Transplantation Clinical Trial
Official title:
Prospective Study of Drug Resistant Pathogens Among Liver, Intestinal and Multivisceral Transplant Recipients
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.
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 and/or 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 and/or 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 he/she will be followed clinically to determine
the impact of the organism on the patient's 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. Paterson's 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 participant's condition, laboratory results, current medication use, and
any other prior medical problems/history, 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
and/or 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 (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. 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 Paterson's 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-cefotaxime/clavulanic acid and ceftazidime-ceftazidime/clavulanic 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.
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