Outcome and prognostic factors of Pneumocystis jirovecii pneumonia in immunocompromised adults: a prospective observational study

Abstract

BackgroundPneumocystis jirovecii pneumonia (PJP) remains a severe disease associated with high rates of invasive mechanical ventilation (MV) and mortality. The objectives of this study were to assess early risk factors for severe PJP and 90-day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis.MethodsWe prospectively enrolled all patients meeting pre-defined diagnostic criteria for PJP admitted at Nantes university hospital, France, from January 2012 to January 2017. Diagnostic criteria for PJP were typical clinical features with microbiological confirmation of P. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (PCR) assay. Severe PJP was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least 50% FiO2, non-invasive ventilation, or MV.ResultsOf 2446 respiratory samples investigated during the study period, 514 from 430 patients were positive for P. jirovecii. Of these 430 patients, 107 met criteria for PJP and were included in the study, 53 (49.5%) patients had severe PJP, including 30 who required MV. All patients were immunocompromised with haematological malignancy ranking first (n = 37, 35%), followed by solid organ transplantation (n = 27, 25%), HIV-infection (n = 21, 20%), systemic diseases (n = 13, 12%), solid tumors (n = 12, 11%) and primary immunodeficiency (n = 6, 8%). By multivariate analysis, factors independently associated with severity were older age (OR, 3.36; 95% CI 1.4–8.5; p < 0.05), a P. jirovecii microscopy-positive result from bronchoalveolar lavage (BAL) (OR, 1.3; 95% CI 1.54–9.3; p < 0.05); and absence of a BAL fluid alveolitis profile (OR, 3.2; 95% CI 1.27–8.8; p < 0.04). The 90-day mortality rate was 27%, increasing to 50% in the severe PJP group. Factors independently associated with 90-day mortality were worse SOFA score on day 1 (OR, 1.05; 95% CI 1.02–1.09; p < 0.001) whereas alveolitis at BAL was protective (OR, 0.79; 95% CI 0.65–0.96; p < 0.05). In the subgroup of HIV-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher 90-day mortality (OR, 1.25; 95% CI 1.02–1.55; p < 0.05).ConclusionsOlder age and P. jirovecii oocysts at microscopic examination of BAL were independently associated with severe PJP. Both initial PJP severity as evaluated by the SOFA score and viral co-infection predicted 90-day mortality. Alveolitis at BAL examination was associated with less severe PJP. The pathophysiological mechanism underlying this observation deserves further investigation.

Burden of serious fungal infections in the Netherlands

“…Pneumocystis jirovecii pneumonia patients in the Netherlands have been primarily treated with corticosteroids as their main risk factor. The immunosuppressive properties of corticosteroids, biologicals and chemotherapy are a known risk factor for PJP 48,49 . Studies have described PJP incidences in solid organ transplantation patients in Switzerland (1.4%) 50 and global incidences (including the Netherlands) in recipients of first allogeneic and autologous HSCTs (0.63% and 0.28%, respectively) 51 .…”

Pneumocystis pneumonia in patients with primary nephrotic syndrome: analysis of 18 cases

“…Previous studies have found a higher mortality of 2 to 28% in patients with rheumatoid arthritis [30], 13 to 43% in patient with kidney transplant [31], and 30 to 60% in patients with hematological malignancies [23]. According to previous studies, possible prognostic factors in HIV-negative patients were old age, coinfections, respiratory failure, pre-existing lung disease and a higher LDH level [32][33][34]. The reason that no patients died in our study may be due their relatively younger age (average 48.5 years) and the disease itself.…”

Evaluation of a commercial Loop‐mediated Isothermal Amplification (LAMP) assay for rapid detection of Pneumocystis jirovecii

“…4 Next to HIV/AIDS, there are also other risk factors for PCP, for example solid organ transplantation, haematological or solid malignancy, congenital immunodeficiency and immunosuppressive therapy. [5][6][7][8] In contrast to P jirovecii infections in patients with HIV/ AIDS, non-HIV-infected patients have been reported to suffer from a more acute onset of PCP, linked to faster disease progression and more threatening outcome. 1, [9][10][11][12] The diagnosis of PCP in critical ill patients is challenging, due to the fact that P jirovecii is frequently colonising the respiratory tract, and distinguishing between colonisation and infection in patients is crucial.…”

“…It is known that P jirovecii pneumonia (PCP) is a relevant cause of an opportunistic fungal infection in patients with HIV/AIDS 4 . Next to HIV/AIDS, there are also other risk factors for PCP, for example solid organ transplantation, haematological or solid malignancy, congenital immunodeficiency and immunosuppressive therapy 5‐8 . In contrast to P jirovecii infections in patients with HIV/AIDS, non‐HIV‐infected patients have been reported to suffer from a more acute onset of PCP, linked to faster disease progression and more threatening outcome 1,9‐12 .…”