Abstract: Background: Pneumocystis jirovecii is an opportunistic fungus recognized for causing P. jirovecii pneumonia. The global prevalence is thought to be higher than 400,000 annual cases, although detailed information about epidemiological patterns is scarce. Methodology: A retrospective longitudinal descriptive study was performed among patients with diagnosis of pneumocystosis according to Classification of Diseases 9th edition, Clinical Modification (code 136.3 for the cases from 1997 to 2015; and 10th edition code B59.0 for cases from 2016 to 2020 in Spanish public hospitals from 1 January 1997-31 December 2020. Results: A total of 25289 cases were diagnosed. The period incidence rate was 2.36 (95 % CI, 2.33-2.39) cases per 100,000 person-years. Infection was more frequent among men (72.2 %) than among women (27.8 %). Comorbidity was the main characteristic of this cohort. Up to 72.3 % of pneumocystis-infected patients (18293) had HIV coinfection. During the study period, there was a progressive decrease in the number of HIV coinfected cases as the group of patients without HIV infection increased, with the largest group in 2017. The lethality rate in the cohort was 16.7 %. The global cost was €229,234,805 and the average ( ± SD) cost per patient was €9065 ( ± 9315). Conclusions: The epidemiology of pneumocystosis in Spain has changed in the last two decades. We noted in our study the possibility of a reemergence among non-HIV immunocompromised patients as patients with hematological and nonhematological neoplasia and other risk groups. The lethality of pneumocystosis continues to be high, and the underlying diseases are the main variable associated with lethality

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