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4 results on '"Boyles, T.H."'

1. Association between minimum inhibitory concentration, beta-lactamase genes and mortality for patients treated with piperacillin/tazobactam or meropenem from the MERINO study.

Author

Beatson S.A., Cottrell K.K., Bauer M.J., Tan E., Chaw K., Nimmo G.R., Harris-Brown T., Harris P.N.A., Boyles T.H., Looke D.F.M., Runnegar N.J., Miyakis S., Walls G., Ai Khamis M., Zikri A., Crowe A., Ingram P.R., Daneman N.N., Griffin P., Athan E., Peleg A.Y., Roberts L., Henderson A., Paterson D.L., Chatfield M.D., Tambyah P.A., Lye D.C., De P.P., Lin R.T.P., Chew K.L., Yin M., Lee T.H., Yilmaz M., Cakmak R., Alenazi T.H., Arabi Y.M., Falcone M., Bassetti M., Righi E., Ba R., Kanj S.S., Bhally H., Iredell J., Mendelson M., Beatson S.A., Cottrell K.K., Bauer M.J., Tan E., Chaw K., Nimmo G.R., Harris-Brown T., Harris P.N.A., Boyles T.H., Looke D.F.M., Runnegar N.J., Miyakis S., Walls G., Ai Khamis M., Zikri A., Crowe A., Ingram P.R., Daneman N.N., Griffin P., Athan E., Peleg A.Y., Roberts L., Henderson A., Paterson D.L., Chatfield M.D., Tambyah P.A., Lye D.C., De P.P., Lin R.T.P., Chew K.L., Yin M., Lee T.H., Yilmaz M., Cakmak R., Alenazi T.H., Arabi Y.M., Falcone M., Bassetti M., Righi E., Ba R., Kanj S.S., Bhally H., Iredell J., and Mendelson M.

Abstract

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHOD(S): Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULT(S): 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam non-susceptible breakpoint (MIC > 16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% CI 2.8 - 87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3% - 15%) and 8% (95% CI 2% - 15%) for the original PA population and the post-hoc MA populations, which reduced to 5% (95% CI -1% - 10%) after excluding strains with piperacillin/tazobactam MIC values > 16 mg/L. Isolates co-harboring ESBL and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-mortality of 14% (95% CI 2% - 28%). CONCLUSION(S): After excluding non-susceptible strains, the 30-day mortality difference was from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA co-harboring ESBLs suggests meropenem remains the preferred choice for definitive treatment of ceftriaxone non-susceptible E. coli and Klebsiella.Copyright © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permission

Published
2020

2. Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance

Author

Harris, P.N.A., Tambyah, P.A., Lye, D.C., Mo, Y., Lee, T.H., Yilmaz, M., Alenazi, T.H., Arabi, Y., Falcone, M., Bassetti, M., Righi, E., Rogers, B.A., Kanj, S., Bhally, H., Iredell, J., Mendelson, M., Boyles, T.H., Looke, D., Miyakis, S., Walls, G., Al Khamis, M., Zikri, A., Crowe, A., Ingram, P., Daneman, N., Griffin, P., Athan, E., Lorenc, P., Baker, P., Roberts, L., Beatson, S.A., Peleg, A.Y., Harris-Brown, T., Paterson, D.L., Robinson, J.O., Harris, P.N.A., Tambyah, P.A., Lye, D.C., Mo, Y., Lee, T.H., Yilmaz, M., Alenazi, T.H., Arabi, Y., Falcone, M., Bassetti, M., Righi, E., Rogers, B.A., Kanj, S., Bhally, H., Iredell, J., Mendelson, M., Boyles, T.H., Looke, D., Miyakis, S., Walls, G., Al Khamis, M., Zikri, A., Crowe, A., Ingram, P., Daneman, N., Griffin, P., Athan, E., Lorenc, P., Baker, P., Roberts, L., Beatson, S.A., Peleg, A.Y., Harris-Brown, T., Paterson, D.L., and Robinson, J.O.

Abstract

Importance: Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective “carbapenem-sparing” option to treat extended-spectrum β-lactamase producers. Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6

Published
2018

3. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with e coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance.

Author

Pollard J., Arabi Y., Athan E., Lorenc P., Baker P., Roberts L., Beatson S.A., Peleg A.Y., Harris-Brown T., Paterson D.L., McNamara J., Sieler R., Garlick J., Costa J., Roney J., Pratt N., Tabaja H., Kmeid J., Tayyar R., El Zein S., Jones S., Cowan R., Lin B., Rad B., MacMorran E., Dinleyici R., Istanbullu A., Ceylan B., Mert A., Hashhoush M., Dalwi T., Korman T., Azzam R., Birrell M., Hughes C., Khan S., Lau J., Lee L., Lim K., Lin Y.D., Lister D., New D., Rafiei N., Stewart J., Tai A., Trad M.A., Aye Yeung V., McBride S., Holland D., Hopkins C., Luey C., Taylor S., Morpeth S., Finney M., Martin M., Holland U., Ali J., Jureen R., Underwood N., Henderson A., Runnegar N., Slavin M., Robinson O., Rishu A., Shawkat S., Fish J., Chin Liew K., Newton P., Merelli M., Carnelutti A., Ussai S., Pecori D., Izharuddin E., Young B., Ding Y., Ram R., Kelly J., Joshi N., Richards G., Smith O., Alli A., Vermeulen I., Wright B., Grey C., Stewart A., Reddy D., Wasserman S., Richi H., Sultana K., Alanazi N., Bin Awad E., Franzetti F., Stolz A., De Kock E., Magongoa T., Dutoit M., Russo A., Dentone C., Eisen D., Heyer L., Harris P.N.A., Tambyah P.A., Lye D.C., Mo Y., Lee T.H., Yilmaz M., Alenazi T.H., Falcone M., Bassetti M., Righi E., Rogers B.A., Kanj S., Bhally H., Iredell J., Mendelson M., Boyles T.H., Looke D., Miyakis S., Walls G., Al Khamis M., Zikri A., Crowe A., Ingram P., Daneman N., Griffin P., Pollard J., Arabi Y., Athan E., Lorenc P., Baker P., Roberts L., Beatson S.A., Peleg A.Y., Harris-Brown T., Paterson D.L., McNamara J., Sieler R., Garlick J., Costa J., Roney J., Pratt N., Tabaja H., Kmeid J., Tayyar R., El Zein S., Jones S., Cowan R., Lin B., Rad B., MacMorran E., Dinleyici R., Istanbullu A., Ceylan B., Mert A., Hashhoush M., Dalwi T., Korman T., Azzam R., Birrell M., Hughes C., Khan S., Lau J., Lee L., Lim K., Lin Y.D., Lister D., New D., Rafiei N., Stewart J., Tai A., Trad M.A., Aye Yeung V., McBride S., Holland D., Hopkins C., Luey C., Taylor S., Morpeth S., Finney M., Martin M., Holland U., Ali J., Jureen R., Underwood N., Henderson A., Runnegar N., Slavin M., Robinson O., Rishu A., Shawkat S., Fish J., Chin Liew K., Newton P., Merelli M., Carnelutti A., Ussai S., Pecori D., Izharuddin E., Young B., Ding Y., Ram R., Kelly J., Joshi N., Richards G., Smith O., Alli A., Vermeulen I., Wright B., Grey C., Stewart A., Reddy D., Wasserman S., Richi H., Sultana K., Alanazi N., Bin Awad E., Franzetti F., Stolz A., De Kock E., Magongoa T., Dutoit M., Russo A., Dentone C., Eisen D., Heyer L., Harris P.N.A., Tambyah P.A., Lye D.C., Mo Y., Lee T.H., Yilmaz M., Alenazi T.H., Falcone M., Bassetti M., Righi E., Rogers B.A., Kanj S., Bhally H., Iredell J., Mendelson M., Boyles T.H., Looke D., Miyakis S., Walls G., Al Khamis M., Zikri A., Crowe A., Ingram P., Daneman N., and Griffin P.

Abstract

IMPORTANCE Extended-spectrum beta-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum beta-lactamase producers. OBJECTIVES To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. DESIGN, SETTING, AND PARTICIPANTS Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. INTERVENTIONS Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. RESULTS Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6

Published
2018

4. Guidelines for the management of acute meningitis in children and adults in South Africa

Author

Boyles, T.H., primary, Bamford, C., additional, Bateman, K., additional, Blumberg, L., additional, Dramowski, A., additional, Karstaedt, A., additional, Korsman, S., additional, le Roux, D.M., additional, Maartens, G., additional, Madhi, S., additional, Naidoo, R., additional, Nuttall, J., additional, Reubenson, G., additional, Taljaard, J., additional, Thomas, J., additional, van Zyl, G., additional, von Gottberg, A., additional, Whitelaw, A., additional, and Mendelson, M., additional

Published
2013
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