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J Antimicrob Chemother. 2015 Nov;70(11):3042-50. doi: 10.1093/jac/dkv221. Epub 2015 Jul 24.

In vitro pharmacodynamics of fosfomycin against clinical isolates of Pseudomonas aeruginosa.

Author information

1
Centre for Medicine Use and Safety, Monash University, Parkville, Victoria, Australia.
2
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
3
Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia Department of Microbiology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
4
Centre for Medicine Use and Safety, Monash University, Parkville, Victoria, Australia phillip.bergen@monash.edu.

Abstract

BACKGROUND:

The use of fosfomycin for treatment of systemic infections due to MDR Pseudomonas aeruginosa is increasing. However, pharmacodynamic data for fosfomycin are limited.

METHODS:

Sixty-four clinical isolates of P. aeruginosa (MDR and non-MDR) from two Australian hospitals were collected; 59 isolates were from patients with cystic fibrosis and 5 isolates were from critically ill patients. The in vitro pharmacodynamic properties of fosfomycin (disodium) were investigated via MICs (all isolates) and, for selected isolates, via time-kill kinetics (static and dynamic models; concentration range, 1-1024 mg/L), population analysis profiles (PAPs) and post-antibiotic effect (PAE). Two inocula (∼10(6) and ∼10(8) cfu/mL) were included in static time-kill studies to examine the effect of inocula on bacterial killing.

RESULTS:

MICs ranged from 1 to >512 mg/L, with 61% of isolates considered fosfomycin susceptible (MIC ≤64 mg/L). The MIC distributions for MDR and non-MDR isolates were similar. Baseline PAPs indicated heteroresistance in all isolates tested. Time-kill studies showed moderate (maximum killing ∼3 log10 cfu/mL), time-dependent killing at the low inoculum with regrowth at 24 h. Most concentrations resulted in complete replacement of fosfomycin-susceptible colonies by fosfomycin-resistant colonies. Bacterial killing was virtually eliminated at the high inoculum. The PAE ranged from 0.3 to 5.5 h.

CONCLUSIONS:

These data suggest monotherapy with fosfomycin may be problematic for the treatment of infections caused by P. aeruginosa. Further investigation of fosfomycin combination therapy is warranted.

PMID:
26209311
DOI:
10.1093/jac/dkv221
[Indexed for MEDLINE]

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