tacrolimus and Pneumonia

The use of inhibitors of mammalian target of rapamycin is associated with adverse pulmonary effects. Although sirolimus-related pneumonitis has been well described, reports on pneumonitis with everolimus are scarce. We report a case of everolimus-induced pneumonitis in a renal transplant recipient 5 years after initiation of everolimus treatment, and we also review the literature regarding everolimus-induced pneumonitis in renal transplant patients.

Topics: Aged; Drug Substitution; Everolimus; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Pneumonia; Tacrolimus; Tomography, X-Ray Computed; Treatment Outcome

Patients on immunosuppression are at risk of unusual infections. We present a man diagnosed to have adult-onset Still's disease who, on high-dose oral steroid and tacrolimus, developed a cavitating pneumonia due to co-infection with Aspergillus flavus and Nocardia. Timely diagnosis and institution of appropriate therapy resulted in a favourable clinical outcome. Such co-infection in a patient receiving tacrolimus is rare in the published literature. This case serves to emphasise the need to be vigilant for unusual infections in patients who are immunosuppressed, either due to drugs or underlying disease condition.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Coinfection; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Nocardia Infections; Pneumonia; Radiography, Thoracic; Steroids; Still's Disease, Adult-Onset; Tacrolimus; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Atorvastatin; COVID-19 Drug Treatment; Ezetimibe; Humans; Kidney Transplantation; Liver; Myotoxicity; Pneumonia; SARS-CoV-2; Tacrolimus

Talaromyces marneffei causes life-threatening opportunistic fungal infections in immunocompromised patients. It often has a poorer prognosis in non-human immunodeficiency virus (HIV)-infected than in HIV-infected individuals because of delayed diagnosis and improper treatment.. A 51-year-old man presented with complaints of pyrexia, cough, and expectoration that had lasted for 15 day. This patient has been taking anti-rejection medication since kidney transplant in 2011.. T marneffei pneumonia; post renal transplantation; renal insufficiency; hypertension.. Intravenous moxifloxacin was administered on admission. After the etiology was established, moxifloxacin was discontinued and replaced with voriconazole. The tacrolimus dose was adjusted based on the blood concentration of tacrolimus and voriconazole.. The patient was successfully treated and followed-up without recurrence for 1 year.. A high degree of caution should be maintained for the possibility of T marneffei infection in immunodeficient non-HIV patients who live in or have traveled to T marneffei endemic areas. Early diagnosis and appropriate treatment can prevent progression of T marneffei infection and achieve a cure. Metagenomic next-generation sequencing (mNGS) can aid the physician in reaching an early pathogenic diagnosis. Close monitoring of tacrolimus and voriconazole blood levels during treatment remains a practical approach at this time.

Topics: Antifungal Agents; HIV Infections; Humans; Kidney Transplantation; Moxifloxacin; Mycoses; Pneumonia; Tacrolimus; Talaromyces; Voriconazole

Immune checkpoint inhibitor (ICI)-related pneumonitis is a relatively rare but clinically serious and potentially life-threatening adverse event. The majority of cases can be managed by drug discontinuation, with the administration of corticosteroids added in severe cases. However, worsening of pneumonitis can develop in a subset of patients despite treatment with high doses of corticosteroids. We herein report a case of steroid-refractory ICI-related pneumonitis in a recurrent non-small cell lung cancer (NSCLC) patient treated with pembrolizumab that was successfully improved by triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide). After 3 weeks of initial pembrolizumab administration, the patient was diagnosed with ICI-related pneumonitis. Chest computed tomography (CT) showed patchy distributed bilateral consolidation and ground-glass opacities (GGOs) with traction bronchiectasis and bronchiolectasis resembling the diffuse alveolar damage (DAD) radiographic pattern. Although methylprednisolone pulse therapy was initiated, worsening of respiratory failure resulted in the patient being transferred to the intensive care unit. Because of an insufficient therapeutic response to high-dose corticosteroids, tacrolimus and cyclophosphamide pulse therapy were additively performed as triple combination therapy according to the treatment strategy for pulmonary complications of clinically amyopathic dermatomyositis (CADM). In response to this triple combination therapy, the patient's respiratory condition gradually improved, and chest CT showed the marked amelioration of pulmonary opacities. This is the first report suggesting the efficacy of triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide) for steroid-refractory ICI-related pneumonitis complicated with respiratory failure.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lung Neoplasms; Male; Middle Aged; Pneumonia; Prognosis; Tacrolimus

Lung toxicity is a rare but serious side effect of sirolimus, a mammalian target of rapamycin inhibitor used as an immunosuppressive agent in solid-organ transplant recipients. We report a case of 67-year-old man who had living-related renal transplant 12 years previously that was complicated by chronic allograft dysfunction. He presented with fever, cough, and shortness of breath, and his chest imaging showed bilateral patchy and ground glass opacities. Before symptoms of lung toxicity, the patient's sirolimus levels were in the range of high normal. Bronchoalveolar lavage ruled out infection, and a transbronchial biopsy was inconclusive. A fluorodeoxyglucose positron emission tomogram scan showed high uptake in the area of lung opacities with a standard uptake value of 4.7. His symptoms improved after he was switched from sirolimus to tacrolimus, and a thoracic computed tomography scan after 6 weeks showed complete resolution. Pulmonary toxicity should be considered in any patient on sirolimus with respiratory symptoms and opacities on chest imaging. The role of fluorodeoxyglucose positron emission tomogram scan in evaluation of sirolimus-induced lung toxicity has not been previously described, and this is the first report of this type of scan finding indicating intense inflammation in this condition.

Topics: Aged; Drug Substitution; Fluorodeoxyglucose F18; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Lung; Male; Pneumonia; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Sirolimus; Tacrolimus; Treatment Outcome

The lung is a prototypic organ that was evolved to reduce immunopathology during the immune response to potentially hazardous endogenous and exogenous antigens. In this study, we show that donor CD4

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histone Deacetylase Inhibitors; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interferon gamma Receptor; Interferon-gamma; Kynurenine; Lung; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Pneumonia; Receptors, Aryl Hydrocarbon; Receptors, Interferon; T-Lymphocytes; T-Lymphocytes, Regulatory; Tacrolimus

We examined integrated national transplant registry, pharmacy fill, and medical claims data for Medicare-insured kidney transplant recipients in 2000-2011 (n = 45 164) from the United States Renal Data System to assess the efficacy and safety endpoints associated with seven early (first 90 days) immunosuppression (ISx) regimens. Risks of clinical complications over 3 years according to IS regimens were assessed with multivariate regression analysis, including the adjustment for covariates and propensity for receipt of a nonreference ISx regimen. Compared with the reference ISx (thymoglobulin induction with tacrolimus, mycophenolate, and prednisone maintenance), sirolimus-based ISx was associated with significantly higher three-year risks of pneumonia (adjusted hazard ratio, aHR 1.45; P < 0.0001), sepsis (aHR 1.40; P < 0.0001), diabetes (aHR 1.21; P < 0.0001), acute rejection (AR; adjusted odds ratio, aOR 1.33; P < 0.0001), graft failure (aHR 1.78; P < 0.0001), and patient death (aHR 1.40; P < 0.0001), but reduced skin cancer risk (aHR 0.71; P < 0.001). Cyclosporine-based IS was associated with increased risks of pneumonia (aHR 1.17; P < 0.001), sepsis (aHR 1.16; P < 0.001), AR (aOR 1.43; P < 0.001), and graft failure (aHR 1.39; P < 0.001), but less diabetes (aHR 0.83; P < 0.001). Steroid-free ISx was associated with the reduced risk of pneumonia (aHR 0.89; P = 0.002), sepsis (aHR 0.80; P < 0.001), and diabetes (aHR 0.77; P < 0.001), but higher graft failure (aHR 1.35; P < 0.001). Impacts of ISx over time warrant further study to better guide ISx tailoring to balance the efficacy and morbidity.

Topics: Adolescent; Adult; Cyclosporine; Diabetes Mellitus; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Pneumonia; Renal Insufficiency; Risk; Sepsis; Sirolimus; Tacrolimus; United States; Young Adult

Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients.

Topics: Abscess; Candida glabrata; Candidiasis; Creatinine; Disease Susceptibility; Drug Substitution; Erythrocytes, Abnormal; Everolimus; Female; Hemoglobins; Humans; Immunosuppressive Agents; L-Lactate Dehydrogenase; Lung Transplantation; Male; Middle Aged; Myositis; Nocardia Infections; Platelet Transfusion; Pneumonia; Postoperative Complications; Tacrolimus; Thrombotic Microangiopathies; Young Adult

Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function.

Topics: Acute Disease; Adult; Antibodies, Monoclonal; Basiliximab; Coinfection; Cystic Fibrosis; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lung Transplantation; Male; Mycophenolic Acid; Pneumonia; Prednisone; Recombinant Fusion Proteins; Recovery of Function; Renal Dialysis; Respiratory Insufficiency; Tacrolimus

Invasive fungal infections (IFIs) are a major cause of death in organ transplant patients. The murine hydrocortisone-mediated immunosuppression model of pulmonary aspergillosis is commonly used to characterise IFIs in these patients. However, this model does not take into account the effects of calcineurin inhibitors on transplant immunity to IFIs or the fungal calcineurin pathway, which is required for both virulence and antifungal drug resistance. To address these two issues, a new and clinically relevant transplant immunosuppression model of tacrolimus (FK506) and hydrocortisone-associated pulmonary aspergillosis was developed. We first characterised IFIs in 406 patients with a lung transplant. This showed that all of the patients with pulmonary aspergillosis were immunosuppressed with calcineurin inhibitors and steroids. Murine pharmacokinetic studies demonstrated that an ideal dose of 1 mg/kg/day of FK506 intraperitoneally produced blood trough levels in the human therapeutic range (5-12 ng/ml). There was increased mortality from pulmonary aspergillosis in a transplant-relevant immunosuppression model using both FK506 and hydrocortisone as compared with immunosuppression using hydrocortisone only. Lung histopathology showed neutrophil invasion and tracheobronchitis that was associated with reduced lung tumour necrosis factor-α (TNFα), JE (homologue of human MCP-1) and KC (homologue of human IL-8) at 24 hours, but increased lung TNFα, JE and KC at 48 hours when fungal burden was high. Furthermore, FK506 directly impaired fungal killing in alveolar macrophages in vitro, with FK506-mediated inhibition of the radial growth of Aspergillus fumigatus in vitro occurring at the low concentration of 5 ng/ml. Taken together, these findings show that the immunosuppressive activity of FK506 outweighs its antifungal activity in vivo. These observations demonstrate that FK506 impairs innate immune responses and leads to an incremental increase in susceptibility to IFIs when it is combined with steroids. This new and clinically relevant mouse model of invasive aspergillosis is a valuable addition to the further study of both fungal immunity and antifungal therapy in organ transplantation.

Topics: Animals; Aspergillus fumigatus; Chemokine CCL2; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Immunosuppression Therapy; Immunosuppressive Agents; Injections, Intraperitoneal; Interleukin-8; Lung Transplantation; Male; Mice; Pneumonia; Pulmonary Aspergillosis; Risk Factors; Steroids; Survival Analysis; Tacrolimus; Tumor Necrosis Factor-alpha

We have recently shown that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial membrane protein, associates with VE-cadherin and is required for optimal VE-cadherin function and endothelial cell contact integrity. The dissociation of VE-PTP from VE-cadherin is triggered by vascular endothelial growth factor (VEGF) and by the binding of leukocytes to endothelial cells in vitro, suggesting that this dissociation is a prerequisite for the destabilization of endothelial cell contacts. Here, we show that VE-cadherin/VE-PTP dissociation also occurs in vivo in response to LPS stimulation of the lung or systemic VEGF stimulation. To show that this dissociation is indeed necessary in vivo for leukocyte extravasation and VEGF-induced vascular permeability, we generated knock-in mice expressing the fusion proteins VE-cadherin-FK 506 binding protein and VE-PTP-FRB* under the control of the endogenous VE-cadherin promoter, thus replacing endogenous VE-cadherin. The additional domains in both fusion proteins allow the heterodimeric complex to be stabilized by a chemical compound (rapalog). We found that intravenous application of the rapalog strongly inhibited VEGF-induced (skin) and LPS-induced (lung) vascular permeability and inhibited neutrophil extravasation in the IL-1β inflamed cremaster and the LPS-inflamed lung. We conclude that the dissociation of VE-PTP from VE-cadherin is indeed required in vivo for the opening of endothelial cell contacts during induction of vascular permeability and leukocyte extravasation.

Topics: Animals; Antigens, CD; Cadherins; Capillary Permeability; Chlorocebus aethiops; COS Cells; DNA Primers; Endothelial Cells; Gene Knock-In Techniques; Immunoblotting; Immunoprecipitation; Leukocytes; Lipopolysaccharides; Lung; Mice; Pneumonia; Receptor-Like Protein Tyrosine Phosphatases, Class 3; Recombinant Fusion Proteins; Tacrolimus; Transendothelial and Transepithelial Migration; Vascular Endothelial Growth Factor A

Topics: Adrenal Cortex Hormones; Adult; Azathioprine; Bronchoalveolar Lavage Fluid; Diagnosis, Differential; Diarrhea; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Metronidazole; Mycophenolic Acid; Pneumonia; Pneumonia, Bacterial; Pneumonia, Viral; Postoperative Complications; Sirolimus; Tacrolimus; Tomography, X-Ray Computed

To investigate whether FK506 (tacrolimus) can inhibit Fas- or A23187-induced interleukin (IL)-8 expression and cell death in A549 human alveolar epithelial cells, plus Fas-mediated acute lung injury in vivo.. Assays for IL-8, cell death, and caspase-3 activity were performed. A549 cells were treated with 25 micromol A23187 or 0.2 microg/ml agonistic anti-Fas antibody plus 5 ng/ml interferon-gamma (IFN-gamma). Tacrolimus was treated at 0.1-10 ng/ml. For in vivo experiment, agonistic anti-Fas antibody (Jo2) at 2.5 microg/g was intratracheally instilled into C57BL/6 mice. Neutrophils and protein contents in bronchoalveolar lavage (BAL) fluid were measured within 24 h of instillation. Mice were orally treated with 32 mg/kg of tacrolimus 24 h and 1 h prior to instillation.. Both Fas and A23187 caused significant IL-8 expression and cell death in A549 cells. Tacrolimus inhibited A23187-induced IL-8 expression alone while it protected all Fas-mediated responses. Mice instilled intratracheally with Jo2 at 2.5 microg/g had significant increases in neutrophils, protein contents in BAL fluid and in expression of chemoattractants for neutrophils. These increases were reversed by tacrolimus.. Tacrolimus serves as a therapeutic option for improving lung injury through inhibition of Fas-mediated inflammation.

Topics: Animals; Antibodies, Monoclonal; Calcimycin; Caspase 3; Cell Death; Cell Line; Dose-Response Relationship, Drug; fas Receptor; Gene Expression Regulation; Gene Expression Regulation, Enzymologic; Humans; Immunosuppressive Agents; Inflammation; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Pneumonia; Pulmonary Alveoli; Respiratory Mucosa; RNA, Messenger; Tacrolimus

Acute graft-versus-host disease is a common complication after allogeneic stem cell transplantation. It normally affects the skin, liver, and gut. We report a 54-year-old male who developed shortness of breath, cough, and bilateral pulmonary infiltrates in which the work-up failed to demonstrate an infectious etiology 165 days post-HLA-matched allogeneic peripheral blood stem cell transplant. Eighteen days before, his tacrolimus had been tapered and it was subtherapeutic on admission. A transbronchial biopsy showed a perivascular and interstitial lymphocytic infiltrate without evident pathogens on histology or extensive work-up. The clinical picture was suggestive of pulmonary acute graft-versus-host disease. No disease was present elsewhere. Accordingly, the patient was treated with steroids and tacrolimus. After 12 hr on methylprednisolone, his symptoms disappeared with eventual resolution radiologically. Acute graft-versus-host disease of the lung is a very uncommon complication after stem cell transplant, but it should be considered in patients who are at high risk for graft-versus-host disease or developing symptoms soon after discontinuing immunosuppression. Its diagnosis requires work-up to rule out an infectious etiology and a biopsy to confirm histology.

Topics: Acute Disease; Anti-Inflammatory Agents; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Lung; Lung Diseases; Lymphocytes; Male; Methylprednisolone; Middle Aged; Peripheral Blood Stem Cell Transplantation; Pneumonia; Radiography, Thoracic; Steroids; Tacrolimus; Tomography, X-Ray Computed; Transplantation, Homologous

A 42-year-old woman who underwent single lung transplantation who received tacrolimus and a 58-year-old woman with pneumonia and multiple comorbidities who received haloperidol both experienced drug-induced prolongation of cardiac repolarization. The second woman also developed torsade de pointes. Critically ill patients are particularly susceptible to developing torsade de pointes due to various comorbidities, electrolyte disturbances, and receipt of numerous drugs. These two case reports illustrate the increased risk for drug-induced cardiotoxicity in the critically ill patient. They also indicate the need for current knowledge derived from basic research and retrospective case reports on drug-induced torsade de pointes to be integrated into the existing body of knowledge. Guidelines can then be developed to help prospectively reduce the frequency of adverse effects in intensive care patients. Research is necessary regarding identification of high-risk patients before drugs are administered, and clarification of the proper role of therapeutic QT monitoring in clinical practice.

Topics: Administration, Oral; Adult; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Electrocardiography; Female; Haloperidol; Heart Conduction System; Humans; Hypertension, Pulmonary; Injections, Intravenous; Long QT Syndrome; Middle Aged; Pneumonia; Tachycardia, Ventricular; Tacrolimus; Torsades de Pointes

The aim of this study is to evaluate the effects of RAPA conversion in patients undergoing cyclosporine (CsA) or tacrolimus (Tac) toxicity.. Twenty renal transplant recipients were switched to fixed dose rapamycin (RAPA) (5 mg/day) 0 to 204 months posttransplant. Drug monitoring was not initially used to adjust doses. The indications for switch were chronic CsA or Tac nephrotoxicity (12), acute CsA or Tac toxicity (3), severe facial dysmorphism (2), posttransplant lymphoproliferative disorder (PTLD) in remission (2), and hepatotoxicity in 1. Follow-up is 7 to 24 months.. In the 12 patients switched because of chronic nephrotoxicity there was a significant decrease in serum creatinine [233+/-34 to 210+/-56 micromol/liter (P<0.05) at 6 months]. Facial dysmorphism improved in two patients. No relapse of PTLD was observed. Five patients developed pneumonia (two Pneumocystis carinii pneumonia, one infectious mononucleosis with polyclonal PTLD lung infiltrate) and two had bronchiolitis obliterans. There were no deaths. RAPA was discontinued in four patients, because of pneumonia in two, PTLD in one, and oral aphtous ulcers in one. RAPA levels were high (>15 ng/ml) in 7 of 13 (54%) patients.. RAPA conversion provides adequate immunosuppression to enable CsA withdrawal. However, when converting patients to RAPA drug levels should be monitored to avoid over-immunosuppression and adequate antiviral and Pneumocystis carinii pneumonia prophylaxis should be given.

Topics: Adult; Blood Pressure; Cyclosporine; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Lymphoproliferative Disorders; Male; Middle Aged; Pneumonia; Sirolimus; Tacrolimus

A 40-year-old Asian man, 6 months post renal transplant and receiving tacrolimus therapy, presented to the emergency department with a complaint of sudden-onset left eye pain with blurred vision, headache on the left side, and nausea and vomiting. On being admitted, the patient was intubated for respiratory depression, and erythromycin was initiated for suspected atypical pneumonia. Tacrolimus concentrations (whole blood) drawn on the 3rd day of hospitalization were reported to be > 60.0 ng/ml. Before hospitalization, tacrolimus concentrations were reported to be 9.8 ng/ml on a maintenance dose of 7 mg twice daily. Six days after discontinuation of erythromycin and a decrease in tacrolimus dose, the concentration decreased to 11.5 ng/ml and the original dose of tacrolimus was restarted. It is recommended that concurrent administration of erythromycin and tacrolimus be avoided. However, if concomitant therapy is necessary, tacrolimus concentrations, serum creatinine, blood urea nitrogen, and urine output should be monitored.

Topics: Adult; Anti-Bacterial Agents; Drug Interactions; Erythromycin; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Pneumonia; Postoperative Complications; Tacrolimus

Pulmonary infections are a significant cause of morbidity after liver transplantation; Gram-negative bacilli, cytomegalovirus, and Pneumocystis carinii were the usual pulmonary pathogens in the earlier studies in liver transplant recipients receiving cyclosporine. We prospectively assessed the impact of pulmonary infection in 101 consecutive liver transplant recipients receiving the new immunosuppressive agent tacrolimus (FK506). Fifteen percent (15/101) of the patients had 19 episodes of pneumonia; 58% (11/19) of the pneumonias were bacterial, 37% (7/19) were fungal, and 5% (1/19) were protozoal (Toxoplasma gondii). Twenty-seven percent of the bacterial pneumonias were due to Legionella. None of the patients had cytomegalovirus or P carinii pneumonia. Seven percent (7/10) of the study patients had fungal pneumonitis; 4% had invasive aspergillosis and 3% had cryptococcosis. Mortality was significantly higher (53%, 8/15) for patients with pneumonia than for patients without pneumonia (10%, 9/86, P = 0.0004). Only fungal pneumonias were the direct cause of death; 63% (5/8) of the deaths were in patients with fungal pneumonitis. Our data suggest a changing pattern of microbial etiologies of pneumonitis in the era of modern immunosuppressive agents. We show that P carinii pneumonia and cytomegalovirus can be effectively curtailed with appropriate prophylaxis. Fungal infections, on the contrary, not only constituted a major proportion of the pneumonia, but also carried the highest pneumonia-associated mortality. Legionella infections can be overlooked unless specialized laboratory methodology (cultured on selective media, urinary antigen) are applied routinely on all cases of pneumonia. We recommend routine culture on the water supply for Legionella in all transplant centers.

Topics: Adult; Aged; Community-Acquired Infections; Cross Infection; Female; Humans; Immunosuppressive Agents; Legionnaires' Disease; Liver Transplantation; Lung Diseases, Fungal; Lung Diseases, Parasitic; Male; Middle Aged; Pneumonia; Pneumonia, Bacterial; Prospective Studies; Risk Factors; Tacrolimus; Toxoplasmosis

Topics: Animals; Drug Therapy, Combination; Graft Survival; Immunosuppression Therapy; Immunosuppressive Agents; Lung Transplantation; Macaca; Methotrexate; Papio; Pneumonia; Pneumothorax; Postoperative Complications; Splenectomy; Surgical Wound Infection; Tacrolimus; Transplantation, Heterologous

Topics: Eosinophilia; Female; Humans; Liver Transplantation; Lung; Middle Aged; Pneumonia; Radiography; Tacrolimus