Pentamidine isethionate in the treatment of Pneumocystis carinii pneumonia.
01 Nov 1970-Annals of Internal Medicine (American College of Physicians)-Vol. 73, Iss: 5, pp 695-702
TL;DR: In an 18-month period 164 patients with suspected or proved interstitial pneumonia due to Pneumocystis carinii were treated with pentamidine isethionate, with positive results.
Abstract: In an 18-month period 164 patients with suspected or proved interstitial pneumonia due toPneumocystis cariniiwere treated with pentamidine isethionate. Side effects were noted in 69 patien...
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TL;DR: Pneumocystis carinii pneumonia was identified antermortem in 81% of the cases usually by biopsy or needle aspiration of the lung, procedures associated with considerable morbidity and morbidity, and mortality as mentioned in this paper.
Abstract: Analysis of 194 patients with confirmed Pneumocystis carinii pneumonia in the United States over a 3-year period revealed that P. carinii pneumonia occurred almost exclusively in the immunosuppressed host who had a serious underlying disease. The epidemiologic features of pneumocystis pneumonia primarily reflected those of the underlying disease. P. carinii was identified antermortem in 81% of the cases usually by biopsy or needle aspiration of the lung, procedures associated with considerable morbidity and morbidity and mortality. Laboratory identification of P. carinii was usually accurate, but errors resulting from fault staining tecnique occurred. Most patients had been ill less than 2 weeks with bilateral diffuse interstitial pneumonia. Leukopenia (white blood cell count less than or equal to 3,00/mm3) and probably severe hypoxia were negative prognostic factors. Although treatment with pentamidine was effective, the drug frequently cased adverse reactions, particularly impaired renal function, when given with other nephrotoxic agents.
495 citations
TL;DR: Pentamidine, recently released for clinical use, is effective in therapy for the hemolymphatic stage of Gambian trypanosomiasis, antimony-resistant leishmaniasis, and Pneumocystis carinii pneumonia, with no appreciable increase in drug levels on successive dosing and no correlation between levels and creatinine clearance or adverse reactions.
Abstract: Pentamidine, recently released for clinical use, is effective in therapy for the hemolymphatic stage of Gambian trypanosomiasis, antimony-resistant leishmaniasis, and Pneumocystis carinii pneumonia. The mechanism of action is unclear and may differ for different organisms. Trypanosomes actively transport pentamidine intracellularly, and the drug may then interfere with DNA biosynthetics. However, pentamidine appears to kill nonreplicating P. carinii. The mechanism of killing is unexplained. The pharmacokinetics of pentamidine has been incompletely studied in humans. The estimated volume of distribution is 3 liters/kg. Levels in plasma of pentamidine range from 0.3-1.4 microgram/ml after standard 4 mg/kg dosing, with no appreciable increase in drug levels on successive dosing and no correlation between levels and creatinine clearance or adverse reactions. The drug appears to be concentrated in the kidney and excreted in the urine, with levels detectable six to eight weeks after cessation of therapy. Immediate adverse reactions have included hypotension, nausea, and vomiting. Local pain or abscess formation at an injection site, mild azotemia, leukopenia, abnormal findings from liver function tests, and hypoglycemia may also occur.
334 citations
Cites background from "Pentamidine isethionate in the trea..."
...Anemia has occurred in 4% of patients and five cases of thrombocytopenia have been reported [56, 64, 69]....
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...Data are from [56, 58, 64, 66, 67]....
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...Reactions have conveniently been categorized as immediate, local, and systemic and have also included deaths [56]....
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...There have been only five reported pentamidineassociated deaths [46, 56]....
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...The CDC review of pentamidine therapy of P carinii pneumonia for the period of 1967-1970 has suggested a recovery rate of 63%-76% in those patients receiving nine or more days of therapy [56, 58]....
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TL;DR: In this article, patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate.
Abstract: Forty patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate. The two groups did not differ significantly in the severity of pulmonary or systemic processes at enrollment. Five patients treated initially with trimethoprim-sulfamethoxazole and one patient treated initially with pentamidine died during the 21-day treatment period (p = 0.09, Fisher's exact test). No significant differences were seen between groups in rates of improvement, pulmonary function tests, or 67Ga uptake by the lungs in the survivors at completion of therapy. Adverse reactions necessitated changing from the initial drug in 10 patients in the trimethoprim-sulfamethoxazole group and 11 in the pentamidine group. Minor reactions occurred in all patients. In patients with AIDS, trimethoprim-sulfamethoxazole and pentamidine do not have statistically significant differences in efficacy or frequency of adverse reactions.
325 citations
Journal Article•
TL;DR: In patients with AIDS, trimethoprim-sulfamethoxazole and pentamidine do not have statistically significant differences in efficacy or frequency of adverse reactions, and the two groups did not differ significantly in the severity of pulmonary or systemic processes at enrollment.
Abstract: Forty patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes ofPneumocystis cariniipneumonia were assigned at random to receive either trimethoprim-sulfametho...
289 citations
TL;DR: For example, by the middle of the 20th century, Pneumocystis carinii pneumonitis had not been recognized in North America as mentioned in this paper. Yet within the past two decades the prevalence has increased to the point that several...
271 citations
References
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Journal Article•
TL;DR: It is essential that American pediatricians be aware of this parasite as a potential human pathogen and establish clearly what role this organism plays in the pathogenesis of human disease and settle the controversy as to whether it is fungal or protozoan.
Abstract: Pneumocystis carinii, a parasite found almost a half century ago in the lungs of small mammals and of man in Brazil and, subsequently, in the lungs of man and of wild and laboratory rodents in Europe, has been identified with increasing frequency in the lungs of patients dying from interstitial plasma cell pneumonia of premature and young infants The microorganism is found with considerable regularity in such patients, and has, in addition, been found in material obtained by lung puncture during life Although its morphologic characteristics and life cycle have been well worked out, its taxonomic position remains a matter of conjecture It has been tentatively classed as a protozoan of the Class Haplosporidia, but many authors believe it to be a fungus The organism is not often encountered in the lungs in serial, unselected necropsies, but it has been found occasionally in lungs of older children and adults debilitated by chronic infections or malignant neoplasm and rather more frequently in association with cytomegalic inclusions in the lungs and salivary glands of infants and adults However, it has been regularly identified in lungs of interstitial plasma cell pneumonia patients with only rare exceptions Recently infection with what appears to be this microorganism has been transmitted to infant mice and kittens The wide geographic distribution of natural infection with this agent in wild and domestic mammals of many species, the fact that it was first discovered in man and animals in South America, its frequent identification in the lungs of infants afflicted with this unique pneumonia of infancy, a disease which has now been reported in the United States, and the recent identification of Pneumocystis carinii in a diseased human lung from Canada, make it essential that American pediatricians be aware of this parasite as a potential human pathogen Only further study will establish clearly what role this organism plays in the pathogenesis of human disease and settle the controversy as to whether it is fungal or protozoan
230 citations
134 citations
TL;DR: Pentamidine is useful in preventing disease due to Trypanosoma gambiense as well as effective in the treatment of diffuse interstitial pneumonia due to Pneumocystis carinii and the frequency of this type of pneumonia in cancer patients and in patients undergoing organ transplantation suggests the need for studies in animals and man.
Abstract: Patients with malignant disease complicated by diffuse interstitial pneumonia due to proved or suspected Pneumocystis carinii were given pentamidine in the dosage schedule recommended for this infection. By means of a sensitive method of assay, the plasma levels and urinary excretion of pentamidine during therapy were studied in these patients. Following the intramuscular administration of pentamidine, plasma levels were low and urinary excretion prolonged. After a single intraperitoneal injection in mice, the tissue distribution levels and excretion pattern for pentamidine were determined at various time intervals. There was storage of the drug in tissues and excretion was delayed. The highest concentration of pentamidine was found in the kidney. In mice pentamidine is eliminated primarily intact with little, if any, altered. The available data in man also suggested that pentamidine is retained, bound to tissues, and excreted over an extended period. Although renal abnormalities followed pentamidine, it was not possible to implicate the drug in all cases because of the seriousness of the illness and the concomitant use of other drugs. Pentamidine is useful in preventing disease due to Trypanosoma gambiense as well as effective in the treatment of diffuse interstitial pneumonia due to Pneumocystis carinii. The frequency of this type of pneumonia in cancer patients and in patients undergoing organ transplantation suggests the need for studies in animals and man.
84 citations
TL;DR: Two patients with underlying lymphoreticular malignant processes were successfully treated for documented Pneumocystis carinii pneumonia with pentamidine isethionate, and decreased renal function occurred on therapy in both patients.
Abstract: Two patients with underlying lymphoreticular malignant processes were successfully treated for documented Pneumocystis carinii pneumonia with pentamidine isethionate. The diagnosis of pneumocystis infection was confirmed in each case by percutaneous pulmonary needle biopsy. Decreased renal function occurred on therapy in both patients; in one, this seemed to be primarily a tubular disorder that was related to increased dose of pentamidine isethionate and that was reversible. In the proper clinical setting, this infection should be strongly suspected, a pulmonary needle biopsy performed, and adequate therapy given. Further experience with pentamidine isethionate in histologically documented cases will permit a valid assessment of its therapeutic efficacy. Physicians using pentamide isethionate should anticipate its potential renal toxicity.
75 citations