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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1072-1083 |
| Number of pages | 12 |
| Journal | Clinical Infectious Diseases |
| Volume | 58 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 15 2014 |
Keywords
- adverse events
- continuous infusion
- extended infusion
- pharmacodynamics
- pharmacokinetics
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
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DALI : Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients? / Roberts, Jason A.; Paul, Sanjoy K.; Akova, Murat; Bassetti, Matteo; De Waele, Jan J.; Dimopoulos, George; Kaukonen, Kirsi Maija; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C.; Lipman, Jeffrey; Margarit Ribas, Antonio; De Crop, Luc; Spapen, Herbert; Wauters, Joost; Dugernier, Thierry; Jorens, Philippe; Dapper, Ilse; De Backer, Daniel; Taccone, Fabio S.; Ruano, Laura; Afonso, Elsa; Alvarez-Lerma, Francisco; Gracia-Arnillas, Maria Pilar; Fernández, Francisco; Feijoo, Neus; Bardolet, Neus; Rovira, Assumpta; Garro, Pau; Colon, Diana; Castillo, Carlos; Fernado, Juan; Lopez, Maria Jesus; Fernandez, Jose Luis; Arribas, Ana Maria; Teja, Jose Luis; Ots, Elsa; Carlos Montejo, Juan; Catalan, Mercedes; Prieto, Isidro; Gonzalo, Gloria; Galvan, Beatriz; Blasco, Miguel Angel; Meyer, Estibaliz; Del Nogal, Frutos; Vidaur, Loreto; Sebastian, Rosa; Garde, Pila Marco; Martin Velasco, Maria Del Mar; Zaragoza Crespo, Rafael; Esperatti, Mariano; Torres, Antoni; Baldesi, Olivier; Dupont, Herve; Mahjoub, Yazine; Lasocki, Sigismond; Constantin, Jean Michel; Payen, Jean François; Albanese, Jacques; Malledant, Yannick; Pottecher, Julien; Lefrant, Jean Yves; Jaber, Samir; Joannes-Boyau, Olivier; Orban, Christophe; Ostermann, Marlies; McKenzie, Cathrine; Berry, William; Smith, John; Lei, Katie; Rubulotta, Francesca; Gordon, Anthony; Brett, Stephen; Stotz, Martin; Templeton, Maie; Ebm, Claudia; Moran, Carl; Pettilä, Ville; Xristodoulou, Aglaia; Theodorou, Vassiliki; Kouliatsis, Georgios; Sertaridou, Eleni; Anthopoulos, Georgios; Choutas, George; Rantis, Thanos; Karatzas, Stylianos; Balla, Margarita; Papanikolaou, Metaxia; Myrianthefs, Pavlos; Gavala, Alexandra; Fildisis, Georgios; Koutsoukou, Antonia; Kyriakopoulou, Magdalini; Petrochilou, Kalomoira; Kompoti, Maria; Michalia, Martha; Clouva-Molyvdas, Fillis Maria; Gkiokas, Georgios; Nikolakopoulos, Fotios; Psychogiou, Vasiliki; Malliotakis, Polychronis; Akoumianaki, Evangelia; Lilitsis, Emmanouil; Koulouras, Vassilios; Nakos, George; Kalogirou, Mihalis; Komnos, Apostolos; Zafeiridis, Tilemachos; Chaintoutis, Christos; Arvaniti, Kostoula; Matamis, Dimitrios; Kydona, Christina; Gritsi-Gerogianni, Nikoleta; Giasnetsova, Tatiana; Giannakou, Maria; Soultati, Ioanna; Chytas, Ilias; Antoniadou, Eleni; Antipa, Elli; Lathyris, Dimitrios; Koukoubani, Triantafyllia; Paraforou, Theoniki; Spiropoulou, Kyriaki; Bekos, Vasileios; Spring, Anna; Kalatzi, Theodora; Nikolaou, Hara; Laskou, Maria; Strouvalis, Ioannis; Aloizos, Stavros; Kapogiannis, Spyridon; Soldatou, Ourania; Adembri, Chiara; Villa, Gianluca; Giarratano, Antonio; Maurizio Raineri, Santi; Cortegiani, Andrea; Montalto, Francesca; Strano, Maria Teresa; Ranieri, V. Marco; Sandroni, Claudio; De Pascale, Gennaro; Molin, Alexandre; Pelosi, Paolo; Montagnani, Luca; Urbino, Rosario; Mastromauro, Ilaria; De Rosa, Francesco G.; Cardoso, Teresa; Afonso, Susana; Gonçalves-Pereira, João; Baptista, João Pedro; Özveren, Arife.
In: Clinical Infectious Diseases, Vol. 58, No. 8, 15.04.2014, p. 1072-1083.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - DALI
T2 - Defining antibiotic levels in intensive care unit patients: Are current ß-lactam antibiotic doses sufficient for critically ill patients?
AU - Roberts, Jason A.
AU - Paul, Sanjoy K.
AU - Akova, Murat
AU - Bassetti, Matteo
AU - De Waele, Jan J.
AU - Dimopoulos, George
AU - Kaukonen, Kirsi Maija
AU - Koulenti, Despoina
AU - Martin, Claude
AU - Montravers, Philippe
AU - Rello, Jordi
AU - Rhodes, Andrew
AU - Starr, Therese
AU - Wallis, Steven C.
AU - Lipman, Jeffrey
AU - Margarit Ribas, Antonio
AU - De Crop, Luc
AU - Spapen, Herbert
AU - Wauters, Joost
AU - Dugernier, Thierry
AU - Jorens, Philippe
AU - Dapper, Ilse
AU - De Backer, Daniel
AU - Taccone, Fabio S.
AU - Ruano, Laura
AU - Afonso, Elsa
AU - Alvarez-Lerma, Francisco
AU - Gracia-Arnillas, Maria Pilar
AU - Fernández, Francisco
AU - Feijoo, Neus
AU - Bardolet, Neus
AU - Rovira, Assumpta
AU - Garro, Pau
AU - Colon, Diana
AU - Castillo, Carlos
AU - Fernado, Juan
AU - Lopez, Maria Jesus
AU - Fernandez, Jose Luis
AU - Arribas, Ana Maria
AU - Teja, Jose Luis
AU - Ots, Elsa
AU - Carlos Montejo, Juan
AU - Catalan, Mercedes
AU - Prieto, Isidro
AU - Gonzalo, Gloria
AU - Galvan, Beatriz
AU - Blasco, Miguel Angel
AU - Meyer, Estibaliz
AU - Del Nogal, Frutos
AU - Vidaur, Loreto
AU - Sebastian, Rosa
AU - Garde, Pila Marco
AU - Martin Velasco, Maria Del Mar
AU - Zaragoza Crespo, Rafael
AU - Esperatti, Mariano
AU - Torres, Antoni
AU - Baldesi, Olivier
AU - Dupont, Herve
AU - Mahjoub, Yazine
AU - Lasocki, Sigismond
AU - Constantin, Jean Michel
AU - Payen, Jean François
AU - Albanese, Jacques
AU - Malledant, Yannick
AU - Pottecher, Julien
AU - Lefrant, Jean Yves
AU - Jaber, Samir
AU - Joannes-Boyau, Olivier
AU - Orban, Christophe
AU - Ostermann, Marlies
AU - McKenzie, Cathrine
AU - Berry, William
AU - Smith, John
AU - Lei, Katie
AU - Rubulotta, Francesca
AU - Gordon, Anthony
AU - Brett, Stephen
AU - Stotz, Martin
AU - Templeton, Maie
AU - Ebm, Claudia
AU - Moran, Carl
AU - Pettilä, Ville
AU - Xristodoulou, Aglaia
AU - Theodorou, Vassiliki
AU - Kouliatsis, Georgios
AU - Sertaridou, Eleni
AU - Anthopoulos, Georgios
AU - Choutas, George
AU - Rantis, Thanos
AU - Karatzas, Stylianos
AU - Balla, Margarita
AU - Papanikolaou, Metaxia
AU - Myrianthefs, Pavlos
AU - Gavala, Alexandra
AU - Fildisis, Georgios
AU - Koutsoukou, Antonia
AU - Kyriakopoulou, Magdalini
AU - Petrochilou, Kalomoira
AU - Kompoti, Maria
AU - Michalia, Martha
AU - Clouva-Molyvdas, Fillis Maria
AU - Gkiokas, Georgios
AU - Nikolakopoulos, Fotios
AU - Psychogiou, Vasiliki
AU - Malliotakis, Polychronis
AU - Akoumianaki, Evangelia
AU - Lilitsis, Emmanouil
AU - Koulouras, Vassilios
AU - Nakos, George
AU - Kalogirou, Mihalis
AU - Komnos, Apostolos
AU - Zafeiridis, Tilemachos
AU - Chaintoutis, Christos
AU - Arvaniti, Kostoula
AU - Matamis, Dimitrios
AU - Kydona, Christina
AU - Gritsi-Gerogianni, Nikoleta
AU - Giasnetsova, Tatiana
AU - Giannakou, Maria
AU - Soultati, Ioanna
AU - Chytas, Ilias
AU - Antoniadou, Eleni
AU - Antipa, Elli
AU - Lathyris, Dimitrios
AU - Koukoubani, Triantafyllia
AU - Paraforou, Theoniki
AU - Spiropoulou, Kyriaki
AU - Bekos, Vasileios
AU - Spring, Anna
AU - Kalatzi, Theodora
AU - Nikolaou, Hara
AU - Laskou, Maria
AU - Strouvalis, Ioannis
AU - Aloizos, Stavros
AU - Kapogiannis, Spyridon
AU - Soldatou, Ourania
AU - Adembri, Chiara
AU - Villa, Gianluca
AU - Giarratano, Antonio
AU - Maurizio Raineri, Santi
AU - Cortegiani, Andrea
AU - Montalto, Francesca
AU - Strano, Maria Teresa
AU - Ranieri, V. Marco
AU - Sandroni, Claudio
AU - De Pascale, Gennaro
AU - Molin, Alexandre
AU - Pelosi, Paolo
AU - Montagnani, Luca
AU - Urbino, Rosario
AU - Mastromauro, Ilaria
AU - De Rosa, Francesco G.
AU - Cardoso, Teresa
AU - Afonso, Susana
AU - Gonçalves-Pereira, João
AU - Baptista, João Pedro
AU - Özveren, Arife
N1 - Funding Information: Financial support. This work was supported by the European Society of Intensive Care Medicine (ESICM) European Critical Care Research Network (ECCRN), the Royal Brisbane and Women’s Hospital Foundation, and the Antimicrobial Use in ICU Working Group in the Infection Section of the ESICM. J. A. R. is funded by a Career Development Fellowship from the National Health and Medical Research Council of Australia (APP1048652). Potential conflicts of interest. All authors: No reported conflicts. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/4/15
Y1 - 2014/4/15
N2 - 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.
AB - 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.
KW - adverse events
KW - continuous infusion
KW - extended infusion
KW - pharmacodynamics
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=84897414453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897414453&partnerID=8YFLogxK
U2 - 10.1093/cid/ciu027
DO - 10.1093/cid/ciu027
M3 - Article
C2 - 24429437
AN - SCOPUS:84897414453
VL - 58
SP - 1072
EP - 1083
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 8
ER -