key: cord-0811981-c9x2fxwi
authors: Tellapragada, C.; Giske, C.
title: The Unyvero Hospital-Acquired pneumonia panel for diagnosis of secondary bacterial pneumonia in COVID-19 patients
date: 2020-11-27
journal: nan
DOI: 10.1101/2020.11.24.20237263
sha: 0afc6d7d690f693ff674361b0e41caa2e8f9c680
doc_id: 811981
cord_uid: c9x2fxwi

The study was undertaken to evaluate the performance of Unyvero Hospitalized Pneumonia Panel (HPN) Application, a multiplex PCR based method for the detection of bacterial pathogens from lower respiratory tract (LRT) samples, obtained from COVID-19 patients with suspected secondary hospital-acquired pneumonia. Residual LRT samples obtained from critically ill COVID-19 patients with predetermined microbiological culture results were tested using the Unyvero HPN Application. Performance evaluation of the HPN Application was carried out using the standard-of-care (SoC) microbiological culture findings as the reference method. Eighty-three LRT samples were used in the evaluation. The HPN Application had a full concordance with SoC findings in 59/83 (71%) samples. The new method detected additional bacterial species in 21 (25%) and failed at detecting a bacterial species present in lower respiratory culture in 3 (3.6%) samples. Overall the sensitivity, specificity, positive and negative predictive values of the HPN Application were 95.1% (95%CI: 96.5-98.3%); 98.3% (95% CI: 97.5-98.9%); 71.6% (95% CI: 61.0-80.3%) and 99.8% (95% CI: 99.3-99.9%) respectively. In conclusion, the HPN Application demonstrated higher diagnostic yield in comparison with the culture and generated results within 5 hours.

Amidst these pre-existing challenges with reference to etiological diagnosis of LRTIs, 72 COVID-19 has rapidly emerged as a major public health concern, worldwide. Current 73 estimates suggest that nearly 80% of the patients admitted in the ICU with COVID-19 receive 74 antibiotics [2]. In contrast, from a recent meta-analysis that included 24 studies from various 75 countries, it was reported that bacterial co-infections were reported in only 7-15% of the 76 patients admitted in the ICU [3] . Antibiotic therapy in the absence of etiological diagnosis of 77 infection has both clinical and public health implications. Inappropriate use of antibiotics is a 78 well-established driver for emergence of antimicrobial resistance among bacterial pathogens. 79 suspicion of secondary bacterial infection. Microbiology culture reports, sample types and 97 baseline demographic characteristics of the subjects were extracted from the laboratory 98 information system using the laboratory identification numbers of the samples available in the 99 biobank. Selection of the samples was carried out based on the following inclusion criteria: i) 100 samples obtained from adult patients; ii) obtained from subjects admitted in the intensive-care 101 unit; iii) samples that were either positive for normal respiratory microbiota or positive for 102 one or more of the organism targets of the Unyvero HPN panel. Selected samples were tested 103 with the Unyvero HPN Application. 104

Standard-of-Care (SoC) testing: Quantitative culture methods were used for both invasive and 105 non-invasive sample types at the study laboratory. Detailed description of the sample 106 volumes, culture media used and incubation conditions for various bacterial species are 107 described previously [5] . Results from the cultures were reported in colony-forming units 108 (CFU) per milliliter. Identification of the bacterial species was performed using MALDI-TOF 109 (Bruker), as per the manufacturer's instructions. Antimicrobial susceptibility testing was 110 performed using the disk-diffusion test and result interpretation was according to the 111 consisted of a sample tube with lysis buffer, a sealed master mix tube and a cartridge where 124 the multiplex PCR is performed. List of the organisms and the antimicrobial resistance genes 125 available on the Unyvero HPN panel for testing are shown in Table 1 In total, we tested 83 samples consisting of 61 (73.5%) tracheal secretions, 11 (13.4%) BAL, 151 8 (9.7%) PSB, 2 (2.4%) bronchial secretions and 1 (1.2%) sputum sample. The 83 samples 152 All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted November 27, 2020. ; https://doi.org/10.1101/2020.11.24.20237263 doi: medRxiv preprint Application concorded fully with the culture results from 59 (71.1%) samples (Table S3) and 196 detected additional organisms among 21 (25.3%) samples (Table S4) . Of the 11 non-panel 197 organisms found on SoC (Table S2) , 55% (6/11) were common oropharyngeal colonizing 198 organisms that generally do not necessitate antibiotic escalation, and a further 45.5% (5/11) 199

were organisms that would have been covered with empirical treatment. seems to be based on the prior experience with bacterial super-infections, that were reported 221 All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. detecting additional bacterial species only by the molecular methods (in the absence of culture 255 All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted November 27, 2020. ; https://doi.org/10.1101/2020.11.24.20237263 doi: medRxiv preprint confirmation) remain unclear and most often it is speculated that the higher yield of the 256 molecular tests can be attributed to their ability to detect nonviable bacteria from a past 257 infection [15] . However, in our study we also observed that the HPN Application could detect 258 a bacterial pathogen from samples (from patients 4, 5, 9 and 11 in Table S1) preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted November 27, 2020. ; https://doi.org/10.1101/2020.11.24.20237263 doi: medRxiv preprint

Factors impacting on length of stay and mortality of community-acquired 318 pneumonia

Bacterial co-infection and secondary infection in patients with COVID-19: a living 321 rapid review and meta-analysis