Table 4.
Antifungal drug therapy in patients with invasive fungal disease due to Candida spp., Cryptococcus spp., uncommon yeasts, Aspergillus spp., uncommon moulds, Pneumocystis jirovecii, and endemic fungi according to causative pathogen (adapted from published guidelines [4,194,263,332,333,334,335]).
| Pathogen | First Line (Preferred) Antifungal Agent | Alternate Antifungal Agent | Antifungal Drugs to Avoid |
|---|---|---|---|
| Candida spp. * | |||
| Candidemia (prior to susceptibility testing results) [335,336,337,338,339,340] | Echinocandin | FLU # (or other broad-spectrum azole); refer to in vitro susceptibility results | FLU as initial therapy in critically ill and neutropenic patients |
| Other forms of invasive candidiasis +/− candidemia, e.g., endocarditis, intraabdominal candidiasis [335,336,337,338,339,340] | Various: preferred agent(s) will vary with site of infection (seek Infectious Diseases advice); combination therapy may be appropriate | Various; will vary with site of infection; seek Infectious Diseases advice | - |
| Cryptococcus spp. | |||
| CNS disease and disseminated infection (all patients) [332] | L-AmB + 5FC initial therapy followed by FLU # |
AmB-d + 5-FC or L-AmB only or 5-FC + FLU followed by FLU |
FLU monotherapy; Echinocandins |
| Pulmonary infection only: Severe disease and/or large cryptococcomas (>2 cm diameter) [332] | As for CNS cryptococcosis | Echinocandins | |
| Pulmonary infection only: Mild or asymptomatic pulmonary cryptococcosis (e.g., solitary nodules, <2 cm diameter) and without crypotcoccomas [332] | FLU | Alternative broad-spectrum azole | Echinocandins |
| Uncommon yeasts | |||
| Saprochaete/Magnusiomyces spp. [4] | L-AmB +/− 5FC | VRC | Echinocandins |
| Rhodotorula spp. [4] | L-AmB +/− 5-FC | AmB-d +/− 5-FC | Triazoles, echinocandins |
| Trichosporon spp. [4] | VRC or POS | FLU or POS | Echinocandins |
| Other | |||
| Pneumocystis jirovecii [341] | TMP-SMX $ | Clindamycin plus primaquine; or Dapsone plus TMP |
Although intravenous pentamidine has had efficacy against PCP in HIV-infected persons, survival rates were significantly lower compared with TMP-SMX and clindamycin-primaquine [342] |
| Moulds | |||
| Aspergillus spp. [333] | VRC | POS or ISA | AmB-d ** |
| Lomentospora spp. [263,334] | VRC + TRB | VRC | L-AmB, AmB-d |
| Scedosporium spp. [263,334] | VRC | VRC + L-AmB/ echinocandin/TRB |
L-AmB, AmB-d |
| Fusarium spp. Complex [263,334] | VRC +/− L-AmB | L-AmB | Amb-d |
| Mucorales [263] | L-AmB | POS or ISA | AmB-d |
| Dematiaceous fungi, e.g., Exserohilum spp. [263] | VRC +/− L-AmB | L-AmB + triazole other than VRC | Amb-d |
| Endemic mycoses | |||
| Blastomyces spp. [194] | L-AmB followed by ITR | ||
| Coccidioiddes spp. [194] | L-AmB followed by azole | ||
| Histoplasma spp. [194] | L-AmB followed by ITR | ||
| Sporothrix spp. [194] | L-AmB +/− ITR |
Abbreviations: 5-FC, 5 flucytosine; AmB-d, amphotericin deoxycholate; CNS, central nervous system; FLU, fluconazole; HIV, human immunodeficiency virus; ISA, isavuconazole; ITR, itraconazole; L-AmB, liposomal amphotericin B; PCP, pneumocystis jirovecii pneumonia; POS, posaconazole; TMP, trimethoprim; TMP-SMX, trimethroprim-sulphamethoxazole; TRB, terbinafine; VRC, voriconazole; *Antifungal susceptibility testing should always be performed in invasive Candida infections; ** Except may be used in neonates; # alternate triazoles may be used after expert consultation; $ Consider desensitization in all patients with allergy to TMP-SMX as clinically indicated and after expert consultation [341].