Invasive Group A Streptococcal Infections: Benefit of Clindamycin, Intravenous Immunoglobulins and Secondary Prophylaxis.

Delphine Laho,Pierre R Smeesters,Anne Botteaux,Sophie Blumental

doi:10.3389/fped.2021.697938

Abstract

Introduction: Mortality associated with invasive group A streptococcal infections (iGAS) remains high among adults, with lower mortality in children. The added value of both clindamycin and immunoglobulins in such treatment is still controversial, as is the need for antibiotic secondary prophylaxis. It is unlikely that conclusive randomized clinical studies will ever definitively end these controversies.Materials and Methods: A clinical and experimental literature review was conducted in Pubmed, Cochrane, and lay literature to determine the benefit of adding clindamycin and immunoglobulins to β-lactams in the management of iGAS, as well as the need for secondary prophylaxis measures in close contacts.Results: This review includes two meta-analyses, two randomized controlled trials, four prospective studies, five retrospective studies, and microbiological studies. To reduce mortality and morbidity, it appears useful to add clindamycin to β-lactams in severe clinical presentations, including necrotizing fasciitis or streptococcal toxic shock syndrome, and immunoglobulins for the latter two presentations. The high risk of secondary infection in household contacts justifies the need of taking preventive measures.Conclusions: Both clinical studies and available experimental evidence suggest that adding clindamycin and immunoglobulins as adjunctive therapies in the management of invasive group A streptococcal infections may reduce mortality. Household contacts should be warned about the increased risk of secondary infection, and chemoprophylaxis may be considered in certain situations.

Highlights

Mortality associated with invasive group A streptococcal infections remains high among adults, with lower mortality in children
Group A Streptococcus (GAS) is always sensitive to penicillin [even if some mutations in penicillin-binding protein genes conferring reduced susceptibility to β-lactam antibiotics have been reported [3]], the mortality from these infections remains high, especially among adults which can reach up to 24% for necrotising fasciitis (NF) and 36% for streptococcal toxic shock syndrome (STSS) [4], with lower mortality in children in high-resource settings
A clinical and experimental literature review was conducted in Pubmed, Cochrane, and lay literature using the following keywords: ≪ AND AND.≫ The articles were selected regarding their language (English and French) without any time limit

Summary

Introduction

Mortality associated with invasive group A streptococcal infections (iGAS) remains high among adults, with lower mortality in children. GAS is always sensitive to penicillin [even if some mutations in penicillin-binding protein genes conferring reduced susceptibility to β-lactam antibiotics have been reported [3]], the mortality from these infections remains high, especially among adults which can reach up to 24% for NF and 36% for streptococcal toxic shock syndrome (STSS) [4], with lower mortality in children in high-resource settings. Variety of treatment protocols exists in the potential use of adjuvant therapies such as clindamycin and intravenous immunoglobulins (IVIG) (Table 1) Their use is overall supported by both biological and microbiological experimental data, as well as by observational studies, conclusive clinical data supporting their efficacy in reducing iGAS mortality remain limited. We aimed to assess the benefits and optimal regimen of antibiotic prophylaxis in close contacts of patients

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