HIV-Associated Pneumocystis Pneumonia

Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California 94110, USA.
Proceedings of the American Thoracic Society 06/2011; 8(3):294-300. DOI: 10.1513/pats.201009-062WR
Source: PubMed


During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).

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Available from: Saskia Den Boon, Jan 13, 2014
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    • "During the past 30 years, the worldwide epidemic of HIV dramatically increased the prevalence of PCP, and it is recognized as one of its most common complications [6]. At present, PCP remains an important cause of HIV-associated pneumonia but the incidence of PCP has decreased largely due to highly active antiretroviral therapy (HAART) and the use of routine prophylaxis against PCP when the CD4 count is <200 cells/µl [7]–[9]. However, the number of patients receiving hematopoietic stem cell and solid organ transplants has increased, and oncologists and rheumatologists have treated patients with progressively more potent immunosuppressive drugs, including high-dose corticosteroids, radiotherapy, tumor necrosis factor-α inhibitors and immunomodulating monoclonal antibodies, which led to an increase in cases of PCP in these populations [10]–[13]. "
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    ABSTRACT: Background Pneumocystis pneumonia (PCP) is an emerging infectious disease in immunocompromised hosts. However, the clinical characteristics of these patients are poorly understood in mainland China. Methods We performed a retrospective study of PCP from 2008 to 2012. Information was collected regarding clinical manifestations, hospitalization, and outcome. A prognostic analysis was performed using a Cox regression model. Results 151 cases of PCP were included; 46 non-HIV and 105 HIV cases. All-cause mortality (15.2% vs. 12.4%, p = 0.64) and the results of time-to-event analysis (log-rank test, p = 0.62) were similar between non-HIV and HIV infected cases, respectively. From 2008 to 2012, time from admission to initial treatment in non-HIV infected PCP patients showed declining trend [median (range) 20 (9–44) vs. 12 (4–24) vs. 9 (2–23) vs. 7 (2–22) vs. 7 (1–14) days]. A similar trend was observed for all-cause mortality (33.3% vs. 20.0% vs.14.3% vs. 14.3% vs. 6.7%). Patients with four or more of the following clinical manifestations (cough, dyspnea, fever, chest pain, and weight loss) [adjusted HR (AHR) 29.06, 95% CI 2.13–396.36, P = 0.01] and admission to intensive care unit (ICU) [AHR 22.55, 95% CI 1.36–375.06, P = 0.03] were independently associated with all-cause mortality in non-HIV infected PCP patients. Variables associated with mortality in HIV infected PCP patients were admission to ICU (AHR 72.26, 95% CI 11.76–443.87, P<0.001) and albumin ≤30 g/L (AHR 9.93 95% CI 1.69–58.30, P = 0.01). Conclusions Upon admission comprehensive clinical assessment including assessment of four or more clinical manifestations (cough, dyspnea, fever, chest pain, and weight loss) in non-HIV infected PCP patients and albumin ≤30 g/L in HIV infected patients might improve prognosis.
    PLoS ONE 07/2014; 9(7):e101943. DOI:10.1371/journal.pone.0101943 · 3.23 Impact Factor
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    • "Cotrimoxazole (combination of trimethoprim and sulfamethoxazole) is an antimicrobial agent which has both prophylactic and therapeutic indications for Pneumocystis jirovecii infection which represents a high risk among immunosuppressed patients. Pneumocystis is an opportunistic infection which often presents as fever, nonproductive cough, and dyspnoea in HIV patients although symptoms are not as marked and with a relatively shorter duration in immunocompromised patients for reasons other than HIV [1]. It is typically identified on microscopy which can be obtained from bronchoscopy with bronchoalveolar lavage. "
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    ABSTRACT: Cotrimoxazole is a commonly used antimicrobial agent which is traditionally indicated in the management of pneumocystis infection of which HIV and immunosuppressed individuals are at high risk. Furthermore, it can be used on the long term for prophylactic indications. Hypoglycaemia following commencement of cotrimaoxazole is a rare adverse effect which was first described in 1988. We describe a case of hypoglycaemia shortly following initiation of cotrimoxazole indicated as long-term prophylaxis on a background of Churg-Strauss syndrome. The patient was symptomatic for hypoglycaemia despite simultaneous use of high-dose prednisolone; however, the hypoglycaemia did not require a hospital admission. We will explore the risk factors, monitoring requirements, and the mechanism by which co-trimoxazole induces hypoglycaemia.
    Case Reports in Endocrinology 09/2013; 2013:415810. DOI:10.1155/2013/415810
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    • "Pneumocystis pneumonia (PcP) is a common and serious life-threatening opportunistic disease in hosts with impaired/debilitated immune systems, especially HIV-positive persons, but also in patients who are undergoing immunosuppressive treatments related to malignancies, connective tissue diseases or organ transplantation. These organisms are also emerging as a co-morbidity factor associated with chronic diseases such as chronic obstructive pulmonary disorder (COPD) [3]–[7]. "
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    ABSTRACT: Pneumocystis pneumonia (PcP) is a major cause of mortality and morbidity in immunocompromised patients. There are limited alternative therapeutic choices to trimethoprim-sulfamethoxazole (TMP-SMX) which is the standard first line therapy/prophylaxis for PcP. The efficacy of low doses of caspofungin and caspofungin in association with TMP-SMX standard-prophylactic dose was evaluated in an experimental model of Pneumocystis. Susceptibility of Pneumocystis spp. to low doses of caspofungin and caspofungin/TMP-SMX was evaluated in Balb/c immunosuppressed mice, infected intranasally with P. murina. Caspofungin was administered once daily at 0.1 mg/kg, 0.05 mg/kg, and 0.001 mg/kg and TMP-SMX was administered by oral gavage (12.25 mg/62.5 mg/day), for 21 days. Efficacy was calculated based on the reduction in organism burden determined through quantitative fluorescent-based real-time PCR (qPCR). Serum β-1,3-D-glucan was measured as an additional marker of infection. The present data showed that caspofungin demonstrated anti-Pneumomocystis effect. However, the doses administrated were too low to achieve Pneumocystis eradication, which suggests that echinocandin treatment should not be administrated as mono-therapy. After 21 days of treatment, P. murina was not detected in the lungs of mice with either TMP-SMX or caspofungin/TMP-SMX. The results showed that, even at the lowest concentrations tested, the efficacy of caspofungin in association with TMP-SMX was higher than the efficacy of either drug used alone. The administration of caspofungin/TMP-SMX was at least 1.4 times more effective against P. murina infection than TMP-SMX used alone. The most promising result was achieved with the combination of caspofungin 0.05 mg/kg/day with TMP-SMX 12.5 mg-62.5 mg/day, which reduced the parasite burden to undetectable levels immediately at the 14(th) day of treatment, showing a highly marked anti-Pneumomocystis effect. These data suggest that the administration of low doses of caspofungin in combination with low doses of TMP-SMX may provide an improved treatment protocol for Pneumocystis infection clearance.
    PLoS ONE 08/2013; 8(8):e70619. DOI:10.1371/journal.pone.0070619 · 3.23 Impact Factor
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