Bacteremia among kidney transplant recipients: a case-control study of risk factors and short-term outcomes

Kidney transplant recipients are highly susceptible to life-threatening infections, including bacteremia. To determine the risk factors for bacteremia within the first month after renal transplantation we performed a non-concurrent transplant population-based case-control study involving all 1,000 consecutively operated adult patients at Helsinki University Central Hospital in 1987-93. All patients with at least 1 positive blood culture within 31 d of transplantation were defined as cases. Control patients were drawn systematically from the transplant population with no positive blood cultures within the first 31 d post-transplant. The study included 35 cases and 123 controls. The overall rate of bacteremia in the population was 3.5%. The case patients were more likely to have been on haemodialysis prior to transplantation (71%, vs. 43%, p < 0.05) and to have experienced acute rejection (46% vs. 20%, p < 0.05) than the controls. Local infections (46% vs. 12%, p < 0.05) were also more common among case patients. In the crude analysis an additive interaction of acute rejection and haemodialysis was found, with a 10% rate of bacteremia occurring if both conditions were present. The mortality rate within 2 months of follow-up was higher among case patients than among controls (14%, vs. 1%, p < 0.05) and they also returned more often to dialysis (23% vs. 4%, p < 0.05). Bacteremia during the immediate postoperative period might still have severe outcomes measured as allograft and patient survival at 2 months post-transplant. Further evaluation will confirm whether a lower rate of bacteremia among kidney transplantation patients can be achieved if peritoneal dialysis is preferred to haemodialysis whenever possible.     

Bacteremia in transplant recipients: a prospective study of demographics, etiologic agents, risk factors, and outcomes.

BACKGROUND: Bacteremic infections are a major cause of death among organ transplant recipients. We sought to identify the risk factors associated with death and examine the timing of the bacteremic episode after operation to recognize patients who may benefit from perioperative prophylactic antibiotic therapy. METHODS: A total of 125 episodes of bacteremia or fungemia in 16 heart, 26 kidney, and 70 liver recipients were monitored prospectively in 1 year. RESULTS: The urinary tract was the most frequent portal for kidney recipients, the gastrointestinal and biliary tracts were frequent for liver recipients, and the lung was frequent in heart recipients. Heart and liver recipients were more severely ill at the time of bacteremia and had bacteremia sooner after operation. Death at 14 days after onset of bacteremia was 33% in heart recipients, 24% in liver recipients, and 11% in kidney recipients. Risk of death was associated with the severity of the underlying condition of the transplant recipient, the source of the bacteremia, and the microbial agent. Pseudomonas aeruginosa and Enterobacter species had fatality rates of 47% and 63%, respectively. P. aeruginosa and Enterobacter were also most commonly associated with failures of perioperative antibiotic prophylaxis. CONCLUSIONS: There are distinct clinical patterns of bacteremia in transplant recipients. The emergence of P. aeruginosa and Enterobacter species in the immediate postoperative period appeared to be a significant cause of morbidity and death among transplant recipients.     

Bacteremia and antimicrobial susceptibilities in HIV-infected patients at Siriraj Hospital

Bacterial infections in human immunodeficiency virus (HIV) infected patients may frequently develop into septicemia. Our study evaluated the bacterial pathogens isolated from hemocultures of HIV-infected patients at Siriraj Hospital and their antimicrobial susceptibility tests. The percentages of positive hemocultures were 24.64, 21.38, 23.88, and 28.46% in 1996, 1997, 1998, and 1999, respectively. Salmonella spp was the most pathogen isolated, followed by Escherichia coil (10.93%), Staphylococcus aureus (8.2%), coagulase-negative staphylococci (6.56%), nonfermentative gram-negative rods (6.01%), Pseudomonas aeruginosa (5.46%), Klebsiella pneumoniae (4.37%), and Enterobacter spp (4.37%). Salmonella, serogroup C was the most frequently isolated serogroup. It was sensitive to amoxicillin/clavulanate in 100%, ampicillin/sulbactam in 89%, cefazolin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, imipenem, gentamicin, amikacin, netilmycin, ofloxacin, and ciprofloxacin in 100%. The changing spectrum of bacteria and antimicrobial susceptibility patterns in HIV-1 infected patients may provide a guideline for the selection of appropriate drugs for treatment.     

Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.     

Optimal blood concentration of cyclosporine among Iranian kidney transplant recipients

Introduction. Clinical information concerning cyclosporine dose reduction in Iranian kidney transplant recipients is limited. There are data in Asian, Caucasian, and Iranian ethnic kidney transplant recipients that recommend the trough level (C0) and 2-hour postdose level (C2) of cyclosporine may be different. Our aim was to determine therapeutic levels of C0 and C2 at different time after transplantation among Iranian transplant patients. Materials and Methods. Blood concentrations of cyclosporine were assessed in 4419 samples of kidney transplant recipients between 2008 and 2010. The patients were divided into 3 groups according to the time of laboratory studies (< 3 months, 4 to 12 months, and > 1 year after transplantation). Both univariable and multivariable analyses were performed to determine the correlation between cyclosporine blood levels and serum creatinine. Results. A total of 1270 kidney transplant patients with 4419 blood samples enrolled. The mean age of the donor was 28 ± 6 years (range, 6 to 64 years) and 82.6% were men and 17.4% were women. In the subset of patients with serum creatinine values of at least 1.6 mg/dL for men and 1.4 mg/dL for women, we determined C0 and C2 levels between therapeutic and undertherapeutic creatinine ranges at 3 different time interval after transplantation, as follows: the first 3 months, 230 ng/mL to 240 ng/mL and 725 ng/mL to 775 ng/mL; 4 to 12 months, 135 ng/mL to 156 ng/mL and 535 ng/mL to 612 ng/mL; and after 1 year, 95 ng/mL to 120 ng/mL and 420 ng/mL to 479 ng/mL for C0 and C2, respectively. Conclusions. The present study suggests that the cyclosporine levels for Iranian kidney transplant patients are lower compared to the recommended levels in western countries.     

Cryptococcosis in liver and kidney transplant recipients receiving anti-thymocyte globulin or alemtuzumab

Rabbit anti-thymocyte globulin (ATG) and alemtuzumab have been used for induction or preconditioning and for the treatment of acute rejection in organ transplant recipients in many centers. Such regimens may lead to a substantial decline in the CD4 lymphocyte count to levels seen in other population groups at high risk of cryptococcosis. In view of this, we examined the impact of such therapy on the cumulative incidence of cryptococcosis among liver and kidney recipients. A total of 834 liver and 727 kidney transplants were performed during the study period. Seven hundred and eighty-one patients did not receive ATG or alemtuzumab; 646 received 1 dose of either drug, and 134 patients received 2 doses of either drug. The cumulative incidence of cryptococcosis was 0.26% (2/781) among those who did not receive ATG or alemtuzumab; 0.3% (2/646) among those who received only 1 dose, and 2.24% (3/134) among those who received 2 doses (P=0.03). There were 5 cases of cryptococcosis in liver recipients and 2 in kidney recipients. There were 3 cases of cryptococcal meningitis, 3 of pneumonia, and 1 of disseminated disease. The 2 kidney recipients had meningitis. Diagnosis occurred at a median of 255 days (range 7-517) after transplantation. The mortality rate was 14.2%. We conclude that the use of 1 dose of ATG or alemtuzumab is not associated with an increased cumulative incidence of cryptococcosis, but that those patients receiving 2 doses are at increased risk.     

The predictors of post-transplant coronary events among liver transplant recipients

Background/purpose

Cardiac morbidities can occur during the peri- and post-liver transplant (LT) period, affecting the long-term survival. The purpose of this study was to identify the potential factors that predict a coronary event post-transplantation.

Methods

Medical records of patients who underwent liver transplantation at Johns Hopkins Hospital between 2009 and 2013 were retrospectively reviewed. We looked at pre-liver transplant cardiac risk factors and the diagnostic tests utilized for coronary artery disease screening. Patients with and without post-liver transplant coronary events were compared.

Results

There were a total of 146 patients with a mean age at LT of 55.3 years. The prevalence of hypertension, tobacco use and diabetes within the patient population was 61.6 % (n = 90), 39 % (n = 57) and 37.6 % (n = 55), respectively. There were 29 deaths and 30 coronary events over a median follow-up period of 1.75 years. Age at the time of liver transplant was predictive of coronary event (OR 1.11, CI 1.01–1.20). The 1-year survival in patients with a coronary event was 47 versus 94 % in patients without a coronary event. The combined use of a dobutamine stress echocardiogram and coronary artery calcium score predicted a coronary event with a sensitivity of 62.5 % and specificity of 66.7 %.

Conclusion

In conclusion, LT recipients with cardiac events had limited survival as compared to the cohort without coronary events. Identification of such patients with noninvasive screening may provide a practical alternative to an invasive cardiac workup. Further improvement in screening strategies may minimize the liver transplant cardiac morbidity.

     

Pharmaceutical management of hepatitis B and C in liver and kidney transplant recipients

The combination of hepatitis B immune globulin with entecavir or tenofovir (at least for a certain period of time) seems to be the most reasonable prophylaxis against recurrent hepatitis B after liver transplantation. Entecavir represents an attractive option for treatment of naïve kidney transplant recipients, because of its high efficacy and the low rates of resistance. However antiviral treatment should be individualized in the view of kidney function and the previous resistance. To date, new captivating therapeutic strategies could make interferon-free regimens viable for treatment of hepatitis C virus positive liver transplant recipients. The recent combinations of sofosbuvir with simeprevir or daclatasvir or ledipasvir plus/minus ribavirin have boosted the on treatment and sustained virological response to rates approaching 100% within liver transplant recipients with recurrent chronic hepatitis C (CHC). Preliminary data showed that the second generation direct oral antivirals could result to high treatment rates of recurrent CHC in kidney transplant recipients as well. Ongoing studies will clarify the optimal treatment of recurrent CHC in kidney transplant recipients.     

Safety and efficacy of granulocyte colony-stimulating factor in kidney and liver transplant recipients

Background: Leukopenia is not infrequently encountered following solid organ transplantation, most often in the setting of cytomegalovirus (CMV) disease and/or its treatment with ganciclovir. The present study was undertaken to determine the safety and efficacy of granulocyte colony‐stimulating factor (G‐CSF) in renal and liver transplant recipients with leukopenia. Methods: Between 1 June 1991 and 1 June 1998, patients received G‐CSF for 2 indications: 1) white blood cell count (WBC) <3000/mm³, with a decline from baseline; 2) to shorten the duration of leukopenia associated with chemotherapy. A retrospective review of the outcome of such therapy was undertaken. Results: 50 patients were given 100 courses of treatment with G‐CSF; 35 of 168 liver transplant recipients (20.8%), 14 of 391 kidney transplant recipients (3.6%), and 1 of 4 recipients of combined liver–kidney transplants (25.0%) received from 1 to 9 courses of G‐CSF. Presumed causes of leukopenia were identified as ganciclovir in 28 cases (28.0%), CMV in 21 (21.0%), chemotherapy in 12 (12.0%), sepsis in 11 (11.0%), azathioprine in 5 (5.0%), interferon in 3 (3.0%) and other causes in 20 cases (20.0%). The median length of therapy was 10.0 days (range 1–154 days) and the average dose of daily G‐CSF received was 3.9±1.5 μg/kg/day. The average WBC was (2.4±1.3)×10³/μl at the beginning of therapy, and (13.8±9.1)×10³/μl at the end of therapy. In 7 of 100 treatments (7.0%) a WBC of 5.0×10³/μl was not reached during G‐CSF therapy; in 6 of these 7 cases, G‐CSF therapy lasted fewer than 4 days. The mean time needed to reach a WBC count of 5×10³/μl was 3.7±3.3 days among 71 patients who had daily WBC counts sent. Eight G‐CSF treatments (8.0%) were followed by episodes of rejection appearing during or within 2 months of treatment; 5 of them were biopsy‐documented. No relation was found between the highest WBC obtained during G‐CSF therapy and the risk of rejection. Eight patients (16.0%) died while receiving G‐CSF, all from infection. Six of these 8 patients were receiving G‐CSF for leukopenia secondary to sepsis. Overall, 25 patients (50.0%) received 49 courses of G‐CSF secondary to CMV and/or ganciclovir therapy. In 40 of 49 courses (81.6%), ganciclovir could be continued at recommended doses. Twenty‐one of 22 patients (95.5%) with symptomatic CMV infection had a clinical response to ganciclovir. Sixteen of 18 patients (88.9%) treated for a CMV infection and followed with serial antigenemia assays attained microbiological cure; both patients who did not were infected with ganciclovir resistant CMV. Conclusion: G‐CSF was well tolerated in solid organ transplant recipients. It was particularly useful in patients with CMV disease, allowing optimal ganciclovir therapy ( Note Presented in part at the American Society of Transplant Physicians Meeting, Chicago, Illinois, May 1999.
).     

Polyomavirus in kidney and kidney--pancreas transplant recipients

Abstract: Purpose. To report the incidence and clinical characteristics of polyomavirus (PV) nephritis in kidney (KTX) and kidney–pancreas transplant (KPTX) recipients. Methods. Single center retrospective analysis of all cases of PV nephritis in KTX and KPTX patients transplanted between 1994 and 1999. Results. Thirteen (5 KTX and 8 KPTX) patients (2.1%) had PV nephritis diagnosed on multiple biopsies (n = 22) among 504 KTX and 106 KPTX recipients. The incidence of PV nephritis was higher in cadaver donor transplants (2.6% cadaver vs. 0.7% living donors), after KPTX (1% KTX vs. 7.5% KPTX), in males (3.3% male vs. 0.7% female), and in diabetic patients (4.4% diabetic vs. 0.8% nondiabetic). The mean time to diagnosis of PV nephritis was 18 (range 6–48) months after KTX and 17 (range 9–31) months after KPTX. Three KTX patients and 5 KPTX patients had calcineurin inhibitor toxicity on biopsy prior to developing PV nephritis. Reduction in immunosuppression occurred in 100% of KTX and 63% of KPTX patients. Three patients (23%) developed rejection within 3 months of diagnosis of PV, 1 after a reduction in immunosuppression. Despite multiple antiviral treatment regimens, renal allograft failure requiring dialysis occurred in 60% of KTX and 50% of KPTX patients. All KPTX patients remain insulin independent and 2 were successfully retransplanted with living donor kidneys. 2 patients (15%) died but there was no mortality directly related to the virus. Conclusions. Polyomavirus nephritis may be increasing in incidence and appears to be unresponsive to either conventional antiviral agents or a reduction in immunosuppression. Most of our cases occurred in male diabetic patients undergoing cadaveric donor transplantation and were preceded by biopsy‐proven nephrotoxicity. Further studies are needed to better define the pathogenesis of PV and effective antiviral treatment.     

Infections in liver transplant recipients

Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications.In this article,we review the contemporary state of infectious complications during the post-operative period,with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation.Bacteria,and less commonly Candida infections,remain the predominant pathogens during the immediate post-operative period,especially during the first month,and infections caused by drugresistant strains are emerging.Infections caused by cytomegalovirus and Aspergillus sp.present clinically during the"opportunistic"period characterized by intense immunosuppression.As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed,one potential adverse effect is an increase in certain infections.Hence,it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk,local antimicrobial resistance patterns,and surveillance.A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.     

Lipids in liver transplant recipients

Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drugdrug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation.