Pharmacokinetics and Pharmacodynamics of Fosfomycin in Urinary Tract Infections

Fosfomycin is a broad-spectrum bactericidal antibiotic that irreversibly inhibits the initial step of peptidoglycan synthesis. Following oral administration of the trometamol salt, bioavailability is moderate, achieving high urinary concentrations that exceed minimum inhibitory concentrations for common uropathogens for up to 48 hours after a single 3 g dose. Intravenous formulations distribute into extracellular fluids with a two-compartment profile and are subject to renal clearance, with dosage adjustments required in renal impairment and during renal replacement modalities. Fosfomycin displays concentration- and time-dependent killing, with pharmacodynamic indices such as the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) and peak concentration to MIC (Cmax/MIC) predicting efficacy. Its low protein binding and extensive tissue penetration support use in complicated urinary tract infections, while continuous or prolonged infusion strategies have been explored to optimise time above breakpoint and suppress resistance emergence. Clinically, fosfomycin has resurged as a key agent against multidrug-resistant Enterobacterales in both uncomplicated and complicated settings, offering simplicity of dosing, minimal toxicity and a favourable ecological footprint.

Research from Nature Portfolio

A recent population pharmacokinetic investigation in critically ill patients undergoing continuous venovenous haemodialysis delineated a two-compartment model with distinct renal and dialysis clearances. Simulations suggested that standard 5 g doses every 6 hours require adjustment based on creatinine clearance and dialysis settings, with recommendations rising to 15–16 g daily divided into three to four doses for patients with preserved residual renal function. This work emphasises individualised dosing in high-acuity settings to maintain therapeutic exposures and informs future clinical trials in similar cohorts.

Pharmacokinetics and Pharmacodynamics of Fosfomycin in Urinary Tract Infections publication trend

The graph below shows the total number of articles in pharmacokinetics and pharmacodynamics of fosfomycin in urinary tract infections across all publications each year (not limited to Nature Index journals).

Technical terms

Pharmacokinetics: The study of drug absorption, distribution, metabolism and excretion over time.

Pharmacodynamics: The relationship between drug concentration at the site of action and its therapeutic effect.

AUC/MIC: The ratio of the area under the concentration-time curve to the minimum inhibitory concentration, indicating overall drug exposure relative to pathogen susceptibility.

Cmax/MIC: The ratio of peak plasma concentration to the minimum inhibitory concentration, reflecting the importance of achieving high transient drug levels.

Continuous venovenous haemodialysis (CVVHD): A renal replacement therapy modality used in critically ill patients affecting drug clearance.

Bioavailability: The proportion of an administered dose that reaches the systemic circulation in an active form.

References

1. Stability Study of Fosfomycin in Elastomeric Pumps at 4 °C and 34 °C: Technical Bases for a Continuous Infusion Use for Outpatient Parenteral Antibiotic Therapy. Pharmaceutics (2023).
2. Rediscovering the value of fosfomycin trometamol in the era of antimicrobial resistance: A systematic review and expert opinion. International Journal of Antimicrobial Agents (2023).
3. Population pharmacokinetic modeling of multiple-dose intravenous fosfomycin in critically ill patients during continuous venovenous hemodialysis. Scientific Reports (2023).
4. Fosfomycin: Pharmacological, Clinical and Future Perspectives. Antibiotics (2017).
5. Pharmacokinetics and Pharmacodynamics of Fosfomycin and Its Activity against Extended-Spectrum-β-Lactamase-, Plasmid-Mediated AmpC-, and Carbapenemase-Producing Escherichia coli in a Murine Urinary Tract Infection Model. Antimicrobial Agents and Chemotherapy (2018).
6. Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studies. European Journal of Clinical Microbiology & Infectious Diseases (2021).