In a 55-year-old man with candiduria and a concurrent bacterial uncomplicated urinary tract infection and normal renal function (eGFR ≥ 60 mL/min), can fluconazole be co‑administered with nitrofurantoin, and what are the appropriate dosing and safety considerations?

Co-Administration of Fluconazole and Nitrofurantoin in Candiduria with Concurrent Bacterial UTI

In a 55-year-old man with both candiduria and bacterial UTI, fluconazole and nitrofurantoin can be co-administered, but this combination should be approached with caution due to a documented case report of combined pulmonary and hepatic toxicity when these agents were used together. 1

Drug Interaction and Safety Considerations

Known Toxicity Risk

• A case report documented combined pulmonary and hepatic toxicity in a patient taking chronic nitrofurantoin who then received fluconazole, with hepatic enzymes elevated 5 times the upper limit of normal and bilateral pulmonary disease developing within 2 months. 1
• The mechanism of this potential interaction is unknown, but pharmacokinetic changes induced by fluconazole may have precipitated nitrofurantoin-induced toxicity. 1
• Both drugs individually can cause hepatotoxicity, making it difficult to attribute causality when used together. 1

Clinical Decision Algorithm

If both infections require treatment simultaneously:

• Monitor hepatic enzymes (AST, ALT, bilirubin) at baseline and weekly during the first month of combined therapy. 1
• Assess for pulmonary symptoms (dyspnea, pleuritic pain, cough) at each follow-up, as nitrofurantoin pulmonary toxicity can be precipitated or worsened. 1
• Consider treating the bacterial UTI first with nitrofurantoin (if the organism is susceptible), then addressing candiduria with fluconazole sequentially rather than concurrently, especially if the candiduria is asymptomatic. 2

Treatment Approach for Symptomatic Candiduria

First-Line Therapy

• Fluconazole 200 mg orally daily for 14 days is the preferred treatment for symptomatic Candida cystitis in patients with fluconazole-susceptible organisms. 2, 3
• Fluconazole achieves high urinary concentrations of active drug, ensuring effective pathogen eradication. 3, 4, 5

Essential Non-Pharmacologic Management

• Remove any indwelling urinary catheter immediately, as this single intervention resolves candiduria in approximately 50% of cases without antifungal therapy. 2, 3
• Discontinue unnecessary broad-spectrum antibiotics, which are major risk factors for candiduria development. 3

Treatment Approach for Bacterial UTI

Nitrofurantoin Dosing

• For uncomplicated bacterial cystitis in a patient with normal renal function (eGFR ≥60 mL/min), nitrofurantoin 100 mg orally every 6-12 hours is appropriate. 2
• Nitrofurantoin is contraindicated if eGFR <60 mL/min due to inadequate urinary concentrations and increased toxicity risk. 2

When Asymptomatic Candiduria Does Not Require Treatment

Observation Rather Than Treatment

• Asymptomatic candiduria should not be treated in most patients, as it almost always represents colonization rather than infection and treatment does not improve mortality or outcomes. 2, 3
• Candiduria progresses to candidemia in less than 5% of cases and serves as a marker of illness severity rather than a cause of morbidity itself. 3

High-Risk Exceptions Requiring Treatment

• Neutropenic patients with persistent unexplained fever and candiduria require aggressive treatment despite being asymptomatic. 2, 3
• Very low birth weight neonates are at risk for invasive candidiasis and require treatment. 2, 3
• Patients undergoing urologic procedures or instrumentation are at high risk for candidemia and require treatment with fluconazole 200-400 mg daily for several days before and after the procedure. 2, 3

Species-Specific Considerations

Fluconazole-Resistant Species

• For Candida glabrata (often fluconazole-resistant), use amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily for 1-7 days, with or without oral flucytosine 25 mg/kg four times daily. 2, 3
• For Candida krusei (intrinsically fluconazole-resistant), amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily for 1-7 days is the treatment of choice. 3

Critical Pitfalls to Avoid

Inappropriate Agent Selection

• Do not use echinocandins (caspofungin, micafungin, anidulafungin) for urinary Candida infections, as they achieve inadequate urine concentrations and have documented treatment failures. 2, 3, 4, 5
• Avoid lipid formulations of amphotericin B for UTI, as they do not achieve adequate urine concentrations and have documented treatment failures. 2

Monitoring During Combined Therapy

• If concurrent fluconazole and nitrofurantoin therapy is deemed necessary, establish baseline hepatic and pulmonary function before initiating treatment. 1
• Discontinue both agents immediately if hepatotoxicity (transaminases >3 times upper limit of normal) or pulmonary symptoms develop. 1
• The toxicity resolved upon discontinuation of both drugs in the documented case, emphasizing the importance of early recognition. 1

Upper Tract Involvement

Pyelonephritis Dosing

• For symptomatic Candida pyelonephritis with fluconazole-susceptible organisms, increase fluconazole to 200-400 mg (3-6 mg/kg) orally daily for 14 days; use the higher 400-mg dose when upper-tract involvement is confirmed. 2, 3
• Development of flank pain, fever >38.3°C, or systemic manifestations should raise suspicion for pyelonephritis. 3