P130 Pseudomonas aeruginosa impairs growth of aspergillus from CF airway samples

2021 
Objectives Fungal infection is associated with poor lung health in CF but may go undetected. The low sensitivity of standard fungal culture is well recognised but poorly understood. Pseudomonas aeruginosa (Pa) has been shown to inhibit growth of Aspergillus (Asp) in vitro. We hypothesised that similar inhibitory mechanisms may, in part, account for the poor sensitivity of Asp cultures. Methods We retrospectively studied sputum/BAL standard culture results from all CF patients in our centre between 2012–2017. 16,736 positive airway samples were identified from 1001 subjects. Correlation analysis identified relationships between pairs of relevant CF-pathogens. As part of a previous study, 318 sputum samples had Internal transcribed spacer-2 (ITS2) fungal sequencing data. Samples with 1% of total reads aligned to the genus of interest were considered positive. Contingency tables examined fungal culture performance compared with ITS2 sequencing with co-infecting bacteria, using relative risk (RR, [95% CI]) and Fisher’s exact test. Results We observed a strong bias towards single rather than dual growths in patients who had isolated Pa and Asp over the study period. This was not observed with other bacterial/fungal combinations. In the 48% (149/311) of samples Asp positive by ITS2 sequencing, only 19% (28/149) were positive on culture. 39% of the culture results were considered to be false negative for Asp (fn-Asp). Fn-Asp cultures were more likely in Pa-infected than Pa-free samples (RR 1.6 [1.1–2.4], p=0.01). This effect was only seen when non-mucoid (nm)-Pa was present and not when mucoid (m)-Pa was present alone (nmPa (RR 1.90 [1.2–3.0], p=0.006); mn+mPa (RR 1.91 [1.3–2.9], p=0.002), mPa (RR 1.22 [0.8–1.9], ns). The Asp-fn risk was not increased by co-infection with other bacteria. Furthermore, Pa did not impact on fn-culture of Candida or non-aspergillus filamentous fungi. Conclusions In patients who have serial cultures demonstrating both Pa and Asp infections, dual positive cultures are uncommon. Molecular analysis demonstrated a significantly increased false negative Asp culture in the presence of Pa, particularly in it’s non-mucoid form. These data suggest that Pa can inhibit Asp growth in vivo and/or during culture of sputum and presents an important area for future research.
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