Healthcare-Associated Fungal Infections

Rachel M. Smith

Scott K. Fridkin

Benjamin J. Park

INTRODUCTION

Over the past several decades, advances in medical and surgical therapy have changed the type of patients cared for in today’s healthcare facilities. In addition, advances in immunosuppressive agents, treatments for malignancy, chemotherapeutic agents, and bone marrow, stem cell, and solid organ transplantation have resulted in many immunocompromised individuals. Care provided in specialized units, including parenteral nutrition, broad-spectrum antimicrobials, and mechanical ventilation, have helped treat patients suffering from previously devastating diseases and provided life to neonates previously thought to be nonviable. These successes have resulted in more severely ill, immunocompromised patients who are highly susceptible to infections caused by fungi previously considered to be of low virulence or “nonpathogenic.” Fungal infections among these patients often are severe and difficult to diagnose and treat. In addition, changes in healthcare delivery, such as increased movement of care to the outpatient setting, are driving changes in the location these patients are treated, spreading the risk of invasive fungal infections well beyond the walls of the transplant unit of a short-stay acute care hospital.

Fungi are eukaryotic organisms, genetically more complex than bacteria, which can be categorized into two morphological forms: molds and yeast. Molds are multicellular fungi that reproduce via hyphae and have a characteristic wooly or cotton-like appearance in culture. Yeast are unicellular fungi that reproduce by budding and form smooth colonies in culture. Many fungi, such as Aspergillus spp., are acquired via inhalation of airborne conidia (commonly known as spores) from the environment; others, like Candida spp., are commensal residents of humans, causing true infection only under certain circumstances.

An appreciation of the unique features of healthcare-associated fungal infections is needed among clinicians, epidemiologists, and infection prevention staff (IPs) to best implement measures to prevent these infections. This chapter reviews the epidemiology of healthcare-associated infections (HAIs) caused by fungi, including surveillance, prevention, control, advances in diagnostics, antifungal susceptibility testing, and fungal molecular typing.

MOLD

INVASIVE ASPERGILLOSIS

Epidemiology

Aspergillus spp. infections cause substantial morbidity and mortality. A study using U.S. National Hospital Discharge Data from the 1990s estimated that >10,000 aspergillosis-related discharges occurred annually (1). These hospitalizations resulted in 1,970 deaths and $633.1 million in costs (1). In addition, excess length of stay was ˜12 days and excess cost was $50,000 compared with patients without aspergillosis (1). Although this large study, which relied on an administrative database, likely overestimated the number of patients with invasive aspergillosis annually (2), it does suggest that aspergillosisrelated hospitalizations are frequent and costly. A more recent study assessing the burden of aspergillosis to the healthcare system used patient-level data from a database of >2,200 hospitals across the United States and analyzed >1,800 admissions for aspergillosis (3). In this study, the in-hospital mortality was 36.7% with a median length of stay of 23 days costing in excess of $50,000 (3). Despite advances in antifungal therapy, 1-year mortality rates reported for invasive aspergillosis remain high, exceeding 50% among patients with solid organ transplants (4) and exceeding 70% among hematologic stem cell transplant (HSCT) patients (5,6).

The incidence of invasive aspergillosis is estimated to be in the range of 5% to >20% in high-risk groups (7). Aspergillosis has been estimated to occur after 6% to 11% of allogeneic HSCT (8,9,10,11) and in 1% to 15% of solid organ transplant recipients (11,12). The risk of invasive aspergillosis is lower after autologous HSCT, with reports describing a 1-year incidence rate of 1% to 2% (8). Some studies suggest that the incidence of Aspergillus spp. infection among allogeneic HSCT increased in the 1990s (9,13), perhaps due to more frequent use of high-risk donor sources and more intense immunosuppression. Data suggest that diagnoses during the postengraftment period could be occurring more frequently (8,10,13,14,15,16,17,18), perhaps due to decreased duration of neutropenia leading to decreased risk immediately postengraftment and increased survival beyond the early transplant period. Additionally, increased use of HLA-mismatched transplants, which increases the risk for graft vs. host disease (GVHD), also may be a contributing factor.

These measures of risk should only be considered estimates; assessing the incidence of invasive aspergillosis has inherent inaccuracies for a variety of reasons. Historically, the lack of a consistent case definition and absence of effective surveillance mechanisms made it difficult to compare incidence rates from different studies. This problem is not unique to aspergillosis, but applies to other invasive mold infections as well. Although an international consensus definition for opportunistic invasive fungal infections has been developed, these definitions were developed for multicenter clinical trials in HSCT or cancer patients (19). Multicenter epidemiologic studies, such as those coordinated by the Transplant Associated Infection Surveillance Network (TransNet), have adopted these definitions, which require evidence of histopathologic or microbiologic
evidence of tissue invasion to classify a patient as having “proven” disease; in the past, diagnosis of invasive aspergillosis and other invasive fungal infections could have required neither. Because these strict definitions require the use of more invasive diagnostic procedures that may not be performed in all patients, incidence estimates likely will underestimate the true burden of disease.

The most common Aspergillus spp. associated with infection is Aspergillus fumigatus followed by Aspergillus flavus (Table 44.1). Some recent reports have documented a shift in pathogen profile to a profile with more non-fumigatus species of Aspergillus. One example is A. terreus, which has been reported to have increased in some institutions (20,21,22,23). Infections due to A. terreus are concerning because these isolates demonstrate in vitro resistance to amphotericin B, and these infections often respond poorly to treatment (21,22,24,25). A. terreus has been isolated from showerheads, hospital water systems, and potted plants (26,27). While most bloodstream isolates of Aspergillus spp. represent pseudofungemia, A. terreus (as well as other fungi such as Fusarium, Scedosporium, and Acremonium spp.) isolated from blood cultures should be considered true disease until proven otherwise (23,28,29,30). The emergence of A. terreus could be due, in part, to improved means of laboratory recovery, altered microbial flora among patients with prior exposure to amphotericin B, and/or other unmeasured environmental factors.

TABLE 44.1 Frequent Sites of Infections and Common Pathogens for Healthcare-Associated Invasive Fungal Infections

Site of Infection	Fungal Pathogens
Bloodstream (CVC-related)	Candida spp. Rhodotorula spp. Trichosporon asahii Trichosporon mucoides
Bloodstream (regardless of CVC)	Aspergillus terreus Acremonium spp. Candida spp. Fusarium spp. Scedosporium spp.
Central nervous system	Aspergillus fumigatus Scedosporium spp.
Eye	Acremonium spp. Aspergillus spp. (A. fumigatus, A. nidulans, A. ustus, A. versicolor) Candida spp. Fusarium spp. Scedosporium spp. Zygomycetes (Rhizopus, Rhizomucor, Absidia)
Gastrointestinal tract	Candida spp.
Lungs	Aspergillus spp. (A. fumigatus, A. nidulans, A. niger, A. versicolor) Cunninghamella spp. Scedosporium spp.
Skin/soft tissue	Acremonium spp. Aspergillus spp. (A. fumigatus, A. nidulans, A. ustus, A. versicolor) Fusarium spp. Scedosporium spp. Zygomycetes (Rhizopus, Rhizomucor, Absidia)
Sinuses	Aspergillus spp. (A. flavus, A. fumigatus) Zygomycetes (Rhizopus, Rhizomucor, Absidia)
CVC, central venous catheter.

Clinical Disease

Risk Factors. Invasive mold infections, including invasive aspergillosis, usually occur in immunosuppressed persons. The groups at greatest risk remain those undergoing HSCT and those receiving cytotoxic chemotherapy. Allogeneic HSCT recipients are at high risk for invasive aspergillosis due to disruption of mucosal barriers, delayed engraftment, GVHD, and the use of steroids and broad-spectrum antibacterial agents (8,13,31,32). Recently, the presence of viral lower respiratory tract infections has been associated with an increased risk of invasive aspergillosis in HSCT patients (33,34). During the early period after transplant, neutropenia due to the conditioning regimen is the major risk factor for fungal infection, whereas immunosuppressive therapy for GVHD is the major risk factor during the postengraftment period (14). Solid organ transplant recipients are another group of patients at risk for invasive aspergillosis. The percent of solid organ transplant recipients developing invasive aspergillosis is highest among lung recipients (6% to 13%), followed by heart and liver transplant recipients (1% to 8%) (35,36,37,38), but is the lowest among kidney recipients (39). In solid organ transplant patients, the most important risk factor remains the net degree of immunosuppression due to immunosuppressive regimen (12,37).

IPs should be mindful that other immunosuppressed patients also are at risk for invasive aspergillosis—those with chronic lung diseases (i.e., chronic obstructive pulmonary disease), acquired immunodeficiency syndrome (AIDS), chronic granulomatous disease, and other hereditary immunodeficiency syndromes as well as those taking immunosuppressive medications such as high-dose corticosteroids (40). Numerous reports of invasive aspergillosis in patients receiving infliximab and other tumor necrosis factor (TNF)-a inhibitor therapies have been reported (41,42,43,44). The extent to which these therapies increase the risk of fungal infection remains to be established; however, vigilance in the care of these patients is essential while more data are accumulated. In these immunosuppressed groups, as well as HSCT and solid organ transplant recipients, it often is quite difficult to prevent environmental exposures to mold because these patients either are managed predominantly in the community or have prolonged periods of risk in nonhospital settings.

Clinical Diagnosis. The clinical sites of Aspergillus spp. infection may vary depending on the host. In the immunocompetent person, Aspergillus spp. can cause localized infection of the lungs or sinuses. In the immunocompromised patient, however, these pathogens often cause invasive disease of the lungs or sinuses and, because of their tendency to invade blood vessels, often spread to distant organs (Table 44.1).

Invasive infection often is suggested by compatible, but nonspecific, symptoms and signs in highly susceptible hosts (e.g., those with severe or prolonged neutropenia, those taking immunosuppressive medications including solid organ
transplant recipients and those with GVHD). Imaging studies often are essential to establishing a diagnosis. However, plain chest radiographs are nonspecific because findings compatible with aspergillosis overlap with other etiologies. Chest computerized tomography (CT) scan is more helpful. Compatible findings by CT scan usually precede those of plain films, and specific findings such as the halo sign (45) and air-crescent sign are more specific for Aspergillus spp. infection than findings on plain films; however, both can be seen in a variety of pulmonary pathology (46,47). Positron emission tomography (PET) can prove useful for the diagnosis and staging of invasive fungal infections, but currently remains a research tool (48,49).

Histopathologic evidence of tissue invasion by fungal elements is generally required to confirm a diagnosis of invasive aspergillosis. Blood cultures often are negative, even in episodes of widely disseminated disease (50,51). In contrast, sinus, sputum, or bronchoalveolar lavage (BAL) fluid can yield Aspergillus spp., but this may reflect either colonization or infection (52). However, among patients who are bone marrow transplant recipients and those who are neutropenic, the value of these cultures to predict disease can be as high as 75% to 80% (51), although it is likely much less among immunocompetent patients. Therefore, from a clinical standpoint, culture results should be evaluated in the context of the immune status of the host, clinical signs and symptoms, and supporting diagnostic evidence for invasive disease.

The nonspecific presentation of invasive mold infections and poor performance of standard diagnostics have spurred interest in other methods for diagnosing these infections. Briefly, several categories of nonculture-based tests may be useful to the clinician in diagnosing invasive mold infections, especially aspergillosis (53). However, these tests by themselves are not adequate for a definitive diagnosis of invasive mold infections, or for surveillance or reporting purposes. Measurement of serum (1,3)-beta-D(β-D)-glucan, a polysaccharide present in most fungal cell walls, has been used as a screening tool for invasive aspergillosis despite issues with specificity. In 2004, the U.S. Food and Drug Administration (FDA) approved a commercial test, Fungitell^TM (Associates of Cape Cod, Inc., East Falmouth, Massachusetts), for the detection of invasive fungal infections. With few exceptions, studies have shown Fungitell^TM to have high sensitivity for detecting Aspergillus (54,55,56) or Candida spp. (54,55,56,57); the test does not detect mucormycetes and has limited detection of Cryptococcus spp. due to the absence or low levels of (1,3)-β-D-glucan in these fungi.

A commercial enzyme immunoassay to detect Aspergillus galactomannan circulating in human serum (Platelia Aspergillus EIA, Bio-Rad Laboratories, Redmond, Washington) was FDA-approved in 2003 for the diagnosis of invasive aspergillosis. The Infectious Disease Society of America (IDSA) clinical practice guidelines for aspergillosis endorsed the use of galactomannan testing as a “useful adjunctive test to establish an early diagnosis,” especially in high-risk patients (58). This test and the (1,3)-β-D-glucan assay can provide laboratory evidence needed by clinicians to determine whether to treat a patient for invasive aspergillosis, and the European Organization for Research and Treatment of Cancer/National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) has incorporated both tests in their diagnostic criteria for invasive aspergillosis (59). The limitations of the galactomannan assay include potential for false-positive results in patients exposed to β-lactam antibiotics (60,61,62,63) as well as the lack of agreement on the cutoff value for a positive result. Additionally, although experimental use of galactomannan has been increasingly described in specimens of other body fluids, including urine, BAL, and cerebrospinal fluid, routine use in nonserum samples is discouraged (64).

In addition, research on the detection of Aspergillus DNA in human specimen using polymerase chain reaction (PCR) techniques is ongoing. A recent meta-analysis on the use of PCR for Aspergillus spp. diagnosis included data from 16 studies and >10,000 whole-blood or serum samples. While the diagnostic accuracy and sensitivity of a single PCR test were high (diagnostic odds ratio of 16.41 and sensitivity of 88%), significant heterogeneity existed among study populations, limiting the conclusions drawn from these pooled results (65). Additionally, no standard PCR protocol for the detection of Aspergillus spp. exists, making validation studies difficult. At this time, PCR techniques for the diagnosis of Aspergillus spp. remain a tool for research settings only.

OUTBREAKS OF ASPERGILLUS

Likely Sources and Routes of Exposure

Infection with Aspergillus spp. requires an exposure to the fungus from the environment in a susceptible host. It often is impossible to link specific exposures to disease, especially in sporadic episodes. Regardless, an understanding of the sources and routes of exposure associated with healthcare-associated aspergillosis, based largely on reports from outbreak investigations (Table 44.2), has contributed to the rational basis for the development of evidence-based preventive measures. A review of healthcare-associated aspergillosis reviewed 53 reported outbreaks in 458 patients. The majority (65%) of outbreaks occurred in HSCT patients or patients with other hematologic malignancy, followed by solid organ transplant patients (10%) (66).

Inhalation of Aspergillus spp. conidia from contaminated air is thought to be the primary means of acquiring aspergillosis. If dispersed into the air by disturbing soil, where they are commonly found, conidia are able to remain viable for prolonged periods of time. Because fungal conidia are relatively small (<10 pm in size), they can be suspended in air for extended periods, settle on other surfaces, or subsequently be inhaled. When conidia eventually settle, they can contaminate environmental surfaces in the hospital or be aerosolized again following disturbance of the surface.

The best evidence implicating contaminated air as a source of exposure comes from multiple outbreaks temporally associated with demolition, renovation, and construction projects (66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92) both within or adjacent to healthcare facilities. Malfunctions of hospital ventilation systems, which can allow contaminated air into patient areas, also have been implicated in the development of healthcare-associated fungal infections during construction (77,84,87,93,94). A hospital ventilation system can malfunction in multiple ways owing to gaps between filters and framework (84), inappropriate air pressurization allowing flow of air from dirty to clean areas (87,93), or improper maintenance of high-efficiency particulate air (HEPA) filters. Lutz et al. found direct contamination of an air-handling system by using a confined-space video camera to identify moisture and contaminated insulating material in ductwork downstream

of final filters associated with an operating room after an outbreak of postsurgical infections (94). Contaminated air has also been reported as a result of improperly sealed windows (74,87), use of fire-proofing material (95), presence of false ceilings (67,72,75,96,97,98), and insulating material (94,98,99).

TABLE 44.2 Selected Published Outbreaks of Aspergillus spp. in Healthcare Facilities, 1990 to 2012

Author (year, country)	Patient Population	No.	Primary Site(s)	Species	Probable Source	Control Measures Recommended or Applied
Pelaez et al. (2012, Spain) (88)	Cardiac ICU	7	LRTI, mediastinitis	A. fumigatus	Construction	ICU closed for 1 month with HEPA filters installed
Mueller et al. (2009) (370)	Transplant recipients	5	Transplanted organs	A. fumigatus	Donor	Rapid notification of recipients
Kidd et al. (2009, Australia) (371)	Hematology	3	LRTI	A. fumigatus	Undetermined	Improved infection control measures; ICU closed and cleaned; faulty structures replaced
Chang et al. (2008, Australia) (89)	Hematology	6 LRTI	A. fumigatus	Construction	Unit relocation; impermeable barriers at construction site; N95 face masks for patients during transport; voriconazole prophylaxis for other high-risk patients; relocation of patient garage
Rodigo et al. (2007, Sri Lanka) (115)	Obstetric	6	Meningitis	A. fumigatus	Contaminated syringes and spinal needles, poorly maintained storage area	Withdrawal and incineration of all unused syringes
Raviv et al. (2007, Israel) (90)	Transplant	8	LRTI, endophthalmitis	A. fumigatus, A. flavus, A. terreus, A. niger	Construction	Not reported
Saracli et al. (2007, Turkey) (92)	Ophthalmology	3	Endophthalmitis	A. ustus	Construction	Not reported
Kronman et al. (2007, USA) (372)	Pediatric cardiac ICU	3	SSI	A. fumigatus	Undetermined	Cleaning of all involved rooms; HEPA vacuuming areas; mold inspection; evaluation and improvement of infection control practices
Panackal et al. (2006, USA) (91)	Hematology	6	SSI, LRTI	A. ustus	Construction	Not reported
Heinemann et al. (2004, Belgium) (116)	Cardiac ICU	9	SSI	A. flavus	Water damage	Cleaning; disinfection of ORs; repeat environmental surveys
Panackal et al. (2003, USA) (81)	Renal transplant	7	LRTI	A. fumigatus	Construction	Impermeable barriers; HEPA filters in HVAC system; N95 respirator use during patient transport; reduce traffic; designated elevator for construction workers
Myoken et al. (2003, Japan) (373)	Hematology	6	Stomatitis	A. flavus	Undetermined	Not reported
Lutz et al. (2003, USA) (94)	Surgical	6	SSI	A. fumigatus, A. flavus	Air-handling system, moist insulation	Remediation of air-handling unit: remove interior insulation; coat units with fungicide; cleaning diffusers
Pegues et al. (2002, USA) (118)	Transplant ICU	3 SSI, LRTI	A. fumigatus	Debriding and dressing wounds	Minimize disruption of wound; keep wound covered
Hahn et al. (2002, USA) (374)	Hematology-oncology	10	LRTI	A. flavus, A. niger	Contaminated wall insulation from non-BMT wing	Impermeable barriers; decontamination of wall insulation; HEPA filters in non-BMT wing
Oren et al. (2001, Israel) (80)	Hematology-oncology	10	LRTI	Not reported	Construction, renovation	Prophylaxis with low-dose systemic and inhaled amphotericin B and systemic; locate patients in special ward with HEPA-filtered air
Lai (2001, USA) (76)	Hematology-oncology	3	LRTI	A. flavus	Construction	BMT unit closed for 2 weeks; air intake ducts cleaned; filters and prefilters replaced; impermeable barriers; alarm installed and air pressure made negative in stairwell leading to construction site; edge guards around doors to anterooms; carpeting replaced by vinyl flooring; special unit that allowed breathing filtered air during patient transport
Burwen (2001, USA) (70)	Hematology-oncology	6	LRTI	A. flavus	Construction	Identify high-risk patients and locate in rooms with HEPA or laminar airflow
Thio et al. (2000, USA) (141)	Hematology-oncology	21	LRTI	A. flavus	Adjacent connected hospital with higher air pressure than unit	Stop elective admissions; plants and produce prohibited in patient rooms; doors connecting to adjacent hospital engineered to close automatically; wipe or mop all surfaces wet; maximize pressure relationships; doors to individual patient rooms kept closed; N95 masks for neutropenic patients during transport; resealed windows; employee entrance near construction area closed
Gaspar et al. (1999, Spain) (71)	Hematology-oncology	11	LRTI	Not reported	Construction	Sealing of construction area; patients relocated
Tabbarra and al Jabarti (1998, Saudi Arabia) (85)	Cataract surgery	5	Eye infection	A. fumigatus	Construction	Not reported
Singer et al. (1998, Germany) (375)	NICU	4	Skin infection	A. fumigatus, A. flavus	Latex finger stall attached to penis to collect urine samples from male preterms	Removal of finger stalls
Loo et al. (1996, Canada) (78)	Hematology-oncology	36	LRTI, sinusitis	A. flavus, A. fumigatus	Construction	Portable HEPA filter units; copper-8-quinolinolate-formulated paint to walls, doors, baseboards, vents, and above false ceiling; windows sealed; replacement of perforated ceiling tiles with nonperforated, vinyl-faced aluminum tiles; horizontal dust-accumulating blinds replaced with roller shades; temporary relocation of patients
Leenders et al. (1996, Netherlands) (376)	Hematology-oncology	5	LRTI, sinusitis, eye infection, mastoiditis	A. fumigatus, A. flavus	No single source	Reinforce policies for maintaining HEPA-filtered rooms; keep windows closed at all times
Bryce et al. (1996, Canada) (68)	Surgical and burn units	4	Skin infection	Not reported	Construction, contaminated packages of dressing supplies	Sealing off construction area; supply room damp-dusted and vacuumed; boxes and supplies wiped with cloth with buffered bleach
Tang et al. (1994, UK) (377)	Renal transplant unit	2	LRTI	A. fumigatus	Construction	Impermeable barriers
Iwen et al. (1994, USA) (74)	Hematology-oncology	5	LRTI	A. fumigatus, A. flavus	Construction	Multiple measures prior to construction; environmental monitoring with gravity air-settling plates during construction; guiding additional measures
Buffington et al. (1994, USA) (69)	Hematology-oncology	7	LRTI	A. fumigatus, A. flavus	Construction	HEPA filters; proper pressure relationships; physical barriers; area decontamination
Tritz et al (1993, USA) (378)	Hematology-oncology	4	LRTI	A. terreus, A. fumigatus	Not reported	Not reported
Flynn et al. (1993, USA) (93)	Hematology-oncology, medical ICU	4	LRTI	A. terreus	Construction, improper air pressure relationships	Reestablish positive pressure and unidirectional airflow in ICU
Richet et al. (1992, USA) (379)	Open heart surgery	6	SSI	A. fumigatus	Undetermined	Not reported
Pla et al. (1992, Spain) (380)	Liver transplant	2	SSI	A. fumigatus	Contaminated operating room	Not reported
Loosveld et al. (1992, Netherlands) (381)	Hematology-oncology	6	LRTI	A. fumigatus	Cracked plasterwork	Renovation of plastering; HEPA filters installed in each room; intensified cleaning procedures
Humphreys et al. (1991, UK) (99)	General ICU	6	LRTI	A. fumigatus, A. flavus	Perforated metal ceiling with contaminated insulation	Extensive cleaning of ICU; temporary relocation of patients; old ICU replaced by new ICU with enhanced ventilation system and without false ceilings
Arnow et al. (1991, USA) (96)	Hematology-oncology, solid organ transplant	15	LRTI	A. flavus, A. fumigatus	Contaminated air filters	Remediate air-handling unit; removal of contaminated air filters; damp-wipe surfaces in patient areas; remove carpet
Weber et al. (1990, USA) (86)	Hematology-oncology	18	LRTI	Not reported	Construction	Not reported
Mehta (1990, India) (382)	Open heart surgery	4	Endocarditis	A. fumigatus	Air-handling system, broad-spectrum antibiotics	Weekly scrub of V filters and cooling coils; replacement of filters with series of prefilters and HEPA filters; increase air changes; restriction of broad-spectrum antibiotics
LRTI, lower respiratory tract infection; SSI, skin and soft-tissue infection.

Dust particles disturbed during demolition, renovation, and construction could subsequently contaminate other surfaces in the healthcare setting. In one Aspergillus outbreak, a fire that had destroyed a building near the hospital was thought to have dispersed conidia through an open window, contaminating a hall carpet, which was believed to be the ongoing source of infection (100). Wound infections due to Aspergillus spp. have been traced to the outside of packages of dressing supplies in a central supply area that were contaminated during construction (68). Two outbreaks of pseudofungemia associated with construction have occurred when laboratory specimens were contaminated (97,101). In one of these pseudo-outbreaks, a breakdown in specimen-processing protocols was noted (97).

Attempts to correlate conidial air concentrations with disease or colonization have produced mixed results. One study found a correlation between incidence of invasive aspergillosis in immunocompromised patients and the indoor air concentration of conidia (96). However, two longitudinal studies found no correlation between concentration and sporadic episodes (102,103). Additionally, a study evaluating mold contamination in patient areas during hospital construction demonstrated no influence of construction work with airborne Aspergillus spp. contamination in the setting of appropriate protective measures (104). Currently, there is no established consensus on a safe concentration of airborne conidia (105,106).

Much debate surrounds the role of hospital water systems as a source for airborne molds, including but not limited to Aspergillus spp. (26,107,108,109,110). Aspergillus spp. have been isolated from hospital and municipal water supplies in several countries, including the United States (26,109,110,111,112,113

Only gold members can continue reading. Log In or Register to continue