Molecular diagnostics improve the yield of diagnosis of community-acquired pneumonia and multidrug-resistant pathogens in hospitalised patients with HIV in a low-income setting

Background. Community-acquired pneumonia (CAP) remains an important cause of morbidity and mortality in people with HIV (PWH), and antimicrobial resistance (AMR) leads to poor treatment outcomes. Better tests are required to overcome the low sensitivity of sputum Gram stain and culture for pneumonia diagnosis. Molecular diagnostic tests rapidly detect respiratory pathogens and markers of AMR, but few studies have examined their role in PWH. Objectives. To investigate the additional yield of the Biofire FilmArray Pneumonia Panel plus (FilmArrayPN-PCR), an automated nested multiplex polymerase chain reaction system, over culture for diagnosis of CAP, and determine clinical predictors of AMR in PWH. Methods. We enrolled adult PWH hospitalised with cough <2 months in a prospective cohort in Kampala, Uganda. Participants provided expectorated sputum samples for testing by FilmArrayPN-PCR and culture. We performed drug susceptibility testing of cultured sputum isolates and detection of genetic markers of AMR on sputum by FilmArrayPN-PCR. Results. The 107 participants enrolled had a median (interquartile range) age of 40 (31-46) years, 50.5% (n=54/107) were female, and 74.8% (n=80/107) had recent antibiotic use. The median duration of cough was 3 (1-4) weeks. FilmArrayPN-PCR increased the detection of respiratory pathogens by 64.5% (95% confidence interval (CI) 54.8-73.1; p<0.001) and detected AMR in 25.2% (n=27/107). Baseline room air oxygen saturation <92% (adjusted odds ratio (aOR) 9.20; 95% CI 2.52-33.57; p=0.001) and prior antibiotic use (aOR 4.14; 95% CI 1.04-16.51; p=0.04) were independent predictors of AMR. Conclusion. FilmArrayPN-PCR increased the diagnostic yield of pathogens, and a low baseline oxygen saturation (<92%) and prior antibiotic use were associated with an increased risk of AMR in hospitalised PWH with CAP.