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- 1. A 26-year-old man is evaluated for a 3-day history of fever, lower abdominal pain, tenesmus, hematochezia, and watery diarrhea. Seven months ago, he underwent a cadaveric kidney transplantation. At the time of transplantation, the transplant donor was seropositive for cytomegalovirus, and the patient was seronegative for this virus. Current medications are tacrolimus, mycophenolate mofetil, prednisone, and trimethoprim-sulfamethoxazole. Valganciclovir was discontinued 1 month ago after 6 months of prophylaxis as per standard protocol. On physical examination, temperature is 38.8 C (101.8 F), blood pressure is 100/70 mm Hg, pulse rate is 104/min, and respiration rate is 18/min. BMI is 24. Cardiopulmonary examination is normal. Abdominal examination reveals increased bowel sounds but no tenderness to palpation. There is no organomegaly. WBC 2.1, ALT 72, AST 60, Cr 1.4 Which of the following is the most likely diagnosis? A. Clostridium difficile infection B. Cytomegalovirus infection C. Mycophenolate mofetil toxicity D. Tacrolimus toxicity
- 15. Year Stool Samples Collected Stool Samples Positive % Samples Positive 2015 2194 136 6.2 2017 2037 225 11
- 16. 2015 2017 Aeromonas spp. 22 (16.2%) 20 (8.9%) Campylobacter spp. 67 (49.3%) 44 (19.6%) Pleisiomonas spp. 2 (1.5%) 0 (0%) Shiga-toxin producing E. coli 2 (1.5%) 12 (5.3%) Salmonella spp. 15 (11%) 10 (4.4%) Shigella spp. 4 (2.9%) 22 (9.8%) Vibrio spp. 7 (5.2%) 4 (1.8%) Yersinia spp. 1 (0.7%) 4 (1.8%) Mixed 5 (3.7%) 9 (4%) Norovirus 11 (8%) 87 (38.7%) Rotavirus 0 (0%) 13 (5.8%) Total 136 225
- 17. 2015 2017 Campylobacter spp. 3096.6 495.48 P<0.0001 Shiga-toxin producing E. coli 2954 198.33 P=0.11 Salmonella spp. 3077.1 660.2 P=0.0005 Shigella spp. 4346.3 654.45 P<0.0001 Vibrio spp. 4293.4 209.5 P=0.0004 Yersinia spp. 4393 193.25 Mixed 4805 728.11 P=0.0003 Norovirus 5457.6 220 P<0.0001 Total 3603 (2 days 12 hours and 3 minutes) 368 (6 hours and 8 minutes) P<0.0001
- 18. P < .0001P < .0001
Editor's Notes
- The most likely diagnosis is cytomegalovirus (CMV) infection. Despite advances in immunosuppressive therapy and infection prophylaxis, more than 50% of kidney transplant recipients develop at least one infection during the first year after transplantation. CMV infection is particularly common in these patients. CMV infection is often suspected when patients have leukopenia and fevers during the posttransplant period. Viremia is best detected by polymerase chain reaction (PCR), a fast, sensitive, and reliable technique compared with serology, culture, or early antigen or CMV antigenemia detection. CMV infection can result in CMV disease, with organ involvement manifesting as retinitis, pneumonia, encephalitis, hepatitis, and gastrointestinal tract ulceration. This patient underwent kidney transplantation 7 months ago and discontinued his CMV prophylaxis therapy 1 month ago as per standard protocol. Kidney transplantation from a donor who is seropositive for CMV to a recipient who is seronegative for this virus places the recipient at high risk for developing this condition. Furthermore, this patient&apos;s fever, leukopenia, and diarrhea are consistent with CMV infection, and his elevated liver chemistry studies raise suspicion for CMV-related hepatitis. Diagnosis of CMV infection is confirmed with a positive serum PCR test for viremia, and disease is confirmed by the presence of mucosal ulcers or erosion and CMV inclusion bodies seen on a biopsy specimen from the wall of the bowel obtained during colonoscopy. Clostridium difficile infection may cause diarrhea and fever but does not explain this patient&apos;s leukopenia or elevated aminotransferase levels. Mycophenolate mofetil can cause diarrhea and leukopenia but is rarely associated with elevated liver chemistry studies and does not explain this patient&apos;s fever. In addition, toxicity associated with mycophenolate mofetil usually occurs after a recent dosage change. Tacrolimus toxicity can cause diarrhea but does not manifest as fever, leukopenia, or abnormal findings on liver chemistry studies.
- Causes of diarrhea is transplant recipients is similar to the ones for nontransplant recipeints with a few exceptions: -- higher indcidence of opp infections -- higher likelihood for development of chronic infections -- medication induced diarrhea -- dev of GVHD Tend to have more severe course with worse outcomes and complications, higher morbidity related to graft dysfunction A large, prospective study from Belgium – DIDACT looked at identifying the cause of post-transplant diarrhea in renal transplant recipients Medications – both immunosupressants and non-immunosupressants followed by infectious causes MMF results in the decrease in purine synthesis in cells inhibiting the cell cycle of rapidly dividing cells, including B and T lymphocytes and enterocytes. Diarrhea is the most common side effects and it occurs in 36% of pts
- The same study tried to identify a step-wise approach in the ID and mgmt. of diarrhea in SOT
- Highest risk of infection in those who are donor +, recipient -
- Because CMV produces lifelong latent infection, distinguishing active disease from latent infection and asymptomatic reactivation presents an additional diagnostic challenge.
- The reproducibility of viral load tests is such that changes in viral load need to exceed three- to fivefold to represent meaningful changes in viral replication
- In 2016, Virginia Mason adopted a multiplex panel as a screen for common diarrheal illnesses Verigene Enteric Pathogen Test These panels allow HC providers to cast a broad net and achieve a timely diagnosis, which may be really important in certain patient populations, such as immunocompromised hosts and critically ill patients.
- Comparison of workflow, throughput, and turnaround time among three commercial, FDA-cleared multiplex GI platforms. (A) The Luminex xTag GPP assay requires an initial sample preparation step (45 to 60 min), followed by nucleic acid extraction (∼45 min) and multiplex PCR using a standard thermocycler (2.5 h). Subsequently, the amplified product is incubated with tagged beads to allow for hybridization (1 h), and, finally, data are acquired and analyzed on either the Magpix or Luminex 100/200 analyzers (∼10 min). (B) The Nanosphere Verigene enteric pathogens (EP) test involves pipetting 200 μl of sample into a supplied extraction tray. The extraction tray, reagents, and test cartridge are then loaded into the Verigene Processor SP (∼2 min). The Processor SP automates nucleic acid extraction, amplification, and hybridization with gold nanoparticles. Finally, the test cartridge is removed from the Processor and inserted into the Verigene Reader for data analysis, with a total turnaround time of ∼2 h per test. (C) The BioFire FilmArray GI panel uses a loading station to facilitate the addition of hydration solution and patient sample into the test pouch via a vacuum-controlled syringe (∼2 min). Once the sample has been added, the test pouch is inserted into the FilmArray instrument, which then automates nucleic acid extraction, nested PCR, and data acquisition using melting curve analysis (∼60 min).
- Objectives: What is the turnaround time for pathogen identification? How long does it take from stool sample collection to antibiotic prescription? Retrospective chart review was performed on all stool cultures that returned positive in 2015. Additionally, retrospective chart review was performed on all positive RT PCR results in 2017. Clinical chart review by two resident physicians collected the following data: identification of microbial pathogen, antibiotics prescribed (if any), time of prescription and duration of antibiotics course. T test was used to examine the difference in time to identification of the pathogen and time to prescription between 2015 and 2017
- There was a significantly shorter time to microbial identification with the use of Multiplex PCR as compared with stool culture Multiplex PCR assays for enteric pathogens is a more sensitive test when compared to stool culture identification When the clinician felt antibiotics were indicated, there was a significantly shorter time to the prescription of antibiotics. Molecular assays detect an increased number of pathogens from a single specimen. This has an important impact on infection prevention and appropriate treatment. Future studies should be aimed at determining whether Multiplex PCR assays help to reduce the amount of unnecessary antibiotics prescribed for infectious acute diarrhea when compared to stool culture identification