DALI: Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?

Roberts, J. A.; Paul, S. K.; Akova, M.; Bassetti, M.; De Waele, J. J.; Dimopoulos, G.; Kaukonen, K. -M.; Koulenti, D.; Martin, C.; Montravers, P.; Rello, J.; Rhodes, A.; Starr, T.; Wallis, S. C.; Lipman, J.; Margarit Ribas, A.; De Crop, L.; Spapen, H.; Wauters, J.; Dugernier, T.; Jorens, P.; Dapper, I.; De Backer, D.; Taccone, F. S.; Ruano, L.; Afonso, E.; Alvarez-Lerma, F.; Gracia-Arnillas, M. P.; Fernandez, F.; Feijoo, N.; Bardolet, N.; Rovira, A.; Garro, P.; Colon, D.; Castillo, C.; Fernado, J.; Lopez, M. J.; Fernandez, J. L.; Arribas, A. M.; Teja, J. L.; Ots, E.; Carlos Montejo, J.; Catalan, M.; Prieto, I.; Gonzalo, G.; Galvan, B.; Blasco, M. A.; Meyer, E.; Del Nogal, F.; Vidaur, L.; Sebastian, R.; Garde, P. M.; Martin Velasco, M. D. M.; Zaragoza Crespo, R.; Esperatti, M.; Torres, A.; Baldesi, O.; Dupont, H.; Mahjoub, Y.; Lasocki, S.; Constantin, J. M.; Payen, J. F.; Albanese, J.; Malledant, Y.; Pottecher, J.; Lefrant, J. -Y.; Jaber, S.; Joannes-Boyau, O.; Orban, C.; Ostermann, M.; Mckenzie, C.; Berry, W.; Smith, J.; Lei, K.; Rubulotta, F.; Gordon, A.; Brett, S.; Stotz, M.; Templeton, M.; Ebm, C.; Moran, C.; Pettila, V.; Xristodoulou, A.; Theodorou, V.; Kouliatsis, G.; Sertaridou, E.; Anthopoulos, G.; Choutas, G.; Rantis, T.; Karatzas, S.; Balla, M.; Papanikolaou, M.; Myrianthefs, P.; Gavala, A.; Fildisis, G.; Koutsoukou, A.; Kyriakopoulou, M.; Petrochilou, K.; Kompoti, M.; Michalia, M.; Clouva-Molyvdas, F. -M.; Gkiokas, G.; Nikolakopoulos, F.; Psychogiou, V.; Malliotakis, P.; Akoumianaki, E.; Lilitsis, E.; Koulouras, V.; Nakos, G.; Kalogirou, M.; Komnos, A.; Zafeiridis, T.; Chaintoutis, C.; Arvaniti, K.; Matamis, D.; Kydona, C.; Gritsi-Gerogianni, N.; Giasnetsova, T.; Giannakou, M.; Soultati, I.; Chytas, I.; Antoniadou, E.; Antipa, E.; Lathyris, D.; Koukoubani, T.; Paraforou, T.; Spiropoulou, K.; Bekos, V.; Spring, A.; Kalatzi, T.; Nikolaou, H.; Laskou, M.; Strouvalis, I.; Aloizos, S.; Kapogiannis, S.; Soldatou, O.; Adembri, C.; Villa, G.; Giarratano, A.; Maurizio Raineri, S.; Cortegiani, A.; Montalto, F.; Strano, M. T.; Ranieri, V. M.; Sandroni, C.; De Pascale, G.; Molin, A.; Pelosi, P.; Montagnani, L.; Urbino, R.; Mastromauro, I.; De Rosa, F. G.; Cardoso, T.; Afonso, S.; Goncalves-Pereira, J.; Baptista, J. P.; Ozveren, A.

doi:10.1093/cid/ciu027

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 α-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f TMIC) and 100% (100% f T MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f TMIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =. 009). Positive clinical outcome was associated with increasing 50% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P <. 03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

DALI: Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?

Roberts J. A.;Paul S. K.;Akova M.;Bassetti M.;De Waele J. J.;Dimopoulos G.;Kaukonen K. -M.;Koulenti D.;Martin C.;Montravers P.;Rello J.;Rhodes A.;Starr T.;Wallis S. C.;Lipman J.;Margarit Ribas A.;De Crop L.;Spapen H.;Wauters J.;Dugernier T.;Jorens P.;Dapper I.;De Backer D.;Taccone F. S.;Ruano L.;Afonso E.;Alvarez-Lerma F.;Gracia-Arnillas M. P.;Fernandez F.;Feijoo N.;Bardolet N.;Rovira A.;Garro P.;Colon D.;Castillo C.;Fernado J.;Lopez M. J.;Fernandez J. L.;Arribas A. M.;Teja J. L.;Ots E.;Carlos Montejo J.;Catalan M.;Prieto I.;Gonzalo G.;Galvan B.;Blasco M. A.;Meyer E.;Del Nogal F.;Vidaur L.;Sebastian R.;Garde P. M.;Martin Velasco M. D. M.;Zaragoza Crespo R.;Esperatti M.;Torres A.;Baldesi O.;Dupont H.;Mahjoub Y.;Lasocki S.;Constantin J. M.;Payen J. F.;Albanese J.;Malledant Y.;Pottecher J.;Lefrant J. -Y.;Jaber S.;Joannes-Boyau O.;Orban C.;Ostermann M.;McKenzie C.;Berry W.;Smith J.;Lei K.;Rubulotta F.;Gordon A.;Brett S.;Stotz M.;Templeton M.;Ebm C.;Moran C.;Pettila V.;Xristodoulou A.;Theodorou V.;Kouliatsis G.;Sertaridou E.;Anthopoulos G.;Choutas G.;Rantis T.;Karatzas S.;Balla M.;Papanikolaou M.;Myrianthefs P.;Gavala A.;Fildisis G.;Koutsoukou A.;Kyriakopoulou M.;Petrochilou K.;Kompoti M.;Michalia M.;Clouva-Molyvdas F. -M.;Gkiokas G.;Nikolakopoulos F.;Psychogiou V.;Malliotakis P.;Akoumianaki E.;Lilitsis E.;Koulouras V.;Nakos G.;Kalogirou M.;Komnos A.;Zafeiridis T.;Chaintoutis C.;Arvaniti K.;Matamis D.;Kydona C.;Gritsi-Gerogianni N.;Giasnetsova T.;Giannakou M.;Soultati I.;Chytas I.;Antoniadou E.;Antipa E.;Lathyris D.;Koukoubani T.;Paraforou T.;Spiropoulou K.;Bekos V.;Spring A.;Kalatzi T.;Nikolaou H.;Laskou M.;Strouvalis I.;Aloizos S.;Kapogiannis S.;Soldatou O.;Adembri C.;Villa G.;Giarratano A.;Maurizio Raineri S.;Cortegiani A.;Montalto F.;Strano M. T.;Ranieri V. M.;Sandroni C.;De Pascale G.;Molin A.;Pelosi P.;Montagnani L.;Urbino R.;Mastromauro I.;De Rosa F. G.;Cardoso T.;Afonso S.;Goncalves-Pereira J.;Baptista J. P.;Ozveren A.

2014-01-01

Abstract

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 α-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f TMIC) and 100% (100% f T MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f TMIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =. 009). Positive clinical outcome was associated with increasing 50% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P <. 03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.