Potential for the Use of Fosfomycin in the Topical Treatment of Periprosthetic Joint Infection

Clinical Microbiology and Antimicrobial Chemotherapy. 2016; 18(2):104-112

Type
Journal article

Objective.

To assess a potential for the use of fosfomycin as a component of polymethyl methacrylate-based bone cement in the topical treatment of periprosthetic infection.

Materials and Methods.

The most common pathogens of periprosthetic joint infection isolated during the 2013–2014 were studied. Susceptibility of 358 S. aureus and 19 E. coli strains to vancomycin, fosfomycin, and gentamicin was determined. Antimicrobial activity duration for the control samples of the gentamicin-containing bone cement (DEPUY CMW 1 GENTAMICIN) and the experimental samples with addition (per 20 g of cement) of 1 g or 2 g of vancomycin (5% or 10%), 2 g or 4 g of fosfomycin (10% or 20%) was investigated. Antimicrobial activity was tested against reference ATCC strains of MSSA, MRSA, K. pneumoniae and E. coli. Ultimate strength against bending and compression, and coefficient of elasticity were determined for all cement samples tested.

Results.

The members of Staphylococcaceae (57.6%) and Enterobacteriaceae (10.1%) families were the common pathogens of periprosthetic infection. S. aureus (including 21.8% of MRSA) was a leading pathogen; Klebsiella pneumoniae (36.1%) and Escherichia coli (12.1%) were the most predominant pathogens among Enterobacteriaceae. No significant differences in anti-MSSA activity between vancomycin, gentamicin and fosfomycin were found. Gentamicin was significantly less active against MRSA than fosfomycin (p<0.01). No vancomycin-resistant S. aureus isolates were observed. Susceptibility of E. coli isolates to fosfomycin and gentamicin was 100% (MIC ≤32 mcg/ml) and 63.2%, respectively (p<0.05). The control samples of the gentamicin-containing bone cement demonstrated the least antimicrobial activity duration. The samples with 5% vancomycin remained active against MRSA and E. coli for 2 days and against MSSA and K. pneumoniae for 3 days and 5 days, respectively. The 2-fold increase in vancomycin concentration failed to prolong antimicrobial activity substantially. The samples with 10% or 20% fosfomycin were active against MRSA for 3 days and 5 days, respectively, and against MSSA and K. pneumoniae for 28 days, and against E. coli for 17 days. Significant changes in the bone cement strength measures compared to the control samples were noted when adding vancomycin (10%) and fosfomycin (20%).

Conclusions.

Fosfomycin has a high activity against the most common pathogens of periprosthetic joint infection. Its addition to the gentamicin-containing bone cement significantly prolongs antimicrobial activity duration. Administration of gentamicin-containing bone cement with 10% fosfomycin for the spacer formation in the treatment of periprosthetic infection may be considered useful.

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