title: Biofilm in group A streptococcal necrotizing soft tissue infections.
abstract: Necrotizing fasciitis caused by group A streptococcus (GAS) is a life-threatening, rapidly progressing infection. At present, biofilm is not recognized as a potential problem in GAS necrotizing soft tissue infections (NSTI), as it is typically linked to chronic infections or associated with foreign devices. Here, we present a case of a previously healthy male presenting with NSTI caused by GAS. The infection persisted over 24 days, and the surgeon documented the presence of a "thick layer biofilm" in the fascia. Subsequent analysis of NSTI patient tissue biopsies prospectively included in a multicenter study revealed multiple areas of biofilm in 32% of the patients studied. Biopsies associated with biofilm formation were characterized by massive bacterial load, a pronounced inflammatory response, and clinical signs of more severe tissue involvement. In vitro infections of a human skin tissue model with GAS NSTI isolates also revealed multilayered fibrous biofilm structures, which were found to be under the control of the global Nra gene regulator. The finding of GAS biofilm formation in NSTIs emphasizes the urgent need for biofilm to be considered as a potential complicating microbiological feature of GAS NSTI and, consequently, emphasizes reconsideration of antibiotic treatment protocols.
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Siemens
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Bhavya
authors.initials: B
authors.lastname: Chakrakodi
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Srikanth Mairpady
authors.initials: SM
authors.lastname: Shambat
authors.affiliation: Department of Microbiology, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
authors.forename: Marina
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Bergsten
authors.affiliation: Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Hyldegaard
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Steinar
authors.initials: S
authors.lastname: Skrede
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Arnell
authors.affiliation: Department of Intensive Care, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Madsen
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Johansson
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Julius
authors.initials: J
authors.lastname: Juarez
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lidija
authors.initials: L
authors.lastname: Bosnjak
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
mesh_terms: D000328:Adult; D018441:Biofilms; D002478:Cells, Cultured; D019115:Fasciitis, Necrotizing / Q000382:microbiology*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D018461:Soft Tissue Infections / Q000382:microbiology*; D013290:Streptococcal Infections / Q000473:pathology*; D013297:Streptococcus pyogenes