Fosfomycin iv

Based on the activity of fosfomycin against multi-drug resistant pathogens (Enterobacteriaceae, P. aeruginosa, S. aureus incl. MRSA) and the favorable safety profile, this revived antibiotic could have a role in the treatment of infections with few therapeutic options. Fosfomycin does not display any cross-resistance with other antibacterial drug classes. It inhibits MurA, an essential protein involved in the bacterial cellwall synthesis, thus inhibits a single target. Consequently, a high mutation frequency as observed in vitro translates into a considerable potential for emergence of resistance during therapy when used as monotherapyeven and even when used in combination. Thus, fosfomycin is mainly used in combination with other antibiotics to reduce the risk of development of resistance.

In contrast to the oral fosfomycin trometamol products, the intravenous formulation is not widely available and “redeveloping” of this last resort antibiotic is not a priority. Hardly any PK/PD studies guide the optimisation of the dosage strategies. Similarly, only limited observational evidence on the effectiveness of fosfomycin in critically ill patients suffering from extensively resistant infections is available. The recently published Greek observational study reports the usage of fosfomycin iv  at a median dose of 24g/day for a median of 14 days, mainly in combination with colistin or tigecycline (K. Pontikis et al 2013).

Dosage recomendations of fosfomycin in European product informations (SPC) range from 3 to 16 g. Fosfomycin is used primarily as last resort treatment option in case of multidrug resistant Gram-negative bacteria. In such situation a dose of 3g daily is clearly not adequate. Even 16 g may not provide the drug exposure that is required for difficult to treat pathogens. The EUCAST breakpoint applies to a dosage of 4-8 g x 3. Fosfomycin is well tolerated and it is not clear how much the dose could be increased, especially in patients with volume overload or hypernatremia. Clinical information is lacking.

Updating and harmonising the Fosfomycin SPCs in Europe is urgently needed.

Reviews:
Fosfomycin: an old, new friend?
Fosfomycin: Use Beyond Urinary Tract and Gastrointestinal Infections
Fosfomycin: an old—new antibiotic
The revival of fosfomycin
Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

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