Pembunuh bayi dalam kandungan
Group B Streptococcus
agalactiae
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:
o 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
o 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.
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.
.
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