Excerpt
Ventilator-associated pneumonia (VAP) remains the leading cause of nosocomial infection in the ICU despite increasing efforts to reduce it. Although most, if not all, VAP is due to bacteria, the role, if any, of fungal pathogens is unclear in immunocompetent hosts [
1]. Indeed, many studies have reported the presence of
Candida species in the lungs of immunocompetent, ventilated patients [
2‐
4], but the extent to which this presence is linked to authentic fungal pneumonia remains debated. Several reasons may account for these uncertainties. First of all, the diagnosis of pneumonia in mechanically ventilated patients is difficult whatever the microorganism. Clinical criteria for suspecting VAP are unspecific and microbial confirmation may, in some instances, be subject to caution [
1]. Second, some microbiology laboratories do not pursue the study of fungi when rapidly growing yeasts are found in respiratory samples. Third, if for bacteria the threshold of 10
3 or 10
4 CFU/mL for protected brush specimens or BAL, respectively, is now widely accepted to confirm VAP, no such threshold has been established for fungi. There is thus no gold standard routine method to diagnose
Candida pneumonia and the most accepted method relies on lung histology. Taken together, it is usually accepted that
Candida lung infection is quite rare in the ICU and that
Candida spp. in respiratory specimens should not be treated unless there is clear histological evidence for such an infection. Because histological sampling of the lung is rarely performed (whether it be during lung biopsy or on autopsy); it is possible that
Candida pneumonia remains unrecognized and hence under-diagnosed. The alternative is that
Candida pneumonia is simply not encountered in the ICU. This may be regarded as a futile debate. However, when presented with a clinical vignette of a mechanically ventilated patient with positive respiratory samples for
Candida, a substantial number of physicians would give antifungal treatment [
5]. Given the high incidence of
Candida-positive respiratory specimens in ventilated, ICU patients; this attitude may lead to excessive treatment, undue costs, and risk of increased resistance to antifungal agents. Although autopsy studies in cancer patients have identified some cases of
Candida pneumonia, exhaustive and convincing data in ICU patients is lacking. In this issue of Intensive Care Medicine, Meersseman and colleagues provide clear (and definite?) evidence for the absence of
Candida pneumonia in ICU patients [
6]. Over a two-year period, they were able to perform post-mortem examinations on 77% of their patients. It is indeed routine practice in their institution to perform autopsies for all patients who die in the ICU. This is already, in itself, an accomplishment for which authors should be commended! On the basis of the results of routine tracheal surveillance cultures, patients were classified as having or not
Candida spp in their respiratory tract. Diagnosis of
Candida pneumonia was established using a predefined procedure for pathologic examination of the lungs and rigorous histological criteria that included the presence of both pseudohyphae and budding yeasts with various amounts of acute inflammation. Patients were then divided into four groups: positive
Candida samples and pneumonia at autopsy, positive samples no pneumonia, negative samples with pneumonia at autopsy, and negative samples no pneumonia. With these definitions, no single case of
Candida pneumonia was found among the 232 patients autopsied, even in those (
n = 77) with pre-mortem positive samples for
Candida spp and histological signs of pneumonia. In these patients,
C. albicans was the most common species identified (55%). Overall rate of
Candida colonization in the whole population study (taking into account those without pneumonia at autopsy) was high, 53%. Antifungal therapy was used in only seven patients (9%) with
Candida spp in their airways, so the risk that unrecognised
Candida pneumonia was successfully treated is limited. One may argue that pneumonia was not seen, simply because the study was underpowered. Given the high incidence of
Candida colonization, one of the highest in the literature, and the number of patients with pneumonia, this possibility seems unlikely. Meersseman et al. [
6] thus provide convincing data on the absence of
Candida pneumonia. Rather than waiting for yet another study to confirm this, the next question could be why does
Candida colonization not lead to pneumonia? It is beyond the scope of this editorial to provide an in-depth explanation, but several points deserve attention. Recognition of
Candida species by professional phagocytes depends on a variety of receptors that are expressed on their surface, for example Toll-like receptors (TLR), mannose receptor, dendritic cell-specific adhesion molecule, and Dectin-1 [
7]. Knowing which receptors bind to the organism is important in determining the host immune response. TLR2 and TLR4 recognize
C. albicans and modulate the host defense. Recognition of the fungus in its yeast form by these TLRs induces mainly a Th1 cytokine pattern with high levels of IFN-gamma and TNF-alfa [
8]. This response controls the pathogen [
9,
10]. In addition, other experiments show that IFN-gamma favors the intracellular killing of the fungus after internalization in professional phagocytes [
11]. Conversely, only TLR2 is able to recognize the hyphae form of
C. albicans and induces the release of Th2 cytokines with high levels of anti-inflammatory cytokine IL-10 but no IFN-gamma. Such a pattern favors the dissemination of the fungus [
8]. Moreover, the mode of antigen presentation affects the development of the Th subsets and presentation by macrophages favored the generation of Th1 cells [
12]. Thus, because pulmonary macrophages constitute the first defense line against
C. albicans; one possible clue for the absence of
Candida pneumonia could be that
Candida predominates in its yeast form in the respiratory tract of ICU patients, thereby yielding a Th1 response enabling control of the fungi. …
