Prevention of nosocomial aspergillosis

Prepared for the Aspergillus website by:

Dr Amanda J. Barnes
Consultant Microbiologist
St James's University Hospital,
Beckett Street,
Leeds LS9 7TF, UK

July 2000

Introduction:

The prevention of nosocomial aspergillosis is problematic, not least because recent years have seen an inexorable increase in the numbers of highly immunocompromised patients potentially at risk in a hospital environment. Neutropenic patients, notably allogeneic transplant recipients, are at risk for invasive infection; but recent reports also highlight the occurrence of disease due to Aspergillus species in neonates, and other categories of immunosuppressed patients, including renal and rheumatology patients on aggressive immunosuppressive regimens and patients with late-stage HIV disease (8-12). In addition, implementation of preventive measures may be costly, disruptive, and involve diverse groups of hospital personnel. There are currently no UK or European guidelines in this area, so much of this article is based on the US, CDC Guidelines, updated in 1997 (1).

What follows is an attempt to briefly summarise those guidelines on prevention of nosocomial aspergillosis, and to highlight some of the difficult issues which may arise - issues which have led some experts to ask whether the prevention of invasive aspergillosis IA) is even an realistic aim (3).

Risk factors for infections with Aspergillus spp:

Infection depends upon the interplay between host susceptibility, and environmental exposure. Those at risk are first, patients with severe granulocytopenia, whether leukaemics undergoing remission-induction chemotherapy, or recipients of allogeneic or autologous transplants of bone marrow or peripheral blood stem cells. Secondly, patients receiving solid organ transplants, the risk varying according to the organ transplanted, highest in those undergoing lung transplantation for cystic fibrosis. In addition, other factors are known to predispose to invasive aspergillosis: long-term corticosteroid use, diabetes mellitus, major burns, alcoholic liver disease, and recent major surgery. The most important nosocomial infection due to Aspergillus species is pneumonia : most of the hospital outbreaks of aspergillosis have involved pulmonary disease and have occurred in bone marrow transplant units.

Sources of Aspergillus species:

The species of Aspergillus documented to cause infection in the setting of nosocomial infection include A fumigatus, A flavus and A terreus. Unsurprisingly, given the ubiquitous nature of Aspergillus spores in the external environment, numerous reservoirs have been identified in hospitals: unfiltered air; ventilation systems; contaminated dust dislodged during hospital construction; carpeting (and a ward vacuum cleaner - 13) ; food, and ornamental plants (1,2,6-8, 13).

Aspergillus spores are very well adapted to airborne dissemination, and this is the route by which at-risk patients acquire infection. Clearly, patients may be colonised with Aspergillus species from their home environment, the invasive infection only being detected later during neutropenia. Nevertheless, the presence of aspergilli in the hospital environment is the major extrinsic risk factor for the occurrence of nosocomial IA (2,4,6,7).

Sources of infection: endogenous versus exogenous

A major issue in the prevention of nosocomial aspergillosis is the question of whether infection in an individual patient was acquired in hospital, or in the community: our most energetic prevention efforts in the hospital will not prevent the latter. There are many uncertainties in this area, not least the incubation period of the disease (estimated to vary from 48 hours to 3 months). Some light has been shed by the use of molecular typing methods (2,15,16,19). If the criterion used for "hospital-acquired infection" is the isolation of the same fungal strain from the patient and the environment, some 40 % of cases of invasive aspergillosis appear nosocomial (19). Further use of increasingly accurate typing methods will help to elucidate this question in the future.

Prevention of nosocomial aspergillosis:

Outbreaks of nosocomial aspergillosis occur mainly among neutropenic patients. These have occurred in association with environmental disturbances: hospital construction; contaminated fire-proofing materials, or air filters in the hospital ventilation system; contaminated carpeting.

Routes of transmission: airborne route

The first evidence for the protective effect of air filtration came from Sherertz and colleagues. The recognition of a high incidence of aspergillosis in the hospital's BMT patients led to the installation of high-efficiency particulate air (HEPA) filters. This was associated with a dramatic fall both in environmental counts of Aspergillus sp, and in cases of invasive disease (14).

Rhame, writing in 1991, identified at least 25 outbreaks of nosocomial aspergillosis, and cited three hospitals "reporting a decline in endemic nosocomial aspergillosis coincident with improvements in ventilation which produced lower ambient spore concentrations".(4) Moreover, these three reports show that modern ventilation and filtration systems are capable of dramatically reducing aspergillus spore counts.(4,7)

In summary, the prevention of nosocomial aspergillosis involves the proper installation, use, and maintenance of ventilation systems; and the elimination of exposure to fungal spores generated by construction.(1,15,16) The environmental controls required to protect vulnerable patients are detailed in the CDC recommendations, shown in tables 1 and 2. Table 1 shows the measures needed to minimize exposure to fungal spores to produce the "protected environment" required for neutropenic patients: essentially HEPA filtration, directed air flow, positive pressure, a well sealed room, and high rates of room air changes.

Table 2 contains the full guidelines on prevention and control. Section 4 pertains to existing facilities with no cases of nosocomial aspergillosis: a couple of additional points may be made. It is worth emphasising the importance of preventing dust-accumulation by daily damp-dusting of horizontal surfaces. Some authorities feel that mould proliferation around sink outlets, etc, may represent another environmental reservoir: so water leaks should be cleaned up and repaired. BMT units should minimize exposure of patients to activities such as carpet cleaning or vacuuming, that may cause aerosolization of Aspergillus spores, and the ward vacuum cleaner should be fitted with HEPA filters.

When construction is undertaken, the measures suggested to protect vulnerable patients include the use of impermeable barriers between patient care and construction areas; directing pedestrian traffic away from the area to prevent dust dispersal; and cleaning of the new premises before patients are moved there. Finally, air and environmental monitoring for spores may be indicated when building works are taking place adjacent to an area housing high-risk patients.

Is water a source of Aspergillus?

At this point, we should consider the recent suggestion that hospital water supplies may be a source of Aspergillus species spores. Anaissie and colleagues initially reported that Aspergillus spp could be recovered from water supply structures. They went on, in an abstract presented at the 39th ICAAC, to describe the results of air sampling carried out in a patient's room with the shower on and off: counts were higher in the bathroom, and in wet air versus dry. They concluded that showering resulted in aerosolization of spores and was a potential source of exposure (17). The Norwegian-led group of Warris and colleagues carried out a study in a paediatric BMT unit, sampling water from the taps in the unit as well as the mains supply. Filamentous fungi were recovered from all water samples, Aspergillus fumigatus from 60 % of tap samples (18). These results are of considerable interest, but larger scale studies are required.

TABLE 1

TABLE 2: Prevention & control of nosocomial pulmonary aspergillosis:

Abbreviations:

HEPA = high efficiency particulate air
BMT = bone marrow transplant
IA = invasive aspergillosis

UNRESOLVED QUESTIONS:

As mentioned initially, there are many problems in the area of prevention of nosocomial aspergillosis. Some of these are outlined below, to raise discussion rather than to provide answers!

2. How to protect patients outside the protected environment?

4. What is the role of air sampling in infection control?

References:

back to index