Herpes zoster incidence in a multicenter cohort of solid organ transplant recipients

S.A. Pergam, C.W. Forsberg, M.J. Boeckh, C. Maynard, A.P. Limaye, A. Wald, N.L. Smith, B.A. Young. Herpes zoster incidence in a multicenter cohort of solid organ transplant recipients.
Transpl Infect Dis 2011: 13: 15–23. All rights reserved Background. Immunosuppressed patients are at increased risk for herpes zoster (HZ), but incidence in solid organ transplant (SOT) recipients has varied in multiple studies. To assess incidence of HZ, we examined patients who underwent SOT and received follow‐up care within the large multicenter US Department of Veteran's Affairs healthcare system. Methods. Incident cases of HZ were determined using ICD‐9 coding from administrative databases. A multivariable Cox proportional hazards model, adjusted for a priori risk factors, was used to assess demographic factors associated with development of HZ. Results. Among the 1077 eligible SOT recipients, the cohort‐specific incidence rate of HZ was 22.2 per 1000 patient‐years (95% confidence interval [CI], 18.1–27.4). African Americans (37.6 per 1000 [95% CI, 25.0–56.6]) and heart transplants recipients (40.0 per 1000 [95% CI, 23.2–68.9]) had the highest incidence of HZ. Patients transplanted between 2005 and 2007 had the lowest incidence (15.3 per 1000 [95% CI, 8.2–28.3]). In a multivariable model, African Americans (hazard ratio [HR] 1.88; 95% CI: 1.12, 3.17) and older transplant recipients (HR 1.13; 95% CI: 1.01, 1.27 [per 5‐year increment]) had increased relative hazards of HZ. Conclusions. These data demonstrate that HZ is a common infectious complication following SOT. Future studies focused on HZ prevention are needed in this high‐risk population.     

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis

M.G.J. de Boer, F.P. Kroon, S. le Cessie, J.W. de Fijter, J.T. van Dissel. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.
Transpl Infect Dis 2011: 13: 559–569. All rights reserved Abstract: Risk stratification‐based duration of trimethoprim‐sulfamethoxazole (TMP‐SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence‐based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time‐matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni‐ and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3–5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1–17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2–7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9–18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients – and during the first year posttransplantation for patients >55 years of age or those treated for rejection – would result in very low PCP incidence and optimal avoidance of TMP‐SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.     

Multidrug‐resistant tuberculosis in transplant recipients: Case report and review of the literature

Transplant recipients are at increased risk of tuberculosis (TB). We describe a case of pulmonary and vertebral multidrug‐resistant TB (MDR‐TB) in a kidney transplant patient who required neurosurgical intervention and unfortunately developed fatal nosocomial complications. Thirteen transplant recipients with MDR‐TB were previously reported in the literature (one hematopoietic cell transplant, one heart transplant, one lung transplant, one heart‐lung transplant, and nine kidney transplant recipients). Extrapulmonary disease, severe treatment complications, and deaths were observed in patients who developed MDR‐TB after transplantation.     

Trends in invasive disease due to Candida species following heart and lung transplantation

Abstract: Although invasive candidiasis (IC) causes significant morbidity and mortality in patients who undergo heart, lung, or heart–lung transplantation, a systematic study in a large cohort of thoracic organ transplant recipients has not been reported to date. Clinical and microbiological data were reviewed for 1305 patients who underwent thoracic organ transplantation at Stanford University Medical Center between 1980 and 2004. We identified and analyzed 76 episodes of IC in 68 patients (overall incidence 5.2% per patient). The incidence of IC was higher in lung (LTx) and heart–lung transplant (HLTx) recipients as compared with heart transplant (HTx) recipients (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.1–2.7). The incidence of IC decreased over time in all thoracic organ transplant recipients, decreasing from 6.1% in the 1980–1986 time period to 2.1% in the 2001–2004 era in the HTx recipients, and from 20% in the 1980–1986 period to 1.8% in the 2001–2004 period in the LTx and HLTx recipients. The most common site of infection differed between the HTx and LTx cohorts, with bloodstream or disseminated disease in the former and tracheobronchitis in the latter. IC in the first year after transplant was significantly associated with death in both HTx (RR 2.9, 95% CI 1.8–4.6, P=0.001) and LTx and HLTx patients (RR 3.0, 95% CI 1.9–4.6, P<0.001). The attributable mortality from IC decreased during the 25‐year period of observation, from 36% to 20% in the HTx recipients and from 39% to 15% in the LTx and HLTx recipients. There were a significant number of cases caused by non‐albicans Candida species in all patients, with a trend toward higher mortality in the HTx group. In conclusion, the incidence and attributable mortality of IC in thoracic organ transplant recipients has significantly declined over the past 25 years. The use of newer antifungal agents for prophylaxis and treatment, the decrease in the incidence of cytomegalovirus disease, and the use of more selective immunosuppression, among other factors, may have been responsible for this change.     

Risk of diffuse large B‐cell lymphoma after solid organ transplantation in the United States

Non‐Hodgkin lymphoma arising in the context of immunosuppression is an important adverse outcome after solid organ transplantation. Diffuse large B‐cell lymphoma (DLBCL) is the most commonly diagnosed subtype of post‐transplantation non‐Hodgkin lymphoma, but few studies of transplant recipients have examined subtype‐specific risks. Therefore, we examined DLBCL risk in the Transplant Cancer Match Study, including registry‐based cancer ascertainment among 96,615 solid organ transplants performed from 2000 to 2008. We determined standardized incidence ratios (SIRs) and 95% confidence intervals comparing DLBCL risk in transplant recipients with that in the general population, and used multivariable Poisson regression models to assess the impact of potential risk factors. We identified 321 incident cases of DLBCL, over 12 times more than expected based on general population rates (SIR = 12.6, 95% confidence interval = 11.2–14.0). SIRs were highest in young recipients and those receiving a lung or pancreas/kidney–pancreas transplant, and were greatly elevated for extranodal DLBCLs at the site of the transplantation compared with other sites. DLBCL risk was highest in the first year following transplantation, and SIRs for early‐onset DLBCL risk were elevated in association with Epstein‐Barr virus‐negative serostatus and use of polyclonal antibody induction therapy. In conclusion, associations between recipient and transplant factors and post‐transplantation DLBCL risk suggest a complicated interrelationship among multiple risk factors and timing of disease. Am. J. Hematol. 89:714–720, 2014. © 2014 Wiley Periodicals, Inc.     

Hepatitis C in transplant recipients of solid organs, other than liver

Hepatitis C virus (HCV) infection is prevalent in candidates for, and recipients of, solid organ transplants. HCV infection can lead to diminished patient and allograft survival in the long-term in recipients of kidney transplants. Outcomes in recipients of other solid organ transplants (lung, heart, small bowel, pancreas, pancreas-kidney) are not well established. Large, well-designed, prospective studies are needed to answer these questions. Interferon therapy for HCV before transplantation can lead to improved outcomes. Therefore, transplant candidates should be considered for and offered interferon therapy before embarking on organ transplantation. Posttransplant interferon therapy can be complicated by acute allograft rejection and is not recommended, except with advanced liver disease.     

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.     

Incidence of cancer after immunosuppressive treatment for heart transplantation

Prolonged or intensive immunosuppressive therapy used after organ transplantation is complicated by an increased incidence of cancer. Striking differences in incidence are observed in heart and heart-lung transplant recipients when compared with renal transplant patients. The most significant increase was in the incidence of lymphomas in cardiac versus renal patients. Moreover, a two-fold greater increase of all neoplasms was found in cardiac recipients, with nearly a six-fold increase in visceral tumors. Several factors may account for these differences. In cardiac allograft recipients, intensive immunosuppression is frequently used to reverse acute rejection and the highest number of cardiac transplants was performed in the era of polypharmacy, usually consisting of triple therapy.     

Burkitt lymphoma risk in U.S. solid organ transplant recipients

Case reports of Burkitt lymphoma (BL) in transplant recipients suggest that the risk is markedly elevated. Therefore, we investigated the incidence of BL in 203,557 solid organ recipients in the U.S. Transplant Cancer Match Study (1987–2009) and compared it with the general population using standardized incidence ratios. We also assessed associations with demographic and clinical characteristics, and treatments used to induce therapeutic immunosuppression. BL incidence was 10.8 per 100,000 person‐years, representing 23‐fold (95% confidence interval (CI) 19–28) greater risk than in the general population, and it peaked 3–8 years after the time of transplantation. In adjusted analyses, BL incidence was higher in recipients transplanted when <18 vs. ≥35 years (incidence rate ratio [IRR] 3.49, 95% CI 2.08–5.68) and in those transplanted with a liver (IRR 2.91, 95% CI 1.68–5.09) or heart (IRR 2.39, 95% CI 1.30–4.31) compared with kidney. BL incidence was lower in females than males (IRR 0.45, 95% CI 0.28–0.71), in blacks than whites (IRR 0.33, 95% CI 0.12–0.74), in those with a baseline Epstein‐Barr virus (EBV)‐seropositive versus EBV‐seronegative status (IRR 0.34, 95% CI 0.13–0.93), and in those treated with azathioprine (IRR 0.56, 95% CI 0.34–0.89) or corticosteroids (IRR 0.48, 95% CI 0.29–0.82). Tumors were EBV‐positive in 69% of 32 cases with results. EBV positivity was 90% in those aged <18 years and 59% in those aged 18+ years. In conclusion, BL risk is markedly elevated in transplant recipients, and it is associated with certain demographic and clinical features. EBV was positive in most but not all BL cases with results. Am. J. Hematol. 88:245–250, 2013. © 2012 Wiley Periodicals, Inc.     

Epidemiology,outcomes, and mortality predictors of invasive mold infections among transplant recipients: a 10‐year,single‐center experience

Background

The epidemiology of invasive mold infections (IMI) in transplant recipients differs based on geography, hosts, preventative strategies, and methods of diagnosis.

Methods

We conducted a retrospective observational study to evaluate the epidemiology of proven and probable IMI, using prior definitions, among all adult hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients in the era of “classic” culture‐based diagnostics (2000–2009). Epidemiology was evaluated before and after an initiative was begun to increase bronchoscopy in HSCT recipients after 2005.

Results

In total, 106 patients with one IMI were identified. Invasive aspergillosis (IA) was the most common IMI (69; 65.1%), followed by mucormycosis (9; 8.5%). The overall rate of IMI (and IA) was 3.5% (2.5%) in allogeneic HSCT recipients. The overall incidence for IMI among lung, kidney, liver, and heart transplant recipients was 49, 2, 11, and 10 per 1000 person‐years, respectively. The observed rate of IMI among human leukocyte antigen‐matched unrelated and haploidentical HSCT recipients increased from 0.6% annually to 3.0% after bronchoscopy initiation (P < 0.05). The 12‐week mortality among allogeneic HSCT, liver, kidney, heart, and lung recipients with IMI was 52.4%, 47.1%, 27.8%, 16.7%, and 9.5%, respectively. Among allogeneic HSCT (odds ratio [OR]: 0.07, P = 0.007) and SOT (OR: 0.22, P = 0.05) recipients with IA, normal platelet count was associated with improved survival. Male gender (OR: 14.4, P = 0.007) and elevated bilirubin (OR: 5.7, P = 0.04) were significant predictors of mortality for allogeneic HSCT and SOT recipients with IA, respectively.

Conclusions

During the era of culture‐based diagnostics, observed rates of IMI were low among all transplants except lung transplant recipients, with relatively higher mortality rates. Diagnostic aggressiveness and host variables impact the reported incidence and outcome of IMI and likely account for institutional variability in multicenter studies. Definitions to standardize diagnoses among SOT recipients are needed.     

Different behaviour of BK-virus infection in liver transplant recipients

Polyomavirus BK(BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A Pub Med search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease(CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication.     

Cryptococcal meningitis: an analysis among 5521 consecutive organ transplant recipients

Abstract: Cryptococcal meningitis has been reported to be an important cause of morbidity and mortality in renal transplant recipients. However, additional studies of recipients of other organ transplants suggested that these patients might be at low risk for cryptococcal meningitis. We examined the incidence and clinical features of cryptococcal meningitis among different groups of organ transplant patients at the University of Pittsburgh Medical Center. From January 1989 through July 1999, 28 patients were diagnosed with cryptococcal meningitis among 5521 transplant recipients. These included liver (11/2539), heart (8/372), kidney (7/2122), lung (1/432), and small bowel (1/56) recipients. The incidence of cryptococcal meningitis was higher in heart and small bowel recipients compared to other transplant populations ( P  = 0.005). The cryptococcal meningitis-related mortality in transplant recipients was 50% and was associated with altered mental status ( P  = 0.001), absence of headache ( P  = 0.02), and liver failure ( P  = 0.002). Multivariable analysis indicated that liver failure was the only independent risk factor for poor prognosis ( P  = 0.043). All cases of liver failure occurred among liver transplant recipients. Cryptococcal meningitis is associated with significant mortality among organ transplant recipients. The presence of allograft failure in liver transplant recipients with cryptococcal meningitis may be an indicator of poor prognosis in this patient population.     

Treatment issues surrounding hepatitis C in renal transplantation: a review

Hepatitis C infection is prevalent in candidates for and recipients of solid organ transplants. In the renal transplant population, HCV infection has been shown to decrease long-term patient and graft survival. The outcomes of HCV in recipients of other solid organ transplants are yet to be established and prospective studies will be needed in the future. In the absence of effective and safe antiviral treatment for HCV infection in renal, heart, and lung transplant recipients, the management of these patients remains a challenge and has led to an increased focus on identifying and treating hepatitis C in patients prior to transplantation. Interferon-based therapy for HCV prior transplantation appears to improve outcomes after transplantation. On the other hand, post-transplant interferon therapy is associated with an increased risk of graft rejection. Given the paucity of information on HCV treatment in solid organ transplant recipients, there is a great need for large-scale, multi-centre randomized controlled trials to determine the optimal approach to HCV infection in this population. This article will summarize the current peer-reviewed literature focusing on the efficacy of amantadine, ribavirin and both standard and pegylated interferon in the treatment of chronic hepatitis C in renal, transplant recipients.     

Low rates of vaccination in listed kidney transplant candidates

Despite clear consensus and strong recommendations, vaccination rates of kidney transplant (KT) recipients have remained below targets. As vaccination is most effective if it is given prior to transplantation and the initiation of immunosuppression, patients should ideally have their vaccination status assessed and optimized in the pre‐transplant period. We performed a retrospective chart review to characterize vaccination rates and factors associated with gaps in vaccination in a single‐center population of waitlisted patients being evaluated for kidney transplantation. We evaluated 362 KT patients. Three‐quarters were receiving dialysis at the time of evaluation. Immunization rates were low with 35.9% of patients having completed vaccination for Pneumococcus, 55% for influenza, 6.9% for zoster, and 2.5% for tetanus. On multivariable analysis, patients who received other vaccines, including influenza, tetanus, or zoster vaccine (odds ratio [OR] 10.55, 95% confidence interval [CI] 5.65–19.71) were more likely to receive pneumococcal vaccine. Blacks (OR 0.24, 95% CI 0.12–0.47) were less likely to receive pneumococcal vaccine compared to whites. Patients on dialysis, and those active on the waiting list were more likely to receive pneumococcal vaccine than other groups (OR 2.81, 95% CI 1.44–5.51, and OR 1.84, 95% CI 1.08–3.14, respectively). We found that the overall immunization rate against common vaccine‐preventable infections was low among patients evaluated for kidney transplantation. A significant gap remains between recommendations and vaccine uptake in clinical practice among this high‐risk population.     

Mycobacterial infections in lung transplant recipients

BACKGROUND: Immunosuppression and chronic lung disease are known risk factors for mycobacterial infection and might be expected to develop with an increased frequency in lung transplant recipients. We therefore sought to document the incidence and type of mycobacterial infections in a large lung transplant program. METHODS: A retrospective review of 219 transplant procedures (60 single lung transplants and 159 double lung transplants) in 210 patients was conducted. All patients had scheduled surveillance bronchoscopies at 3, 6, 9, 12, 18, and 24 months, and yearly thereafter. BAL samples were processed routinely for mycobacterium. RESULTS: Eight patients (3.8%) had evidence of infection (5 men, 3 women; age range, 26 to 63 years). The reasons for transplant were obstructive lung disease (six), cystic fibrosis (one), and pulmonary fibrosis (one). Five recipients had infection in their native lungs; two of five cultured mycobacterium from BAL following transplantation. At least four of five patients had nontuberculous mycobacterium (one showed acid fast bacilli and granuloma on a biopsy specimen that was not sent for culture). None of the five developed disease (mean follow-up = 22 months; range, 3 to 30 months). The organisms were Mycobacterium avium complex (three), Mycobacterium xenopi (one), and unidentified (one). Of the three remaining patients who developed infection after transplantation, one grew Mycobacterium chelonae and the others grew Mycobacterium tuberculosis (both received double lung transplants and had no evidence of mycobacterium in their native lungs). The only definite symptomatic disease occurred in the patients with M tuberculosis, one of whom had evidence of dissemination. The patients with M tuberculosis responded to standard treatment. There have been no deaths due to mycobacterium. CONCLUSION: Mycobacterial disease rarely occurs following lung transplantation. Cultures for mycobacterium in surveillance BALs in the absence of symptoms are likely unnecessary.     

JC virus‐associated nephropathy in a post‐heart and ‐kidney transplantation patient

JC virus‐associated nephropathy is rare in kidney transplant recipients, and even rarer in recipients of other solid organ transplants. We present a case of JC virus‐associated nephropathy in a heart‐kidney transplant recipient, which to our knowledge is the first case reported in the literature. We discuss the findings on renal biopsy for JC virus nephropathy and our management approach to this rare complication.     

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients

STUDY OBJECTIVES: To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). DESIGN: A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. SETTING: A university hospital. Patients or participants: Lung transplant recipients with CF or other indications for transplantation. INTERVENTIONS: None. Measurements and results: Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. CONCLUSIONS: The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect TBA, particularly in recipients with pretransplant colonization.     

Iatrogenic immunosuppression and risk of non‐Hodgkin lymphoma in solid organ transplantation: A population‐based cohort study in Australia

Iatrogenic immunosuppression is a strong risk factor for non‐Hodgkin lymphoma (NHL) but the dose‐related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population‐based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984–2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (<1 year after transplantation; n = 29) and late (≥1 year; n = 61) NHL using the Fine and Gray proportional subdistribution hazards model that accounted for death as a competing risk. After adjustment for immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21–4·01] and late NHL (HR 1·78, 95% CI: 1·12–2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk.     

Clinical features and outcome of tuberculosis in solid organ transplant recipients

BACKGROUND:: Taiwan is an area with moderate to high incidence of Mycobacterium tuberculosis infection. The risk of M tuberculosis infection in transplantation recipients is considered to be significant. Our aim in this study was to investigate the clinical spectrums of M tuberculosis-infected transplantation recipients in a southeast Asian country, Taiwan. METHODS:: We retrospectively analyzed the demographic data, clinical features, treatment, and outcome of M tuberculosis infection in kidney, heart, and liver transplant recipients from May 1996 to April 2005 at the National Taiwan University Hospital. RESULTS:: Fifteen patients who had received solid organ transplantation developed tuberculosis (kidney = 6, heart = 7, liver = 2). The median duration from transplantation to diagnosis of tuberculosis was 31 months. The cumulative incidence of post-transplantation tuberculosis was 2.0% (15/760), ie, approximately 3 times that of the general population. Ten patients (66.7%) had pulmonary tuberculosis, 1 (6.7%) had extrapulmonary tuberculosis, and 4 (26.7%) had disseminated tuberculosis. Nine patients completed the anti-tuberculosis treatment; the median treatment duration was 12 months (pulmonary: 9 months; extrapulmonary: 13.5 months). No treatment failure was noted in patients receiving the complete treatment course. The graft failure and mortality rates of post-transplantation tuberculosis were 13.3% each (2/15). The tuberculosis-associated mortality rate was 6.7% (1/15). CONCLUSIONS:: Cumulative incidence of tuberculosis was slightly higher in transplant recipients than in the general population in Taiwan. Conventional 4-combined anti-tuberculosis regimen for 12 months can treat the potentially fatal infection successfully in post-transplantation tuberculosis patients without recurrence.     

Pseudomonas aeruginosa bacteremia over a 10-year period: multidrug resistance and outcomes in transplant recipients

Abstract: Aim. Transplant recipients are at risk for hospital‐acquired infections (HAIs), including those caused by Pseudomonas aeruginosa. Of all HAIs, bloodstream infection (BSI) remains one of the most life‐threatening. Methods. Over a 10‐year period, we studied 503 patients, including 149 transplant recipients, with pseudomonal BSI from the University of Pittsburgh Medical Center. Trends in antimicrobial susceptibility, risk factors for multidrug resistance (MDR), and outcomes were compared between transplant and non‐transplant patients. Results. Resistance to all antibiotic classes was significantly greater in pseudomonal blood culture isolates from transplant compared with non‐transplant patients (P<0.001). Of isolates from transplant recipients (n=207), 43% were MDR, compared with 18% of isolates from non‐transplant patients (n=391) (odds ratio [OR] 3.47; 95% confidence interval [CI] 2.34–5.14, P<0.001). Among all patients, independent risk factors for MDR P. aeruginosa BSI included previous transplantation (OR 2.38; 95% CI 1.51–3.76, P<0.001), hospital‐acquired BSI (OR 2.41; 95% CI 1.39–4.18, P=0.002), and prior intensive care unit (ICU) admission (OR 2.04; 95% CI 1.15–3.63, P=0.015). Mortality among transplant recipients was 42%, compared with 32% in non‐transplant patients (OR 1.55; 95% CI 0.87–2.76, P=0.108). For transplant recipients, onset of BSI in the ICU was the only independent predictor of mortality (OR 8.00; 95% CI 1.71–37.42, P=0.008). Conclusions. Transplant recipients are at greater risk of MDR P. aeruginosa BSI, with an appreciable mortality. Future management must concentrate on the implementation of effective preventative strategies.