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Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients : a retrospective observational study

Liesbet De Bus (UGent) , WOUTER DENYS (UGent) , JULIE CATTEEUW (UGent) , Bram Gadeyne (UGent) , Karel Vermeulen (UGent) , Jerina Boelens (UGent) , Geert Claeys (UGent) , Jan De Waele (UGent) , Johan Decruyenaere (UGent) and Pieter Depuydt (UGent)
(2016) INTENSIVE CARE MEDICINE. 42(6). p.1029-1039
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Abstract
Purpose: Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics, but proof that it prevents the emergence of resistance is lacking. We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance. Methods: Antibiotic treatments, starting with empirical beta-lactam prescriptions, were prospectively documented during 2013 and 2014 in a tertiary intensive care unit (ICU) and categorized as continuation, de-escalation or escalation of the empirical antimicrobial treatment. Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression; the continuation category was used as the reference group. Using systematically collected diagnostic and surveillance cultures, we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy, with adjustment for ICU discharge and death as competing risks. Results: Of 478 anti-pseudomonal antibiotic prescriptions, 42 (9 %) were classified as escalation of the antimicrobial treatment and 121 (25 %) were classified as de-escalation, mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum. In multivariate analysis, de-escalation was associated with the identification of etiologic pathogens (p < 0.001). The duration of the antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 (range 6-10) versus 5 (range 4-7) days, respectively (p < 0.001). Mortality did not differ between patients in the de-escalation and continuation categories. The cumulative incidence estimates of the emergence of resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 % for de-escalation and continuation, respectively (p = 0.22). For the selection of multi-drug resistant pathogens, these values were 23.5 (de-escalation) and 18.6 % (continuation) respectively (p = 0.35). Conclusion: The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation.
Keywords
Antibiotic stewardship, Beta-lactam antibiotics, Multi-drug resistance, De-escalation, Information technology system, INTENSIVE-CARE-UNIT, CRITICALLY-ILL PATIENTS, SEVERE SEPSIS, ANTIMICROBIAL TREATMENT, COMPETING RISKS, INFECTION SURVEILLANCE, ACQUIRED PNEUMONIA, SEPTIC SHOCK, THERAPY, GUIDELINES

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Chicago
De Bus, Liesbet, WOUTER DENYS, JULIE CATTEEUW, Bram Gadeyne, Karel Vermeulen, Jerina Boelens, Geert Claeys, Jan De Waele, Johan Decruyenaere, and Pieter Depuydt. 2016. “Impact of De-escalation of Beta-lactam Antibiotics on the Emergence of Antibiotic Resistance in ICU Patients : a Retrospective Observational Study.” Intensive Care Medicine 42 (6): 1029–1039.
APA
De Bus, L., DENYS, W., CATTEEUW, J., Gadeyne, B., Vermeulen, K., Boelens, J., Claeys, G., et al. (2016). Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients : a retrospective observational study. INTENSIVE CARE MEDICINE, 42(6), 1029–1039.
Vancouver
1.
De Bus L, DENYS W, CATTEEUW J, Gadeyne B, Vermeulen K, Boelens J, et al. Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients : a retrospective observational study. INTENSIVE CARE MEDICINE. 2016;42(6):1029–39.
MLA
De Bus, Liesbet, WOUTER DENYS, JULIE CATTEEUW, et al. “Impact of De-escalation of Beta-lactam Antibiotics on the Emergence of Antibiotic Resistance in ICU Patients : a Retrospective Observational Study.” INTENSIVE CARE MEDICINE 42.6 (2016): 1029–1039. Print.
@article{7205808,
  abstract     = {Purpose: Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics, but proof that it prevents the emergence of resistance is lacking. We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance. 
Methods: Antibiotic treatments, starting with empirical beta-lactam prescriptions, were prospectively documented during 2013 and 2014 in a tertiary intensive care unit (ICU) and categorized as continuation, de-escalation or escalation of the empirical antimicrobial treatment. Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression; the continuation category was used as the reference group. Using systematically collected diagnostic and surveillance cultures, we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy, with adjustment for ICU discharge and death as competing risks. 
Results: Of 478 anti-pseudomonal antibiotic prescriptions, 42 (9 \%) were classified as escalation of the antimicrobial treatment and 121 (25 \%) were classified as de-escalation, mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum. In multivariate analysis, de-escalation was associated with the identification of etiologic pathogens (p {\textlangle} 0.001). The duration of the antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 (range 6-10) versus 5 (range 4-7) days, respectively (p {\textlangle} 0.001). Mortality did not differ between patients in the de-escalation and continuation categories. The cumulative incidence estimates of the emergence of resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 \% for de-escalation and continuation, respectively (p = 0.22). For the selection of multi-drug resistant pathogens, these values were 23.5 (de-escalation) and 18.6 \% (continuation) respectively (p = 0.35). 
Conclusion: The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation.},
  author       = {De Bus, Liesbet and DENYS, WOUTER and CATTEEUW, JULIE and Gadeyne, Bram and Vermeulen, Karel and Boelens, Jerina and Claeys, Geert and De Waele, Jan and Decruyenaere, Johan and Depuydt, Pieter},
  issn         = {0342-4642},
  journal      = {INTENSIVE CARE MEDICINE},
  language     = {eng},
  number       = {6},
  pages        = {1029--1039},
  title        = {Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients : a retrospective observational study},
  url          = {http://dx.doi.org/10.1007/s00134-016-4301-z},
  volume       = {42},
  year         = {2016},
}

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