Streptococcus agalactiae- An Overview

Streptococcus agalactiae (also known as group B streptococcus or GBS) is a gram-positive coccus (round bacterium) that belongs to the genus Streptococcus. It is a beta-hemolytic, catalase-negative, and facultative anaerobe that can grow in the presence or absence of oxygen. It is the only member of the Lancefield group B of streptococci, which are classified based on their cell wall carbohydrate antigens. It has ten different serotypes (Ia, Ib, II-IX) that are distinguished by their capsular polysaccharide structures.

S. agalactiae is a part of the normal flora of the human gastrointestinal and genitourinary tracts, where it usually does not cause any harm. However, it can also be a pathogen that causes serious infections in neonates, pregnant women, older adults, and immunocompromised individuals. It is the leading cause of neonatal sepsis and meningitis, and can also cause pneumonia, endocarditis, osteomyelitis, arthritis, skin and soft tissue infections, and urinary tract infections.

S. agalactiae was first recognized as a cause of bovine mastitis (inflammation of the udder) by Edmond Nocard in 1887. The species name `agalactiae` means `want of milk` in Greek, reflecting its effect on milk production in cows. It was later found to be a human pathogen by Rebecca Lancefield in the 1930s after she isolated it from the blood of women with postpartum sepsis. Since then, S. agalactiae has emerged as a major public health concern due to its high morbidity and mortality rates in vulnerable populations.

The prevention and treatment of S. agalactiae infections depend on the identification and characterization of the organism by various laboratory methods. These include morphological, cultural, biochemical, immunological, and molecular tests that can detect and differentiate S. agalactiae from other streptococci and bacteria. The use of intrapartum antibiotic prophylaxis for colonized pregnant women has reduced the incidence of early-onset neonatal disease significantly. However, late-onset neonatal disease and adult infections remain challenging to prevent and manage. Therefore, there is a need for developing effective vaccines and novel therapies against S. agalactiae infections.

In this article, we will provide an overview of S. agalactiae, covering its classification, habitat, morphology, cultural characteristics, biochemical characteristics, virulence factors, pathogenesis, clinical manifestations, laboratory diagnosis, treatment, and prevention.

• Group B Streptococcus (GBS) is another name for Streptococcus agalactiae, a type of bacteria that can cause serious infections in humans, especially newborns and pregnant women.
• GBS is the only member of the Lancefield group B antigen grouping, which is based on the presence of a specific carbohydrate on the bacterial cell wall.
• GBS can be classified into 10 different serotypes (Ia, Ib, II–IX) based on the variation in their capsular polysaccharide, which is a major virulence factor and a target for vaccine development.
• GBS is part of the normal flora of the gastrointestinal and genital tracts of many healthy adults and does not cause any symptoms or problems.
• However, GBS can sometimes cause invasive infections when it crosses the mucosal barrier and enters the bloodstream or other sterile sites.
• GBS is a leading cause of neonatal sepsis, meningitis, and pneumonia worldwide. It can also cause infections in pregnant women, such as urinary tract infections, chorioamnionitis, endometritis, and bacteremia.
• In addition, GBS can cause infections in older adults and people with chronic medical conditions, such as diabetes, cancer, or liver disease. These infections may include skin and soft tissue infections, bone and joint infections, endocarditis, and meningitis.
• GBS can be transmitted from person to person through direct contact with respiratory secretions or body fluids. The most common route of transmission is from mother to baby during labor and delivery when the baby is exposed to GBS in the birth canal.
• GBS can also be transmitted through sexual contact, although this is rare. GBS is not spread through food or water.
• The risk of developing GBS infection depends on several factors, such as age, immune status, underlying medical conditions, and presence of invasive devices or procedures.
• The prevention of GBS infection mainly relies on screening pregnant women for vaginal and rectal colonization with GBS at 35 to 37 weeks of gestation and providing intrapartum antibiotic prophylaxis to those who test positive or have other risk factors.
• The diagnosis of GBS infection is based on the isolation and identification of the bacteria from clinical specimens, such as blood, cerebrospinal fluid, urine, or swabs. Various methods are available for laboratory detection of GBS, such as culture, latex agglutination, automated identification systems, and molecular techniques .
• The treatment of GBS infection involves the administration of appropriate antibiotics according to the site and severity of infection. Penicillin is the drug of choice for most cases of GBS infection. Alternative antibiotics are available for patients who are allergic to penicillin or have resistant strains of GBS.

Streptococcus agalactiae is a gram-positive, non-motile, non-spore-forming coccus that belongs to the genus Streptococcus, which consists of more than 50 different species of lactic acid bacteria.

The genus Streptococcus is differentiated from other lactic acid bacteria by the arrangement of the cells in chains, the presence of a cell wall composed of peptidoglycan and teichoic acids, and the ability to ferment carbohydrates.

Based on 16S rRNA gene sequence analysis, the genus Streptococcus belongs to the low (< 50 mol%) G+C branch of the gram-positive eubacteria, and is a member (type genus) of the family Streptococcaceae.

Streptococcus agalactiae is one of the thirteen species that belong to the pyogenic groups of streptococci, most of which are characterized by beta-hemolytic activity and its 16S rRNA sequencing. The species found in humans are also termed hemolytic streptococci.

Streptococcus agalactiae is also the only species present in the Lancefield Group B based on the presence of B antigen on its capsular polysaccharide. The Lancefield grouping is a serological classification of streptococci based on their cell wall carbohydrate antigens.

The capsular polysaccharide serves as the basis for serotyping of S. agalactiae in the reference laboratory and is also considered a major virulence factor of S. agalactiae. The capsular polysaccharide is made up of more than 100 repeating units of the monosaccharides galactose, glucose, N-acetylglucosamine, and N-acetylneuraminic acid (sialic acid).

S. agalactiae is subclassified into ten serotypes (Ia, Ib, II–IX) depending on the immunologic reactivity of their polysaccharide capsule. The serotypes differ in their distribution among human and animal hosts, their association with different clinical syndromes, and their susceptibility to vaccine-induced immunity.

The following is the taxonomical classification of S. agalactiae:

• Domain: Bacteria
• Phylum: Bacillota
• Class: Bacilli
• Order: Lactobacillales
• Family: Streptococcaceae
• Genus: Streptococcus
• Species: S. agalactiae

Streptococcus agalactiae has two major permanent hosts: humans and cattle. It was first isolated from cattle by Lehmann and Neumann in 1896, but later it was also found to be part of the human normal flora.

In humans, S. agalactiae primarily colonizes the gastrointestinal tract and the genitourinary tract of up to 30% of healthy adults, without causing any symptoms. However, it can also cause severe invasive infections in neonates, pregnant women, older adults, and immunocompromised individuals.

The gastrointestinal tract is recognized as a major reservoir for S. agalactiae and possibly the source of vaginal colonization. The bacteria can be transmitted to newborns from the infected or asymptomatic mothers via the birth canal during delivery. The bacteria can also penetrate through intact membranes and cause intrauterine infections or abortions.

In cattle, S. agalactiae is mostly found in the udder, where it causes bovine mastitis or inflammation of the udder in dairy cows. The species name `agalactiae` meaning `want of milk` alludes to this condition. It can also affect other animals such as chickens, dogs, dolphins, horses, lizards, camels, cats, fish, frogs, mice, and monkeys.

S. agalactiae is considered a pathobiont that can convert from the asymptomatic mucosal carriage state to a major bacterial pathogen causing severe invasive infections. It can overcome different barriers and invade various host compartments such as blood, cerebrospinal fluid, lungs, bones, joints, and skin.

The cells of S. agalactiae are spherical or ovoid Gram-positive cocci of the size 0.6–1.2 µm in diameter . However, some species may develop rod-like cells depending on the growth conditions.

The arrangement of the cells is characteristic of all Streptococci as the cells are arranged in chains, occurring in chains of seldom less than four cells and frequently in pairs or very long chains. The chains might be longer if the bacteria originate from a fluid culture.

Cross-walls during cell division are formed at right angles to the chain, and after division, an appearance of pairing may remain.

The organism is surrounded by a bacterial capsule composed of polysaccharide or exopolysaccharide that surrounds and protects the bacterium by preventing complement deposition and opsonization .

The capsular polysaccharide is covalently bound to the cell wall peptidoglycan, thus creating the mucoid capsule layer covering the bacterial surface.

The cell wall of S. agalactiae is composed of the typical peptidoglycan, along with various carbohydrate structures like teichoic acids, and a number of proteins.

The peptidoglycan present on the cell wall of S. agalactiae is of the type Lys–Ala1–3(Ser) and the group B-specific polysaccharide antigen is composed of rhamnose, N-acetylglucosamine, and galactose. This antigen not thought to be a virulence factor of the organism, nor is it important in natural immunity; however, it is a useful tool to identify these organisms in the clinical laboratory.

The cell membrane had a lipid-protein bilayer that helps in the transport of different molecules in and out of the cells through different transport channels or systems.

The growth of Streptococcus agalactiae on ordinary nutrient media is generally low in contrast to that of other Gram-positive species. Growth is more profuse on media enriched with blood, serum, or a fermentable carbohydrate. To avoid competition and to inhibit other Gram-positive organisms, selective media such as Granada medium or selective Strep agar are used . Many strains are capable of growing in media containing 40% bile. Some strains produce a yellow, orange, or brick-red pigment, and the growth may be enhanced by the addition of starch to the medium or by incubation with 5% carbon dioxide. Ideal growth is observed at the temperature of 20-35°C, whereas no growth is observed at either 10°C or 45°C. Growth is observed under neutral to acidic pH, but no growth is seen beyond the pH of 9.

The following are some cultural characteristics of S. agalactiae on different culture media:

• Nutrient Agar (NA): White to grey colored colonies of an average size of 1 mm in diameter. The colonies were round with raised elevation and an entire margin. Growth is mostly poor and requires air with supplied carbon dioxide.
• Blood Agar (BA): Typical smooth, non-pigmented, convex colonies with entire margin are observed on blood agar. Growth occurs readily on blood agar and exhibits various types of hemolysis viz. typical β-hemolysis, but with a narrow zone, α-double zone, or no hemolysis. The CAMP factor produced by most group B streptococci binds to erythrocyte membrane altered by Staphylococcus aureus sphingomyelinase C. This result in the unique ‘arrowhead’ pattern of hemolysis is seen on sheep blood agar when GBS is grown near colonies of S. aureus.
• Granada Medium: This is a selective and differential medium that allows the isolation and identification of S. agalactiae based on the production of a specific pigment called granadaene. On this medium, beta-hemolytic strains of S. agalactiae produce orange to salmon colonies that are easily visible under normal light. The pigment production is enhanced by incubation in anaerobic conditions. The colony coloration is very specific and does not occur with streptococci other than group B or other organisms.
  
  Biochemical characteristics of Streptococcus agalactiae
  

The biochemical characteristics of S. agalactiae can be used to differentiate it from other streptococci and to identify the species in the clinical laboratory. The following are some of the biochemical tests and their results for S. agalactiae:

• Fermentation: S. agalactiae can ferment various carbohydrates, producing acid but not gas. The fermentation pattern varies depending on the serotype and strain of the bacteria. Some of the carbohydrates that are commonly fermented by S. agalactiae are fructose, galactose, glucose, glycerol, lactose, maltose, ribose, sucrose, and trehalose . However, some carbohydrates that are not fermented by S. agalactiae are adonitol, arabinose, arabitol, arbutin, cellobiose, dulcitol, erythritol, glycogen, inulin, mannitol, melibiose, raffinose, salicin, sorbitol, and xylose .
• Enzymatic reactions: S. agalactiae can produce some enzymes that are involved in different metabolic pathways or virulence factors. Some of the enzymatic reactions that are positive for S. agalactiae are alkaline phosphatase and arginine dehydrolase . However, some of the enzymatic reactions that are negative for S. agalactiae are catalase, coagulase, esculin hydrolysis, gelatinase, oxidase, pyrrolidonyl arylamidase (PYR), urease, and Voges-Proskauer (VP) test .
• CAMP test: The CAMP test is a specific test for the identification of S. agalactiae based on the production of a diffusible extracellular protein called CAMP factor. The CAMP factor enhances the hemolytic activity of staphylococcal beta-hemolysin on sheep blood agar. When S. agalactiae is streaked perpendicular to Staphylococcus aureus on a blood agar plate and incubated overnight, a characteristic arrowhead-shaped zone of enhanced hemolysis is observed at the junction of the two streaks. This indicates a positive CAMP test for S. agalactiae.
• Hippurate hydrolysis: Hippurate hydrolysis is another specific test for the identification of S. agalactiae based on the ability of the bacteria to hydrolyze hippurate to glycine and benzoic acid. The test is performed by inoculating a tube containing sodium hippurate broth with S. agalactiae and incubating it for 2 hours at 37°C. Then, a few drops of ninhydrin reagent are added to the tube and heated in a boiling water bath for 10 minutes. A purple color indicates a positive hippurate hydrolysis test for S. agalactiae.

These biochemical tests can help in the rapid and accurate identification of S. agalactiae in clinical specimens and can also provide some insights into the metabolic capabilities and virulence factors of this important human pathogen.

Virulence factors are the factors, which a microorganism possess to causes disease in the host. Streptococcus agalactiae has many virulence factors that enable it to colonize, invade, and damage the host tissues, as well as evade the host immune system. Some of the major virulence factors of S. agalactiae are:

• Capsule: The capsule is a polysaccharide layer that surrounds the bacterial cell and protects it from phagocytosis and complement-mediated killing . The capsule is composed of repeating units of galactose, glucose, N-acetylglucosamine, and sialic acid. The capsule also serves as the basis for serotyping of S. agalactiae, as there are ten different serotypes (Ia, Ib, II–IX) based on the antigenic variation of the capsule .
• Lipoteichoic acid: Lipoteichoic acid (LTA) is a cell wall polymer that consists of glycerol phosphate or ribitol phosphate units. LTA mediates the adherence of S. agalactiae to various host cells, such as epithelial cells, erythrocytes, and placental cells . LTA also stimulates the production of pro-inflammatory cytokines by the host cells, which may contribute to tissue damage and inflammation.
• Beta hemolysin: Beta hemolysin is a pore-forming toxin that lyses red blood cells and other host cells by creating holes in their membranes . Beta hemolysin also induces the release of interleukin-8 (IL-8), a chemokine that attracts neutrophils to the site of infection . However, excessive neutrophil recruitment may cause tissue injury and inflammation.
• Hyaluronate lyase: Hyaluronate lyase is an enzyme that degrades hyaluronic acid, a major component of the extracellular matrix of connective tissues and nervous tissues . Hyaluronate lyase acts as a spreading factor, allowing S. agalactiae to penetrate deeper into the host tissues and overcome the mucosal barrier . Hyaluronate lyase may also facilitate the translocation of S. agalactiae across the placental barrier, leading to fetal infection.
• CAMP factor: CAMP factor is a protein that enhances the hemolytic activity of staphylococcal sphingomyelinase C on blood agar . CAMP factor also binds to the Fc portion of immunoglobulins, interfering with their opsonizing function . CAMP factor is used as a diagnostic test for S. agalactiae, as it produces a characteristic arrowhead-shaped zone of hemolysis when grown near Staphylococcus aureus colonies on blood agar.
• C5a peptidase: C5a peptidase is an enzyme that cleaves C5a, a complement component that acts as a potent chemoattractant for phagocytes . By degrading C5a, S. agalactiae reduces the recruitment of phagocytes to the site of infection, thus evading the host immune response .

• Surface proteins: S. agalactiae expresses various surface proteins that mediate adhesion, invasion, and immune evasion . Some examples are:

  • Alpha C protein: Alpha C protein is a surface protein that binds to fibrinogen and inhibits its conversion to fibrin by thrombin . This prevents clot formation and allows S. agalactiae to disseminate through the bloodstream .
  • Rib protein: Rib protein is a surface protein that binds to IgA1 and cleaves its hinge region, rendering it ineffective for opsonization and neutralization . Rib protein also binds to factor H, a complement regulator that inhibits the alternative pathway of complement activation .
  • Lmb protein: Lmb protein is a surface protein that binds to laminin, a component of the basement membrane of the placenta . Lmb protein may facilitate the invasion of S. agalactiae into the fetal compartment and cause intrauterine infection .

Streptococcus agalactiae is an important human pathogen that causes different severe neonatal as well as adult infections. The course of infection by S. agalactiae begins with the colonization and invasion of a number of different host compartments. Different virulence factors present in the bacteria like the polysaccharide capsule, the hemolysin, the C-proteins, the hyaluronate lyase, and the lipoteichoic acid, and a number of unknown bacterial components are involved in the pathogenesis of infection .

The following is the pathogenesis of infections caused by S. agalactiae:

• Transmission: Maternal colonization and vertical transmission of S. agalactiae are found in more than 95% of neonatal carriers, except for rare cases of transmission through nursery personnel or human milk. The colonization of the birth canal and perinatal transmission of S. agalactiae play a vital role in the pathogenesis of GBS disease. Most of the infections develop in the uterus, and the ascending bacteria reach the amniotic fluid, and the intake of contaminated fluid by the infant leads to the development of the invasive disease. However, penetration of S. agalactiae through intact membranes can also occur, leading to severe cases of intrauterine infection or abortion.
• Colonization: Colonization of the maternal genitourinary or gastrointestinal tract is the most important risk factor for GBS disease. Different factors like the proteinaceous component LTA of the bacterial cell wall and the surface proteins are assumed to be necessary for the adhesion of S. agalactiae to vaginal epithelial cells, buccal epithelial cells, pulmonary epithelial cells, and endothelial cells. Studies have demonstrated that streptococci adhere in two steps; the first is a relatively weak and reversible first interaction mediated by components of the cell wall and a second interaction mediated by proteins, leading to a firm adhesion of bacteria to eukaryotic cells. The adhesion of S. agalactiae to extracellular matrix proteins has been described for fibronectin and fibrinogen, but the corresponding adhesins on the streptococcal surface have not been defined. However, a novel surface protein (Lmb) of S. agalactiae has been identified that mediates the binding to human placental laminin, the major component of the placental basement membrane. Heavy colonization with S. agalactiae is with premature rupture of membranes, and several cases of penetration of S. agalactiae through intact membranes have been seen. In these situations, the bacteria get into close contact with basement membranes and Lmb protein might contribute to the ability of S. agalactiae to overcome the mucosal barrier.
• Invasion: During infection, S. agalactiae encounters a number of different barriers. In some cases of GBS disease, infection of the infant occurs through intact chorioamniotic membranes, requiring the bacteria to transverse chorion cells, amnion cells, and the placental basement membrane. S. agalactiae can enter different eukaryotic cells and has the ability to survive inside these cells, which is an essential mechanism for the invasion of different host compartments. Bacterial cells are taken up by active endocytosis, and inside the cells, bacteria are found within vacuoles. The ability of the organism to invade eukaryotic cells in vitro results in the ability to cause invasive infection. The invasion of eukaryotic cells is mediated through proteins of the cell surface and the capsular polysaccharide. Following evasion, the bacteria might enter the lower respiratory tract where numerous bacteria enclosed in atypical hyaline membranes after evading the host immune system. β-hemolysin produced by the bacteria results in marked pulmonary epithelial and endothelial cell injury, ultimately leading to pneumonia. Further intravascular invasion of bacteria and failure of the host to eliminate the pathogen might result in sepsis. The ability of S. agalactiae to induce proinflammatory cytokine production results in the release of tumor necrosis factor-alpha (TNF-α) IL-1 and IL-6, which causes further inflammatory damage to different parts of the body like the brain.

• Interaction with the host immune system: Following the entry of bacteria into sterile body sites, the host immune system attempts to clear the infecting organisms mainly by phagocytosis. Effective phagocytosis of S. agalactiae relies on opsonization through complement and serotype-specific antibodies. Employing different mechanisms, S. agalactiae can impair opsonophagocytosis. Capsular polysaccharides inhibit the deposition of complement component C3 and the activation of the alternative pathway. Proteins like the beta C protein and CAMP factor bind nonspecifically to the Fc portion of immunoglobulins, presumably rendering antibodies ineffective for opsonization. The recruitment of neutrophils to sites of infection through the chemotactic signal of complement component C5a is impaired by cleavage of this molecule through the C5a peptidase of S. agalactiae. S. agalactiae can evade phagocytosis as it can survive for more than 24 h inside of macrophages. Despite the lack of catalase activity, S. agalactiae is more resistant to killing through oxygen radicals.
  
  Clinical Manifestations of Streptococcus agalactiae
  

Streptococcus agalactiae can cause various types of infections in different populations, ranging from mild to severe and life-threatening. The most common clinical manifestations of S. agalactiae infection are:

• Neonatal infections: S. agalactiae is a leading cause of neonatal sepsis, meningitis, and pneumonia, especially in infants born prematurely or with low birth weight. Neonatal infections can be classified into early-onset (within the first week of life) and late-onset (after the first week of life) disease. Early-onset disease is usually acquired during delivery from the colonized maternal genital tract, whereas late-onset disease is acquired from the environment or other sources. The signs and symptoms of neonatal infection may include fever, low body temperature, difficulty feeding, sluggishness, weak muscle tone, difficulty breathing, irritability, jitteriness, seizures, rash, and jaundice.
• Pregnant individuals: S. agalactiae can cause urinary tract infection, chorioamnionitis (infection of the membranes and amniotic fluid), postpartum endometritis (infection of the uterus lining), and bacteremia (bacteria in the blood) in pregnant individuals. These infections can result in complications such as preterm labor, premature rupture of membranes, stillbirth, and maternal sepsis. Pregnant individuals may not have any symptoms or may have nonspecific symptoms such as fever, abdominal pain, vaginal discharge, or burning sensation during urination.

• Nonpregnant adults: S. agalactiae can cause bacteremia without a known focus and skin or soft tissue infections in nonpregnant adults. It can also cause other focal infections such as pneumonia, osteomyelitis (bone infection), septic arthritis (joint infection), endocarditis (heart valve infection), and meningitis. These infections are more common in adults with certain chronic conditions such as diabetes, cardiovascular disease, liver disease, renal disease, cancer, or immunosuppression. The symptoms of nonpregnant adult infection may vary depending on the site and severity of infection but may include fever, chills, malaise, pain, swelling, redness, pus formation, cough, shortness of breath, chest pain, headache, stiff neck, confusion, or altered mental status.

  Laboratory Diagnosis of Streptococcus agalactiae

The laboratory diagnosis of Streptococcus agalactiae (GBS) infection can be done by various methods, depending on the type of sample, the clinical presentation, and the availability of resources. The following are some of the common methods used for the identification and confirmation of GBS:

Sample collection

The type of sample collected depends on the site of infection and the patient`s condition. For example:

• For screening pregnant women for GBS colonization, vaginal and rectal swabs are taken between 35 and 37 weeks of gestation and sent in a transport medium within four hours of collection.
• For diagnosing neonatal sepsis or meningitis, blood and cerebrospinal fluid (CSF) samples are collected and cultured as soon as possible.
• For diagnosing skin or soft tissue infections, wound swabs or pus samples are collected and cultured.
• For diagnosing urinary tract infections, midstream urine samples are collected and cultured.

Morphological, Cultural and Biochemical characteristics

The initial identification of GBS can be done by observing the morphological, cultural, and biochemical characteristics of the isolates. For example:

• Gram stain: GBS appear as Gram-positive cocci in pairs or chains.
• Blood agar: GBS grow as small, round, grey-white colonies with a narrow zone of beta-hemolysis (complete lysis of red blood cells) on sheep or rabbit blood agar .
• CAMP test: GBS produce a CAMP factor that enhances the hemolysis caused by Staphylococcus aureus. When GBS are grown near S. aureus on blood agar, a characteristic arrowhead-shaped zone of hemolysis is seen .
• Bacitracin test: GBS are resistant to bacitracin, unlike other beta-hemolytic streptococci. A disc containing bacitracin is placed on a blood agar plate inoculated with GBS. No zone of inhibition around the disc indicates a negative test .
• Hippurate hydrolysis test: GBS can hydrolyze sodium hippurate to benzoic acid and glycine. A colorimetric reagent (ninhydrin or ferric chloride) is added to the hippurate broth inoculated with GBS. A purple or blue color indicates a positive test .

Immunological test

The definitive identification of GBS can be done by detecting the group B antigen on the bacterial cell wall using immunological methods. For example:

• Latex agglutination test: This test uses latex particles coated with antibodies against the group B antigen. A drop of latex reagent is mixed with a bacterial suspension on a glass slide. Agglutination (clumping) of latex particles indicates a positive test .
• Lancefield precipitation test: This test uses antisera against the group B antigen to form a precipitate with GBS in a capillary tube. The tube is centrifuged and examined for a visible line of precipitation at the bottom .

Automated identification systems

Some commercial systems can perform rapid and accurate identification of GBS based on batteries of physiological tests or molecular methods. For example:

• VITEK 2: This system uses cards containing different substrates and indicators to measure the metabolic activity of GBS. The results are interpreted by a computer software that assigns an identification code to the isolate .
• MALDI-TOF MS: This system uses matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to measure the mass-to-charge ratio of proteins extracted from GBS. The spectra are compared with a database of reference spectra to identify the isolate .

Molecular diagnosis

Molecular methods can provide rapid and accurate identification of GBS based on the detection of specific genes or sequences. For example:

• PCR: Polymerase chain reaction (PCR) can amplify and detect specific DNA targets in GBS, such as the cfb gene (encoding CAMP factor), the cps gene (encoding capsular polysaccharide), or the serotype-specific genes (encoding serotype antigens) . PCR can be performed in singleplex or multiplex formats, depending on the number of targets to be detected.
• DNA sequencing: DNA sequencing can determine the nucleotide sequence of specific genes or regions in GBS, such as the 16S rRNA gene, the housekeeping genes, or the serotype-specific genes . DNA sequencing can provide accurate identification and typing of GBS, as well as information on antimicrobial resistance and virulence factors.

Treatment of Streptococcus agalactiae

Streptococcus agalactiae (Group B Streptococcus or GBS) is a gram-positive bacterium that can cause serious infections in neonates, pregnant women, and immunocompromised adults. The treatment of S. agalactiae infections depends on the site and severity of the infection, the susceptibility of the isolate, and the patient`s allergy status.

• The mainstay of treatment for invasive S. agalactiae infections is intravenous penicillin G or ampicillin . These antibiotics are effective against most strains of S. agalactiae and have a narrow spectrum of activity, minimizing the risk of adverse effects and resistance.
• In patients who are allergic to penicillin or ampicillin, alternative therapies include clindamycin, erythromycin, vancomycin, or fluoroquinolones . However, some strains of S. agalactiae may be resistant to these antibiotics, so susceptibility testing is recommended before initiating therapy.
• In some cases, a combination of antibiotics may be used to enhance the efficacy or prevent the emergence of resistance. For example, an aminoglycoside (such as gentamicin) may be added to penicillin or ampicillin for endocarditis or meningitis caused by S. agalactiae . Similarly, a beta-lactamase inhibitor (such as sulbactam) may be added to ampicillin for skin and soft tissue infections caused by S. agalactiae.
• The duration of therapy depends on the type and severity of the infection. Generally, 10 days of therapy is sufficient for bacteremia, pneumonia, pyelonephritis, and skin and soft tissue infections caused by S. agalactiae . Longer courses of therapy (14 days or more) are required for meningitis, endocarditis, osteomyelitis, and ventriculitis caused by S. agalactiae .
• In addition to antibiotic therapy, supportive care and surgical interventions may be needed for some patients with S. agalactiae infections. For example, patients with septic shock may require fluid resuscitation and vasopressors; patients with abscesses may require drainage; and patients with endocarditis may require valve replacement .

Prevention of Streptococcus agalactiae

The prevention of Streptococcus agalactiae infections is mainly focused on reducing the risk of neonatal and maternal disease, as these are the most severe and common outcomes of GBS colonization and invasion. The following are some of the strategies for preventing S. agalactiae infections:

• Intrapartum antibiotic prophylaxis (IAP): This is the administration of antibiotics to pregnant women who are colonized with GBS or have risk factors for GBS transmission during labor and delivery. The aim of IAP is to reduce the bacterial load in the maternal genital tract and prevent early-onset GBS disease in the newborn. The recommended agent for IAP is penicillin or ampicillin, with alternatives for women who are allergic to beta-lactams . IAP is only effective for early-onset disease and does not prevent late-onset disease or maternal infections.
• Screening and treatment of GBS colonization: This is the testing of vaginal and rectal swabs for GBS culture or PCR in pregnant women at 35 to 37 weeks of gestation, and treating those who are positive with oral antibiotics before labor . This may reduce the need for IAP and the emergence of antibiotic resistance. However, this strategy has some limitations, such as false-negative results, recolonization after treatment, and lack of evidence for its effectiveness.
• Vaccination: This is the development and administration of vaccines that can induce protective immunity against GBS capsular polysaccharides or other antigens in pregnant women, infants, or other high-risk groups . Vaccination may offer a long-term and broad-spectrum solution for preventing GBS disease, especially late-onset disease and maternal infections. However, there are currently no licensed vaccines for GBS, and several challenges remain in vaccine development, such as safety, efficacy, coverage, and acceptability.

Streptococcus agalactiae (Group B Streptococcus or GBS) is a gram-positive bacterium that can cause serious infections in neonates, pregnant women, and immunocompromised adults. The treatment of S. agalactiae infections depends on the site and severity of the infection, the susceptibility of the isolate, and the patient`s allergy status.

• The mainstay of treatment for invasive S. agalactiae infections is intravenous penicillin G or ampicillin . These antibiotics are effective against most strains of S. agalactiae and have a narrow spectrum of activity, minimizing the risk of adverse effects and resistance.
• In patients who are allergic to penicillin or ampicillin, alternative therapies include clindamycin, erythromycin, vancomycin, or fluoroquinolones . However, some strains of S. agalactiae may be resistant to these antibiotics, so susceptibility testing is recommended before initiating therapy.
• In some cases, a combination of antibiotics may be used to enhance the efficacy or prevent the emergence of resistance. For example, an aminoglycoside (such as gentamicin) may be added to penicillin or ampicillin for endocarditis or meningitis caused by S. agalactiae . Similarly, a beta-lactamase inhibitor (such as sulbactam) may be added to ampicillin for skin and soft tissue infections caused by S. agalactiae.
• The duration of therapy depends on the type and severity of the infection. Generally, 10 days of therapy is sufficient for bacteremia, pneumonia, pyelonephritis, and skin and soft tissue infections caused by S. agalactiae . Longer courses of therapy (14 days or more) are required for meningitis, endocarditis, osteomyelitis, and ventriculitis caused by S. agalactiae .
• In addition to antibiotic therapy, supportive care and surgical interventions may be needed for some patients with S. agalactiae infections. For example, patients with septic shock may require fluid resuscitation and vasopressors; patients with abscesses may require drainage; and patients with endocarditis may require valve replacement .

The prevention of Streptococcus agalactiae infections is mainly focused on reducing the risk of neonatal and maternal disease, as these are the most severe and common outcomes of GBS colonization and invasion. The following are some of the strategies for preventing S. agalactiae infections:

• Intrapartum antibiotic prophylaxis (IAP): This is the administration of antibiotics to pregnant women who are colonized with GBS or have risk factors for GBS transmission during labor and delivery. The aim of IAP is to reduce the bacterial load in the maternal genital tract and prevent early-onset GBS disease in the newborn. The recommended agent for IAP is penicillin or ampicillin, with alternatives for women who are allergic to beta-lactams . IAP is only effective for early-onset disease and does not prevent late-onset disease or maternal infections.
• Screening and treatment of GBS colonization: This is the testing of vaginal and rectal swabs for GBS culture or PCR in pregnant women at 35 to 37 weeks of gestation, and treating those who are positive with oral antibiotics before labor . This may reduce the need for IAP and the emergence of antibiotic resistance. However, this strategy has some limitations, such as false-negative results, recolonization after treatment, and lack of evidence for its effectiveness.
• Vaccination: This is the development and administration of vaccines that can induce protective immunity against GBS capsular polysaccharides or other antigens in pregnant women, infants, or other high-risk groups . Vaccination may offer a long-term and broad-spectrum solution for preventing GBS disease, especially late-onset disease and maternal infections. However, there are currently no licensed vaccines for GBS, and several challenges remain in vaccine development, such as safety, efficacy, coverage, and acceptability.

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