Background:Fosfomycin has retained activity against many multi-drug resistant (MDR) Gram-negatives, and may be useful against extended spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Enterobacteriaceae. There are few data from the UK on the susceptibility of invasive Gram-negative isolates to fosfomycin, especially in the era of increasing use of oral fosfomycin for UTIs.


1. We evaluated, in 100 consecutive Gram-negative bloodstream infections (BSI), the in-vitro activity of fosfomycin. Disc diffusion and MIC test strip methods applying revised EUCAST guidelines for fosfomycin were used.

2. A secondary objective was testing for synergy in combination with 10 further antibiotics. Isolates were selected if:

a) Fosfomycin resistant

b) AMP-C/ESBL/carbapenemase producers (or carbapenem resistant)

c) ‘MDR’: defined as ‘resistance to ≥3 classes of antibiotics’ (based on prior routine sensitivity testing).

For eligible isolates, MICs were determined individually, and subsequently in combination using the MTS ‘cross’ synergy method.

Results:96/100 isolates were susceptible to fosfomycin by MIC test strip. 30/100 isolates were eligible for synergy testing. Synergy was most commonly detected between fosfomycin and piperacillin/tazobactam (32.1%), ceftazidime/avibactam (30%), and temocillin (28.5%). An additive effect was most commonly detected with aztreonam (85.7%) and meropenem (82.1%), but 100% indifference was found with tigecycline. No antagonism was identified.

Conclusions:Synergistic or additive effects were detected for beta-lactam/fosfomycin combinations in a high proportion of isolates; >80% for all suggesting such combinations should be preferred when using fosfomycin combination therapy. Agents with a different site of antibiotic action, were more likely to result in indifference.


Article metrics loading...

Loading full text...

Full text loading...


Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error