Streptococcus mitis- An Overview

Streptococcus mitis is a type of bacteria that is part of the normal flora of the human body, especially in the oropharynx, skin, and gastrointestinal tract . It is a Gram-positive coccus that is arranged in chains or pairs . It can cause infections such as endocarditis, bacteremia, and septicemia if it escapes from its niche or in immunocompromised patients . It may also be associated with colon adenocarcinoma.

The genus name `mitis` has been derived from the Latin term `mitis` meaning mild, indicating that it is an organism with low pathogenicity and virulence that is involved in different types of mild infections. It was first isolated and discovered by Andrewes and Horder in 1906 from the human oropharynx region. S. mitis is the primary species of the mitis group consisting of twelve other species including the highly pathogenic S. pneumoniae. The species are put under the mitis group of Streptococci on the basis of their 16S rRNA gene sequences and nucleic acid hybridization data.

S. mitis is a mesophilic alpha-hemolytic species of Streptococcus that inhabits the oral cavity. It is a coccus (spherical shaped), gram-positive, catalase negative, and facultative anaerobe. It was previously classified as Streptococcus mitior. Streptococcus mitis is known to cause several medical conditions one of them being infective endocarditis.

S. mitis is competent for natural genetic transformation, which means that it can take up exogenous DNA and incorporate it into its genome by homologous recombination. This allows it to acquire new genes and traits from other bacteria, such as antibiotic resistance or virulence factors. S. mitis can also employ a predatory fratricidal mechanism for active acquisition of homologous DNA, where it kills other bacteria and uses their DNA as a source of genetic material.

S. mitis has been reported to survive for over two years on the Surveyor 3 probe on the Moon, but this is most likely due to contamination upon return to Earth. The Apollo 12 crew received pieces of Surveyor in 1969, one of these was the TV camera. The probe was then analyzed to consider how the lunar environment affected the material. S. mitis was found inside a piece of foam located inside the camera, but it was probably introduced during handling or storage after landing.

Streptococcus mitis belongs to the genus Streptococcus, which is a diverse group of gram-positive, non-spore-forming bacteria that produce lactic acid as a major end product of carbohydrate metabolism. The genus Streptococcus is classified within the phylum Firmicutes, class Bacilli, order Lactobacillales, and family Streptococcaceae .

The genus Streptococcus currently consists of over 50 recognized species, most of which fall within “species groups” that are identified on the basis of their 16S rRNA gene sequences . The 16S rRNA gene sequence analysis is the most reliable method for the classification and identification of streptococci at the species level .

Streptococcus mitis is one of the pioneer species of the mitis group, which comprises 12 other species, including the highly pathogenic Streptococcus pneumoniae (pneumococcus) . The mitis group of streptococci is characterized by their alpha-hemolytic activity on blood agar, their susceptibility to optochin, and their lack of Lancefield antigens .

The species name ‘mitis’ is derived from the Latin word meaning ‘mild’, indicating that it is an organism with low pathogenicity and virulence that is involved in different types of mild infections . However, S. mitis can also cause serious infections such as bacteremia and infective endocarditis in immunocompromised individuals or those with underlying medical conditions .

Streptococcus mitis was first isolated and described by Andrewes and Horder in 1906 from the human oropharynx region . Since then, it has been poorly classified with several synonyms being applied to the same species. However, recent phenotypic and genetic studies have provided a more clear and accurate taxonomic description of the species .

According to the latest taxonomic update by the List of Prokaryotic Names with Standing in Nomenclature (LPSN), the valid name for this species is Streptococcus mitis Andrewes and Horder 1906 (Approved Lists 1980). Some of the synonyms for this species are:

• Streptococcus mitior
• Streptococcus oralis subsp. mitis
• Streptococcus sanguinis subsp. mitis
• Streptococcus salivarius subsp. mitior
• Streptococcus salivarius subsp. salivarius var. mitior
• Streptococcus salivarius var. mitior

Streptococcus mitis is a commensal bacterium that primarily resides in the oral cavity, which includes the mouth, nasopharynx, and throat. It is one of the pioneer species that colonize the oral cavity of healthy human neonates, along with S. oralis. It can adhere to various surfaces in the oral cavity, such as the teeth, the mucosal membrane, and the saliva-coated pellicle. It can also participate in the initial colonization of tooth enamel and may be involved in dental caries.

Besides the oral cavity, S. mitis can also colonize other areas of the human body, such as the skin, the gastrointestinal tract, and the genital tract. However, these are less common sites of colonization and may depend on the host factors and environmental conditions. S. mitis can also cause infections when introduced into normally sterile compartments of the body or in immunocompromised patients. Some of the infections caused by S. mitis include bacteremia, endocarditis, meningitis, eye infections, pneumonia, and urinary tract infections.

S. mitis is a facultative anaerobe that can grow in both aerobic and anaerobic conditions. It prefers a temperature range of 18-40°C, with an optimum temperature of 37°C, which is the average body temperature of the host. It can also tolerate fluctuations in pH, nutrient availability, oxygen tension, and osmolality that occur in the oral cavity. S. mitis requires enriched media for growth, such as blood agar or chocolate agar, where it produces α-hemolysis. It can also grow on selective media like brain heart infusion agar or trypticase soy agar with defibrinated sheep blood. Most strains of S. mitis are unable to grow in the presence of 6.5% NaCl, whereas a few strains may grow in 4% NaCl.

The cells of S. mitis are Gram-positive, oval, or elliptical in shape with an average diameter of 0.6 to 0.8 µm. The cells are arranged in chains, like all other Streptococci, but the cells are frequently observed in pairs and short chains. Longer chains are observed when grown in agar media. The arrangement of Streptococci is the result of successive division planes that are parallel to one another as in rod-shaped bacteria.

The organism is catalase-negative, facultative anaerobe, not capsulated, and usually carries sparsely distributed, long fibrils on the surface. Extracellular surface structures and a variety of ell appendages of different lengths frequently occur in most strains. The density of the structures and the appendages differs with strains.

The cell wall is composed of peptidoglycan, C-polysaccharide, and teichoic acid. The peptidoglycan type is Lys-direct. As in other gram-positive cell walls, the peptidoglycan consists of multiple glycan chains that are cross-linked through short peptides, and the glycan moiety is composed of alternating β-1,4-linked units of N-acetylglucosamine and N-acetylmuramic acid. The cell wall contains ribitol teichoic acid and lacks significant amounts of rhamnose. It contains phosphorylcholine residues in the teichoic acids of its cellular envelope.

There are various cell-wall-associated surface proteins present on the cell wall that aid in the binding of the organism to different host surfaces. Underneath the cell wall is a cell membrane composed of the lipid-protein bilayer, along with different transport mechanism for the movement of molecules in and out of the cell.

Figure: (A) Cells of S. mitis (Gram stain). (B) Colonies of S. mitis (TPY agar plate). (C) Colonies of S. mitis (BHI agar plate). (D) Colonies of S. mitis (stereomicroscope). Image Source: Atlas of Oral Microbiology (ScienceDirect).

Streptococcus mitis grows poorly on general media like nutrient agar and thus requires the addition of some antimicrobials and carbohydrates to make the media more selective for the organism. Media supplemented with blood, sucrose, and serum show more profuse growth. Blood agar and chocolate agar are commonly used in the identification of S. mitis to observe the hemolysis. It is a facultative anaerobe, so abundant growth is observed in the air with 5% carbon dioxide at 37°C. Most strains are unable to grow in the presence of 6.5% NaCl, whereas a few strains may grow in 4% NaCl.

• Nutrient Agar: White to grey colored colonies of an average size of 1 mm in diameter are observed on nutrient agar. The colonies are round with raised elevation and an entire margin. Growth is mostly poor and requires air with supplied carbon dioxide.
• Blood agar: 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, but mostly α-hemolysis. About 1-2 mm of a green-colored zone of hemolysis is observed on blood agar. Pronounced greening is observed on chocolate agar.

The biochemical characteristics of S. mitis can be determined by performing various tests that measure the fermentation of different carbohydrates and the production of different enzymes. The following table summarizes some of the common biochemical tests and their results for S. mitis:

S. mitis can also be differentiated from other Streptococci by its ability to ferment different carbohydrates. The following table shows the fermentation patterns of S. mitis for some common sugars:

The biochemical characteristics of S. mitis can help in the identification and confirmation of the organism from clinical specimens. However, these tests may not be sufficient to distinguish S. mitis from other closely related species, such as S. oralis and S. pneumoniae. Therefore, additional tests, such as serological or molecular methods, may be required for more accurate diagnosis.

S. mitis has generally been considered a relatively benign oral streptococcus and member of the oral commensal flora. Nevertheless, S. mitis is involved in a range of invasive disease in humans and lately, has emerged as a cause of bloodstream infections in immune-compromised patients, and in patients undergoing cytotoxic anti-cancer chemotherapy. S. mitis is considered a leading cause of infective endocarditis and bacteremia, among the oral streptococci.

Very few studies have been done regarding the role of S. mitis virulence factors, which is why there is minimal information about the streptococcal virulence factors and their roles in disease pathogenesis. Some of the known and studied virulence factors of S. mitis that is involved in the pathogenesis of diseases are:

• Phage proteins: The binding of S. mitis to human platelets contributes to the pathogenesis of S. mitis infective endocarditis. Platelet binding by S. mitis is mediated in part by two bacteriophages encoded proteins, PblA and PblB. Both PblA and PblB produced by the bacteriophage mediate the attachment of the bacteriophage to the choline residues present on the cell walls of viable bacteria where they then enable the binding of viable bacteria to platelets on the host. The sialic acid of the platelet membrane ganglioside is the target receptor for the phage-encoded proteins PblA and PblB. Other virulence factors, in addition to PblA and PblA that mediate the binding of the bacteria to platelets, are yet not wholly understood.

• Immunoglobulin A1 protease: Streptococcus mitis can produce an IgA1 protease, which is homologous to the IgA1 proteases of S. oralis. These proteases are cell-wall-anchored zinc metalloproteases that cleave peptide bonds in IgA1. This proteolytic cleavage of IgA1 by the protease generates Fab and Fc fragments which can dissociate the recognition of S. mitis antigens from mechanisms for their elimination. In addition to this, the remaining bacterial bound Fab fragments could mask the epitopes from the immune system and prevent the binding of other antibody isotypes, activation of complement, and complement-mediated lysis.

• Wall-associated surface proteins: There are about 18 predicted cell-wall-associated surface proteins bearing the cell wall attachment motif LPXTG encoded within the genome of S. mitis. Some of these proteins include the NanA2 protein that binds to sialic acid of the platelets and MonX, which is a platelet-binding adhesion. These proteins are involved in the colonization of the host surfaces and pathogenesis of the disease.

• Cytolysin: Streptococcus mitis does not produce a wide range of toxins, but it has been shown to encode and produce a toxin, which is structurally and functionally similar to the S. pneumoniae pneumolysin and the S. intermedius intermedilysin. The S. mitis -specific toxin, named mitilysin, is functionally similar to pneumolysin in hemolytic assays and cross-reacts with pneumolysin antibodies. However, this cytotoxin has only been identified in a few strains of S. mitis, and studies related to its role in the pathogenesis of the infections have yet not been done.

  Pathogenesis of Streptococcus mitis

Streptococcus mitis is a commensal bacterium that colonizes the oral cavity and other mucosal surfaces of the human body. However, under certain conditions, it can act as an opportunistic pathogen and cause various infections, such as endocarditis, bacteremia, meningitis, and pneumonia. The pathogenesis of S. mitis involves several steps, such as transmission, adhesion, invasion, and interaction with the immune system.

• Transmission: S. mitis is transmitted from person to person through direct contact or respiratory droplets. It can also be acquired from the environment or from other sites of the body where it normally resides as a part of the normal flora. S. mitis can enter the bloodstream through oral trauma, dental procedures, or mucosal lesions and reach other organs or tissues where it can cause infection.
• Adhesion: S. mitis expresses various surface proteins and adhesins that enable it to adhere to different host cells and surfaces, such as epithelial cells, platelets, fibrinogen, collagen, and extracellular matrix. These adhesins also facilitate the formation of biofilms, which are complex communities of bacteria embedded in a matrix of extracellular polymeric substances. Biofilms provide protection from host defenses and antibiotics and enhance the persistence and virulence of S. mitis.
• Invasion: S. mitis can invade host cells and tissues by producing enzymes, toxins, and other factors that damage the cell membrane or disrupt the cytoskeleton. One of the toxins produced by S. mitis is mitilysin, which is a pore-forming cytotoxin that lyses erythrocytes, leukocytes, endothelial cells, and epithelial cells. Mitilysin also activates the complement system and induces inflammation and tissue damage. Another factor involved in invasion is the IgA1 protease, which cleaves IgA1 antibodies and impairs the mucosal immunity.
• Interaction with the immune system: S. mitis can evade or modulate the host immune system by various mechanisms, such as antigenic variation, molecular mimicry, immune suppression, and immune evasion. Antigenic variation refers to the ability of S. mitis to alter its surface antigens and avoid recognition by antibodies or immune cells. Molecular mimicry refers to the expression of molecules that resemble host molecules and interfere with immune recognition or activation. Immune suppression refers to the production of factors that inhibit or downregulate the immune response, such as cytokines, chemokines, or nitric oxide. Immune evasion refers to the escape from phagocytosis or complement-mediated lysis by using capsules, surface proteins, or biofilms.

The pathogenesis of S. mitis depends on the host factors, such as age, immunity, underlying diseases, and medical interventions. S. mitis is more likely to cause infection in immunocompromised patients or patients with damaged heart valves or prosthetic devices. The most common infections caused by S. mitis are endocarditis and bacteremia, which are associated with high mortality and morbidity rates.

Clinical manifestations of Streptococcus mitis

Streptococcus mitis is usually a harmless commensal of the human oral cavity, but it can also cause various infections in immunocompromised or elderly patients, or in patients undergoing cytotoxic chemotherapy. Some of the common clinical manifestations of S. mitis infections are:

• Strep throat: S. mitis can cause pharyngitis or tonsillitis, which are characterized by sore throat, fever, swollen lymph nodes, and difficulty swallowing. Strep throat can be diagnosed by throat swab culture or rapid antigen test, and treated with antibiotics such as penicillin or amoxicillin.
• Bacteremia and endocarditis: S. mitis can enter the bloodstream through oral trauma, dental procedures, or mucosal lesions, and cause bacteremia, which is the presence of bacteria in the blood. Bacteremia can lead to infective endocarditis, which is the infection of the heart valves or endocardium. S. mitis is one of the leading causes of infective endocarditis among the oral streptococci. Bacteremia and endocarditis can manifest as fever, chills, fatigue, anemia, heart murmur, embolic complications, and positive blood cultures . Bacteremia and endocarditis can be treated with antibiotics such as penicillin or vancomycin, sometimes in combination with gentamicin or rifampin . In some cases, surgical removal or replacement of the infected valve may be required.
• Meningitis: S. mitis can cause meningitis, which is the inflammation of the meninges, the membranes that cover the brain and spinal cord. Meningitis can occur as a complication of bacteremia, endocarditis, sinusitis, otitis media, or head trauma. Meningitis can present as headache, neck stiffness, photophobia, nausea, vomiting, altered mental status, and positive cerebrospinal fluid (CSF) culture. Meningitis can be treated with antibiotics such as ceftriaxone and ampicillin.
• Lung abscess: S. mitis can cause lung abscess, which is a localized collection of pus in the lung parenchyma. Lung abscess can occur as a result of aspiration of oral secretions, especially in patients with poor oral hygiene or dental infections. Lung abscess can manifest as cough, sputum production, chest pain, fever, weight loss, and positive sputum culture. Lung abscess can be treated with antibiotics such as clindamycin or metronidazole, sometimes in combination with surgical drainage or percutaneous aspiration.
• Urinary tract infection: S. mitis can cause urinary tract infection (UTI), which is the infection of the urethra, bladder, ureters, or kidneys. UTI can occur as a result of hematogenous spread from other sites of infection, or from direct inoculation during catheterization or sexual intercourse. UTI can present as dysuria, frequency, urgency, hematuria, flank pain, fever, and positive urine culture. UTI can be treated with antibiotics such as nitrofurantoin or trimethoprim-sulfamethoxazole.
• Septic arthritis: S. mitis can cause septic arthritis, which is the infection of the joint space. Septic arthritis can occur as a complication of bacteremia or endocarditis, or from direct inoculation during trauma or surgery. Septic arthritis can manifest as joint pain, swelling, redness, warmth, reduced range of motion, fever, and positive synovial fluid culture. Septic arthritis can be treated with antibiotics such as ceftriaxone or vancomycin.

Lab Diagnosis of Streptococcus mitis

The diagnosis of S. mitis from clinical specimens is primarily involved in the identification of the organism from these specimens. Depending on the site of infection, different samples are taken for diagnosis. For oral infection, swabs and dental plaques are collected, whereas for urinary tract infections, urine is collected. The following are different types of diagnostic methods that can be employed for the correct isolation and identification of S. mitis:

• Morphological, cultural, and biochemical characteristics: Oral streptococci can often be isolated on selective media where colony morphology provides the first basis for the identification of the organism. The appearance of typical smooth, non-pigmented, convex colonies with entire margin on blood agar with α-hemolysis indicates the presence of S. mitis. Isolation is then followed by the microscopic observation of the organism for the cell morphology and arrangement. The appearance of Gram-positive, non-motile, non-spore-forming cocci in pairs or short chains provide further basis for the presence of S. mitis. Biochemical tests are then performed for the species determination and confirmation of the organism. Lancefield antigen grouping can also be performed as some strains of S. mitis react to K and O antisera while others are non-groupable.

• Rapid diagnosis: Besides the traditional methods of species identification, commercial rapid identification kits for species identification of Streptococcus are also available now. Commercial kits such as Rapid Strep 32 can be used for the identification of Streptococcus species. In the case of S. mitis, the identification is based on the analysis of their microbial cellular fatty acid compositions.

• Molecular diagnosis: Determination of 16S rRNA sequence is the most critical molecular method for the confirmation of S. mitis. Besides, tests like PCR and DNA sequencing can be performed for a more accurate confirmation and diagnosis. To some extent, identification may also be achieved with DNA probes that hybridize exclusively with the individual species.

  Treatment of Streptococcus mitis infections

Streptococcus mitis infections are usually mild and can be treated with antibiotics. However, some strains of S. mitis have developed resistance to certain antibiotics, such as penicillin, erythromycin, and clindamycin. Therefore, antibiotic susceptibility testing is recommended before initiating therapy.

The choice of antibiotic depends on the type and severity of the infection, the patient`s medical history, and the local resistance patterns. Some of the commonly used antibiotics for S. mitis infections are:

• Penicillin G: This is the preferred antibiotic for most S. mitis infections, especially endocarditis and meningitis . It is given intravenously in high doses (2-4 million units every 4 hours) for at least 4 weeks for endocarditis and 10-14 days for meningitis. Penicillin G can be combined with gentamicin for synergy against some strains of S. mitis.
• Ceftriaxone: This is an alternative antibiotic for patients who are allergic to penicillin or have penicillin-resistant S. mitis infections . It is given intravenously in a single dose of 2 grams per day for endocarditis and meningitis. Ceftriaxone can also be combined with gentamicin for synergy against some strains of S. mitis.
• Clindamycin: This is another alternative antibiotic for patients who are allergic to penicillin or have penicillin-resistant S. mitis infections . It is given intravenously in doses of 600-900 mg every 8 hours or orally in doses of 300-450 mg four times a day for endocarditis and meningitis.
• Vancomycin: This is a last-resort antibiotic for patients who have severe or life-threatening S. mitis infections that are resistant to other antibiotics . It is given intravenously in doses of 15 mg/kg every 12 hours for endocarditis and meningitis.

In addition to antibiotic therapy, some patients may require surgical intervention to remove or replace infected devices, such as prosthetic heart valves or catheters, that may serve as a source of persistent infection .

Patients with S. mitis infections should also receive supportive care, such as hydration, pain relief, fever control, and nutritional support, as needed.

Streptococcus mitis is usually a harmless commensal of the human oral cavity, but it can also cause various infections in immunocompromised or elderly patients, or in patients undergoing cytotoxic chemotherapy. Some of the common clinical manifestations of S. mitis infections are:

• Strep throat: S. mitis can cause pharyngitis or tonsillitis, which are characterized by sore throat, fever, swollen lymph nodes, and difficulty swallowing. Strep throat can be diagnosed by throat swab culture or rapid antigen test, and treated with antibiotics such as penicillin or amoxicillin.
• Bacteremia and endocarditis: S. mitis can enter the bloodstream through oral trauma, dental procedures, or mucosal lesions, and cause bacteremia, which is the presence of bacteria in the blood. Bacteremia can lead to infective endocarditis, which is the infection of the heart valves or endocardium. S. mitis is one of the leading causes of infective endocarditis among the oral streptococci. Bacteremia and endocarditis can manifest as fever, chills, fatigue, anemia, heart murmur, embolic complications, and positive blood cultures . Bacteremia and endocarditis can be treated with antibiotics such as penicillin or vancomycin, sometimes in combination with gentamicin or rifampin . In some cases, surgical removal or replacement of the infected valve may be required.
• Meningitis: S. mitis can cause meningitis, which is the inflammation of the meninges, the membranes that cover the brain and spinal cord. Meningitis can occur as a complication of bacteremia, endocarditis, sinusitis, otitis media, or head trauma. Meningitis can present as headache, neck stiffness, photophobia, nausea, vomiting, altered mental status, and positive cerebrospinal fluid (CSF) culture. Meningitis can be treated with antibiotics such as ceftriaxone and ampicillin.
• Lung abscess: S. mitis can cause lung abscess, which is a localized collection of pus in the lung parenchyma. Lung abscess can occur as a result of aspiration of oral secretions, especially in patients with poor oral hygiene or dental infections. Lung abscess can manifest as cough, sputum production, chest pain, fever, weight loss, and positive sputum culture. Lung abscess can be treated with antibiotics such as clindamycin or metronidazole, sometimes in combination with surgical drainage or percutaneous aspiration.
• Urinary tract infection: S. mitis can cause urinary tract infection (UTI), which is the infection of the urethra, bladder, ureters, or kidneys. UTI can occur as a result of hematogenous spread from other sites of infection, or from direct inoculation during catheterization or sexual intercourse. UTI can present as dysuria, frequency, urgency, hematuria, flank pain, fever, and positive urine culture. UTI can be treated with antibiotics such as nitrofurantoin or trimethoprim-sulfamethoxazole.
• Septic arthritis: S. mitis can cause septic arthritis, which is the infection of the joint space. Septic arthritis can occur as a complication of bacteremia or endocarditis, or from direct inoculation during trauma or surgery. Septic arthritis can manifest as joint pain, swelling, redness, warmth, reduced range of motion, fever, and positive synovial fluid culture. Septic arthritis can be treated with antibiotics such as ceftriaxone or vancomycin.

The diagnosis of S. mitis from clinical specimens is primarily involved in the identification of the organism from these specimens. Depending on the site of infection, different samples are taken for diagnosis. For oral infection, swabs and dental plaques are collected, whereas for urinary tract infections, urine is collected. The following are different types of diagnostic methods that can be employed for the correct isolation and identification of S. mitis:

• Morphological, cultural, and biochemical characteristics: Oral streptococci can often be isolated on selective media where colony morphology provides the first basis for the identification of the organism. The appearance of typical smooth, non-pigmented, convex colonies with entire margin on blood agar with α-hemolysis indicates the presence of S. mitis. Isolation is then followed by the microscopic observation of the organism for the cell morphology and arrangement. The appearance of Gram-positive, non-motile, non-spore-forming cocci in pairs or short chains provide further basis for the presence of S. mitis. Biochemical tests are then performed for the species determination and confirmation of the organism. Lancefield antigen grouping can also be performed as some strains of S. mitis react to K and O antisera while others are non-groupable.

• Rapid diagnosis: Besides the traditional methods of species identification, commercial rapid identification kits for species identification of Streptococcus are also available now. Commercial kits such as Rapid Strep 32 can be used for the identification of Streptococcus species. In the case of S. mitis, the identification is based on the analysis of their microbial cellular fatty acid compositions.

• Molecular diagnosis: Determination of 16S rRNA sequence is the most critical molecular method for the confirmation of S. mitis. Besides, tests like PCR and DNA sequencing can be performed for a more accurate confirmation and diagnosis. To some extent, identification may also be achieved with DNA probes that hybridize exclusively with the individual species.

  Treatment of Streptococcus mitis infections

Streptococcus mitis infections are usually mild and can be treated with antibiotics. However, some strains of S. mitis have developed resistance to certain antibiotics, such as penicillin, erythromycin, and clindamycin. Therefore, antibiotic susceptibility testing is recommended before initiating therapy.

The choice of antibiotic depends on the type and severity of the infection, the patient`s medical history, and the local resistance patterns. Some of the commonly used antibiotics for S. mitis infections are:

• Penicillin G: This is the preferred antibiotic for most S. mitis infections, especially endocarditis and meningitis . It is given intravenously in high doses (2-4 million units every 4 hours) for at least 4 weeks for endocarditis and 10-14 days for meningitis. Penicillin G can be combined with gentamicin for synergy against some strains of S. mitis.
• Ceftriaxone: This is an alternative antibiotic for patients who are allergic to penicillin or have penicillin-resistant S. mitis infections . It is given intravenously in a single dose of 2 grams per day for endocarditis and meningitis. Ceftriaxone can also be combined with gentamicin for synergy against some strains of S. mitis.
• Clindamycin: This is another alternative antibiotic for patients who are allergic to penicillin or have penicillin-resistant S. mitis infections . It is given intravenously in doses of 600-900 mg every 8 hours or orally in doses of 300-450 mg four times a day for endocarditis and meningitis.
• Vancomycin: This is a last-resort antibiotic for patients who have severe or life-threatening S. mitis infections that are resistant to other antibiotics . It is given intravenously in doses of 15 mg/kg every 12 hours for endocarditis and meningitis.

In addition to antibiotic therapy, some patients may require surgical intervention to remove or replace infected devices, such as prosthetic heart valves or catheters, that may serve as a source of persistent infection .

Patients with S. mitis infections should also receive supportive care, such as hydration, pain relief, fever control, and nutritional support, as needed.

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