What is the recommended treatment for an immunocompromised patient diagnosed with Acremonium citrinum infection?

Treatment of Acremonium citrinum Infection in Immunocompromised Patients

For an immunocompromised patient with Acremonium citrinum infection, initiate voriconazole immediately as first-line therapy, combined with aggressive surgical debridement of infected tissue and removal of any indwelling catheters. 1, 2

Primary Antifungal Therapy

Voriconazole is the preferred first-line agent based on ESCMID/ECMM joint guidelines for hyalohyphomycosis, which includes Acremonium species. 1, 2 The recommendation stems from superior clinical outcomes observed in case reports and the drug's favorable CNS penetration for potential disseminated disease. 1, 3, 4

Dosing Strategy

• Loading dose: 6 mg/kg IV every 12 hours for 2 doses 1
• Maintenance: 4 mg/kg IV every 12 hours, then transition to oral 200 mg twice daily when clinically stable 1, 2
• Therapeutic drug monitoring is mandatory to maintain trough levels between 1-5.5 mcg/mL, as voriconazole exhibits significant pharmacokinetic variability 2

Alternative Antifungal Options

If voriconazole cannot be used due to drug interactions, hepatotoxicity, or treatment failure:

• Amphotericin B lipid formulations (liposomal amphotericin B 3-5 mg/kg IV daily) are recommended as second-line therapy 1, 2
• Posaconazole (300 mg twice daily on day 1, then 300 mg daily) serves as salvage therapy 1, 2
• Amphotericin B deoxycholate (1-1.5 mg/kg daily) is less preferred due to nephrotoxicity but remains an option 1

Important caveat: Recent in vitro data demonstrate high MICs for most antifungals against Acremonium species except terbinafine, though clinical correlation remains uncertain. 1, 5 Do not delay treatment while awaiting susceptibility results. 2

Mandatory Surgical Intervention

Surgical debridement is not optional—it is a critical component of successful management. 1, 2

Absolute Indications for Surgery:

• Progressive cavitary lung lesions despite antifungal therapy 1, 2
• Hemoptysis from solitary cavitary lesions 1, 2
• Infiltration into pericardium, great vessels, bone, or thoracic soft tissue 1, 2
• Osteomyelitis or septic arthritis 1
• Before initiating cytotoxic chemotherapy to prevent dissemination during subsequent immunosuppression 1, 2

Remove all indwelling catheters immediately in catheter-related infections, as catheter retention is associated with treatment failure. 1, 4

Immune Reconstitution Strategy

Reversal of immunosuppression is the single most important determinant of survival and must be attempted whenever feasible. 1, 2

• Reduce corticosteroid doses if possible without risking graft rejection or GVHD 2, 6
• Consider granulocyte colony-stimulating factor (G-CSF) to shorten neutropenia duration, though evidence is limited to case reports 1
• Delay cytotoxic chemotherapy until infection is controlled if oncologically safe 1

Treatment Duration and Monitoring

• Minimum duration: 6-12 weeks depending on extent of disease, immune status, and clinical response 2
• Obtain serial CT imaging every 2-4 weeks to assess treatment response 2
• Continue therapy until radiographic resolution and immune reconstitution 2
• Secondary prophylaxis with voriconazole or posaconazole is required if ongoing immunosuppression continues, as relapse risk is substantial 1, 2

Critical Pitfalls to Avoid

Do not misidentify the organism: Acremonium species grow slowly and require at least 2 weeks of culture incubation. 1 Ensure proper species-level identification, as some Acremonium species have been reclassified (e.g., A. kiliense is now Sarocladium kiliense). 1, 2

Do not rely on blood cultures alone: Blood cultures become positive only in advanced disseminated disease. 1 Diagnosis requires isolation from infected tissue sites. 1

Do not use fluconazole or itraconazole: These agents demonstrate poor in vitro activity against Acremonium species and are associated with treatment failures. 1, 5

Do not ignore occult sources: Onychomycosis has been documented as a source of subsequent disseminated infection in immunocompromised patients. 1 Evaluate for and treat any superficial Acremonium infections before immunosuppressive therapy. 1

Management of Treatment Failure

If the patient fails to respond after 2 weeks of appropriate therapy:

1. Verify antifungal drug levels via therapeutic drug monitoring 2
2. Review susceptibility testing results if available 1, 2
3. Assess for drug interactions that may reduce voriconazole levels (rifampin, phenytoin, carbamazepine) 2
4. Switch to amphotericin B lipid formulation or consider combination therapy (voriconazole plus amphotericin B), though combination data are limited to case reports 1, 7
5. Re-evaluate for undrained collections requiring additional surgical intervention 2