Drug Interactions Between Cefuroxime and Fosfomycin
Direct Answer
There are no clinically significant drug interactions between cefuroxime and fosfomycin, and these antibiotics can be safely co-administered. In fact, the combination demonstrates synergistic or additive antibacterial effects against various pathogens without antagonism 1.
Evidence for Safety of Combination
Pharmacodynamic Compatibility
Fosfomycin shows predominantly synergistic or additive interactions with cephalosporins (including cefuroxime's class), accounting for 33% synergistic interactions with cephalosporins against Enterobacterales, with antagonism occurring in only 0.9% of all tested combinations 1.
The combination of fosfomycin with cephalosporins has been successfully used in clinical practice for carbapenem-resistant infections, where fosfomycin is added to cephalosporin-based regimens (such as ceftazidime-avibactam plus fosfomycin) without adverse pharmacodynamic interactions 2.
Biochemical Interaction Studies
In vitro enzyme studies demonstrate that both cefuroxime and fosfomycin can inhibit human serum paraoxonase-I enzyme through different mechanisms (cefuroxime via competitive inhibition, fosfomycin via noncompetitive inhibition), but this biochemical finding has no established clinical relevance to their combined use as antibiotics 3.
This enzyme interaction is a laboratory observation only and does not translate to contraindications or clinically meaningful drug-drug interactions in patient care 3.
Clinical Experience
Both drugs have been used together in surgical prophylaxis studies and multidrug-resistant infection treatment protocols without reported adverse interactions 4, 2.
Fosfomycin-containing combination regimens with various beta-lactams (including cephalosporins) demonstrate enhanced bactericidal effects and prevention of antimicrobial resistance development 1.
Practical Considerations
When Combination May Be Beneficial
For multidrug-resistant Gram-negative infections where susceptibility testing confirms fosfomycin activity, combining it with cefuroxime or other cephalosporins can provide synergistic coverage 1.
The combination is particularly relevant for ESBL-producing organisms where both agents retain activity 5.
Monitoring Requirements
If fosfomycin is used (particularly intravenous formulation), monitor serum potassium levels due to risk of hypokalemia (approximately 6% incidence in ICU patients) 6.
Avoid fosfomycin in patients with hypernatremia, cardiac insufficiency, or renal insufficiency due to high sodium content 7, 6.
Standard monitoring for cephalosporin therapy (renal function, hypersensitivity reactions) remains unchanged when combined with fosfomycin 4.
Clinical Bottom Line
Cefuroxime and fosfomycin have no contraindicated interactions and can be safely prescribed together. The combination may offer therapeutic advantages through synergistic antibacterial activity without increased risk of adverse effects beyond those expected from each agent individually 1, 4.