Mycobacterium tuberculosis infection and laboratory diagnosis in solid-organ transplant recipients

Tuberculosis (TB) is an unusual infection in transplant recipients. We evaluated (i) the frequency of TB, (ii) the duration to develop the TB infection, and (iii) clinical consequences, in 380 solid-organ recipients from January 1995 to December 2000. A total of 10 (2.63%) patients (eight renal, two liver transplant recipients) were found to have post-transplantation TB. The frequency of TB in this patient population is 8.5-fold higher than the prevalance in the general Turkish population. Tuberculosis developed within 2-33 months after transplantation, with a median of 15 months. In all of these 10 patients, Mycobacterium tuberculosis (MTB) was isolated from the culture. All the patients continued to have low dose immunosuppressive treatment, and also quadriple antituberculosis treatment [isoniazid (INH), rifampin (RIF), pyrazinamide (PRZ) and ethambutol (ETB)] has been given. The two recipients had died of disseminated form of TB. Relapse was detected in one patient 6 months after the completion of the treatment. As post-transplant TB infection develops mostly within the first year after transplantation, clinicians should be more careful for early and fast diagnosis and treatment should be started immediately.     

Mycobacterium tuberculosis infection in solid organ transplant recipients: experience from a single center in China

OBJECTIVE: We sought to explore the prevalence, clinical manifestations, diagnostic procedures, and treatment of tuberculosis (TB) after solid organ transplantation. PATIENTS AND METHODS: In this study, we retrospectively analyzed data of 1947 renal transplant recipients and 85 liver transplant recipients. RESULTS: TB developed in 28 organ transplant recipients with a prevalence of 1.38% (28/2032). The median interval between transplantation and development of TB was 32 months (range, 1-142 months). Mycobacterium tuberculosis isolation, histologic signs of caseating granulomas, and TB-DNA detection directly supported the diagnosis in 10 (35.71%), 7 (25.00%), and 5 (17.86%) patients, respectively. In addition, 6 patients (21.43%) highly suspected of TB infection received tentative antituberculosis treatment with favorable responses. Most renal transplant recipients (22/25; 78.57%) received isoniazid, rifampicin (or rifabutin), and ethambutal (or pyrazinamide) for a mean duration of 10 months (range, 6-14 months). Three liver transplant recipients received a different protocol: isoniazid, rifabutin, ethambutal, and ofloxacin for 3 months; then isoniazid and rifabutin for 6 months. Upon follow-up, 8 subjects (28.57%) died; 5 of the deaths were related to TB. During the antituberculosis therapy, toxic hepatitis was seen in 12 patients (42.86%); cyclosporine levels decreased in 15 patients (53.57%); and allograft rejection developed in 6 of them. CONCLUSIONS: The peak incidences of TB in liver and kidney transplantations are in the first year and after the first year posttransplantation, respectively. Response to antituberculosis treatment should be considered to make a diagnosis among patients highly suspected of TB infections. Except in special circumstances, antituberculosis treatment protocols including isoniazid and rifampicin for about 10 months seem significantly effective and tolerable for non-liver transplant patients. Fluoroquinolones should be emphasized in posttransplantation TB treatment.     

Safety and efficacy of isoniazid chemoprophylaxis administered during liver transplant candidacy for the prevention of posttransplant tuberculosis

BACKGROUND: Optimal timing of initiation of isoniazid chemoprophylaxis in liver transplant recipients who test positive on the tuberculin skin test has not been defined. We sought to determine whether isoniazid prophylaxis administered during liver transplant candidacy was safe and effective for the prevention of posttransplantation tuberculosis. METHODS: During a 9-year period, 18 liver transplant candidates with tuberculin skin test greater than 5 mm or recent conversion to positive tuberculin skin test were identified and received isoniazid chemoprophylaxis for 12 months. For each case, a control matched with the patient for underlying liver disease and age (within 5 years of the case) was included. Liver function tests were assessed monthly. The median follow-up was 55 months and ranged up to 107 months for the cases. RESULTS: At baseline, the cases had a total bilirubin of 2.2 mg/dL, alanine aminotransferase of 106 IU/L, prothrombin time of 14.2 sec, and serum albumin of 2.9 gm/dL (mean values). Hepatic function tests did not differ significantly for the cases at 3, 6, 9, and 12 months when compared with those at baseline or between the cases and controls at each of the above time points. Discontinuation of prophylaxis was not required in any of the patients. The outcome (proportion of patients who underwent transplantation or were dead or alive at the last follow-up) and survival time for the cases did not differ significantly from those of the controls (P >0.20). CONCLUSION: In liver transplant candidates at risk for infection after transplantation, isoniazid chemoprophylaxis used during candidacy was well tolerated and did not adversely effect hepatic function or outcome as compared with the control patients.     

Successful management of pulmonary tuberculosis in renal allograft recipients in a single center

BACKGROUND: Pulmonary infections, especially tuberculosis, are responsible for significant mortality and morbidity among renal transplant recipients in developing countries. Conventional diagnostic modalities are associated with a low yield, delaying specific therapy. METHODS: All patients transplanted within a 1.5-year period were prospectively followed-up for one year. Patients were on a cyclosporine-based triple immunosuppressive regimen. None received isoniazid prophylaxis, and those transplanted in the last seven months of the study period received daily cotrimoxazole. Patients exhibiting unequivocal evidence of pulmonary infections underwent further evaluation. Search for offending organisms was made by sputum examination and bronchoalveolar lavage (BAL). RESULTS:. Thirty-nine infection episodes were recorded in 34 patients. M. tuberculosis was isolated during 10 episodes, pyogenic bacteria and Pneumocystis carinii in 6 each, candida in 4, aspergillus in 3, cytomegalovirus (CMV) in 3, and nocardia and mucor in one episode each. More than one organism was isolated during five episodes. Bacterial pneumonia and tuberculosis were diagnosed in another seven and two patients, respectively, on the basis of a therapeutic response to specific chemotherapy. Over two thirds of the organisms were identified by examination of BAL fluid. BAL was useful in the diagnosis of tuberculosis and P. carinii pneumonia but was relatively insensitive for CMV and bacterial infections. An increased frequency of acute rejection and higher serum creatinine were factors that predisposed to infections. All patients with pulmonary tuberculosis made a full recovery. CONCLUSIONS: Tuberculosis and P. carinii are the most common nonpyogenic infections in the first year after transplantation in developing countries. An aggressive search for tubercle bacilli should be made using bronchoscopy and examination of BAL fluid in patients not responding to a short trial of antibiotics. A four-drug regime without rifampicin given for 18 months is effective for pulmonary tuberculosis in patients on cyclosporine. We recommend routine prophylactic use of one single-strength tablet of cotrimoxazole daily for at least six months after transplantation.     

Tuberculosis in renal transplant recipients

BACKGROUND: Tuberculosis is an important cause of morbidity and mortality in renal transplant recipients, but there are insufficient data regarding the efficacy and complications of therapy and of INH prophylaxis. METHODS: This study is a retrospective review of the records of 880 renal transplant recipients in two centers in Turkey. RESULTS: Tuberculosis developed in 36 patients (4.1%) at posttransplant 3-111 months, of which 28 were successfully treated. Eight patients (22.2%) died of tuberculosis or complications of anti-tuberculosis therapy. Use of rifampin necessitated a mean of 2-fold increase in the cyclosporine dose, but no allograft rejection occurred due to inadequate cyclosporine levels. Hepatotoxicity developed in eight patients during treatment, two of whom died due to hepatic failure. No risk factor, including age, gender, renal dysfunction, hepatitis C, or past hepatitis B infection, was found to be associated with development of hepatic toxicity. A subgroup of 36 patients with a past history of or radiographic findings suggesting inactive tuberculosis, was considered to be at high risk for developing active disease, of whom 23 were given isoniazid (INH) prophylaxis. None versus 1 of 13 (7.7%) of cases with and without INH prophylaxis, respectively, developed active disease (P>0.05). None of the patients receiving INH had hepatic toxicity or needed modification of cyclosporine dose. CONCLUSIONS: These data show that tuberculosis has a high prevalence in transplant recipients, that it can effectively be treated using rifampin-containing antituberculosis drugs with a close follow-up of serum cyclosporine levels, and that INH prophylaxis is safe but more experience is needed to define the target population.     

Tuberculous meningitis in a renal transplant recipient

Tuberculous meningitis is a very rare, but serious extrapulmonary complication of mycobacterial infections in immunocompromised patients, such as organ transplant recipients. We describe here a 66-year-old Turkish woman without any history of tuberculosis, who received a renal allograft transplant in 1994. After a pilgrimage to an endemic area for tuberculosis, she presented with fever and headache in August 1998. Clinical examination revealed positive meningism and hyperreflexia. Lymphocytosis was noted in her cerebrospinal fluid (CSF) and Mycobacterium tuberculosis infection was detected by PCR within the CSF. Despite immediate triple antituberculosis therapy, the patient's clinical condition deteriorated rapidly, with the development of septic shock syndrome, and she died three weeks after admission due to cardiovascular and respiratory failure. Mycobacterial infections, including extrapulmonary manifestations, should thus be considered in all renal transplant recipients presenting with unexplained fever. Preventive therapy, i.e. isoniazid prophylaxis, may also be recommended for patients risking exposure in areas endemic for tuberculosis.     

Diagnosis and treatment of latent tuberculosis infection in liver transplant recipients in an endemic area

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) with isoniazid is recommended for transplant recipients with positive tuberculin skin test (TST). However, TST could be an imperfect identifier of LTBI in this population. In addition, the risk of isoniazid hepatotoxicity could be high in liver transplant recipients (LTR). A retrospective cohort study was performed to evaluate the diagnosis and treatment of LTBI in LTR. METHODS: Charts of all 547 patients who received primary liver transplantation at a University Hospital in Spain between 1988 and 1998 were reviewed. RESULTS: TST was performed in 373 patients (71%) before transplantation. The result was positive in 89 (24%). The median follow-up after transplantation was 49 months. None of the TST-positive patients developed tuberculosis (TB), but 5 out of 284 patients with negative TST (1.76%) had active TB (P=0.6). Twenty-three patients received isoniazid as treatment of LTBI according to the decision of the attending physician. None of these patients developed TB, but 4 of them (17%) presented isoniazid hepatotoxicity. Among patients who did not receive isoniazid, 2 out of 21 (9.52%) with radiologic previous TB developed active TB versus 0.44% (2/452) among the remaining patients (relative risk [RR], 27.8, 95% CI, 3.2-147). CONCLUSIONS: Treatment of LTBI with isoniazid can not be recommended to LTR on the basis of a positive TST because it is an imperfect identifier of patients at risk of TB. LTR with radiologic features of previous TB are at higher risk of posttransplant active TB. Isoniazid-related hepatotoxicity is more frequent among LTR than in the general population.     

Tuberculosis after renal transplantation: experience of one Turkish centre

Background: In this study, renal transplant recipients with tuberculosis of different organs, were retrospectively analysed with respect to prevalence, outcome and drug toxicity. Patients and methods: In 520 patients, 22 (4.2%) tuberculosis of various organs was diagnosed. The time interval between transplantation and diagnosis of tuberculosis was 44.4±33.5 (range 3-111) months. In 18 (82%) of the patients, tuberculosis was detected after the first year of transplantation. The most common form was pleuro/pulmonary tuberculosis (54%), and other localizations included jejunum, liver, bone, and urogenital tract. Results: Sixteen of the 22 patients responded favourably to the treatment and maintain excellent allograft function, whereas six patients (27.2%) died. Toxic hepatitis was seen in four (18%) patients, and one case was complicated with acute hepatocellular failure due to isoniazide (INH). However, of the 23 patients at risk of tuberculosis who had had INH prophylaxis for 1 year, neither tuberculosis, nor hepatotoxicity was observed. Conclusion: Tuberculosis is a common infection of renal transplant recipients in developing countries. The peak incidence is after the first year of transplantation and mortality is considerable. Hepatoxicity is a considerable risk of treatment, possibly as a result of additive toxic effects of immunosuppressive drugs.     

Coccidioidomycosis in Liver Transplant Recipients in an Endemic Area

Coccidioidomycosis is an infection caused by Coccidioides species, which are endemic for the Southwestern United States and parts of Central America and South America. Most infected individuals are asymptomatic or have mild‐to‐moderate respiratory illness. Coccidioidomycosis is more severe in patients with depressed cellular immunity, such as organ transplant recipients. We retrospectively reviewed charts of 391 liver transplant recipients (mean follow‐up, 38.7 months; range, 2–105 months). Before transplantation, 12 patients had a history of coccidioidomycosis and 13 patients had asymptomatic seropositivity. Of these 25 patients, 23 had no active coccidioidomycosis posttransplantation and 2 had reactivated infection. One of 5 patients with indeterminate serology before transplantation died of disseminated coccidioidomycosis shortly after transplantation. De novo coccidioidomycosis developed in 12 patients (3%) who had no evidence of coccidioidomycosis pretransplantation. Of 15 total episodes of posttransplantation coccidioidomycosis, 10 (66%) occurred during the first year. Dissemination was noted in 33% of active coccidioidomycosis after transplantation; two patients (13%) died of coccidioidomycosis. Because most coccidioidal infections occurred in the first posttransplantation year despite targeted antifungal prophylaxis, we recommend a new strategy of universal antifungal prophylaxis for 6–12 months for liver transplant recipients who reside in the endemic area.     

Nocardiosis in tropical renal transplant recipients

BACKGROUND: The epidemiology of nocardiosis in the tropics among renal transplant recipients has not been reported. METHODS: An evaluation of nocardiosis for 30 yr in one of the large transplant centres in South Asian region. RESULTS: Of the 1968 patients who received primary renal allografts at Christian Medical College & Hospital, 27 patients developed nocardiosis over 30 yr. Early nocardiosis (2 yr). Seventeen patients (63%) had two or more associated post-transplant infections, of whom 10 had tuberculosis. Mortality in these patients was associated with chronic liver disease. CONCLUSIONS: Nocardiosis manifests earlier (<2 yr) in CsA treated patients who have chronic liver disease. Among renal transplant recipients of the tropics nocardiosis is a marker of a high susceptibility to tuberculosis and other infections, the association with tuberculosis is stronger in those developing early nocardiosis (<2 yr). Chronic liver disease is a risk factor for death in patients with nocardiosis especially when associated with tuberculosis. This report constitutes the largest single centre experience among renal transplant recipients.     

Tuberculosis in Egyptian kidney transplant recipients: study of clinical course and outcome

BACKGROUND: Tuberculosis (TB) is an important infection encountered post-transplantation especially in developing countries, with high incidences of morbidity and mortality. In this report, we study the risk factors and impact of TB on the outcome of kidney transplantation. METHODS: Of 1200 live-donor Egyptian kidney transplantations, 45 (3.8%) patients developed post-transplant TB. Of these, five had had TB pre-transplantation and 40 were male. The mean age was 32.6 +/- 10.5 years. Primary immunosuppression treatment for 39 (86.7%) patients was cyclosporine (CsA). RESULTS: The mean time interval between transplantation and TB diagnosis was 49.8 +/- 41.5 (range 2-180) months. In 86.7% of patients, TB was diagnosed one year post-transplantation. Urinary TB was the most common form (53%), while pleuropulmonary TB accounted for 38%. All post-transplant TB patients received a triple anti-tuberculous therapy (rifampicin, ethambutol and INH) with a favorable response in all but two patients who needed another 24-month course. Hepatotoxicity was seen in 11 patients, eight were mild with normalization after temporary withdrawal of rifampicin, and three cases were severe, but mortality was not attributable to hepatocellular failure. Twelve patients died, 11 of them due to unrelated causes. Chronic rejection occurred in more than half of the patients (55.6%), of whom 24 (96%) were CsA-treated, which can be attributed to rifampicin/CsA interaction. More than 35% of TB patients lost their graft as a result. Pre-transplant tuberculosis patients had a comparable post-transplant course. CONCLUSIONS: TB is a common infection in renal transplant recipients with a peak incidence occurring one year post-transplant. Chronic rejection is a serious complication that had a negative impact on the graft survival, especially in CsA-treated recipients. INH prophylaxis is safe in pre-transplant TB. The post-transplantation outcome in the pre-transplant tuberculosis patients is no different from non-TB patients.     

Chronologically different incidences of post-transplant malignancies in renal transplant recipients: single center experience

The incidence of malignancy in transplant recipients is known to be higher than the same in the general population. However, the types of malignancies vary geographically, and the relative risks (RR) for malignancy in transplant recipients, compared with that of the general population, also differ country-by-country. In this study, we investigated the incidence and characteristics of malignancies after renal transplantation in a single center. A total of 2630 renal recipients who underwent surgery between April 1979 and June 2007 were enrolled in this study. The cumulative and interval incidences of malignancies were calculated for every 3 years post-transplantation. One-hundred ninety cases of postrenal transplant malignancies among 177 recipients (6.73%) were reported until 2007. The post-transplant malignancies were detected from 6 to 290 months after transplantation, with a mean duration of 112.6 ± 66.0 months. Skin cancer [35 (18.4%)] was the most common post-transplant malignancy, followed by thyroid [25 (13.2%)], stomach [22 (11.6%)], colorectal [22 (11.6%)], and urologic cancers [19 (10.0%)]. As the post-transplant period increased, the interval incidence of malignancy correspondingly increased. Virus-related malignancies, such as Kaposi's sarcoma and cervical cancer, developed earlier within the post-transplant period, while urologic cancer, colorectal cancer developed late in the post-transplant period. The recipient's age at the time of transplantation was the sole independent risk factor for post-transplant malignancy based on the multivariate analysis (RR = 2.723, P  < 0.0001 in the >50-year-old age group). We should establish strategies for post-transplant malignancy-screening based on the recipient's age at the time of transplantation, the post-transplant interval, and the national trend of post-transplant malignancy.     

Invasive aspergillosis in the recipients of liver retransplantation.

Retransplantation is a major risk factor for invasive aspergillosis in liver transplant recipients. However, the risk for invasive aspergillosis with time elapsed since retransplantation, clinical characteristics, and outcome of patients who develop this infection after retransplantation of the liver has not been defined. Patients comprised 17 liver retransplant recipients with invasive aspergillosis between 1990 and 2004. Retransplantation was considered early if it was performed within 30 days and late if performed after 30 days of the first or primary transplant. Retransplant recipients comprised 25% of all cases of invasive aspergillosis after liver transplantation. Fifty-three percent of the Aspergillus infections occurred within 30 days, and 76% within 90 days of retransplantation. In all, 53% (9/17) of the patients were late retransplant recipients. Late compared to early retransplant recipients with invasive aspergillosis were more likely to have central nervous system involvement with invasive aspergillosis (56% vs. 0%, P = 0.03). Mortality rate was 100% for late and 63% for early retransplant recipients with Aspergillus infections. In conclusion, time-varying risk for invasive aspergillosis after retransplantation has implications relevant for guiding antifungal prophylaxis. Given a greater risk for disseminated infection and poor outcome in late retransplant recipients with aspergillosis, potent and aggressive antifungal therapy should be considered upfront in these patients.     

Mycobacterial infections in renal allograft recipients

Primary mycobacterial infections developed in five of 565 patients who had transplants during a 15-year period. All had negative PPDs and normal chest roentgenograms; none had tuberculosis before transplantation. Atypical mycobacteria were cultured in three of five infections. All were treated with a multiple-drug regimen, including isoniazid, rifampin, ethambutol, and streptomycin sulfate. In four of five patients, there were serious drug-related complications. No major initial alteration of immunosuppressive therapy was necessary in any of the patients. During the study, a treatment policy was followed that included one year of isoniazid treatment of all recipients with a positive PPD, history of tuberculosis, chest x-ray film suggestive of tuberculosis, or PPD-positive donor. An additional 14 transplant recipients were treated in accordance with this policy without complications or subsequent mycobacterial infections (32-month average follow-up). Despite the low incidence of mycobacterial infection in this series, the potential lethality and morbidity mandate constant vigilance.     

Viral and fungal infections after liver transplantation--part II.

Viral and fungal infections in liver transplant recipients are important to recognize and treat early because of their association with substantial morbidity and mortality. Some viruses, such as cytomegalovirus and human herpesvirus 6, have immunomodulatory properties and can facilitate other infections, including fungal infections. Cytomegalovirus has long been recognized as an important virus in transplantation, but in the past decade other viruses have also received attention in the medical literature because of their association with particular clinical syndromes. Although human herpesvirus 6 has been associated with fever, rash, and encephalitis, a direct cause-and-effect relationship is still lacking. Human herpesvirus 8 has been found to be the cause of Kaposi sarcoma. Molecular techniques (e.g., pp65 antigenemia and polymerase chain reaction) that have been introduced for routine diagnosis of viruses have facilitated the diagnosis of asymptomatic viral infections and the institution of preemptive therapy. Nonetheless, the diagnosis of invasive fungal infections in liver transplant recipients is often delayed and thus associated with high mortality. Despite the use of new antifungal agents in clinical practice and the reduced incidence of fungal infections because of antifungal prophylaxis regimens, mortality has not decreased. Future patient outcomes may improve with early identification of patients who have risk factors for invasive fungal infections and with the development of new molecular diagnostic techniques for early detection.     

Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients.

The efficacy and safety of valganciclovir (VGCV) for cytomegalovirus (CMV) prophylaxis in liver transplant recipients has not been established. We retrospectively compared the efficacy and safety of low-dose oral VGCV (450 mg once daily for 90 days) and standard oral ganciclovir (1 g three times a day for 90 days, GCV) in preventing CMV disease in 109 adult liver transplant recipients who survived at least 1 month between January 2001 and April 2003 (49 GCV and 60 VGCV). The incidence of CMV disease at 1 year post-transplant was similar among patients treated with VGCV and GCV (3% and 4%, respectively). Three of the four CMV disease cases occurred in high-risk recipients with CMV serotype of donor+/recipient- (D+/R-) and all cases presented after completion of CMV prophylaxis, ranging 114-152 days post-transplant. Severe neutropenia was rare, and thrombocytopenia and anemia occurred at similar frequencies with both prophylaxis regimens. In conclusion, a 90-day regimen of low-dose oral VGCV has a similar efficacy and safety profile to high-dose oral GCV in adult liver transplant recipients. D+/R- liver transplant recipients remain at risk of developing CMV disease after completion of antiviral prophylaxis. Additional prospective studies with close monitoring for CMV viremia and drug resistance are needed to further establish the optimal dose and duration of VGCV in liver transplant recipients.     

The impact of the prevention strategies on the indirect effects of CMV infection in solid organ transplant recipients

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.     

Pneumocystis jirovecii Pneumonia in Liver Transplant Recipients: A Systematic Review

BackgroundPneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients.MethodsWe searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms “liver transplantation” and “pneumocystis.” Our search yielded 60 articles, 35 of which were used for our review.ResultsP. jirovecii pneumonia (PJP) has an incidence of 1%–11% in liver transplant recipients without prophylaxis and mortality rates of 7%–88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%–3%. The duration of its use varies from 3 months to 1 year after the liver transplantation.ConclusionsPJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.     

Safety of anidulafungin in solid organ transplant recipients

The aim of this study was the evaluation of the safety of anidulafungin in adult solid organ transplantation (SOT) recipients. During the study period (14 months), we included all consecutive SOT recipients from 14 centers who received anidulafungin for at least 48 hours for the treatment of invasive fungal infections (IFIs) or as prophylaxis. Relevant clinical and analytical information on clinical charts was reviewed. Clinical side effects, liver function tests, and serum creatinine levels were assessed at least weekly. The need for the modification of immunosuppressive drugs was also recorded by the investigators. All patients were followed for at least 1 week after the end of treatment (EOT) or until death. Eighty-six SOT recipients were evaluated (56 transplant recipients, 20 lung transplant recipients, 8 kidney transplant recipients, and 2 heart transplant recipients). Sixty-two patients (72%) received anidulafungin for prophylaxis, and 24 (28%) received anidulafungin for the treatment of IFIs [candidemia/invasive candidiasis (16) or invasive aspergillosis (8)]. At the baseline, only 5% of the patients were neutropenic (<500 neutrophils/mL). There was no need for the modification of immunosuppressive drug doses because of anidulafungin therapy. No patient discontinued anidulafungin because of severe adverse effects. While receiving anidulafungin, 1 patient developed mild liver toxicity, but the liver function normalized without the discontinuation of anidulafungin. At EOT, the median serum creatinine, aspartate aminotransferase, and alanine aminotransferase levels were significantly lower than the baseline levels, even in liver transplant recipients and patients who had higher baseline levels of serum creatinine. In conclusion, these results show that anidulafungin is a well-tolerated drug in SOT recipients.     

Obesity following kidney transplantation and steroid avoidance immunosuppression

Abstract:  Obesity is an important co-morbidity within end-stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post-transplant. With the recent adoption of steroid-sparing immunosuppressive strategies, we evaluated the effect of these strategies on body mass index (BMI) after renal transplantation. We examined 95 renal transplant recipients enrolled in National Institutes of Health clinical transplant trials over the past three yr who received either lymphocyte depletion-based steroid sparing or traditional immunosuppressive therapy that included steroids for maintenance immunosuppression. Recipients were overweight prior to transplant and no significant differences existed in pre-transplant BMI among treatment groups. Regardless of therapy, BMI increased post-transplant in all recipients. The BMI increase consisted of an average weight gain of 5.01 ± 7.12 kg (mean, SD) post-transplant. Additionally, in a number of recipients placed on maintenance steroids, subsequent withdrawal at a mean of 100 d post-transplant had no impact on weight gain. Thus, body weight and BMI increase following kidney transplantation, even in the absence of steroids. Thus, patients gain weight after renal transplantation regardless of the treatment strategy. Steroid avoidance alone does not reduce risk factors associated with obesity in our patient population.