A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia

Objective: To determine the relative efficacies of alternative antipneumocystis agents in human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia unresponsive to primary drug treatment with a combination product of trimethoprim and sulfamethoxazole or parenteral pentamidine. Methods: Meta-analysis of 27 published clinical drug trials, case series, and case reports involving P carinii pneumonia. Data extracted included underlying disease, primary antipneumocystis treatment, days of failed primary treatment, salvage regimen, use of systemic corticosteroids and antiretroviral drugs, and clinical outcome. Results: In 497 patients with microbiologically confirmed P carinii pneumonia (456 with HIV or acquired immunodeficiency syndrome), initial antipneumocystis treatment failed and they therefore required alternative drug therapy. Failed regimens included trimethoprimsulfamethoxazole (160 patients), intravenous pentamidine (63 patients), trimethoprim-sulfamethoxazole and/or pentamidine (258 patients), aerosolized pentamidine (6 patients), atovaquone (3 patients), dapsone (3 patients), a combination product of trimethoprim and dapsone (2 patients), and trimethoprim-sulfamethoxazole followed by a combination of clindamycin and primaquine phosphate (2 patients). Efficacies of salvage regimens were as follows: clindamycin-primaquine (42 to 44 [88%-92%] of 48 patients; P<10^-8), atovaquone (4 [80%] of 5), eflornithine hydrochloride (40 [57%] of 70; P<.01), trimethoprim-sulfamethoxazole (27 [53%] of 51; P<.08), pentamidine (64 [39%] of 164), and trimetrexate (47 [30%] of 159). Conclusion: The combination of clindamycin plus primaquine appears to be the most effective alternative treatment for patients with P carinii pneumonia who are unresponsive to conventional antipneumocystis agents.