What is the appropriate oral antibiotic (po abx) treatment for a patient with a urine culture positive for both Candida glabrata and Proteus mirabilis?

Treatment for Polymicrobial UTI with Candida glabrata and Proteus mirabilis

For a urine culture positive for both Candida glabrata and Proteus mirabilis, treat the bacterial infection first with an appropriate oral antibiotic covering Proteus (such as a fluoroquinolone or trimethoprim-sulfamethoxazole based on susceptibilities), then address the C. glabrata only if the patient is symptomatic, high-risk, or undergoing urologic procedures—otherwise, removing predisposing factors like catheters is sufficient. 1

Step 1: Assess Clinical Context and Risk Factors

First, determine if antifungal treatment is even necessary:

• Most candiduria represents colonization, not infection, and does NOT require antifungal therapy 1
• Remove indwelling bladder catheters if present—this alone resolves candiduria in approximately 50% of asymptomatic patients 1, 2, 3
• Discontinue unnecessary antibiotics that may be promoting fungal overgrowth 4, 5

Treat C. glabrata ONLY if the patient meets high-risk criteria:

• Neutropenic patients 1
• Very low birth weight infants (<1500g) 1
• Patients undergoing urologic manipulation or procedures 1
• Symptomatic cystitis or pyelonephritis with pyuria and clinical signs 1
• Evidence of disseminated candidiasis 1

Step 2: Treat the Bacterial Component (Proteus mirabilis)

Address the Proteus mirabilis infection with standard oral antibiotics based on susceptibility testing:

• Fluoroquinolones (ciprofloxacin or levofloxacin) are typically first-line for Proteus UTI if susceptible
• Trimethoprim-sulfamethoxazole is an alternative if susceptible
• Duration: 7-14 days depending on whether cystitis or pyelonephritis is present
• Treating the bacterial infection and removing catheters may resolve the candiduria without antifungal therapy 4, 5

Step 3: Antifungal Treatment for C. glabrata (If Indicated)

C. glabrata is inherently less susceptible to fluconazole, making treatment more challenging:

For Symptomatic Cystitis:

• Oral flucytosine 25 mg/kg four times daily for 7-10 days is the preferred oral option 1
• Amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily for 1-7 days is an alternative (not oral, but achieves adequate urine concentrations) 1
• Fluconazole is NOT recommended as first-line for C. glabrata due to reduced susceptibility 1
• Amphotericin B bladder irrigation (50 mg/L sterile water daily for 5 days) may be considered as adjunctive therapy for refractory cystitis 1

For Pyelonephritis:

• 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 1
• Oral flucytosine monotherapy 25 mg/kg four times daily for 2 weeks can be considered for less severe cases 1
• Duration: 2 weeks total 1
• Eliminate urinary tract obstruction—this is critical for cure 1

For High-Risk Patients Undergoing Urologic Procedures:

• Amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily for several days before and after the procedure 1
• Fluconazole 400 mg daily is an alternative only if susceptibility testing confirms susceptibility 1

Critical Pitfalls to Avoid

Do not treat asymptomatic candiduria in non-high-risk patients:

• This leads to unnecessary antifungal exposure, promotes resistance, and provides no clinical benefit 1, 2
• The IDSA strongly recommends against treatment unless high-risk criteria are met 1

Do not use fluconazole empirically for C. glabrata:

• C. glabrata has dose-dependent susceptibility to fluconazole at best, and many isolates are resistant 1
• Obtain susceptibility testing if fluconazole is being considered 1, 6

Do not use echinocandins or lipid amphotericin formulations for isolated UTI:

• Echinocandins (caspofungin, micafungin, anidulafungin) do not achieve therapeutic urine concentrations 1, 4, 5
• Lipid amphotericin formulations similarly fail to achieve adequate urinary levels 1, 5

Do not forget source control:

• Failure to remove catheters, relieve obstruction, or address fungus balls leads to treatment failure regardless of antifungal choice 1, 3
• Imaging (ultrasound or CT) should be performed if infection persists despite appropriate therapy to identify anatomical abnormalities or fungus balls 1, 3

Monitor flucytosine toxicity closely:

• Flucytosine can cause bone marrow suppression, hepatotoxicity, and GI toxicity 1
• Monitor CBC, liver function, and renal function during therapy 1, 5