Preventing Fungal Infection: Does Clean Air Matter?

Abstract & Commentary

By J. Peter Donnelly, PhD, Clinical Microbiologist, University Hospital, Nijmegen, The Netherlands, Section Editor, Microbiology, is Associate Editor for Infectious Disease Alert.

Dr. Donnelly is a consultant for Ortho Biotech, and does research for Janssen, Merck, Novartis, Numico, Pharmacia, and Pfizer.

Synopsis: Systematic review of 16 studies showed HEPA filtration appeared to help reduce the incidence, but did not influence mortality, of fungal infections among patients treated for acute leukemia or receiving a haematopoietic stem cell transplant.

Source: Eckmanns T, et al. The Influence of High-Efficiency Particulate Air Filtration on Mortality and Fungal Infection Among Highly Immunosuppressed Patients: A Systematic Review. J Infect Dis. 2006;193:1408-1418.

It is widely accepted that vulnerable patients are best protected from acquiring invasive mold diseases by placing them in a protected environment, supplying sterile air by means of HEPA filtration with or without laminar air flow (LAF). However, there is little to support this contention. To rectify this, Eckmanns and colleagues undertook a metaanalysis of studies in this area. They found only 16 formal trials of this type of protected environment involving nearly 1000 subjects. These had been admitted to 7 centers in the United States, and 5 elsewhere, for an HSCT or for chemotherapy of acute leukemia. Each study was scrutinized, and the data were subjected to meta-analysis to evaluate the efficacy of this measure in lowering the occurrence of invasive fungal diseases and mortality. Only 8 studies were randomized, controlled trials (RCT), and only 3 reported on both measures. While there was a reduction in the incidence of invasive fungal disease in 9 of the 10 studies that reported these data (see Figure 1), the difference was only significant for the 4 that were RCTs. HEPA filtration/LAF led to reduced mortality in 5 of 9 studies (see Figure 2), but did not significantly reduced the relative risk of death among neutropenic patients treated for hematological malignancies, whether the studies were randomized, controlled trials (8 studies; RR = 0.86, 95%; CI = 0.65-1.14) or not (8 studies, RR = 0.87, 95%; CI = 0.60-1.25). So whilst employing HEPA/LAF appears beneficial, unequivocal evidence to support this type of facility is still waiting to be gathered.


The question of whether or not HEPA filtration/LAF should be used to create a protected environment for patients at risk of developing invasive fungal diseases — namely being treated for cancer and are receiving hematopoietic stem cell and solid organ transplants — is a real and an expensive one. Most centers dealing with these patients push hard for the best facilities supplied with HEPA filtered air to keep out fungal spores. On the face of it, this is not unreasonable, as the air is loaded with the very fungal spores that are inhaled by the patients that lead to invasive fungal diseases. Also, common sense dictates that if the air is the bearer of deadly spores, then patients ought to be protected while they are at their most vulnerable (ie, in hospital for intensive chemotherapy, with or without radiation therapy, for cancer or to prepare for an HSCT). Moreover, the experts who drafted the CDC/IDSA guidelines ( strongly recommend "All allogeneic recipients should be placed in rooms with > 12 air exchanges/hour and point-of-use HEPA filters that are capable of removing particles > 0.3 µm in diameter" (ie, fungal spores). And again "Correct filtration is critical in HSCT centers with ongoing construction and renovation." However, they did so on the basis of expert opinion only. Why?

First, invasive fungal diseases can be devastating for the patient, his or her family and friends, other patients and their carers, and it is costly in many ways. Second, treatment is still often given too late because of the difficulties in confirming the diagnosis. Third, there is no approved broad-spectrum antifungal prophylaxis. That leaves only one measure that hospitals can take — reducing exposure to the offending spores. In the series of published studies, however, times have changed, even since 2000 when these recommendations were published, not least because of tighter budget control and the climate of evidence-based medicine to help decide between competing priorities. Consequently, a report like that of Eckmanns et al would be seized upon for showing that there is a lack of the evidence, even though Eckmanns et al have very carefully stated that no definite conclusions could be drawn from the data. The gauntlet has been thrown to the ground and awaits a group of intrepid researchers to take up the challenge. In the meantime, the original recommendation of the CDC/IDSA should stand until evidence to the contrary is actually found.