Treatment of Candida glabrata Infection in Myeloperoxidase-Deficient Patients
An echinocandin (caspofungin, micafungin, or anidulafungin) is the mandatory first-line therapy for C. glabrata infection in MPO-deficient patients, and strong consideration should be given to adding liposomal amphotericin B given the patient's severely impaired fungicidal capacity. 1
Immediate Treatment Initiation
Start an echinocandin immediately upon diagnosis:
- Caspofungin: 70 mg loading dose, then 50 mg daily 2, 1
- Micafungin: 100 mg daily 2, 1
- Anidulafungin: 200 mg loading dose, then 100 mg daily 2, 1
The IDSA specifically designates echinocandins as preferred therapy for C. glabrata due to this species' intrinsic reduced susceptibility to azoles and increasing resistance rates 2, 1, 3. This preference is even more critical in MPO-deficient patients who lack the oxidative burst mechanism essential for fungal killing 1.
Combination Therapy Consideration for MPO Deficiency
Add liposomal amphotericin B (3-5 mg/kg daily) to the echinocandin regimen in MPO-deficient patients to compensate for their impaired fungicidal capacity 1. The IDSA guidelines suggest this combination approach may be necessary for complete clearance of C. glabrata in immunocompromised hosts with defective neutrophil function 1. MPO deficiency eliminates the hypochlorous acid-mediated killing pathway, making fungicidal drug activity paramount rather than relying on host immune mechanisms 1.
Critical Source Control Measures
Remove all central venous catheters as early as possible if the infection is presumed catheter-related 2, 1. This is strongly recommended in non-neutropenic patients and remains crucial even in immunocompromised states 2, 1. Catheter retention is independently associated with treatment failure and increased 28-day mortality 4, 5.
Monitoring Requirements
Obtain daily or every-other-day blood cultures until clearance is documented 1, 3. This aggressive monitoring is essential in MPO-deficient patients where treatment response may be delayed 1.
Perform dilated ophthalmologic examination within the first week after diagnosis to detect metastatic endophthalmitis 1, 3.
Azole Therapy: Contraindicated Without Susceptibility Testing
Do NOT use fluconazole or voriconazole without documented susceptibility testing 2, 1, 3. C. glabrata has intrinsic reduced susceptibility to azoles, with many isolates demonstrating resistance 2, 3. If susceptibility is confirmed and the patient is clinically stable with negative repeat cultures, transition to fluconazole 800 mg daily or voriconazole 200-300 mg twice daily may be considered only after 5-7 days of echinocandin therapy 1, 3. However, in MPO-deficient patients, maintaining fungicidal therapy throughout the treatment course is strongly preferred 1.
The FDA label data shows only 33% success rates for voriconazole against C. glabrata candidemia, identical to amphotericin B comparator rates, highlighting the limited efficacy of azoles for this species 6, 7.
Treatment Duration
Continue therapy for a minimum of 2 weeks after documented clearance from the bloodstream AND complete resolution of symptoms 2, 1, 3. In MPO-deficient patients with combination therapy, maintain both agents until these endpoints are achieved 1.
Alternative Therapy
If echinocandin intolerance develops or resistance is documented, switch to liposomal amphotericin B 3-5 mg/kg daily as monotherapy 2, 1, 3. Amphotericin B deoxycholate (0.5-1.0 mg/kg daily) is a less preferred alternative due to toxicity 2, 3.
Common Pitfalls to Avoid
Do not use standard echinocandin doses expecting fungicidal activity in neutropenic hosts—pharmacodynamic studies demonstrate that currently licensed human dosages achieve only fungistatic effects in neutropenic models, and higher doses may be required for fungicidal activity 8. This is particularly relevant in MPO deficiency where fungistatic activity may be insufficient 1.
Do not assume all echinocandins perform equally against C. glabrata—while caspofungin achieves >99% target attainment in both ICU and general populations, micafungin and anidulafungin show lower cumulative fraction of response rates, particularly for C. albicans 9.
Do not delay catheter removal—this intervention is independently associated with improved outcomes and must occur early in the treatment course 4, 5.