Hospital Infection Control

Yeast/molds - Fusarium

What are the key principles of preventing yeast/molds - non Aspergillus molds?

Non-Aspergillus molds include mucormycetes such as Rhizopus and Mucor species, hyaline (colorless) molds such as Fusarium species, and dematiaceous (dark, melanin-containing) molds such as Curvularia and Exophiala species.

Infection with non-Aspergillus molds occurs after exposure to infectious conidia acquired from the environment by inhalation or by direct content through contaminated fomites or contaminated water. Immunosuppressed hosts are primarily at risk for these infections.

Prevention includes:

  • identifying vulnerable individuals and reducing their exposure to contaminated air, water, and/or fomites, especially during hospital construction and renovation.

  • appropriate cleaning and disinfection to reduce spore counts on environmental surfaces.

  • appropriate usage and disinfection of solutions, sterile, or single-use devices, and other hospital equipment.

  • antifungal prophylaxis (in some circumstances).

  • immunomodulatory drugs such as CM-CSF or G-CSF (in some circumstances).

What are the key conclusions for available clinical trials and meta-analyses that inform control of non Aspergillus molds?

No clinical trials or meta-analyses have been conducted to evaluate the impact of these control measures.

What are the consequences of ignoring key concepts related to control of non-Aspergillus molds?

The consequences of ignoring control of non-Aspergillus molds are unknown but may include an increase in infections caused by these organisms.

What other information supports the key conclusions of studies of non-Aspergillus molds, e.g., case-control studies and case series?

The epidemiology of non-Aspergillus mold infections in the health care environment has not been well studied.

Summary of current controversies.

1. The incubation period of non-Aspergillus mold infections is largely unknown. This means that determining whether these infections are community-acquired or nosocomial can be difficult.

2. A dramatic increase in prevalence of mucormycosis has been recognized in some institutions. This could be attributable to increased utilization of voriconazole prophylaxis, to an unrelated fluctuation in the environmental reservoir due to temporal or local climate changes, or to an increase in the numbers of susceptible patients over time. The actual cause(s) are still not clear.

3. The role of environmental sampling during a hospital outbreak and the appropriate interpretation of sampling data can be controversial.

What is the role of and impact of non-Aspergillus molds - or infections and the need for control relative to infections at other sites or other specific pathogens?

In general, non-Aspergillus mold infections all have lower prevalence than invasive aspergillosis, but largely affect the same immunocompromised patient population. Control measures are similar to measures for control of airborne molds such as Aspergillus.


Mucormycosis occurs largely in patients with host defense defects and/or serum iron overload.

Risk factors include immunosuppression due to malignancy or transplantation, use of various hospital procedures and devices (contaminated bandages, catheters, tongue depressors, and adhesives), deferoxamine therapy, diabetes, and steroid use.

Infection has also been spread through transplant of organs from an infected donor.

The major organisms involved include Rhizopus, Mucor, Lichtheimia (formerly Absidia), and Rhizomucor species, as well as the less prevalent agents Cunninghamella, Syncephalastrum,Apophysomyces, and Saksenaea species.

These are all members of the taxonomic group Mucormycetes (formerly zygomycetes). These organisms are found worldwide in soil, decaying organic matter, and foods.

The incidence of mucormycosis is very low (1.7 cases per million population per year) but the mortality is very high (up to 65% in some studies). Prophylaxis with itraconazole or voriconazole has been implicated in predisposing to mucormycosis, but this is controversial.

Fusarium infections

Fusarium infections occur in the immunosuppressed population, including transplant recipients, patients with burns or leukemia, and those receiving steroids or who are neutropenic.

Fusarium is present in water and on water-related surfaces in hospitals. Colonized hospital water systems have been identified as contributing to spread of infections.

Manifestations of disease include skin lesions, sinus and pulmonary disease, brain abscess, and dissemination.

Large increases in prevalence have been seen in some institutions. Mortality rates are high, ranging from 50 to nearly 100% in persistently immunosuppressed patients with disseminated disease.

Scedosporium species cause infections in the same patient populations as Fusarium, with HSCT recipients again at highest risk. Other molds that have been involved in outbreaks and clusters include Phialemonium species (associated with contaminated water systems and dialysis devices), Curvularia (contaminated water used for breast implants), Exophiala (contaminated hospital water; contaminated injected medications), and Paecilomyces (contaminated skin lotion).

Overview of important clinical trials, meta-analyses, case control studies, case series, and individual case reports related to infection control and non-Aspergillus molds.

See Table I.

Table I.

Selected published studies describing outbreaks caused by non-Aspergillus molds
Study Organism Outbreak cause
Rao C, 2009 Phialemonium curvatum Contaminated dialysis water system
Proia L, 2004 Phialemonium curvatum Hemodialysis-associated
Kainer M, 2005 Curvularia species Contaminated saline in breast implants
Nucci M, 2002 Exophiala jeanselmei Contaminated hospital water
Engemann J, 2002 Exophiala dermatitidis Contaminated injectable steroids
Itin P, 1998 Paecilomyces lilacinus Contaminated skin lotion

Controversies in detail.

The question of whether voriconazole exposure is a risk factor for mucormycete infections is controversial. The arguments on each side were recently reviewed.

Arguments for voriconazole exposure as a risk factor

A prospective single-institution study suggests that prior voriconazole prophylaxis was an independent risk factor for developing mucormycosis rather than invasive aspergillosis in patients with hematologic malignancies (odds ratio 10.37). Several other centers have reported an apparent rise in incidence of mucormycosis following the introduction of voriconazole.

An animal study suggests that exposure of Rhizopus oryzae to voriconazole increases the virulence of this fungus in an immunosuppressed mouse model of pulmonary zygomycosis. The increase in virulence did not occur with other azoles, and reverted when voriconazole was withdrawn.

This suggests that upregulation of virulence factor expression or an increase in adhesion could occur specifically with this drug-organism combination.

Arguments against voriconazole exposure as a risk factor

It is possible that risk factors associated with transfusions and high-dose corticosteroid use to treat graft versus host disease might predispose HSCT patients to mucormycosis in the late period (>3 months) after transplant, independently of voriconazole use.

Epidemiologic evidence suggests that the incidence of mucormycosis was already increasing prior to the widespread use of voriconazole.

For example, the incidence of mucormycosis was reported to have increased from 0.0079/1000 patient-days in 1999, prior to the introduction of voriconazole, to 0.095/1000 patient days in 2002-04. Furthermore, in a clinical trial comparing fluconazole and voriconazole in HSCT recipients, excess cases of mucormycosis were not demonstrated in the voriconazole arm.

Environmental sampling and interpretation of data

The role of environmental sampling, and the appropriate interpretation of sampling data, is controversial.

Very few data exist enumerating the levels of mucormycete sporangiospores in outdoor and indoor air. The numbers of spores appear to depend on the ability of the local climate to support growth and dispersal. Seasonal variations for some mold spore counts in some geographic regions have been reported.

Mucormycetes are relatively absent in studies of the fungi that can be cultured from indoor air samples in the United States, although one report of a Rhizopus outbreak associated with hospital linens suggests that mucormycetes in the environment can be linked to cases of disease. All these factors suggest that interpreting the results of local hospital environmental sampling is often difficult.

Isolation of a particular mold species from an environmental source should be taken as suggestive evidence, rather than definitive evidence, for the role of that environment as the source of disease. Furthermore, failure to identify a particular mold species in a given environmental sample does not mean that the fungus is not present in that environment.

Targeted environmental sampling could be considered in the context of an outbreak investigation, but has not been formally evaluated.

Environmental sampling in an outbreak investigation should be carefully planned, and factors to be considered should include choice of the appropriate sampler and analytical method, as well as selection of surfaces to be sampled, sampling period, sample volume, and sampling medium.

Culture-based methods of fungal identification often fail to identify all molds in a given environmental sample, because not all fungi in the sample are viable or will grow on the culture media employed.

Identification methods that use total conidia counts do not discriminate among fungal conidia from different genera. Novel nucleic-acid methods including quantitative polymerase chain reaction (qPCR) that can both enumerate and describe multiple fungal nucleic acids in a sample are being evaluated experimentally.

Environmental sampling during an outbreak investigation is helpful only if directed by epidemiologic data.

Steps that should be taken include maintaining a high index of suspicion for healthcare-associated mold infection in severely compromised patients, and conducting surveillance for mold infections by periodically reviewing the hospital’s microbiologic, post-mortem, and histopathology data.

An epidemiologic investigation should be conducted if one or more episodes of hospital-associated mold infections are detected.

Routine periodic surveillance cultures of patients (nasopharynx or nares) or of hospital environments (equipment and dust levels in rooms) are not informative of nosocomial transmission and are not encouraged. Infection control in acute-care hospital settings has recently been reviewed.

What national and international guidelines exist related to non-Aspergillus molds?

The guidelines that address prevention of non-Aspergillus mold infections include:

  • HICPAC guidelines for environmental infection control in healthcare facilities (2003).

  • HICPAC guidelines for preventing healthcare-associated pneumonia (2003).

  • Fungal infection prevention after hematopoietic stem cell transplantation (2009).

What other consensus group statements exist and what do key leaders advise?

The importance of fungus culture and histopathology in diagnosis of these diseases cannot be overstated. Key leaders recognize the need for more rapid and specific diagnostics for these organisms.

There is also a need for studies evaluating the role of newer antifungal drugs such as posaconazole and of combination antifungal therapy in treatment.


"Disclaimer: The findings and conclusions in this article are those of the author and do not necessarily represent the views of the CDC".

Cornely, OA. "Aspergillus to zygomycetes: causes, risk factors, prevention and treatment of invasive fungal infections". Infection. vol. 36. 2008. pp. 296-313.

Pongas, GN, Lewis, RE, Samonis, G, Kontoyannis, DP. "Voriconazole-associated zygomycosis: a significant consequence of evolving antifungal prophylaxis and immunosuppression practices?". Clin Microbiol Infect. vol. 15. 2009. pp. 93-7.

Antoniadou, A. "Outbreaks of zygomycosis in hospitals". Clin Microbiol Infect. vol. 15. 2009. pp. 55-9.

Rees, JR, Pinner, RW, Hajjeh, RA. "The epidemiologic features of invasive mycotic infections in the San Francisco Bay Area 1992-93: results of population based laboratory active surveillance". Clin Infect Dis. vol. 27. 1998. pp. 1138-47.

Nucci, M, Anaissie, E. "Fusarium infections in immunocompromised patients". Clin Microbiol Rev. vol. 20. 2007. pp. 695-704.

Anaissie, EJ, Kuchar, RT, Rex, JH. "Fusariosis associated with pathogenic Fusarium species colonization of a hospital water system: a new paradigm for the epidemiology of opportunistic mold infections". Clin Infect Dis. vol. 33. 2001. pp. 1871-8.

Nucci, M, Marr, KA, Queiroz-Telles, F. "Fusarium infection in hematopoietic stem cell transplant recipients". Clin Infect Dis. vol. 38. 2004. pp. 1237-42.

Rao, CY, Pachucki, C, Cali, S. "Contaminated product water as the source of Phialemonium curvatum bloodstream infection among patients undergoing hemodialysis". Infect Control Hosp Epidemiol. vol. 30. 2009. pp. 840-7.

Proia, LA, Hayden, MK, Kammeyer, PL. "Phialemonium: an emerging mold pathogen that caused 4 cases of hemodialysis-associated endovascular infection". Clin Infect Dis. vol. 39. 2004. pp. 373-9.

Kainer, MA, Keshavarz, H, Jensen, BJ. "Saline-filled breast implant contamination with Curvularia species among women who underwent cosmetic breast augmentation". J Infect Dis. vol. 192. 2005. pp. 170-7.

Nucci, M, Akiti, T, Barreiros, G. "Nosocomial outbreak of Exophiala jeanselmei fungemia associated with contamination of hospital water". Clin Infect Dis. vol. 34. 2002. pp. 1475-80.

Engemann, J, Kaye, K, Cox, G. "Exophiala infection from contaminated injectable steroids prepared by a compounding pharmacy-United States-July-November 2002". Morb Mortal Wkly Rpt. vol. 51. 2002. pp. 1109-12.

Itin, PH, Frei, R, Lautenschlager, S. "Cutaneous manifestations of Paecilomyces lilacinus infection induced by a contaminated skin lotion in patients who are severely immunosuppressed". J Am Acad Dermatol. vol. 39. 1998. pp. 401-9.

Kontoyannis, DP, Lionakis, MS, Lewis, RE. "Zygomycosis in a tertiary care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases". J Infect Dis. vol. 191. 2005. pp. 1350-60.

Siwek, GT, Pfaller, MA, Polgreen, PM. "Incidence of invasive aspergillosis among allogeneic hematopoietic stem cell transplant patients receiving voriconazole prophylaxis". Diagn Microbiol Infect Dis. vol. 55. 2006. pp. 209-212.

Vigoroux, S, Morin, O, Moreau, P. "Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: attention required". Clin Infect Dis. vol. 40. 2005. pp. e35-7.

Upton, A, Marr, KA. "Emergence of opportunistic mould infections in the hematopoietic stem cell transplant patient". Curr Infect Dis Repts. vol. 8. 2006. pp. 434-41.

Lamaris, GA, Ben-Ami, R, Lewis, RE, Chamilos, G, Samonis, G, Kontoyannis, DP. "Increased virulence of Zygomycete organisms following exposure to voriconazole: a study involving fly and murine models of zygomycosis". J Infect Dis. vol. 199. 2009. pp. 1399-1406.

Kontoyannis, DP, Wessel, VC, Bodey, GP. "Zygomycosis in the 1990s in a tertiary care cancer center". Clin Infect Dis. vol. 30. 2000. pp. 851-6.

Wingard, JR, Carter, SL, Walsh, TJ. "Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation". Blood. vol. 116. 2010. pp. 5111-8.

Richardson, M. "The ecology of the Zygomycetes and its impact on environmental exposure". Clin Microbiol Infect. vol. 15. 2009. pp. 2-9.

Shelton, BG, Kirkland, KH, Flanders, WD. "Profiles of airborne fungi in buildings and outdoor environments in the United States". Appl Environ Microbiol. vol. 68. 2002. pp. 1743-53.

Chang, DC, Blossom, DB, Fridkin, SK, Jarvis, WR. "Healthcare-associated fungal infections". Bennett and Brachman’s Hospital Infections. Lippincott Williams and Wilkins. 2007.

Sydnor, ERM, Perl, TM. "Hospital epidemiology and infection control in acute care settings". Clin Microbiol Rev. vol. 24. 2011. pp. 141-73.

"Guidelines for environmental infection control in health-care facilities". Recommendations of the Centers for Disease Control and Prevention and the Healthcare Infection Control Practices Advisory Committee. 2003.

"Guidelines for preventing healthcare-associated pneumonia". Recommendations of the Centers for Disease Control and Prevention and the Healthcare Infection Control Practices Advisory Committee. 2003.

Tomblyn, M, Chiller, T, Einsele, H, Gress, R, Sepkowitz, K, Storek, J, Wingard, JR, Young, J-AH, Boeckh, MJ. "(Executive Committee). Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Recommendations of the Center for International Blood and Marrow Transplant Research (CIBMTR®), the National Marrow Donor Program (NMDP), the European Blood and Marrow Transplant Group (EBMT), the American Society of Blood and Marrow Transplantation (ASBMT), the Canadian Blood and Marrow Transplant Group (CBMTG), the Infectious Disease Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the Association of Medical Microbiology and Infectious Diseases Canada (AMMI), and the Centers for Disease Control and Prevention (CDC)". Bone Marrow Transplantation. vol. 44. 2009. pp. 453-558.

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