G. adiacens is a bacterium that has garnered increasing medical attention due to its potential to cause infections, particularly within the heart. Historically, this organism was often overlooked or misidentified in clinical settings because of its specific and demanding growth requirements. It is now recognized as a significant pathogen, especially in cases of infective endocarditis (IE), an infection of the inner lining of the heart’s chambers and valves. Understanding the unique characteristics of G. adiacens, the challenges associated with its detection, and the complexities of its treatment is important for improving patient outcomes.
Defining the Organism
G. adiacens is a species of Gram-positive bacteria that appears as pleomorphic cocci, often in pairs or short chains. It belongs to a group formerly known as nutritionally variant streptococci (NVS), reflecting its fastidious nature and demanding nutritional needs. Specifically, G. adiacens requires pyridoxal (Vitamin B6) or L-cysteine to grow optimally. Without this supplementation, the organism grows slowly or not at all, making isolation difficult.
Genetically, Granulicatella species were reclassified from the Streptococcus genus after 16S ribosomal RNA gene sequencing showed low homology with other streptococcal species. This highlights its distinct evolutionary path. The natural habitat of G. adiacens is typically as a commensal organism, living harmlessly on human mucosal surfaces. It is part of the normal flora found in the oral cavity, the gastrointestinal tract, and the genitourinary tract.
Associated Clinical Conditions
Although G. adiacens is part of the normal flora, it becomes an opportunistic pathogen when it enters the bloodstream, leading to severe systemic infections. The most frequently reported condition associated with this organism is infective endocarditis (IE). Granulicatella species cause approximately 5–6% of all endocarditis cases attributed to streptococcal-like bacteria.
The organism causes IE by adhering to and colonizing heart valves, forming large, bulky vegetations. These vegetations increase the risk of systemic emboli. The aortic and mitral valves are the most common sites of infection. Patients with pre-existing valve damage or prosthetic heart valves are at higher risk, often following dental procedures that introduce the organism into the bloodstream (bacteremia).
Beyond IE, G. adiacens can cause other invasive infections, including septic arthritis, osteomyelitis, brain abscesses, and infections related to implanted medical devices. The clinical presentation of Granulicatella endocarditis is often subacute, with non-specific symptoms like fever, fatigue, and malaise developing over weeks or months. This slow onset often delays diagnosis and treatment, contributing to high morbidity and mortality rates and frequently resulting in severe complications like heart failure.
Challenges in Laboratory Identification
Identifying G. adiacens in a clinical laboratory is challenging due to its unique growth requirements and tendency toward misidentification. Because the organism is nutritionally demanding, it often fails to grow, or grows minimally, on standard culture media like sheep blood agar. This frequently leads to an initial classification of “culture-negative endocarditis,” delaying appropriate treatment.
To overcome this deficiency, culture media must be supplemented with pyridoxal or L-cysteine. Alternatively, the organism may exhibit a “satellite phenomenon” on blood agar plates. Here, G. adiacens colonies grow as tiny spots clustered around colonies of other bacteria, such as Staphylococcus aureus, which naturally secrete the required pyridoxal growth factor.
Even when growth is achieved, conventional biochemical testing often leads to incorrect identification, misclassifying the organism as a different species of Granulicatella or related genera like Abiotrophia or Gemella. This misidentification complicates treatment decisions due to varied antibiotic susceptibility patterns. Therefore, accurate species identification necessitates molecular methods, such as 16S rRNA gene sequencing, to provide definitive identification and guide targeted therapy.
Standardized Therapeutic Management
The treatment of G. adiacens infections, particularly endocarditis, is complex and requires prolonged antimicrobial therapy. Protocols are guided by recommendations for nutritionally variant streptococci, often involving combination therapy to achieve synergistic killing. Treatment failure and relapse rates can be high due to the organism’s tendency to form large vegetations and persist.
The standard regimen for infective endocarditis involves a cell wall-active agent, such as high-dose penicillin G or ampicillin, combined with an aminoglycoside like gentamicin. The aminoglycoside is added for the first two weeks to achieve a synergistic bactericidal effect necessary to eliminate the infection from the heart valve. Therapy duration is typically four to six weeks for native valve endocarditis and a full six weeks for prosthetic valve endocarditis.
Antibiotic susceptibility testing (AST) is necessary, as G. adiacens has shown reduced susceptibility to beta-lactam antibiotics. In cases of penicillin allergy or resistance, the alternative first-line agent is vancomycin, administered intravenously for four to six weeks. When vancomycin is used, the addition of an aminoglycoside may not be required. Close monitoring by infectious disease specialists is essential throughout the treatment course to ensure proper drug levels and detect signs of treatment failure.