Epidemiology and treatment approaches in management of invasive fungal infections

Figures & data

Table 1 Proportion of invasive fungal infections reported in the literature

	IA	Zygomycosis	IC	Other	Reference(s)
HCT	43%	8%	28%	15%	^Citation2
SOT	18.8%	2.3%	52.9%	19%	^Citation4
HM	33%–69%	–	13.5%–44%	–	^Citation10,Citation11
ICU	11%	–	79%	10%	^Citation15

Abbreviations: HCT, hematopoietic cell transplantation; HM, hematologic malignancy; IA, invasive aspergillosis; IC, invasive candidiasis; ICU, intensive care unit; SOT, solid organ transplantation.

Table 2 Risk factors for invasive fungal infections

	Risk factors
IFI	Host predisposition
	Neutropenia ≥3 weeks
	Environmental factors
IA	GVHD (acute grades 2–4 or chronic)
	HCT type (mismatched-related donor at greatest risk)
	Underlying hematologic disease (MDS or AML)
	Corticosteroid (dose and duration)
	T cell-depleting therapy
	CMV infection
	Ganciclovir use
	Polymorphisms (TLR4, TNF, or IL-10)
	HCT in nonlaminar air flow room
IC	Colonization
	Presence of central venous catheter
	Hemodialysis
	Surgery (complicated or repeated abdominal)
	Clinical unstable presentation (acute renal failure, shock, disseminated intravascular coagulation)
	Antianerobic antibiotic agents
	Total parental nutrition or intralipid agents
	Prolonged ICU stay

Abbreviations: AML, acute myelogenous leukemia; CMV, cytomegalovirus; GVHD, graft versus host disease; HCT, hematopoietic cell transplantation; HM, hematologic malignancy; IA, invasive aspergillosis; IC, invasive candidiasis; ICU, intensive care unit; IFI, invasive fungal infection; IL-10, interleukin-10; MDS, myelodysplastic syndrome; SOT, solid organ transplantation; TLR4, toll-like receptor 4; TNF, tumor necrosis factor.

Table 3 Antifungal agents: uses, pros, and cons

Drug	Uses	Comments
Polyenes	Salvage therapy and empiric use due to broad activity	Nephrotoxicity and infusion reactions are the largest drawbacks
Fluconazole	IC in stable patients or stepdown agents; prophylaxis in HCT; no need to monitor blood levels	No mold activity
Itraconazole	May be used as stepdown therapy where other azoles are unavailable or intolerant in IC or invasive aspergillosis; should monitor blood levels	Limited usefulness, other agents may be preferred: variable oral absorption, food and pH-dependent, side effect profile (GI, cardiac, hepatic)
Voriconazole	First-line therapy in invasive aspergillosis; IC in stable patients or stepdown therapy	IV formulation contraindicated in renal impairment CrCl ≤ 50 mL/min; side effect profile (rash, visual, hepatic, cardiac); DDI; associated emergence of zygomycosis; need to monitor blood levels
Posaconazole	Prophylaxis in HCT/HM; salvage therapy for IFI (eg, zygomycosis)	Absorption dependent on high fat meals; side effect profile (hepatic, cardiac although least toxic of azoles after fluconazole); oral formulation only; need to monitor blood levels
Echinocandins	Primary indication for IC; micafungin for prophylaxis in HCT; caspofungin for empiric therapy in febrile neutropenia; salvage therapy for invasive aspergillosis; potential addition for combination therapy; few side effects or DDI	Not for primary monotherapy in invasive aspergillosis Breakthrough IFI have been seen
Flucytosine	Used in combination with other antifungal agents in IC	Marrow toxic; only oral formulation available

Abbreviations: CrCl, creatinine clearance; DDI, drug-drug interactions; GI, gastrointestinal; HCT, hematopoietic cell transplantation; HM, hematologic malignancy; IA, invasive aspergillosis; IC, invasive candidiasis; IFI, invasive fungal infection.

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