Treatment of Pneumocystis jirovecii pneumonia in non-human immunodeficiency virus-infected patients using a combination of trimethoprim-sulfamethoxazole and caspofungin

BACKGROUND Pneumocystis jirovecii pneumonia(PJP)is an infectious disease common in immunocompromised hosts.However,the currently,the clinical characteristics of non-HIV patients with PJP infection have not been fully elucidated.AIM To explore efficacy of trimethoprim–sulfamethoxazole(TMP-SMX)and caspofungin for treatment of non-human immunodeficiency virus(HIV)-infected PJP patients.METHODS A retrospective study enrolled 22 patients with non-HIV-infected PJP treated with TMP-SMX and caspofungin from 2019 to 2021.Clinical manifestations,treatment and prognosis of the patients were analyzed.RESULTS Five patients presented with comorbidity of autoimmune diseases,seven with lung cancer,four with lymphoma,two with organ transplantation and four with membranous nephropathy associated with use of immunosuppressive agents.The main clinical manifestations of patients were fever,dry cough,and progressive dyspnea.All patients presented with acute onset and respiratory failure.The most common imaging manifestation was ground glass opacity around the hilar,mainly in the upper lobe.All patients were diagnosed using next-generation sequencing,and were treated with a combination of TMP-SMX and caspofungin.Among them,17 patients received short-term adjuvant glucocorticoid therapy.All patients recovered well and were discharged from hospital.CONCLUSION Non-HIV-infected PJP have rapid disease progression,high risk of respiratory failure,and high mortality.Combination of TMP-SMX and caspofungin can effectively treat severe non-HIVinfected PJP patients with respiratory failure.

Metagenomic next-generation sequencing for pneumocystis jirovecii pneumonia in patients with connective tissue disease

Background:Accurate diagnosis of Pneumocystis jirovecii pneumonia(PJP)is challenging,and the delayed diagnosis of PJP is associated with high mortality in patients with connective tissue disease(CTD).Metagenomic next-generation sequencing(mNGS)technology facilitates etiological diagnosis of various infectious diseases,with promising application in diagnosing PJP.This study aimed to investigate the value of mNGS using bronchoalveolar lavage fluid(BALF)for diagnosing PJP infection.Methods:Data from 55 patients with CTD and suspected pulmonary infection was retrospectively collected and analysed.A PJP group and non-PJP group were formed.The clinical manifestations,laboratory test results,treatment methods,and outcomes were summarized.BALF mNGS results were compared with traditional pathogen tests(TPT)and serum 1,3-beta-D-glucan(BDG)testing.Results:The mean age of PJP patients was 54 years,and 59%(10/17)of the patients were female.A significant difference was found between the average daily dose of prednisone administered to the PJP group and non-PJP group(25 mg vs.16 mg,P<0.001).The PJP group had a significantly higher incidence of dyspnoea(88%[15/17]vs.16%[6/38],P<0.001)and elevated serum BDG level(167.73 vs.30.67 pg/mL,P<0.001).BALF mNGS was more sensitive than both TPT(100%[95%confidence interval{CI}:77.1%-100%]vs.11.8%[95%CI:2.1%-37.7%],P<0.001)and serum BDG(100%[95%CI:77.1%-100%]vs.85.7%[95%CI:42%-99.2%],P<0.001).BALF mNGS was more specific than serum BDG(89.5%[95%CI:74.3%-96.6%]vs.46.7%[95%CI:22.3%-72.6%],P=0.493).Co-infection with cytomegalovirus(CMV)was more common in the PJP patients than in the non-PJP patients(59%[10/17]vs.11%[4/38],respectively,P<0.001).Conclusion:BALF mNGS technology is highly effective for diagnosing PJP in patients with CTD and identifying co-infections.

Pneumocystis jirovecii diagnosed by next-generation sequencing of bronchoscopic alveolar lavage fluid: A case report and review of literature

BACKGROUND The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma(RCC), thus significantly improving patient survival. The incidence of rare drug-related adverse events has gained increased attention.CASE SUMMARY We report a patient with advanced RCC treated with multiple lines of molecular targeted agents and immune checkpoint inhibitors, who developed a pulmonary infection after treatment with everolimus in combination with lenvatinib. Determining the pathogenic organism was difficult, but it was eventually identified as Pneumocystis jirovecii by next-generation sequencing(NGS) of bronchoscopic alveolar lavage fluid(BALF) and successfully treated with trimethoprim-sulfamethoxazole.CONCLUSION Rare pulmonary infections caused by molecular targeted agents are not uncommon in clinical practice, but their diagnosis is difficult. Evaluating BALF with NGS is a good method for rapid diagnosis of such infections.

A clinical comparative study of polymerase chain reaction assay for diagnosis of pneumocystis pneumonia in non-AIDS patients

Background Pneumocystis jirovecii pneumonia （PCP） is one of the most common and fatal infections in non-AIDS immunocompromised patients, which is difficult to diagnose by traditional morphologic methods. This study evaluated polymerase chain reaction （PCR） assays of Pneumocystis jirovecii mitochondrial large subunits ribosomal RNA in sputum and bronchioalveolar lavage fluid （BALF） for diagnosing PCP. Methods Sputum and BALF specimens from two groups were collected： one group （PCP group） included 20 patients definitely diagnosed of PCP by Gomori methenamine silver （GMS） stains of BALF; the other group （non-PCP group） included 40 patients. Each specimen was examined by GMS stains and PCR assays. Results GMS stains of BALF in PCP group were 100% positive （20/20）, GMS stains of sputum in PCP group were 35% positive （7/20）; GMS stains of BALF in non-PCP group were 100% negative （40/40）, GMS stains of sputum in non-PCP group were 100% negative （40/40）. PCR assays of BALF in PCP group were 100% positive （20/20）, PCR assays of sputum in PCP group were 100% positive （20/20）; PCR assays of BALF in non-PCP group were 100% negative （40/40）, PCR assays of sputum in non-PCP group were 100% negative （40/40）. Sensitivity and specificity of PCR assays of sputum and BALF were both 100%; positive and negative predictive values were also both 100%. Conclusion The diagnostic value of PCR assays of Pneumocystisjirovecii mitochondrial large subunits ribosomal RNA on sputum and BALF for pneumocystis pneumonia are both high and equivalent.