tacrolimus and Respiratory-Tract-Infections

The safety and efficacy of a 1% cream formulation of pimecrolimus, a selective, nonsteroid immunomodulator, was studied in infants with atopic dermatitis (AD).. During a 6-week double-blind phase, 186 infants with mild/moderate AD were randomly assigned to twice-daily pimecrolimus cream 1% or vehicle. All patients were subsequently treated with open-label pimecrolimus for 20 weeks.. At the end of the double-blind phase, 54.5% and 23.8% of patients in the pimecrolimus and vehicle groups, respectively, were clear or almost clear of AD (P <.001). Similar improvements were observed in the Eczema Area and Severity Index, pruritus assessment, and the care giver's assessment. By the first return visit, 69.9% and 36.5% of pimecrolimus and vehicle-treated patients, respectively, achieved absent or mild pruritus. Efficacy during the double-blind phase was maintained throughout the open-label phase. Vehicle-treated patients transferring to open-label pimecrolimus rapidly achieved disease control comparable to those receiving continuous pimecrolimus. There were no significant differences between groups in application site reactions or skin infections. Most adverse events were mild or moderate and unrelated to treatment.. Pimecrolimus was safe in infants with AD, with rapid and sustained efficacy. Pimecrolimus holds promise as a valuable new treatment option for the youngest patients with AD.

Topics: Administration, Cutaneous; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Atopic; Dermatologic Agents; Diarrhea; Double-Blind Method; Female; Fever; Humans; Infant; Male; Ointments; Pharyngitis; Respiratory Tract Infections; Safety; Severity of Illness Index; Tacrolimus; Time Factors; Treatment Outcome

In clinical practice, some IgA nephropathy (IgAN) patients show resistance to or are unable to achieve complete remission using steroids and/or immunosuppressants. The current study aimed to assess the efficacy and safety of tacrolimus in the treatment of cases of refractory IgAN.In this retrospective observational study, 34 primary IgAN patients with refractory proteinuria received tacrolimus for at least 12 months. Complete remission, partial remission, and other clinical data were measured at 1, 3, 6, and 12 months after the initiation of treatment.After 12 months, complete remission was achieved in 20 (58.8%) patients and partial remission in 5 (14.7%) patients, yielding a total response rate of 73.5%. The mean time for response to tacrolimus for those who achieved complete remission and partial remission was 7.0 ± 4.7 weeks. Serum creatinine (Scr), uric acid, estimated glomerular filtration rate, alanine aminotransferase, aspartate transaminase, white blood cell count, blood pressure, blood glucose, total cholesterol, and total triglyceride were stable over time. Three patients demonstrated a loss of eGFR >15 mL/min·1.73 m from baseline. Three cases of upper respiratory infection and 2 cases of urinary tract infection were observed during the study. Patients who achieved complete remission had better renal function and lower baseline proteinuria than partial remission and nonresponder patients. Crescent formation in biopsy specimens was seen more often in nonresponder patients.Tacrolimus was safe and effective at lowering proteinuria in refractory IgAN patients. Lower baseline proteinuria and better renal function were associated with a higher probability of complete remission, while crescent formation was associated with a worse prognosis.

Topics: Adult; Female; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Male; Middle Aged; Proteinuria; Remission Induction; Respiratory Tract Infections; Retrospective Studies; Tacrolimus; Urinary Tract Infections; Young Adult

Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy.

Topics: Adolescent; Anti-Bacterial Agents; Cystic Fibrosis; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Nafcillin; Respiratory Tract Infections; Tacrolimus; Withholding Treatment

Topics: Adolescent; Adult; Calcineurin Inhibitors; Cyclophosphamide; Drug Resistance; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Nephrotic Syndrome; Phospholipases A2; Prednisolone; Proteinuria; Receptors, Phospholipase A2; Recurrence; Respiratory Tract Infections; Tacrolimus; Treatment Outcome; Young Adult

Rhinovirus is the most common cause of respiratory viral infections and leads to frequent respiratory symptoms in lung transplant recipients. However, it remains unknown whether the rhinovirus load correlates with the severity of symptoms.. This study aimed to better characterize the pathogenesis of rhinoviral infection and the way in which viral load correlates with symptoms.. We assessed rhinovirus load in positive upper respiratory specimens of patients enrolled prospectively in a cohort of 116 lung transplant recipients. Rhinovirus load was quantified according to a validated in-house, real-time, reverse transcription polymerase chain reaction in pooled nasopharyngeal and pharyngeal swabs. Symptoms were recorded in a standardised case report form completed at each screening/routine follow-up visit, or during any emergency visit occurring during the 3-year study.. Rhinovirus infections were very frequent, including in asymptomatic patients not seeking a specific medical consultation. Rhinovirus load ranged between 4.1 and 8.3 log copies/ml according to the type of visit and clinical presentation. Patients with highest symptom scores tended to have higher viral loads, particularly those presenting systemic symptoms. When considering symptoms individually, rhinovirus load was significantly higher in the presence of symptoms such as sore throat, fever, sputum production, cough, and fatigue. There was no association between tacrolimus levels and rhinovirus load.. Rhinovirus infections are very frequent in lung transplant recipients and rhinoviral load in the upper respiratory tract is relatively high even in asymptomatic patients. Patients with the highest symptom scores tend to have a higher rhinovirus load.

Topics: Adult; Aged; Cohort Studies; Female; Humans; Lung Transplantation; Male; Middle Aged; Nasopharynx; Picornaviridae Infections; Prospective Studies; Real-Time Polymerase Chain Reaction; Respiratory Tract Infections; Rhinovirus; Tacrolimus; Time Factors; Transplant Recipients; Viral Load

Bronchiectasis is characterized by abnormal, permanent and irreversible dilatation of the bronchi, usually responsible for daily symptoms and frequent respiratory complications. Many causes have been identified, but only limited data are available concerning the association between bronchiectasis and renal transplantation.. We conducted a retrospective multicenter study of cases of bronchiectasis diagnosed after renal transplantation in 14 renal transplantation departments (French SPIESSER group). Demographic, clinical, laboratory and CT scan data were collected.. Forty-six patients were included (mean age 58.2 years, 52.2 % men). Autosomal dominant polycystic kidney disease (32.6 %) was the main underlying renal disease. Chronic cough and sputum (50.0 %) were the major symptoms leading to chest CT scan. Mean duration of symptoms before diagnosis was 1.5 years [0-12.1 years]. Microorganisms were identified in 22 patients, predominantly Haemophilus influenzae. Hypogammaglobulinemia was observed in 46.9 % patients. Bronchiectasis was usually extensive (84.8 %). The total bronchiectasis score was 7.4 ± 5.5 with a significant gradient from apex to bases. Many patients remained symptomatic (43.5 %) and/or presented recurrent respiratory tract infections (37.0 %) during follow-up. Six deaths (13 %) occurred during follow-up, but none were attributable to bronchiectasis.. These results highlight that the diagnosis of bronchiectasis should be considered in patients with de novo respiratory symptoms after renal transplantation. Further studies are needed to more clearly understand the mechanisms underlying bronchiectasis in this setting.

Topics: Adult; Agammaglobulinemia; Aged; Aged, 80 and over; Azathioprine; Bronchiectasis; Chronic Disease; Cough; Cyclosporine; Everolimus; Female; Forced Expiratory Volume; Graft Rejection; Haemophilus Infections; Haemophilus influenzae; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Polycystic Kidney, Autosomal Dominant; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Rituximab; Sirolimus; Tacrolimus; Tomography, X-Ray Computed; Vital Capacity; Young Adult