Clinical course, treatment and outcome of Pneumocystis pneumonia in immunocompromised adults: a retrospective analysis over 17\xa0years

Julius J Schmidt,Stefan Ziesing,Matthias Stoll,Matthias Eder,Hermann Haller,Jens Gottlieb,Catherina Lueck,Sascha David,André Scherag,Marius M Hoeper,Tobias Welte

doi:10.1186/s13054-018-2221-8

Abstract

BackgroundDespite modern intensive care with standardized strategies against acute respiratory distress syndrome (ARDS), Pneumocystis pneumonia (PcP) remains a life-threatening disease with a high mortality rate. Here, we analyzed a large mixed cohort of immunocompromised patients with PcP, with regard to clinical course and treatment, and aimed at identifying predictors of outcome.MethodsThis was a single-center retrospective analysis in a tertiary care institution across 17 years. Diagnosis of PcP required typical clinical features and microbiological confirmation of Pneumocystis jirovecii. Epidemiological, clinical, laboratory and outcome data were collected from patient records.ResultsA total of 52,364 specimens from 7504 patients were sent for microbiological assessment (3653 with clinical suspicion of Pneumocystis pneumonia). PcP was confirmed in 240 patients, about half of them HIV positive (52%). The remaining subjects were either solid organ transplant recipients (16.3%) or suffered from malignancy (15.8%) or autoimmune diseases (11.7%). Of note, 95% of patients with PcP were not receiving chemoprophylaxis. Overall in-hospital mortality was 25.4%, increasing to 58% if ICU admission was required. Multivariable regression identified lactate dehydrogenase (LDH) as predictor of in-hospital mortality (adjusted OR 1.17 (95% CI 1.09–1.27), p < 0.0001). Mortality in LDH quartiles increased from 8% to 49%, and a cutoff value of 495 U/L predicted mortality with sensitivity and specificity of 70%. With regard to treatment, 40% of patients received trimethoprim-sulfamethoxazole at doses that were lower than recommended, and these patients had a higher mortality risk (HR 1.80 (95% CI 1.10–3.44), p = 0.02).ConclusionsPcP remains a life-threatening disease among immunocompromised patients. About half of patients with PcP do not have HIV infection. Initial LDH values might serve as a stratifying tool to identify those patients at high risk of death among patients with HIV and without HIV infection.

Highlights

Despite modern intensive care with standardized strategies against acute respiratory distress syndrome (ARDS), Pneumocystis pneumonia (PcP) remains a life-threatening disease with a high mortality rate
With regard to the actual treatment of PcP we found that a reduction in the recommended TMP-SMX dose below 15 mg/kg BW might be associated with higher mortality (13.1 vs. 55.8%)
Initial lactate dehydrogenase (LDH) levels - if validated by others - might be a useful predictor of in-hospital mortality, and TMP-SMX treatment doses in patients at high risk of death (e.g. intensive care unit (ICU) admission + LDH > 495 U/L) should probably not be reduced below 15 mg/kg BW

Summary

Introduction

Despite modern intensive care with standardized strategies against acute respiratory distress syndrome (ARDS), Pneumocystis pneumonia (PcP) remains a life-threatening disease with a high mortality rate. Pneumocystis pneumonia (PcP) is a severe disease with high morbidity and mortality, which almost exclusively affects immunocompromised patients. PcP has long been known for its high prevalence among human immunodeficiency virus (HIV)-positive patients [1]. Most patients with HIV-associated PcP are treatment-naïve with very low CD4 cell counts; some of these patients do not know that they are HIV positive until they attend hospital [3]. PcP is frequently diagnosed in non-HIV-positive patients as immunosuppressive regimens are being increasingly used in a wide range of patient populations. The incidence of PcP in non-HIV-positive patients is increasing [2]

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