tacrolimus and Pneumonia--Bacterial

Legionella micdadei (Pittsburgh pneumonia agent) is the second most common cause of Legionella pneumonia, and occurs predominantly in immunocompromised hosts. L micdadei is the cause of nosocomial pneumonia in renal transplant recipients, but has not been described in other adult solid organ transplant recipients. This report describes the first case of L micdadei pneumonia in an adult liver transplant recipient on immunosuppressive therapy. Importantly, this case highlights the difficulties in establishing the diagnosis, as the Legionella urinary antigen is negative, and special culture conditions are required. Furthermore, this case illustrates several atypical clinical features of L micdadei pneumonia in a transplant recipient, including a community acquired mode of transmission, occurrence several years after organ transplantation, and lung abcess formation. The patient was successfully treated with limited surgical resection and quinolone antimicrobial monotherapy.

Topics: Adult; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Ciprofloxacin; Diabetes Mellitus, Type 2; Hepatitis B; Humans; Immunosuppressive Agents; Legionellosis; Liver Transplantation; Lung Abscess; Male; Pneumonia, Bacterial; Postoperative Complications; Tacrolimus; Tomography, X-Ray Computed

A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary immunosuppressive agent after lung transplantation.. Between October 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying disease.. One-year and 2-year survival rates were similar in the two groups, although the trend was toward increased survival with tacrolimus. Acute rejection episodes per 100 patient-days were fewer (p = 0.07) in the tacrolimus group (0.85) than in the cyclosporine group (1.09). Obliterative bronchiolitis developed in significantly fewer patients in the tacrolimus group (21.7%) compared with the cyclosporine group (38%) (p = 0.025), and there was greater freedom from obliterative bronchiolitis over time for patients receiving tacrolimus (p < 0.03). Significantly more cyclosporine-treated patients (n = 13) required crossover to tacrolimus than tacrolimus-treated patients to cyclosporine (n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acute rejection in 6 of 9 patients. The overall incidence of infections was similar in the two groups, although bacterial infections were more common with cyclosporine (p = 0.0375), whereas the risk of fungal infection was higher with tacrolimus (p < 0.05).. This trial demonstrates the advantage of tacrolimus in reducing the risk of obliterative bronchiolitis, the most important cause of long-term morbidity and mortality after lung transplantation.

Topics: Acute Disease; Adult; Bronchiolitis Obliterans; Cross-Over Studies; Cyclosporine; Female; Follow-Up Studies; Fungemia; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Lung Transplantation; Male; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Risk Factors; Survival Rate; Tacrolimus

Nocardia thyroid abscess with pneumonia is a rare clinical presentation. We reported a liver transplant recipient with Nocardia thyroiditis and pneumonia after receiving high dose immunosuppressants to preserve his graft. The patient is a 50-year-old male who developed hepatitis C virus-related liver cirrhosis and received a liver transplant. Seven months post-transplantation the patient developed graft rejection, which was treated with 3 days pulse dose methyl-prednisolone followed by an increased dose of his tracolimus, mycophenolate and prednisolone. He presented to the hospital with a 2 week history of fever, tenderness in his anterior neck and dry cough. On admission his temperature was 39.5°C. The right wing of his thyroid gland was swollen to 3 cm in size, fluctuant and tender. On auscultation of his lungs there were fine crepitations and increased vocal resonance in the right middle lung field. On laboratory testing, a complete blood count (CBC) revealed leukocytosis (19,900/mm3) with neutrophils (97%). A chest X-ray showed an patchy infiltrates and round circumscribed densities in the superior segment of the right lower lobe of his lung. A CT scan of his neck revealed a diffusely enlarged right wing of the thyroid gland, 3.8 cm in diameter that had an abnormal hyposignal area. A CT of his chest revealed consolidation of the superior segment of the right lower lobe and necrotic right paratracheal lymph nodes with inflamed strap muscles. Fine needle aspiration of the right lobe of thyroid gland was performed. Modified acid-fast bacilli (MAFB) staining showed partially acid-fast beaded branching filamentous organisms and a culture grew out Nocardia asteroides. He was treated with trimethoprim-sulfamethoxazole for 6 months. He improved clinically and his chest X-ray also cleared.

Topics: Abscess; Fever; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Nocardia Infections; Pneumonia, Bacterial; Prednisolone; Tacrolimus; Thyroiditis

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

Hepatotoxicity, including cholestasis, is a rare but significant complication of treatment with calcineurin inhibitors. Timely life-saving therapy with revision of immunosuppression is mandatory. A 43-year-old woman with pulmonary hypertension was found to have severe cholestasis (serum bilirubin up to 35 mg/dL) after a living-donor lobar lung transplantation. Calcineurin-inhibitor cholestasis markedly improved after withdrawal of the calcineurin inhibitor, initiation of sirolimus, and interleukin-2 receptor blockade. Awareness of the diagnostic criteria of this rare posttransplant complication is important to initiate timely therapy.

Topics: Adult; Calcineurin; Calcineurin Inhibitors; Cholestasis; Disease Progression; Fatal Outcome; Female; Graft Rejection; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Living Donors; Lung Transplantation; Methylprednisolone; Pneumonia, Bacterial; Postoperative Complications; Pseudomonas Infections; Risk Assessment; Sirolimus; Tacrolimus; Transplantation Immunology

One-hundred and fourteen limb transplantations have been performed across a major histoincompatibility barrier between donor ACI (RT1a) and recipient Lewis (RT1l) rats immunosuppressed with various dosages of FK-506 and cyclosporine. Three-hundred and thirty biopsy specimens from 64 animals have been evaluated histologically for signs of rejection. A new histologic grading system is introduced to classify the process of rejection in the component tissues (skin, muscle, bone, and articular cartilage) of a limb allograft. The results indicate that FK-506 is a more potent immunosuppressive agent than cyclosporine in preventing the rejection of the skin component of a limb transplant. With twice-weekly intermittent immunosuppression with FK-506, the rejection of muscle, bone, and cartilage can be prevented for an indefinite time, although all long-term surviving animals died at around 300 days, probably of graft-versus-host disease. Based on the histologic stages of rejection in the different tissues at the same point in time, it is evident that each component tissue of a limb transplant rejects over a different time period. This probably reflects a hierarchy of antigenicity, with skin being most antigenic, muscle being intermediate in antigenicity, and bone and cartilage being least antigenic. Although this grading system is not the ultimate solution, it may allow a more objective comparison of experimental limb transplantation in the future.

Topics: Analysis of Variance; Animals; Biopsy; Bone and Bones; Cartilage, Articular; Cyclosporine; Drug Administration Schedule; Epidermis; Fibrosis; Graft Rejection; Hindlimb; Immunosuppression Therapy; Muscle, Skeletal; Necrosis; Pneumonia, Bacterial; Rats; Rats, Inbred ACI; Rats, Inbred Lew; 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