Rifabutin for treating tuberculosis in solid organ transplant recipients: A retrospective observational study and literature review.

BACKGROUND: The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. METHODS: A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin-containing regimens were compared and a literature review was conducted. RESULTS: We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62 years (interquartile range 50-20). There were no significant differences between patients treated with rifabutin (n = 12), rifampin (n = 14), and non-rifamycins (n = 5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P = .21), side effects (25%, 37.5%, and 20%, respectively; P = .74), or mortality (16.7%, 35.7%, and 0%, respectively; P = .21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin-containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. CONCLUSIONS: Rifabutin-containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

Is hospital-acquired pneumonia different in transplant recipients?

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are serious complications in transplant patients. The aim of this review is to summarize the evidence regarding nosocomial pneumonia in transplant recipients, including HAP in non-ventilated patients and VAP, and to identify future directions for improvement.A comprehensive literature search in the PubMed/MEDLINE database was performed. Articles written in English and published between 1990 and November 2018 were included. HAP/VAP in transplant patients usually occurs early post-transplant, particularly during neutropenia in haematopoietic stem cell transplant recipients. Bacteria are the leading cause of nosocomial pneumonia for both immunocompetent and transplant recipients, being Gram negative organisms, and especially Pseudomonas aeruginosa, highly prevalent. Multidrug-resistant bacteria are of special concern. Pneumonia in the transplant setting may be caused by opportunistic pathogens, and the differential diagnosis needs to be extended to other non-infectious complications. The most relevant opportunistic pathogens are Aspergillus fumigatus, Pneumocystis jirovecii and cytomegalovirus. Nevertheless, they are an exceptional cause of nosocomial pneumonia, and usually occur in severely immunosuppressed patients not receiving antimicrobial prophylaxis. Performing bronchoalveolar lavage may improve the rate of aetiological diagnosis, leading to a change in therapeutic management and improved outcomes. The optimal length of antibiotic therapy for bacterial HAP/VAP has not been well defined, but it should perhaps be longer than in the general population. Mortality associated with HAP/VAP is high. HAP/VAP in transplant patients is frequent and is associated with increased mortality. There is room for improvement in gaining knowledge about the management of HAP/VAP in this population.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Clinical impact of culture-positive preservation fluid on solid organ transplantation: A systematic review and meta-analysis.

Contamination of the preservation fluid (PF) used for donated organs is a potential source of post-transplant infection. However, the information on this issue is scarce. We therefore conducted a systematic review and meta-analysis to assess the incidence of culture-positive PF and its impact on solid organ transplant (SOT) recipients. Seventeen studies were identified and included. The overall incidence of culture-positive PF was 37% (95% CI: 27% to 49%), and the incidence of PF-related infections among SOT recipients with PF cultures that grew pathogenic microorganisms was 10% (95% CI: 7% to 15%). There were differences in the rates of infections due to pathogenic microorganisms between SOT recipients who received pre-emptive treatment and those who did not, but without statistical significance. The mortality rate among SOT recipients with PF-related infection was 35% (95% CI: 21% to 53%). In conclusion, although contamination of the PF of donated organs is frequent, the incidence of PF-related infection is relatively low. A closely clinical and microbiologic monitoring of the SOT recipient in case of culture-positive PF, regardless of the type of microorganism isolated might be do in order to establish a prompt diagnosis of PF-related infection.

Cutaneous leishmaniasis associated with anti-tumour necrosis factor-α drugs: an emerging disease.

Leishmaniasis is endemic in several geographic areas of the world. In each of these areas, particular species of Leishmania with differing aggressiveness to humans predominate. In the European Mediterranean basin, cutaneous leishmaniasis usually presents with discrete, self-healing skin lesions. Although it is known that tumour necrosis factor (TNF) inhibitors may increase the risk of developing infections such as tuberculosis, there is scarce literature on Leishmania infections in patients treated with these drugs. In recent months, we have observed three patients resident in the Catalan coast of Spain who were treated with TNF inhibitors for Crohn disease, and who developed unusually large and persistent cutaneous lesions of leishmaniasis. These lesions responded only to treatment with intravenous liposomal amphotericin B. In countries with a high incidence of infection by aggressive species of Leishmania, serological screening may be indicated to detect a possible latent leishmanial infection before prescription of TNF inhibitors.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Contribution of Population Pharmacokinetics to Dose Optimization of Ganciclovir-Valganciclovir in Solid-Organ Transplant Patients.

Treatment of solid-organ transplant (SOT) patients with ganciclovir (GCV)-valganciclovir (VGCV) according to the manufacturer's recommendations may result in over- or underexposure. Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing, achieving the area under the curve (AUC) therapeutic target. We conducted a two-arm, randomized, open-label, 40% superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection. Group A was treated according to the manufacturer's recommendations. For group B, the dosing was adjusted based on target exposures using a Bayesian prediction model (NONMEM). Fifty-three patients were recruited (27 in group A and 26 in group B). About 88.6% of patients in group B and 22.2% in group A reached target AUC, achieving the 40% superiority margin (P< 0.001; 95% confidence interval [CI] difference, 47 to 86%). The time to reach target AUC was significantly longer in group A than in group B (55.9 ± 8.2 versus 15.8 ± 2.3 days,P< 0.001). A shorter time to viral clearance was observed in group B than in group A (12.5 versus 17.6 days;P= 0.125). The incidences of relapse (group A, 66.67%, and group B, 9.01%) and late-onset infection (group A, 36.7%, and group B, 7.7%) were higher in group A. Neutropenia and anemia were related to GCV overexposure. GCV-VCGV dose adjustment based on a population pharmacokinetics Bayesian prediction model optimizes GCV-VGCV exposure. (This study has been registered at ClinicalTrials.gov under registration no. NCT01446445.).

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Factors influencing mortality in solid organ transplant recipients with bloodstream infection.

Although bloodstream infection (BSI) is a major cause of mortality after solid organ transplantation, information regarding its prognostic factors is scarce. To identify risk factors for 30-day mortality in solid organ transplant (SOT) recipients with BSI, we prospectively recorded all episodes of BSI occurring in adult SOT recipients from January 2007 to October 2014 at a university hospital. We identified 361 consecutive episodes of BSI involving 246 patients. The 30-day case-fatality rate from the onset of BSI was 11.4%. Factors independently associated with 30-day mortality in a logistic regression analysis were shock at presentation (OR 13.658; 95% CI 5.985-31.168), acute graft rejection in the previous 6 months (OR 3.681; 95% CI 1.059-12.795), and a platelet count of <50,000 × 10(9)/L (OR 3.070; 95% CI 1.173-8.038). Kidney recipients were the patients with the best prognosis (OR 0.375; 95% CI 0.156-0.900). Our findings may help to identify SOT recipients with BSI who are at the highest risk of death.

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.

Effect of delaying prophylaxis against CMV in D+/R- solid organ transplant recipients in the development of CMV-specific cellular immunity and occurrence of late CMV disease.

OBJECTIVES: Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT). METHODS: Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models. RESULTS: We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09). CONCLUSIONS: A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.

Risk factors, clinical features and outcomes of visceral leishmaniasis in solid-organ transplant recipients: a retrospective multicenter case-control study.

Visceral leishmaniasis (VL) is a rare disease in solid-organ transplant (SOT) recipients. Therefore, little is known about the risk factors and disease behavior in the transplant setting. This multicenter, matched case-control study (1:2 ratio) was designed to determine the risk factors, clinical features and outcomes of VL among this population. Control and case subjects were matched by center, transplant type and timing. Thirty-six VL cases were identified among 25 139 SOT recipients (0.1%). VL occurred 5.7-fold more frequently in Brazil than in Spain, presenting a median time of 11 months after transplantation. High-dose prednisone in the preceding 6 months was associated with VL. Patients were diagnosed over 1 month after symptom onset in 25% of cases. Thirty-one patients (86%) were febrile upon diagnosis, 81% exhibited visceromegaly and 47% showed pancytopenia. Concomitant infection was common. Parasites were identified in 89% of patients; the remaining patients were diagnosed by serology. The majority of the patients received amphotericin B. Relapses occurred in 25.7% of cases, and the crude mortality rate was 2.8%. VL after SOT is related to the VL prevalence in the general population. Delayed diagnosis frequently occurs. Liposomal amphotericin is the most commonly used therapy; mortality is low, although relapses are common.

Donor-transmitted malaria after heart transplant managed successfully with artesunate.

Donor-transmitted malaria is a rare complication in solid organ transplantation, which causes high mortality. Data concerning the use of artesunate in solid organ transplant recipients are lacking. We report a heart transplant patient who developed donor-derived severe Plasmodium falciparum malaria, successfully treated with artesunate. Transmission of malaria to 2 of the other transplant recipients from the same donor was also documented.

Daptomycin is safe and effective for the treatment of gram-positive cocci infections in solid organ transplantation.

INTRODUCTION: Infections caused by resistant gram-positive cocci (GPC), especially to glycopeptides, are difficult to treat in solid organ transplant (SOT) recipients as a result of lower effectiveness and high rates of renal impairment. The aim of this study was to evaluate the use of daptomycin in this population. METHODS: Over a 2-year period (March 2008-2010) in 9 Spanish centers, we enrolled all consecutive recipients who received daptomycin to treat GPC infection. The study included 43 patients, mainly liver and kidney transplant recipients. RESULTS: The most frequent infections were catheter-related bacteremia caused by coagulase-negative staphylococci (23.2%), skin infection caused by Staphylococcus aureus (11.5%), and intra-abdominal abscess caused by Enterococcus faecium (20.9%). The daily daptomycin dose was 6 mg/kg in 32 patients (74.4%). On day 7 of daptomycin treatment, median estimated area under the curve was 1251 µg/mL/h. At the end of follow-up, analytical parameters were similar to the values at the start of therapy. No changes were observed in tacrolimus levels. No patient required discontinuation of daptomycin because of adverse effects. Clinical success at treatment completion was achieved in 37 (86%) patients. Three patients died while on treatment with daptomycin. CONCLUSION: In summary, daptomycin was a safe and useful treatment for GPC infection in SOT recipients.

Candida arteritis occurring in a liver transplant recipient.

We report the first case, to our knowledge, of Candida arteritis in a liver transplant recipient. The patient presented with hemorrhagic shock requiring emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida glabrata were growing in the arterial tissue, the patient received antifungal therapy for 5 months, but died because of chronic graft dysfunction. No evidence of fungal infection was found in the tissue on postmortem examination.

Risk factors, clinical characteristics, and outcomes of invasive fungal infections in solid organ transplant recipients.

BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity and mortality among solid organ transplant (SOT) recipients. We sought to assess risk factors, clinical characteristics, and current outcomes of IFI in SOT recipients. METHODS: We reviewed all episodes of IFI occurring among SOT recipients in a university hospital from 2008 to 2011. To determine risk factors for IFI we carried out a matched case-control study (1:2 ratio). Control subjects were matched for transplant type and timing. RESULTS: We documented 20 episodes of IFI among 744 SOT recipients (2.7%). Sixty-five percent of cases were proven IFI and 35% were probable IFI. The types of IFI documented were aspergillosis in 8 cases, candidiasis in 7, pneumocystosis in 3, Emmonsia species in infection 1, and disseminated cryptococcosis in 1. Ninety-nine percent of the patients had received a prior antibiotic therapy (3 months), 40% presented allograft rejection (3 months), and 40% had prior kidney injury. Complications of IFI included septic shock (50%), respiratory failure (55%), multiple-organ dysfunction (55%), and intensive care unit (ICU) admission (50%). Median days from transplantation to diagnosis was 103 for candidiasis (range, 27-4644) and 1195 for aspergillosis (range, 0-4319). In a comparison of case patients with 40 matched control subjects, case patients more frequently presented prior ICU stay (3 months; P = .05), hemodialysis requirement (P = .02), receipt of high-dose prednisone (6 months; P = .006), and prior antibiotic therapy (P < .001). Prior use of antibiotic treatment was the only risk factor for IFI (odds ratio [OR] 93; 95% confidence interval [CI], 8.3-1042). Case-fatality rate was 60%. CONCLUSIONS: In our recent experience, 2.7% of SOT recipients developed IFI, mainly aspergillosis followed by candidiasis. Prior ICU admission, hemodialysis, receipt of high-dose prednisone, and prior antibiotic use were more frequent in cases when compared with control subjects, with the latter factor being the only independent risk factor for developing IFI. Case-fatality rate was high (60%).

Clinical features and outcomes of tuberculosis in solid organ transplant recipients.

BACKGROUND: Tuberculosis (TB) remains a significant opportunistic infection in solid organ transplant (SOT) recipients. Moreover, its optimal treatment in SOT recipients is challenging due to the toxicity and potential drug-drug interactions of antituberculus drugs. We sought to assess the frequency, clinical characteristics, treatments, and outcomes of TB among SOT recipients. METHODS: We reviewed retrospectively the medical charts of all TB cases occurring among SOT recipients from January 2000 to December 2011, retrieving data regarding baseline and clinical features, as well as treatment and outcomes. RESULTS: Eighteen of 2005 SOT recipients developed TB (0.9%). The frequency according to the type of allograft was 0.9% (10 of 1120) for kidney, 1% (7 of 701) for liver, and 0.5% (1 of 184) for heart recipients. Six patients (33%) had prior exposure to TB: a positive tuberculin test (n = 3), a positive quantiferon-TB (n = 1) for a prior history of TB (n = 3). None of them received antituberculus prophylaxis. The mean time after transplantation to TB diagnosis was 64 months (range 2-169). Five patients (28%) developed TB within the first year posttransplantation. The mean duration of symptoms before diagnosis was 30 days (range 1-180). Nine patients (50%) displayed pulmonary TB; 7 (39%) had disseminated infections, and 2 (11%) had lymph node involvement. None of the Mycobacterium tuberculosis isolates were resistant to first-line antituberculus drugs. All patients were given isoniazide. Most of them received a 3-drug regimen. Rifampin was prescribed in 11 cases. Seven patients (5 liver and 2 kidney recipients) developed hepatotoxicity. One patient developed rejection without allograft loss. Mortality during antituberculus treatment was 17% (3/18). CONCLUSIONS: In this study, 0.9% of SOT recipients developed TB, which frequently presented with extrapulmonary involvement, causing considerable mortality. Hepatotoxicity mainly among liver transplant recipients was a significant therapeutic drawback.

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors.

Ganciclovir-resistant (GanR) cytomegalovirus (CMV) infection after organ transplantation is emerging as a significant therapeutic challenge. We report two cases of GanR CMV infection successfully managed by switching immunosuppression from calcineurin inhibitors to an mTOR inhibitor-based regimen. This salvage therapy should be considered when other options are not available.

Pandemic influenza A(H1N1) virus infection in solid organ transplant recipients: impact of viral and non-viral co-infection.

Solid organ transplant recipients (SOTR) are at risk of serious influenza-related complications. The impact of respiratory co-infection in SOTR with 2009 pandemic influenza A(H1N1) is unknown. A multicentre prospective study of consecutive cases of pandemic influenza A(H1N1) in SOTR was carried out to assess the clinical characteristics and outcome and the risk factors for co-infection. Overall, 51 patients were included. Median time from transplant was 3.7 years, 5.9% of the cases occurred perioperatively and 7.8% were hospital-acquired. Pneumonia was diagnosed in 15 (29.4%) patients. Ten cases were severe (19.6%): 13.7% were admitted to intensive care units, 5.9% suffered septic shock, 5.9% developed acute graft rejection and 7.8% died. Co-infection was detected in 15 patients (29.4%): eight viral, six bacterial and one fungal. Viral co-infection did not affect the outcome. Patients with non-viral co-infection had a worse outcome: longer hospital stay (26.2 ± 20.7 vs. 5.5 ± 10.2) and higher rate of severe diseases (85.7% vs. 2.3%) and mortality (42.8% vs. 2.3%). Independent risk factors for non-viral co-infection were: diabetes mellitus and septic shock. Other factors associated with severe influenza were: delayed antiviral therapy, diabetes mellitus, time since transplantation <90 days and pneumonia. In conclusion, pandemic influenza A can cause significant direct and indirect effects in SOTR, especially in the early post-transplant period, and should be treated early. Clinicians should be aware of the possibility of non-viral co-infection, mainly in diabetic patients and severe cases. An effort should be made to prevent influenza with immunization of the patient and the environment.