Pneumocystis Jirovecii Pneumonia In Patients Research Articles

Low-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia: a systematic review and meta-analysis

BackgroundThe recommended standard treatment for Pneumocystis jirovecii pneumonia (PJP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) (15–20 mg/kg/d TMP). However, the standard regimen may cause a high incidence of dose-related adverse events (AEs). Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose TMP-SMX regimens (<15 mg/kg/d of TMP) compared with the standard regimen in patients with PJP.MethodsWe searched PubMed, Embase, and the Cochrane database for relevant articles from inception to 10 March 2024. Studies were included if they focused on PJP patients receiving a low-dose TMP-SMX regimen compared with a standard regimen. The primary outcome was mortality. We assessed study quality and performed subgroup analysis and sensitivity analysis to explore potential heterogeneity among the included studies.ResultsSeven studies were included. Overall, the low-dose regimen significantly reduced the risk of mortality (odds ratio [OR] = 0.49; 95% CI, 0.30–0.80; I2 = 16%; P = 004). This finding was confirmed in further sensitivity and subgroup analyses. The low-dose regimen also significantly reduced total AEs (OR = 0.43; 95% CI, 0.29–0.62; I2 = 0%; P < 0.0001), and improved the incidence of most specific AEs (ORs ranged from 0.13 to 0.89). In addition, the low-dose regimen had significantly more patients completing the initial regimen (P = 0.002), fewer patients requiring dose reductions (P = 0.04), and almost significantly fewer patients requiring a switch to a second-line regimen (P = 0.06).ConclusionThe limited available evidence suggests that a low-dose TMP-SMX regimen significantly reduced mortality and total AEs in PJP patients. Thus, it is one of the potentially promising therapies to PJP and more high-quality and multi-center randomized trials should be conducted in the future.

Prognostic analysis of Pneumocystis jirovecii pneumonia in patients with systemic vasculitides: a retrospective cohort study

ObjectivesPneumocystis jirovecii pneumonia (PJP) is a serious complication of autoimmune and inflammatory diseases. This study aimed to describe the characteristics of PJP in patients with various systemic vasculitides and explore potential prognostic factors.MethodData on 62 enrolled PJP patients with systemic vasculitis were analyzed. Patients were stratified based on the outcomes. Prognostic factors were investigated using Cox-regression models. Characteristics of patients with and without interstitial lung disease (ILD) were compared.ResultsAmong 62 vasculitis-PJP patients, 48 had anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), with microscopic polyangiitis (MPA) being the most common subtype (28 patients). MPA (HR 4.33, p = 0.001), concomitant aspergillosis (HR 2.68, p = 0.019), and higher D-dimer at PJP diagnosis (HR 1.07, p = 0.004) were independent adverse prognostic factors for overall survival. Stable disease activity of vasculitis was an independent favorable prognostic factor (HR 0.28, p = 0.027). Patients with MPA were older than non-MPA patients (median age: 69 vs. 58 years, p = 0.001); both ILD and fibrotic ILD were more prevalent in MPA patients (ILD: 78.6% vs. 35.3%, p = 0.001; fibrotic ILD: 57.1% vs. 11.8%, p < 0.001). At the diagnosis of PJP, patients with preexisting ILD had higher counts of white cells, lymphocytes, and neutrophils, as well as higher levels of immunoglobulin (Ig) G and IgA, than patients without preexisting ILD.ConclusionsMPA was associated with a higher risk of death in patients with vasculitis-PJP, possibly due to a higher prevalence of ILD. In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.Key Points• Data from this study showed that MPA was the most common subtype of vasculitis among vasculitis-PJP patients.• Compared with non-MPA patients in this study, patients with MPA were older, had more ILD and fibrotic ILD, and had a poorer prognosis.• In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA.

Prognostic analysis of concurrent Pneumocystis jirovecii pneumonia in patients with systemic lupus erythematosus: a retrospective study

BackgroundSystemic lupus erythematosus (SLE) has been less deadly since the advent of corticosteroid-sparing medications. SLE patients still have a higher mortality rate than the general population. Infectious disease is reported as one of the major causes of death in patients with SLE. Although bacteria are the most often isolated pathogens from patients with SLE, Pneumocystis jirovecii pneumonia (PJP) is more deadly than bacterial infection.MethodsWe retrospectively enrolled consecutive patients with SLE concurrent with PJP (SLE-PJP) in our center between January 2014 and December 2022. The participants were classified into two groups: survivors and non-survivors. Cox regression models and Kaplan‒Meier survival analyses were conducted to explore prognostic factors for survival.ResultsThere were 57 patients with SLE (42.0 ± 15.8 years old, 78.9% female) complicated with PJP, 22 (38.6%) of whom died. Compared with the survival group, the non-survival group had more patients with hyperglycemia or diabetes mellitus, invasive ventilation (p < 0.01), respiratory failure, intensive care unit admission, non-invasive ventilation, and hospital-acquired pneumonia (p < 0.05). The non-survival group showed a higher neutrophil percentage, lactate dehydrogenase, D-dimer (p < 0.001), urea, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), and ferritin (p < 0.05). It also had lower minimal albumin, hemoglobin (p < 0.001), immunoglobulin G, complement 3, peripheral lymphocyte count, platelet, NK cell count, and CD4+ T-cell count (p < 0.05). Multivariate analysis indicated that hyperglycemia or diabetes mellitus (HR = 4.25, p < 0.01, 95% CI: 1.51–11.97), thrombocytopenia (HR = 4.22, p < 0.01, 95% CI: 1.63–10.91) and lower complement 3 (C3) (HR = 4.06, p < 0.01, 95% CI: 1.60-10.33) were independent risk factors for the survival of SLE-PJP patients.ConclusionsThe mortality rate of patients with SLE-PJP is still high. Hyperglycemia, decreased C3, and thrombocytopenia are independent survival risk factors.

Metagenomic next-generation sequencing promotes diagnosis and treatment of Pneumocystis jirovecii pneumonia in non-HIV infected children: a retrospective study

BackgroundMetagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children.MethodsTotally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-β-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed.ResultsPneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26–100%). The sensitivity of BDG was 57.58% (95% CI: 39.22–74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts.ConclusionsThe mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.

Identification of predictive markers of Pneumocystis jirovecii pneumonia in kidney transplant recipients

BackgroundKidney transplantation has emerged as the most effective treatment for patients with uremia. Advances in immunosuppressant medications have significantly reduced the risk of rejection. However, a notable increase in opportunistic infections, such as Pneumocystis jirovecii pneumonia (PJP), demands special attention in clinical practice. Our study aims to evaluate risk factors and identify predictive markers associated with PJP in kidney transplantation recipients. MethodsWe conducted a case-control study (1:2 ratio) involving kidney transplant recipients with and without PJP, matched based on the same surgical date. The study was carried out at Zhongnan Hospital of Wuhan University, China. ResultsNinety-three participants were enrolled at Zhongnan Hospital of Wuhan University, comprising 31 with PJP and 62 without PJP. All patients tested negative for HIV. Our findings indicate that PJP patients exhibited lower levels of serum albumin (P = 0.001), reduced counts of total and CD3+ (P < 0.001), CD4+ (P = 0.001), and CD8+ T lymphocytes (P < 0.001), and a lower rate of prophylactic trimethoprim-sulfamethoxazole (TMP-SMZ) usage compared to non-PJP patients (P = 0.02). Conversely, urea levels in PJP patients were significantly higher than in non-PJP controls (P < 0.001). We developed a model combining CD8+ T cell count (< 241.11/μL, P < 0.001) and ALB levels (< 35.2 g/L, P = 0.003), which demonstrated excellent discriminatory power in distinguishing PJP from non-PJP cases, with an area under the curve (AUC) of 0. 920 (95% CI, 0.856–0.989). ConclusionsOur study suggests that a baseline CD8+ T cell count (< 241.11/μL) and serum ALB levels (< 35.2 g/L) offer robust predictive value for the occurrence of PJP infections in kidney transplant recipients.

A combined immune and inflammatory indicator predict the prognosis of severe Pneumocystis jirovecii pneumonia patients: a 12-year, retrospective, observational cohort

Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP). Therefore, we aimed to investigate the correlation between the combined immune and inflammatory indicator: the neutrophil-to-lymphocyte ratio (NLR) and prognosis of non-human immunodeficiency virus (non-HIV) PjP.In the retrospective analysis conducted in ICUs at Beijing Chao-Yang Hospital, we examined data from 157 patients diagnosed with non-HIV PjP. Our findings reveal a concerning hospital mortality rate of 43.3%, with the 28-day mortality rate reaching 47.8%.Through multivariable logistic and Cox regression analyses, we established a significant association between elevated NLR levels and hospital mortality (adjusted odd ratio, 1.025; 95% CI, 1.008-1.043; p = 0.004) or 28-day mortality (adjusted hazard ratio, 1.026; 95% CI, 1.008-1.045; p = 0.005). Specifically, patients with an NLR exceeding 20.3 demonstrated markedly lower overall survival rates, underscoring the biomarker's predictive value for both hospital and 28-day mortality.In conclusion, non-HIV PjP patients in the ICU still have a high rate of mortality and a poor short-term prognosis after discharge. A high level of NLR was associated with an increased risk of hospital mortality and 28-day mortality.

Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) μmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

The Clinical Value of Metagenomic Next-Generation Sequencing in Pneumocystis jirovecii Pneumonia.

The incidence of Pneumocystis jirovecii pneumonia (PJP) is increasing. 108 patients were analysed retrospectively at the Wuhan Union Hospital. The patients were classified into the PJP group or the P. jirovecii colonisation (PJC) group based on clinical diagnosis. Clinical data included demographics, laboratory examinations, treatment, and outcomes. A notable difference in the fungal load was seen between two groups, with median reads of 3215.79 vs. 5.61 in two groups, respectively (P<0.001). The optimal threshold value for discriminating P. jirovecii infection between colonisation for mNGS was six, and serum (1,3)-β-D-glucan (BDG) was 47.6 pg/mL. Besides, the positive detection rate of mNGS for co-pathogens in PJP patients was significantly higher than that of culture (88.16% vs. 22.37%, P<0.0001). Epstein-Barr virus and cytomegalovirus were the most common pathogens of co-infection in PJP patients. The antibiotic therapy in PJP patients was adjusted according to the mNGS results, of which seventeen (22.37%) were downgraded, 38 (50.0%) patients were upgraded, and 21 (27.63%) were unchanged. And almost all patients showed significant improvement in C-reactive protein. mNGS is a promising and valuable technique with good performance for differentiating P. jirovecii infection and colonisation, the detection of pathogens, and antibiotic treatment.

Immune checkpoint inhibitor increased mortality in lung cancer patients with Pneumocystis jirovecii pneumonia: a comparative retrospective cohort study.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection in immunocompromised individuals. Immune checkpoint inhibitor (ICI) has brought significant survival benefit in lung cancer patients. Although the few studies showed there was high mortality in PJP patients with ICI use, these studies had no comparative control groups. A retrospective study was conducted to compare the mortality in PJP patients with lung cancer between those treated with ICI and a concurrent control group treated without ICI. A total number of 20 non-human immunodeficiency virus (HIV) patients with confirmed PJP and co-existing lung cancer were included in the current study, and classified into ICI group (n=9) and non-ICI group (n=11).There was a clear trend to a shorter onset of PJP in ICI group than non-ICI group (118.9 ± 60.9 vs 253.0 ± 185.1 days), although without statistical significance (p=0.053). Bronchoscopic alveolar lavage fluid were collected from all patients and used to identify Pneumocystis jirovecii. In both groups, metagenomics next-generation sequencing (mNGS) were the most used diagnostic techniques. Within 28 days after the onset of PJP, mortality was significantly higher in the ICI group than non-ICI group (33.3% vs 0, p=0.042). Lung cancer patients with ICI use had a higher mortality rate after PJP infection than patients without ICI use. Prospective studies with larger sample size and a multi-center design are warranted to further verify the present results.

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Clinical Characteristics and Prognostic Predictors of Pneumocystis Jirovecii Pneumonia in Patients with and without Chronic Pulmonary Disease: A Retrospective Cohort Study.

Pneumocystis jirovecii pneumonia (PJP) is a severe respiratory infection caused by Pneumocystis jirovecii in immunocompromised hosts. The role of P. jirovecii colonization in the development or progression of various pulmonary diseases has been reported. Our aim was to explore serial change in serum biomarkers and the independent risk factors for mortality in patients with and without chronic pulmonary diseases who developed PJP. We performed a retrospective study to select patients with Pneumocystis jirovecii pneumonia between January 1, 2012, and December 31, 2021. Information regarding demographics, clinical characteristics, underlying diseases, laboratory tests, treatment, and outcomes was collected. Univariate and multivariate logistic regression analyses were used to identify independent predictors of in-hospital mortality. A total of 167 patients diagnosed with PJP were included in the study: 53 in the CPD-PJP group and 114 in the NCPD-PJP group. The number of patients with PJP showed an increasing trend over the 10-year period. A similar trend was observed for in-hospital mortality. Independent risk factors associated with death in the NCPD-PJP group were procalcitonin level (adjusted OR 1.08, 95% CI 1.01-1.16, P=0.01), pneumothorax (adjusted OR 0.07, 95% CI 0.01-0.38, P=0.002), neutrophil count (adjusted OR 1.27, 95% CI 1.05-1.53, P=0.01) at 14 days, and hemoglobin level (adjusted OR 0.94, 95% CI 0.91-0.98; P=0.002) at 14 days after admission. The risk factor associated with death in the CPD-PJP group was neutrophil count (adjusted OR 1.19, 95% CI 0.99-1.43; P=0.05) at 14 days after admission. The risk factors for death were different between patients with PJP with and without chronic pulmonary disease. Early identification of these factors in patients with PJP and other underlying diseases may improve prognosis.

Diagnostic values of BALF metagenomic next-generation sequencing, BALF real-time PCR and serum BDG for Pneumocystis jirovecii pneumonia in HIV-infected patients.

This study aimed to assess the diagnostic values of bronchoalveolar lavage fluid (BALF) real-time polymerase chain reaction (PCR) and BALF metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PJP) in patients infected with human immunodeficiency virus (HIV). A total of 99 HIV-infected PJP patients and 61 HIV-infected patients diagnosed with non-PJP pneumonia between March 2019 and December 2022 were enrolled. P. jirovecii and multiple other co-pathogens detected in BALF by mNGS were analyzed. The clinical final diagnosis was employed as a benchmark. We compared the diagnostic performance of mNGS in PJP with serum BDG and BALF real-time PCR. The mixed infections detected by mNGS and modifications of antimicrobial treatment were also analyzed. The sensitivity of mNGS test of BALF samples reached 85.86%, which was significantly higher than serum BDG (39.39%, P < 0.001). The sensitivity of BALF P. jirovecii PCR (84.85%) was similar with mNGS (P > 0.05). The specificity of mNGS (100%) was also same as PCR (100.0%), and superior to serum BDG (88.52%, P < 0.001). Besides, mNGS performs remarkably well in identifying co-pathogens of PJP patients infected with HIV. In addition to P. jirovecii, 82 cases (82.83%) of other co-pathogens were identified based on mNGS. Moreover, thirty-four patients (34.34%) increased therapeutic dose of trimethoprim-sulfamethoxazole (TMP-SMZ) based on BALF P. jirovecii PCR. Based on the mNGS results, initial antimicrobial treatment was modified in 86.87% (86/99) of PJP patients. BALF mNGS and real-time PCR are two powerful techniques for rapid diagnosis of PJP with high specificity and sensitivity. Moreover, the benefit of mNGS is that it may identify other organisms besides PJP and it may benefit proper and prompt treatment.

Dismal prognosis of Pneumocystis jirovecii pneumonia in patients with multiple myeloma

Patients with multiple myeloma (MM) are at high risk for infections, including opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). We conducted a retrospective analysis of patients with MM developing PJP over a 6-year period between January 2016 and December 2021 at the University Hospital of Würzburg by screening cases of microbiologically documented PJP. A total of 201 positive results for P. jirovecii in respiratory specimens were retrospectively retrieved through our microbiology database. Of these cases, 13 patients with MM fulfilled the definition of probable PJP according to EORTC fungal disease definitions. We observed two peaks in PJP incidence, one after stem cell transplantation during first-line treatment (n = 5) and the other in heavily pretreated patients with six or more prior lines of therapy (n = 6). There was high morbidity with nine (69%) patients admitted to the ICU, seven of whom (78%) required mechanical ventilation, and high mortality (62%, n = 8). Notably, only two of the 13 patients (15%) had received PJP prophylaxis. The main reason for discontinuation of prophylaxis with trimethoprim-sulfamethoxazole was grade IV neutropenia. The observed morbidity and mortality of PJP in MM patients are significant and even higher than reported for patients with other hematologic malignancies. According to most current guidelines, the use of prophylaxis would have been clearly recommended in no more than three (23%) of the 13 patients. This illustrates the need to critically reconsider the indications for PJP prophylaxis, which remain incompletely defined.

Diagnostic challenge of Pneumocystis jirovecii pneumonia infection mimicking interstitial lung disease in initially HIV negative patient

Background: Pneumocystis jirovecii pneumonia (PJP) infections are common in immunocompromised patients and are rarely found in immunocompetent patients. Lung radiology in PJP patients could mimic the appearance of interstitial lung disease (ILD) and could be used to diagnose HIV-negative patients. Clinicians should rule out false negatives in patients with patterns suggestive of opportunistic infections and risk factors for HIV infection. Case illustration: A 34-year-old man presented with a chief complaint of shortness of breath, had history of 15 years of smoking, and daily chlorine exposure. The radiology pattern and initial HIV-negative test results suggested an ILD diagnosis. Owing to persistent symptoms despite initial management and the presence of risk factors, repeat HIV testing was initiated and was positive. The patient was treated with cotrimoxazole and showed rapid clinical improvement. Discussion: The diagnosis of PJP in our patient was based on radiology and an HIV-positive status. In patients who are not immunocompromised, the diagnosis of PJP is unlikely, and other diagnoses, such as ILD, should be considered. However, in the HIV testing window period of infection, a poor advanced state of HIV could cause a false negative result. Therefore, clinical judgement is essential in suspecting such a result. The empirical treatment course of cotrimoxazole has been shown to provide better clinical outcomes in PJP. Conclusion: The possibility of PJP must be considered in patients with initially HIV-negative results, especially in patients with risk factors and clinical symptoms suggestive of immunocompromise. While some ILD showed similar PJP, the risk factors for ILD and PCP could be distinguishing factors. Retesting for HIV infection can confirm the diagnosis and rule out false-negative results.

Prevalence of Pneumocystis jirovecii Colonization in Non-Critical Immunocompetent COVID-19 Patients: A Single-Center Prospective Study (JiroCOVID Study).

Pneumocystis jirovecii pneumonia (PJP) is an invasive fungal infection (IFI) that occurs mainly in immunocompromised hosts. After observing a high prevalence of PJP as a complication of COVID-19 in immunocompetent patients, we conducted a study to evaluate the prevalence of P. jirovecii colonization with PCR on oral washing samples (OWS) among non-immunocompromised and non-critical patients admitted with COVID-19 pneumonia at our university hospital. All patients over 18 years of age admitted to the Infectious Diseases Unit for SARS-CoV-2 pneumonia between July 2021 and December 2022 were included. Patients undergoing invasive mechanical ventilation or ECMO, those with risk factors for developing PJP, and those receiving prophylaxis for P. jirovecii were excluded. Samples were collected by gargling with 10 mL of 0.9% NaCl on day 14 of the hospital stay or at discharge. Of 290 screened patients, 59 (20%) met the inclusion criteria and were enrolled. Only 1 of 59 patients (1.7%) tested positive for P. jirovecii detection with PCR, and the same patient was the only one to develop PJP in the follow-up period. Our results are in line with the previous findings of other studies that confirmed a very low prevalence of P. jirovecii colonization on OWS in the immunocompetent population. Despite the limitations of the study, the fact that the only patient who tested positive for P. jirovecii was the only one in our cohort to develop PJP leads us to reflect on the role of this non-invasive sample in predicting the risk of PJP in patients with COVID-19.

Negative serum (1,3) -β-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR

ObjectiveThe current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.MethodsThis was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.ResultsTwo hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.ConclusionsSerum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

IMMU-54. PNEUMOCYSTIS JIROVECII PNEUMONIA INFECTION IN A PATIENT WITH ANAPLASTIC ASTROCYTOMA AND RADIATION NECROSIS IN THE SETTING OF CORTICOSTEROID AND PEMBROLIZUMAB USE

Abstract We present a case with anaplastic astrocytoma and radiation-induced brain necrosis, diagnosed with pneumocystis jirovecii pneumonia(PJP) while receiving corticosteroid and pembrolizumab, an immune checkpoint inhibitor(ICI). ICIs have significantly changed management of many cancer types and are known to be associated with immune related adverse events(irAEs). Recently, concerns have emerged regarding the potential relationship between ICI use and infection risks, and PJP, a rare opportunistic infection, has been reported in patients with ICI treatments with or without corticosteroid use. A 40-year-old man with anaplastic astrocytoma and radiation-induced brain necrosis on corticosteroid and pembrolizumab presented with high fever and tachycardia over three days, and the patient later developed hypoxia and cough. The patient was on dexamethasone for brain radiation necrosis for two months and he received one dose of pembrolizumab two weeks prior to his symptom onset, based on genetic information that showed hypermutated tumor and abnormal DNA mismatch repair protein expression. Chest CT showed abnormal findings from infectious or inflammatory process. Bronchoalveolar lavage sample confirmed positive pneumocystis jiroveci PCR test, confirmed PJP, and he was treated with clindamycin, primaquine, and prednisone. To the best of our knowledge, this is the first reported case of PJP in a patient with primary brain tumor receiving corticosteroid and pembrolizumab. ICIs are being investigated in patients with primary brain tumors and wildly used in patients with malignancies with frequent central nervous system involvements, such as malignant melanomas and non-small cell lung cancers. Awareness of risk for infectious conditions including PJP in patients on ICI treatment, especially with corticosteroid use is crucial for implementing appropriate prophylactic measures and prompt diagnosis and treatment interventions.

Clinical significance of mutations in dihydropteroate synthase in Pneumocystis jirovecii pneumonia among non-HIV-infected patients

BackgroundDihydropteroate synthase (DHPS) mutations may be associated with trimethoprim-sulfamethoxazole resistance in Pneumocystis jirovecii pneumonia (PCP) and worse clinical outcomes. However, the clinical significance of DHPS mutations in PCP among non-human immunodeficiency virus (HIV)-infected patients remains unclear. MethodsPatients with PCP in three tertiary referral hospitals in Taiwan between 2016 and 2020 were retrospectively enrolled. Two point mutations, Thr55Ala and Pro57Ser, in the DHPS protein were analysed. Patients with invalid DHPS mutations in the respiratory specimen, chronic respiratory failure, receiving endotracheal intubation for surgical intervention, HIV infection, Pneumocystis jirovecii colonisation, and no lactate dehydrogenase (LDH) data were excluded. The primary outcome was 30-day survival. ResultsA total of 215 patients were analysed. Mutants inside DHPS were found in 78 patients (36.3%) and 68 patients (31.6%) died within 30 days. A total of 214 patients (99.5%) received trimethoprim-sulfamethoxazole as the first-line treatment. The rates of mechanical ventilation, 30-day, and in-hospital mortality were similar between wild-type and mutant DHPS PCP. After adjusting for important confounders, LDH > 500 µ/L (adjusted hazard ratio [aHR] = 2.448, P = 0.001), pneumonia severity index > 135 mg/dL (aHR = 1.689, P = 0.049), and having solid tumours (aHR = 1.832, P = 0.034) were independently associated with higher mortality. In subgroup analysis, mutant DHPS PCP patients had less 30-day mortality among patients aged > 65 years (P = 0.049), with lymphopenia (P = 0.040), and those without solid tumour (P = 0.045). ConclusionsIn non-HIV-infected PCP, point mutants inside DHPS may not be associated with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted.

MO8-5 Pneumocystis jiroveci pneumonia in patients receiving ddAC for breast cancer: A single center retrospective study

MO8-5 Pneumocystis jiroveci pneumonia in patients receiving ddAC for breast cancer: A single center retrospective study