What is the relevance of fosfomycin pharmacokinetics in the treatment of serious infections in critically ill patients? A systematic review

As treatment options for critically ill patients with multidrug-resistant bacteria diminish, older antibiotics such as fosfomycin are being investigated for use as last-resort drugs. Fosfomycin is a broad-spectrum antibiotic with activity both against Gram-positive and Gram-negative bacteria. The aim of this review was to examine the effectiveness of current fosfomycin dosing strategies in critically ill patients. These patients can be subject to pathophysiology that can impact antibiotic pharmacokinetic (PK) profiles and potentially the effectiveness of their treatment. As a hydrophilic drug with negligible protein binding, fosfomycin is eliminated almost entirely by glomerular filtration and is subject to patient renal function. If altered as seen in augmented renal clearance, renal function in a critically ill patient may lead to low blood concentrations and predispose patients to the risk of treatment failure. If altered as seen in acute kidney injury, toxic blood concentrations may develop. Fosfomycin has a volume of distribution comparable with β-lactams and aminoglycosides and may therefore increase in critically ill patients. Altered dosing strategies may be required to optimise dosing given these PK changes, although the current paucity of data on fosfomycin in critically ill patients prevents accurate dosing guidance being recommended at this time.