RESUMO
BACKGROUND: Serum (1,3)-ß-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. METHODS: This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden's index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. RESULTS: Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG's area under the receiver operating characteristic curve was 0.90 (0.87-0.93). At manufacturer's 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09-20.88, p < 0.001), other invasive fungal infections (OR 4.46; 95% CI 2.10-9.49, p < 0.001) and gram-negative bacteremia (OR 29.02; 95% CI 9.03-93.23, p < 0.001). The application of optimal BDG cut-off values determined by Youden's index (252 pg/ml, 390 pg/ml, and 202 pg/ml) specific for all patients and subgroups with or without confounders improved the specificity (79%, 74%, and 88%) and corresponding PPV (75%, 65%, and 85%), while maintaining reasonable sensitivity and NPV. CONCLUSIONS: Tailoring serum BDG cutoff specific to PJP and incorporating consideration of confounders could enhance serum BDG's diagnostic performance in the ICU settings.
Assuntos
Unidades de Terapia Intensiva , Pneumocystis carinii , Pneumonia por Pneumocystis , beta-Glucanas , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/sangue , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , beta-Glucanas/sangue , Pneumocystis carinii/isolamento & purificação , Idoso , Hospedeiro Imunocomprometido , Proteoglicanas , Curva ROC , Sensibilidade e Especificidade , Estado Terminal , AdultoRESUMO
INTRODUCTION: Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. CASE PRESENTATION: A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. CONCLUSION: The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates.
Assuntos
Síndrome Nefrótica , Nocardiose , Nocardia , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/isolamento & purificação , Pneumocystis carinii/genética , Síndrome Nefrótica/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/complicações , Nocardia/isolamento & purificação , Nocardia/genética , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Nocardiose/diagnóstico , Nocardiose/complicações , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/diagnósticoRESUMO
BACKGROUND: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-ß-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. METHODS: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve. RESULTS: Participants had a median age of 60 years (interquartile range [IQR] 49-68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71-0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. CONCLUSION: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.
Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Feminino , Masculino , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Pneumocystis carinii/isolamento & purificação , Fatores de Risco , Canadá/epidemiologia , Broncoscopia , Medição de Risco , Hospitalização , Curva ROC , Modelos LogísticosRESUMO
We report a rare case of a patient with Janus kinase 2-positive myelofibrosis on ruxolitinib, presenting with indolent pneumonia and cavitary lung lesions. Initial transthoracic biopsy was non-specific, but thoracoscopic biopsy revealed necrotising granulomatous disease caused by Pneumocystis jirovecii pneumonia (PJP). The patient, initially treated with trimethoprim-sulfamethoxazole, was switched to atovaquone due to gastrointestinal intolerance. Given the patient's immunosuppression and extensive cavitary lesions, an extended course of atovaquone was administered, guided by serial imaging, resulting in clinical and radiological improvement. Unfortunately, the patient later passed away from a severe SARS-CoV-2 infection before complete radiographic resolution was observed. This case highlights the importance of recognising atypical PJP presentations causing granulomatous disease in immunosuppressed patients. While rare, documenting such cases may improve diagnosis using less invasive methods and help determine optimal treatment durations for resolution of these atypical infections.
Assuntos
Nitrilas , Pneumocystis carinii , Pneumonia por Pneumocystis , Mielofibrose Primária , Pirazóis , Pirimidinas , Humanos , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/diagnóstico , Pirimidinas/uso terapêutico , Pirazóis/uso terapêutico , Pneumocystis carinii/isolamento & purificação , Masculino , Evolução Fatal , COVID-19/complicações , Atovaquona/uso terapêutico , Hospedeiro Imunocomprometido , Idoso , SARS-CoV-2RESUMO
Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection. Herein, we exploited a novel detection method for P. jirovecii by combining recombinase polymerase amplification (RPA) of nucleic acids isothermal amplification and the trans cleavage activity of Cas12a. The factors influencing the efficiency of RPA and Cas12a-mediated trans cleavage reaction, such as RPA primer, crRNA, the ratio of crRNA to Cas12a and ssDNA reporter concentration, were optimized. Our RPA-Cas12a-based fluorescent assay can be completed within 30-40 min, comprising a 25-30 min RPA reaction and a 5-10 min trans cleavage reaction. It can achieve a lower detection threshold of 0.5 copies/µL of target DNA with high specificity. Moreover, our RPA-Cas12a-based fluorescent method was examined using 30 artificial samples and demonstrated high accuracy with a diagnostic accuracy of 93.33%. In conclusion, a novel, rapid, sensitive, and cost-effective RPA-Cas12a-based detection method was developed and demonstrates significant potential for on-site detection of P. jirovecii in resource-limited settings.
Assuntos
Técnicas de Amplificação de Ácido Nucleico , Pneumocystis carinii , Sensibilidade e Especificidade , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Técnicas de Diagnóstico Molecular/métodos , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Proteínas Associadas a CRISPR/genética , DNA Fúngico/genética , Recombinases/metabolismo , Recombinases/genética , Proteínas de BactériasRESUMO
BACKGROUND: Systemic 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. METHODS: We 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 KaplanâMeier survival analyses were conducted to explore prognostic factors for survival. RESULTS: There 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. CONCLUSIONS: The mortality rate of patients with SLE-PJP is still high. Hyperglycemia, decreased C3, and thrombocytopenia are independent survival risk factors.
Assuntos
Lúpus Eritematoso Sistêmico , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Feminino , Masculino , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/mortalidade , Adulto , Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/microbiologia , Prognóstico , Pessoa de Meia-Idade , Pneumocystis carinii/isolamento & purificação , Estimativa de Kaplan-MeierAssuntos
Reação em Cadeia da Polimerase , Humanos , Reações Falso-Negativas , Pneumocystis/genética , Pneumocystis/isolamento & purificação , Pneumocystis/classificação , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Reação em Cadeia da Polimerase/métodosRESUMO
BACKGROUND: Metagenomic 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. METHODS: Totally 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-ß-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. RESULTS: Pneumocystis 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. CONCLUSIONS: The 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.
Assuntos
Líquido da Lavagem Broncoalveolar , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Pneumocystis carinii/isolamento & purificação , Pneumocystis carinii/genética , Líquido da Lavagem Broncoalveolar/microbiologia , Lactente , Criança , Metagenômica/métodos , beta-Glucanas , Unidades de Terapia Intensiva PediátricaRESUMO
Background: Compared with Human Immunodeficiency Virus (HIV) patients, non-HIV patients with Pneumocystis pneumonia (PCP) have more rapid onset, more rapid progression, and higher mortality. Objectives: To investigate the predictive value of variables obtained upon hospital admission for in-hospital death and 90-day outcomes in non-HIV-PCP patients with respiratory failure (RF). Methods: This was a single center retrospective study in a tertiary care institution over 15 years. It included all adults inpatients (≥18 years old) with laboratory confirmed non-HIV-PCP with RF who were discharged or died from Peking University First Hospital between April 1st, 2007 and November 1st, 2022. Epidemiological, clinical, laboratory, imaging and outcome data were collected from patient records. Results: In this study, a total of 146 non-HIV-PCP patients with RF were included. There were 57 patients (39%) died during hospitalization, 44 patients (53%) died in Intensive care unit (ICU). A total of 137 patients completed 90 days of follow-up, of which 58 (42.3%) died. The multivariable regression analysis revealed that a CD8+ T cell count <115/µl (P=0.009), bronchoalveolar lavage fluid (BALF)-neutrophil percentage ≥50% (P=0.047), the time from corticosteroids withdrawal to symptom onset ≤5 days (P=0.012), and the time from visit to initiation of sulfonamides ≥2 days (P=0.011) were independent risk factors for in-hospital death. Furthermore, a CD8+ T cell count < 115/µl (P=0.001) and the time from visit to initiation of sulfonamides therapy ≥2 days (P=0.033) was independently associated with 90-day all-cause death. Conclusions: A low CD8+ T cell count in peripheral blood, a high percentage of BALF-neutrophils, a short time from corticosteroids withdrawal to symptom onset, and a long time from visit to initiation of sulfonamides are associated with poor prognosis in non-HIV-PCP patients with RF.
Assuntos
Pneumonia por Pneumocystis , Insuficiência Respiratória , Humanos , Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Líquido da Lavagem Broncoalveolar/microbiologia , Linfócitos T CD8-Positivos/imunologia , Unidades de Terapia Intensiva , Hospitalização , Centros de Atenção Terciária , Neutrófilos , Fatores de Risco , Mortalidade Hospitalar , Infecções por HIV/complicações , Pneumocystis carinii/isolamento & purificaçãoRESUMO
BACKGROUND: Kidney transplant recipients (KTRs) are at an elevated risk of progressing to severe infections upon contracting COVID-19. We conducted a study on risk factors and multi-pathogen infections in KTRs with SARS-CoV-2 Omicron variant. METHODS: KTRs were subjected to a thorough etiological evaluation. Whenever feasible, they were also provided with bronchoscopy and bronchoalveolar lavage to enable metagenomic next-generation sequencing (mNGS), ideally within a 48-hour window post-admission. We performed a retrospective analysis for pathogens and risk factors of KTRs with the COVID-19 virus variant Omicron. RESULTS: We included thirty patients in our study, with sixteen exhibiting single infection of COVID-19 and fourteen experiencing co-infections, predominantly with Pneumocystis jirovecii. Notably, patients with severe cases demonstrated significantly elevated levels of C-reactive protein (CRP) and interleukin-6 compared to those with moderate cases (P < 0.05). Furthermore, individuals whose conditions progressed had markedly higher baseline serum creatinine levels than those without such progression (P < 0.05). The presence of heart failure, acute exacerbation of renal dysfunction, and a history of opportunistic infections were significantly associated with a higher likelihood of deterioration and hospital admission due to the SARS-CoV-2 Omicron variant, as compared to the control group (P < 0.05). In subsequent follow-up analysis, the all-cause rehospitalization rate was observed to be 21.4%, with Pneumocystis jirovecii infection accounting for half of these cases. CONCLUSION: Among KTRs, a significant coinfection rate of 47% was observed, with Pneumocystis jirovecii emerging as the predominant pathogen in these cases. The development of heart failure, acute exacerbation of chronic renal dysfunction, and a prior history of opportunistic infections have been identified as potential risk factors that may contribute to clinical deterioration in KTRs. Additionally, Pneumocystis jirovecii infection has been established as a critical factor influencing the rate of all-cause rehospitalization within this patient population.
Assuntos
COVID-19 , Coinfecção , Transplante de Rim , SARS-CoV-2 , Transplantados , Humanos , Transplante de Rim/efeitos adversos , COVID-19/epidemiologia , COVID-19/virologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Fatores de Risco , Adulto , Coinfecção/microbiologia , Coinfecção/virologia , Coinfecção/epidemiologia , Idoso , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/virologia , Pneumonia por Pneumocystis/epidemiologiaRESUMO
BACKGROUND: This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations. METHODS: A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined. RESULTS: Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients. CONCLUSIONS: On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.
Assuntos
Líquido da Lavagem Broncoalveolar , Hospedeiro Imunocomprometido , Pneumonia por Pneumocystis , Sensibilidade e Especificidade , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Humanos , Líquido da Lavagem Broncoalveolar/microbiologia , Reação em Cadeia da Polimerase/métodos , Escarro/microbiologia , Sistema Respiratório/microbiologia , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Infecções por HIV/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
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.
Assuntos
Mortalidade Hospitalar , Neutrófilos , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Pneumocystis carinii/isolamento & purificação , Linfócitos , China/epidemiologia , Modelos Logísticos , Unidades de Terapia Intensiva/estatística & dados numéricos , Biomarcadores/sangue , Modelos de Riscos Proporcionais , AdultoRESUMO
A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis presented to hospital with worsening subacute shortness of breath. CT pulmonary angiogram demonstrated ground glass changes involving all lung lobes with an apicobasal gradient. These changes, combined with long-term steroid exposure for granulomatous hepatitis without pneumocystis prophylaxis, raised concern for pneumocystis jirovecii pneumonia (PJP). A subsequent bronchoscopic lavage specimen was positive on PCR for PJP and the patient was started on appropriate therapy. Clinical and radiological changes initially improved but after completion of therapy, symptoms and radiological abnormalities returned. Retreatment with second-line treatment resulted again in initial improvement followed by relapse with acute deterioration. Further investigations for an alternate diagnosis were made, with a surgical lung biopsy performed finally revealing immunosuppression-related Epstein-Barr virus positive large B cell lymphoma with lymphomatoid granulomatosis of grade 3 pattern.
Assuntos
Granulomatose Linfomatoide , Pneumonia por Pneumocystis , Humanos , Granulomatose Linfomatoide/diagnóstico , Granulomatose Linfomatoide/tratamento farmacológico , Masculino , Diagnóstico Diferencial , Adulto , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumocystis carinii/isolamento & purificação , Tomografia Computadorizada por Raios X , Pulmão/diagnóstico por imagem , Pulmão/patologiaRESUMO
We assessed predictive models (PMs) for diagnosing Pneumocystis jirovecii pneumonia (PCP) in AIDS patients seen in the emergency room (ER), aiming to guide empirical treatment decisions. Data from suspected PCP cases among AIDS patients were gathered prospectively at a reference hospital's ER, with diagnoses later confirmed through sputum PCR analysis. We compared clinical, laboratory, and radiological data between PCP and non-PCP groups, using the Boruta algorithm to confirm significant differences. We evaluated ten PMs tailored for various ERs resource levels to diagnose PCP. Four scenarios were created, two based on X-ray findings (diffuse interstitial infiltrate) and two on CT scans ("ground-glass"), incorporating mandatory variables: lactate dehydrogenase, O2sat, C-reactive protein, respiratory rate (> 24 bpm), and dry cough. We also assessed HIV viral load and CD4 cell count. Among the 86 patients in the study, each model considered either 6 or 8 parameters, depending on the scenario. Many models performed well, with accuracy, precision, recall, and AUC scores > 0.8. Notably, nearest neighbor and naïve Bayes excelled (scores > 0.9) in specific scenarios. Surprisingly, HIV viral load and CD4 cell count did not improve model performance. In conclusion, ER-based PMs using readily available data can significantly aid PCP treatment decisions in AIDS patients.
Assuntos
Serviço Hospitalar de Emergência , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/diagnóstico por imagem , Masculino , Pneumocystis carinii/isolamento & purificação , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome da Imunodeficiência Adquirida/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Carga ViralRESUMO
OBJECTIVES: To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia. METHODS: We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics. RESULTS: Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-ß-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved. CONCLUSION: Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Masculino , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Sistema Respiratório/microbiologia , Adulto Jovem , Técnicas de Diagnóstico Molecular/métodosAssuntos
Síndrome de Cushing , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/diagnóstico , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Masculino , Feminino , Pneumocystis carinii/isolamento & purificação , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an interstitial pneumonia caused by pneumocystis jirovecii (PJ). The diagnosis of PJP primarily relies on the detection of the pathogen from lower respiratory tract specimens. However, it faces challenges such as difficulty in obtaining specimens and low detection rates. In the clinical diagnosis process, it is necessary to combine clinical symptoms, serological test results, chest Computed tomography (CT) images, molecular biology techniques, and metagenomics next-generation sequencing (mNGS) for comprehensive analysis. PURPOSE: This study aims to overcome the limitations of traditional PJP diagnosis methods and develop a non-invasive, efficient, and accurate diagnostic approach for PJP. By using this method, patients can receive early diagnosis and treatment, effectively improving their prognosis. METHODS: We constructed an intelligent diagnostic model for PJP based on the different Convolutional Neural Networks. Firstly, we used the Convolutional Neural Network to extract CT image features from patients. Then, we fused the CT image features with clinical information features using a feature fusion function. Finally, the fused features were input into the classification network to obtain the patient's diagnosis result. RESULTS: In this study, for the diagnosis of PJP, the accuracy of the traditional PCR diagnostic method is 77.58%, while the mean accuracy of the optimal diagnostic model based on convolutional neural networks is 88.90%. CONCLUSION: The accuracy of the diagnostic method proposed in this paper is 11.32% higher than that of the traditional PCR diagnostic method. The method proposed in this paper is an efficient, accurate, and non-invasive early diagnosis approach for PJP.
Assuntos
Redes Neurais de Computação , Pneumocystis carinii , Pneumonia por Pneumocystis , Reação em Cadeia da Polimerase , Tomografia Computadorizada por Raios X , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumocystis carinii/isolamento & purificação , Pneumocystis carinii/genética , Reação em Cadeia da Polimerase/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Diagnóstico Precoce , Adulto , IdosoRESUMO
BACKGROUND: The prevalence of non-HIV related Pneumocystis jirovecii pneumonia (PJP) is increasing with use of immunosuppressive therapies. There are case reports of solid organ transplant recipients on immunosuppressive therapy presenting with mild hypercalcemia, leading to a diagnosis of PJP. Recent studies have shown efficacy of PJP prophylaxis for patients treated with rituximab with a favourable adverse effect profile. CASE PRESENTATION: A 78-year-old male with a history of PR3-ANCA vasculitis, chronic kidney disease and heart failure with reduced ejection fraction presented to our tertiary care hospital with a two-week history of confusion and non-productive cough. Background immunosuppression with rituximab was completed every six months. The patient was found to have hypercalcemia and new infiltrates and ground glass opacities on cross-sectional imaging. Bronchoscopy was performed that was positive for Pneumocystis jirovecii. He was treated with 21 days of trimethoprim-sulfamethoxazole and prednisone with resolution of symptoms and hypercalcemia. CONCLUSIONS: Herein, we present a novel case of PJP in a non-transplant recipient preceded by hypercalcemia. Our case demonstrates the importance for a high suspicion for PJP in chronically immunosuppressed patients on rituximab presenting with PTH-independent hypercalcemia.
Assuntos
Hipercalcemia , Hospedeiro Imunocomprometido , Pneumocystis carinii , Pneumonia por Pneumocystis , Rituximab , Combinação Trimetoprima e Sulfametoxazol , Humanos , Masculino , Idoso , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Prednisona/uso terapêutico , BroncoscopiaRESUMO
INTRODUCTION: With the increasing use of blinatumomab in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), including minimal residual disease (MRD)-positive cases, awareness of its adverse effects has gradually improved. Pneumocystis jirovecii pneumonia (PCP) associated with blinatumomab therapy is rare. CASE PRESENTATION: We present a case of PCP in a patient undergoing blinatumomab therapy. A 70-year-old female diagnosed with Philadelphia-like CRLF2 overexpression B-cell precursor ALL received blinatumomab as consolidation therapy after achieving complete remission with prior induction chemotherapy. On the second day of blinatumomab infusion, she developed intermittent low-grade fever, and chest computed tomography (CT) revealed subtle infiltrates and nodules. Despite empiric trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, she progressed to significant shortness of breath and type I respiratory failure, with increased lactate dehydrogenase and ß-D-glucan assays. Chest CT showed diffuse ground-glass opacities with scattered small nodules. The dry cough prompted next-generation sequencing of peripheral blood, which tested positive for pneumocystis jirovecii without evidence of other pathogens. Consequently, the patient was diagnosed with PCP. The first cycle of blinatumomab had to be discontinued, and therapeutic dosages of TMP-SMX and dexamethasone were administered, resulting in full recovery and stable condition during follow-ups. CONCLUSION: PCP is rare in B-cell precursor ALL patients receiving blinatumomab therapy but manifests with early onset and rapid disease progression. Despite prophylaxis, PCP infection cannot be ignored during blinatumomab therapy. Therefore, heightened attention is warranted when using blinatumomab therapy.
Assuntos
Anticorpos Biespecíficos , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Feminino , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/diagnóstico , Idoso , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/efeitos adversos , Pneumocystis carinii/isolamento & purificação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Tomografia Computadorizada por Raios X , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversosRESUMO
Seronegative human immunodeficiency virus (HIV) infection, where an HIV-specific antibody response is lacking even in chronic or late-stage HIV infections, is extremely rare. Here, we report the case of a 50-year-old Japanese man presenting with Pneumocystis pneumonia who did not produce antibodies against HIV-1 until the initiation of antiretroviral therapy (ART). Fourth-generation antigen-antibody testing temporarily reverted from weakly positive to negative soon after initiating ART, likely due to a reduction in viral load (assessed by p24 antigen levels). His HIV-1 antibody titers remained low or indeterminate even after four years of ART. A literature review suggested that the absence of HIV-1-specific antibody production may be associated with unimpeded HIV replication and rapid CD4+ T cell decline. Seronegative HIV infection can lead to deferred diagnosis and treatment, thereby increasing the risk of transmitting the virus to others or developing opportunistic illnesses. It is important to combine multiple tests for diagnosis, depending on the medical condition. Further studies are required to investigate the host factors involved in the production of HIV-1-specific antibodies.