Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22607
Title: Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.
Authors: Tong, Steven Y C;Lye, David C;Yahav, Dafna;Sud, Archana;Robinson, J Owen;Nelson, Jane;Archuleta, Sophia;Roberts, Matthew A;Cass, Alan;Paterson, David L;Foo, Hong;Paul, Mical;Guy, Stephen D;Tramontana, Adrian R;Walls, Genevieve B;McBride, Stephen;Bak, Narin;Ghosh, Niladri;Rogers, Benjamin A;Ralph, Anna P;Davies, Jane;Ferguson, Patricia E;Dotel, Ravindra;McKew, Genevieve L;Gray, Timothy J;Holmes, Natasha E;Smith, Simon;Warner, Morgyn S;Kalimuddin, Shirin;Young, Barnaby E;Runnegar, Naomi;Andresen, David N;Anagnostou, Nicholas A;Johnson, Sandra A;Chatfield, Mark D;Cheng, Allen C;Fowler, Vance G;Howden, Benjamin P;Meagher, Niamh;Price, David J;van Hal, Sebastiaan J;O'Sullivan, Matthew V N;Davis, Joshua S
Affiliation: Department of Infectious Diseases, Middlemore Hospital, Auckland, New Zealand
Nepean Clinical School, University of Sydney, Sydney, New South Wales, Australia
Nepean Hospital, Kingswood, New South Wales, Australia
Wollongong Public Hospital, Wollongong, New South Wales, Australia
Flinders Medical Centre, Adelaide, South Australia, Australia
Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
National Centre for Infectious Diseases, Singapore
Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore
Department of Infectious Diseases, Singapore General Hospital, Singapore
Duke-NUS Medical School, Singapore
Rambam Health Care Campus, Haifa, Israel
Technion-Israel Institute of Technology, Haifa, Israel
Division of Infectious Diseases, National University Hospital, Singapore
Department of Medicine, National University of Singapore, Singapore
Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore
Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
Victorian Infectious Disease Service, Royal Melbourne Hospital, and University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Menzies School of Health Research, Charles Darwin University, Casuarina, Northern Territory, Australia
Royal Perth Hospital, Perth, Western Australia, Australia
Fiona Stanley Hospital, Murdoch, Western Australia, Australia
Pathwest Laboratory Medicine WA, Murdoch, Western Australia, Australia
Antimicrobial Resistance and Infectious Diseases Research Laboratory, School of Veterinary and Life Sciences, Murdoch University, Murdoch, Western Australia, Australia
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia
Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia
School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
Monash Infectious Diseases, Monash Medical Centre, Clayton, Victoria, Australia
Division of Medicine, Royal Darwin Hospital, Tiwi, Northern Territory, Australia
Department of Infectious Diseases, Blacktown Hospital, Blacktown, New South Wales, Australia
Centre for Infectious Diseases and Microbiology, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
Department of Microbiology and Infectious Diseases, Concord Repatriation General Hospital, Concord, New South Wales, Australia
Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
The Queen Elizabeth Hospital, Woodville, South Australia, Australia
University of Adelaide, Adelaide, South Australia, Australia
Infection Management Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia
Southern Clinical School, Faculty of Medicine, University of Queensland, Brisbane, Australia
St Vincent's Public Hospital Sydney, Darlinghurst, New South Wales, Australia
School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia
Centre for Clinical Research, University of Queensland, Herston, Australia
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Victoria, Australia
Austin Centre for Infection Research (ACIR), Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Microbiological Diagnostic Unit Public Health Laboratory, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Victorian Infectious Diseases Reference Laboratory Epidemiology Unit, Royal Melbourne Hospital, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia
New South Wales Health Pathology, Westmead Hospital, Westmead, Australia
Department of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia
Department of Microbiology and Infectious Disease, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
Cairns Hospital, Cairns, Queensland, Australia
Royal Adelaide Hospital, Adelaide, South Australia, Australia
Footscray Hospital, Western Health, Footscray, Victoria, Australia
Department of Microbiology and Infectious Diseases, NSW Health Pathology, Liverpool, New South Wales, Australia
Issue Date: 11-Feb-2020
Citation: JAMA 2020; 323(6): 527-537
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days. The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. ClinicalTrials.gov Identifier: NCT02365493.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22607
DOI: 10.1001/jama.2020.0103
PubMed URL: 32044943
Type: Journal Article
Appears in Collections:Journal articles

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