Fungal Infections by Organ System
Fungi reach organs by inhalation, inoculation through skin and mucosa, ingestion, contiguous spread, and the bloodstream. The organ involved narrows the differential diagnosis by pointing to a limited set of pathogens, the specimens to collect, the drugs that reach the site, and the need for surgery. Host status then decides which of these pathogens is likely. This article organises fungal disease by site, with the pathogens, the presentation, the diagnostic approach, and the principles of treatment.
| Syndrome | Main pathogens | Features | Diagnosis | Treatment |
|---|---|---|---|---|
| Meningitis or meningoencephalitis | Cryptococcus neoformans, Cryptococcus gattii; Coccidioides; Histoplasma; Candida; Blastomyces | Subacute headache, fever, confusion, raised intracranial pressure, cranial nerve palsies, and low grade course | Cerebrospinal fluid opening pressure, cell count (lymphocytes), glucose (low), protein (high), cryptococcal antigen, fungal culture, India ink, Histoplasma and Coccidioides antigen and antibody, and imaging | Cryptococcosis: liposomal amphotericin B 3 to 4 mg per kg daily with flucytosine 100 mg per kg per day in 4 doses, for 1 to 2 weeks, then fluconazole 800 mg daily for 8 weeks, then 200 mg daily; coccidioidal meningitis: fluconazole 800 to 1200 mg daily for life; histoplasmosis and blastomycosis: liposomal amphotericin B 5 mg per kg daily for 4 to 6 weeks, then an azole for at least 12 months |
| Brain abscess and cerebritis | Aspergillus (including Aspergillus fumigatus), Mucorales (rhino-orbital-cerebral extension), Scedosporium (near drowning), dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis, Rhinocladiella mackenziei), Candida, Cryptococcus gattii (cryptococcoma) | Fever, focal deficits, seizures, and altered consciousness; ring enhancing lesions, infarcts, and vasculitis | Magnetic resonance imaging, tissue biopsy or aspiration, galactomannan in cerebrospinal fluid, and polymerase chain reaction | Surgery (drainage or resection) with voriconazole 6 mg per kg every 12 hours for 2 doses then 4 mg per kg every 12 hours for aspergillosis, liposomal amphotericin B 5 to 10 mg per kg daily for Mucorales, voriconazole for Scedosporium, and voriconazole with other agents for dematiaceous moulds |
| Spinal and epidural infection | Aspergillus, Candida, Coccidioides, Blastomyces | Back pain, neurological deficit; contiguous vertebral disease | Magnetic resonance imaging and biopsy | Antifungal therapy with surgical decompression |
| Outbreak related infection | Exserohilum rostratum (contaminated methylprednisolone injections in 2012 caused meningitis and spinal infection) | Epidural and paraspinal infection | Culture and histology | Voriconazole, with or without liposomal amphotericin B |
| Others | Neonatal Candida meningoencephalitis; fungal shunt infection | Intraventricular device infection | Culture of cerebrospinal fluid | Amphotericin B with flucytosine, and device removal |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Fungal keratitis | Fusarium, Aspergillus, Candida, Curvularia, Scedosporium | Corneal ulcer after trauma with plant matter or contact lens wear; feathery margins, satellite lesions, and hypopyon; natamycin 5 percent hourly, with topical voriconazole 1 percent, and surgery for progression |
| Endophthalmitis, endogenous | Candida, Aspergillus, Cryptococcus | Chorioretinitis and vitritis from bloodstream spread; fluconazole or voriconazole systemic therapy, with intravitreal injection (voriconazole 100 micrograms per 0.1 mL or amphotericin B 5 to 10 micrograms per 0.1 mL) and vitrectomy for vitreous involvement |
| Endophthalmitis, exogenous | Candida, Aspergillus, Purpureocillium, Fusarium | After intraocular surgery or trauma; intravitreal and systemic antifungal therapy with vitrectomy |
| Orbital disease | Mucorales, Aspergillus | Proptosis, ophthalmoplegia, and visual loss; surgery and systemic therapy |
| Chorioretinitis (ocular histoplasmosis syndrome) | Histoplasma (immune mediated) | Peripheral atrophic scars, with choroidal neovascularisation treated with anti vascular endothelial growth factor agents |
| Ocular findings in cryptococcal meningitis | Cryptococcus | Papilloedema, optic nerve damage, and visual loss from raised pressure |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Otomycosis | Aspergillus niger, Aspergillus fumigatus, Candida | Itching, fullness, and debris in the canal with black or white spores; cleaning and topical clotrimazole or acidifying drops |
| Malignant (necrotising) otitis externa | Mainly Pseudomonas aeruginosa, with Aspergillus in some | Pain and cranial nerve palsy in diabetic patients; voriconazole for fungal cases |
| Fungal sinusitis, allergic | Aspergillus, dematiaceous moulds (Bipolaris, Curvularia) | Nasal polyps, eosinophilic mucin, and type I hypersensitivity; surgery with corticosteroids, and itraconazole in selected cases |
| Fungus ball (mycetoma) | Aspergillus fumigatus | A maxillary or sphenoid ball in the immunocompetent; surgical removal alone is curative |
| Chronic invasive fungal sinusitis | Aspergillus flavus | Slow progression in the semi-immunocompromised, with orbital apex syndrome; surgery with voriconazole for months |
| Acute invasive fungal sinusitis | Mucorales, Aspergillus, Fusarium | Necrosis of the turbinate, palate, or face in the immunocompromised; emergency debridement and liposomal amphotericin B |
| Laryngeal and pharyngeal disease | Candida, Histoplasma, Blastomyces, Paracoccidioides | Hoarseness, odynophagia; mimic carcinoma; biopsy and azole therapy |
| Oropharyngeal candidiasis | Candida albicans | White plaques, angular cheilitis, and denture stomatitis; nystatin, clotrimazole, miconazole buccal tablets, and fluconazole 100 to 200 mg daily for 7 to 14 days |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Invasive pulmonary aspergillosis | Aspergillus fumigatus and other species | Neutropenia, transplant, corticosteroids, influenza, and COVID-19; nodules, halo sign, cavities; voriconazole, isavuconazole, or liposomal amphotericin B |
| Chronic pulmonary aspergillosis | Aspergillus fumigatus | Chronic cough, haemoptysis, and cavities after tuberculosis; itraconazole or voriconazole for at least 6 months, with surgery or embolisation |
| Allergic bronchopulmonary aspergillosis | Aspergillus fumigatus | Asthma and cystic fibrosis; raised IgE; prednisolone and itraconazole |
| Mucormycosis | Mucorales | Reverse halo sign, haemoptysis; liposomal amphotericin B and surgery |
| Pneumocystis pneumonia | Pneumocystis jirovecii | Dry cough and hypoxaemia; trimethoprim sulfamethoxazole |
| Cryptococcosis | Cryptococcus | Nodules and pneumonia in the immunocompetent, and diffuse disease with meningitis in the immunocompromised; fluconazole, or amphotericin B for severe disease |
| Endemic mycoses | Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, Talaromyces, Emergomyces | Pneumonia, cavities, nodules, and mediastinal disease; antigen and serology; azoles and amphotericin B |
| Candida in the airway | Candida | Usually colonisation; treated only with tissue invasion, which is rare |
| Fungal colonisation in cystic fibrosis | Aspergillus, Scedosporium, Exophiala | Chronic bronchitis and allergic disease; itraconazole or voriconazole for allergic disease |
| Lung abscess and empyema | Candida, Aspergillus | After aspiration or surgery; drainage and antifungal therapy |
| Fungal pneumonia in children | Pneumocystis, Aspergillus, Histoplasma | Immunocompromised and endemic regions |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Endocarditis | Candida (Candida albicans, Candida parapsilosis), Aspergillus, Histoplasma, Cryptococcus | Prosthetic valve, injection drug use, and central lines; large vegetations and embolic events; negative cultures in aspergillosis; liposomal amphotericin B 3 to 5 mg per kg daily or an echinocandin in high dose with valve surgery, and lifelong suppression with fluconazole 400 to 800 mg daily if surgery is not possible |
| Pericarditis | Histoplasma, Coccidioides, Candida | Effusion and constriction; anti-inflammatory drugs, drainage, and antifungal therapy for the pathogen |
| Myocarditis | Candida, Aspergillus, Cryptococcus | Rare; in disseminated disease |
| Vascular graft and device infection | Candida, Aspergillus | Device removal and prolonged therapy |
| Fungal mycotic aneurysm | Aspergillus, Mucorales, Candida | Rupture and haemorrhage; surgery and antifungal therapy |
| Candidaemia | Candida | A bloodstream infection with a catheter or gut source; echinocandin, catheter removal, eye examination, and echocardiography |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Oesophagitis | Candida albicans, Candida glabrata | Odynophagia and dysphagia in HIV and after corticosteroids; fluconazole 200 to 400 mg daily for 14 to 21 days; echinocandin or amphotericin B for refractory disease |
| Gastric and intestinal disease | Mucorales, Histoplasma, Candida, Aspergillus | Ulcers, perforation, and haemorrhage; surgery with antifungal therapy |
| Colitis, enteritis | Histoplasma, Candida | Diarrhoea and ileocaecal masses in disseminated disease |
| Hepatosplenic (chronic disseminated) candidiasis | Candida (after neutropenia) | Fever after neutrophil recovery, raised alkaline phosphatase, and microabscesses on computed tomography and magnetic resonance imaging; liposomal amphotericin B or an echinocandin first, then fluconazole for months until resolution |
| Hepatic infection | Histoplasma, Cryptococcus, Talaromyces, Candida | Disseminated disease with hepatomegaly and raised liver tests |
| Peritonitis in peritoneal dialysis | Candida, Aspergillus, Fusarium, Trichoderma, Paecilomyces | Cloudy effluent and pain; remove the catheter, and give fluconazole or an echinocandin for 2 weeks after removal |
| Intra-abdominal candidiasis | Candida | After perforation, surgery, pancreatitis, and anastomotic leak; echinocandin, source control, and de-escalation with susceptibility |
| Spontaneous fungal peritonitis in cirrhosis | Candida | Ascitic fluid neutrophil count rise with a negative bacterial culture; fluconazole or echinocandin |
| Cholangitis and biliary stent infection | Candida | After stent use and surgery |
| Pancreatic fungal infection | Candida | Infected necrosis |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Candiduria and urinary tract infection | Candida albicans, Candida glabrata, Candida tropicalis, Candida auris | Usually colonisation in catheterised patients; treatment of symptomatic cystitis and pyelonephritis, and in neutropenia, in urological procedures, and in neonates: fluconazole 200 mg daily for 14 days, or flucytosine or amphotericin B deoxycholate for fluconazole resistant species; removal or change of the catheter; echinocandins have poor urinary levels |
| Renal fungus balls | Candida | Obstruction; surgical removal or irrigation |
| Renal abscess and isolated renal mucormycosis | Mucorales, Candida, Aspergillus | Fever and flank pain; nephrectomy in unilateral Mucorales disease |
| Prostatitis and epididymitis | Blastomyces, Cryptococcus, Histoplasma, Coccidioides | Sterile pyuria, prostatic infection; prolonged azole therapy |
| Vulvovaginal candidiasis | Candida albicans, Candida glabrata | Itching, curdy discharge, erythema, and fissures; clotrimazole 500 mg pessary once, or fluconazole 150 mg once; recurrent disease needs fluconazole 150 mg weekly for 6 months |
| Balanitis | Candida | Erythema, white papules; topical azoles |
| Fungal prostatic and testicular disease | Blastomyces | Genitourinary involvement in 10 to 30 percent |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Osteomyelitis | Candida, Aspergillus, Blastomyces, Coccidioides, Histoplasma duboisii, Cryptococcus, Mucorales, Scedosporium | Chronic pain, sinus tracts, and lytic lesions; debridement and azole therapy for at least 6 to 12 months |
| Vertebral osteomyelitis and discitis | Candida, Aspergillus, Coccidioides, Blastomyces | After bloodstream infection and surgery; biopsy and long antifungal courses |
| Septic arthritis | Candida, Coccidioides, Sporothrix, Aspergillus | Joint pain and effusion; drainage and antifungal therapy for 6 to 12 weeks, and longer in prosthetic infection |
| Prosthetic joint infection | Candida (often with bacteria) | Removal of the prosthesis with fluconazole or an echinocandin |
| Sternal wound and device infection | Candida, Aspergillus | After cardiac surgery |
| Eumycetoma | Madurella mycetomatis, Scedosporium, Falciformispora | Swelling, sinuses, and grains with bone destruction; itraconazole and surgery |
| Sporotrichosis, osteoarticular | Sporothrix | Chronic arthritis in alcohol misuse and immunosuppression; itraconazole |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Superficial mycoses | Dermatophytes (Trichophyton, Microsporum, Epidermophyton), Candida, Malassezia | Tinea, pityriasis versicolor, candidal intertrigo; topical azoles, terbinafine, and oral therapy for extensive disease |
| Onychomycosis | Trichophyton rubrum, Trichophyton interdigitale, Candida, non dermatophyte moulds | Terbinafine 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails) |
| Subcutaneous mycoses | Sporothrix, Fonsecaea, Madurella, Basidiobolus, Conidiobolus, Lacazia, Rhinosporidium | Nodules, abscesses, verrucous plaques, and swelling after inoculation; itraconazole and surgery |
| Cutaneous signs of disseminated disease | Candida, Cryptococcus, Histoplasma, Talaromyces, Emergomyces, Fusarium, Mucorales | Papules, nodules, ulcers, and necrotic lesions; biopsy for culture and histology is the quickest route to diagnosis |
| Primary cutaneous aspergillosis | Aspergillus | At catheter sites, in burns, and in neonates |
| Cutaneous mucormycosis | Mucorales | Trauma, burns, and contaminated dressings; surgical debridement and amphotericin B |
| Necrotising soft tissue infection | Mucorales, Candida, Aspergillus | Rapid necrosis in the immunocompromised |
| Chromoblastomycosis and phaeohyphomycosis | Dematiaceous fungi | Warty plaques, and cysts or abscesses; itraconazole and surgery |
| Syndrome | Main pathogens | Features and treatment |
|---|---|---|
| Lymphadenitis | Histoplasma, Sporothrix, Paracoccidioides, Cryptococcus, Talaromyces | Painless nodes with suppuration; biopsy and antifungal therapy |
| Bone marrow and pancytopenia | Histoplasma, Talaromyces, Emergomyces, Candida | Fever, cytopenias, and haemophagocytic syndrome; marrow culture and histology |
| Splenic abscess | Candida, Aspergillus | Fever and left upper quadrant pain; drainage or splenectomy |
| Adrenal disease | Histoplasma, Paracoccidioides, Cryptococcus, Coccidioides | Bilateral enlargement and adrenal insufficiency; hydrocortisone with antifungal therapy |
| Fungaemia | Candida, Fusarium, Trichosporon, Rhodotorula, Saprochaete, Talaromyces, Histoplasma | Positive blood cultures; a high mortality unless treated early |
| Principle | Details |
|---|---|
| Collect the right specimen from the site | Tissue or fluid, not a swab, and not only a superficial specimen; for central nervous system disease, cerebrospinal fluid or biopsy; for lung, bronchoalveolar lavage or biopsy; for skin, a punch biopsy from the edge |
| Request the tests the site and the host require | Direct microscopy, histology, culture, antigen, and polymerase chain reaction |
| Consider the epidemiology | Travel, residence in endemic regions, soil and animal exposure, occupation |
| Seek extrapulmonary disease | In endemic mycoses, cryptococcosis, and candidaemia (eye, heart, liver, spleen, skin) |
| Review the drug penetration | Echinocandins do not reach the urine, the eye, or the central nervous system well; amphotericin B and azoles differ; fluconazole penetrates the urine, central nervous system, and eye; voriconazole penetrates the brain and eye |
| Combine drug and source control | Surgery for necrotic tissue, abscesses, vegetations, and fungus balls, and removal of catheters and devices |
| Site | Good penetration | Poor penetration |
|---|---|---|
| Cerebrospinal fluid and brain | Fluconazole, voriconazole, flucytosine, liposomal amphotericin B (brain tissue), isavuconazole (brain tissue) | Echinocandins, itraconazole, posaconazole |
| Eye (vitreous) | Fluconazole, voriconazole (with intravitreal injection) | Echinocandins, amphotericin B (poor) |
| Urine | Fluconazole, flucytosine, amphotericin B deoxycholate | Echinocandins, azoles other than fluconazole, lipid amphotericin B |
| Bone | Azoles, liposomal amphotericin B | Echinocandins (variable) |
| Lung | Azoles, amphotericin B, echinocandins (epithelial lining fluid) | None clinically important |
| Peritoneum | Fluconazole, echinocandins (adequate) | Variable |
