A Randomized Trial of Three Antipneumocystis Agents in Patients with Advanced Human Immunodeficiency Virus Infection

Bozzette, Sam; Finkelstein, Dianne M.; Spector, Stephen A.; Frame, Peter T.; Powderly, William G.; He, Weili; Phillips, Louise Lang; Craven, Donald E.; Horst, Charles van der; Feinberg, Judith

doi:10.1056/nejm199503163321101

Cited by 314 publications

(158 citation statements)

References 20 publications

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“…10 Based on that study and other recent reports comparing dapsone to TMP/SMX, it appears that daily dosing of dapsone is required to provide protection comparable to TMP/SMX prophylaxis. [21][22][23][24][25] (5) Late-onset CMV pneumonia has emerged as an important complication. 26,27 In a prior study, one-third of late viral infections were caused by CMV, and CMV was responsible for 57% of late life-threatening viral infections.…”

Section: Discussionmentioning

confidence: 99%

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Chen

Boeckh

Seidel

et al. 2003

Bone Marrow Transplant

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Summary:The incidence, etiology, outcome, and risk factors for developing pneumonia late after hematopoietic stem cell transplantation (SCT) were investigated in 1359 patients transplanted in Seattle. A total of 341 patients (25% of the cohort) developed at least one pneumonic episode. No microbial or tissue diagnosis (ie clinical pneumonia) was established in 197 patients (58% of first pneumonia cases). Among the remaining 144 patients, established etiologies included 33 viral (10%), 31 bacterial (9%), 25 idiopathic pneumonia syndrome (IPS, 7%), 20 multiple organisms (6%), 19 fungal (6%), and 16 Pneumocystis carinii pneumonia (PCP) (5%). The overall cumulative incidence of first pneumonia at 4 years after discharge home was 31%. The cumulative incidences of pneumonia according to donor type at 1 and 4 years after discharge home were 13 and 18% (autologous/syngeneic), 22 and 34% (HLA-matched related), and 26 and 39% (mismatched related/unrelated), respectively. Multivariate analysis of factors associated with development of late pneumonia after allografting were increasing patient age (RR 0.5 for o20 years, 1.2 for 440 years, P ¼ 0.009), donor HLA-mismatch (RR 1.6 for unrelated/mismatched related, P ¼ 0.01), and chronic graft-versus-host disease (GVHD; RR 1.5, P ¼ 0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted.

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Section: Discussionmentioning

confidence: 99%

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Chen

Boeckh

Seidel

et al. 2003

Bone Marrow Transplant

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“…If preventive therapy is tolerated, both regimens are more effective in preventing toxoplasmosis than pentamidine, which by itself will not prevent the disease (13). There are only limited data on the use of atovaquone as primary prophylaxis against toxoplasmosis.…”

Section: Review Of Clinical Trialsmentioning

confidence: 99%

“…Even in the era of highly active antiretroviral therapy there remains a substantial morbidity and mortality from PCP in human immunodeficiency virus (HIV)-infected persons (63). The drug of choice for the prophylaxis and treatment of PCP is SXT (19,37,69), which in numerous comparative trials has been demonstrated to have efficacy superior to that of other agents (13,44,53,60,108,110). Despite its efficacy, many patients managed with SXT will experience treatment-limiting side effects such as rash, renal dysfunction, hepatitis, and bone marrow suppression (53,60,108).…”

Section: Review Of Clinical Trialsmentioning

confidence: 99%

Antiparasitic Agent Atovaquone

Baggish

Hill

2002

Antimicrob Agents Chemother

210

147

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“…The recently reported estimated 36 month cumulative risks of PCP were 21% [4] and 22% [23], as compared to 23% in our analysis. Thus, our breakthrough episodes can be regarded as representative and valid cases for analysis of our subject.…”

Section: Discussionmentioning

confidence: 51%

“…These qualities prove to be of growing clinical relevance in the long-term administration, as concurrent medications with its inherent considerable toxicities are frequently indicated in advanced HIV disease. Accordingly, a study comparing regimens for primary prophylaxis with 48 months of observation time reported that 88% of patients on aerosolized pentamidine but only 23% on co-trimoxazole and dapsone, respectively, were still receiving the drug which they were prescribed originally when they completed the study [4].…”

mentioning

confidence: 99%

Effect of long-term primary aerosolized pentamidine prophylaxis on breakthrough Pneumocystis carinii pneumonia

Ewig¹,

Schäfer²,

Rockstroh³

et al. 1996

Eur Respir J

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Aerosolized pentamide is a well-tolerated primary prophylaxis regimen for Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. It is now commonly administered for prolonged periods. We therefore studied the effect of long-term inhalation on breakthrough PCP.We recorded clinical, immunological, radiological and microbiological data, as well as therapy and clinical course of all episodes with confirmed PCP diagnosed at our institution between January 1, 1990 and June 30, 1995. Furthermore, data of all patients on primary aerosolized pentamidine since May 1, 1989 were retrieved. Prophylaxis failures were subdivided into "early" (≤12 months of inhalation time) and "late" (>12 months of inhalation time) failures and were compared with episodes without any prophylaxis.Thirty patients without any prophylaxis, six with early and 14 with late failures represented the study population. Mean±SD inhalation times were 4.9±4.8 and 26.3±14.1 months, respectively. No significant differences could be detected with regard to clinical presentation, severity of PCP, and in-hospital as well as long-term outcome. Early as well as late prophylaxis failures had a higher incidence of upper lobe infiltrates on chest radiography (50% without prophylaxis versus 100% with early and 83% with late failure, respectively; p<0.05). No extrapulmonary or disseminated pneumocystosis was observed in either group. The sensitivity of sitedirected bronchoalveolar lavage was conserved after long-term inhalation (86% versus 100% without prophylaxis and 97% in early failure; p=NS).The severity and outcome of Pneumocystis carinii pneumonia is not altered by long-term primary aerosolized pentamidine prophylaxis. Presentation with upper lobe infiltrates is a radiographic pattern also of late failures. Bronchoalveolar lavage should, therefore, be performed using the site-directed technique in this setting.

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A Randomized Trial of Three Antipneumocystis Agents in Patients with Advanced Human Immunodeficiency Virus Infection

Cited by 314 publications

References 20 publications

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation

Antiparasitic Agent Atovaquone

Effect of long-term primary aerosolized pentamidine prophylaxis on breakthrough Pneumocystis carinii pneumonia

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