The genus Streptococcus is composed of a large, diverse group of Gram-positive bacteria, many of which are harmless residents of the human body. Viridans Streptococci (VS) represent a specific, heterogeneous collection of these organisms, often characterized by their hemolytic properties on blood agar. While these bacteria are typically part of the body’s normal flora, their presence can become a serious health concern. This shift from commensal to pathogen, coupled with a growing ability to resist common antimicrobial treatments, presents a significant challenge in modern medicine.
Understanding Viridans Streptococci
The name Viridans Streptococci refers to the green (viridans) coloration many species produce on a blood agar plate, resulting from alpha-hemolysis where the bacteria partially degrade hemoglobin. This group is characterized by the absence of Lancefield antigens, used to classify other streptococci. VS are categorized into five major groups, including the S. mitis and S. mutans groups, which contain species such as S. sanguinis and S. oralis.
These bacteria are most abundant in the oral cavity, where they constitute a significant part of the normal microbial community, but they also colonize the upper respiratory and gastrointestinal tracts. In a healthy host, they serve a commensal role, often preventing colonization by more harmful invaders. However, disruption of the mucosal barrier, such as through a dental procedure or injury, provides a direct route for these organisms to enter the bloodstream.
Once in the blood, VS transition from harmless residents to opportunistic pathogens, capable of causing infection in susceptible tissues. Underlying conditions, particularly structural heart defects or immunocompromised states, dictate whether this entry into the bloodstream results in a severe, localized infection. This dual nature—being part of the healthy flora yet possessing pathogenic potential—is central to their clinical importance.
Primary Infections Caused by Viridans Streptococci
The most severe consequence of VS entering the bloodstream is Infective Endocarditis (IE), an inflammation of the inner lining of the heart’s chambers and valves. This occurs when the bacteria colonize pre-existing damage on a heart valve, such as a prosthetic valve or one damaged by rheumatic fever. Certain VS species, like S. sanguinis and S. mutans, possess the ability to synthesize dextrans from glucose.
These dextrans are sticky polysaccharides that enable the bacteria to adhere firmly to the exposed fibrin-platelet aggregates on the damaged heart surface. The accumulating mass of bacteria, fibrin, and platelets forms a vegetation, which continuously releases bacteria into the bloodstream and can impair valve function. Untreated IE carries a high mortality risk due to heart failure, valve destruction, or the showering of infected emboli.
While IE is the most life-threatening complication, the most common pathology caused by VS is dental caries, or tooth decay. Species like Streptococcus mutans metabolize dietary sugars and produce lactic acid as a byproduct. This acid erodes the tooth enamel, leading to the formation of cavities.
Beyond the mouth and heart, members of the Streptococcus anginosus group (formerly S. milleri) are associated with deep-seated pyogenic infections. These infections often manifest as abscesses in internal organs, including the brain, liver, or abdominal sites. VS can also cause life-threatening sepsis and bacteremia in highly vulnerable patients, particularly those with neutropenia due to cancer chemotherapy.
Mechanisms of Antibiotic Resistance
The effectiveness of penicillin, the traditional treatment for streptococcal infections, is increasingly threatened by resistance mechanisms in VS. The most significant mechanism involves the alteration of Penicillin-Binding Proteins (PBPs), enzymes located in the bacterial cell wall. Penicillin and related beta-lactam antibiotics normally work by binding to and inactivating these PBPs, preventing cell wall synthesis and leading to bacterial death.
In resistant VS strains, mutations in the genes encoding PBPs, specifically pbp2b and pbp2x, cause structural changes in the target proteins. This modification decreases the affinity of the PBP for the antibiotic, meaning the drug can no longer bind effectively to inhibit cell wall construction. The bacteria can then continue to grow and divide even in the presence of the antibiotic.
VS can acquire these modified PBP genes through horizontal gene transfer, a process where bacteria exchange genetic material. They often take up genetic fragments from other resistant bacteria, such as penicillin-resistant Streptococcus pneumoniae, which colonize the nasopharynx. This acquisition results in “mosaic” PBP genes—a combination of sensitive and resistant gene sequences—which propagates resistance within the VS population.
Resistance to other drug classes is common, further complicating treatment. Macrolide resistance, targeting drugs like erythromycin, is often mediated by the acquisition of ermB or mefE genes. The ermB gene modifies the antibiotic’s ribosomal target site, while the mefE gene codes for an efflux pump that actively pumps the drug out.
Clinical Management and Prevention
Treating an established VS infection, particularly Infective Endocarditis, requires prompt diagnosis, typically confirmed by blood cultures and echocardiography. For penicillin-susceptible strains, a prolonged course of high-dose penicillin or ceftriaxone is the standard approach. If penicillin non-susceptibility is present, treatment often requires the addition of an aminoglycoside, such as gentamicin, which works synergistically with the beta-lactam to achieve rapid bacterial killing.
For highly resistant VS strains, or in patients with a severe penicillin allergy, the glycopeptide antibiotic vancomycin is the required alternative. Monitoring the patient’s response and adjusting the regimen based on the minimum inhibitory concentration (MIC) values of the isolated strain is necessary. Antibiotic resistance significantly narrows therapeutic options and increases the complexity and duration of treatment.
Prevention remains the most effective strategy against VS-IE. Since the majority of IE cases caused by VS originate from the oral cavity, maintaining excellent oral hygiene and receiving regular dental care is a fundamental preventive measure. Antibiotic prophylaxis (AP) is recommended for a small, high-risk group of patients undergoing invasive dental procedures.
This high-risk group includes individuals with a prosthetic heart valve, a history of IE, or certain types of congenital heart disease. A single dose of amoxicillin, or an alternative drug like clindamycin for allergic patients, is administered shortly before the procedure to temporarily reduce the bacterial load in the bloodstream. This targeted use of AP aims to prevent bacteremia from seeding the susceptible heart tissue without promoting widespread antibiotic resistance.