Correcting a Deficiency

Written as an editorial commentary regarding Wright and Myers. Nutritionally Variant Streptococcal Bacteremia in the 21st Century: Report of 26 Episodes for a 12-Year Period (2006–2017) at a Large Community Teaching Hospital and Review of the Literature pages 263–267 of the Journal. The present report by Wright and Myers,1 entitled “Nutritionally Variant Streptococcal Bacteremia in the 21st Century: Report of 26 Episodes Over 12-year Period (2006–2017) at a Large Community Teaching Hospital and Review of the Literature,” appears to be the largest case series in the published literature to date and, as such, warrants an in-depth look. “Nutritionally variant strep” is an obsolete term. Over the last several decades, these misunderstood microorganisms have also been called “nutritionally deficient streptococci,” “satelliting streptococci,” “pyridoxal-dependent streptococci,” “B6-dependent streptococci,” “nutritionally deficient streptococci,” Streptococcus defectivus, and Streptococcus adjacens, until genomic studies showed that these organisms were not related to Streptococcus. They were renamed Abiotrophia, and then based on further genetic work, some Abiotrophia were reclassified as Granulicatella.2–5 However, the terminology of “nutritionally variant strep” (AG) persists to this day, perhaps because old habits continue and also because the older nomenclature is catchy, conjuring up visions of bacteria that are somehow bizarre and different. They do remain an elusive enemy, probably underdiagnosed, and not fully understood. The present study retrospectively studied all cases of bloodstream infections of AG bacteremia over a 12-year period at a large teaching hospital in Ohio. Most of the patients were older (median age, 66.0 years) and had significant comorbidities, and many had chronic intravenous lines. A significant portion of the patients (7 of 26) had definite or probable endocarditis, including 3 with pacemaker endocarditis. Interestingly, 4 of 7 of the endocarditis cases had only a single blood culture positive. Somewhat surprisingly, 12 of 26 patients had polymicrobial bacteremia, which ranged from skin flora–type organisms that may or may not have been contaminants, to oral flora, and even 1 gram-negative agent. Besides endocarditis, the range of disease in the present study also included skin and soft tissue infection and bone and joint infection, as well as intravenous access infection. The mortality rate was quite high, as 4 of the 26 patients died, including one who died of severe sepsis in the emergency department before antibiotics could be given. The present study also highlights some important diagnostic data with clinical implications: (1) long time of incubation, including 7 patients whose isolates grew from blood after the customary 5-day cutoff; (2) disappointingly, new technology in the form of the Biofire Film Array Assay did not perform well: of 6 blood culture–positive AG patients who were tested, there was 1 true-positive and 2 false-negatives, and 3 AG patients were read as being positive for Streptococcus in the Biofire assay, but also grew Streptococcus in blood culture, so it is unclear if the AG was detected or not. Traditionally, penicillin plus an aminoglycoside was considered optimal therapy, but β-lactam resistance is not uncommon. Most isolates are sensitive to vancomycin.6–8 The patients in this study were treated with many different regimens, some with β-lactams, some with vancomycin, and some with a combination of both. There are take-home messages from this study. In cases where AG is a possibility and blood cultures are still negative on day 4, the clinician should consider asking the laboratory to hold blood cultures for a longer period. When AG is diagnosed, an echocardiography is warranted, as endocarditis is common. If the microbiology laboratory uses the Biofire Film Array Assay and the assay is positive for Streptococcus, AG is in the differential. Per the authors' recommendation, consider sending isolates to a reference laboratory for more accurate antibiotic susceptibility testing. Vancomycin may be reasonable initial therapy, pending final sensitivities. Of course, there is more work to be done. Both conventional blood culture techniques and 1 newer diagnostic test, the Biofire Film Array Assay, do not appear to be optimal for diagnosing AG infections, probably leading to underdiagnosis. It would be most helpful to the clinician to diagnose AG accurately and sooner. It would also be of benefit if we could define the optimal antibiotic regimen for AG bacteremia. Armed with such knowledge, perhaps we could treat AG bacteremia more successfully. Maybe then we could finally cast off the obsolete term “nutritionally deficient strep.”