Nutritionally Variant Streptococci: Definition and Clinical Significance
Nutritionally variant streptococci are fastidious bacteria now classified as Abiotrophia defectiva and Granulicatella species (G. elegans, G. adiacens, G. paraadiacens, and G. balaenopterae) that require special growth supplements (pyridoxal or L-cysteine) and are important causes of culture-negative endocarditis. 1
Microbiological Characteristics
Growth Requirements and Laboratory Detection
These organisms are detected by automated blood culture systems but will not grow on routine subculture media unless chocolate agar or media supplemented with pyridoxal hydrochloride or L-cysteine is used. 1
They may yield pleomorphic forms on Gram stain, making initial identification challenging. 1
The organisms were historically called "nutritionally variant streptococci" (NVS) because they form satellite colonies adjacent to "helper" bacteria that provide necessary growth factors. 2
Brucella HK agar or GAM agar plates are particularly helpful for detection of these species. 3
Taxonomic Classification
These organisms were previously considered nutritional mutants of viridans streptococci but are now recognized as distinct species. 1, 2
The current nomenclature includes Abiotrophia defectiva and four Granulicatella species. 1
Clinical Significance
Endocarditis Characteristics
Endocarditis caused by nutritionally variant streptococci is more difficult to cure microbiologically than endocarditis caused by typical viridans group streptococci. 1
These organisms account for approximately 5% of infective endocarditis cases. 3
They are responsible for a significant proportion of so-called "culture-negative" endocarditis because they grow poorly on conventional media. 3, 4
Other Clinical Manifestations
Nutritionally variant streptococci are normal inhabitants of the oral cavity. 2
Beyond endocarditis, they have been isolated from pyogenic discitis and a wide range of other clinical specimens. 3, 2
Treatment Implications
Antimicrobial Susceptibility Testing Challenges
Determination of antimicrobial susceptibilities for Abiotrophia defectiva and Granulicatella species is often technically difficult, and results may not be accurate. 1
Susceptibility profiles differ among species despite similar phenotypic characteristics. 5
Recommended Treatment Approach
Because of the difficulty in curing endocarditis caused by these organisms, the American Heart Association recommends treating them with regimens used for enterococcal endocarditis rather than standard viridans streptococcal regimens. 1
This means combination therapy with penicillin (or ampicillin) plus an aminoglycoside for extended duration. 1
When vancomycin is the chosen antibiotic, addition of gentamicin is not necessary. 1
Critical Clinical Pitfalls
Laboratory Communication
The microbiology laboratory must be specifically notified when these organisms are suspected, as they require special subculture techniques that are not part of routine protocols. 1
Failure to use supplemented media will result in false-negative cultures and missed diagnoses. 3, 6
Underestimation of Disease Burden
The fastidious nature of these organisms means many cases are likely falsely classified as culture-negative infections, and their true role in various infections may be significantly underestimated. 3
In spinal infections, causative organisms remain unidentified in 25-40% of cases, and nutritionally variant streptococci may account for some of these. 3
Treatment Duration
More aggressive and prolonged combination antimicrobial therapy is required compared to typical viridans streptococcal infections. 1
The relative resistance to antibiotic treatment may be related to bacterial ultrastructural alterations that occur within infected tissues, including formation of large bacterial clusters surrounded by exopolysaccharide. 4