Fosfomycin

Question 1

What is the mechanism of action of fosfomycin?

Answer 1

Inhibits bacterial cell wall synthesis by blocking the enzyme enolpyruvyl transferase (MurA), which catalyzes the first step of peptidoglycan precursor synthesis. Bactericidal.

Question 2

What is the spectrum of activity of fosfomycin?

Answer 2

• Gram-positive: Covers some Staphylococcus saprophyticus
• Enterococcus (including some VRE).
• Gram-negative: Effective against Enterobacter, E. coli, Proteus mirabilis, and Klebsiella pneumoniae.
• Commonly used in carbapenem-resistant enterobacteriaceae in uncomplicated UTI
• NO activity against: Pseudomonas, Acinetobacter, or anaerobes.

Question 3

What is the primary clinical use of fosfomycin?

Answer 3

Uncomplicated lower UTI (acute cystitis) in women caused by E. coli or Enterococcus. Single-dose oral treatment is first-line therapy for acute cystitis in cases where nitrofurantoin and TMP-SMX are not preferred. Not used for pyelonephritis.

Question 4

What are the advantages of fosfomycin for UTIs?

Answer 4

• Single oral dose (3 g PO once) = High patient compliance.
• Safe in pregnancy (Category B).
• Minimal resistance development compared to other UTI antibiotics.
• Well-tolerated with few side effects.

Question 5

What is the mechanism of resistance to fosfomycin?

Answer 5

Enzymatic modification of MurA enzyme, leading to decreased binding affinity. Efflux pumps may decrease intracellular concentration. Plasmid-mediated resistance is rare but increasing.

Question 6

What are the main side effects of fosfomycin?

Answer 6

Mild GI upset (nausea, diarrhea). Headache. Rarely, Clostridioides difficile infection (low risk compared to fluoroquinolones). Hepatic toxicity (rare).

Question 7

How does fosfomycin compare to nitrofurantoin in treating UTIs?

Answer 7

Both drugs are first-line for uncomplicated UTI. Fosfomycin: Single-dose regimen, less frequent use. Nitrofurantoin: 5-day regimen but covers a broader range of UTI pathogens. Both are safe in pregnancy (except nitrofurantoin in 3rd trimester).

Question 8

Why is fosfomycin NOT effective for pyelonephritis?

Answer 8

Does not achieve therapeutic renal tissue levels. Only concentrates in the bladder, making it unsuitable for kidney infections.