal group B streptococcal meningitis”. Rev Infect Dis.. vol. 12. 1990. pp. 273-6. (A comparison of the clinical features of 5 postpartum group B streptococcal meningitis cases with 34 nonparturient adult cases from the literature.)

Lee, N-Y, Yan, J-J, Wu, J-J, Lee, H-C, Liu, K-H, Ko, W-C. “Group B streptococcal soft tissue infections in non-pregnant adults”. Clin Microbiol Infect. vol. 11. 2005. pp. 577-9. (A series of 71 nonpregnant adults with GBS soft tissue infections identified from a single institution between 1991 and 1999.)

Garcia-Lechuz, JM, Bachiller, P, Vasallo, F, Munoz, P, Padilla, B, Bouza, E. “Group B streptococcal osteomyelitis in adults”. Medicine (Baltimore). vol. 78. 1999. pp. 191-9. (Retrospective review of six cases of GBS osteomyelitis from a referral hospital in Spain between 1985 and 1997 and review of 33 additional cases from the literature.)

Zeller, V, Lavigne, M, Biau, D, Leclerc, P, Ziza, JM, Mamoudy, P, Despaces, N. “Outcome of group B streptococcal prosthetic hip infections compared to that of other bacterial infections”. Joint Bone Spine. vol. 79. 2009. pp. 491-6. (Prospective surveillance for prosthetic joint infections at a single referral hospital in France. 24 cases of GBS bacteremia identified since 1994 and compared with 115 consecutive non-GBS infections from 2003 to 2006.)

Jenkins, PJ, Clement, ND, Gaston, P, Breusch, S, Simpson, H, Dave, J. “Invasive group B streptococcal disease in an orthopaedic unit”. J Hosp Infect. vol. 76. 2010. pp. 231-3. (Retrospective database review of adult GBS orthopedic infections at a large teaching hospital in the United Kingdom between 2006 and 2009 that identified 17 cases of mostly prosthetic joint infections and calculated infection rates/procedures performed)

Triesenberg, SN, Clark, NM, Kauffman, CA. “Group B streptococcal prosthetic joint infection following sigmoidoscopy”. Clin Infect Dis. vol. 15. 1992. pp. 374-5. (Case report)

Corvec, S, Illiaquer, M, Touchais, S. “Clinical features of group B prosthetic joint infections and molecular characterization of isolates”. J Clin Microbiol. vol. 49. 2011. pp. 380-2. (Case series of 12 cases of GBS prosthetic joint infection identified at a single institution between 2002 and 2006. Isolates characterized with serotyping, pulsed field gel electrophoresis, multilocus sequence typing, susceptibility testing, and assessment of several other virulence factors.)

Corvec, S, Illiaquer, M, Touchais, S. “Clinical Features of Group B Streptococcus Prosthetic Joint Infections and Molecular Characterization of Isolates”. Journal of Clinical Microbiology. vol. 49. 2011. pp. 380-382. (Review of 12 GBS prosthetic joint infections seen at an academic medical center in France from 2002-2006. Study authors identified 7 hip infections and 5 knee infections in the patients, which were all either serotype Ia, III, or V. Five of the patients had no clear predisposing risk factors for GBS infection.)

Sendi, P, Christensson, B, Uckay, I. “Group B streptococcus in prosthetic hip and knee joint-associated infections”. Journal of Hospital Infection. vol. 79. 2011. pp. 64-69. (Review of 34 cases of GBS prosthetic joint infections seen in 10 medical centers in Switzerland and Sweden. Examines patient risk factors, presentation, treatment, and outcomes.)

Zeller, V, Lavigne, M, Leclerc, P. “Group B streptococcal prosthetic joint infections: a retrospective study of 30 cases”. Presse Med. vol. 38. 2009. pp. 1577-1584. (Review of 30 patients with GBS prosthetic joint infections seen at a medical center in France from 1994-2006. Describes patient presentation, suspected source of the infection, treatment, and outcomes.)

Glaser, P, Rusniok, C, Buchrieser, C. “Genome sequence of , a pathogen causing invasive neonatal disease”. Mol Microbiol. vol. 45. 2002. pp. 1499-1513. (Complete genomic sequence for serotype III strain NEM316.)

Maisey, HC, Doran, KS, Nizel, V. “Recent advances in understanding the molecular basis of group B virulence”. Exp Rev Mol Med. vol. 10. 2008. pp. 1-16. (Review of the pathogenic steps and virulence factors involved in GBS infection.)

Lindahl, G, Stålhammar-Carlemalm, M, Areschoug, T. “Surface proteins of and related proteins in other bacterial pathogens”. Clin Microbiol Rev. vol. 18. 2005. pp. 102-27. (Comprehensive 2005 review of key GBS surface proteins and their potential role in vaccine development.)

Lauer, P, Rinaudo, CD, Soriani, M. “Genome analysis reveals pili in group B “. Science. vol. 309. 2005. pp. 105(Pilus-like structures were identified on group B streptococci by genomic analysis that confer protection in a mouse model of maternal immunization.)

Dramsi, S, Caliot, E, Bonne, I. “Assembly and role of pili in group B streptococci”. Mol Microbiol. vol. 60. 2006. pp. 1401-13. (Potential candidate for a multivalent GBS protein-based vaccine.)

Rosini, R, Rinaudo, CD, Soriani, M. “Identification of novel genomic islands coding for antigenic pilus-like structures in “. Mol Microbiol. vol. 61. 2006. pp. 126-41. (Potential candidate for a multivalent GBS protein-based vaccine.)

No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.

Jump to Section

Streptococcus agalactiae (Group B)