Amphotericin B

Class: Polyenes
VA Class: AM700
CAS Number: 1397-89-3
Brands: Amphotec, Abelcet, AmBisome

Introduction

Antifungal; macrocyclic polyene.^{135 201 202 203 417}

Uses for Amphotericin B

Aspergillosis

Treatment of invasive aspergillosis.^{146 201 203 204 207 211 219 230 231 232 235 236 237 238 239 240 241 242 243 244 248 268 269 288 396 379 420 423 436}

IDSA considers voriconazole the drug of choice for primary treatment of invasive aspergillosis in most patients and IV amphotericin B liposomal the preferred alternative.⁴²³ Although conventional IV amphotericin B has historically been used for treatment of invasive aspergillosis, IDSA states that data to date indicate the lipid formulations of amphotericin B are as effective and less nephrotoxic and generally are preferred, if available.⁴²³ For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends IV amphotericin B (a lipid formulation), caspofungin, micafungin, posaconazole, or itraconazole.⁴²³ For empiric or preemptive therapy of presumed aspergillosis, IDSA recommends IV amphotericin B liposomal, caspofungin, itraconazole, or voriconazole.⁴²³

For treatment of invasive aspergillosis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend voriconazole as the drug of choice;⁴⁴⁰ IV amphotericin B (conventional or lipid formulation), IV caspofungin, and oral posaconazole are alternatives.⁴⁴⁰ Voriconazole also is considered the drug of choice for treatment of invasive aspergillosis in HIV-infected children;⁴⁴¹ IV amphotericin B (conventional or lipid formulation) and IV caspofungin are alternatives.⁴⁴¹

Blastomycosis

Treatment of pulmonary and extrapulmonary blastomycosis caused by Blastomyces dermatitidis.^{146 211 267 269 288 319 320 321 322 424 436 448} A drug of choice.^{146 227 267 283 319 320 424 436 448}

IV amphotericin B is preferred for initial treatment of severe blastomycosis, especially infections involving the CNS,^{146 269 288 319 320 321 322 424 436 448} and for initial treatment of presumptive blastomycosis in immunocompromised patients, including HIV-infected individuals.^{267 424} Oral itraconazole is the drug of choice for treatment of mild to moderate pulmonary blastomycosis or mild to moderate disseminated blastomycosis (without CNS involvement) and also is recommend for follow-up therapy in patients with more severe infections after an initial response has been obtained with IV amphotericin B.^{291 424 436}

Conventional IV amphotericin B or a lipid formulation of IV amphotericin B can be used for initial treatment of blastomycosis.⁴²⁴ However, IDSA and others state that a lipid formulation (e.g., amphotericin B liposomal) is preferred for treatment of CNS blastomycosis since higher CSF concentrations may be obtained.^{424 448}

IDSA states that long-term suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole may be required to prevent relapse or recurrence of blastomycosis in immunocompromised patients and in other patients who experience relapse despite appropriate therapy.⁴²⁴ Such prophylaxis is not addressed in current CDC, NIH, and IDSA guidelines for prevention of opportunistic infections in individuals infected with HIV.^{440 441}

Candida Infections

Treatment of disseminated or invasive infections caused by Candida, including candidemia, cardiovascular infections (endocarditis, pericarditis, myocarditis), or meningitis, and other serious Candida infections, including osteoarticular infections (osteomyelitis, septic arthritis), peritonitis, intra-abdominal abscesses, urinary tract infections (symptomatic cystitis, pyelonephritis, urinary fungus balls), and endophthalmitis.^{126 211 146 222 223 224 225 248 254 283 293 425 436} Also used for treatment of certain severe or refractory mucocutaneous Candida infections†.^{425 436}

Generally effective against infections caused by C. albicans, C. glabrata, C. krusei, C. parapsilosis, or C. tropicalis.^{223 254 425} A drug of choice for many infections caused by fluconazole-resistant Candida.⁴²⁵

Choice of an antifungal for treatment of candidemia or invasive Candida infections should take into consideration any history of recent exposure to azole antifungals or intolerance to antifungals, local and/or institutional epidemiologic data regarding prevalence of the various Candida strains and their patterns of resistance, severity of illness, relevant comorbidities, presence and duration of neutropenia or immunosuppression, and evidence of involvement of the CNS, cardiac valves, and/or visceral organs.⁴²⁵ Amphotericin B generally is preferred for severe Candida infections caused by strains that may be fluconazole-resistant (e.g., C. glabrata, C. krusei) and for treatment of Candida infections in patients who have recently received fluconazole or are immunocompromised (e.g., those with HIV infection).^{227 288 346 347 425 436}

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis† in nonneutropenic patients, IDSA recommends fluconazole or an echinocandin (caspofungin, micafungin, anidulafungin) for initial therapy;⁴²⁵ amphotericin B (conventional or lipid formulation) is an alternative when these drugs have been ineffective or cannot be used because of intolerance or resistance.⁴²⁵ Initial therapy with an echinocandin is preferred in patients with moderately severe to severe infections and for those who recently received an azole antifungal or are likely to be infected with C. glabrata or C. krusei;⁴²⁵ consider transition from the echinocandin to fluconazole in clinically stable patients if strains susceptible to fluconazole (e.g., C. albicans) are likely.⁴²⁵ Fluconazole is the drug of choice for treatment of infections caused by C. parapsilosis in these patients.⁴²⁵

For treatment of candidemia in neutropenic patients, IDSA recommends an echinocandin (caspofungin, micafungin, anidulafungin) or amphotericin B (a lipid formulation) for initial therapy;⁴²⁵ fluconazole is a reasonable alternative in those who are less critically ill or have not recently received an azole;⁴²⁵ voriconazole can be used as an alternative when broader antifungal coverage is required.⁴²⁵ An echinocandin, amphotericin B (a lipid formulation), or voriconazole is recommended for C. krusei infections.⁴²⁵ An echinocandin is preferred for C. glabrata infections;⁴²⁵ fluconazole or amphotericin B (a lipid formulation) is preferred for C. parapsilosis infections.⁴²⁵ For infections known to be caused by C. krusei, an echinocandin, amphotericin B (a lipid formulation), or voriconazole is recommended.⁴²⁵ For initial empiric treatment of suspected invasive candidiasis† in neutropenic patients, amphotericin B (a lipid formulation), caspofungin, or IV voriconazole is recommended;⁴²⁵ alternatives are fluconazole or itraconazole.⁴²⁵

Conventional IV amphotericin B usually is the drug of choice for treatment of disseminated candidiasis in neonates (neonatal candidiasis).^{146 425} IDSA states that fluconazole is a reasonable alternative if amphotericin B cannot be used.⁴²⁵

For treatment of CNS candidiasis, IDSA recommends initial treatment with IV amphotericin B (with or without oral flucytosine) and follow-up treatment with fluconazole.⁴²⁵ A lipid formulation of IV amphotericin B may be preferred, but conventional IV amphotericin B can be used.⁴²⁵ Conventional amphotericin B has been given intrathecally† as an adjunct to systemic antifungal for treatment of Candida meningitis.^{126 211 455}

Mucocutaneous or noninvasive Candida infections (e.g., oropharyngeal, esophageal, or vaginal candidiasis) usually can be adequately treated with an appropriate oral or topical antifungal.^{147 269 283 425 436} Severe mucocutaneous infections (e.g., oropharyngeal candidiasis†, esophageal candidiasis†) caused by azole-resistant Candida or infections that fail to respond to such therapy may require IV amphotericin B.^{146 425 436} Also has been recommended as an alternative for treatment of initial episodes of oropharyngeal candidiasis† or esophageal candidiasis† in patients who cannot tolerate oral therapy.⁴²⁵

Treatment of urinary tract infections caused by Candida.^{126 146 211 232 251 260 262 292 425 436 433 434 435 466 467 468 469 470 471 472 473 474} IDSA states that antifungal treatment not usually indicated for asymptomatic cystitis, unless there is high risk of disseminated candidiasis (e.g., neutropenic patients, low birthweight infants, patients undergoing renal transplantation or urologic manipulations).⁴²⁵ If treatment is indicated, fluconazole usually is the drug of choice for symptomatic cystitis, pyelonephritis, or fungus balls likely to be caused by fluconazole-susceptible Candida.⁴²⁵ When fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) are likely, IV amphotericin B or oral flucytosine is recommended for symptomatic cystitis, IV amphotericin B (with or without flucytosine) or oral flucytosine alone is recommended for pyelonephritis, and IV amphotericin B (with or without flucytosine) is recommended for fungus balls.⁴²⁵

Has been administered by bladder irrigation† for treatment of candiduria (funguria),^{126 146 211 232 251 260 262 292 425 436 433 434 435 466 467 468 469 470 471 472 473 474} but such therapy is controversial.^{292 434 467 468 469 471 472 473 474} IDSA states that bladder irrigation† with amphotericin B is not generally recommended, but may be useful for patients with refractory symptomatic cystitis caused by fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) or as an adjunct to systemic antifungal therapy for the treatment of urinary fungus balls,⁴²⁵

Treatment of endophthalmitis† caused by Candida.⁴²⁵ IDSA states that IV amphotericin B (conventional formulation) used in conjunction with flucytosine is the regimen of choice in patients with advancing lesions or lesions threatening the macula;⁴²⁵ fluconazole is an acceptable alternative for less severe endophthalmitis.⁴²⁵ Ophthalmic consultation for consideration of partial vitrectomy and intravitreal† administration of conventional amphotericin B is recommended for patients with severe endophthalmitis and vitreitis.⁴²⁵

Coccidioidomycosis

Treatment of coccidioidomycosis caused by Coccidioides immitis or C. posadasii.^{126 135 146 248 269 285 288 385 394 396 426 436}

Antifungal treatment may not be necessary for mild, uncomplicated coccidioidal pneumonia since such infections may resolve spontaneously;^{146 426} treatment is recommended for patients with more severe or rapidly progressing infections, those with chronic pulmonary or disseminated infections, and immunocompromised or debilitated individuals (e.g., HIV-infected individuals, organ transplant recipients, those receiving immunosuppressive therapy, those with diabetes or cardiopulmonary disease).^{146 426 440 441}

For initial treatment of symptomatic pulmonary coccidioidomycosis and chronic fibrocavitary or disseminated (extrapulmonary) coccidioidomycosis, IDSA states that an oral azole (fluconazole or itraconazole) usually is recommended.⁴²⁶ IV amphotericin B is recommended as an alternative and is preferred for initial treatment of severely ill patients who have hypoxia or rapidly progressing disease, for immunocompromised individuals, or when azole antifungals cannot be used (e.g., pregnant women).^{146 426}

For treatment of clinically mild coccidioidomycosis (e.g., focal pneumonia, a positive coccidioidal serologic test alone) in HIV-infected adults or adolescents, CDC, NIH, and IDSA recommend oral fluconazole or oral itraconazole.⁴⁴⁰ For treatment of diffuse pulmonary infections or extrathoracic disseminated coccidioidomycosis (nonmeningeal) in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend initial therapy with IV amphotericin B followed by oral azole therapy.⁴⁴⁰ Alternatively, some experts recommend initial therapy with IV amphotericin B used in conjunction with an oral azole (e.g., fluconazole) followed by an oral azole alone.⁴⁴⁰

For treatment of diffuse pulmonary or disseminated coccidioidomycosis in HIV-infected infants and children, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B followed by oral fluconazole or oral itraconazole.⁴⁴¹ In those with severe disseminated disease, some experts recommend initial therapy with IV amphotericin B used in conjunction with an oral azole (e.g., fluconazole) followed by an oral azole alone.⁴⁴¹ Use of fluconazole or itraconazole alone may be sufficient for treatment of coccidioidomycosis in HIV-infected infants and children with only mild disease (e.g., focal pneumonia) and also can be considered an alternative for those with stable pulmonary or disseminated coccidioidomycosis (nonmeningeal).⁴⁴¹

For treatment of coccidioidal meningitis in HIV-infected adults, adolescents, or children or for other individuals, fluconazole (with or without intrathecal† amphotericin B) is the regimen of choice;^{146 426 440 441} itraconazole is an alternative in adults or adolescents.^{426 440} If patient does not respond to azole therapy alone, consider intrathecal† amphotericin B (with or without continued azole therapy) or IV amphotericin B used in conjunction with intrathecal† amphotericin B.^{146 426 440 441} Consultation with an expert is recommended.^{146 440 441}

CDC, NIH, and IDSA state that long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral itraconazole is recommended to prevent relapse or recurrence of coccidioidomycosis in HIV-infected adults, adolescents, or children who have been adequately treated for the disease.^{440 441} Secondary prophylaxis with oral fluconazole or oral itraconazole also necessary in any other individual treated for coccidioidal meningitis.^{146 426}

Cryptococcosis

Treatment of infections caused by Cryptococcus neoformans.^{126 135 145 146 153 158 162 169 170 177 182 183 184 188 189 196 197 201 202 211 213 214 215 216 220 230 231 269 393 427 436} A drug of choice, especially for initial treatment of meningitis.^{126 135 145 146 153 158 162 169 170 177 182 183 184 196 197 211 213 214 269 393 427 436} Because of reported in vitro and in vivo synergism, usually used in conjunction with flucytosine for initial treatment,^{146 197 211 213 214 346 427} including in HIV-infected patients.^{145 146 169 172 182 183 185 192 427}

For treatment of cryptococcal meningitis in HIV-infected adults, adolescents, and children, CDC, NIH, IDSA, and others state that the preferred regimen is initial (induction) therapy with conventional IV amphotericin B given in conjunction with oral flucytosine for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then follow-up (consolidation) therapy with oral fluconazole administered for at least 8 weeks.^{146 427 436 440 441} A lipid formulation of amphotericin B (e.g., amphotericin B lipid complex, amphotericin B liposomal) could be substituted for conventional amphotericin B in this preferred regimen in patients who have or are predisposed to renal dysfunction.^{427 440 441}

Alternative regimens for treatment of cryptococcal meningitis in HIV-infected adults, adolescents, and children who cannot receive the preferred regimen are induction and consolidation therapy with conventional IV amphotericin B or a lipid formulation of IV amphotericin B (e.g., amphotericin B lipid complex, amphotericin B liposomal) given for 4–6 weeks; induction therapy with conventional IV amphotericin B given in conjunction with oral fluconazole for at least 2 weeks until there is evidence of clinical improvement and negative CSF culture after repeat lumbar puncture, then consolidation therapy with oral fluconazole administered for at least 8 weeks;^{146 427 440 441} induction and consolidation therapy with oral fluconazole used in conjunction with oral flucytosine for 4–6 weeks;^{146 427 440 441} or induction and consolidation therapy with oral fluconazole given for 10–12 weeks.⁴²⁷ These alternative regimens may be less effective and are recommended only in patients who cannot tolerate or have not responded to the preferred regimen.^{427 440 441} IDSA states that use of intrathecal† or intraventricular† conventional amphotericin B in the treatment of cryptococcal meningitis generally is discouraged and rarely necessary.⁴²⁷

For treatment of cryptococcal CNS infections in organ transplant recipients, IDSA recommends induction therapy with IV amphotericin B liposomal or amphotericin B lipid complex given in conjunction with oral flucytosine for at least 2 weeks, then consolidation therapy with oral fluconazole given for 8 weeks.⁴²⁷ Induction regimen should be continued for at least 4–6 weeks if flucytosine isn’t included.⁴²⁷ Conventional amphotericin B not usually recommended for first-line treatment of cryptococcosis in transplant recipients because of the risk of nephrotoxicity.⁴²⁷

In adults and children who do not have HIV infection and are not transplant recipients, IDSA states that the preferred regimen for treatment of cryptococcal meningitis is induction therapy with conventional IV amphotericin B given in conjunction with oral flucytosine for at least 4 weeks (consider a 2-week induction period in those who are immunocompetent, are without uncontrolled underlying disease, and are at low risk for therapeutic failure), then consolidation therapy with oral fluconazole administered for an additional 8 weeks or longer.⁴²⁷

For treatment of mild to moderate pulmonary cryptococcosis (nonmeningeal) in immunocompetent or immunosuppressed adults or children, IDSA states that the regimen of choice is oral fluconazole given for 6–12 months.⁴²⁷ However, severe pulmonary cryptococcosis, cryptococcemia, and disseminated cryptococcal infections in immunocompetent or immunosuppressed adults, adolescents, or children should be treated using regimens recommended for cryptococcal meningitis.^{427 440 441}

Alternative to oral fluconazole for long-term suppressive or chronic maintenance therapy (secondary prophylaxis)† to prevent relapse of cryptococcal meningitis in HIV-infected individuals.^{155 160 169 177 185 197 213 427} Oral fluconazole is the drug of choice for secondary prophylaxis of cryptococcosis in HIV-infected adults, adolescents, and children or other individuals who have had documented, adequately treated cryptococcal meningitis;^{427 440 441} conventional IV amphotericin B may be less effective and should be used only if necessary in those who cannot receive azole antifungals.⁴²⁷

Although data are limited, IDSA states that recommendations for treatment of CNS, pulmonary, or disseminated infections caused by Cryptococcus gattii and recommendations for secondary prophylaxis of C. gattii infections are the same as recommendations for C. neoformans infections.⁴²⁷ IDSA states that single, small cryptococcoma may be treated with oral fluconazole; induction therapy with a regimen of conventional IV amphotericin B and flucytosine given for 4–6 weeks, followed by consolidation therapy with fluconazole given for 6–18 months, should be considered for very large or multiple cryptococcomas caused by C. gattii.⁴²⁷ Regimens that include amphotericin B (conventional or liposomal formulations), flucytosine, and fluconazole have been effective in a few patients with CNS infections known to be caused by C. gattii.^{450 451 454}

Histoplasmosis

Treatment of histoplasmosis caused by Histoplasma capsulatum.^{126 146 269 288 428 436}

IV amphotericin B and oral itraconazole are the drugs of choice for treatment of histoplasmosis.^{146 227 248 269 283 318 436} IV amphotericin B is preferred for initial treatment of severe, life-threatening histoplasmosis, especially in immunocompromised patients (e.g., those with HIV infection).^{126 146 197 227 269 283 288 318 428 436} Oral itraconazole generally used for initial treatment of less severe disease (e.g., mild to moderate acute pulmonary histoplasmosis, chronic cavitary pulmonary histoplasmosis) and as follow-up therapy in severe infections after a response has been obtained with amphotericin B.^{227 283 288 318 428 436 440 441}

For treatment of moderately severe to severe acute pulmonary histoplasmosis or progressive disseminated histoplasmosis in HIV-infected adults and adolescents and other adults, CDC, NIH, and IDSA recommend initial treatment with a lipid formulation of IV amphotericin B and follow-up treatment with oral itraconazole.^{428 440} IV amphotericin B liposomal may be the preferred lipid formulation for treatment of progressive disseminated histoplasmosis and in HIV-infected individuals, but other lipid formulations may be preferred in some patients because of cost or tolerability.^{428 440} Conventional IV amphotericin B can be used instead of a lipid formulation for initial treatment of moderately severe to severe acute pulmonary or progressive disseminated histoplasmosis in patients at low risk for nephrotoxicity.^{428 440}

For treatment of progressive disseminated histoplasmosis in children, IDSA states that conventional IV amphotericin B or an initial regimen of conventional IV amphotericin B and follow-up treatment with oral itraconazole can be used.⁴²⁸ IDSA states that conventional amphotericin B usually is well tolerated in children, but a lipid formulation may be substituted if necessary.⁴²⁸ For treatment of moderately severe to severe disseminated histoplasmosis in HIV-infected infants and children, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B liposomal and follow-up treatment with oral itraconazole;⁴⁴¹ conventional IV amphotericin B can be used as an alternative to the lipid formulation for initial treatment in these children.⁴⁴¹ Although oral itraconazole may be used alone for treatment of mild to moderate disseminated histoplasmosis in children, including HIV-infected infants and children, it is not recommended for more severe infections.^{428 441}

For treatment of meningitis caused by H. capsulatum in HIV-infected adults, adolescents, or children and in other individuals, CDC, NIH, and IDSA recommend initial treatment with IV amphotericin B liposomal and follow-up treatment with oral itraconazole.^{428 440 441} Amphotericin B liposomal generally preferred for treatment of CNS histoplasmosis^{428 440 441} because higher CSF concentrations may be obtained than with some other amphotericin B formulations.^{428 441}

Long-term suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole is indicated to prevent relapse or recurrence of histoplasmosis in HIV-infected adults, adolescents, and children and other immunosuppressed individuals who have been adequately treated for histoplasmosis.^{428 440 441}

Paracoccidioidomycosis

Treatment of paracoccidioidomycosis† (South American blastomycosis) caused by Paracoccidioides brasiliensis.^{126 146 221 282 288 436}

IV amphotericin B is the drug of choice for initial treatment of severe paracoccidioidomycosis.^{126 146 221 282 436} Oral itraconazole is the drug of choice for treatment of less severe or localized paracoccidioidomycosis and for follow-up therapy in more severe infections after initial treatment with IV amphotericin B.^{126 146}

Penicilliosis

Treatment of penicilliosis† caused by Penicillium marneffei.^{406 407 408 410 440}

For treatment of severe or disseminated P. marneffei infections, including in HIV-infected adults or adolescents, an initial regimen of IV amphotericin B followed by oral itraconazole is recommended.^{406 407 410 440} Oral itraconazole can be used alone for treatment of mild infections.⁴⁴⁰

Chronic suppressive or maintenance therapy (secondary prophylaxis) with oral itraconazole is recommended to prevent relapse of penicilliosis in HIV-infected adults or adolescents who respond to an initial treatment regimen of IV amphotericin B and/or oral itraconazole.^{407 408 440}

Sporotrichosis

Treatment of disseminated, pulmonary, osteoarticular, and meningeal sporotrichosis caused by Sporothrix schenckii.^{126 146 211 269 288 289 291 429 436}

IV amphotericin B is the drug of choice for initial treatment of severe, life-threatening sporotrichosis and sporotrichosis that is disseminated or has CNS involvement.^{126 288 289 291 429 436} Oral itraconazole is considered the drug of choice for treatment of cutaneous, lymphocutaneous, or mild pulmonary or osteoarticular sporotrichosis and for follow-up treatment of severe infections after a response has been obtained with IV amphotericin B.^{288 289 291 429 436}

IDSA and others state that a lipid formulation of amphotericin B is preferred for treatment of sporotrichosis since the lipid formulations generally are associated with fewer adverse effects.^{429 436}

Zygomycosis

Treatment of zygomycosis, including mucormycosis, caused by susceptible species of Absidia, Mucor, or Rhizopus and treatment of infections caused by susceptible species of Conidiobolus or Basidiobolus.^{126 231 232 384 126 135 269 324 366 367 396 436 465}

Drug of choice for zygomycosis.^{269 324 436} However, severe cases of GI basidiobolomycosis caused by Basidiobolus ranarum may not respond to amphotericin B.^{413 414 415 416} GI basidiobolomycosis has been successfully treated with oral itraconazole after partial surgical resection of the GI tract.^{413 415 416}

Empiric Therapy in Febrile Neutropenic Patients

Empiric therapy of presumed fungal infections in febrile, neutropenic patients† who have not responded to empiric treatment with broad-spectrum antibacterial agents.^{126 195 202 248 252 273 277 290 344 372 373 374 376 422 452}

IV amphotericin B generally has been the drug of choice for empiric antifungal treatment in patients who remain febrile and neutropenic despite 5–7 days of empiric treatment with an appropriate broad-spectrum antibacterial agent.⁴²² Fluconazole is an alternative if infection with Aspergillus or fluconazole-resistant Candida (e.g., C. glabrata, C. krusei) is unlikely.⁴²²

Prevention of Fungal Infections in Transplant Recipients, Cancer Patients, or Other Patients at High Risk

Prevention of fungal infections† (e.g., aspergillosis, candidiasis) in neutropenic cancer patients† or patients undergoing BMT† or solid organ transplantation†.^{126 211 249 274 277 286 287 358 371 372 375 422}

For postoperative antifungal prophylaxis in recipients of solid organ transplants† at high risk for invasive candidiasis (i.e., liver, pancreas, or small bowel transplant recipients), IDSA recommends fluconazole or IV amphotericin B liposomal.⁴²⁵ Risk of invasive candidiasis after other solid organ transplants (e.g., kidney, heart) appears to be too low to warrant routine antifungal prophylaxis.⁴²⁵

Conventional amphotericin B,^{211 243 261 276 286 287 460 463} amphotericin B lipid complex,^{423 460 461} and amphotericin B liposomal^{460 462 464} have been administered by nasal instillation† or nebulization† in an attempt to prevent aspergillosis in immunocompromised patients, including solid organ transplant recipients† (e.g., lung transplant recipients) and neutropenic chemotherapy patients†.

Leishmaniasis

Treatment of American cutaneous leishmaniasis caused by Leishmania braziliensis or L. mexicana and for mucocutaneous leishmaniasis caused by L. braziliensis.^{102 103 104 105 106 107 108 109 126 135 269 271 381 442 443} Drugs of choice for cutaneous or mucocutaneous leishmaniasis are sodium stibogluconate (not commercially available in the US, but may be available from CDC), meglumine antimonate (not commercially available in the US), and miltefosine (not commercially available in the US);^{256 271 381 442} amphotericin B is an additional drug of choice for mucosal infections.^{271 381 442 443}

Treatment of visceral leishmaniasis (kala-azar).^{108 115 116 117 126 135 187 202 247 253 256 382 383 404 442 443 444} Drugs of choice for initial treatment of visceral leishmaniasis caused by L. donovani (usually endemic in Asia and Africa), L. infantum (usually endemic in the Mediterranean basin), or L. chagasi (usually endemic in Latin America) are amphotericin B (lipid formulation), sodium stibogluconate (not commercially availa