Can fluconazole (antifungal medication) and metronidazole (antibacterial and antiprotozoal medication) be administered together in a patient with a fungal infection and a bacterial or protozoal infection?

Can Fluconazole and Metronidazole Be Given Together?

Yes, fluconazole and metronidazole can be safely co-administered together, as there are no documented drug-drug interactions between these medications, and this combination is clinically appropriate when treating mixed anaerobic-fungal infections. 1

Safety Profile of Co-Administration

• No pharmacokinetic interactions exist between metronidazole and fluconazole, as fluconazole's CYP450 interactions do not significantly affect metronidazole metabolism 1
• Fluconazole has been studied extensively for drug interactions with other medications, and while potential interactions are common in hospitalized patients (occurring in 70% of admissions), clinically significant adverse events from fluconazole drug interactions are rare 2
• Metronidazole is metabolized primarily by the liver to 5 metabolites and has low protein binding (<20%), making it less susceptible to displacement interactions 3

Clinical Scenarios Requiring Both Medications

Mixed anaerobic-fungal infections are the primary indication for combining these agents:

• In critically ill patients with intra-abdominal sepsis, both anaerobes and Candida species may be present, requiring metronidazole for anaerobic coverage and fluconazole for fungal coverage 1
• The IDSA recommends empiric antifungal therapy in critically ill patients with risk factors for invasive candidiasis, which frequently overlap with anaerobic infection risk factors 1

Dosing Recommendations When Using Both Agents

For mixed anaerobic-fungal infections:

• Start metronidazole 500 mg IV/PO every 8 hours for anaerobic coverage 1
• Add fluconazole 800 mg loading dose on Day 1, then 400 mg daily for empiric Candida coverage 4, 1

For sequential therapy (when candidiasis develops during metronidazole treatment):

• Add fluconazole 150 mg single dose for uncomplicated vulvovaginal candidiasis 1
• Use fluconazole 400 mg daily for more severe or invasive infections 1

High-Risk Populations Requiring Dual Coverage

Consider empiric coverage for both anaerobes and Candida in ICU patients with multiple risk factors including:

• Recent abdominal or bowel surgery 1
• Prolonged broad-spectrum antibiotic use 1
• Central venous catheters 1
• Parenteral nutrition 1
• Dialysis 4

Important Caveats

Pregnancy considerations:

• Metronidazole is acceptable for anaerobic infections in pregnant women 1
• Fluconazole should be used cautiously in pregnancy, with amphotericin B deoxycholate preferred for invasive candidiasis 1

Duration of therapy:

• Fluconazole should be continued for 14 days after the first negative blood culture for candidemia 1
• Metronidazole duration depends on the specific anaerobic infection being treated 3, 5

Monitoring:

• Both medications can cause elevation of liver enzymes, though this rarely requires treatment modification 6
• No specific additional monitoring is required when these drugs are used together beyond standard monitoring for each individual agent 1