Annals of Internal Medicine · 1988 · 362 citations · 21 references
PharmacyInfectious DiseasesPharmacologyAntimicrobial PharmacotherapyClinical PharmacologyRenal PharmacotherapyAntimicrobial DosingDose OptimizationEmpiric Antimicrobial TherapyPneumonia PharmacotherapyAcquired Immunodeficiency SyndromeDrug Dosing OptimizationPharmacokinetics Of Antimicrobial AgentsPneumocystis InfectionPneumonia Empiric TherapySerum Creatinine AssessmentTertiary Care OrganizationTrimethoprim-sulfamethoxazole Therapy
STUDY OBJECTIVE: To ascertain the efficacy and toxicity of trimethoprim-sulfamethoxazole or pentamidine when either is given alone during the entire treatment period for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective, randomized, noncrossover comparison of trimethoprim-sulfamethoxazole with pentamidine. Trimethoprim-sulfamethoxazole dosage was adjusted to maintain serum trimethoprim at 5 to 8 micrograms/mL. Pentamidine dosage was reduced by 30% to 50% for an absolute rise in serum creatinine of more than 88 mumol/L (1 mg/dL). SETTING: Tertiary care hospital and AIDS clinic. PATIENTS: Thirty-six patients were treated with trimethoprim-sulfamethoxazole and 34 with pentamidine. Pretreatment clinical features and laboratory test results were similar in the two groups. MEASUREMENTS AND MAIN RESULTS: Thirty-six recipients of trimethoprim-sulfamethoxazole and 33 recipients of pentamidine completed therapy without crossover. Trimethoprim-sulfamethoxazole caused a rash (44%) and anemia (39%) more frequently (P less than or equal to 0.03, whereas pentamidine caused nephrotoxicity (64%), hypotension (27%), or hypoglycemia (21%) more frequently (P less than or equal to 0.01). The (A - a)DO2 improved by greater than 1.3 kPa (10 mmHg) 8 days earlier for trimethoprim-sulfamethoxazole recipients (95% CI for the difference in response, -1 to 17; P = 0.04). Thirty-one (86%) patients treated with trimethoprim-sulfamethoxazole and 20 (61%) with pentamidine survived and were without respiratory support at completion of treatment (95% CI for the difference in response, 5% to 45%; P = 0.03). CONCLUSIONS: For most patients with AIDS and P. carinii pneumonia, successful treatment with a single agent is possible. Toxicity associated with the two standard treatments is rarely life-threatening and may be diminished if the trimethoprim-sulfamethoxazole dosage is modified by pharmacokinetic monitoring and the pentamidine dosage is reduced for nephrotoxicity. Oxygenation improved more quickly and survival was better with trimethoprim-sulfamethoxazole.
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Pulmonary Complications of the Acquired Immunodeficiency Syndrome
John F. Murray, Charles P. Felton, Stuart M. Garay et al. · New England Journal of Medicine · 1984 · 694 citations