Longitudinal study of cryptococcosis in adult solid-organ transplant recipients

While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solid-organ transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n=13), lung (n=4), liver (n=28), kidney (n=9) and small bowel (n=1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation (P=0.02). In contrast, pneumonia (P=0.003) and meningitis (P=0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia (P=0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.     

Risk of Kaposi Sarcoma after Solid-Organ Transplantation: Multicenter Study in 4767 Recipients in Italy, 1970-2006

Given the high prevalence of infection with human herpesvirus type 8, Italy is an area of utmost interest for studying Kaposi sarcoma (KS). We investigated the risk of KS in transplant recipients compared with the general population. A longitudinal study was performed from 1970 to 2006 in 4767 kidney, heart, liver, and lung transplant recipients from 7 Italian transplantation centers. The sample included 72.3% male patients with an overall patient median age of 48 years. Patient-years (PYs) at risk for KS were computed from 30 days posttransplantation to the date of KS, death, last follow-up, or study closure (December 31, 2007). Standardized incidence ratios (SIRs) and 95% confidence intervals were computed to quantify the risk of KS in transplant recipients compared with the general Italian population. Incidence rate ratios were computed to identify risk factors using adjusted Poisson regression. Based on 33,621 PYs, KS was diagnosed in 73 patients (62 men): 31 in kidney recipients, 27 in heart recipients, 8 in liver recipients, and 7 in lung recipients. The overall incidence was 217 cases per 10⁵ PYs, with a significantly increased SIR of 125. SIR was particularly high in women (n = 34) and lung recipients (n = 428) but decreased significantly with time posttransplantation. The primary predictors of increased risk of KS were male sex, older age, and lung transplantation. A 5-fold reduction was observed after 18 months posttransplantation. After adjustment, patients born in southern Italy compared with northern Italy demonstrated a significant 2.2-fold increased risk. Our findings confirm that in the early posttransplantation period, Italian patients who have undergone solid-organ transplantation, particularly those from southern Italy and those who are lung recipients, are at greater risk of KS compared with the general population. These findings underscore the need for appropriate models for monitoring transplant recipients for KS, especially those at greater risk and, in particular, in the early postoperative period.     

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS-CoV-2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS-CoV-2 infection who underwent antibody testing with a single commercially available anti-nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty-six (51%) had positive anti-nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti-nucleocapsid antibodies, and transplant-related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID-19 may be less likely to form SARS-CoV-2 antibodies.     

Clinical and Radiologic Factors Associated with Pulmonary Nodule Etiology in Organ Transplant Recipients

Identifying clinical and radiographic factors that are associated with a specific etiology of pulmonary nodules (PNs) in solid-organ transplant (SOT) recipients might be helpful in guiding empiric therapy. Multivariable logistic regression was used to assess the relationship of clinical and radiographic variables to the etiology of PN in a retrospectively identified cohort of SOT recipients at a single transplant center. PNs in 55 SOT recipients (lung 15%, heart 22%, liver 42%, kidney 18% or kidney/pancreas 5%) were diagnosed at a mean of 1061 days post-transplant and were infectious in 31 of 55 (56%) (bacterial 22%, fungal 33%, viral 2%) and noninfectious in 24 of 55 (44%) [post-transplant lymphoproliferative disorder (PTLD) 25%, carcinoma 18%]. Radiographic 'consolidation' was independently associated with an infectious etiology (OR, 20.2, p < 0.01). Epstein-Barr virus seronegativity and lung transplant were each associated with PTLD (OR, 21.7, p < 0.01) and (OR, 36.6, p < 0.001), respectively. Diagnosis less than 90 days post-transplant was associated with Aspergillus infection (OR, 12.9, p = 0.007). Specific clinical and radiographic features are associated with specific etiologies of PNs in SOT recipients and might be useful for guiding empiric therapy while awaiting results of definitive diagnostic studies.     

The diagnostic yield of CT‐guided percutaneous lung biopsy in solid organ transplant recipients

Hsu JL, Kuschner WG, Paik J, Bower N, Guillamet MCV, Kothary N. The diagnostic yield of CT‐guided percutaneous lung biopsy in solid organ transplant recipients. Abstract: Background: Despite the widespread use of computed tomography (CT)‐guided percutaneous lung biopsy (PLB) in immunocompetent patients, the diagnostic yield and safety in solid organ transplant (SOT) recipients is unknown. The purpose of this investigation was to determine the test performance of CT‐PLB in SOT recipients. Methods: We performed a 10‐yr single‐center, retrospective analysis among heart, lung, kidney, and liver transplant recipients. We included all adult patients who underwent a PLB of a parenchymal lung nodule following their transplantation. Results: Within the study period, 1754 SOTs were performed, of which 45 biopsies met study criteria. Overall, the incidence of PLB in SOT was 3%. PLB established a diagnosis in 24 of 45 cases. The yield of PLB was better for combined biopsy technique (fine‐needle aspiration biopsy [FNAB]) and core biopsy than for FNAB alone (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.2, 15.6), and for lesions that were malignant (OR: 10.0, 95% CI: 1.8, 75.4) or caused by an invasive fungal infection (OR: 5.0, 95% CI: 1.1, 27.9). Complications occurred in 13% (6/45) of patients. Conclusion: CT‐guided PLB is a safe modality that provides a moderate yield for diagnosing pulmonary nodules of malignant or fungal etiology in SOT recipients.     

Zygomycosis and other rare filamentous fungal infections in solid organ transplant recipients.

Fungi cause severe infections in solid organ transplant (SOT) recipients. Recently, a shift towards non-Aspergillus filamentous fungal infections (nAFFI) was noticed. In a series of 2878 SOTs (kidney, pancreas, islets, liver, heart, lung, and bowel) performed between January 1995 and December 2006 at the Innsbruck medical university, eleven cases of nAFFI were diagnosed. The encountered species included Zygomyzetes (n = 8), and Alternaria alternate, Pseudallescheria boydii, Trichoderma spp. (one each); there were three liver and three heart, one intestinal, pancreas, lung, bilateral forearm and renal recipient each. Five patients died from nAFFI (zygomycosis: 4, Pseudallerichia boydii: 1); four were diagnosed postmortem. In five cases infection was surgically treated in combination with antifungals. Risk factors for nAFFI were renal failure (73%) and intensified immunosuppression (73%); two cases were associated with post-transplant lymphoproliferative disorder, one with graft versus host disease. An increase in the incidence of nAFFI was observed parallel to introduction of caspofungin and voriconazole (three cases until 12/2003, seven cases thereafter). NAFFI are increasingly found in SOT recipients. If diagnosed in time, the outcome seems acceptable. Intensified immunosuppression and exposure to antifungals not active against zygomycetes may be risk factors. Surgical therapy may play an important role in these infections.     

Solid organ transplantation in survivors of hematopoietic cell transplantation: a single institution case series and literature review

Beitinjaneh A, Burns LJ, Majhail NS. Solid organ transplantation in survivors of hematopoietic cell transplantation: a single institution case series and literature review.
Clin Transplant 2010: 24: E94–E102.
© 2009 John Wiley & Sons A/S. Abstract: For selected hematopoietic cell transplant (HCT) survivors with severe organ dysfunction, solid organ transplantation (SOT) may offer the best chance for better quality of life and extended survival. However, SOT following HCT has not been well described. We report our institutional experience of SOT in 12 HCT recipients and present a review of the published literature of this procedure in HCT survivors. Our experience with transplanted organs included kidney (n = 7), lung (n = 3), liver (n = 2) and heart (n = 1). Age at HCT ranged from 2 to 56 yr. Median time between HCT and SOT was 7.9 yr (range 1.2–15.9 yr). Among the 11 patients with post‐SOT follow‐up information, 10 had normal function of the transplanted solid organ at the time of last contact or death. Infections and secondary malignancy were the most common complications. Four other institutional experiences with kidney transplant, 21 case reports of liver transplant, 11 case reports of lung transplant and one cardiac transplant are also summarized. SOT is feasible for selected HCT survivors with organ failure and may be associated with favorable long‐term survival and graft function. More research is needed to further delineate the subset of survivors who will benefit the most from SOT with the least risk of complications.     

The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation

Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community‐acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction.     

Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta‐analysis – Part II: Non‐kidney transplant

Immunoglobulin (IG) is commonly used to desensitize and treat antibody‐mediated rejection in solid organ transplant (SOT) recipients. The impact of IG on other outcomes such as infection, all‐cause mortality, graft rejection, and graft loss is not clear. We conducted a similar systematic review and meta‐analysis to our previously reported Part I excluding kidney transplant. A comprehensive literature review found 16 studies involving the following organ types: heart (6), lung (4), liver (4), and multiple organs (2). Meta‐analysis could only be performed on mortality outcome in heart and lung studies due to inadequate data on other outcomes. There was a significant reduction in mortality (OR 0.34 [0.17‐0.69]; 4 studies, n = 455) in heart transplant with hypogammaglobulinemia receiving IVIG vs no IVIG. Mortality in lung transplant recipients with hypogammaglobulinemia receiving IVIG was comparable to those of no hypogammaglobulinemia (OR 1.05 [0.49, 2.26]; 2 studies, n = 887). In summary, IVIG targeted prophylaxis may decrease mortality in heart transplant recipients as compared to those with hypogammaglobulinemia not receiving IVIG, or improve mortality to the equivalent level with those without hypogammaglobulinemia in lung transplant recipients, but there is a lack of data to support physicians in making decisions around using immunoglobulins in all SOT recipients for infection prophylaxis.     

Remdesivir in Solid Organ Recipients for COVID-19 Pneumonia

Solid organ transplant (SOT) recipients represent a vulnerable patient population and are of high risk for airborne viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Treatment of COVID-19 is still challenging, as no proven therapeutic regimen is available for immunocompromised patients. Our aim was to evaluate the efficacy and safety of remdesivir (RDV) therapy in infected hospitalized SOT patients. All transplanted recipients (N = 25; lung: 19; kidney: 3, liver: 2, heart: 1) who needed hospital care were reviewed in the time period between September 2020 and May 2021 out of the 945 patients treated at the Department. Case control matched patients receiving RDV (all in need of supplementary oxygen) and standard of care (SOC) were included as controls. Among the 25 SOT patients (female:male = 11:14; average age = 53.2 ± 12.7 years), 15 received RDV medication (RDV-TX), and in 10 cases SOC treatment was used (SOC-TX). Significantly worse clinical score was noted in RDV patients compared with RDV-TX; however, transfer to a higher intensity care unit as well as 60-day survival of RDV-TX patients were significantly worse. All SOT fatalities within 60 days of follow-up were lung transplant recipients (6 out of 19 lung transplant patients). No adverse events were noted related to RDV therapy. In SOT patients, especially lung transplant recipients, with severe COVID-19 needing supplementary oxygen, RDV treatment was safe; however, outcome was significantly worse as compared with nontransplanted individuals with initially worse clinical parameters.     

Risk Factors for Clostridioides Difficile Diarrhea In Solid Organ Transplantation Recipients

BackgroundThere is limited knowledge about risk factors for Clostridioides difficile infection (CDI) and recurrent CDI in solid organ transplant (SOT) recipients.MethodsA case-control study of CDI in SOT recipients compared with controls (SOT recipients who did not present CDI).ResultsSixty-seven patients from 1089 SOT recipients (6.2%) suffered at least one episode of CDI. The mean age was 55 ± 12 years and 20 cases (69%) were men. The accumulated incidence was 8% in liver transplantation, 6.2% in lung transplantation, 5.4% in heart transplantation, and 4.7% in kidney transplantation. Twenty-nine cases (43.3%) were diagnosed during the first 3 months after SOT. Forty-one cases (61.2%) were hospital acquired. Thirty-one patients with CDI presented with mild-moderate infection (46.3%), 30 patients with severe infection (44.8%), and 6 patients with severe-complicated disease (9%). Independent variables found to be related with CDI were hospitalization in the previous 3 months (odds ratio: 2.99; [95% confidence interval 1.21-7.37]) and the use of quinolones in the previous month (odds ratio: 3.71 [95% confidence interval 1.16-11.8]). Eleven patients (16.4%) had at least one recurrence of CDI. Previous treatment with amoxicillin-clavulanate, severe-complicated index episode, and high serum creatinine were associated with recurrent CDI in the univariant analysisConclusionsLiver transplant recipients presented the highest incidence of CDI among SOT recipients. Risk factors for CDI were hospitalization in the previous 3 months and the use of quinolones in the previous month.     

Human Ehrlichiosis in Transplant Recipients

To characterize the impact of immunosuppression on human ehrlichiosis, we reviewed cases of ehrlichiosis occurring in transplant recipients and immunocompetent patients at three hospitals in Nashville, Tennessee. Between 1998 and 2006, 15 transplant patients were identified as having ehrlichiosis, diagnosed either by whole blood polymerase chain reaction (PCR) (n = 14) or serology (n = 1). They were compared with 43 immunocompetent patients diagnosed by whole blood PCR. We retrospectively collected demographic and clinical information. The species of Ehrlichia (E. ewingii or E. chaffeensis) was determined for patients diagnosed by PCR. The 15 transplant recipients with ehrlichiosis included 7 kidney recipients, 6 heart recipients, 1 liver recipient and 1 lung recipient. Transplant recipients had more infections with E. ewingii than immunocompetent patients (23% vs. 5%, p = 0.08). Transplant recipients experienced less rash (0% vs. 36%, p = 0.006) and presented with significantly lower hepatic enzymes, but more leukopenia and renal dysfunction than immunocompetent patients. Doxycycline therapy was started within 48 h of presentation in 73% of transplant recipients and 78% of immunocompetent patients (p = 0.7). No patient died in either group. Ehrlichia infections can occur in transplant recipients who live in an endemic area. With prompt treatment, the infected transplant recipients in our study had similar, favorable outcomes compared to immunocompetent patients.     

A Surveillance Study of Adenovirus Infection in Adult Solid Organ Transplant Recipients

Little is known about adenovirus infections in adult organ transplant recipients. We prospectively assessed adenovirus infection in 263 transplant recipients using polymerase chain reaction (PCR) on plasma samples at regular intervals post-transplant. Adenovirus DNA was detected in 19 of 263 patients (7.2%). Viremia by transplant type was: liver (n = 10 of 121 [8.3%]), kidney (n = 6 of 92 [6.5%]) and heart (n = 3 of 45 [6.7%]). Time to viremia onset was within 10 days post-transplant (n = 4), on day 28 (n = 1), on day 100 (n = 7) and between months 6 and 12 (n = 7). At the time of viremia, 11 of 19 (58%) patients had no symptoms, 2 of 19 (10.5%) had gastrointestinal (GI) symptoms, 2 of 19 (10.5%) had respiratory symptoms and 4 patients (21%) had vague/non-specific symptoms. All patients recovered spontaneously. Only 1 of 19 (5%) patients had subsequent acute rejection. Adenovirus viremia is relatively common in adult liver, kidney and heart transplant recipients and most infections are asymptomatic, transient and self-limited. No serious clinical sequelae or effects on subsequent acute rejection were observed.     

Burden,epidemiology, and outcomes of microbiologically confirmed respiratory viral infections in solid organ transplant recipients: a nationwide,multi-season prospective cohort study

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61–5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7–20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62–3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15–5.52), and influenza (aHR 3.57; 95% CI 1.75–7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies.     

Retrospective review of the incidence of cytomegalovirus infection and disease after liver transplantation in pediatric patients: comparison of prophylactic oral ganciclovir and oral valganciclovir

Cytomegalovirus (CMV) is the most common viral infection after solid organ transplantation (SOT). Safe and effective prophylactic regimens that decrease its incidence after SOT are essential for long-term graft survival. Although valganciclovir is not Food and Drug Administration-approved for CMV prophylaxis in liver transplant recipients, postmarketing studies have shown valganciclovir to be as effective as ganciclovir in high-risk adult patients undergoing SOT. Currently, data are lacking for pediatric liver transplantation. The purpose of this study was to compare the efficacy and safety of valganciclovir and ganciclovir for CMV infection prophylaxis in pediatric liver transplant recipients. This was a retrospective study of 56 pediatric liver transplant recipients who were prescribed either oral ganciclovir (n = 37) or valganciclovir (n = 19). Patients were followed until 200 days after transplantation or death. The primary outcome measure compared the rates of early-onset CMV infection and CMV disease in the 2 medication groups. Secondary outcome measures identified patient-specific factors that contributed to CMV acquisition and the incidence of late-onset CMV infection or disease. The rates of adverse drug effects and discontinuation were also evaluated. Early-onset CMV disease was documented in 0% of valganciclovir patients and in 5.4% of ganciclovir patients (P = 0.54). There were no statistically significant differences in the secondary outcomes. An increased incidence of late-onset CMV disease was seen in the valganciclovir group versus the ganciclovir group (22.2% versus 8.1%, P = 0.23). No differences in adverse events were reported. In conclusion, no statistically significant differences were found in the incidence of CMV infection or disease between patients receiving oral valganciclovir and patients receiving oral ganciclovir.     

Portal Hypertension and Granulomatous Liver Disease in a Lung Transplant Recipient due to Disseminated Atypical Mycobacterial Infection

The incidence of atypical mycobacterial infection among solid organ transplant recipients is increasing. While lung transplant recipients in particular are at greater risk of atypical mycobacterial infection than other solid organ transplant recipients, it is typically confined to the lung and disseminated infection remains quite rare. We describe a case of disseminated Mycobacterium avium-complex (MAC) in a lung transplant recipient presenting as granulomatous liver disease with signs of portal hypertension. After identification of the infection and institution of proper therapy, the patient had significant improvement in both clinical signs of portal hypertension and liver function tests. Current literature suggests a favorable prognosis in most cases of MAC infection in lung transplant recipients with appropriate treatment. This case highlights the need to maintain an elevated index of suspicion for atypical pathogens with unusual clinical presentations among the lung transplant population.     

Diagnostic utility of flexible bronchoscopy in recipients of solid organ transplants

Background

Solid organ transplant (SOT) recipients are prone to develop pulmonary complications (PC) due to their immunocompromised state. Flexible bronchoscopy (FB) is frequently performed to diagnose the nature of these complications. The aim of this study was to evaluate the diagnostic utility of FB in SOT recipients with suspected PC.

Method

We examined the medical records of patients who underwent FB between 2000 and 2010; patients who received SOT were included patient demographics, transplantation type, primary diagnoses, thorax computed tomography results, total blood count and chemistries, immunosuppressant therapies, indication, results, specimen cultures, as well as suspected and final diagnoses were recorded.

Results

Among 1368 either liver or kidney transplant recipients 61 subjects including 49 male patients of overall mean age 42.8 ± 12 years underwent FB. FB was performed for lung infiltrates (n = 42), lung nodules (n = 2), atelectasis (n = 1), bronchopleural fistula (n = 1), stridor (n = 1), mediastinal lymphadenopathy (n = 2), pleural effusion (n = 1), fever (n = 9), and/or hemoptysis (n = 2). FB was unremarkable in 17. Other findings were as follows: increased secretions (n = 24), chronic mucosal changes (n = 7), endobronchial lesion (n = 1), edematous mucosa (n = 3), submucosal narrowing (n = 1), necrotic plaque (n = 2), hemorrhage (n = 2), tracheal stenosis (n = 1), and/or friable mucosa (n = 3). We performed bronchial washings (n = 56) and/or bronchoalveolar lavage (n = 5). In 24 patients the microorganisms were Mycobacterium tuberculosis, Staphylococcus aureus, Moraxella catharralis, Candida albicans, Klebsiella pneumonia, Escherichia coli, Streptococcus pneumonia, Stenotrofomonas maltofilia, Aspergillus fumigatus, and Pseudomonas aerigunosa. In 34 patients a final diagnosis was established using FB (diagnostic yield, 55.7%). Thirty-one patients had received tacrolimus (10.5 ± 5.3 ng/ng/mL); 22 cyclosporine (187.1 ± 79.3 ng/mL); and 8, sirolimus (6.2 ± 2.2 ng/mL). No significant difference was observed between high versus low drug levels and the culture results (P > .05).

Conclusion

Suspected pulmonary infection is the most common indication for FB in SOT recipients. It may identify the causative organism in more than 30% of patients and should be considered in the presence of a lung infection.     

Determining the conversion ratios for oral versus sublingual administration of tacrolimus in solid organ transplant recipients

Tacrolimus is utilized as maintenance immunosuppression in solid organ transplant (SOT). Current literature has reported conflicting conversion ratios when transitioning between oral and sublingual tacrolimus, and the exact conversion ratio has not been fully established in SOT. The purpose of this study was to determine the conversion ratios between oral and sublingual tacrolimus needed to achieve equivalent whole blood concentrations in heart, kidney, liver, and lung transplant recipients. A retrospective, single‐center analysis was conducted at Mayo Clinic in Florida. One hundred and eighteen hospitalized SOT recipients who received oral and sublingual tacrolimus during the same inpatient admission from June 1, 2012, through June 1, 2017, were reviewed. The median conversion ratio of sublingual to oral tacrolimus was 1.34 (IQR: 1.03‐1.93) in all SOT, 1.25 (IQR: 1.08‐1.64) in heart transplant, 1.23 (IQR: 1.1‐2.06) in kidney transplant, 1.64 (IQR: 1.27‐2.29) in liver transplant, and 1.34 (IQR: 0.94‐1.93) in lung transplant. A slightly higher dose of oral tacrolimus is needed in the majority of solid organ recipients in our population when converting between sublingual to oral tacrolimus administration.     

Predictors of persistent diarrhea in norovirus enteritis after solid organ transplantation

Solid organ transplant (SOT) recipients may develop protracted diarrheal illness from norovirus. We performed a retrospective chart review between January 2010 and April 2014 to identify predictors of persistent diarrhea in transplant recipients with norovirus enteritis. A total of 152 SOT recipients with mean age of 31.5 years (SD 23.1) were included: 43.4% male, 34.2% pediatric patients. Allograft types were abdominal 136 (89.5%) (kidney [39.5%], liver‐small bowel [23%], other [27%]) and thoracic 16 (10.5%). The median time to diagnosis of first norovirus enteritis episode from date of transplantation was 1.7 (0.3‐5.3) years. At time of presentation, diarrhea was present in 141 (93%). Thirty percent had persistent diarrhea at 2 weeks. Hospitalization was required for treatment in 121 (80%) of episodes with the mean length of stay of 10±15.2 days. Most (91%) infections were due to norovirus genogroup II, and gastrointestinal coinfections were seen in 23 (19%) norovirus enteritis episodes. Nausea at time of diagnosis (P=.002) and cytomegalovirus (CMV) infection in the preceding 90 days (P=.036) were identified as independent risk factors for persistent diarrhea using univariate and multivariable logistic regression. Our study shows that nausea on presentation and prior CMV infection were associated with persistent diarrhea in patients with norovirus enteritis.