Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00235664
Status:
COMPLETED
Last Update Posted:
2008-12-17
First Post:
2005-10-06
Brief Title:
Prospective Study of Drug Resistant Pathogens Among Liver Intestinal and Multivisceral Transplant Recipients
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
Prospective Study of Drug Resistant Pathogens Among Liver Intestinal and Multivisceral Transplant Recipients
Status:
COMPLETED
Status Verified Date:
2008-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Infections caused by multidrug resistant bacteria have become more prevalent at many tertiary care and academic centers These infections are associated with increased morbidity and mortality The initial empiric antibiotic choice may not be adequate and delay in initiating appropriate therapy is a reason for poorer outcomes Furthermore not uncommonly the only therapeutic options available are associated with significant toxicity This is a particular challenge for solid organ transplant recipients who are immunosuppressed and have a higher risk of acquiring infections Exposure to different classes of antibiotics has been linked to development of antibiotic resistance Determining the risk factors for acquisition of drug-resistant bacteria and the molecular mechanisms by which resistance occurs would allow the development and implementation of strategies to minimize these infections and therefore improve outcomes We the researchers at the University of Pittsburgh aim to collect surveillance cultures on patients undergoing liver intestinal and multivisceral transplantation in order to determine the prevalence and risk factors for Pseudomonas aeruginosa P aeruginosa extended-spectrum β-lactamases ESBL-Klebsiella and methicillin-resistant Staphylococcus aureus MRSA as well as determine the molecular mechanisms associated with the development of resistance in P aeruginosa
Detailed Description:
Methods
Day 1 is when patients are admitted to the Transplant intensive care unit ICU following liver intestinal or multivisceral transplantation Stool samples in the case of patients with rectal bags andor diarrhea for cefotaxime-resistant Gram negative rods would be obtained within 24 hours of admission to the ICU and weekly thereafter until discharge from the hospital or isolation of MDR P aeruginosa and ESBL- K pneumoniae whichever occurs first While patients are intubated endotracheal aspirates would also be obtained on a weekly basis Nasal swabs for MRSA would be obtained within 24 hours of admission to the ICU and weekly thereafter until discharge from the hospital or isolation of MRSA whichever comes first
If there are no bowel movements on the days that stool is to be collected a rectal swab 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 If the swab obtained on day 1 is positive for the organisms being studied no further samples will be obtained
No pregnancy testing will occur since all potential patients undergoing transplant must not be pregnant Pregnant women or women who are currently breast-feeding an infant will not be allowed to take part in this study
Once a drug-resistant organism MDR P aeruginosa ESBL K pneumoniae andor MRSA is isolated skin swabs from the groin and subclavian areas will be obtained once No further swabs will be obtained from the patient but heshe will be followed clinically to determine the impact of the organism on the patients clinical outcome
Cultures obtained at the discretion of the treating physician will be reviewed and if P aeruginosa ESBL-K pneumoniae or MRSA are isolated they will be collected from the diagnostic microbiology laboratory and stored in Dr Patersons laboratory for further analysis of molecular mechanisms of resistance These samples would have been discarded once identification and susceptibility testing is completed by the diagnostic lab
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 participants condition laboratory results current medication use and any other prior medical problemshistory history of prior admission reason for transplantation history of prior transplantation immunosuppression used antimicrobials received other surgeries performed duration of mechanical ventilation requirement for dialysis microbiological studies available simplified acute physiologic score SAPS on admission duration of ICU stay This information will be obtained from the medical records andor the subject and become part of the research record
The patient will be seen as an inpatient at the University of Pittsburgh Medical Center and each visit will take approximately 30 minutes The patient will be seen by a member of the research team
Sample storage of the organism
The biologic samples will be under the control of the principal investigator of this research project To protect confidentiality all personal identifiers ie 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 All samples will be provided de-identified 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 Patersons laboratory in Scaife Hall Room 812 3550 Terrace Street Pittsburgh PA
The patient has completed the study once the patient is discharged from the hospital
Laboratory methods
Swabs for P aeruginosa and ESBL-K pneumoniae will be planted on cetrimide agar and nutrient agar supplemented with cefotaxime vancomycin and amphotericin B Antimicrobial susceptibility testing will be performed using disk diffusion test and E-test ESBL screening will be performed using double disk diffusion test and E-test with cefotaxime-cefotaximeclavulanic acid and ceftazidime-ceftazidimeclavulanic acid
Swabs for MRSA will be planted in a chromogenic media selective for MRSA
In order to study the molecular mechanisms responsible for the development of antimicrobial resistance among the P aeruginosa isolates quantitative real-time PCR on genes encoding common efflux pumps PCR for mutations in quinolone resistance determining regions gyrA gyrB and parC genes and PCR for beta-lactamases will be performed
Pulsed-field gel electrophoresis PFGE will be performed on the isolates of each single patient to determine if the isolates are genotypically similar PFGE will also be done in all MDR P aeruginosa isolates in order to determine if they belong to a single or multiple clones within the ICU
Day 1 is when patients are admitted to the Transplant intensive care unit ICU following liver intestinal or multivisceral transplantation Stool samples in the case of patients with rectal bags andor diarrhea for cefotaxime-resistant Gram negative rods would be obtained within 24 hours of admission to the ICU and weekly thereafter until discharge from the hospital or isolation of MDR P aeruginosa and ESBL- K pneumoniae whichever occurs first While patients are intubated endotracheal aspirates would also be obtained on a weekly basis Nasal swabs for MRSA would be obtained within 24 hours of admission to the ICU and weekly thereafter until discharge from the hospital or isolation of MRSA whichever comes first
If there are no bowel movements on the days that stool is to be collected a rectal swab 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 If the swab obtained on day 1 is positive for the organisms being studied no further samples will be obtained
No pregnancy testing will occur since all potential patients undergoing transplant must not be pregnant Pregnant women or women who are currently breast-feeding an infant will not be allowed to take part in this study
Once a drug-resistant organism MDR P aeruginosa ESBL K pneumoniae andor MRSA is isolated skin swabs from the groin and subclavian areas will be obtained once No further swabs will be obtained from the patient but heshe will be followed clinically to determine the impact of the organism on the patients clinical outcome
Cultures obtained at the discretion of the treating physician will be reviewed and if P aeruginosa ESBL-K pneumoniae or MRSA are isolated they will be collected from the diagnostic microbiology laboratory and stored in Dr Patersons laboratory for further analysis of molecular mechanisms of resistance These samples would have been discarded once identification and susceptibility testing is completed by the diagnostic lab
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 participants condition laboratory results current medication use and any other prior medical problemshistory history of prior admission reason for transplantation history of prior transplantation immunosuppression used antimicrobials received other surgeries performed duration of mechanical ventilation requirement for dialysis microbiological studies available simplified acute physiologic score SAPS on admission duration of ICU stay This information will be obtained from the medical records andor the subject and become part of the research record
The patient will be seen as an inpatient at the University of Pittsburgh Medical Center and each visit will take approximately 30 minutes The patient will be seen by a member of the research team
Sample storage of the organism
The biologic samples will be under the control of the principal investigator of this research project To protect confidentiality all personal identifiers ie 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 All samples will be provided de-identified 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 Patersons laboratory in Scaife Hall Room 812 3550 Terrace Street Pittsburgh PA
The patient has completed the study once the patient is discharged from the hospital
Laboratory methods
Swabs for P aeruginosa and ESBL-K pneumoniae will be planted on cetrimide agar and nutrient agar supplemented with cefotaxime vancomycin and amphotericin B Antimicrobial susceptibility testing will be performed using disk diffusion test and E-test ESBL screening will be performed using double disk diffusion test and E-test with cefotaxime-cefotaximeclavulanic acid and ceftazidime-ceftazidimeclavulanic acid
Swabs for MRSA will be planted in a chromogenic media selective for MRSA
In order to study the molecular mechanisms responsible for the development of antimicrobial resistance among the P aeruginosa isolates quantitative real-time PCR on genes encoding common efflux pumps PCR for mutations in quinolone resistance determining regions gyrA gyrB and parC genes and PCR for beta-lactamases will be performed
Pulsed-field gel electrophoresis PFGE will be performed on the isolates of each single patient to determine if the isolates are genotypically similar PFGE will also be done in all MDR P aeruginosa isolates in order to determine if they belong to a single or multiple clones within the ICU
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None