Abstract
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. STUDY SYNOPSIS: What the study adds. The Biofire FilmArray Pneumonia Panel plus detected 64.5% more respiratory pathogens compared with culture, and detected antimicrobial resistance (AMR) genes in 25.2% of patients with HIV hospitalised with community-acquired pneumonia (CAP). Baseline room air oxygen saturation <92% and prior antibiotic use were associated with nine times and four times increased odds of AMR, respectively.Implications of the findings. Multiplex polymerase chain reaction (PCR) assays increase the speed of detection and diagnostic yield of respiratory pathogens and may be useful for diagnosis of AMR in hospitalised patients with HIV and CAP. The clinical implications of these findings should be evaluated further in prospective studies and cost-effectiveness studies to define the role of multiplex PCR tests in the patient care pathway.