What is the recommended management for a suspected invasive Penicillium infection in an immunocompromised patient (e.g., HIV/AIDS, organ transplant, prolonged neutropenia), including first‑line therapy, options for severe disease, alternatives for a penicillin‑allergic patient, and how should mold exposure be addressed in a non‑immunocompromised individual?

Management of Suspected Invasive Penicillium Infection in Immunocompromised Patients

Initiate systemic antifungal therapy immediately with liposomal amphotericin B 5 mg/kg IV daily as first-line treatment for suspected invasive Penicillium infection in immunocompromised patients, combined with urgent surgical debridement when feasible, and do not dismiss Penicillium isolates as contaminants in this population. 1, 2, 3

Risk Stratification and Clinical Context

• Penicillium species are emerging opportunistic pathogens that cause life-threatening infections primarily in patients with hematologic malignancies, prolonged neutropenia (>10 days), solid organ or hematopoietic stem cell transplantation, HIV/AIDS with CD4 <200 cells/µL, and those receiving high-dose corticosteroids (≥20 mg prednisone daily for ≥2 weeks). 4, 2, 3, 5

• The most common sites of invasive Penicillium infection are pulmonary (presenting with fever, cough, and infiltrates on imaging), followed by disseminated disease involving skin, blood, and other organs; angioinvasive cutaneous lesions have been documented in acute myeloid leukemia patients. 2, 3, 6, 5

• Critical pitfall: Penicillium isolates from respiratory specimens, blood, or normally sterile sites in immunocompromised patients should never be dismissed as laboratory contaminants without thorough clinical correlation, as this genus contains pathogenic species that cause fatal infections. 2, 3, 5, 7

Diagnostic Workup

• Obtain tissue biopsy from affected sites (lung, skin, or other organs) for histopathology demonstrating septate, dichotomously branching hyphae with tissue invasion, plus fungal culture for species identification by molecular sequencing (D1-D2 and ITS regions). 2, 3, 6

• Perform bronchoscopy with bronchoalveolar lavage (BAL) when pulmonary infection is suspected and sputum is unavailable or nondiagnostic; BAL fluid should be sent for fungal stains (calcofluor white, GMS), culture, and galactomannan testing. 1, 4, 2

• Send blood cultures from two separate sites before initiating antifungal therapy, as disseminated Penicillium infection with fungemia occurs in severely immunocompromised hosts including transplant recipients. 4, 6

• Order high-resolution chest CT rather than plain radiography as the initial imaging modality, because CT reliably identifies nodules, infiltrates, cavitation, and halo signs that narrow the differential diagnosis in invasive mold infections. 1, 4

First-Line Antifungal Therapy

• Administer liposomal amphotericin B 5 mg/kg IV daily as the primary treatment for proven or probable invasive Penicillium infection; higher doses up to 10 mg/kg/day may be considered in severe cases or when surgical intervention is not feasible. 1

• Amphotericin B deoxycholate 1.0–1.5 mg/kg IV daily is an alternative when liposomal formulation is unavailable, though it carries higher nephrotoxicity risk. 1

• Continue systemic antifungal therapy for a minimum of 6–12 weeks depending on clinical response, resolution of neutropenia, reduction in immunosuppression, and radiographic improvement; some cases require prolonged therapy beyond 12 weeks. 1

Surgical Management

• Perform surgical debridement or excision of infected tissue as soon as the patient is medically stable, because systemic antifungals have poor penetration into necrotic tissue and fungal masses; surgical intervention combined with medical therapy improves outcomes in localized invasive mold infections. 1

• Surgical debridement is mandatory for angioinvasive cutaneous lesions, necrotizing soft tissue infections, and localized pulmonary lesions when technically feasible and the patient can tolerate the procedure. 1, 3

• Avoid surgical intervention in patients with disseminated disease or uncontrolled neutropenia, as debridement may increase mortality in profoundly neutropenic patients; prioritize resolution of neutropenia and medical management in these cases. 1

Alternative and Adjunctive Therapies

• Voriconazole 6 mg/kg IV every 12 hours for two doses on day 1 (loading), then 4 mg/kg IV every 12 hours may be used as alternative therapy, though in vitro susceptibility data show variable MIC values for Penicillium species; therapeutic drug monitoring is essential to maintain trough levels of 1–5 µg/mL. 1, 2

• Posaconazole (oral suspension 200 mg four times daily initially, then 400 mg twice daily after stabilization; or delayed-release tablets/IV formulation 300 mg twice daily on day 1, then 300 mg daily) can be considered as salvage therapy for refractory cases or as step-down therapy after clinical stabilization. 1

• Itraconazole 200 mg orally twice daily is an option for step-down therapy in stable patients, though oral bioavailability is variable and therapeutic drug monitoring is required to ensure adequate serum levels. 1

• Echinocandins (caspofungin, micafungin, anidulafungin) have no activity against Penicillium and other filamentous molds and should not be used as monotherapy; they are reserved for Candida and Aspergillus infections only. 1

Management in Penicillin-Allergic Patients

• Penicillin allergy is irrelevant to antifungal selection for invasive Penicillium infection, because the genus name refers to the fungus, not the antibiotic; all recommended antifungal agents (amphotericin B formulations, azoles) can be safely administered regardless of penicillin allergy status. 1, 8

• If concurrent bacterial infection requires antibiotics in a penicillin-allergic patient, use fluoroquinolones (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) or vancomycin 15 mg/kg IV every 8–12 hours for gram-positive coverage, plus an antipseudomonal agent if indicated. 1, 4, 8

Adjunctive Host Factor Optimization

• Reduce or discontinue corticosteroid therapy as rapidly as clinically feasible, because resolution of immunosuppression is the single most important factor affecting outcome in invasive mold infections; taper prednisone to <20 mg daily if possible. 1, 4

• Administer granulocyte colony-stimulating factor (G-CSF) to accelerate neutrophil recovery in patients with chemotherapy-induced neutropenia, as resolution of neutropenia dramatically improves survival in invasive fungal infections. 1

• Optimize HIV antiretroviral therapy to achieve CD4 >200 cells/µL in HIV-infected patients, and continue HAART throughout antifungal treatment. 1, 4

Monitoring and Reassessment

• Obtain follow-up chest CT and inflammatory markers (CRP, ESR) at 1–2 weeks after initiating therapy to assess radiographic response; lack of improvement or progression at 48–72 hours mandates repeat imaging and consideration of alternative diagnoses or resistant organisms. 1, 4

• Perform antifungal susceptibility testing on all Penicillium isolates when available, because some strains exhibit elevated MIC values to multiple antifungal drugs including amphotericin B and azoles; adjust therapy based on susceptibility results and clinical response. 1, 2

• Monitor serum creatinine, electrolytes (potassium, magnesium), and liver function tests twice weekly during amphotericin B therapy to detect nephrotoxicity and hepatotoxicity early. 1

Management of Mold Exposure in Non-Immunocompromised Individuals

• Non-immunocompromised individuals exposed to Penicillium molds in the environment (e.g., water-damaged buildings, contaminated food) do not require antifungal prophylaxis or treatment, as invasive infection occurs exclusively in immunocompromised hosts. 1, 5

• Advise environmental remediation by removing water-damaged materials, improving ventilation, and using HEPA filtration to reduce airborne spore counts in homes or workplaces with visible mold growth. 1

• Recommend that immunocompetent individuals with respiratory symptoms (cough, wheezing) from mold exposure seek evaluation for allergic bronchopulmonary disease or hypersensitivity pneumonitis, which are managed with corticosteroids and environmental control rather than antifungal therapy. 1