Pneumocystis Carinii Pneumonia In Patients Research Articles

Pneumocystis pneumonia in HIV-positive and non-HIV patients: a retrospective comparative study from a lower-middle income country.

In this study, we compared the predisposing factors, key demographic and clinical characteristics, clinical outcomes, and factors associated with poor prognosis in pneumocystis pneumonia (PCP) infection among the human immunodeficiency virus (HIV)-positive and non-HIV patient populations. This retrospective analysis was conducted at the Aga Khan University Hospital, Karachi, via the collection and analysis of patient records with a diagnosis of "pneumocystosis" between January 2015 and October 2020. Additionally, the laboratory database was evaluated, and patients with a laboratory-confirmed diagnosis of PCP were included. During the study period, 52 laboratory-confirmed hospitalized PCP patients were identified. Of these, 23 and 29 patients were diagnosed using microscopy and polymerase chain reaction, respectively. 34.6% of our patients were HIV positive, with a median CD4 count of 20.5 cells/mm3 (range: 10.7-50.5). Other conditions identified were corticosteroid use, autoimmune diseases, malignancy, radiation, and chemotherapy. On chest imaging, consolidation was found in 30%, ground-glass opacities in 24%, and nodular infiltrates in 20% of the cases. HIV-positive patients had a lower hemoglobin level and a higher level of β-D-glucan at the time of admission, whereas non-HIV patients were found to have more co-morbid conditions than HIV patients. We observed no difference in clinical outcomes between the two populations. Factors associated with a poor prognosis among our patients included concomitant infections at the time of diagnosis, the need for invasive mechanical ventilation, and a longer duration of stay in the hospital as well as the intensive care unit.

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.

Pulmonary co-infections by Pneumocystis jirovecii and Herpesviridae: a seven-year retrospective study

BackgroundPneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.MethodsOur main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.ResultsOne hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.ConclusionOur results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.

High prevalence of pneumocystis pneumonia in interstitial lung disease: a retrospective study.

Interstitial lung disease (ILD) is a new risk category for pneumocystis pneumonia (PCP) with a high mortality rate. The definite diagnostic criteria of PCP in ILD patients have not been established until now. The aims of this study were to identify potential risk factors of PCP in patients with ILD, and to evaluate the performance of metagenomic next-generation sequencing (mNGS), CD4 + T cell count, (1-3)-β-D-Glucan (BG) and lactate dehydrogenase (LDH) in the diagnosis of PCP in ILD patients. This is a retrospective, single-center, case-control study. ILD patients who underwent mNGS from December 2018 to December 2022 were included in the study. Based on the diagnosis criteria of PCP, these patients were divided into PCP-ILD and non-PCP-ILD groups. The potential risk factors for PCP occurrence in ILD patients were analysed via logistic regression. The diagnostic efficacy of mNGS was compared with serological biomarkers. 92 patients with ILD were enrolled, 31 of which had a definite PCP and were assigned to the PCP-ILD group while 61 were to the non-PCP-ILD group. The infection rate of PJ in ILD patients was 33.7% (31/92). The history of glucocorticoid therapy, CD4 + T cell count, BG level and traction bronchiectasis on HRCT were associated with PCP occurrence in ILD patients. LDH level did not reach statistical significance in the logistic regression analysis. mNGS was confirmed as the most accurate test for PCP diagnosis in ILD patients. ILD is a new risk group of PCP with high PCP prevalence. Clinicians should pay close attention to the occurrence of PCP in ILD patients who possess the risk factors of previous glucocorticoid therapy, decreased CD4 + T cell count, increased BG level and absence of traction bronchiectasis on HRCT. mNGS showed the most excellent performance for PCP diagnosis in ILD patients. Peripheral blood CD4 + T cell count and BG level are alternative diagnostic methods for PCP in ILD patients. However, the diagnostic value of serum LDH level was limited in ILD patients.

Role of glucocorticoids in pneumocystis pneumonia in patients with non-HIV infection/AIDS (HIV/AIDS) and related mechanisms

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis carinii and is the most common fungal infection in HIV/AIDS patients. With the routine use of antiretroviral therapy (ART), the incidence of PCP infection in HIV/AIDS patients has decreased and the prognosis has improved significantly. On the other hand, the use of chemoradiotherapy and immunotherapy in patients with cancer, post-transplantation and autoimmune diseases are increasing dramatically, which has led to a similar increase in the incidence of PCP in these non-HIV/AIDS patients. There is a global shift in research on PCP from HIV-infected co-infected PCP (HIV-PCP) to non-HIV-infected co-infected PCP. The clinical course of non-HIV-PCP is rapid and severe, and the morbidity and mortality rates are higher than those of HIV-PCP. Studies have shown that 90% of non-HIV-PCP patients have a history of glucocorticoid use prior to infection, such as in patients with hematologic malignancies, solid organ transplants, and rheumatic diseases, and that long-term high-dose glucocorticoid use is an important risk for PCP susceptibility. Clinical practice has shown that PCP often occurs during the tapering of glucocorticoids, and a higher proportion of patients develop diffuse pulmonary lesions and, in more severe cases suffer from life-threatening acute respiratory failure. The pathogenesis of non-HIV infections associated with PCP is not yet clarified, and there is a lack of effective therapeutic practices that require further investigation.

Relationship between clinical features and droplet digital PCR copy number in non-HIV patients with pneumocystis pneumonia

ObjectiveDroplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj.MethodsA total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed.ResultsPj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support.ConclusionThe scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.

Prevention of pneumocystis pneumonia in patients with hematological diseases: Efficacy oflow-dose atovaquone.

At our institution, patients with hematological disease who require Pneumocystis jirovecii pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness. We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration. 85 patients were included in the study. The median age of the study population was 72 years (range: 33-97). The duration of atovaquone treatment and follow-up time were 150 days (22-1,018) and 258 days (22-1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period. In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.

Efficacy of initial caspofungin plus trimethoprim/sulfamethoxazole for severe PCP in patients without human immunodeficiency virus infection

BackgroundThe number of pneumocystis pneumonia (PCP) cases is increasing in immunocompromised patients without human immunodeficiency virus infection (HIV), causing serious morbidity with high mortality. Trimethoprim/sulfamethoxazole (TMP/SMZ) monotherapy has limited effectiveness in the treatment of PCP. Clinical data on whether initial caspofungin plus TMP/SMZ for this disease is superior to monotherapy in non-HIV-infected patients are limited. We aimed to compare the clinical effectiveness of these regimens for severe PCP in non-HIV patients.MethodsA retrospective study reviewed 104 non-HIV-infected patients with confirmed PCP in the intensive care unit between January 2016 and December 2021. Eleven patients were excluded from the study because TMP/SMZ could not be used due to severe hematologic disorders or clinical data were missing. All enrolled patients were divided into three groups according to different treatment strategies: Group 1 received TMP/SMZ monotherapy, Group 2 received caspofungin combined with TMP/SMZ as first-line therapy, and Group 3 initially received TMP/SMZ monotherapy and later received caspofungin as salvage therapy. The clinical characteristics and outcomes were compared among the groups.ResultsA total of 93 patients met the criteria. The overall positive response rate of anti-PCP treatment was 58.06%, and the overall 90-day all-cause mortality rate was 49.46%. The median APACHE II score was 21.44. The concurrent infection rate was 74.19%, among whom 15.05% (n = 14) of those patients had pulmonary aspergillosis, 21.05% (n = 20) had bacteremia, and 23.65% (n = 22) had CMV infections. The patients who received initial caspofungin combination with TMP/SMZ had the best positive response rate (76.74%) compared to others (p = 0.001). Furthermore, the group that received initial caspofungin combined with TMP/SMZ had a 90-day all-cause mortality rate (39.53%) that was significantly different from that of the shift group (65.51%, p = 0.024), but this rate showed no statistically significant difference compared with that in the monotherapy group (48.62%, p = 0.322). None of the patients had serious adverse events from caspofungin therapy.ConclusionsFor non-HIV-infected patients with severe PCP, initial combination therapy with caspofungin and TMP/SMZ is a promising first-line treatment option compared with TMP/SMZ monotherapy and combination therapy as salvage therapy.

Metagenomic next-generation sequencing performed on blood samples for the early recognition of severe Pneumocystis pneumonia in critical hematological patients

Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.

Rising incidence of Pneumocystis pneumonia: A population-level descriptive ecological study in England

Pneumocystis pneumonia (PCP) is an opportunistic infection that causes significant morbidity and mortality in the immunocompromised population. This population is growing and diversifying, yet contemporary epidemiology is lacking. We investigated the population-level incidence of PCP over the past decade. We conducted a descriptive study of all hospital admissions in England from April 2012 to March 2022. PCP episodes, age, median length of stay, gender and episodes of other respiratory fungal infections were collected. Consumption of Trimethoprim-Sulfamethoxazole was obtained between January 2019 and May 2022. The incidence of PCP increased from 2·2-4·5/100,000 population between 2012/2013 and 2019/2020 (p<0·0001). There was a drop in 2020/2021 to 2·7/100,000 before returning to 3.9/100,000 in 2021/2022. PCP episodes rose as a proportion of all-cause admissions as well as a proportion of episodes due to other fungal infections. The proportion of PCP patients aged 75+increased from 14% to 26%. The median length of stay was 13.5 days. Consumption of intravenous Trimethoprim-Sulfamethoxazole increased from 0.24×100,000 to 0.30 ×100,000 defined daily doses. The incidence of PCP is rising rapidly and represents a significant burden to the healthcare system. Further study into who is at risk of PCP is needed to better determine who should be given prophylaxis.

Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients

PurposeOne of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation.Materials and methodsThis is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression.ResultsAmong the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01–1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86–0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05–40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29–53.20; p = 0.026).ConclusionPatients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.

Pneumocystis pneumonia in COVID-19 patients: A comprehensive review

The admitted patients of intensive care units with coronavirus disease 2019 (COVID-19) meet the challenges of subsequent infections. Opportunistic fungal infections such as Pneumocystis pneumonia (PCP) are among the important factors in the context of COVID-19 patients affecting illness severity and mortality. We reviewed the literature on COVID-19 patients with PCP to identify features of this infection. Although studies confirmed at least the presence of one immunosuppressive condition in half of PCP patients, this disease can also occur in immunocompetent patients who developed the immunosuppressive condition during Covid-19 treatment. The major risk factors associated with COVID-19 patients with PCP can be considered low lymphocyte counts and corticosteroid therapy. Diagnostic and treatment options are complicated by the overlapping clinical and radiologic characteristics of PCP and COVID-19 pneumonia. Therefore, physicians should comprehensively evaluate high-risk patients for PCP prophylaxis.

Application of Metagenomic Next Generation Sequencing in the Diagnosis of Pulmonary Infectious Pathogens from Bronchoalveolar Lavage Samples in Patients Underwent Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Infection remains an important cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the impaired immune function of allo-HSCT patients, the clinical manifestations of pulmonary infection are diverse and the imaging characteristics are atypical. Meanwhile, pulmonary infections are often mixed and opportunistic pathogens are common. Therefore, diagnosis of these infections is difficult. Compared with the traditional culture method, metagenomic next-generation sequencing (mNGS) has the advantages of culture-independent, unbiased, short time-consuming and broad-spectrum detection. It is also able to detect rare and new pathogens. To further investigate the value of mNGS among allo-HSCT patients, we compared the results of mNGS of bronchoalveolar lavage (BAL) samples and microbiological culture among pulmonary infection patients after allo-HSCT. Materials and Methods: From May 28, 2018 to December 28, 2021, BAL samples were collected from 64 patients after allo-HSCT with pulmonary infection. mNGS and microbial culture of BAL were performed to evaluate the effectiveness of mNGS in the diagnosis of pulmonary infectious pathogens. Patients with disease relapse after allo-HSCT were excluded, and the follow-up was up to March 24, 2022. Results: 64 patients were enrolled in this study. The median age was 36 (17-67) years old, including 45 males (70.3%) and 19 females (29.7%), and the median time between transplantation and mNGS detection was 11.1 (0.7-91.2) months. Among 64 patients, the number of patients with only positive mNGS results was 33, 4 patients were only culture-positive, 13 patients were double negative, and 14 patients were double positive. For the double-positive group, 78.6% (11/14) of them showed completely or partly matched results. (Figure 1) In total, 47 patients (73.4%) were positive for mNGS and 18 patients (28.1%) were positive for culture, with the positive rate of mNGS higher than that of culture (p<0.01). Further analysis showed that the positive rate of fungi detected by mNGS was higher than that of culture (P = 0.043), and there was no significant difference between the positive rate of bacteria detected by mNGS and culture (P = 0.067), but the number of bacteria detected by mNGS (p=0.001) was higher than that of culture. Cytomegalovirus (CMV) (n=17) and Epstein Barr virus (EBV) (n=10) were the most commonly detected viruses in mNGS of BAL, and Pneumocystis yersini (n=13) was the most commonly detected fungus in BAL mNGS. (Figure 2) The number of Nocardia and Aspergillus fumigatus detected by BAL mNGS was higher than culture with no statistical significance. Previous the diagnosis of Pneumocystis carinii pneumonia (PCP) was based on the clinical manifestations, imaging examination, and Pneumocystis yersini detected by microscopic examination. Among 13 PCP patients, 12 patients (92.3%) had fever, cough，chest tightness，and shortness of breath, and 1 patient (7.7%) had no symptoms. 11 patients received G test, only one test result slightly exceeded the upper limit, and the other 10 tests were negative. 9 patients had typical pulmonary imaging changes of PJP, and 1 patient's CT finding of lung was consistent with the imaging findings of aspergillus pneumonia. The results showed that mNGS of BAL had advantage in the diagnosis of PCP after allo-HSCT. Conclusion: The study indicated that for patients with pulmonary infection after allo-HSCT, the positive rate of mNGS of BAL samples was higher than that of microbial culture especially for fungal infections. Furthermore, mNGS of BAL samples showed advantages over traditional methods in the detection of PCP after allo-HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: A multicentric self-controlled case series study

IntroductionPneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. MethodsThe self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. ResultsFifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01–0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. ConclusionOur study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.

Clinical cases of pneumocystis pneumonia in patients with HIV infection and underlying COVID-19

During the COVID-19 pandemic, additional difficulties have emerged in the differential diagnosis of interstitial pulmonary abnormalities, especially in patients with HIV infection, in whom this kind of injury can be caused by a wide range of pathogens, including opportunistic diseases. The high probability of an adverse outcome of pulmonary disease in patients with severe immunodeficiency requires an urgent choice of effective therapy.The article describes clinical cases of pneumocystis pneumonia in two COVID-19 patients with newly diagnosed HIV infection, illustrating the difficulties of differential diagnosis in these conditions.

Pneumocystis pneumonia in patients with Cushing's syndrome: A French multicenter retrospective study

ObjectivePneumocystis pneumonia (PcP) is an opportunistic infection occurring in immunocompromised patients. Cushing's syndrome (CS) impairs the immune system, and several authors have reported PcP in patients with CS. The present study aimed to characterize PcP occurring in a CS context and its management in French tertiary centers, in order to highlight the similarities in clinical presentation and treatment according to whether prophylaxis is implemented or not. MethodsThis was a multicenter retrospective study conducted in several French University Hospitals and Cancer Centers. Patients with PcP and confirmed CS regardless of etiology were included. We excluded patients with other known causes of acquired immunodeficiency with increased risk of PcP. ResultsTwenty-five patients were included. CS etiology was neoplastic in 84.0% of cases. CS clinical presentation associated predominant catabolic signs (76.0%), hypokalemia (91.7%) and lymphopenia (89.5%). CS was intense in most patients, with mean plasma cortisol levels at diagnosis of 2.424±1.102nmol/L and urinary free cortisol>10× the upper limit of normal in 85.0%. In all patients, PcP onset followed introduction of cortisol blockers, at a median 5.5 days. Patients were treated with 1 to 3 cortisol blockers, mainly metyrapone (88%), which significatively lowered plasma cortisol levels to 667±541nmol/L at the onset of PcP (P<0.001). PcP occurred in 7 patients despite prophylaxis. Finally, 60.0% patients were admitted to intensive care, and 20.0% died of PcP. ConclusionHigh mortality in patients with PcP implies that clinicians should be better informed about this rare infectious complication. Prophylaxis remains controversial, requiring comparative studies.

Risk factors of in-hospital mortality in patients with pneumocystis pneumonia diagnosed by metagenomics next-generation sequencing.

ObjectivesThe metagenomic next-generation sequencing (mNGS) test is useful for rapid and accurate detection and identification of pathogenic microorganisms. The aim of the present study was to investigate the factors associated with in-hospital mortality in pneumocystis pneumonia (PCP) patients with mNGS-assisted diagnosis.MethodsOur study enrolled 154 patients with mNGS-positive PCP from August 2018 to February 2022 at the First Affiliated Hospital of Zhengzhou University respectively. Patients were divided into the survivor group (n=98) and the death group (n=56) according to whether in-hospital death occurred. Baseline characteristics, patients’ pre-hospital symptoms and patients’ CT imaging performance during hospitalization were carefully compared between the two groups. Risk factors for the occurrence of in-hospital death were sought by selecting indicators that were significantly different between the two groups for modelling and performing multiple logistic regression analysis.ResultsCompared with the in-hospital death patients, the survivors were younger and had higher levels of albumin (ALB) (age: 50.29 ± 14.63 years vs 59.39 ± 12.27 years, p<0.001; ALB: 32.24 ± 5.62 g/L vs 29.34 ± 5.42g/L, p=0.002; respectively), while the levels of lactate dehydrogenase (LDH) and C-reactive protein CRP were lower (LDH: 574.67 ± 421.24 U/L vs 960.80 ± 714.94 U/L, p=0.001; CRP: 54.97 ± 55.92 mg/L vs80.45 ± 73.26 mg/L, p=0.018; respectively). Multiple logistic regression analysis revealed that age, the baseline LDH and CRP levels were all positively associated with high in-hospital mortality [age: OR(95%CI): 1.115 (1.062-1.172), p<0.001; LDH: OR(95%CI): 1.002 (1.001-1.003), p<0.001; CRP: OR(95%CI): 1.008 (1.000-1.017), p=0.045; respectively] while the platelet counts was negatively associated with it [OR(95%CI): 0.986 (0.979-0.992), p<0.001].ConclusionsOld age, high baseline levels of LDH and CRP and low platelet counts were risk factors of the in-hospital mortality in mNGS positive PCP patients.

The medication for pneumocystis pneumonia with glucose-6-phosphate dehydrogenase deficiency patients.

Pneumocystis pneumonia (PCP) is an opportunity acquired infection, which is usually easy to occur in patients with AIDS, organ transplantation, and immunosuppressive drugs. The prevention and treatment must be necessary for PCP patients with immunocompromise. And the oxidants are currently a typical regimen, including sulfanilamide, dapsone, primaquine, etc. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked gene-disease that affects about 400 million people worldwide. The lack of G6PD in this population results in a decrease in intracellular glutathione synthesis and a weakening of the detoxification ability of the oxidants. As a result, oxidants can directly damage haemoglobin in red blood cells, inducing methemoglobin and hemolysis. When patients with G6PD deficiency have low immunity, they are prone to PCP infection, so choosing drugs that do not induce hemolysis is essential. There are no clear guidelines to recommend the drug choice of this kind of population at home and abroad. This paper aims to demonstrate the drug choice for PCP patients with G6PD deficiency through theoretical research combined with clinical cases.

Is Pneumocystis Jirovecii Transmitted by the Airborne Route?

<h3>Background</h3> Pneumocystis jirovecii (p.jirovecii) is a fungus responsible for causing opportunistic Pneumocystis pneumonia (PCP) in immunocompromised patients. Currently the Centers for Disease Control and Prevention (CDC) recommends following standard precautions while also avoiding placing a PCP patient in the same room with an immunocompromised patient. There has been recent scientific evidence that indicates P.jirovecii may be transmitted by the airborne route. The purpose of this literature review is to evaluate the recent research findings to assess whether escalating transmission-based precautions from droplet to airborne isolation is necessary to best prevent transmission of P.jirovecii in the immunocompromised oncologic patient population at a 514-bed inpatient comprehensive cancer center. <h3>Methods</h3> PubMed was utilized to identify articles describing PCP outbreaks, the fungal characteristics, and mode of transmission. The articles reviewed comprised of systematic reviews, case control, and case report studies published between years 2016 through 2021, with one influential case control study published in 2010. The patient population studied in the outbreaks included those with heart, kidney, or liver transplants and patient populations with other immunocompromising conditions. <h3>Results</h3> Nine articles, including 4 systematic reviews, 4 case control studies, and 1 case report were reviewed. The scientific evidence of the fungal characteristics, mode of transmission, and occurrence of clusters of PCP cases favored the hypothesis that airborne transmission is possible. There are still some unknowns including the length of time that the fungal cysts can remain in the air and if the cysts are spread via droplet or aerosolized route. <h3>Conclusions</h3> Despite the recent findings demonstrating possible airborne transmission, until further studies increase the strength of evidence for airborne transmission, droplet precautions should be considered for PCP patients to prevent transmission in the immunocompromised population.

Efficacy of Trimethoprim-Sulfamethoxazole in Combination with an Echinocandin as a First-Line Treatment Option for Pneumocystis Pneumonia: A Systematic Review and Meta-Analysis.

Although combination therapy using trimethoprim–sulfamethoxazole (TMP–SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis pneumonia (PCP), it remains unclear whether it is more effective than TMP–SMX monotherapy, the current first-line treatment for this disease. Hence, we performed a systematic review and meta-analysis to compare the efficacies of these treatment options for PCP. The Scopus, EMBASE, PubMed, CINAHL, and Ichushi databases were searched for studies (up to January 2022) reporting the mortality and positive response rates (fewer clinical symptoms, improved partial pressure of arterial oxygen, and resolution of pneumonitis on chest imaging) of PCP patients receiving monotherapy or combination therapy. Four studies met the inclusion criteria. All four presented mortality data and one had positive response rates. Compared with the monotherapy, the combination therapy resulted in significantly lower mortality and higher positive response rates (mortality: odds ratio (OR) 2.20, 95% confidence interval (CI) 1.46–3.31; positive response rate: OR 2.13, 95%CI 1.41–3.23), suggesting it to be an effective and promising first-line therapy for PCP. However, further safety evaluations are needed to establish this as a fact.