Fosfomycin: Pharmacological, Clinical and Future Perspectives
Centre for Human Drug Research, Leiden, 2333 CL, The Netherlands
Department of Medical Microbiology, Albert Schweitzer Hospital, Dordrecht, 3318 AT, The Netherlands
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands
Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, 3015 CN, The Netherlands
Hospital Pharmacy, The Hague Hospitals, The Hague, 2545 AB, The Netherlands
Department of Internal Medicine, Haga Teaching Hospital, The Hague, 2566 MJ, The Netherlands
Groningen Research Institute for Asthma and COPD, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands
Author to whom correspondence should be addressed.
Academic Editor: Christopher C. Butler
Antibiotics 2017, 6(4), 24; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics6040024
Received: 30 May 2017 / Revised: 18 October 2017 / Accepted: 19 October 2017 / Published: 31 October 2017
Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided.