CLINICAL SYNERGISM: COMBINED FUNGAL AND BACTERIA INTRA-ABDOMINAL INFECTIONS ASSOCIATED WITH INCREASED MORTALITY
OBJECTIVES: Multiple synergistic interactions have been identified between fungi and bacteria, including coaggregation into mixed biofilms, enhanced growth via signaling molecules, and shared metabolic byproducts. However, the clinical implications of these interactions are largely unknown. While fungal and bacterial co-infection is common in complicated intra-abdominal infections (IAI), outcomes from combined infection have not been well studied. We hypothesized that synergistic interactions between fungus and bacteria would lead to higher mortality in patients with combined IAI.
METHODS: All surgical patients admitted to a single academic institution between 1996 and 2014 were queried for presence of a culture-proven bacterial IAI. Univariate analyses compared characteristics between patients with a combined fungal and bacterial IAI and those with bacterial IAI alone. Multivariable logistic regression evaluated the effect of fungal presence in IAI on in-hospital mortality, while controlling for APACHE II score and select comorbidities. A subgroup analysis evaluated unadjusted mortality rates for common fungal-bacterial combinations.
RESULTS: Of 1887 patients with culture-proven bacterial IAI, 503 (26.7%) were co-infected with fungi. Patients with a fungal component were older (57.0 vs. 55.5 years, p=0.025) with a higher median APACHE II score (15 vs 13, p < 0.01) but without differences in trauma or transplant status or comorbidities including diabetes, coronary artery disease, liver disease or kidney disease. The most common bacterial pathogens were Enterococcus spp. (25.6%), E. coli (16.9%) and Streptococcus spp. (12.0%). The most common fungal pathogens were Candida albicans (40.4%) and Candida glabrata (24.9%.) The presence of fungal species was associated with increased crude in-hospital mortality (16.9% vs. 9.8%, p<0.01), and on multivariable regression, fungal co-infection remained associated with death (Table).
The highest mortalities were associated with fungal co-infection with Enterobacter spp. (28.6%), Enterococcus spp. (28.3%), and P. aeruginosa (26.3%).
CONCLUSION: We identified an association between fungal presence and in-hospital mortality in patients with bacterial IAI. Continued research into cross-kingdom synergistic relationships will identify potential therapeutic targets in the management of IAI.