{"id":385645,"date":"2024-10-16T00:01:00","date_gmt":"2024-10-15T22:01:00","guid":{"rendered":"https:\/\/medizinonline.com\/?p=385645"},"modified":"2024-10-18T11:48:07","modified_gmt":"2024-10-18T09:48:07","slug":"three-approaches-to-reduce-p-jirovecii-mortality","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/three-approaches-to-reduce-p-jirovecii-mortality\/","title":{"rendered":"Three approaches to reduce P. jirovecii mortality"},"content":{"rendered":"\n

Pneumocystis jirovecii pneumonia (PcP<\/em>) is associated with a high mortality rate, but the influence of an immunocompromised underlying disease on the clinical presentation, severity and mortality of PcP has not yet been sufficiently investigated.\nFrench physicians have taken on this task. <\/strong><\/p>\n\n\n\n

The increasing number of patients undergoing immunosuppressive treatments as well as the development of new therapies for hematologic malignancies have led to new conditions for the development of opportunistic pulmonary fungal infections.\nThe increase in solid organ transplants and immune-mediated inflammatory diseases (IMIDs) have also contributed to this. <\/p>\n\n

Currently, about three-quarters of all cases of Pneumocystis jirovecii pneumonia (PcP<\/em>) are diagnosed in patients who are HIV-negative in high-income countries.\nHIV-negative PcP is associated with higher morbidity and mortality and can be more difficult to diagnose than in HIV-positive patients.\nIn the HIV-negative population, the prognosis of PcP is highly variable, suggesting that both the underlying disease and immunosuppressive therapies have an impact on the severity and outcome of this infection.\nPrevious corticosteroid therapy has been identified as a risk factor for PcP and has been associated with mortality.\nWith the advent of new immunosuppressive treatments, the question arises as to the appropriate criteria for the introduction of primary prophylaxis. <\/p>\n\n

However, the influence of the underlying disease and specific immunological disorders on the clinical presentation, severity and mortality of PcP has so far been insufficiently investigated.\nDr. Romain L\u00e9cuyer and colleagues from the Department of Internal Medicine and Infectious Diseases at the Centre Hospitalier Bretagne-Atlantique in Vannes, France, have now presented a multicenter retrospective observational study that included patients with probable or confirmed PcP from three French hospitals [1]. <\/p>\n\n

Delayed diagnosis can contribute to a poor prognosis<\/h3>\n\n

During the 10-year study period, a total of 481 participants were included in the study, of whom 180 (37.4%) were defined as patients with proven PcP and 301 (62.6%) as patients with probable PcP.<\/p>\n\n

Patients with immune-mediated inflammatory diseases had the most severe forms of PcP on admission, with a higher Sequential Organ Failure Assessment ( <\/em>SOFA) score and the highest mortality rate due to PcP in HIV-negative patients.\nOn the other hand, PcP patients with solid tumors had higher 90-day mortality and poorer long-term outcome despite a lower SOFA score at PcP diagnosis.\nPatients who were HIV-positive had the best 90-day survival rate (Fig. 1).<\/strong> <\/p>\n

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The results suggest that these patients (most of whom had metastatic-stage disease) may not have developed the most severe forms of PcP, but that the presence of this opportunistic infection could be a marker for their frailty, the authors say.<\/p>\n\n

In addition, previous long-term corticosteroid therapy appeared to be an important risk factor and was associated with a poorer prognosis, particularly in patients with IMID.\nThe higher mortality rate in patients with long-term corticosteroid exposure decreases after one year, which may be explained by the mortality associated with each underlying disease in the HIV-negative group.\nThe longer time to diagnosis and higher severity of PcP in patients with IMID at admission suggest that the delayed diagnosis may be partly responsible for their poor prognosis. <\/p>\n\n

In almost 90% of patients, no PcP prophylaxis had been prescribed.\nTo reduce PcP mortality in patients with IMIDs, the first step would be to improve prophylaxis against this preventable opportunistic infection, the authors write.\nHowever, defining criteria for Pneumocystis prophylaxis<\/em>in patients with IMIDs is a challenge given the broad spectrum of diseases involved.\nSpecific prophylaxis guidelines have been developed for vasculitis associated with antineutrophil cytoplasmic antibodies, scleroderma and autoimmune inflammatory myopathies, as well as for patients receiving prolonged corticosteroid therapy, but for rarer IMIDs there are currently insufficient data to make specific prophylaxis recommendations.\nThe present study demonstrates that high-dose corticosteroids are an important issue in HIV-negative patients due to the risk of PcP, and in contrast to HIV-positive patients, CD4 cell count cannot be used as an indication for prophylaxis in these patients. <\/p>\n\n

Rheumatoid arthritis as the most common IMID in the cohort<\/h3>\n\n

Rheumatoid arthritis (RA) was the most common IMID in the study cohort.\nThis highlights the difficulty in identifying patients who would benefit from Pneumocystis prophylaxis<\/em>and explains the lack of official recommendations\/consensus guidelines for these patients.\nMore than half of patients with RA developed PcP <6 months after starting or intensifying their immunosuppressive therapy.\nAccording to the authors, atovaquone prophylaxis in the year following initiation of immunosuppressive therapy could be an effective alternative with a favorable benefit-risk ratio, avoiding the risk of cumulative myelotoxicity of methotrexate and trimethoprim-sulfamethoxazole.\nSarcoidosis appears to be another disease that responds strongly to corticosteroids and for which there are as yet no recommendations for Pneumocystis prophylaxis<\/em>. <\/p>\n\n

Another important factor in improving the outcomes of IMID patients with PcP would be earlier treatment.\nIt is particularly important to identify patients with IMIDs who have features consistent with a severe PcP diagnosis as early as possible and to provide prompt treatment.\nDr. L\u00e9cuyer and colleagues emphasize that their work suggests that delayed treatment in patients with IMIDs has a potentially dramatic impact on their prognosis. <\/p>\n\n

BAL examination can provide important markers<\/h3>\n\n

Analysis of 90-day risk factors in the HIV-negative patients in the expanded cohort confirms that BAL examination can provide several important markers of mortality, including direct examination of cysts, neutrophilic alveolitis profile, and respiratory co-infection with CMV at the time of PcP diagnosis.\nIn addition, previous corticosteroid therapy has been reported to impair the anti-PcP immune response, leading to inefficient neutrophilic alveolitis and subsequent alveolo-interstitial inflammatory lesions in PcP.\nPositive direct examination of cysts in airway specimens may indeed indicate profound immunosuppression.\nIn HIV-positive patients, highly active antiretroviral therapy may contribute to a more rapid control of the infectious process through an earlier recovery of the immune system.\nIn HIV-negative patients, patterns of immunosuppression, including long-term corticosteroid therapy, appear to be associated with an inappropriate inflammatory response in high fungal burden.\nTo improve the treatment of PcP in IMIDs, the benefit of immunomodulatory therapies other than corticosteroids in reducing the deleterious pulmonary immune response needs to be investigated, the authors conclude. <\/p>\n\n

In their work, Dr. L\u00e9cuyer et al.\nIMIDs, solid tumors and long-term corticosteroid therapy as independent mortality factors in HIV-negative patients.\nPatients with IMIDs are the most exposed to long-term corticosteroid therapy and have the worst prognosis due to PcP compared to other immunocompromised patients.\nThe occurrence of PcP in patients with solid tumors is associated with the highest 90-day mortality and is likely related to very advanced tumor disease.\nAccording to Dr. L\u00e9cuyer and colleagues, expanding the indications for primary prophylaxis against P. jirovecii<\/em> in patients with underlying immunocompromised disease, earlier sensitization, diagnosis and probabilistic treatment, and new therapeutic approaches for severe forms are the three key factors that could contribute to reducing P. jirovecii mortality in HIV-negative patients. <\/p>\n\n

Literature:<\/p>\n\n

    \n
  1. L\u00e9cuyer R, et al.: Characteristics and Prognosis Factors of Pneumocystis jirovecii Pneumonia According to Underlying Disease. A Retrospective Multicenter Study. Chest Journal 2024; 165(6): 1319\u20131329; doi: 10.1016\/j.chest.2024.01.015.<\/li>\n<\/ol>\n\n

    InFo PNEUMOLOGIE & ALLERGOLOGIE 2024; 6(3): 30\u201331<\/em><\/p>\n\n

    <\/p>\n\n

    <\/p>\n\n

    Cover picture: Pneumocystis jiroveci transbronchial biopsy, \u00a9Yale Rosen, wikimedia<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    Pneumocystis jirovecii pneumonia (PcP) is associated with a high mortality rate, but the influence of an immunocompromised underlying disease on the clinical presentation, severity and mortality of PcP has not…<\/p>\n","protected":false},"author":7,"featured_media":385646,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"Fungal infections of the lungs","footnotes":""},"category":[11508,11406,11455,11548,11503],"tags":[78386,78383,36012,78384,78381,78379,78380,78385,78382,15026],"powerkit_post_featured":[],"class_list":["post-385645","post","type-post","status-publish","format-standard","has-post-thumbnail","category-education","category-infectiology","category-pneumology","category-rx-en","category-studies","tag-bal-en","tag-fungal-infections","tag-imid-en","tag-immune-mediated-inflammatory-diseases","tag-immunodeficiency-en","tag-pcp-en","tag-pneumocystis-en","tag-pneumocystis-jirovecii-en","tag-pneumocystis-prophylaxis","tag-pneumonia","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-14 05:31:51","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":385640,"slug":"trois-approches-pour-reduire-la-mortalite-due-a-p-jirovecii","post_title":"Trois approches pour r\u00e9duire la mortalit\u00e9 due \u00e0 P.-jirovecii","href":"https:\/\/medizinonline.com\/fr\/trois-approches-pour-reduire-la-mortalite-due-a-p-jirovecii\/"},"it_IT":{"locale":"it_IT","id":385633,"slug":"tre-approcci-per-ridurre-la-mortalita-di-p-jirovecii","post_title":"Tre approcci per ridurre la mortalit\u00e0 di P. jirovecii","href":"https:\/\/medizinonline.com\/it\/tre-approcci-per-ridurre-la-mortalita-di-p-jirovecii\/"},"pt_PT":{"locale":"pt_PT","id":385626,"slug":"tres-abordagens-para-reduzir-a-mortalidade-por-p-jirovecii","post_title":"Tr\u00eas abordagens para reduzir a mortalidade por P. jirovecii","href":"https:\/\/medizinonline.com\/pt-pt\/tres-abordagens-para-reduzir-a-mortalidade-por-p-jirovecii\/"},"es_ES":{"locale":"es_ES","id":385619,"slug":"tres-enfoques-para-reducir-la-mortalidad-por-p-jirovecii","post_title":"Tres enfoques para reducir la mortalidad por P. jirovecii","href":"https:\/\/medizinonline.com\/es\/tres-enfoques-para-reducir-la-mortalidad-por-p-jirovecii\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/385645","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=385645"}],"version-history":[{"count":2,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/385645\/revisions"}],"predecessor-version":[{"id":388235,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/385645\/revisions\/388235"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/385646"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=385645"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=385645"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=385645"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=385645"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}