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Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection.
Gatin, L; Mghir, A Saleh; Mouton, W; Laurent, F; Ghout, I; Rioux-Leclercq, N; Tattevin, P; Verdier, M C; Cremieux, A C.
Afiliação
  • Gatin L; UMR U1173 Université Versailles St-Quentin, Versailles, France; Service d'Orthopédie et traumatologie, Hôpital Raymond Poincaré, Garches, France.
  • Mghir AS; UMR U1173 Université Versailles St-Quentin, Versailles, France.
  • Mouton W; Laboratoire de Bactériologie, Hôpital de la Croix Rousse, Centre National de Référence des Staphylocoques Unité Inserm 851, Faculté de Médecine Lyon Est, Lyon, France.
  • Laurent F; Laboratoire de Bactériologie, Hôpital de la Croix Rousse, Centre National de Référence des Staphylocoques Unité Inserm 851, Faculté de Médecine Lyon Est, Lyon, France.
  • Ghout I; URC Paris-Ouest, Laboratoire de Biostatistiques, Hôpital Ambroise Paré, Boulogne-Billancourt, France.
  • Rioux-Leclercq N; Service d'Anatomopathologie, Hôpital Pontchaillou, CHU de Rennes, Rennes, France.
  • Tattevin P; Service de Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, CHU de Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex, France. Electronic address: pierre.tattevin@chu-rennes.fr.
  • Verdier MC; Laboratoire de Pharmacologie Biologique, Hôpital Pontchaillou, CHU de Rennes, Rennes, France.
  • Cremieux AC; UMR U1173 Université Versailles St-Quentin, Versailles, France; Service des maladies infectieuses Hôpital Saint Louis AP-HP, Université Paris 7, Paris, France.
Int J Antimicrob Agents ; 54(4): 456-462, 2019 Oct.
Article em En | MEDLINE | ID: mdl-31319190
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 (<0.1% at 24 h) but reached a local concentration of ≥20 mg/L (>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.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Artrite / Infecções por Klebsiella / Infecções Relacionadas à Prótese / Colistina / Enterobacteriáceas Resistentes a Carbapenêmicos / Klebsiella pneumoniae / Antibacterianos Limite: Animals Idioma: En Revista: Int J Antimicrob Agents Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Artrite / Infecções por Klebsiella / Infecções Relacionadas à Prótese / Colistina / Enterobacteriáceas Resistentes a Carbapenêmicos / Klebsiella pneumoniae / Antibacterianos Limite: Animals Idioma: En Revista: Int J Antimicrob Agents Ano de publicação: 2019 Tipo de documento: Article