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Clin Infect Dis. 2014 Apr;58(8):1072-83. doi: 10.1093/cid/ciu027. Epub 2014 Jan 14.

DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients?

Collaborators (159)

Roberts JA, Lipman J, Starr T, Wallis SC, Paul SK, Margarit Ribas A, De Waele JJ, De Crop L, Spapen H, Wauters J, Dugernier T, Jorens P, Dapper I, De Backer D, Taccone FS, Rello J, Ruano L, Afonso E, Alvarez-Lerma F, Gracia-Arnillas MP, Fernández F, Feijoo N, Bardolet N, Rovira A, Garro P, Colon D, Castillo C, Fernado J, Lopez MJ, Fernandez JL, Arribas AM, Teja JL, Ots E, Carlos Montejo J, Catalan M, Prieto I, Gonzalo G, Galvan B, Blasco MA, Meyer E, Del Nogal F, Vidaur L, Sebastian R, Garde PM, Martin Velasco Mdel M, Zaragoza Crespo R, Esperatti M, Torres A, Montravers P, Baldesi O, Dupont H, Mahjoub Y, Lasocki S, Constantin JM, Payen JF, Martin C, Albanese J, Malledant Y, Pottecher J, Lefrant JY, 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, Rhodes A, Ebm C, Moran C, Kaukonen KM, Pettilä V, Dimopoulos G, Koulenti D, 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 FM, 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, Chaintoutis C, 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, Bassetti M, Adembri C, Villa G, Giarratano A, Maurizio Raineri S, Cortegiani A, Montalto F, Strano MT, Ranieri VM, Sandroni C, De Pascale G, Molin A, Pelosi P, Montagnani L, Urbino R, Mastromauro I, De Rosa FG, Ranieri VM, Cardoso T, Afonso S, Gonçalves-Pereira J, Baptista JP, Akova M, Ozveren A.

Author information

1
Burns Trauma and Critical Care Research Centre, University of Queensland.

Abstract

BACKGROUND:

Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-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 β-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 T>MIC) 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 T>MIC 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 T>MIC and 100% f T>MIC 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.

KEYWORDS:

adverse events; continuous infusion; extended infusion; pharmacodynamics; pharmacokinetics

PMID:
24429437
DOI:
10.1093/cid/ciu027
[Indexed for MEDLINE]

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