New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.
New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.
复制标题
针对免疫抑制患者机会性感染的新药开发：卡氏肺孢子虫。
DOI：
10.1021/jm00024a001
复制
发表时间：
1995
影响因子：
7.3
通讯作者：
Queener,SF
中科院分区：
文献类型：
--
作者：
Queener,SF
Widespread organ transplantation programs, aggressive chemotherapy of cancer, andthe AIDS epidemic have created large numbers of immunosuppressed patients who are at increased risk from opportunistic infections, including thosecaused by fungi. Fungal infections in AIDS patients include candiasis, crypto-coccosis, histoplasmosis, and others, but the most common is pneumonia caused by Pneumocystis carinii. Reports of P. carinii pneumonia in the pre-AIDS era were sporadic, with fewer than 100 cases reported yearly in the United States, 1 but with the AIDS epi-demic, thenumber of cases of P. carinii pneumonia in the United States has been estimated at 50 000 annu-ally, and P. carinii pneumonia has been theleading cause of death in AIDS patients in this country. 2 Even with widespread prophylaxis for P. carinii pneumonia, the disease is still common in AIDS patients. 3 Because of the seriousness and prevalence of disease caused by P. carinii, this review will focus on that organism. P. carinii was originally discovered in 1909, but was misidentified as a form of Trypanosoma cruzi. Although it was later recognized as an independent organism, its exact taxonomic position remained unsettled for 80 years. 4 When modem techniques were applied, P. carinii was found to be related more closely to fungi than to protozoans. 3 The full life cycle of the organism is still unclear. Horizontal transmission by theairborne route occurs in animals and probably occurs in humans. 5 Pathophysiology of Pneumocystis carinii Pneumonia. P. carinii is an extracellular pathogen that attaches to type 1 pneumocytes, damaging those cells and increasing alveolar capillary permeability. Histologically, the alveoli appear tofill with foamy exudate; mild interstitial pneumonitis is characterized by a corresponding degree of interstitial chronic inflammation, as well as proliferation of type II pneumocytes. 6 Fibrosis is common. Surfactant phospholipids are also altered by the disease, changing the surface tension of the alveolus. These effects of infection progressively impair gas exchange. Clinically, patients with pneumonia caused by P. carinii experience increasing dif-ficulty breathing as the disease progresses and more alveoli become blocked with masses of P. carinii organisms and the characteristic foamy exudate. 7 Fevers and nonproductive cough are common but pulmonary ex-amination often fails to reveal signs sufficient to estab-lish a diagnosis. Most infections in humans are re-stricted to pulmonary sites, but disseminated or extra-pulmonary infections are possible. 8 P. carinii pneumonia followsvarious clinical courses, depending upon the age and immune status of the patient. 7 9 Before 1950, P. carinii was a rare cause of clinical disease, mostly in young children. Malnourish-ment was recognized to predispose patients to P. carinii pneumonia. 10 Early reportsin children described a disease with a slow, subtle onset characterized by mildly increased respiration ratesand poor appetite in its early stages; respiratory distressincreased after 7—14 days and about one-fourth of the patients died if untreated. 9 Recovery took 4—6 weeks. The entire disease process could occur without fever. In adults without HIV who develop P. carinii pneumonia, nearly all have genetic or drug-induced immunosuppression. 7 These patients and immunosuppressed children develop severe P. carinii pneumonia much more rapidly than AIDS patients and are less likely to show interstitial fibrosis and severe alveolar exudate. 7 Among highly immune sup-
