Can Candida glabrata colonize in a patient with myeloperoxidase (MPO) deficiency?

Can Candida glabrata Colonize in MPO-Deficient Patients?

Yes, Candida glabrata can absolutely colonize and cause invasive infection in myeloperoxidase (MPO)-deficient patients, with MPO deficiency representing a significant risk factor for progression from colonization to life-threatening disseminated candidiasis.

Understanding the Relationship Between MPO Deficiency and Candida

MPO deficiency creates a critical vulnerability in the host's antifungal defense mechanisms. A fatal case report documented a 27-year-old woman with MPO deficiency who developed lethal Candida sepsis with invasive esophagitis and disseminated pulmonary candidiasis, demonstrating that MPO deficiency directly supports invasive Candida infection 1. This case underscores that MPO deficiency doesn't merely permit colonization—it facilitates rapid progression to invasive disease.

Colonization Patterns and Risk

General Colonization Dynamics

• Candida colonization precedes invasive infection in the vast majority of cases, with 86% of patients who develop invasive candidiasis being colonized prior to infection 2
• The gastrointestinal tract and skin serve as primary colonization sites, with translocation across mucosal barriers occurring once critical colonization levels are reached 3
• C. glabrata specifically has emerged as an increasingly common colonizing species, particularly in healthcare settings 3

C. glabrata-Specific Considerations

• C. glabrata colonization rates have remained stable even with widespread fluconazole prophylaxis, with no significant increase observed after 3 years of routine prophylaxis 4
• C. glabrata now accounts for a substantial proportion of non-albicans Candida colonization, with one ICU study identifying 24 patients colonized with C. glabrata compared to only one patient 16 years earlier 5
• C. glabrata demonstrates reduced susceptibility to fluconazole, with cross-resistance to other triazoles noted 3

Clinical Implications for MPO-Deficient Patients

Heightened Surveillance Requirements

MPO-deficient patients require aggressive monitoring for Candida colonization given their impaired cellular immunity against fungal pathogens 3. Specific surveillance should include:

• Throat, perineum, and urine sampling within 72 hours of ICU admission and twice weekly thereafter, as this captures 84% of subsequent invasive candidiasis cases 2
• Colonization at any single site is predictive of invasive disease, with urine colonization carrying the highest relative risk (RR=2.25) 2
• Colonization at ≥2 sites increases risk substantially (RR=2.25), while heavy colonization at ≥1 site further elevates risk (RR=3.7) 2

Distinguishing Colonization from Infection

In MPO-deficient patients, the threshold for treating colonization as presumptive infection should be lower:

• Growth from sterile sites (blood, CSF) always indicates infection requiring immediate treatment 6
• Candiduria in non-catheterized patients strongly suggests invasive infection, whereas in catheterized patients it may represent colonization 6
• Clinical symptoms (fever, organ dysfunction, leukocytosis) combined with colonization data should trigger empirical therapy in MPO-deficient patients 3

Treatment Approach for MPO-Deficient Patients

Empirical Therapy Threshold

Given the documented lethality of Candida infections in MPO-deficient patients 1, empirical antifungal therapy should be initiated at a lower threshold than in immunocompetent hosts:

• An echinocandin (caspofungin 70-mg loading dose then 50 mg daily, anidulafungin 200-mg loading dose then 100 mg daily, or micafungin 100 mg daily) is preferred for patients with suspected C. glabrata colonization or recent azole exposure 3
• Fluconazole (800-mg loading dose, then 400 mg daily) remains acceptable for fluconazole-susceptible organisms, but echinocandins are strongly preferred in MPO deficiency given the severity of potential infections 3

Species-Specific Considerations

• For confirmed C. glabrata with fluconazole resistance, amphotericin B deoxycholate (0.3–0.6 mg/kg daily for 1–7 days) or oral flucytosine (25 mg/kg 4 times daily for 7–10 days) is recommended 3
• Antifungal susceptibility testing should be performed on all isolates from MPO-deficient patients to guide definitive therapy 3

Critical Pitfalls to Avoid

• Never dismiss Candida colonization as benign in MPO-deficient patients—the case report of fatal disseminated candidiasis demonstrates the rapid progression possible in this population 1
• Do not rely solely on blood cultures, as they are positive in only 50% of invasive candidiasis cases 3
• Avoid delaying antifungal therapy while awaiting culture confirmation in MPO-deficient patients with clinical sepsis and documented colonization, as delays are associated with increased mortality 3, 7
• Do not assume fluconazole adequacy for C. glabrata without susceptibility testing, as 5% of isolates demonstrate resistance 5

Summary Algorithm for MPO-Deficient Patients

1. Implement aggressive surveillance: throat, perineum, and urine cultures within 72 hours of admission and twice weekly 2
2. If colonization detected at ≥2 sites OR heavy colonization at ≥1 site: consider empirical echinocandin therapy, especially if clinical signs of infection present 3, 2
3. If fever/sepsis develops with any Candida colonization: initiate empirical echinocandin immediately without awaiting blood culture results 3
4. Obtain species identification and susceptibility testing on all isolates to guide definitive therapy 3
5. Remove all intravascular catheters when feasible, as this is critical for source control 3