Fungal and Atypical Organisms

Fungal and Atypical Organisms is a topic covered in the Washington Manual of Medical Therapeutics.

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  • Clinical presentations are varied and not pathogen specific. Consider systemic mycoses in normal hosts with unexplained chronic pulmonary pathology, chronic meningitis, lytic bone lesions, chronic skin lesions, FUO, or cytopenias. In immunocompromised patients, besides the above presentations, the development of new pulmonary, cutaneous, funduscopic, or head and neck signs and symptoms should prompt consideration of fungal and other atypical pathogens.
  • Mycoses can often be identified by considering epidemiologic clues (many are geographically restricted), site of infection, inflammatory response, and microscopic fungal appearance. These infections can be complex and difficult to treat, and infectious disease consultation is recommended in all cases.
  • Antifungal agents have variable doses, depending on severity of infection and the patient’s renal and hepatic function. Lipid formulations of amphotericin B are preferred over the deoxycholate formulation due to its more favorable toxicity profile. Significant drug–drug interactions exist between azole antifungals and many other medications, including immunosuppressant drugs. Loading doses of azole antifungals may be recommended in certain circumstances. Because treatment may be prolonged (weeks to months), it is recommended to check therapeutic levels of several antifungals to minimize toxicity. Levels may be checked for flucytosine, itraconazole, posaconazole, and voriconazole but not for isavuconazole or fluconazole.
  • For details on treatment of fungal pathogens, Nocardia, and Actinomyces, see Table 14-13.
Table 14-13: Treatment of Fungal Infections, , and
Pathogen and TherapyAdditional Comments
Candida spp.
Mucosal
  • Thrush: Clotrimazole troche, nystatin suspension, or Fluc 100–200 mg qday × 7–14 d
  • Esophageal: Fluc 200 mg qday × 14–21 d
  • Vaginal: Topical azole × 3–7 d or Fluc 150 mg PO once
  • Frequent recurrence: Fluc 150 mg/wk × 6 mo
Invasive candidiasis
  • Empirical treatment: Echinocandin
  • Targeted: Based on species and susceptibilities
  • Average duration: 14 d
  • Prophylaxis: May be beneficial in select patients with solid organ transplant, chemotherapy-induced neutropenia, or stem cell transplants.
  • Complicated infection: Duration may be extended if metastatic foci present or continued neutropenia.
Cryptococcus neoformans
Nonmeningeal, local, or mild–moderate disease
  • Fluc 400 mg PO/IV qday × 6–12 mo
Meningeal, disseminated, or moderately severe–severe disease
  • Induction phase: Amb + 5-FC × 2 wk
  • Consolidation phase: Fluc 400 mg PO qday × 8 wk
  • Continuation phase: Fluc 200 mg qday × 6–12 mo
  • Perform LP to rule out meningitis.
  • HIV: Initiate ART 2–10 wk after starting Tx. Continue Fluc 200 mg PO qday for at least 12 mo and until CD4 count ≥100 for 6 mo.
  • Check baseline CSF opening pressure. If ≥25 cm of CSF, reduce by 50% (up to 30 mL). Perform daily serial LPs if pressure elevated (≥25 cm H2O).
Histoplasma capsulatum
Pulmonary
  • Acute, mild–moderate: Observation. May undergo Tx if symptoms >1 mo
  • Acute, moderately severe to severe: Amb for 1–2 wk or until clinically improved, then Itra for 12 wk
  • Chronic cavitary: Itra for 12–24 mo
Progressive disseminated histoplasmosis (PDH)
  • Mild–moderate: Itra for 12 mo
  • Moderately severe to severe: Amb for 1–2 wk or until clinically improved, then Itra for 12 mo
Mediastinal fibrosis
  • Antifungal treatment is not recommended
  • HIV: Itra 200 mg PO qday ppx in areas of high endemicity if CD4 count <150.
  • PDH: Check urine antigen levels during/after Tx to monitor for relapse.
  • TDM for itraconazole is recommended.
Blastomyces dermatitidis
Pulmonary or disseminated extrapulmonary
  • Mild to moderate: Itra for 6–12 mo
  • Moderately severe to severe: Amb for 1–2 wk or until clinically improved, then Itra for 6–12 mo
  • Immunosuppressed: Treat as severe disease for 12 mo
CNS: Amb for 4–6 wk then Fluc 800 mg PO qday for 12 mo
Suppression: Itra lifelong if continued immunosuppression
  • For CNS disease, Itra or Vori can be used instead of Fluc.
Coccidioides immitis
Pulmonary
  • Uncomplicated pneumonia, asymptomatic pulmonary nodule: May not need Tx. If Tx, Fluc 400 mg PO qday for 3–6 mo
  • Diffuse pneumonia: Amb for 1–2 wk or until clinically improved, then Fluc 400 mg PO qday for 12 mo
Disseminated/extrapulmonary
  • Nonmeningeal: Fluc 800–1200 mg IV/PO qday
  • Meningeal: Fluc 800–1200 mg IV/PO qday—if not improving, consider intrathecal Amb; followed by Fluc lifelong
  • Can follow serum CF titers during/after treatment. Rising titers suggest recurrence.
  • Consider surgery if pulmonary cavitary disease >2 yr or rupture.
  • HIV: Continue Tx until CD4 count ≥250.
  • After meningeal disease improves, lifelong Fluc.
  • Hydrocephalus may require shunt for decompression.
Sporothrix
Lymphocutaneous/cutaneous: Itra × 3–6 mo
Severe systemic
  • Pulmonary/disseminated/osteoarticular: Amb for 1–2 wk or until clinically improved, then Itra for 12 mo
  • Meningeal: Amb for 4–6 wk then Itra for 12 mo
  • If no initial response, can use higher doses of Itra or add topical saturated solution of potassium iodide.
Aspergillus
Pulmonary aspergilloma: Surgical resection or arterial embolization in cases of severe hemoptysis
Invasive pulmonary aspergillosis: Vori for at least 6–12 wk until lesions and immunosuppression resolve
Invasive sinonasal aspergillosis: Amb or Vori. Surgical debridement is adjunctive and often required for cure
Allergic bronchopulmonary aspergillosis: Itra or intermittent steroids may decrease exacerbations
Prophylaxis: Posa in high-risk patients may be considered
  • Amb to cover mucormycosis as initial therapy for sinus disease pending confirmation of diagnosis.
  • If immunosuppression recurs, may need to restart ppx or Tx.
Mucormycosis
Cutaneous, rhinocerebral: Aggressive surgical resection and debridement with clean margins followed + Amb at upper dose range until improvement
Pulmonary: Amb
  • Mortality is very high in immunosuppressed patients with disseminated disease.
  • Posa and Isa are alternative Tx, after initial induction therapy with Amb.
Nocardia
Cutaneous: TMP–SMX
Severe infection (including CNS): Induction regimen typically includes two or three drugs including TMP–
SMX, imipenem or linezolid for 4–6 wk with stepdown to oral therapy for 6–12 mo
Suppression/prophylaxis: TMP–SMX
  • TMP–SMX is drug of choice but typically combined with other agents in disseminated disease.
  • Use susceptibility results to guide treatment.
Actinomyces
Penicillin G 18–24 million units IV per day × 4–6 wk then penicillin VK 1 g PO tid × 6–12 mo
  • Surgery or drainage may be helpful in some cases.
  • Clindamycin or doxycycline can be used if penicillin allergy.

5-FC, flucytosine; Amb, amphotericin B; ART, antiretroviral therapy; CF, complement fixation; CNS, central nervous system; CSF, cerebrospinal fluid; Fluc, fluconazole; Isa, isavuconazole; Itra, itraconazole; LP, lumbar puncture; Posa, posaconazole; ppx, prophylaxis; TDM, therapeutic drug monitoring; TMP–SMX, trimethoprim–sulfamethoxazole; Tx, treatment; Vori, voriconazole.

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  • Clinical presentations are varied and not pathogen specific. Consider systemic mycoses in normal hosts with unexplained chronic pulmonary pathology, chronic meningitis, lytic bone lesions, chronic skin lesions, FUO, or cytopenias. In immunocompromised patients, besides the above presentations, the development of new pulmonary, cutaneous, funduscopic, or head and neck signs and symptoms should prompt consideration of fungal and other atypical pathogens.
  • Mycoses can often be identified by considering epidemiologic clues (many are geographically restricted), site of infection, inflammatory response, and microscopic fungal appearance. These infections can be complex and difficult to treat, and infectious disease consultation is recommended in all cases.
  • Antifungal agents have variable doses, depending on severity of infection and the patient’s renal and hepatic function. Lipid formulations of amphotericin B are preferred over the deoxycholate formulation due to its more favorable toxicity profile. Significant drug–drug interactions exist between azole antifungals and many other medications, including immunosuppressant drugs. Loading doses of azole antifungals may be recommended in certain circumstances. Because treatment may be prolonged (weeks to months), it is recommended to check therapeutic levels of several antifungals to minimize toxicity. Levels may be checked for flucytosine, itraconazole, posaconazole, and voriconazole but not for isavuconazole or fluconazole.
  • For details on treatment of fungal pathogens, Nocardia, and Actinomyces, see Table 14-13.
Table 14-13: Treatment of Fungal Infections, , and
Pathogen and TherapyAdditional Comments
Candida spp.
Mucosal
  • Thrush: Clotrimazole troche, nystatin suspension, or Fluc 100–200 mg qday × 7–14 d
  • Esophageal: Fluc 200 mg qday × 14–21 d
  • Vaginal: Topical azole × 3–7 d or Fluc 150 mg PO once
  • Frequent recurrence: Fluc 150 mg/wk × 6 mo
Invasive candidiasis
  • Empirical treatment: Echinocandin
  • Targeted: Based on species and susceptibilities
  • Average duration: 14 d
  • Prophylaxis: May be beneficial in select patients with solid organ transplant, chemotherapy-induced neutropenia, or stem cell transplants.
  • Complicated infection: Duration may be extended if metastatic foci present or continued neutropenia.
Cryptococcus neoformans
Nonmeningeal, local, or mild–moderate disease
  • Fluc 400 mg PO/IV qday × 6–12 mo
Meningeal, disseminated, or moderately severe–severe disease
  • Induction phase: Amb + 5-FC × 2 wk
  • Consolidation phase: Fluc 400 mg PO qday × 8 wk
  • Continuation phase: Fluc 200 mg qday × 6–12 mo
  • Perform LP to rule out meningitis.
  • HIV: Initiate ART 2–10 wk after starting Tx. Continue Fluc 200 mg PO qday for at least 12 mo and until CD4 count ≥100 for 6 mo.
  • Check baseline CSF opening pressure. If ≥25 cm of CSF, reduce by 50% (up to 30 mL). Perform daily serial LPs if pressure elevated (≥25 cm H2O).
Histoplasma capsulatum
Pulmonary
  • Acute, mild–moderate: Observation. May undergo Tx if symptoms >1 mo
  • Acute, moderately severe to severe: Amb for 1–2 wk or until clinically improved, then Itra for 12 wk
  • Chronic cavitary: Itra for 12–24 mo
Progressive disseminated histoplasmosis (PDH)
  • Mild–moderate: Itra for 12 mo
  • Moderately severe to severe: Amb for 1–2 wk or until clinically improved, then Itra for 12 mo
Mediastinal fibrosis
  • Antifungal treatment is not recommended
  • HIV: Itra 200 mg PO qday ppx in areas of high endemicity if CD4 count <150.
  • PDH: Check urine antigen levels during/after Tx to monitor for relapse.
  • TDM for itraconazole is recommended.
Blastomyces dermatitidis
Pulmonary or disseminated extrapulmonary
  • Mild to moderate: Itra for 6–12 mo
  • Moderately severe to severe: Amb for 1–2 wk or until clinically improved, then Itra for 6–12 mo
  • Immunosuppressed: Treat as severe disease for 12 mo
CNS: Amb for 4–6 wk then Fluc 800 mg PO qday for 12 mo
Suppression: Itra lifelong if continued immunosuppression
  • For CNS disease, Itra or Vori can be used instead of Fluc.
Coccidioides immitis
Pulmonary
  • Uncomplicated pneumonia, asymptomatic pulmonary nodule: May not need Tx. If Tx, Fluc 400 mg PO qday for 3–6 mo
  • Diffuse pneumonia: Amb for 1–2 wk or until clinically improved, then Fluc 400 mg PO qday for 12 mo
Disseminated/extrapulmonary
  • Nonmeningeal: Fluc 800–1200 mg IV/PO qday
  • Meningeal: Fluc 800–1200 mg IV/PO qday—if not improving, consider intrathecal Amb; followed by Fluc lifelong
  • Can follow serum CF titers during/after treatment. Rising titers suggest recurrence.
  • Consider surgery if pulmonary cavitary disease >2 yr or rupture.
  • HIV: Continue Tx until CD4 count ≥250.
  • After meningeal disease improves, lifelong Fluc.
  • Hydrocephalus may require shunt for decompression.
Sporothrix
Lymphocutaneous/cutaneous: Itra × 3–6 mo
Severe systemic
  • Pulmonary/disseminated/osteoarticular: Amb for 1–2 wk or until clinically improved, then Itra for 12 mo
  • Meningeal: Amb for 4–6 wk then Itra for 12 mo
  • If no initial response, can use higher doses of Itra or add topical saturated solution of potassium iodide.
Aspergillus
Pulmonary aspergilloma: Surgical resection or arterial embolization in cases of severe hemoptysis
Invasive pulmonary aspergillosis: Vori for at least 6–12 wk until lesions and immunosuppression resolve
Invasive sinonasal aspergillosis: Amb or Vori. Surgical debridement is adjunctive and often required for cure
Allergic bronchopulmonary aspergillosis: Itra or intermittent steroids may decrease exacerbations
Prophylaxis: Posa in high-risk patients may be considered
  • Amb to cover mucormycosis as initial therapy for sinus disease pending confirmation of diagnosis.
  • If immunosuppression recurs, may need to restart ppx or Tx.
Mucormycosis
Cutaneous, rhinocerebral: Aggressive surgical resection and debridement with clean margins followed + Amb at upper dose range until improvement
Pulmonary: Amb
  • Mortality is very high in immunosuppressed patients with disseminated disease.
  • Posa and Isa are alternative Tx, after initial induction therapy with Amb.
Nocardia
Cutaneous: TMP–SMX
Severe infection (including CNS): Induction regimen typically includes two or three drugs including TMP–
SMX, imipenem or linezolid for 4–6 wk with stepdown to oral therapy for 6–12 mo
Suppression/prophylaxis: TMP–SMX
  • TMP–SMX is drug of choice but typically combined with other agents in disseminated disease.
  • Use susceptibility results to guide treatment.
Actinomyces
Penicillin G 18–24 million units IV per day × 4–6 wk then penicillin VK 1 g PO tid × 6–12 mo
  • Surgery or drainage may be helpful in some cases.
  • Clindamycin or doxycycline can be used if penicillin allergy.

5-FC, flucytosine; Amb, amphotericin B; ART, antiretroviral therapy; CF, complement fixation; CNS, central nervous system; CSF, cerebrospinal fluid; Fluc, fluconazole; Isa, isavuconazole; Itra, itraconazole; LP, lumbar puncture; Posa, posaconazole; ppx, prophylaxis; TDM, therapeutic drug monitoring; TMP–SMX, trimethoprim–sulfamethoxazole; Tx, treatment; Vori, voriconazole.

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