title: Clindamycin Affects Group A Streptococcus Virulence Factors and Improves Clinical Outcome.
abstract: Group A Streptococcus (GAS) has acquired an arsenal of virulence factors, promoting life-threatening invasive infections such as necrotizing fasciitis. Current therapeutic regimens for necrotizing fasciitis include surgical debridement and treatment with cell wall-active antibiotics. Addition of clindamycin (CLI) is recommended, although clinical evidence is lacking. Reflecting the current clinical dilemma, an observational study showed that only 63% of the patients with severe invasive GAS infection received CLI. This work thus aimed to address whether CLI improves necrotizing fasciitis outcome by modulating virulence factors of CLI-susceptible and CLI-resistant GAS in vitro and in vivo. Treatment with CLI reduced extracellular DNase Sda1 and streptolysin O (SLO) activity in vivo, whereas subinhibitory CLI concentrations induced expression and activity of SLO, DNase, and Streptococcus pyogenes cell envelope protease in vitro. Our in vivo results suggest that CLI should be administered as soon as possible to patients with necrotizing fasciitis, while our in vitro studies emphasize that a high dosage of CLI is essential.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Federica
authors.initials: F
authors.lastname: Andreoni
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Claudia
authors.initials: C
authors.lastname: Zürcher
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tarnutzer
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schilcher
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Andrina
authors.initials: A
authors.lastname: Neff
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Nadia
authors.initials: N
authors.lastname: Keller
authors.affiliation: Division of Clinical Pathology.
authors.forename: Ewerton
authors.initials: E
authors.lastname: Marques Maggio
authors.affiliation: Centre national de référence des Streptocoques, INSERM 1016, Université Paris Descartes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Poyart
authors.affiliation: Division of Surgical Intensive Care, University Hospital Zurich, University of Zurich, Switzerland.
authors.forename: Reto A
authors.initials: RA
authors.lastname: Schuepbach
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology.
authors.forename: Annelies S
authors.initials: AS
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002981:Clindamycin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D019115:Fasciitis, Necrotizing / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects*; D016896:Treatment Outcome; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D037521:Virulence Factors; D002981:Clindamycin
keywords: Group A Streptococcus; clindamycin; necrotizing fasciitis; protein synthesis inhibitors; virulence factors