rifampin and Pneumonia--Pneumocystis

The population pharmacokinetics of dapsone were examined in human immunodeficiency virus-infected patients receiving dapsone at a dosage of 100 mg twice weekly for the prevention of Pneumocystis carinii pneumonia. Nonlinear mixed-effect modeling was used to determine the best pharmacostatistical model for the data. A one-compartment open model with first-order absorption and elimination was used as the structural pharmacokinetic model. Several covariates were tested for their influence on pharmacokinetic parameters. Rifampin was found to increase the values of clearance/bioavailability (CL/F) and volume of distribution/ bioavailability (V/F) by approximately 70%. CL/F and V/F were 1.83 liters/h and 69.6 liters, respectively, for patients not taking rifampin. The effect of rifampin on the pharmacokinetic parameters of dapsone was appreciably less than expected on the basis of studies with healthy volunteers. Increased bilirubin levels were associated with a significant decrease in the absorption rate constant (Ka). However, this finding may be considered clinically irrelevant because the post hoc Bayesian estimates of Ka for patients with high bilirubin levels ( > 1.2 mg/dl) were at the lower bound of the values for patients with normal bilirubin levels. The value of Ka was 0.957 h-1 for a patient with a bilirubin level of 0.7 mg/dl. After inclusion of covariates in the model, the interpatient variability was 35% for CL/F, not significant for V/F, and 85% for Ka. Simulation of plasma concentration-versus-time curves indicated that the administration of 100 mg of dapsone biweekly is associated with sustained dapsone levels in the plasma of the majority of the patients. Dosage adjustments for patients concomitantly treated with rifampin may be necessary.

Topics: Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Antibiotics, Antitubercular; Dapsone; Drug Interactions; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Rifampin

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Antifungal Agents; Female; Fluconazole; Humans; Hypercalcemia; Pneumonia, Pneumocystis; Rifampin; Tuberculosis, Pulmonary

Topics: Dapsone; Didanosine; Drug Interactions; HIV Infections; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Rifampin

Topics: Dapsone; Drug Interactions; HIV Infections; Humans; Pneumonia, Pneumocystis; Rifampin

Topics: Dapsone; Drug Interactions; Humans; Pneumonia, Pneumocystis; Rifampin

Physicians at a district general hospital in London, England admitted a 26 year old pregnant political refugee from Uganda complaining of shortness of breath, fever, and a productive cough for 1 week. She was at 10 weeks gestation and had not yet sought prenatal care. 6 years earlier she had a child and her pregnancy and delivery were normal. They diagnosed an interstitial pneumonia based on an X ray, arterial gases, and quick breathing and administered intravenous (IV) ampicillin and erythromycin for 3 days. Her condition deteriorated nevertheless, so they had her blood tested for HIV. She tested positive and suspected pneumocystosis (later confirmed) and began treatment with IV Septrin and hydrocortisone. She worsened, and by the 10th day of this treatment she was receiving 60% oxygen. They changed her treatment to IV pentamidine and oral rifampicin and isoniazid. By this time, her white blood cell count was 28.7x109/1 and hemoglobin concentration 8.2g/dl. Her condition would not allow her to undergo general anesthesia so an abortion requested by the patient was not performed. Additional treatment included continuous infusion of eflornithine, but she died despite it. This case poses 2 questions. Could she have lived if there had not been a delay in HIV diagnosis? Research shows that CD4 lymphocytes cell counts fall considerably during pregnancy in HIV positive women. So some advocate prophylaxis earlier in these women than other immunocompromised patients. Was it indeed her pregnancy that contributed to the severity of her illness and its inability to respond to treatment? Some researchers find pregnancy accelerates the progress of HIV infection, but researchers do not yet know if it also accelerates the progress of opportunistic infections. If so, terminating pregnancy may be considered.

Topics: Acquired Immunodeficiency Syndrome; Adult; Eflornithine; Female; Humans; Isoniazid; Opportunistic Infections; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Rifampin

The role of rifampicin in the treatment of serologically proved Pneumocystis carinii pneumonitis was reported recently from Poland (1). Serum antibody or antigen levels alone provide uncertain evidence as by four years of age two-thirds of normal children may have significant titres (2). We present the first case treated with rifampicin, and proven by open lung biopsy.

Topics: Anti-Bacterial Agents; Biopsy; Humans; Infant; Lung; Male; Pneumonia, Pneumocystis; Rifampin

Topics: Humans; Infant; Pneumonia, Pneumocystis; Rifampin

Topics: Humans; Pneumonia, Pneumocystis; Rifampin

A combination of trimethoprim and sulfamethoxazole was effective in the prevention and treatment of Pneumocystis carinii pneumonitis in cortisonetreated rats. Although all of 15 untreated rats died with P. carinii pneumonitis, none of 15 given trimethoprim-sulfamethoxazole prophylactically acquired the infection. After P. carinii pneumonitis was established, 9 of 14 rats recovered after treatment with trimethoprim-sulfamethoxazole compared with only 2 of 14 treated with pentamidine isethionate. Rifampin and clindamycin, separately or in combination with pentamidine, were ineffective in the prevention and treatment of P. carinii infection.

Topics: Alkanesulfonates; Amidines; Animals; Clindamycin; Drug Therapy, Combination; Male; Phenyl Ethers; Pneumonia, Pneumocystis; Rifampin; Sulfamethoxazole; Tetracycline; Trimethoprim