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Aerosolized Pentamidine for Pneumocystis carinii Pneumonia

1989; Elsevier BV; Volume: 96; Issue: 4 Linguagem: Inglês

10.1378/chest.96.4.713

1931-3543

John M. Luce, Philip C. Hopewell,

Synthesis and Biological Evaluation

Aerosolized pentamidine has proven to be safe and effective in the prevention1Leoung GS, Montgomery AB, Abrams DJ, Wardlaw L, Corkery K, et al. Aerosol pentamidine for Pneumocystis carinii pneunia prophylaxis: A 3 arm randomized trial. Abstracts, V International Conference on AIDS, 1989:196Google Scholar and treatment2Montgomery AB Debs RJ Luce JM Corkery KJ Turner J et al.Aerosolized pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.Lancet. 1987; 2: 480-483Abstract PubMed Scopus (148) Google Scholar, 3Conte JE Hollander H Golden JA Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia.Ann Intern Med. 1987; 107: 495-498Crossref PubMed Scopus (82) Google Scholar of Pneumocystis carinii pneumonia (PCP) in patients with the acquired immunodeficiency syndrome (AIDS). The aerosolized form of pentamidine offers the advantage of targeting delivery to the alveoli while reducing drug levels in serum and solid organs.4Montgomery AB Debs RJ Luce JM Corkery KJ Turner J Selective delivery of pentamidine to the lung by aerosol.Am Rev Respir Dis. 1988; 137: 477-478Crossref PubMed Scopus (62) Google Scholar This selective distribution is appropriate because the lung is the primary organ infected by Pneumocystis carinii, whereas the liver and kidney are the most common sites of systemic drug toxicity.5Hughes WT Pneumocystis carinii pneumonia.N Engl J Med. 1977; 297: 1381-1383Crossref PubMed Scopus (85) Google Scholar Despite its pharmacologic properties and proven efficacy, aerosolized pentamidine has at least three potential disadvantages in patients with PCP.6Armstrong D Aerosol pentamidine.Ann Intern Med. 1988; 109: 852-854Crossref PubMed Scopus (30) Google Scholar The first is that the amount of pentamidine reaching the lung parenchyma depends upon the number and size of particles generated by nebulizers used to aerosolize the drug. Alveolar deposition is enhanced with particles of 1-2μ, whereas airway deposition, which may be associated with coughing, occurs with larger particles.7O'Doherty MJ Page C Bradbeer C Thomas S Barlow D Nunan TO, Bateman NT. Differences in relative efficiency of nebulizers for pentamidine administration.Lancet. 1988; 2: 1283-1286Abstract PubMed Scopus (55) Google Scholar Indeed, the relative effectiveness of aerosolized pentamidine in some studies2Montgomery AB Debs RJ Luce JM Corkery KJ Turner J et al.Aerosolized pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.Lancet. 1987; 2: 480-483Abstract PubMed Scopus (148) Google Scholar as compared with others3Conte JE Hollander H Golden JA Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia.Ann Intern Med. 1987; 107: 495-498Crossref PubMed Scopus (82) Google Scholar may be due to the kind of nebulizers used. A second potential disadvantage of aerosolized pentamidine is that alveolar deposition is influenced by the rate and depth of breathing and by differences in ventilation within the lung. That more ventilation goes to the lung bases when pentamidine is inhaled in the upright position probably accounts for the finding of recurrent PCP in the upper lobes of patients receiving the aerosol as prophylaxis.8Abd AG Nierman DM Ilowite JS Pierson RN Loomis AL Bilateral upper lobe Pneumocystis carinii pneumonia in a patient receiving inhaled pentamidine prophylaxis.Chest. 1988; 94: 329-331Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar In order to achieve more even distribution of the drug throughout all lung zones, patients should breathe at a fast rate, breathe higher doses, or periodically breathe from residual volume during aerosol administration.9Corkery KJ Luce JM Montgomery AB Aerosolized pentamidine for treatment and prophylaxis of Pneumocystis carinii pneumonia: an update.Respir Care. 1988; 33: 676-685Google Scholar The third potential disadvantage of aerosolized pentamidine is that Pneumocystis carinii infection is not always limited to the lungs. Systemic dissemination of the organism was well-known in the pre-AIDS era,10Awen CF Baltzan MA Systemic dissemination of Pneumocystis carinii pneumonia.CMAJ. 1971; 104: 809-812PubMed Google Scholar, 11Price RA Hughes WT Histopathology of Pneumocystis carinii infestation and infection in malignant disease in childhood.Human Pathol. 1974; 5: 737-752Abstract Full Text PDF PubMed Scopus (46) Google Scholar and it has been even better reported in patients with AIDS. To date, Pneumocystis carinii has been noted in the skin,12Coulman CU Greene I Archibald RWR Cutaneous pneumocystosis.Ann Intern Med. 1987; 106: 396-398Crossref PubMed Scopus (56) Google Scholar eyes,13Macher AM Bardenstein DS Zimmerman LE Steigman CK Pastore L Poretz DM Eron LJ Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection.N Engl J Med. 1987; 316: 1092Crossref PubMed Scopus (74) Google Scholar ears,14Gherman CR Ward RR Bassis ML Pneumocystis carinii otitis media and mastoiditis as the initial manifestation of the acquired immunodeficiency syndrome.Am J Med. 1988; 85: 250-252Abstract Full Text PDF PubMed Scopus (49) Google Scholar thyroid,15Gallant JE Enriquez RE Cohen KL Hammers LW Pneumocystis carinii thyroiditis.Am J Med. 1988; 84: 303-306Abstract Full Text PDF PubMed Scopus (50) Google Scholar gut,16Carter TR Cooper PH Petri WA Kim CK Walger PD Guerrant RL Pneumocystis carinii of the small intestine in a patient with the acquired immunodeficiency syndrome.Am J Clin Pathol. 1988; 89: 679-683Crossref PubMed Scopus (53) Google Scholar lymph nodes,17Afessa B Green WR Williams WA Hagler NG Gumbs RV Hackney RL Frederick WR Pneumocystis carinii pneumonia complicated by lymphadenopathy and pneumothorax.Arch Intern Med. 1988; 148: 2651-2654Crossref PubMed Scopus (35) Google Scholar kidney,13Macher AM Bardenstein DS Zimmerman LE Steigman CK Pastore L Poretz DM Eron LJ Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection.N Engl J Med. 1987; 316: 1092Crossref PubMed Scopus (74) Google Scholar spleen,18Pilon VA Echols RM Celo JS Elmendorf SL Disseminated Pneumocystis carinii pneumonia infection in AIDS.N Engl J Med. 1987; 316: 1410-1411Crossref PubMed Scopus (30) Google Scholar and liver19Poblete RB Rodriguez K Foust RT Reddy KR Saldana MJ Pneumocystis carinii hepatitis in the acquired immunodeficiency syndrome (AIDS).Ann Intern Med. 1989; 110: 737-738Crossref PubMed Scopus (52) Google Scholar of such patients. In this issue of Chest, (see page 949) Hagopian and Huseby describe Pneumocystis carinii hepatitis and choroiditis in an AIDS patient receiving aerosolized pentamidine prophylaxis. They also speculate that the true incidence of extrapulmonary infection may be higher than previously realized due to the infrequent use of autopsy among AIDS patients. These reports of disseminated Pneumocystis carinii should prompt physicians to aggressively evaluate patients with suspected extrapulmonary involvement even if their lungs are clear of infection, as Hagopian and Huseby recommend. Furthermore, patients with extrapulmonary Pneumocystis carinii should receive systemic therapy in addition to or in place of aerosolized pentamidine. Nevertheless, the use of aerosolized pentamidine in treating and preventing PCP need not be limited, as others3Conte JE Hollander H Golden JA Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia.Ann Intern Med. 1987; 107: 495-498Crossref PubMed Scopus (82) Google Scholar have suggested. Whatever its true histologic incidence, extrapulmonary infection from Pneumocystis carinii was not documented on clinical or laboratory grounds in any of the approximately 240 patients participating in a multicenter double-blind study of aerosolized pentamidine compared with trimethoprim-sulfamethoxazole (AB Montgomery, personal communication). The lack of disseminated disease in this study and the recent prophylaxis trial1Leoung GS, Montgomery AB, Abrams DJ, Wardlaw L, Corkery K, et al. Aerosol pentamidine for Pneumocystis carinii pneunia prophylaxis: A 3 arm randomized trial. Abstracts, V International Conference on AIDS, 1989:196Google Scholar demonstrate that aerosolized pentamidine may be indicated in AIDS patients with PCP Pneumocystis Hepatitis and Choroiditis Despite Successful Aerosolized Pentamidine Pulmonary ProphylaxisCHESTVol. 96Issue 4PreviewA patient who developed Pneumocystis carinii hepatitis and choroiditis despite receiving prophylactic pentamidine therapy by aerosol is described. Liver biopsy showed histology typical of Pneumocystis hepatitis, but his respiratory status was stable and his lungs were free of P carinii organisms on BAL. Thus, inhaled pentamidine prophylaxis did not prevent extrapulmonary pneumocystosis. Patients receiving pentamidine prophylaxis with unexplained symptoms should undergo investigation for possible extrapulmonary P carinii infection. Full-Text PDF