Candida colonization of respiratory tract: to treat or not to treat, will we ever get an answer?

Abstract

In non-immunocompromised intensive care unit (ICU)patients Candida isolation from various sites is common[1]. The association with the risk of invasive candidiasis(IC) is the rational for the use of predictive scores whichinclude the colonization status.However the meaning of Candida spp. recovery fromthe lung is definitely more intriguing. Apart from ICepisodes occurring in deeply immunosuppressed subjectswho may develop true fungal pneumonia, Candidarespiratory tract (RT) isolation should not be considered amarker of lung infection. This issue was addressed byMeersseman et al. [2] who did not identify any autopsy-proven case of Candida pneumonia among 135 autopsieswith histopathological evidence of bacterial infection andhigh rate of Candida isolation from endotracheal aspirate(EA) and/or bronchoalveolar lavage (BAL) (57 %).However there is growing convincing evidence, basedon animal studies and human observations, that Candidaspp. is not definitely an innocent bystander in the respi-ratory tract of ICU ventilated patients [3–13] (Table 1).Beta-glucan (BG), a component of yeast cell wall, mayact as a lung proinflammatory agent causing alveolarmacrophage and neutrophil dysfunction. Additionally,within the environmental biofilm there is a strong inter-play, through quorum-sensing (QS) molecules, betweenand both Gram-positive and Gram-negativebacteria [14]. Live Candida albicans instillation in ratshas been observed to increase the susceptibility to developexperimental Pseudomonas aeruginosa (PA), Escherichiacoli (Ec), and Staphylococcus aureus (Sa) pneumonia,fostering the production of lung inflammatory cytokines(tumor necrosis factor alpha [TNF-alpha], interleukin-6[IL-6], and interferon-gamma [INF-c]) and inhibitingalveolar macrophage phagocytosis [3, 5]. From a clinicalviewpoint, Candida airway colonization has been shownto be associated with prolonged duration of mechanicalventilation, ICU/hospital length of stay, and increasedmortality [8–11]. One of the first reports of this possiblerelationship dates back to almost 10 years ago, whenAzoulay et al. [6] identified Candida bronchial isolationas an independent risk factor for the development of PAventilator-associated pneumonia (VAP) (9 vs 4.8 % innon-colonized patients, p = 0.048). These data werestrengthened just 1 year later by Nseir et al. [7] whoobserved a protective role of antifungal treatment on PAVAP occurrence in a cohort of patients with Candidatracheobronchial colonization. However, recently, the useof nebulized amphotericin B (NAB) was not able toprovide any clinical improvement, albeit increasing therate of Candida decolonization (adjusted HR 2.2; 95 %CI 1.6–3) [13]. Hence the clinical usefulness of respira-tory tract Candida colonization (CC) eradication inmechanically ventilated patients is still a matter of debateand the paper by Albert et al. [15] in the current issue ofIntensive Care Medicine is the first interventional trialaiming to describe the biochemical and clinical effect ofantifungal treatment in ICU patients with VAP and RTCc. In this double-blind, placebo-controlled, multicenterstudy 60 patients were enrolled: 29 in the placebo groupand 31 in the antifungal strategy group. A comparative