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• W2068304578 abstract "When Pneumocystis carinii pneumonia (PCP)appeared in previously healthy patients in the late 1970s, cliniciansquickly recognized that a new form of immunosuppression had occurred, and , thus, PCP was the most prominent feature in the initial reports ofthe syndrome now designated as AIDS. Clinicians promptly recognizedthat the PCP they were seeing in patients with AIDS differed inimportant ways from the PCP that was seen in other patient populations. In fact, most opportunistic pathogens such as Candida, cytomegalovirus, and herpes simplex caused somewhat different manifestations in AIDSpatients compared to patients who had cancer or had undergone organtransplantation. In the early 1980s, Kovacs et al1Kovacs J Hiemenz J Macher A et al.Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and other immunodeficiencies.Ann Intern Med. 1984; 100: 663-671Crossref PubMed Scopus (641) Google Scholar compared the clinicalfeatures of 49 cases of AIDS-associated PCP with 39 episodes of PCPoccurring in patients with other immunosuppressive disorders. Theydescribed AIDS-related PCP as a more indolent disease process. Themedian time to diagnosis was longer for AIDS-related PCP (28 days) thanfor PCP related to other disorders (5 days), yet despite this longersymptomatic period, AIDS-related PCP patients presented with a highermedian room air Pao2 (69 mm Hg)than the non-AIDS patients (52 mm Hg). Despite these differences, thesurvival rate of patients with PCP was similarly dismal in both groups(about 50%). In this issue of CHEST (see page 704), Mansharamani and colleagues assess the management and outcome patterns for adults with, AIDS-related and non-AIDS-related PCP during the period 1985 to 1995,the decade following the report by Kovacs et al.1Kovacs J Hiemenz J Macher A et al.Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and other immunodeficiencies.Ann Intern Med. 1984; 100: 663-671Crossref PubMed Scopus (641) Google Scholar Theyreviewed 605 confirmed cases of HIV-associated PCP and 33 cases ofnon-HIV-associated PCP. They emphasize two interesting observationsabout management. First, over the period of their study, a decliningfraction of patients with HIV-related PCP required hospitalization, while, in contrast, non-HIV-infected patients with PCP almost alwaysrequired hospitalization. Second, the mortality rate for patients with, HIV-related PCP fell during the study period from 11.7 to 6.6%, whilethe mortality rate for non-HIV-infected PCP patients was much higher(39%; there were too few patients in this group to assess achronologic trend). Mansharamani et al conclude that, despite majoradvances in the tools for managing PCP, not nearly as much progress hasbeen made in improving the prognosis of PCP in non-HIV-infectedpatients compared to those with HIV infection. Is HIV-related PCP truly a less severe disease than PCP that isassociated with cancer, organ transplantation, or high-dosecorticosteroid use? Data from many sources support the concept that, while HIV-related PCP can progress rapidly and can be severe and lethal, it is, in fact, much more often a slowly progressive diseasethan the PCP that occurs in other immunosuppressed patients. A recentreview of the experience at a Swiss hospital from 1983 to 1998 supportsthis concept.3Helweg-Larsen J Jensen JS Benfield T et al.Diagnostic use of PCR for detection of Pneumocystis carinii in oral wash samples.J Clin Microbiol. 1998; 36: 2068-2072Crossref PubMed Google Scholar Thus, the biology of the host-pathogeninteraction seems to differ between HIV-infected patients and otherimmunosuppressed individuals, and there is more opportunity tointervene before hypoxemia becomes severe. Do patients with HIV-related PCP truly fare better than patients with, PCP and other immunosuppressive illnesses, as Mansharamani et alreport? The number of non-HIV-infected patients in the study by, Mansharamani et al is small (n = 33 over 10 years), so it is possiblethat real improvements were not recognized. The recent study from, Switzerland2Nuesch R Bellini C Zimmerli W Pneumocystis carinii pneumonia in human immunodeficiency virus (HIV)-positive and HIV-negative immunocompromised patients.Clin Infect Dis. 1999; 29: 1519-1523Crossref PubMed Scopus (93) Google Scholar found that the PCP-related mortalityrate in the two groups was actually similar (HIV-infected group, 11%;non-HIV-infected group, 19%). In the Swiss study, however, the authorsdocument that, while the number of non-HIV-infected patients was alsosmall (n = 32), during the period of their study the non-HIV-infectedpatients with PCP had, in fact, benefited from advances since theirmean length of hospital stay declined during the study period alongwith their mortality rate. There are several additional reasons, as Mansharamani et al comment, why HIV-infected patients might have better outcomes when they develop, PCP: (1) their period of susceptibility can be predicted by anobjective laboratory test, the CD4 T-lymphocyte count; (2) PCP is byfar the most likely cause of diffuse pulmonary disease in those with, CD4 T-lymphocyte counts < 200/μL, while in patients with otherimmunosuppressive disorders the differential diagnosis is much broader, making a focused diagnostic approach and an appropriate empirictherapeutic regimen much more difficult to construct; (3) many, HIV-infected patients are well-educated about the initialmanifestations of PCP and the need for prompt medical interventions; and (4) many HIV-infected patients are free of other confoundingsystemic insults from underlying disease, cytotoxic drug treatment, and concurrent infections. Thus, recognizing the onset of PCP, establishingthe specific diagnosis, and completing a course of therapy are oftenmuch more straightforward in patients with HIV than in patients whohave cancer or have undergone organ transplantation. Over the past 20 years, much has been learned about the diagnosis and treatment of PCP. It is possible to identify patients at high risk for, HIV-related PCP based on peripheral blood CD4 T-lymphocyte counts, and the period of risk for other patients is recognizable in relation tothe immunosuppressive therapies. Effective regimens for prophylaxishave been developed. Sensitive and specific methods for diagnosis haveallowed for earlier diagnosis in many cases. Adjuvant corticosteroidtherapy has decreased the number of patients with HIV-related PCP whodevelop respiratory failure. Finally, the armamentarium of therapeuticagents has increased to include atovaquone, clindamycin-primaquine, and trimetrexate. There is, however, much work yet to be done, especially inpatients who have cancer and have undergone organ transplantation. First, cancer and organ transplant patients would benefit from thedevelopment of an objective test of their susceptibility to PCP; unfortunately, in these populations the circulating CD4 T-lymphocytecount is not nearly as sensitive a marker as it is for patients with, HIV infection. Second, less invasive diagnostic tests would facilitateearly diagnosis: the use of oral washes tested with sensitive and specific nucleic acid amplification techniques hold considerablepromise.3Helweg-Larsen J Jensen JS Benfield T et al.Diagnostic use of PCR for detection of Pneumocystis carinii in oral wash samples.J Clin Microbiol. 1998; 36: 2068-2072Crossref PubMed Google Scholar Third, as sulfonamide-resistant PCP appears tobe a clinically important occurrence,4Helweg-Larsen J Benfield TL Eugen-Olsen J et al.Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. carinii pneumonia.Lancet. 1999; 354: 1347-1351Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar tests for clinicallaboratories to identify resistant organisms and new drugs with novelmechanisms of action need to be developed. There is woefully littleactivity in the are a of drug development, althoughechinocandins5Powles MA Liberator P Anderson J et al.Efficacy of MK-991 (L-743,872), a semisynthetic pneumocandin, in murine models of Pneumocystis carinii.Antimicrob Agents Chemother. 1998; 42: 1985-1989Crossref PubMed Google Scholar and primaquine analogs hold somepromise.6Petty BG Black JR Hendrix CW et al.Escalating multiple-dose safety, and tolerance study of oral WR 206 in HIV-infected subjects: AIDS Clinical Trials Group 173.J Acquir Immune Defic Syndr. 1999; 21: 26-32Crossref PubMed Scopus (6) Google Scholar The dual message of Mansharamani et al is both that progress has beenmade and that there is much yet to be done. Clearly, with this problem, as with so many others, there are “miles to go” before themorbidity and mortality produced by PCP are effectively eliminated." @default.
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