2037. Efficacy of colistin-loaded cement spacer in carbapenem-resistant Klebsiella pneumoniae experimental prosthetic joint infection
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Poster ID week.pdf (566.1 kB)
  • Background:

    Parenteral administration of colistin carries a high risk of adverse effects, including nephrotoxicity and neurotoxicity. Local use of colistin may avoid systemic effects, while ensuring adequate concentrations in situ. In a new rabbit model of carbapenem-resistant Klebsiella pneumoniae (CRKP) knee-prosthesis infection, we evaluated the efficacy of colistin-loaded cement spacer, alone or in combination with intramuscular (i.m.) colistin.

    Methods:

    A partial knee replacement was performed with a silicone implant. Seven days after infection by KPC-99YC (colistin MIC 0.5 mg/L), surgical debridement with removal of the infected prosthesis was performed, and rabbits were randomly assigned to one of 4 treatment groups of 12 rabbits: prosthesis replacement by drug-free cement spacer (control); prosthesis replacement by colistin-loaded cement spacer (3 MUI of colistin/40 g of cement); prosthesis replacement by drug-free cement spacer and i.m. colistin (150 000 IU/kg im tid for 7 days, equivalent to 3 M IU tid in humans); or colistin local + i.m.

    Results:

    Colistin local or i.m did not increase the proportion of rabbits with sterile bones as compared to controls. However, combination of local and i.m. colistin was more effective than controls, both in terms of sterilization rate and bacterial load.

    Treatment

    No. of rabbits with sterile bone/total no. of rabbits

    P versus control group (significant if <0.05)

    log10 CFU/g of bone (mean ± SD)

    P versus control group (significant if <0.05)

    Control

    0/10

     

    5.9 ± 1.6

     

    Colistin local

    3/12

    0.590

    4.0 ± 2.4

    0.206

    Colistin i.m.

    3/10

    0.311

    4.1 ± 2.0

    0.043

    Colistin local + i.m.

    5/9

    0.049

    2.5 ± 1.5

    0.005

    Conclusion:

    Combination of systemic and local colistin is a promising option to optimize the treatment of carbapenem-resistant Klebsiella pneumoniae prosthetic joint infection.

    Laure Gatin, MD, UMR 1173 Université Versailles St-Quentin, Service d’Orthopédie et Traumatologie, Hôpital Raymond Poincaré, Garches, France, Azzam Saleh-Mghir, PhD, UMR 1173 Université Versailles St-Quentin, Garches, France, Frederic Laurent, DPharm, PhD, Laboratory of Bacteriology, Regional Reference Center for Bji, Hospices Civils de Lyon, Lyon, France; INSERM U1111 - International Center for Research in Infectiology - Claude Bernard Lyon 1 University, Lyon, France, Marie-Clémence Verdier, MD, Laboratoire de Pharmacologie Biologique, Hôpital Pontchaillou, Rennes, France, Idir Ghout, Dr, URC Paris-Ouest Laboratoire de Bio statistiques, Hôpital Ambroise Paré, Boulogne-Billancourt, France, Pierre Tattevin, MD, PHD, Pontchaillou University Hospital, Rennes, France and Anne-Claude Crémieux, Pr, Hôpital R. Poincaré, UMR 1173, Univ Versailles St Quentin, Garches, France

    Disclosures:

    L. Gatin, None

    A. Saleh-Mghir, None

    F. Laurent, None

    M. C. Verdier, None

    I. Ghout, None

    P. Tattevin, None

    A. C. Crémieux, None

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