the Revival of Intravenous Fosfomycin therapy in critically ill patients infected with with Colistin Resistant Enterobacteriacae

The Revival of Int ravenous Fosfomycin therapy in critically ill patients infected with with Colistin Resistant Enterobacteriacae

Dr Anas.M

Clinical Pharmacist

KIMS AL-SHIFA Super Speciality Hospital.

Carbapenem resistant enterobacteriacae (CRE) emerged in recent years as one of the most challenging group of antibiotic resistant pathogens. Polymyxins are considered as the last resort for the treatment of infections with Carbapenem resistant gram bacilli (GNB). Inadequate or extensive use of Colistin leads to emergence of Colistin resistance, jeopardizing treatment options in Intensive Care Units (ICU), potentially increasing mortality and morbidity and necessitating prudent use of alternative antibiotics.  Selective pressure by the increased use of Colistin and clonal expansion through horizontal transmission have generated clusters of cases infected with multi-resistant klebsiella pneumonia strains.

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. Its unique mechanism of action may provide a synergistic effect to other antibiotic including beta –lactams, Aminoglycosides and fluoroquinolones. Fosfomycin penetrates sufficiently into various tissues and CSF.

Fosfomycin may be considered an alternative for the treatment of infection due to Carbapenem-resistant bacteria in adult due to its unique mechanism of action and its protective effect against nephrotoxicity induced aminoglycosides or Colistin. Fosfomycin has regained attention because of its in Vivo activity against ESBL –producing Enterobacteriacae and MDR p aeruginosa.

Fosfomycin is a bactericidal agents showing low level of toxicity as well as low level of cross-resistance with other antibiotics. Fosfomycin tromethamine is an oral formulation approved for the treatment of uncomplicated urinary tract infection (UTI), caused by Multi Drug Resistant bacteria. Fosfomycin is also available as sodium/disodium formulations for intravenous use, which is showing promising result against MDR/PDR pathogens

Fosfomycin disodium is given intravenously and on rare occasion intramuscularly. Daily dose ranges from 12-16 g on average, administered in 2-4 infusions. Dose should be reduced if the creatinine clearance is less than 50ml/min. Intravenous administration of fosfomycin is associated with a low incidence adverse effects. The most significant adverse effect related to the administration of fosfomycin disodium is a high sodium intake, which could be a limitation in patients with heart and renal failure. It should be emphasized that 1g of intravenous fosfomycin brings 0.33g (14.4 mEq) of Sodium.

References

1.      The International Journal of Infectious Diseases: The revival of fosfomycin, 732-739, November 2011.

2.      American Journal of Emegency Medicine:Newly Approved antibiotics and antibiotics reserved for resistant infections:Implications for emergency medicine-Vol 35, page 154-158, 2017

3.      Open Journal of Medical Microbiology: Synergistic Combination of Carbapenems and Colistin against P.Aaeruginosa  and A.baumannii, 2013,13,253-258