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1 Supplementary Online Content Oostdijk EAN, Kesecioglu J, Schultz MJ, et al. Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial. JAMA. doi: /jama etable 1. Partipating Hospitals With Level of ICU Care etable 2. Characteristics of Eligible Patients Who Stayed in ICU for >48 Hours But Did Not Receive SDD or SOD etable 3. Definition Highly-Resistant Microorganisms According to thedutch Workingparty on Infection Control (WIP) eappendix. Adjustment Study Regimen and Surveillance Protocol This supplementary matrrial has been provided by the authors to give readers additional information about their work.

2 etable 1. Partipating Hospitals With Level of ICU Care (Level 1 is Lowest, Level 3 is Highest Level of ICU Care) Hospital Start study End study Level Order N patients included SOD Flevo ZIekenhuis Almere Rijnstate Arnhem Rijnland Zieknhuis Leiderdorp Groene Hart Ziekenhuis Gouda Haga Den Haag Catharina Eindhoven Deventer Ziekenhuis Deventer Sint Lucas Andreas Ziekenhuis Amsterdam BovenIJ Amsterdam Leids Universitair Medisch Centrum Leiden Antonius Ziekenhuis Sneek Diakonessenhuis Utrecht Universitair Medisch Centrum Utrecht Utrecht Academisch Medisch Centrum Amsterdam Nij Smellinghe Drachten Maastricht Universitair Medisch Centrum Maastricht 1 August 1 september N patients included SDD 1 SDD-SOD SOD-SDD SOD-SDD >2 (feb 11) SOD-SDD SOD-SDD SDD-SOD SOD-SDD SDD-SOD SDD-SOD March 3 SDD-SOD March 1 April 1 SDD-SOD April 1 May 2 SDD-SOD May 1 June 3 SOD-SDD June 1 July 3 SDD-SOD September 1 Oktober SOD-SDD SOD-SDD SDD, selective decontamination of the digestive tract ; SOD, selective oropharyngeal decontamination ; ICU, intensive care unit

3 etable 2. Characteristics of Eligible Patients Who Stayed in ICU for >48 Hours But Did Not Receive SDD or SOD SOD SDD P-value (n = 1234) (n = 971) Median age at time ICU admission (IQR) 66 (20) 66 (21).67 Male sex (%) 678 (55.0%) 547 (56.3%).53 Mean apache IV score (95% CI) 59 (35) 59 (33).54 Mechanical ventilation (%) 641 (51.9%) 489 (50.1%).78 Mechanical ventilation at least 48hrs 143 (11.6%) 109 (11.2%).79 Surgery in week before ICU admission 573 (46.5%) 455 (46.9%).84 OR (95% CI (pvalue)) ICU-mortality 88 (7.1%) 51 (5.3%) 0.72 ( (.07)) Hospital mortality 180 (14.6%) 116 (11.9%) 0.79 ( (.07)) Day-28 mortality 168 (13.6%) 121 (12.5%) 0.90 ( (.43)) Median length of ICU-stay (IQR) 4 (2) 4 (2).31 Median length of hospital-stay (IQR) 13 (13) 12 (13).09 SDD, selective decontamination of the digestive tract ; SOD, selective oropharyngeal decontamination ; ICU, intensive care unit

4 etable 3. Definition Highly-Resistant Microorganisms According to thedutch Workingparty on Infection Control (WIP) a ESB L Quinolone s Aminoglycosid es Carbapene ms Cotrimoxazol Ceftazidim e Piperacilli n e Escherichia coli A B B A NA NA NA Klebsiella spp A B B A NA NA NA Other A B B A B NA NA Enterobacteriace ae Acinetobacter NA B B A NA B NA spp Stenotrophomon NA NA NA NA A NA NA as maltophilia Other gramnegative nonfermenters (including Pseudomonas spp) NA C C C NA C C A, resistance against an antibacterial agent from one of the indicated groups of this category is sufficient to define the microorganism as highly resistant B, resistance against antibacterial agents from at least two of the indicated groups of this category is required to define the microorganism as highly resistant C, resistance against antibacterial agents from at least three of the indicated groups of this category is required to define the microorganism as highly resistant. ESBL, extended-spectrum β-lactamases ; NA not applicable a Kluytmans-Vandenbergh MF, Kluytmans JA, Voss A. Dutch guideline for preventing nosocomial transmission of highly resistant microorganisms (HRMO). Infection. Oct 2005;33(5-6):

5 eappendix. Adjustment Study Regimen and Surveillance Protocol Surveillance was carried out in all hospitals to monitor the effectiveness of the regimen. During selective oropharyngeal decontamination (SOD) respiratory samples were obtained. During selective digestive tract decontamination (SDD) both respiratory samples and rectal samples were obtained. Based upon these results various adaptions were adviced: During SOD application of oropharyngeal paste was increased to 8 times daily if the first surveillance culture of the throat yielded yeasts, until two consecutive surveillance cultures were negative. There are no restrictions in physicians choices of systemic antibiotic therapy. During SDD several adaptations are possible: (a) application of oropharyngeal paste was increased to 8 times daily, if the first surveillance culture of the throat yielded yeasts, until two surveillance cultures were negative; (b) 5 ml (5 mg) amphotericin B was nebulized 4 times daily if a sputum surveillance culture (not admission culture) yielded yeasts, until two sputum cultures became negative; (c) 5 ml (80 mg) colistin was nebulized 4 times daily if a sputum surveillance culture (not admission culture) yielded Gram negative bacteria, until two sputum cultures are negative. During SDD it is recommended to avoid, as much as possible, antibiotics that have anaerobic activity, to leave the anaerobic flora undisturbed and preserve the so-called colonization resistance. The tobe-avoided antibiotics were penicillin, amoxicillin-clavulanic acid, flucloxacillin, piperacilline +/- tazobactam, carbapenem, clindamycin. Metronidazol is the antibiotic of choice when coverage of anaerobics is intended for clinical reasons. During both SDD and SOD, in patients with tracheostomy the paste was applied around the tracheostomy.