I hope you're doing well and enjoying the end of winter. I also hope that you'll find the following
article about the opportunistic fungi in the hospital environment by Dr. Harriet Burge both interesting
With best wishes,
Sources And Control Of Opportunistic Fungi In The Hospital Environment
By Dr. Harriet Burge, EMLab P&K Chief Aerobiologist and Director of Scientific Advisory Board
Opportunistic fungi attack people with severely compromised immune systems either resulting from
medical treatment or disease. Infections with these pathogens are increasing due to the increased
use of immunosuppressive medications and diseases such as AIDS that reduce immune competence.
Industrial hygienists, hospital infection control personnel, mold investigators and remediators
are more and more frequently being called upon to discover the sources of outbreaks of diseases
caused by these fungi. Unfortunately, while in other types of environments concentrations of
fungi must be relatively high to cause problems, in hospital settings where immunosuppressed
patients are housed, airborne concentrations of pathogenic fungi must be maintained at near zero
levels. Thus, even very limited growth may be important, and unusual sources must be investigated.
The Fungi Involved
The most common opportunist that is also the most frequent cause of disease is Aspergillus fumigatus,
a thermotolerant fungus that not only causes infections, but also colonizes the lungs of asthmatics
and people with cystic fibrosis. Other species of Aspergillus that are frequently reported
as pathogens are A. terreus, A. niger, and A. flavus. Aspergillus ustus
less frequently causes infection (Saracli et al., 2007). Fungi from other genera have also been
reported to cause opportunistic disseminated infections, including Scedosporium prolificans
(Alvarez et al., 1995), Geotrichum candidum (Scora et al., 2009), Mucor (Sochaj
et al., 2009), Pseudallescheria boydii (Thornton 2009), Blastoschizomyces capitatus
(Celik et al., 2009), Trichoderma longibrachiatum and closely related Hypocrea orientalis
(Druzhinina et al., 2008), and Absidia corymbifera (Parra-Ruiz et al., 2008). Candida
albicans, Pneumocystis carinii and other species of Pneumocystis, and
Cryptococcus neoformans are also important opportunistic pathogens. Candida is a
human commensal that attacks the host when immunosuppression occurs. However, the organism can
be transferred between patients and health care workers (Marco et al., 1999). Pneumocystis
probably does not grow in the hospital environment, although the fact that it is not culturable
may contribute to this perception. It can be readily detected through PCR methods and has been
recovered from air (Bartlett et al., 1997). Cryptococcus neoformans is extremely common
in the environment, and many people either have or have had subclinical infections. It may become
invasive and cause central nervous infections in immunosuppressed patients. This is extremely
common in AIDS patients.
The Array of Sources
Person to person transmission. Most fungal opportunists are not transmitted from one person
to another. Candida albicans is an exception as is Pneumocystis jerovecii, and
probably P. carinii as well. Candida is probably transferred between people by direct
contact (Buffington et al., 1994). On the other hand, Pneumocystis is airborne (Yazaki et al., 2009).
Construction. Outbreaks of aspergillosis (invasive Aspergillus infection) related
to hospital construction and remodeling have been reported repeatedly (e.g., Alvarez et al., 1995;
Ansorg et al., 1996; Lai 2001). As discussed below, outbreaks of infection can be avoided if proper
attention is paid to containment during construction activities.
Ventilation Systems. Arnow (1978) was one of the first to note the growth of Aspergillus
fumigatus in ventilation systems and the relationship of this growth to aspergillosis. His
group conducted environmental monitoring in a new hospital, culturing for Aspergillus
and conducting surveillance for aspergillosis cases (Arnow et al., 1991). After airborne
concentrations of Aspergillus flavus and A. fumigatus increased to average levels
>1 colony forming unit per cubic meter (cfu/m3) and the incidence of aspergillosis
increased, filters in the ventilation system were found to be heavily colonized with
Aspergillus fumigatus, and A. flavus was found within the hospital rooms.
Remediation reduced both airborne concentrations of these fungi and the incidence of
aspergillosis. Lutz et al. (2003) reported a similar situation, attributing the contamination to
deterioration of insulating material in variable air volume units.
As is the case in all buildings, cellulosic filters that get wet are inevitably colonized with fungi.
While Cladosporium is often the dominant type in these situations, Penicillium and
Aspergillus species have been recovered as well (Price et al., 2005).
Cleaning Activities. Cleaning activities clearly can raise Aspergillus concentrations
in hospitals as well as other sites. In one study, geometric mean concentrations before cleaning
were 5.5 cfu/m3 compared to 18.9 one hour after cleaning (P=0.0047) (Lee et al., 2007).
In another case, a vacuum cleaner used to clean the floor in a pediatric oncology/hematology ward
was found to be the source of Aspergillus fumigatus that led to an outbreak of infection.
During vacuum cleaner operation, Aspergillus fumigatus recoveries were 65 cfu/m3
compared to less than 6 cfu/m3 in rooms where this vacuum cleaner was not used (Anderson
et al., 1996).
Waste Containers. Hospital waste containers are an obvious potential source for all sorts
of infectious agents. Blenkharn (2006) found many organisms including Aspergillus species
in these reservoirs.
Plants. Controversy over potted plants as a source for fungal aerosols in hospitals has
existed for many years. Thompson et al. (1994) found Aspergillus in 80.5% of his samples
of potted plant soil. The most common species were Aspergillus fumigatus and A.
niger (Thompson et al., 1994).
Water Systems. Water can contain fungi, and water systems may become colonized.
Aspergillus species have been recovered from water taps, patient showers, and ice making
machines (Anaissie 2001). Anaissie et al. (2002) found significantly higher concentrations of
airborne Aspergillus propagules in bathrooms, where water use was highest (2.95 cfu/m3).
In a comparison of different kinds of water sources in hospitals, Kauffmann-Lacroix et al. (2008)
found that 52% of the cold water samples contained fungi while only 4% of the hot-water samples
had positive cultures. In two hospitals there was generalized growth in the water pipes; one with
Exophiala species and the other with Fusarium species. Otherwise, colonization was
usually minimal. Nucci et al. (2002) traced the source of infections with Exophiala jeanselmei
to deionized water in the hospital pharmacy as well as a water tank and a sink. Genetic
comparisons revealed that the cause of the outbreak of infection was the deionized water in the
pharmacy. In another interesting study, filamentous fungi were found in more that 94% of all
water samples taken in a hospital and all of the samples collected from the intake reservoir.
Eighty five percent of the intake reservoir samples contained Aspergillus fumigatus
suggesting that this was the source for the fungus in the hospital water. In a second study,
this group found that Aspergillus fumigatus strains from air were different genetically
from those in water, and that patients had been infected from both sources (Warris et al., 2003).
Matching Sources To Infection Outbreaks
Most of us have our own protocols for building investigations. Hospitals differ primarily in the risk
associated with exposure, and the need to document very low concentrations of specific organisms in air.
Anderson et al. (1996) describe the steps he took in one investigation where the source turned out to
be a vacuum cleaner.
- Identify all sources of air intake.
- Map dispersal routes of air throughout the hospital.
- Visit the site of the outbreak (i.e., specific rooms) on several days to evaluate activities that might be relevant.
- Discuss recent building records with building services managers and engineers.
- Consult external ventilation contractors regarding the overall function of the building ventilation.
- Collect samples in triplicate including at the intakes, inside, and exhausts of each of the mechanical
ventilation units and in each ward. Anderson's group sampled in 15 sites in the suspect ward including the
ceiling void, soft toys (encouraged to release aerosol by firm handling), and the exhausts of the ward vacuum cleaners.
Sampling is most often done using culture (since the organisms must be alive to cause infection).
Having found a possible source one can remove or remediate the source, then continue sampling to
document that the problem has been solved. However, to be sure that the actual source for the
ongoing infections has been identified, it is important to match environmental strains of the
fungi to those recovered from the patients. This is done using DNA fingerprinting. Unfortunately,
this is more complicated than it appears, at least for Aspergillus fumigatus. It appears
that this species is extremely diverse genetically (Symoens et al., 2002). Bart-Delabesse et al.
(1999) analyzed 62 environmental isolates to reveal 43 genotypes represented only once. Likewise,
isolates from patients were diverse. Chazelet et al. (1998) fingerprinted more than 700 clinical
and environmental isolates of Aspergillus fumigatus and found that 85% of the isolates
recovered from air represented different strains. To qualify as nosocomial (hospital acquired)
patients must be infected with an isolate found in the environment, or multiple patients at the
same site must be infected with the same genotype (Bart-Delabesse et al., 1999; Chazelet et al.,
1998). Chazelet et al. (1998) considers that the frequent lack of common strains among patients involved in an
outbreak is due to the extreme genetic diversity of Aspergillus fumigatus. It is also true
that the same strain can appear throughout a hospital, and can persist for many months (Girardin
et al., 1994) and that the same patient can be infected with more than one strain (Menotti et al., 2005).
Aspergillus flavus is less common than A. fumigatus, and infections in
patients appear to be more likely to match environmental isolates. Ao et al. (2007) matched
two patient isolates to two environmental strains of Aspergillus flavus. Three other
patients had strains that differed from those in the environment, but two of these patients
had the same strain. Thus, four out of five of these patients were assumed to have nosocomially
acquired infections. In another Aspergillus flavus case, Buffington et al. (1994) found
environmental strains in a patient and a health care worker, but different strains in two other
patients. Heinemann et al. (2004) investigated an outbreak of surgical site infections with
Aspergillus flavus. He found a single clone of the organism throughout the surgical
suite and in the patients. On the other hand, Leenders et al. (1996) found distinctly different
strains of Aspergillus flavus in a group of patients arguing against a hospital source
for the infections.
Outbreaks related to Aspergillus terreus have also been investigated. Lass-Flori et al.
(2000) was able to match Aspergillus terreus strains from potted plant soil to infections
in four patients.
Some people strongly recommend monitoring of the hospital environment in order to detect the
beginning of an episode of contamination. The problem is, how often and how extensive should
monitoring protocols be? Alberti et al. (2001) recommend monitoring for changes in the entire
fungal population (not just Aspergillus species) as this indicates the potential for
conditions that could lead to growth of opportunists. Falvey & Streifel (2007) found spikes
of Aspergillus associated with infection during a monitoring period and considered this
data useful in the search for sources. Monitoring protocols should include notation of activities
going on before or during the monitoring period. Some transient activities as well as conditions
that become chronic clearly affect aerosolization of fungi and the presence of these conditions
and activities help to focus on the source of spikes. On the other hand, monitoring may reveal
spikes not related to any apparent activity and may indicate the need for more extensive investigations.
Prevention of hospital contamination and patient infection is a multifaceted task. The outdoor
air must be filtered, the systems supplying outdoor air to the hospital environment must be
maintained so that they are water free, activities within the hospital that raise dust must be
minimized or isolated, and patients may have to be protected directly through medications and/or
masking. All of these precautions apply especially to immunocompromised patients.
HEPA filtration of the outdoor air is almost universally recommended (Araujo 2008; Benet et al.,
2007; Brenier-Pinchart et al., 2009; Falvey & Streifel 2007). Comparing outdoor air,
HEPA-filtered air and other hospital locations, Falvey & Streifel (2007) found Aspergillus
species in 95% of outdoor air samples, 33% of HEPA-filtered locations, and 50% of other hospital areas.
Laminar air flow is also sometimes used to protect immunocompromised patients, but it involves
high air exchange rates, is expensive, and causes noise and drafts (Humpfreys 2004).
Air purifiers and mobile units have been marketed to protect immunosuppressed patients either
routinely or under especially hazardous conditions. Poirot et al. (2007) tested a mobile unit
that provided an environment with no detectable airborne fungi regardless of levels outside of
the unit's influence. Bergeron et al. (2007) tested a mobile nonthermal plasma air treatment
unit that significantly reduced airborne spore concentrations. However, portable air filtration
units were not capable of significantly reducing air concentrations in rooms (Englehart et al.,
2003). Of course the amount of air processed per unit time and the amount of disturbance of dust
during unit operation would contribute to these results. On the other hand, compliance was poor
due to noise and thermal discomfort.
Protection from activities within the hospital that may produce fungal aerosols is extremely
important. Many hospitals have installed anterooms next to rooms housing at-risk patients in
part so that gowning and hand washing activities can take place outside of the patient's
environment (Araujo 2008; Brenier-Pinchart et al., 2009). Activity with rooms without anterooms
and other restrictions on aerosol production led to a direct correlation between activity and
fungal spore levels. On the other hand, aerosols in rooms with control measures were related to
outdoor concentrations, emphasizing the need for high quality filtration.
One activity in hospitals that is well known to produce fungal aerosols is construction. Many
approaches have been used to prevent construction-related outbreaks of aspergillosis in hospitals.
Most follow the same principles of containment that should be used for all occupied spaces. Given
the greatly enhanced susceptibility of immunosuppressed patients, additional efforts may need to
be made. Cornet et al. (1999) used laminar flow and HEPA filtration in rooms adjacent to the
construction and no Aspergillus was found in any subsequent air sample in these protected
spaces. In addition to HEPA filtration, Loo et al. (1996) used biocide containing paint and
non-perforated ceiling tiles, sealed all windows, replaced horizontal blinds with roller shades,
and called for systematic and regular cleaning of surfaces. With these efforts he was able to
reduce the incidence of aspergillosis to levels below pre-construction levels, and far below
those that had pertained during the initial phase of construction. Use of water to reduce
airborne dust concentrations in construction areas has been used, but the risk of mold growth
resulting from damp conditions must be considered (Berthelot et al., 2006). Daily particle count
measurements in high risk areas can encourage compliance with infection control measures during
construction (Prezant et al., 2005).
Finally, one can act directly at the patient level to prevent infection. Removing patients from
high risk areas and the use of well fitted masks are two approaches that are commonly used
(Maschmeyer et al., 2009; Chang et al., 2008; Berthelot et al., 2006; Raad et al., 2002). In
addition, some physicians use prophylactic anti-fungal agents in their patients to reduce the
risk of fungal infections (Chang et al., 2008).
There are currently no specific guidelines for acceptable concentrations of any individual
opportunistic fungus in hospitals. It appears that any guideline would have to be in a range
less than 1 cfu/m3 to be effective for immunocompromised patients. Alberti et al.
(2001) reviewed the literature on "safe" levels of Aspergillus. He found
opinions on decreased levels that ranged from 0.009 - <0.2 cfu/m3 (total
Aspergillus spores). On the other hand, risk appears to start increasing near 1 cfu/m3.
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