non-HIV Pneumocystis Pneumonia Research Articles

Outcomes of low-dose trimethoprim-sulfamethoxazole treatment in patients with non-HIV pneumocystis pneumonia: A nationwide Japanese retrospective cohort study

ObjectivesLow-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be a treatment option for patients with Pneumocystis jirovecii pneumonia (PCP). However, its effectiveness in patients without human immunodeficiency virus (HIV) infection has yet to be thoroughly investigated. MethodsThis retrospective cohort study used data extracted from the Japanese Diagnosis Procedure Combination inpatient database. We included immunocompromised patients without HIV having been diagnosed with PCP and had started TMP-SMX treatment between July 2010 and March 2022. We divided eligible patients into conventional-dose (15.0–20.0 mg/kg/d) and low-dose (7.5–15.0 mg/kg/d) groups and performed propensity-score overlap-weighting analysis. The primary outcome was in-hospital mortality rate. Secondary outcomes were completion of the initial treatment and use of alternatives to TMP-SMX for PCP treatment during hospitalization. ResultsAmong 4449 eligible patients, 1682 (37.8 %) and 2767 (62.2 %) received conventional- and low-dose TMP-SMX treatments, respectively. No significant difference was observed in in-hospital mortality (risk difference, −1.4 %; 95 % CI, −4.5–1.7 %; P = 0.388). Low-dose TMP-SMX was associated with increased completion of initial treatment (risk difference, 4.6 %; 95 % CI, 2.3–6.9 %; P < 0.001), and reduced use of alternative agents (risk difference, −4.0 %; 95 % CI, −7.4 to −0.6 %; P = 0.020). ConclusionLow-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

MiR-150 levels are related to in-hospital mortality in non-HIV Pneumocystis pneumonia patients.

Pneumocystis pneumonia (PCP) is a common opportunistic infection that occurs in immunocompromised patients. Compared with HIV patients, PCP in non-HIV patients tends to follow up a more urgent course and poorer prognosis. Therefore, markers that could predict survival of PCP patients in non-HIV population are of great value. MiRNA-150 has been widely studied in many diseases since it has been identified as a vital regulator of immune cell differentiation and activation. We thus conduct this study aiming to evaluate the prognostic value of miR-150 level in non-HIV PCP. First, the expression levels of miR-150 were compared between PCP patients and healthy volunteers. The miR-150 levels in immune cells were also detected in PCP mouse models. Then the prognostic value of miR-150 was further assessed in another PCP population (n=72). The expression levels of miR-150 were measured by reverse transcription real-time PCR (RT-PCR) technique. Our data demonstrated significantly decreased miR-150 expression levels in PCP patients and mouse models compared to controls. The miR-150 levels also decreased in various immune cells of PCP mouse models. With a cut-off value of 3.48, the area under the curve, sensitivity, specificity of miR-150 to predicate PCP mortality were 0.845, 68.2% and 96.0%, respectively. In conclusion, miR-150 expression value might serve as a potential biomarker to identify PCP patients at high risk of death.

Detection of Pneumocystis jirovecii Pneumonia in Infants with Non-Human Immunodeficiency Virus Admitted to Pediatric Intensive Care Using Metagenomics Next-Generation Sequencing

ObjectiveThis study aimed to investigate the characteristics of the non-human immunodeficiency virus (HIV) pneumocystis pneumonia (PCP) via the microbial composition of Pneumocystis jirovecii pneumonia in the lower respiratory tract in infants with severe pneumonia who were hospitalized in the study’s pediatric intensive care unit (PICU).MethodsThe clinical characteristics of 16 infants with non-HIV PCP (the PCP group) and 33 infants with severe pneumonia (the control group) who were hospitalized at the same time in the PICU were analyzed retrospectively. Using metagenomic next-generation sequencing (mNGS), the bronchoalveolar lavage fluid (BALF) of the two groups was analyzed, and the microbial results and clinical data were compared.ResultsCompared with the control group, the infants in the PCP group had a lower incidence of cough (25% vs 78.8%; P < 0.05), a greater history of surgery (50.0% vs 39.1%; P < 0.05), and a more significant decrease in C3, C4, and CD4/CD8 ratios (all P < 0.05). The pathogenic bacteria in the BALF included P. jirovecii, respiratory syncytial virus, cytomegalovirus (CMV), and Staphylococcus aureus. The predominance of viral infection in the PCP group was significantly higher than in the control group (P < 0.05), especially CMV (43.5% vs 15.2%; P < 0.05). The top five symbiotic microorganisms detected in the BALF of the 49 infants were Streptococcus, Propionibacterium, Rothia, Staphylococcus, and Moraxella. There was no significant difference in the relative abundance of common symbiotic microorganisms between the two groups (all P > 0.05).ConclusionNon-HIV PCP has a higher incidence in PICU infants with severe pneumonia, especially those with underlying diseases or who are immunocompromised, which are clinically difficult to treat. A BALF analysis using mNGS is helpful for early and clear diagnoses. It also helps to clarify the distribution of pathogenic and lower respiratory tract colonizing bacteria in infants with severe pneumonia.

Characteristics and Prognostic Factors of Non-HIV Immunocompromised Patients With Pneumocystis Pneumonia Diagnosed by Metagenomics Next-Generation Sequencing.

ObjectiveThe aim of this study was to evaluate the potential of metagenomic next-generation sequencing (mNGS) for the diagnosis of pneumocystis pneumonia (PCP) in patients with non-human immunodeficiency virus-infection and to discuss the clinical characteristics and identify prognostic factors associated with patients with non-HIV PCP.MethodsForty-six patients with PCP who were admitted in respiratory intensive care unit (ICU) between May 2018 and May 2020 were retrospectively reviewed. The subjects were divided into survivor and non-survivor groups according to the patients' outcome. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were analyzed. The patients' demographics, comorbidities, laboratory parameters, and treatments were compared and evaluated in both groups to identify risk factors for mortality by using univariate and multivariate logistic regression.ResultsMetagenomic next-generation sequencing (mNGS) showed a satisfying diagnostic performance of 100% positive of detecting P. jirovecii from bronchoalveolar lavage (BAL) specimens in forty-six patients with non-HIV PCP, compared to only 15.2% for Gomori Methenamine silver (GMS) staining and 84.8% for Serum 1,3-beta-D-glucan (BDG). Among them, the mean age was 46.4-year-old (range 18–79-year-old) and mortality rate was 43.5%. The dominant underlying conditions were connective tissue diseases (34.8%), autoimmune kidney diseases (30.4%), followed by hematologic malignancies (10.9%), and solid organ transplantation (6.5%). A total of 38 cases (82.6%) received glucocorticoid and 19 cases (41.3%) used immunosuppressant within 3 months before diagnosed PCP. Multiple infections were very common, over two thirds' cases had mixed infections. Compared with survivors, non-survivors had a higher acute physiology and chronic health evaluation II (APACHE II) score (14.4 ± 4.8 vs. 10 ± 3.4), Procalcitonin (PCT) [ng/ml: 0.737 (0.122–1.6) vs. 0.23 (0.095–0.35)], lactic dehydrogenase (LDH) [U/L: 1372 (825.5–2150) vs. 739 (490.5–956)], and neutrophil-lymphocyte ratio (NLR) [21.6 (15.67–38.2) vs. 11.75 (5.1–15.52)], but had a lower PaO2/FiO2 ratio (mmHg:108.8 ± 42.4 vs. 150.5 ± 47.5), lymphocytes [×109/L: 0.33 (0.135–0.615) vs. 0.69 (0.325–1.07)] and CD4+ T cells [cell/μl: 112 (53.5–264) vs. 255 (145–303.5)], all P < 0.05. Furthermore, we found non-survivors' PaO2/FiO2 ratio of day 3 and day 7 had not improved when compared with that of day one, and platelet level and NLR became worse. Multivariate analysis showed that other pathogens' co-infection (OR = 9.011, 95% CI was 1.052–77.161, P = 0.045) and NLR (OR = 1.283, 95% CI was 1.046–1.547, P = 0.017) were the independent risk factors of poor prognosis.ConclusionmNGS is a very sensitive diagnostic tool for identifying P. jirovecii in patients who are non-HIV immunocompromised. PCP in patients who are non-HIV infected is associated with a high rate of multiple infections and severe condition. Mixed infection and elevation of NLR were the independent risk factors of poor prognosis.

Low cut-off value of serum (1,3)-beta-d-glucan for the diagnosis of Pneumocystis pneumonia in non-HIV patients: a retrospective cohort study

BackgroundNon-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP) is a fulminant disease with an increasing incidence. The serum beta-d-glucan (BDG) assay is used as an adjunct to the diagnosis of PCP; however, the cut-off value for this assay is not well-defined, especially in the non-HIV PCP population. Therefore, we aimed to identify the assay cut-off value for this population.MethodsIn this retrospective observational study, we reviewed the medical records of all patients (≥ 18 years old) with clinical suspicion of PCP who underwent evaluation of respiratory tract specimens between December 2008 and June 2014 at Kameda Medical Center. We created a receiver operating characteristic curve and calculated the area under the curve to determine the cut-off value for evaluating the inspection accuracy of the BDG assay.ResultsA total of 173 patients were included in the study. Fifty patients showed positive results in specimen staining, loop-mediated isothermal amplification assay, and polymerase chain reaction test, while 123 patients showed negative results. The receiver operating characteristic analyses suggested that the BDG cut-off level was 8.5 pg/mL, with a sensitivity and specificity of 76% and 76%, respectively.ConclusionsThe Wako-BDG cut-off value for the diagnosis of non-HIV PCP is 8.5 pg/mL, which is lower than the classical cut-off value from previous studies. Clinicians should potentially consider this lower BDG cut-off value in the diagnosis and management of patients with non-HIV PCP.Trial registration: The participants were retrospectively registered.

Blood urea nitrogen-to-serum albumin ratio and A-DROP are useful in assessing the severity of Pneumocystis pneumonia in patients without human immunodeficiency virus infection

IntroductionThere is an increasing incidence of Pneumocystis pneumonia (PcP) among individuals without human immunodeficiency virus (HIV) infection (non-HIV PcP). However, prognostic factors for patients with non-HIV PcP have not been identified. Moreover, A-DROP (for classifying the severity of community-acquired pneumonia) or the blood urea nitrogen-to-serum albumin ratio (BUN/Alb), which is reported to be a predictor of mortality of community-acquired pneumonia, has not been established as an efficient prognostic factor in patients with non-HIV PcP. In this study, we analyzed the prognostic factors for non-HIV PcP and evaluated the prognostic ability of A-DROP and the BUN/Alb ratio. MethodsThis retrospective study involved a chart review of the medical records of 102 patients diagnosed with non-HIV PcP between January 2003 and May 2019 at five medical facilities. ResultsOverall, 102 patients were involved in this study. The 30-day mortality rate for non-HIV PcP was 20.5% in this study population. Compared with survivors, non-survivors had significantly lower serum albumin levels and significantly higher age, corticosteroid dosage at the PcP onset, alveolar–arterial oxygen gradient, A-DROP score, lactate dehydrogenase levels, blood urea nitrogen levels, and BUN/Alb ratio. Multivariate analysis showed that a high BUN/Alb ratio at treatment initiation was significantly associated with 30-day mortality risk. The receiver operating characteristic curves showed that A-DROP score had the highest prognostic ability in estimating 30-day mortality. ConclusionsIn patients with non-HIV PcP, a high BUN/Alb ratio is an independent prognostic predictor of mortality risk, and A-DROP is useful for classifying the severity.

Prognostic impact of pre-existing interstitial lung disease in non-HIV patients with Pneumocystis pneumonia.

BackgroundThe increasing incidence of life-threatening Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients is a global concern. Yet, no reports have examined the prognostic significance of pre-existing interstitial lung disease (ILD) in non-HIV PCP.MethodsWe retrospectively reviewed the medical records of non-HIV PCP patients with (ILD group) or without (non-ILD group) pre-existing ILD. The clinical features and outcomes of the ILD group were compared with those of the non-ILD group. Cox regression models were constructed to identify prognostic factors.Results74 patients were enrolled in this study. The 90-day mortality was significantly higher in the ILD group than in the non-ILD group (62.5% versus 19.0%, p<0.001). In the ILD group, patients with a higher percentage of bronchoalveolar lavage fluid neutrophils had worse outcomes compared to those having a lower percentage (p=0.026). Multivariate analyses revealed that pre-existing ILD (p=0.002) and low levels of serum albumin (p=0.009) were independent risk factors for 90-day mortality. Serum levels of β-d-glucan were significantly reduced after treatment of PCP in both groups, whereas levels of Krebs von den Lungen-6 (KL-6) significantly increased in the ILD group. In the ILD group, the 90-day mortality of patients with increasing KL-6 levels after treatment was significantly higher than those with decreasing levels (78.9% versus 0%, p=0.019).ConclusionIn non-HIV PCP patients, pre-existing ILD is associated with a poorer prognosis. Prophylaxis for PCP is needed in patients with pre-existing ILD under immunosuppression.

Adjunctive corticosteroids may be associated with better outcome for non-HIV Pneumocystis pneumonia with respiratory failure: a systemic review and meta-analysis of observational studies

BackgroundEvidence supporting corticosteroids adjunctive treatment (CAT) for Pneumocystis jirovecii pneumonia (PCP) in non-HIV patients is highly controversial. We aimed to systematically review the literature and perform a meta-analysis of available data relating to the effect of CAT on mortality of PCP in non-HIV patients.MethodsWe searched Pubmed, Medline, Embase, and Cochrane database from 1989 through 2019. Data on clinical outcomes from non-HIV PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I2 index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model. We analyzed the impact of CAT on mortality of non-HIV PCP in the whole PCP population, those who had hypoxemia (PaO2 < 70 mmHg) and who had respiratory failure (PaO2 < 60 mmHg).ResultsIn total, 259 articles were identified, and 2518 cases from 16 retrospective observational studies were included. In all non-HIV PCP cases included, there was an association between CAT and increased mortality (odds ratio, 1.37; 95% confidence interval 1.07–1.75; P = 0.01). CAT showed a probable benefit of decreasing mortality in hypoxemic non-HIV PCP patients (odds ratio, 0.69; 95% confidence interval 0.47–1.01; P = 0.05). Furthermore, in a subgroup analysis, CAT showed a significantly lower mortality in non-HIV PCP patients with respiratory failure compared to no CAT (odds ratio, 0.63; 95% confidence interval 0.41–0.95; P = 0.03).ConclusionsOur meta-analysis suggests that among non-HIV PCP patients with respiratory failure, CAT use may be associated with better clinical outcomes, and it may be associated with increased mortality in unselected non-HIV PCP population. Clinical trials are needed to compare CAT vs no-CAT in non-HIV PCP patients with respiratory failure. Furthermore, CAT use should be withheld in non-HIV PCP patients without hypoxemia.

TEMPORAL CHANGES IN EPIDEMIOLOGY AND MORTALITY RELATED TO PNEUMOCYSTIS CARINII PNEUMONIA IN THE UNITED STATES

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Pneumocystis jirovecii is the fungal etiologic agent of Pneumocystis Pneumonia (PCP). PCP occurs mainly in immune-compromised hosts, like patients with HIV, and those receiving immune-suppressive therapy for underlying malignancy, stem cell/solid organ transplant or auto-immune disorders. In recent years, advances in anti-retroviral therapy have led to improved immune function in persons with HIV. At the same time, the widespread use of immune-suppressive therapies has been changing the landscape of opportunistic infections such as PCP. The objective of this study was to assess temporal trends in PCP epidemiology among hospitalized patients in the US, comparing data for PCP in individuals with HIV (HIV-PCP) to that of patients without HIV (non-HIV-PCP) METHODS: We retrospectively analyzed the United States National Inpatient Sample from 2005-2014 to identify a weighted sample of hospitalizations in adults with a primary or secondary discharge diagnosis of PCP (ICD-9 code 136.3). In this cohort, relevant associated co-morbidities like HIV, connective tissue disorders, cancer, solid organ/stem cell transplant, auto-immune disorders were identified using appropriate ICD-9 codes. The study cohort was divided into HIV-PCP and non-HIV-PCP. Temporal trends in the prevalence of co-morbidities and inpatient mortality were analyzed using the Mantel-Haenzsel test for trend. Survey-specific Rao-Scott χ2 test was used for inter-group mortality comparison. RESULTS: We identified 131,303 hospitalizations with PCP during the study period (mean patient age 46±14 years; 67% were male; 32% were White; 38% were Black). HIV was present in 80% of the patients with a diagnosis of PCP. Among non-HIV PCP admissions, diagnosis of cancer was present in 54%, connective tissue disease in 9%, solid organ/stem cell transplant in 7%, and immune disorders in 5%. Among all PCP admissions, rates of HIV-PCP progressively declined from 85% in 2005 to 73% in 2014 (Ptrend< 0.001). Among non-HIV PCP admissions, rates of other comorbid disorders increased between 2005 and 2014 (cancer 52% to 62%, connective tissue disease 8% to 14%, solid organ/stem cell transplant 7% to 8%, immune disorders 4% to 8% ; Ptrend< 0.001). Overall mortality in patients with PCP was 12%, and was significantly higher with non-HIV PCP (21%) than with HIV-PCP (9%; P< 0.001) CONCLUSIONS: Over the period of 2005-2014, rate of PCP in HIV negative patients is on the rise in the United States and associated with a significantly higher mortality. CLINICAL IMPLICATIONS: Awareness of this trend is important for pulmonary clinicians because of the challenges inherent in the bronchoscopic diagnosis of non-HIV PCP. DISCLOSURES: No relevant relationships by Anusha Devarajan, source=Web Response No relevant relationships by Abhay Dhand, source=Web Response No relevant relationships by Oleg Epelbaum, source=Web Response No relevant relationships by Gowthami Kobbari, source=Web Response No relevant relationships by Christopher Nabors, source=Web Response No relevant relationships by Pawan Puli, source=Web Response No relevant relationships by Srikanth Yandrapalli, source=Web Response

Serial change in serum biomarkers during treatment of Non-HIV Pneumocystis pneumonia

BackgroundFor patients with non–human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes. ObjectiveThis study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP. MethodsWe retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (β-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors. ResultsThere were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated β-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0–190.3] vs. 156 [100.8–283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5–1565] vs. 317 [211–448]; p = 0.03). ConclusionSerum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.

Adjunctive Corticosteroids decreased the risk of mortality of non-HIV Pneumocystis Pneumonia

ObjectivesA mortality rate of non-human immunodeficiency virus–infected pneumocystis pneumonia (non-HIV PCP) is 30–60%. But the effectiveness of adjunctive corticosteroids with trimethoprim–sulfamethoxazole has been unclear, and we examined whether it lowered risk of mortality in non-HIV PCP. MethodsWe did an observational study of adult non-HIV PCP patients from April 2010 through March 2016, using Japanese nationwide healthcare records of the Diagnostic Procedure Combination database (DPC). The risk was estimated by the time-dependent Cox regression analyses with inverse probability weights. Result1299 eligible non-HIV PCP patients were identified. 737 patients were severe respiratory status (partial pressure of oxygen in arterial blood [PaO2] ≤60mm Hg) and 562 were moderate (PaO2 >60mm Hg) at hospital admission. Among patients with severe respiratory status, the adjunctive corticosteroids was associated with lower risk of 60-day mortality (HR 0.71; 95% confidence interval [CI], 0.55–0.91), and significantly decreased mortality rates (24.7% vs 36.6%, P=0.006). In contrast, no significant differences were observed in the risk of 60-day mortality (HR 1.17; 95% CI, 0.73–1.86) and the mortality rate (10.9% vs 9.1%, P=0.516) among patients with moderate respiratory status. ConclusionThe adjunctive corticosteroids were associated with lower risk of 60-day mortality in severe non-HIV PCP patients.

Adjunctive Corticosteroids Decreased the Risk of Mortality of Non-HIV Pneumocystis Pneumonia

Background A mortality rate of non-human immunodeficiency virus-infected pneumocystis pneumonia (non-HIV PCP) is 30-60%, but the effectiveness of adjunctive corticosteroids with trimethoprim-sulfamethoxazole has not yet been adequately examined. To determine whether adjunctive corticosteroids with trimethoprim-sulfamethoxazole is associated with decreasing the mortality rate of non-HIV PCP. Methods We did database observational study of adult non-HIV PCP patients from April 2010 through March 2016, using Japanese nationwide healthcare records of the Diagnostic Procedure Combination database. The primary outcome was the 60-day mortality risk estimated by the time-dependent Cox regression analyses with inverse probability weights. Findings 1299 eligible non-HIV PCP patients were identified. 737 patients were severe respiratory status (partial pressure of oxygen in arterial blood [PaO2] ≤60 mm Hg) and 562 were moderate (PaO2 >60 mm Hg) at hospital admission. Among patients with severe respiratory status, the adjunctive corticosteroids was associated with lower risk of 60-day mortality (HR 0.68; 95% confidence interval [CI], 0.51-0.92), and significantly decreased mortality rates (24.7% vs 36.6%, P=.012). In contrast, among patients with moderate respiratory status, the adjunctive corticosteroids was not significantly associated with lower risk of 60-day mortality (HR 1.10; 95% CI, 0.71-1.71) and no significant difference was observed in 60-day mortality rate (10.9% in Adjunctive Corticosteroids group vs 9.1% in TMP-SMX only group; P = .67). Interpretation The adjunctive corticosteroids with TMP-SMX was associated with lower risk of 60-day mortality in severe non-HIV PCP patients. Funding: Ministry of Health, Labour and Welfare; JSPS. Declaration of Interest: The authors declare no conflicts of interest associated with this manuscript. Ethical Approval: The study was approved by the Institutional Review Board at Tokyo Medical and Dental University (M2000-788).

Predictors of high flow nasal cannula failure in immunocompromised patients with acute respiratory failure due to non-HIV pneumocystis pneumonia.

To evaluate the predictors of high flow nasal cannula (HFNC) failure in pneumocystis pneumonia (PCP) patients with acute respiratory failure (ARF). Fifty-two non-HIV-related PCP subjects were divided into a HFNC success group (44%) and a HFNC failure group (who required mechanical ventilation (MV) despite HFNC application) (56%). The clinical characteristics and physiologic effects were retrospectively reviewed and compared between the groups. At baseline, the heart rate, alveolar-arterial PO2 difference [P(A-a)O2], Sequential Organ Failure Assessment (SOFA) score, and proportion of subjects who used vasopressors were significantly higher in the HFNC failure group than in the HFNC success group. The 60-day mortality was 52% in the HFNC failure group and 13% in the HFNC success group (P=0.004). The results of the multivariate analysis indicated that the baseline SOFA score was independently associated with HFNC failure (adjusted odds ratio, 1.74 per each score unit increase; 95% CI, 1.05-2.89; P=0.03). Repeated measures analysis of variance revealed that within 6 h of HFNC initiation, the mean PaO2/FiO2 ratio decreased and the mean P(A-a)O2 increased rapidly in the HFNC failure group. Patients with ARF due to PCP subjected to HFNC therapy should be carefully monitored, and particular attention should be paid to those who had organ dysfunction and did not show early oxygenation improvement.

Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: A single-center retrospective observational cohort study

The efficacy of low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be acceptable for the treatment of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected patients, with a low incidence of adverse reactions. This study is aimed to evaluate the efficacy and safety of such a regimen for the treatment of non-HIV PCP. We retrospectively enrolled 24 consecutive patients diagnosed with non-HIV PCP who were treated with low-dose TMP-SMX (TMP, 4-10mg/kg/day; SMX, 20-50mg/kg/day). Data of the conventional-dose treatment were used as reference. The primary endpoints were the 30- and 180-day survival rates from the day of treatment, and secondary endpoints were the incidence of each adverse reaction and dropout rate from the initial TMP-SMX regimen. The survival rate was estimated using the Kaplan-Meier method with 95% confidence interval (CI). The median age of patients was 72 years (54.2% men), and connective tissue disease was the most frequent underlying disease (66.7%) in the low-dose group. The 30- and 180-day survival rates were 95.8% (95% CI: 88.2-100.0%) and 91.0% (95% CI: 79.9%-100.0%), respectively, in the low-dose group and 69.0% (95% CI: 54.0%-88.0%) and 51.5% (95% CI: 36.1%-73.4%), respectively, in the conventional-dose group. The total adverse reaction rate was 58.3% in the low-dose group and 72.4% in the conventional-dose group. A total of 75.0% of patients in the low-dose group and 31.0% in the conventional-dose group completed treatment with the initial regimen. Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

Clinical features of acute respiratory failure due to pneumocystis pneumonia in non-HIV immunocompromised patients

Objective: To examine the clinical features of patients with acute respiratory failure (ARF) caused by pneumocystis pneumonia (PCP) admitted into two medical intensive care units (ICU) in non- human immunodeficiency virus (HIV) infected immunocompromised patients. Methods: A retrospective review was conducted among 92 non-HIV patients with ARF caused by PCP in medical ICU of Peking Union Medical College Hospital and China-Japan Friendship Hospital between Jan 2010 and Dec 2015. Patient characteristics, clinical presentation, laboratory and radiological findings, complications, as well as therapy and mortality were included in the analysis. Results: All patients were immunocompromised before PCP, among which 69.6% (64/92) patients were suffered from autoimmune disease. The diagnosis of PCP was made by the identification of P. jiroveci organisms with Giemsa or polymerase chain reaction in specimens of bronchoalveolar lavage, sputum or tracheal aspiration. The Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ was high (19±5) and the partial pressure of oxygen/ fraction of inspiration oxygen(PaO2/FiO2) ratio was low[(139.6±65.4) mmHg]on ICU admission, with all patients diagnosed as acute respiratory failure during ICU stay. Radiologic findings showed bilateral diffused ground glass opacity (94.6%, 87/92). All patients received Compound Sulfamethoxazole (SMZ/TMP) and only 3.3% (3/92) patients were not given conjunctive corticosteroid. 57.6% (53/92) and 21.7% (20/92) patients were coinfected by cytomegalovirus (CMV) and aspergillos. Invasive ventilatory support was required in 90% (81/90) patients. 22% (18/82) patients used non-invasive positive pressure ventilation (NPPV) on ICU admission but most of them (83.3%, 15/18) failed and switched to invasive positive pressure ventilation (IPPV). Median ICU and hospital length of stay were 11 and 17 days, respectively. The overall hospital mortality rate was 76.1% (70/92). Conclusions: Among patients with ARF secondary to non-HIV related PCP, autoimmune system diseases are the most common primary diagnosis. The clinical manifestations were severe and coinfections are common, with poor prognosis.

Pneumocystis pneumonia suspected cases in 604 non-HIV and HIV patients.

Pneumocystis pneumonia (PCP) is one of the most devastating fungal diseases in patients with impaired immunity. Effective antiviral therapies have reduced the burden of PCP among AIDS patients, but an increase in the prevalence of this disease among persons receiving immunosuppressive therapies has been reported. We retrospectively reviewed HIV and non-HIV PCP patients diagnosed in our department during a nine year period. Data were collected from the local database completed during the diagnosis procedure. For each patient, demographic, clinical, radiological, biological and therapeutic data were analyzed. A total of 21,274 bronchoalveolar samples were received from patients suspected of pneumocystosis during the study period, leading to a discharge diagnosis of PCP for 604 patients (143 HIV-positive and 461 HIV-negative). The ratio of non-HIV versus HIV patients presenting PCP increased from 1.7 to 5.6 during the study period. The mortality rate at day 14 was 16%, occurring mostly in non-HIV patients (20.6% compared to 1.4%, P<0.0001), while non-HIV patients were less symptomatic at diagnosis than AIDS patients. This study presents one of the higher number of HIV and non-HIV patients presenting with PCP in a single center. Pneumocystosis is now a crucial health challenge for patients receiving immunosuppressive therapy, with a high mortality rate. This study highlights the need for international guidelines for prophylaxis of PCP in non-HIV patients.

Clinical characteristics of severe pneumocystis pneumonia in children without human immunodeficiency virus infection

Objective To investigate the clinical parameters, risk factors, treatment and clinical outcomes of pneumocystis pneumonia(PCP) in children without human immunodeficiency virus(HIV). Methods Retrospective analysis was made for the clinical features, risk factors, treatment and prognoses of the non-HIV infected severe PCP patients hospitalized at Pediatric Intensive Care Unit(PICU) of Children's Hospital Affiliated to Capital Institute of Pediatrics. Results During April of 2010 to April of 2014, there were 10 cases of non-HIV infected severe PCP in PICU of Children's Hospital Affiliated to Capital Institute of Pediatrics.All of the patients had predisposing diseases, in which 3 cases had connective tissue diseases, 2 cases had acute leukemia, 3 cases had severe pneumonia and 2 cases had congenital immunodeficiency.The main clinical manifestations of those 10 patients were fever, cough, tachypnea and obvious dyspnea.All patients developed respiratory failure.The median value of Pediatric Critical Illness Score was 79.The median arterial oxygen pressure was 58 mmHg(1 mmHg=0.133 kPa). The median oxygenation index was 103 mmHg. The median alveolo-arterial oxygen partial pressure difference was 43.8 mmHg. The median CD4+ T-lymphocytes counts was 169×106/L. Eight patients on admission had mixed infection.Acute respiratory distress syndrome(ARDS) occurred in all of the patients, and 7 cases of them had multiple organ dysfunctions.All of the patients required ventilation support.The median day for invasive mechanical ventilation days was 11 and the median day for noninvasive ventilation days was 6.The pneumothorax occurred in 5 patients.All patients received trimethoprim-Sulfamethoxazole as initial therapy and Caspofungin treatment in combination in 7 cases of the patients.Six patients had nosocomial infection. The median time of PICU stay was 15.5 days.Six patients survived and the mortality was 40%(4/10 cases). Conclusions PCP is a kind of fatal diseases which occurred in patients with immunocompromised conditions and concurrent ARDS or multiple organ dysfunctions.Diagnostic suspicion and mechanical ventilation therapy with lung protective ventilation strategies may improve the clinical outcomes of non-HIV-infected PCP in children. Key words: Pneumocystis pneumonia; Acute respiratory distress syndrome; Treatment; Child

Non-HIV pneumocystis pneumonia

Human immunodeficiency virus (HIV)-uninfected Pneumocystis jirovecii pneumonia (non-HIV PCP) can develop in patients with autoimmune diseases, malignancies, and other diseases, and it can lead to potentially lethal respiratory dysfunction showing a high mortality (1-3). Over the past decade, a paradigm shift in the treatment of autoimmune disease such as rheumatoid arthritis (RA) (4, 5) and inflammatory bowel diseases (IBD) has been brought about by the introduction of biologics (6-8). While the emergence of innovative biologic agents targeted at specific molecules and pathways in the immune system have altered the clinical course of autoimmune disease patients and improved their quality of lives and social outcomes, increasing incidence of non-HIV PCP have been noticed (4-8). In the field of solid organ transplant recipients and malignancies, the emergence of new generation of immunosuppressive agents, such as rituximab and cytotoxic agents could result in frequent occurrence of non-HIV PCP (9-13). Today, although every clinician could encounter PCP patients, there is no established standard treatment for non-HIV PCP. We review recent topics and some aspects to improve the treatment of non-HIV PCP.

Prognostic value of bronchoalveolar lavage in patients with non-HIV pneumocystis pneumonia.

Non-HIV patients with pneumocystis pneumonia (PCP) have a poor prognosis. We aimed to evaluate the prognostic factors for in-hospital mortality in terms of the clinical findings, including the results of bronchoalveolar lavage fluid (BALF)-analyses, in non-HIV PCP patients. We retrospectively reviewed non-HIV PCP patients diagnosed using bronchoalveolar lavage between April 2006 and July 2012. For patients with a poor respiratory status, noninvasive positive pressure ventilation (NPPV) was used during the bronchoalveolar lavage (BAL) procedure. Data regarding demographics, laboratory findings and the prognosis were evaluated. A total of 29 non-HIV PCP patients were analyzed. NPPV was carried out safely and successfully in 12 patients during the BAL procedure. Twelve patients (41%) died. The multivariate logistic regression analysis identified only BALF neutrophilia to be a significant prognostic factor determining in-hospital mortality. The log-rank test showed that the patients with BALF neutrophilia (≥ 31%) had a significantly lower survival rate than the other patients (p=0.001). Only BALF neutrophilia was found to be a significant predictor of survival in patients with non-HIV PCP. Our data also emphasize the significance of performing BAL in such patients, as it provides both diagnostic and prognostic information.

Non-HIV Pneumocystis pneumonia: do conventional community-acquired pneumonia guidelines under estimate its severity?

Background: Non-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed patients having malignancy or on immunosuppressive agents. To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65 score of the British Respiratory Society (BTS) and the Pneumonia Severity Index (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in patients with community-acquired pneumonia (CAP) in Japan. To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP. Methods: A total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR) for respiratory samples with chest x-ray and computed tomography (CT) findings. We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI. Also, patients’ characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups. Results: Based on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and 7/15 (46.7%) died. Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%) died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100%) developed respiratory failure and 8/14 (57.1%) died. There were no significant differences in laboratory results in these groups. The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group. Conclusions: Conventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay resulting in high mortality. The most important factor to improve the mortality of non-HIV PCP is early diagnosis and starting of specific-PCP therapy as soon as possible.