Impact of nystatin on Candida and the oral microbiome

In a recent issue of Critical Care, Giglio and colleagues [1] reported that oral nystatin reduced Candida colonization in a cohort of critically ill surgical patients, even when colonization was present at baseline. Colonization is a prerequisite for systemic infection, which is associated with significant morbidity and mortality. Although it is possible to stratify individuals at risk of invasive fungal disease, diagnosing this condition is complex, and the present study [1] represents a potential mechanism for reducing the burden of fungal infection. Candida albicans has a complicated relationship with potential bacterial respiratory pathogens and augments their growth in mixed biofilms [2, 3]. Pseudomonas aeruginosa is unable to bind yeast forms of C. albicans but forms a dense biofilm on C. albicans filaments [3]. This is relevant to clinical investigations in which respiratory tract colonization with C. albicans is associated with an increased risk of Pseudomonas ventilator-associated pneumonia (VAP) [4], which is reduced with antifungal treatment [5]. One impact of nystatin on other infections, such as VAP caused by Pseudomonas or Staphylococcus, or indeed on other indices, such as length of stay and mortality, was not measured [1]. One might anticipate that the benefit of nystatin treatment will extend beyond infections caused directly by Candida, but there is an important caveat. Nystatin generally is used as a suspension with high sucrose content (49.8% wt/vol), and growth of oral plaque is driven by sugars. Dental plaque becomes colonized with potential respiratory pathogens in critically ill patients and is important in the etiology of VAP. Future studies, therefore, should investigate the impact of nystatin on the oral microbiome, VAP, and mortality.

Authors' response

Filomena Puntillo, Mariateresa Giglio, Nicola Brienza and Francesco Bruno

The relationship between bacteria and fungi is gaining interest since it has great environmental, medical, and economic importance. C. albicans favors P. aeruginosa and Staphylococcus aureus growth in mixed biofilms [3]. Fungal colonization increases the risk of Pseudomonas infection [4], and antifungal treatment reduces the risk of Pseudomonas VAP [5]. Therefore, it is intellectually appealing to use a simple antifungal prophylaxis regimen, such as the one recently proposed [1], to reduce the risk of Candida colonization and the risk of Pseudomonas and S. aureus VAP.

Unfortunately, the dynamics of bacterial-fungal interaction are poorly understood, and results in the literature are conflicting, since in vitro studies suggest an antagonistic relationship between C. albicans and P. aeruginosa while in vivo studies described a synergistic one In a murine model, a short-term C. albicans colonization reduces P. aeruginosa-related lung injury, and caspofungin can reverse this effect, depending on the time of administration [6].

We reviewed our data to investigate these interactions. Of 99 patients, 12 exhibited P. aeruginosa and Candida tracheal colonization (six patients in each group) whereas two (both in the C group) showed S. aureus and Candida tracheal colonization. These sparse data do not help to elucidate Candida-bacteria association. Nystatin prophylaxis significantly reduces Candida tracheal colonization [6], but no definite conclusions about nystatin impact on oral microbiome or about intensive care unit stay and mortality can be drawn. Larger trials are needed to study the potential benefit of nystatin prophylaxis on bacterial trachebronchial colonization. Moreover, since nystatin was administered in the nasogastric tube [6], it can be safely used without the risk of dental plaque increase and subsequent bacterial colonization.