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Internal and Emergency Medicine Sep 2023The diagnosis of Pneumocystis jirovecii pneumonia (PCP) in patients presenting with severe pneumonia is challenging and delays in treatment were associated with worse... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The diagnosis of Pneumocystis jirovecii pneumonia (PCP) in patients presenting with severe pneumonia is challenging and delays in treatment were associated with worse prognosis. This study aimed to develop a rapid, easily available, noninvasive machine learning diagnostic model for PCP among patients with severe pneumonia.
METHODS
A retrospective study was performed in West China Hospital among consecutive patients with severe pneumonia who had undergone bronchoalveolar lavage for etiological evaluation between October 2010 and April 2021. Factors associated with PCP were identified and four diagnostic models were established using machine learning algorithms including Logistic Regression, eXtreme Gradient Boosting, Random Forest (RF) and LightGBM. The performance of these models were evaluated by the area under the receiver operating characteristic curve (AUC).
RESULTS
Ultimately, 704 patients were enrolled and randomly divided into a training set (n = 564) and a testing set (n = 140). Four factors were ultimately selected to establish the model including neutrophil, globulin, β-D-glucan and ground glass opacity. The RF model exhibited the greatest diagnostic performance with an AUC of 0.907. The calibration curve and decision curve analysis also demonstrated its accuracy and applicability.
CONCLUSIONS
We constructed a PCP diagnostic model in patients with severe pneumonia using four easily available and noninvasive clinical indicators. With satisfying diagnostic performance and good clinical practicability, this model may help clinicians to make early diagnosis of PCP, reduce the delays of treatment and improve the prognosis among these patients.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Retrospective Studies; beta-Glucans; Bronchoalveolar Lavage
PubMed: 37530943
DOI: 10.1007/s11739-023-03353-1 -
Journal of Medical Case Reports Feb 2024Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus...
INTRODUCTION AND IMPORTANCE
Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus (HIV) + patients. We describe a case of PJP pneumonia which provided a diagnostic challenge in a patient who presented with no known risk factors leading to a delay in initiation of appropriate antibiotic therapy.
CASE PRESENTATION
A 71-year-old previously healthy white/Caucasian male presented with subacute hypoxic respiratory failure due to multifocal pneumonia with diffuse bilateral ground glass opacities with consolidations despite prior treatment with antibiotics and steroids. He was admitted and started on intravenous broad-spectrum antibiotics but continued to deteriorate, eventually requiring intubation and transfer to the ICU. Bronchoscopy revealed PJP and treatment was initiated, but the patient developed refractory shock and multiorgan failure, and ultimately died. It was later discovered that he was HIV-1 positive.
CLINICAL DISCUSSION
PJP, as a potential cause of his presentation, was not considered given that our patient lacked any overt risk factors for PJP pneumonia. He continued to worsen despite broad spectrum antibiotic therapy and hence bronchoscopy was pursued. His clinical profile, in hindsight, was suspicious for PJP pneumonia and early PJP-directed antibiotic therapy may have prevented a fatal outcome, as in this case. There was an element of cognitive bias across multiple providers which may have contributed to the delay in treatment despite his rapid clinical decline while on conventional pneumonia treatment protocol. His diagnosis was later evident when his BAL-DFA grew PJP in addition to his low levels of CD4 and CD8 cells. He was found to be HIV-1 positive five days after his death; there was a delay in this diagnosis since all positive HIV tests from the hospital are reported as 'pending' until the presumptive positive sample goes to the Connecticut Department of Public Health State laboratory for the confirmatory test. PJP-targeted therapies were initiated later in our patient's hospital course when the infection had progressed to refractory septic shock with multiorgan failure and eventual death.
CONCLUSION
PJP pneumonia is a fatal disease if not recognized early in the course of illness, and the patient usually undergoes multiple antibiotic regimens before they are diagnosed and receive appropriate clinical care. The gold standard of diagnostic testing for PJP is by obtaining bronchial washings through a flexible bronchoscopy and the turnaround time for such results may take a few days to result. A significant proportion of patients may not have any overt risk factors of immunosuppression and early empiric treatment for PJP may be clinically appropriate as the delay in diagnosis may be associated with significant morbidity and mortality risk.
Topics: Humans; Male; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Risk Factors; Anti-Bacterial Agents; HIV Infections
PubMed: 38342895
DOI: 10.1186/s13256-024-04350-4 -
BMJ Case Reports May 2024A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis...
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.
Topics: Humans; Lymphomatoid Granulomatosis; Male; Diagnosis, Differential; Adult; Pneumonia, Pneumocystis; Pneumocystis carinii; Tomography, X-Ray Computed; Lung
PubMed: 38821563
DOI: 10.1136/bcr-2024-259969 -
Seminars in Arthritis and Rheumatism Dec 2023Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023.
RESULTS
Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk.
CONCLUSION
Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
Topics: Humans; Connective Tissue Diseases; Cyclophosphamide; Lung Diseases, Interstitial; Mycophenolic Acid; Glucocorticoids; Risk Factors; Diabetes Mellitus; Lymphopenia; Biological Products; Invasive Fungal Infections
PubMed: 37633041
DOI: 10.1016/j.semarthrit.2023.152257 -
Infectious Diseases (London, England) Feb 2024To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens.
OBJECTIVE
To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens.
METHODS
This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing.
RESULTS
A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%).
CONCLUSION
Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.
Topics: Humans; Bronchoalveolar Lavage Fluid; Prospective Studies; Nanopores; Pneumonia; Streptococcus pneumoniae; High-Throughput Nucleotide Sequencing; Sensitivity and Specificity
PubMed: 37934028
DOI: 10.1080/23744235.2023.2276785 -
BMJ Open Oct 2023We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19. (Review)
Review
OBJECTIVES
We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19.
STUDY DESIGN
Scoping review, using PRISMA-ScR reporting standards. Medline, PubMed, AMED, Embase, CINAHL and LitCovid databases were searched between 16 and 22 February 2021, with studies included from any publication date up to and including the search date.
INTERVENTION
Short exercise tests.
PRIMARY OUTCOME MEASURES
Safe discharge from hospital, readmission rate, length of hospital stay, mortality. Secondary outcomes measures: safety, feasibility and reliability.
RESULTS
Of 1612 original records screened, 19 studies were included in the analysis. These used a variety of exercise tests in patients with chronic obstructive pulmonary disease, suspected pulmonary embolism and pneumocystis carinii pneumonia, heart failure or critical illness. Only six studies had examined patients with COVID-19, of these two were still recruiting to evaluate the 1 min sit-to-stand test and the 40-steps test. There was heterogeneity in patient populations, tests used and outcome measures. Few exercise tests have been validated to support discharge decisions. There is currently no support for short exercise tests for triage of care in patients with COVID-19.
CONCLUSIONS
Further research is needed to aid clinical decision-making at discharge from hospital.
Topics: Humans; COVID-19; Patient Discharge; Exercise Test; Reproducibility of Results; Hospitals
PubMed: 37907292
DOI: 10.1136/bmjopen-2022-068169 -
Infection and Drug Resistance 2023We report a case of pneumocystis jiroveci pneumonia (PJP) in a 46-year-old woman, who previously underwent kidney transplant for chronic renal failure. She did not...
Case Report: Comprehensive Management of Pneumocystis Jiroveci Pneumonia (PJP) and Secondary Infections of Multiple-Drug Resistant and in a Kidney Transplant Recipient with Sulfonamide Allergies.
We report a case of pneumocystis jiroveci pneumonia (PJP) in a 46-year-old woman, who previously underwent kidney transplant for chronic renal failure. She did not receive PJP prophylaxis treatment for the history of sulfonamide allergies. Four months after renal transplantation, the patient had cough, chest tightness, and shortness of breath. Procalcitonin (PCT) (0.06 ng/mL) and C-reactive protein (CRP) (5.33 mg/L) were normal, but the level of 1, 3-β-D-glucan test (G test, 193.89 pg/mL) were elevated. Metagenomics next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) rapidly and accurately identified . Through sulfonamide desensitization and sulfamethoxazole-trimethoprim (TMP-SMX) combined with caspofungin (CAS) treatment, PJP was controlled. However, the patients' conditions were worsen for the hospital-acquired secondary pulmonary infection. A second BALF mNGS identified and carrying carbapenem drug resistance genes, which were confirmed by subsequent culture and antimicrobial susceptibility test within 3 days. Finally, symptoms, such as chest tightness, cough, and shortness of breath, were improved and she was discharged after combined treatment with meropenem (MEM), polymyxin B (PMB), CAS, and TMP-SMX. In this case, mNGS, culture, and drug susceptibility testing were combined to monitor pathogenic microbial and adjust medication. At present, there are no case reports of mNGS use and sulfonamide desensitization in a kidney transplant recipient with sulfonamide allergies.
PubMed: 37724091
DOI: 10.2147/IDR.S428890 -
Mycopathologia May 2024Pneumocystis pneumonia is a serious lung infection caused by an original ubiquitous fungus with opportunistic behavior, referred to as Pneumocystis jirovecii. P....
Pneumocystis pneumonia is a serious lung infection caused by an original ubiquitous fungus with opportunistic behavior, referred to as Pneumocystis jirovecii. P. jirovecii is the second most common fungal agent among invasive fungal infections after Candida spp. Unfortunately, there is still an inability to culture P. jirovecii in vitro, and so a great impairment to improve knowledge on the pathogenesis of Pneumocystis pneumonia. In this context, animal models have a high value to address complex interplay between Pneumocystis and the components of the host immune system. Here, we propose a protocol for a murine model of Pneumocystis pneumonia. Animals become susceptible to Pneumocystis by acquiring an immunocompromised status induced by iterative administration of steroids within drinking water. Thereafter, the experimental infection is completed by an intranasal challenge with homogenates of mouse lungs containing Pneumocystis murina. The onset of clinical signs occurs within 5 weeks following the infectious challenge and immunosuppression can then be withdrawn. At termination, lungs and bronchoalveolar lavage (BAL) fluids from infected mice are analyzed for fungal load (qPCR) and immune response (flow cytometry and biochemical assays). The model is a useful tool in studies focusing on immune responses initiated after the establishment of Pneumocystis pneumonia.
Topics: Animals; Pneumonia, Pneumocystis; Disease Models, Animal; Bronchoalveolar Lavage Fluid; Lung; Mice; Pneumocystis; Colony Count, Microbial; Pneumocystis carinii; Immunocompromised Host
PubMed: 38709375
DOI: 10.1007/s11046-024-00846-1 -
Annals of Clinical Microbiology and... Nov 2023The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected...
OBJECTIVE
The 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.
METHODS
This 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.
RESULTS
Two 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.
CONCLUSIONS
Serum 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.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Glucans; Retrospective Studies; beta-Glucans; Lung Neoplasms; HIV Infections; Lung Diseases, Interstitial
PubMed: 37986091
DOI: 10.1186/s12941-023-00650-7 -
BMC Pulmonary Medicine Jul 2023Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly...
Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor.
BACKGROUND
Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition.
CASE PRESENTATION
A 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections.
CONCLUSIONS
This case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.
Topics: Male; Humans; Middle Aged; Pneumocystis carinii; Dermatomyositis; Neoplasms; Autoantibodies; Lung Diseases, Interstitial; Transcription Factors; Pneumonia, Pneumocystis; Opportunistic Infections; Weight Loss; Retrospective Studies
PubMed: 37415133
DOI: 10.1186/s12890-023-02542-0