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Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection.

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 (<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.

journal_name

Int J Antimicrob Agents

journal_title

International journal of antimicrobial agents

authors

Gatin L,Mghir AS,Mouton W,Laurent F,Ghout I,Rioux-Leclercq N,Tattevin P,Verdier MC,Cremieux AC

doi

10.1016/j.ijantimicag.2019.07.009

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

456-462

issue

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(19)30189-X

journal_volume

pub_type

杂志文章

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Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection.