Study Design We will enroll 40 consecutive patients with VRE colonization who are admitted to Transplant ICU of Montefiore Hospital.
Methods:
A total of 40 patients will be randomized to SDD or no SDD by the Investigational Drugs Service of the Pharmacy. No placebo will be used for those assigned not to receive SDD. Patients will either receive standard of care or standard of care + SDD. No treatment of any kind is being withheld from the participants. Enrolled patients will be those known to be colonized with VRE (after obtaining informed consent from patients or patients' proxy). SDD will be given enterally through the nasogastric tube which will then be clamped for 1 hour. SDD will be stopped when patients are extubated. Otherwise SDD will be given for 7 days.
Day 1 is when patients are started on SDD which consists of colistin 100 mg, gentamicin 80mg, and nystatin 2 million/U in 23mL. It is given every 6 hour via a nasogastric tube with the nasogastric tube then clamped for 1 hour. Stool will be collected once a day at baseline (pre administration of SDD), and then days 4, 7 and 14 for quantitative culture of resistant pathogens in the stool. VRE, MRSA and Pseudomonas aeruginosa will be sought. An endotracheal aspirate once a day will also be collected on these days (baseline, 1, 4, 7, and 14) for qualitative culture for the presence of MRSA and Pseudomonas aeruginosa. If there are no bowel movements on the days that stool is to be collected, no samples will be obtained. In addition, if the endotracheal tube is pulled, no further endotracheal aspirates will be obtained. Samples will only be obtained if available.
In addition, for women of child bearing potential (any female who is biologically capable of becoming pregnant), a small sample (about 1 teaspoonful) of blood will be taken from a vein in the subject's arm for a pregnancy test, prior to study drug administration. Pregnant women, or women who are currently breast-feeding an infant, will not be allowed to take part in this study.
The primary microbiologic endpoint will be measurement of fecal density of VRE on day 7, in comparison to measurements on day 1. Secondary endpoints are changes in VRE fecal density from baseline to day 14, changes in MRSA fecal density from baseline to day 14, and presence of colistin resistant Pseudomonas in stool or endotracheal aspirates at day 14.
The following information will also be collected: Demographic data (address, date of birth, etc.) which includes age, sex, height, weight, and state of birth, previous reports associated with the participant's condition, laboratory results, current medication use, and any other prior medical problems/history. This information will be obtain from the medical record and/or the subject and become part of the research record.
Sample storage of the organism
The biologic samples (organism) will be under the control of the principal investigator of this research project. To protect confidentiality, all personal identifiers (i.e., name, social security number, and birth date) will be removed (de-identified) and replaced with a specific code number. The information linking these code numbers to the corresponding subjects' identities will be kept in a separate, secure location. The investigators on this study will keep the samples indefinitely. The biologic samples will be provided to Dr. Curtis Donskey, Case Western Reserve University, Cleveland, Ohio. Dr Donskey will perform colony counts on the samples in order to determine the density of organisms in the sample, using methods he described in work he published in the New England Journal of Medicine (11). All samples will be provided de-identified. Dr Paterson will perform pulsed field gel electrophoresis on the isolates to determine if isolates are genotypically identical between baseline and post-SDD. If a subject withdraws and provides the request in writing, samples collected and not already processed will be destroyed. All samples will be kept in Dr Paterson's laboratory in Scaife Hall, Room 812, 3550 Terrace Street or in Donskey's laboratory at the Cleveland Veterans Affairs Medical Center, East Avenue, Cleveland OH.
