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Rapid Diagnostic Testing of Bronchoalveolar Lavage to Detect Non-Fermenting Gram-Negative Bacteria and Antibiotic Resistance Genes

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A7770 - Rapid Diagnostic Testing of Bronchoalveolar Lavage to Detect Non-Fermenting Gram-Negative Bacteria and Antibiotic Resistance Genes
Author Block: C. Pickens1, C. Qi1, H. Donnelly2, M. Breganio1, R. G. Wunderink2; 1Pulmonary and Critical Care, Northwestern University, Chicago, IL, United States, 2Northwestern University, Chicago, IL, United States.
Rationale: Avoidance of inappropriate antibiotic therapy for pneumonia depends on detection of highly resistant pathogens or unexpected resistance patterns, particularly for non-fermenting Gram-negative bacteria. Carbapenem resistance is one of the most clinically important resistance patterns, with various causative genes including kpc, vim, oxa-24 and ndm. The long turnaround time for culture creates a need for more rapid detection of these genes and microorganisms. Multiplex polymerase chain reaction (mPCR), offers the potential for early detection of pathogens and antibiotic resistance but clinical implications of results, especially if discrepant from culture, are poorly understood. We therefore reviewed clinical data to determine the rate of detection of important resistance genes and to observe clinical outcomes in patients with discrepant results between culture and a rapid sample-to-answer mPCR platform.
Methods: The Unyvero lower respiratory tract (LRT) panel detects 20 microorganisms and 19 antibiotic resistance markers in bronchoalveolar lavage (BAL) samples, with a turnaround time of less than 5 hours. A validation study of the Unyvero system compared to cultures was performed at our institution on residual BAL samples from patients with suspected pneumonia. Discrepant result resolution was performed by independent PCR and sequencing for organisms on the Unyvero panel.
Results: 65 samples were available for comparison. 41 samples were concordant between culture and LRT for both organism and resistance pattern, including 15 cases of non-fermenters. 7 samples were discordant due to a missed organism by Unyvero, 5 because culture missed an organism. Organisms detected by Unyvero but missed by culture included 4 Acinetobacter sp. and 1 Pseudomonas aeruginosa. All Acinetobacter cases had a subsequent BAL culture that grew Acinetobacter; all these patients died in hospital. The missed P. aeruginosa had no resistance markers, was nearly pan-susceptible on culture and was appropriately covered by empirical therapy; the patient survived.
7 samples had discordant susceptibility patterns of unclear clinical significance. The Unyvero system detected 9 of 11 (82%) pathogens with phenotypic carbapenem resistance on culture, including the one ndm.
Conclusion: 82% of carbapenem resistance was detected by the LRT platform within 5 hours of testing, potentially minimizing inappropriate antibiotic duration. Non-fermenters detected by LRT but not grown on culture may be causative and are associated with high mortality. The LRT panel appears to complement standard culture for detection of important pathogens and resistance.
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