L Tuchscherr1, C A Kreis2, V Hoerr3, L Flint4, M Hachmeister4, J Geraci5, S Bremer-Streck6, M Kiehntopf6, E Medina7, M Kribus8, M Raschke2, M Pletz9, G Peters4, B Löffler10. 1. Institute of Medical Microbiology, Jena University Hospital, Jena, Germany Lorena.TuchscherrdeHauschopp@med.uni-jena.de. 2. Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Münster, Münster, Germany. 3. Institute of Medical Microbiology, Jena University Hospital, Jena, Germany Department for Clinical Radiology, University Hospital of Münster, Münster, Germany. 4. Institute of Medical Microbiology, University Hospital of Münster, Münster, Germany. 5. Institute of Medical Microbiology, Jena University Hospital, Jena, Germany. 6. Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany. 7. Helmholtz Center for Infection Research, Braunschweig, Germany. 8. Department of Trauma, Hand and Reconstructive Surgery, Jena University Hospital, Jena, Germany. 9. Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany. 10. Institute of Medical Microbiology, Jena University Hospital, Jena, Germany Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
Abstract
OBJECTIVES: Staphylococcus aureus osteomyelitis often develops to chronicity despite antimicrobial treatments that have been found to be susceptible in in vitro tests. The complex infection strategies of S. aureus, including host cell invasion and intracellular persistence via the formation of dynamic small colony variant (SCV) phenotypes, could be responsible for therapy-refractory infection courses. METHODS: To analyse the efficacy of antibiotics in the acute and chronic stage of bone infections, we established long-term in vitro and in vivo osteomyelitis models. Antibiotics that were tested include β-lactams, fluoroquinolones, vancomycin, linezolid, daptomycin, fosfomycin, gentamicin, rifampicin and clindamycin. RESULTS: Cell culture infection experiments revealed that all tested antibiotics reduced bacterial numbers within infected osteoblasts when treatment was started immediately, whereas some antibiotics lost their activity against intracellular persisting bacteria. Only rifampicin almost cleared infected osteoblasts in the acute and chronic stages. Furthermore, we detected that low concentrations of gentamicin, moxifloxacin and clindamycin enhanced the formation of SCVs, and these could promote chronic infections. Next, we treated a murine osteomyelitis model in the acute and chronic stages. Only rifampicin significantly reduced the bacterial load of bones in the acute phase, whereas cefuroxime and gentamicin were less effective and gentamicin strongly induced SCV formation. During chronicity none of the antimicrobial compounds tested showed a beneficial effect on bone deformation or reduced the numbers of persisting bacteria. CONCLUSIONS: In all infection models rifampicin was most effective at reducing bacterial loads. In the chronic stage, particularly in the in vivo model, many tested compounds lost activity against persisting bacteria and some antibiotics even induced SCV formation.
OBJECTIVES:Staphylococcus aureusosteomyelitis often develops to chronicity despite antimicrobial treatments that have been found to be susceptible in in vitro tests. The complex infection strategies of S. aureus, including host cell invasion and intracellular persistence via the formation of dynamic small colony variant (SCV) phenotypes, could be responsible for therapy-refractory infection courses. METHODS: To analyse the efficacy of antibiotics in the acute and chronic stage of bone infections, we established long-term in vitro and in vivo osteomyelitis models. Antibiotics that were tested include β-lactams, fluoroquinolones, vancomycin, linezolid, daptomycin, fosfomycin, gentamicin, rifampicin and clindamycin. RESULTS: Cell culture infection experiments revealed that all tested antibiotics reduced bacterial numbers within infected osteoblasts when treatment was started immediately, whereas some antibiotics lost their activity against intracellular persisting bacteria. Only rifampicin almost cleared infected osteoblasts in the acute and chronic stages. Furthermore, we detected that low concentrations of gentamicin, moxifloxacin and clindamycin enhanced the formation of SCVs, and these could promote chronic infections. Next, we treated a murineosteomyelitis model in the acute and chronic stages. Only rifampicin significantly reduced the bacterial load of bones in the acute phase, whereas cefuroxime and gentamicin were less effective and gentamicin strongly induced SCV formation. During chronicity none of the antimicrobial compounds tested showed a beneficial effect on bone deformation or reduced the numbers of persisting bacteria. CONCLUSIONS: In all infection models rifampicin was most effective at reducing bacterial loads. In the chronic stage, particularly in the in vivo model, many tested compounds lost activity against persisting bacteria and some antibiotics even induced SCV formation.
Authors: Kathryn McLean; Elizabeth A Holmes; Kelsi Penewit; Duankun K Lee; Samantha R Hardy; Mingxin Ren; Maxwell P Krist; Kevin Huang; Adam Waalkes; Stephen J Salipante Journal: Infect Immun Date: 2019-03-25 Impact factor: 3.441
Authors: Virginia Post; Llinos G Harris; Mario Morgenstern; Leonardos Mageiros; Matthew D Hitchings; Guillaume Méric; Ben Pascoe; Samuel K Sheppard; R Geoff Richards; T Fintan Moriarty Journal: J Clin Microbiol Date: 2017-08-09 Impact factor: 5.948