@article{8c066cc8a3e747a89346004e711e60cb,
title = "Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam Against Pseudomonas aeruginosa: PRIMERS IV",
abstract = "Background. Overcoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy in patients infected by P. aeruginosa. Methods. In this study, we used a heterogeneous collection of 197 P. aeruginosa that included multidrug-resistant isolates to determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify susceptibility to 2 newer β-lactam/β-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO). Results. We found that the studied RMD platforms were able to correctly identify BL-BLI susceptibility (susceptibility sensitivity, 100%; 95% confidence interval [CI], 97%, 100%) for both BLs-BLIs. However, their ability to detect resistance to these BLs-BLIs was lower (resistance sensitivity, 66%; 95% CI, 52%, 78% for TOL/TAZO and 33%; 95% CI, 20%, 49% for CZA). Conclusions. The diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low. Clinicians need to be mindful of the benefits and risks that result from empiric treatment decisions that are based on resistance gene detection in P. aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance, which varies temporally and geographically.",
keywords = "Antimicrobial Resistance, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, Pseudomonas Aeruginosa",
author = "Evans, {Scott R.} and Tran, {Thuy Tien T.} and Hujer, {Andrea M.} and Hill, {Carol B.} and Hujer, {Kristine M.} and Mediavilla, {Jose R.} and Claudia Manca and Domitrovic, {T. Nicholas} and Federico Perez and Michael Farmer and Pitzer, {Kelsey M.} and Wilson, {Brigid M.} and Kreiswirth, {Barry N.} and Robin Patel and Jacobs, {Michael R.} and Liang Chen and Fowler, {Vance G.} and Chambers, {Henry F.} and Bonomo, {Robert A.}",
note = "Funding Information: Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH (award UM1AI104681). Additional NIH support to R. A. B. includes R01AI100560, R01AI063517, and R01AI072219. This study was also supported in part by funds and/or facilities provided by the Department of Veterans Affairs (award 1I01BX001974 to R. A. B.), the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development, and the Geriatric Research Education and Clinical Center VISN 10, and by funds provided by Merck (Merck Investigator Studies Program 53818 to R. A. B.). S. R. E. and R. A. B. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Funding Information: Potential conflicts of interest. B. N. K. consults for Pfizer and Abbott. R. A. B. reports grants from Duke Clinical Research Institute during the conduct of the study and grants from Wockhardt, Merck, Entasis, Roche, GlaxoSmithKline (GSK), Allecra, and Shionogi outside the submitted work. R. P. reports grants from CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and the Medicines Company. R. P. is a consultant to Curetis; monies are paid to Mayo Clinic. In addition, R. P. reports grants from CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and the Medicines Company. R. P. is or has been a consultant to Curetis, Qvella, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest, and Genentech; monies are paid to Mayo Clinic. R. P. has a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. R. P. has served on an Actelion data monitoring board; receives travel reimbursement from American Society for Microbiology (ASM) and the Infectious Diseases Society of America (IDSA); has received an editor{\textquoteright}s stipend from ASM and Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.",
year = "2019",
month = may,
day = "17",
doi = "10.1093/cid/ciy801",
language = "English (US)",
volume = "68",
pages = "1823--1830",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "11",
}