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Clinical Characteristics of Necrotizing Soft Tissue Infection and Early Toxic Shock-Like Syndrome Caused by Group G Streptococcus: Case Report and Review of Literature

Clinical Characteristics of Necrotizing Soft Tissue Infection and Early Toxic Shock-Like Syndrome Caused by Group G Streptococcus: Case Report and Review of Literature Khalil Choucair, M.D., M.Sc.1, Katia El Jurdi, M.D., M.Sc.1, K. James Kallail, Ph.D.1, Thomas A. Moore, M.D.1,2 1University of Kansas School of Medicine-Wichita, Wichita, KS Department of Internal Medicine 2Infectious Disease Consultants, Wichita, KS Received Jan. 2, 2021; Accepted for publication March 10, 2021; Published online June 21, 2021 https://doi.org/10.17161/kjm.vol1415038

Our patient presented with less than two days history of penile shaft entrapment with no clear sign of infection. He was treated solely based on clinical presentation which was highly suggestive of streptococcal TSS. Implication of GGS as the organism responsible for this illness and clinical progression was only later established based on an isolated specimen from surgical tissue and blister fluid which showed Grampositive cocci and GGS growth on culture. The case thus highlighted the importance of early TSLS signs recognition, and the ensuing prompt management based on pure clinical presentation.  While originally identified and described by Lancefield and Hare as part of the normal flora, previous case reports have indicated that GGS also could cause complicated infections, such as cellulitis, osteomyelitis, septic arthritis, meningitis, endocarditis, and bacteremia. [19][20][21][22] Invasive disease due to GGS has been reported mostly in patients with underlying debilitating conditions including malignancy, rheumatoid arthritis, diabetes mellitus, injection drug use, and HIV infection, as well as in more elderly patients (Table 1). 10,11,13,[16][17][18] Our patient was young and healthy with no known history of comorbid conditions. Whether the penile shaft entrapment and the ensuing low blood flow and necrosis could mimic the low terminal vascular supply and/or local impairment in defense mechanism observed in diabetes mellitus patients remains a plausible hypothesis, particularly in light of the observation that most cases had lower extremity involvement and diabetes mellitus (Table 1). Our review of literature did not always suggest an apparent precipitating cause of GGS-NSTI and TSS.
The presented case was unique in respect to two aspects. The first one pertains to the rarity of the underlying causative organism (only 16 reported cases in the English literature); as mentioned earlier GGS historically has been characterized as part of the normal flora with rare cases describing its involvement in pathologic states. Our case was one of these rare occurrences. Second, within the different reported cases, invasive GGS invariably has been linked to existing underlying comorbidities. In contrast, our case was unique in that it reflected the occurrence of this potentially lethal infection in an otherwise young and healthy individual, hence highlighting the importance of a low clinical suspicion threshold for GGS-NSTI.
Over the past years, the number of reported GGS-NSTI cases, with or without TSS, has been on the rise. In fact, this observation prompted Wong et al. 18  unknown and could relate to increase in potential risk factors, such as increased prevalence of diabetes mellitus or cancer, or to improved detection methods. Furthermore, emergence of resistance patterns in response to increased antibiotics use worldwide may explain possible changes/increases in GGS virulence. Hashikawa et al. 23 microbiologically characterized 12 strains of group C and G streptococci that caused TSS. Despite GGS TSS manifesting clinically in a similar fashion to GAS, only the spegg gene, which encodes a super-antigen found in GAS stains, was detected in S. dysgalactiae (GGS strain), but no other apparent virulence factor responsible for the TSS pathogenesis was identified. Further multi-center studies are warranted to characterize the increasing trend of GGS and define underlying host risk factors, and strain virulence factors.
As mentioned, NSTI and TSS treatment in our patient was initiated solely based on clinical presentation and high index of suspicion with no imaging to characterize the depth of tissue involvement. 24 Prompt initiation of therapy took precedence over establishing a clear diagnosis, based on both high clinical suspicion and the significantly high morbidity/mortality associated with delayed initiation of therapy. The actual diagnosis was validated clinically later when the patient positively responded to therapy and shock progression halted.
The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) is a score used in the setting of early infection to define the likelihood of NSTI; it is based on indicators including white blood cell count (WBC), hemoglobin (Hgb), sodium (Na), glucose, creatinine (Cr.), and C-reactive protein (CRP). 25,26 A score greater than six is suggestive of NSTI while less than six is indicative of low risk (but does not exclude risk), suggesting IV antibiotics and serial laboratory monitoring without the need for surgical debridement.
We did not calculate a LRINEC score for our patient. In hindsight, and with the available laboratory values (CRP not obtained), the calculated LRINEC would have been five (WBC = 10.3 x 10 3 / uL; Cr. = 1.8; Na: 126 mEq/L; and Hgb = 12 d/dL), suggestive of low risk. This discrepancy between the low LRINEC score and the actual clinical picture reveals yet again the importance of clinical history and physical exam in clinical decision making. High suspicion for NSTI on clinical ground warrants a straight operative debridement approach, regardless of LRINEC score.
A recent assessment of the LRINEC score has recommended its cautious use given a poor performance in external validation. 27 In this study which involved patients with established diagnoses of cellulitis (n = 948) and necrotizing fasciitis (n = 135), a retrospective computation of the LRINEC score revealed poor predictive value of the score for differentiating between both diseases with a 10.7% false diagnoses of moderate-to-high risk of necrotizing fasciitis in patients with a confirmed diagnosis of cellulitis. Similarly, and within the group of patients with confirmed necrotizing fasciitis, 63.8% were categorized as low risk for necrotizing fasciitis using the LRINC score.
Similar to all NSTI, broad spectrum antibiotics and surgical debridement are necessary for a good outcome. Our patient received piperacillin-tazobactam as a regimen, along with both clindamycin and IVIG. Beyond its antibacterial effects, clindamycin is added for its ability to suppress bacterial toxin production. 28 In fact, use of clindamycin in patients with invasive GAS infection was associated with lower 30-day mortality (15% vs. 39% in those who did not receive clindamycin). 29 Linezolid or tedizolid alternatively can be used in patients with known resistance to clindamycin. 1 The use of IVIG in patients with streptococcal TSS often has been a subject of debate. The proposed rationale for use of IVIG is to boost antibody levels (passive immunity) in the setting of the overwhelming infection seen in TSS. Several mechanisms have been proposed, including bacterial opsonisation, toxin neutralization, inhibition of T cell proliferation, and inhibition of inflammatory cytokines. 30,31 Clinically, IVIG super-antigen neutralizing activity reduced mortality rates in streptococcal TSS. [32][33][34] A recent meta-analysis including five studies of patients with streptococcal TSS treated with clindamycin revealed an association between IVIG use and 30-day reduction in mortality (33.7 vs. 15.7 %). 35 In summary, this work illustrated how NSTI due to GGS can progress, similar to GAS-induced fasciitis, to TSS/TSLS and can be life-threatening. Clinicians should keep a high index of suspicion, especially in patients with underlying co-morbid conditions, and understand the crucial role of early IVIG therapy, the choice of antibiotics with antitoxin properties, and the increasing trend of GGS infections.