1. Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection
- Author
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L. Gatin, Nathalie Rioux-Leclercq, W. Mouton, Idir Ghout, A. Saleh Mghir, Anne-Claude Crémieux, Pierre Tattevin, Frédéric Laurent, Marie-Clémence Verdier, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomopathologie [Rennes], Hôpital Pontchaillou, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Service de pharmacologie biologique et toxicologie [Rennes], and Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
- Subjects
0301 basic medicine ,Microbiology (medical) ,Prosthesis-Related Infections ,Klebsiella pneumoniae ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Meropenem ,Injections, Intramuscular ,Microbiology ,Injections, Intra-Articular ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,In vivo ,polycyclic compounds ,medicine ,Animals ,Pharmacology (medical) ,030212 general & internal medicine ,biology ,business.industry ,Colistin ,Arthritis ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,equipment and supplies ,bacterial infections and mycoses ,biology.organism_classification ,Enterobacteriaceae ,In vitro ,3. Good health ,Anti-Bacterial Agents ,Klebsiella Infections ,Disease Models, Animal ,Infectious Diseases ,Carbapenem-Resistant Enterobacteriaceae ,Treatment Outcome ,Debridement ,bacteria ,Female ,Rabbits ,business ,Bacteria ,medicine.drug - Abstract
Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 108 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11–13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low ( 20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model.
- Published
- 2019