Is fosfomycin (phosphonic acid antibiotic) effective against Proteus mirabilis?

Fosfomycin Coverage of Proteus mirabilis

Yes, fosfomycin has good in vitro activity against Proteus mirabilis, with susceptibility rates ranging from 70-87.5%, making it a viable option for uncomplicated urinary tract infections caused by this organism. 1, 2

FDA-Approved Activity

The FDA drug label explicitly lists Proteus mirabilis among organisms against which fosfomycin demonstrates in vitro activity with minimum inhibitory concentrations (MICs) of 64 mcg/mL or less against most (≥90%) strains. 1

Clinical Susceptibility Data

Fosfomycin demonstrates consistent activity against P. mirabilis across multiple studies:

• In a Spanish multicenter study, more than 70% of P. mirabilis strains were susceptible to fosfomycin trometamol. 2
• A more recent Italian study showed 87.5% susceptibility of P. mirabilis to fosfomycin, which was superior to co-trimoxazole (67%) and nitrofurantoin (0%). 3
• Among multidrug-resistant isolates, fosfomycin inhibited all P. mirabilis strains tested, including ESBL-producing strains. 4
• A US study of 52 Proteus spp. isolates (including ESBL-producing P. mirabilis) demonstrated fosfomycin MIC50 and MIC90 values of 4 and 64 mcg/mL respectively. 5

Important Clinical Caveats

Fosfomycin should ONLY be used for uncomplicated lower urinary tract infections (cystitis) caused by P. mirabilis, NOT for complicated UTIs or pyelonephritis. 6, 7

• Tigecycline, another agent sometimes considered for multidrug-resistant infections, does NOT have in vitro activity against P. mirabilis, making fosfomycin a potentially superior choice in this specific scenario. 6
• The standard dosing is a single 3-gram oral dose of fosfomycin tromethamine, which achieves therapeutic urinary concentrations for 24-48 hours. 7, 1
• Approximately 38% of the dose is recovered in urine with mean concentrations of 706 mcg/mL attained within 2-4 hours. 1

Resistance Considerations

One fosfomycin-resistant P. mirabilis isolate was identified among 658 US UTI isolates tested (0.15% resistance rate), indicating resistance remains uncommon but possible. 8

• Fosfomycin-resistant mutants show reduced virulence, including impaired adherence to uroepithelial cells and urinary catheters, which may limit their clinical significance. 3
• There is generally no cross-resistance between fosfomycin and other antibiotic classes such as beta-lactams and aminoglycosides. 1

Practical Application

For uncomplicated cystitis caused by P. mirabilis, fosfomycin 3g oral powder dissolved in water as a single dose is an appropriate first-line option, particularly when other oral agents show resistance or are contraindicated. 7, 2

• If symptoms do not resolve by the end of treatment or recur within 2 weeks, perform urine culture and antimicrobial susceptibility testing. 7
• Fosfomycin can be taken without regard to food, though peak urinary concentrations occur slightly later with high-fat meals (6-8 hours vs 2-4 hours). 1