Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis

Amy Legg; Matthew A. Roberts; Jane Davies; Alan Cass; Niamh Meagher; Archana Sud; Vered Daitch; Yael Dishon Benattar; Dafna Yahav; Mical Paul; Chen Xinxin; Yeo He Ping; David Lye; Russel Lee; J. Owen Robinson; Hong Foo; Adrian R. Tramontana; Narin Bak; Adelaide Grenfell; Benjamin Rogers; Ying Li; Neela Joshi; Matthew O'Sullivan; Genevieve McKew; Niladri Ghosh; Kellie Schneider; Natasha E. Holmes; Ravindra Dotel; Timothy Chia; Sophia Archuleta; Simon Smith; Morgyn S. Warner; Christina Titin; Shirin Kalimuddin; Jason A. Roberts; Steven Y.C. Tong; Joshua S. Davis

doi:10.1093/ofid/ofad337

Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis

Amy Legg, Matthew A. Roberts, Jane Davies, Alan Cass, Niamh Meagher, Archana Sud, Vered Daitch, Yael Dishon Benattar, Dafna Yahav, Mical Paul, Chen Xinxin, Yeo He Ping, David Lye, Russel Lee, J. Owen Robinson, Hong Foo, Adrian R. Tramontana, Narin Bak, Adelaide Grenfell, Benjamin RogersYing Li, Neela Joshi, Matthew O'Sullivan, Genevieve McKew, Niladri Ghosh, Kellie Schneider, Natasha E. Holmes, Ravindra Dotel, Timothy Chia, Sophia Archuleta, Simon Smith, Morgyn S. Warner, Christina Titin, Shirin Kalimuddin, Jason A. Roberts, Steven Y.C. Tong, Joshua S. Davis

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Abstract

Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI.

Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m²). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model.

Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI],. 59-1.19]; P =. 33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI,. 64-1.68]; P =. 88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.

Original language	English
Article number	ofad337
Pages (from-to)	1-9
Number of pages	9
Journal	Open Forum Infectious Diseases
Volume	10
Issue number	7
DOIs	https://doi.org/10.1093/ofid/ofad337
Publication status	Published - 1 Jul 2023

Bibliographical note

Funding Information:
Financial support. The CAMERA2 trial was supported by the Australian National Health and Medical Research Council (NHMRC) Career Development Fellowships for S. Y. C. T. (1145033) and J. S. D. (1160331). J. A. R. acknowledges funding from the NHMRC for a Centre of Research Excellence (APP2007007) and an Investigator Grant (APP2009736) as well as an Advancing Queensland Clinical Fellowship.

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.

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Legg, A., Roberts, M. A., Davies, J., Cass, A., Meagher, N., Sud, A., Daitch, V., Dishon Benattar, Y., Yahav, D., Paul, M., Xinxin, C., Ping, Y. H., Lye, D., Lee, R., Robinson, J. O., Foo, H., Tramontana, A. R., Bak, N., Grenfell, A., ... Davis, J. S. (2023). Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis. Open Forum Infectious Diseases, 10(7), 1-9. Article ofad337. https://doi.org/10.1093/ofid/ofad337

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title = "Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis",

abstract = "Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI],. 59-1.19]; P =. 33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI,. 64-1.68]; P =. 88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.",

keywords = "acute kidney injury, nephrotoxicity, Staphylococcus aureus bacteremia",

author = "Amy Legg and Roberts, {Matthew A.} and Jane Davies and Alan Cass and Niamh Meagher and Archana Sud and Vered Daitch and {Dishon Benattar}, Yael and Dafna Yahav and Mical Paul and Chen Xinxin and Ping, {Yeo He} and David Lye and Russel Lee and Robinson, {J. Owen} and Hong Foo and Tramontana, {Adrian R.} and Narin Bak and Adelaide Grenfell and Benjamin Rogers and Ying Li and Neela Joshi and Matthew O'Sullivan and Genevieve McKew and Niladri Ghosh and Kellie Schneider and Holmes, {Natasha E.} and Ravindra Dotel and Timothy Chia and Sophia Archuleta and Simon Smith and Warner, {Morgyn S.} and Christina Titin and Shirin Kalimuddin and Roberts, {Jason A.} and Tong, {Steven Y.C.} and Davis, {Joshua S.}",

note = "Funding Information: Financial support. The CAMERA2 trial was supported by the Australian National Health and Medical Research Council (NHMRC) Career Development Fellowships for S. Y. C. T. (1145033) and J. S. D. (1160331). J. A. R. acknowledges funding from the NHMRC for a Centre of Research Excellence (APP2007007) and an Investigator Grant (APP2009736) as well as an Advancing Queensland Clinical Fellowship. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.",

year = "2023",

month = jul,

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doi = "10.1093/ofid/ofad337",

language = "English",

volume = "10",

pages = "1--9",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

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Legg, A, Roberts, MA, Davies, J , Cass, A, Meagher, N, Sud, A, Daitch, V, Dishon Benattar, Y, Yahav, D, Paul, M, Xinxin, C, Ping, YH, Lye, D, Lee, R, Robinson, JO, Foo, H, Tramontana, AR, Bak, N, Grenfell, A, Rogers, B, Li, Y, Joshi, N, O'Sullivan, M, McKew, G, Ghosh, N, Schneider, K, Holmes, NE, Dotel, R, Chia, T, Archuleta, S, Smith, S, Warner, MS, Titin, C, Kalimuddin, S, Roberts, JA, Tong, SYC & Davis, JS 2023, 'Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis', Open Forum Infectious Diseases, vol. 10, no. 7, ofad337, pp. 1-9. https://doi.org/10.1093/ofid/ofad337

Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis. / Legg, Amy; Roberts, Matthew A.; Davies, Jane et al.
In: Open Forum Infectious Diseases, Vol. 10, No. 7, ofad337, 01.07.2023, p. 1-9.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial

T2 - A Post Hoc Analysis

AU - Legg, Amy

AU - Roberts, Matthew A.

AU - Davies, Jane

AU - Cass, Alan

AU - Meagher, Niamh

AU - Sud, Archana

AU - Daitch, Vered

AU - Dishon Benattar, Yael

AU - Yahav, Dafna

AU - Paul, Mical

AU - Xinxin, Chen

AU - Ping, Yeo He

AU - Lye, David

AU - Lee, Russel

AU - Robinson, J. Owen

AU - Foo, Hong

AU - Tramontana, Adrian R.

AU - Bak, Narin

AU - Grenfell, Adelaide

AU - Rogers, Benjamin

AU - Li, Ying

AU - Joshi, Neela

AU - O'Sullivan, Matthew

AU - McKew, Genevieve

AU - Ghosh, Niladri

AU - Schneider, Kellie

AU - Holmes, Natasha E.

AU - Dotel, Ravindra

AU - Chia, Timothy

AU - Archuleta, Sophia

AU - Smith, Simon

AU - Warner, Morgyn S.

AU - Titin, Christina

AU - Kalimuddin, Shirin

AU - Roberts, Jason A.

AU - Tong, Steven Y.C.

AU - Davis, Joshua S.

N1 - Funding Information: Financial support. The CAMERA2 trial was supported by the Australian National Health and Medical Research Council (NHMRC) Career Development Fellowships for S. Y. C. T. (1145033) and J. S. D. (1160331). J. A. R. acknowledges funding from the NHMRC for a Centre of Research Excellence (APP2007007) and an Investigator Grant (APP2009736) as well as an Advancing Queensland Clinical Fellowship. Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.

PY - 2023/7/1

Y1 - 2023/7/1

N2 - Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI],. 59-1.19]; P =. 33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI,. 64-1.68]; P =. 88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.

AB - Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI],. 59-1.19]; P =. 33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI,. 64-1.68]; P =. 88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.

KW - acute kidney injury

KW - nephrotoxicity

KW - Staphylococcus aureus bacteremia

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DO - 10.1093/ofid/ofad337

M3 - Article

AN - SCOPUS:85171190383

SN - 2328-8957

VL - 10

SP - 1

EP - 9

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

IS - 7

M1 - ofad337

ER -

Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis

Abstract

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