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Crit Care Med. 2015 Apr;43(4):774-80. doi: 10.1097/CCM.0000000000000768.

The role of systemic antibiotics in acquiring respiratory tract colonization with gram-negative bacteria in intensive care patients: a nested cohort study.

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1Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. 2Department of Intensive Care, St Anna Hospital, Geldrop, The Netherlands. 3Department of Neurology, Boston University School of Medicine, Boston, MA. 4Department of Medical Microbiology, St Elisabeth Hospital Tilburg, Tilburg, The Netherlands. 5Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. 6Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.



Colonization of the respiratory tract with Gram-negative bacteria in intensive care patients increases the risk of subsequent infections. Application of systemic antibiotics may prevent colonization with Gram-negative bacteria, but this effect has never been quantified. The objective of this study was to determine associations between systemic antibiotic use and acquisition of respiratory tract colonization with Gram-negative bacteria in ICUs.


A nested cohort study.


A university hospital and a teaching hospital.


Patients with ICU stay of more than 48 hours and absence of respiratory tract colonization with Gram-negative bacteria on ICU admission.




Acquisition was determined through protocolized surveillance. Associations were investigated with Cox regression models with antibiotics as a time-dependent covariate. In all, 250 of 481 patients (52%) acquired respiratory tract colonization with Gram-negative bacteria after a median of 5 days (interquartile range, 3-8 d) (acquisition rate, 77.1/1,000 patient-days at risk). Antibiotic exposure during ICU admission was present in 78% and 72% of the patients with and without acquired Gram-negative bacteria colonization, respectively. In Kaplan-Meier curve analysis, the median times to acquisition of Gram-negative bacteria were 9 days (95% CI, 7.9-10.1) and 6 days (95% CI, 4.8-7.2) in patients receiving and not receiving antibiotics, respectively. In time varying Cox regression analysis, however, the association between acquired colonization and systemic antibiotics was not statistically significant (hazard ratio, 0.90; 95% CI, 0.70-1.16).


Among patients not colonized with Gram-negative bacteria in the respiratory tract at admission to ICU, systemic antibiotics during ICU stay were not associated with a reduction in acquisition of Gram-negative bacteria carriage in the respiratory tract during the ICU stay.

[Indexed for MEDLINE]

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