Is Fosfomycin an Antibiotic?
Yes, fosfomycin is a broad-spectrum bactericidal antibiotic with activity against both Gram-positive and Gram-negative bacteria, including multidrug-resistant organisms. 1, 2
Mechanism of Action and Classification
Fosfomycin is a phosphonic acid derivative representing an epoxide class of antibiotics that irreversibly inhibits MurA, an enzyme essential for bacterial cell wall synthesis at an early stage. 2, 3
It has the lowest molecular weight (138 Da) among existing antibacterial agents and is not structurally related to any other antibiotic class, resulting in minimal cross-resistance with β-lactams, aminoglycosides, or other antimicrobial families. 3, 4
Spectrum of Antimicrobial Activity
Fosfomycin demonstrates bactericidal activity against a wide variety of Gram-negative pathogens (including E. coli, Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, and Pseudomonas aeruginosa) and Gram-positive organisms (including MRSA, Enterococcus faecium, and VRE). 2, 5, 6
Susceptibility rates in carbapenem-resistant K. pneumoniae range from 39% to 99%, though FosA-like resistance genes are increasingly prevalent in these strains. 6
Available Formulations
Oral formulation: Fosfomycin tromethamine is available as a single-dose 3-gram sachet (containing 5.631 grams of fosfomycin tromethamine equivalent to 3 grams of fosfomycin) for oral administration. 1
Intravenous formulation: IV fosfomycin disodium is used in many countries for serious systemic infections, though availability varies by region. 3, 7
Pharmacokinetic Properties
Fosfomycin is not metabolized and is excreted unchanged in urine through glomerular filtration, achieving peak urinary concentrations of 1053-4415 mg/L within 4 hours of a single 3-gram oral dose. 2
Urinary concentrations >128 mg/L (adequate to inhibit most urinary pathogens) are maintained for 24-48 hours following a single oral dose. 2
The drug does not bind to plasma proteins, achieves extensive tissue penetration (including CNS, soft tissues, bone, and lungs), and does not require dose adjustment in hepatic dysfunction. 3, 4
Clinical Indications
First-line therapy for uncomplicated cystitis in women: Recommended by the Infectious Diseases Society of America, European Association of Urology, American Urological Association, and American College of Physicians as a first-line option. 8, 2
Multidrug-resistant Gram-negative infections: Fosfomycin-containing combination therapy is recommended for carbapenem-resistant Enterobacteriaceae when the isolate is susceptible or demonstrates synergistic effects. 6, 9
Systemic infections (IV formulation): Used for acute osteomyelitis, nosocomial lower respiratory tract infections, complicated urinary tract infections, bacterial meningitis, bacteremia, and soft tissue infections in ICU settings. 3, 7