Microbiology Case Study: an 11 Month Old with a 3 Day History of Gastroenteritis and High Fever

Clinical History:

An 11 month old female with no significant past medical history was admitted with a fever of 104 degrees Fahrenheit, nausea and vomiting for 3 days (now resolved), watery diarrhea 4-5 times/day (resolved), and a new onset of acute pharyngitis/bilateral cervical adenitis. ER staff was concerned for a bacterial superinfection. She appeared sick with pale skin, but vital signs were stable, and labs were unremarkable except for an elevated CRP (15.7) and an absolute monocytosis (though no elevation in total WBCs). Exam showed a hyperemic pharynx without exudates, and no lymph nodes larger than 1 cm. A CT neck shows bilateral cervical adenitis, left greater than right, with some suggestion of necrotic nodes, as well as a likely left 3^rd or 4^th branchial cleft cyst. Blood cultures were drawn, and they turned up positive in a matter of hours, with the gram stain and plate morphology seen below:

Laboratory Identification:

Gram positive cocci in chains were seen, with small, glossy, gray-white, translucent colonies on blood agar having a wide zone of surrounding beta hemolysis. Catalase testing was negative, PYR testing was positive, and latex agglutination testing for Lancefield antigens was positive for Group A. MALDI-TOF confirmed the presumptive identification of Streptococcus pyogenes.

Discussion:

S. pyogenes (aka Group A Streptococcus [GAS]) is a ubiquitous gram positive cocci that causes a wide range of disease in humans. It is the leading cause of acute pharyngitis, particularly in children aged 5-15, although 15-25% of school aged children are asymptomatically colonized. S. pyogenes can also cause cellulitis, impetigo, necrotizing fasciitis, scarlet fever, toxic shock syndrome, otitis media, osteomyelitis, pneumonia, or even rarely meningitis/brain abscess. It additionally causes several serious post-infectious sequelae, particularly in untreated cases, including acute rheumatic fever with potential rheumatic heart disease, and poststreptococcal glomerulonephritis.

S. pyogenes has numerous virulence factors, most importantly the M protein, of which there are nearly 80 variants. M protein binds fibrinogen, inhibits complement binding, and prevents phagocytosis. As it is the major antigenic target of antibodies formed following infection, immunity is conferred only to the infecting strain, and none of the others, which complicates vaccine development efforts. Streptolysin O is responsible for the organism’s b-hemolysis on blood agar, and is also immunogenic, causing elevated Anti-Streptolysin O antibodies (ASO), which can be useful in diagnosing a recent infection, rheumatic fever, or poststreptococcal glomerulonephritis.

GAS pharyngitis is uncommon in children less than 3 years old, as is the bacteremia seen in the patient, which was presumably secondary to the severity of the throat infection. A later CT scan showed an enlarging abscess in the left lateral neck, corresponding to the earlier supposed branchial cleft cyst, despite IV clindamycin which was begun in the ER. Ceftriaxone was added, and later changed to Piperacillin/Tazobactam to complete a seven day course, though future blood cultures were negative. The additional antimicrobial coverage was due to the concern for other infectious microorganisms, as S. pyogenes is universally susceptible to penicillin.

Interestingly, this patient also developed a severe absolute neutropenia, with her ANC dropping from 7,100 at admission to 300 two days later, and then to 60 after two further days. The hematology/oncology service was consulted, and they determined that this likely represented a reaction to the infection rather than a more sinister bone marrow pathology. Several more days into therapy her ANC did begin to recover.

References:

1. Henningham A, Barnett TC, Maamary PG, Walker MJ. 2012. Pathogenesis of group A streptococcal infections. Discovery medicine 13:329-342.
2. Cunningham MW. 2000. Pathogenesis of group A streptococcal infections. Clinical microbiology reviews 13:470-511.
3. Red Book 2015
4. Journal of Clinical Microbiology, 10^th editionCunningham MW. 2000. Pathogenesis of group A streptococcal infections. Clinical microbiology reviews 13:470-511.

-Paul Yell, M.D. is a 2^nd year anatomic and clinical pathology resident at the University of Texas Southwestern Medical Center.

-Erin McElvania TeKippe, Ph.D., D(ABMM), is the Director of Clinical Microbiology at Children’s Medical Center in Dallas Texas and an Assistant Professor of Pathology and Pediatrics at University of Texas Southwestern Medical Center.