What is the recommended treatment for a patient with myeloperoxidase (MPO) deficiency diagnosed with a Candida glabrata infection?

Treatment of Candida glabrata Infection in MPO-Deficient Patient

An echinocandin (caspofungin, micafungin, or anidulafungin) is the preferred first-line therapy for C. glabrata infection, with particular importance in this MPO-deficient patient who has compromised neutrophil extracellular trap (NET) formation and impaired fungicidal activity. 1, 2

Critical Context: MPO Deficiency and Candida Susceptibility

• MPO-deficient patients have increased susceptibility to Candida infections, particularly C. glabrata, due to impaired neutrophil extracellular trap (NET) formation 2
• Complete MPO deficiency prevents NET formation entirely, while partial deficiency only delays it 2
• NET-dependent inhibition of Candida growth is significantly compromised in MPO-deficient neutrophils, making these patients particularly vulnerable to invasive candidiasis 2

First-Line Treatment Recommendations

Echinocandin therapy is strongly preferred for C. glabrata infections: 1

• Caspofungin: Loading dose 70 mg, then 50 mg daily 1
• Micafungin: 100 mg daily 1
• Anidulafungin: Loading dose 200 mg, then 100 mg daily 1

The IDSA guidelines specifically state that for C. glabrata infections, an echinocandin is preferred over fluconazole or other azoles 1.

Important Caveat: Echinocandin Limitations in Neutropenic/Immunocompromised Hosts

A critical consideration exists for MPO-deficient patients: Research demonstrates that standard echinocandin doses may only achieve fungistatic (not fungicidal) effects in neutropenic or immunocompromised hosts 3. The average human drug exposures following currently licensed echinocandin regimens were predicted to result in fungistatic rather than fungicidal activity in neutropenic patients 3.

Given the MPO deficiency (which functionally mimics aspects of neutrophil dysfunction), consider:

• Higher echinocandin doses may be required to achieve fungicidal effects 3
• Combination therapy with liposomal amphotericin B may be necessary for complete clearance 4

Alternative and Combination Therapy

Lipid formulation amphotericin B (3-5 mg/kg daily) is recommended if: 1

• Intolerance to echinocandins develops
• Limited availability of echinocandins
• Resistance to echinocandins is documented

Combination therapy with liposomal amphotericin B plus an echinocandin: 4

• Complete clearance of C. glabrata infection was achieved only when liposomal amphotericin B was given concomitantly with caspofungin or micafungin in immunosuppressed animal models 4
• This combination markedly improved therapeutic outcomes compared to monotherapy 4
• This approach should be strongly considered in MPO-deficient patients given their impaired fungicidal capacity

Azole Therapy: Use With Extreme Caution

Fluconazole or voriconazole should NOT be used without confirmed susceptibility: 1

• Transition to fluconazole (800 mg daily) or voriconazole (200-300 mg twice daily) should only occur if isolates are documented as susceptible 1
• C. glabrata has inherently reduced susceptibility to azoles, and resistance rates are increasing 5
• Step-down to azole therapy requires clinical stability, negative repeat blood cultures, and confirmed susceptibility 1

Monitoring and Duration

Essential monitoring parameters: 1

• Follow-up blood cultures should be performed daily or every other day to establish clearance 1
• Dilated ophthalmological examination within the first week after diagnosis 1
• Continue therapy for 2 weeks after documented clearance from bloodstream and resolution of symptoms 1

Source Control

Central venous catheter removal is strongly recommended: 1

• Remove CVCs as early as possible when the source is presumed to be catheter-related 1
• This decision should be made urgently given the patient's immunocompromised state

Resistance Surveillance

Monitor for echinocandin resistance development: 6, 5

• C. glabrata can develop reduced echinocandin sensitivity during treatment 6
• Resistance to azoles is common and increasing; echinocandin resistance is also emerging 5
• If clinical failure occurs despite appropriate therapy, repeat susceptibility testing is essential

Practical Algorithm for This Patient

1. Initiate echinocandin immediately (any of the three options at standard loading/maintenance doses) 1
2. Strongly consider adding liposomal amphotericin B (3-5 mg/kg daily) given MPO deficiency and need for fungicidal activity 4
3. Remove any central venous catheters if present 1
4. Obtain daily blood cultures until clearance documented 1
5. Ophthalmology consultation within first week 1
6. Continue combination therapy until blood cultures negative for at least 2 weeks and clinical improvement achieved 1
7. Do NOT step down to azole therapy unless susceptibility confirmed and patient clinically stable with negative cultures 1