Fosfomycin is a novel class of antibacterial drugs Overview of Antibacterial Drugs Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more with a chemical structure unrelated to other known antibiotics. It is a bactericidal drug that disrupts cell wall synthesis by inhibiting phosphoenolpyruvate synthetase and thus interferes with the production of peptidoglycan.
In the US, it is available only as a powder formulation of fosfomycin tromethamine, which can be dissolved in liquid and taken orally. Outside the US, IV formulations are available.
Oral bioavailability of the fosfomycin tromethamine salt is low (about 40%), and, consequently, serum levels are low relative to the minimum inhibitory concentrations (MICs). For this reason, the drug is used to treat uncomplicated lower urinary tract infections Introduction to Urinary Tract Infections (UTIs) Urinary tract infections (UTIs) can be divided into upper tract infections, which involve the kidneys (pyelonephritis), and lower tract infections, which involve the bladder (cystitis), urethra... read more , not pyelonephritis Acute pyelonephritis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more .
Fosfomycin does not bind to plasma proteins and distributes widely into tissues. Fosfomycin is excreted in urine mainly by glomerular filtration without biotransformation. After oral dosing, urinary levels exceed the MICs of susceptible pathogens for over 24 hours.
An IV formulation of fosfomycin is available in some countries and can be useful for more serious infections, including central nervous system infections, osteomyelitis, and pneumonia; when used to treat these infections, it is often used with other antibiotics such as beta-lactams.
Fosfomycin has a broad spectrum of activity against both gram-positive and gram-negative organisms, including many antibiotic-resistant organisms such as
Staphylococcus aureus Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more , including methicillin-resistant S. aureus (MRSA)
Enterococcus Enterococcal Infections Enterococci are gram-positive, facultative anaerobic organisms. Enterococcus faecalis and E. faecium cause a variety of infections, including endocarditis, urinary tract infections, prostatitis... read more species, including vancomycin-resistant enterococci (VRE)
Enterobacteriaceae, including extended-spectrum beta-lactamase (ESBL)–producing and carbapenem-resistant Klebsiella pneumoniae Klebsiella, Enterobacter, and Serratia Infections The gram-negative bacteria Klebsiella, Enterobacter, and Serratia are closely related normal intestinal flora that rarely cause disease in normal hosts. Diagnosis is by culture. Treatment is... read more
Pseudomonas aeruginosa Pseudomonas and Related Infections Pseudomonas aeruginosa and other members of this group of gram-negative bacilli are opportunistic pathogens that frequently cause hospital-acquired infections, particularly in ventilator patients... read more , which has variable rates of intrinsic resistance
Oral fosfomycin should be used only for uncomplicated (ie, lower) urinary tract infections caused by susceptible pathogens. However, because it has a broad spectrum of activity, IV fosfomycin is sometimes used to treat infections with multidrug-resistant organisms at other anatomic sites.
For uncomplicated urinary tract infections in women, a single oral dose of fosfomycin tromethamine 5.61 g (equivalent to 3 g of fosfomycin) dissolved in liquid is used. A longer treatment course is probably necessary for infections at other sites (eg, prostate [1 Dosing considerations reference Fosfomycin is a novel class of antibacterial drugs with a chemical structure unrelated to other known antibiotics. It is a bactericidal drug that disrupts cell wall synthesis by inhibiting phosphoenolpyruvate... read more ]).
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