The revival of fosfomycin

Abstract

Fosfomycin, originally named phosphonomycin, was discovered in Spain in 1969. There are three forms of fosfomycin: fosfomycin tromethamine (a soluble salt) and fosfomycin calcium for oral use, and fosfomycin disodium for intravenous use. Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis in both Gram-positive and Gram-negative bacteria by inhibiting the initial step involving phosphoenolpyruvate synthetase. It has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. It is highly active against Gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Its unique mechanism of action may provide a synergistic effect to other classes of antibiotics including beta-lactams, aminoglycosides, and fluoroquinolones. Oral fosfomycin is mainly used in the treatment of urinary tract infections, particularly those caused by Escherichia coli and Enterococcus faecalis. Intravenous fosfomycin has been administered in combination with other antibiotics for the treatment of nosocomial infections due to multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in serum, kidneys, bladder wall, prostate, lungs, inflamed tissues, bone, cerebrospinal fluid, abscess fluid, and heart valves. Fosfomycin is well tolerated, with a low incidence of adverse events. Further randomized controlled trials are needed in order to evaluate the efficacy of intravenous fosfomycin for the management of nosocomial infections due to MDR pathogens.

Fosfomycin: An Alternative Therapy for the Treatment of UTI Amidst Escalating Antimicrobial Resistance

“…After an aerobic incubation at 37˚C, the plates showing significant growth as per the Kass count (single species count of more than 10 5 organisms per ml of urine) were processed further and the isolates were identified up to the species level by using standard biochemical tests [5][6][7][8]. Antibiotic sensitivity testing was done by the Kirby Bauer disc diffusion method as per CLSI guidelines [9,10].…”

Blocking Peptidoglycan Recycling in Pseudomonas aeruginosa Attenuates Intrinsic Resistance to Fosfomycin

“…2,3,38 An example of such a well-known antibiotic that was reintroduced into clinical practice is fosfomycin. 6,24,26,34 This epoxide derivative of phosphonic acid (cis-1,2-epoxypropyl phosphonic acid) was discovered in 1969, originally named phosphonomycin, and was isolated from cultures of Streptomyces species. 11 Fosfomycin interferes with the first cytoplasmatic step of bacterial cell wall biosynthesis, the formation of the peptidoglycan precursor uridine diphosphate N-acetylmuramic acid (UDP-MurNAc) 15 and, thus, results in decelerated peptidoglycan synthesis, reduced growth, and eventually cell lysis.…”

Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

“…Fosfomycin recently regained attention as an antibiotic that could be effective against multidrug-resistant (MDR) pathogens, such as extended-spectrum ␤-lactamase (ESBL) producers, because there is no structural relationship between the drug and other commonly used antimicrobials, including fluoroquinolones, ␤-lactams, and aminoglycosides (5,6). Fosfomycin is also used to decrease the risk of development of hemolytic-uremic syndrome (HUS), a fatal infectious disease caused by enterohemorrhagic Escherichia coli (EHEC) O157:H7 (7,8).…”