Fosfomycin in treatment of infections caused by multidrug resistant bacteria

Fosfomicin je stari antibiotik otkriven 1969. godine u Španjolskoj. Izoliran je iz kulture Streptomyces species. Baktericidan je antibiotik koji svojim mehanizmom djelovanja inhibira jednu od ranih faza u sintezi peptidoglikana stanične stijenke. Antibakterijski spektar mu je širok te djeluje na mnoge Gram-pozitivne i Gram-negativne bakterije. Farmakokinetski, nakon peroralne primjene dobro se resorbira u gastrointestinalnom traktu. Veže se za proteine plazme u zanemarivim količinama. Gotovo se uopće ne metabolizira u jetrima te se izlučuje u aktivnom, nepromijenjenom obliku bubrezima i zadržava se u mokraći. Službeno odobrene indikacije za primjenu fosofomicina su relativno uske. U peroralnoj formi upotrebljava se za za liječenje nekompliciranih infekcija urinarnog trakta te za antimikrobnu profilaksu urinarnih infekcija. U intravenskoj formi upotrebljava se u liječenju infekcija višestruko otpornim bakterijama te ostalih infekcija kada uobičajenim antibioticima nismo uspjeli postići izlječenje. Međutim, zbog vrlo povoljnih farmakokinetskih karakteristika, dobrog prodora i distribucije u brojna tkiva i organe, te zbog rastuće otpornosti bakterija na druge antibiotike, fosfomicin se razmatra kao vrijedna alternativa u liječenju brojnih infekcija kako u peroralnoj tako i u intravenskoj formi. Kao moguće indikacije navode se komplicirane infekcije mokraćnog sustava, sepsa, osteomijelitis, upala pluća, meningitis, infekcije dijabetičkog stopala te mnoge druge. Također, razmatra se upotreba fosfomicina u liječenju brojnih infekcija uzrokovanih višestruko otpornim bakterijama.Fosfomycin, an old antibiotic, was discovered in Spain in 1969. It was isolated from the Streptomyces spp culture. Fosfomycin is a bactericidal antibiotic which inhibits one of the early stages of peptidoglycan synthesis. Peptidoglycan is a structural element in the cell wall of most bacteria. Consequently fosfomycin has a broad spectrum of activity against a wide range of Gram-negative and Gram-positive bacteria as well as anaerobes. Pharmacokinetically, it is completely absorbed in the digestive tract after oral administration; the percentage of plasma protein binding of fosfomycin is negligible, it is not metabolized in the liver, and it is excreted in the active, unchanged form by the kidneys. Clinical usage is very limited. It is approved for peroral use for uncomplicated urinary tract infections which includes cystitis, urethritis, recurrent urinary tract infections, asymptomatic bacteriuria in pregnancy, and prophylaxis in urologic surgery. Fosfomycin is available for infections caused by multidrug resistant bacteria for intravenous administration as salvage therapy. However, due to its favorable pharmacokinetic characteristics and excellent distribution to many tissues and organs, for example the skin, soft tissue, bones, and cerebrospinal fluid, and because of antimicrobial resistance to first-line treatments for infections caused by multi-drug bacteria, fosfomycin should be taken into consideration as an alternative antibiotic for the treatment of these infections. Possible indications for treatment would be complicated urinary tract infections, ventilator associated pneumonia, shunt-meningitis, cellulitis, and diabetic foot infections