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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 -
Rheumatology (Oxford, England) Jun 2021
Topics: Female; Granulomatosis with Polyangiitis; Humans; Immunologic Factors; Immunosuppression Therapy; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Rituximab
PubMed: 34137871
DOI: 10.1093/rheumatology/keab040 -
The Malaysian Journal of Pathology Dec 2020Report of a 3-month old girl child who died due to multi-systemic infection of cytomegalovirus (CMV) involving the lungs, liver and kidneys along with pneumocystis...
Report of a 3-month old girl child who died due to multi-systemic infection of cytomegalovirus (CMV) involving the lungs, liver and kidneys along with pneumocystis jiroveci pneumonia (PJP). The mother of the child tested positive for CMV IgG and HIV with a very low CD4 count (160/ μl). Co-infection of cytomegalovirus and pneumocystis jiroveci always occurs in the setting of immunocompromise. Congenital CMV infection is transmitted through the placenta, especially during the first trimester and causes severe multi-systemic disease whereas perinatal infection is acquired during childbirth/ breastfeeding where the babies have maternal protective antibodies leading to much milder or asymptomatic infection. PJP is more common in infancy and presents as hypoxic pneumonia. CMV causes cyto-nucleomegaly and classic "owl's eye" inclusions on histology while PJP presents with characteristic fluffy "cotton ball" alveolar exudates.
Topics: Coinfection; Cytomegalovirus Infections; Female; Humans; Immunocompromised Host; Infant; Infectious Disease Transmission, Vertical; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 33361734
DOI: No ID Found -
Zhonghua Jie He He Hu Xi Za Zhi =... Sep 2022To describe the underlying diseases, microbiologic examination and severity of hospitalized patients with pneumonia (PJP) in a tertiary Chinese hospital. We conducted...
To describe the underlying diseases, microbiologic examination and severity of hospitalized patients with pneumonia (PJP) in a tertiary Chinese hospital. We conducted a retrospective analysis of 485 identified PJP patients who were admitted to our hospital between January 2013 and December 2021. Among the 485 enrolled PJP cases, there were 237 males and 248 females, aging (53.3±16.2) years (range from 14 y to 88 y). They were divided into 8 subgroups with variable underlying diseases. There were 209 cases with connective tissue diseases(CTD), 27 cases with non-hematologic malignancies, 38 cases with hematologic malignancies, 81 cases with kidney diseases, 33 cases with idiopathic interstitial pneumonia(IIP), 30 cases infected with human immunodeficiency virus (HIV), and 42 cases with miscellaneous underlying diseases. In the CTD group, there was more females than males, while male patients were predominant in both the malignant and the HIV groups. The was identified in 44.95%(218/485) sputum samples and 92.01%(265/288) bronchoscopic samples. asci were observed at direct microscopic examination with Grocott's methenamine silver stain in 4.95%(24/485)sputum samples and 9.72%(28/288)bronchoscopic samples. DNA fragments were identified by PCR analysis in 43.09%(209/485)sputum samples and 90.63%(261/288)bronchoscopic samples. Among the 8 groups, cytomegaviremia and respiratory failure were most common in the HIV-infected PJP group, but the rates of mechanic ventilation, intensive care unit (ICU) admission and death were the lowest. There were less PJP patients in the IIP group (IIP-PJP) who received mechanic ventilation and admitted to ICU than the other groups except HIV-infected PJP group. However, the mortality rate was highest for the IIP-PJP group. CTD was the most common predisposed underlying disease for our enrolled PJP cases. Cytomegaviremia and respiratory failure were common in HIV-infected PJP patients, but the prognosis of HIV-PJP was slightly better than the others. The disease was more severe, rapidly progressive and fatal in the IIP-PJP group.
Topics: Female; HIV Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiratory Insufficiency; Retrospective Studies
PubMed: 36097925
DOI: 10.3760/cma.j.cn112147-20220303-00170 -
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 -
Journal de Mycologie Medicale Mar 2022To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru.
OBJECTIVES
To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru.
METHODS
A cross sectional study was performed. Infants less than seven months old, without any underlying medical conditions attending the "well baby" outpatient clinic at one hospital in Lima, Peru were prospectively enrolled during a 15-month period from November 2016 to February 2018. All had a nasopharyngeal aspirate (NPA) for detection of P. jirovecii DNA using a PCR assay, regardless of respiratory symptoms. P. jirovecii DNA detection was considered to represent pulmonary colonization contemporaneous with Pneumocystis primary infection. Associations between infants' clinical and demographic characteristics and results of P. jirovecii DNA detection were analyzed.
RESULTS
P. jirovecii DNA was detected in 45 of 146 infants (30.8%) and detection was not associated with concurrent respiratory symptoms in 40 of 45 infants. Infants with P. jirovecii had a lower mean age when compared to infants not colonized (p <0.05). The highest frequency of P. jirovecii was observed in 2-3-month-old infants (p < 0.01) and in the cooler winter and spring seasons (p <0.01). Multivariable analysis showed that infants living in a home with ≤ 1 bedroom were more likely to be colonized; Odds Ratio =3.03 (95%CI 1.31-7.00; p = 0.01).
CONCLUSION
Pneumocystis primary infection in this single site in Lima, Peru, was most frequently observed in 2-3-month-old infants, in winter and spring seasons, and with higher detection rates being associated with household conditions favoring close inter-individual contacts and potential transmission of P. jirovecii.
Topics: Cross-Sectional Studies; Humans; Infant; Peru; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 34598108
DOI: 10.1016/j.mycmed.2021.101202 -
Frontiers in Immunology 2022is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success...
INTRODUCTION
is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success of anti-retroviral therapy for HIV-infected individuals the frequency of PCP in that population has decreased, however, PCP remains a significant cause of morbidity and mortality in individuals with hematologic and solid malignancies, and in individuals treated with immunosuppressive therapies for autoimmune diseases, and following bone marrow and solid organ transplantation. Despite the clinical need, there is no approved vaccine to prevent PCP in vulnerable populations. The ultimate goal of the field is to develop an effective vaccine that can overcome immune deficits in at risk populations and induce long-lasting protective immunity to . Toward this goal, our laboratory has established a model of PCP co-infection in simian immunodeficiency virus (SIV)-infected non-human primates (NHP) and identified a recombinant protein sub-unit vaccine, KEX1, that induces robust anti- immunity in immune-competent macaques that is durable and prevents PCP following simian immunodeficiency virus (SIV)-induced immunosuppression. Type I, or invariant natural killer T (iNKT) cells have the potential to provide B cell help under conditions of reduced CD4+ T cell help.
METHODS
In the present study, we used the SIV model of HIV infection to address whether therapeutic vaccination with the iNKT cell-activating adjuvant α-galactosylceramide (α-GC) and KEX1 (α-GC+KEX1) can effectively boost anti- humoral immunity following virus-induced immunosuppression.
RESULTS
Immunization of antigen-experienced NHPs with α-GC+KEX1 during the early chronic phase of SIV-infection significantly boosted anti- humoral immunity by increasing memory B cells and antibody titers, and enhanced titer durability during SIV-induced immunosuppression. This therapeutic vaccination strategy boosted anti- immune responses during SIV-infection and contributed to protection against co-infection in KEX1-vaccinated macaques.
CONCLUSION
These studies present a novel strategy for stimulating durable anti- humoral immunity in the context of complex, chronic SIV-induced immunosuppression and may be further applied to immunization of other immunosuppressed populations, and toward other common recall antigens.
Topics: Animals; HIV Infections; Pneumocystis; Pneumonia, Pneumocystis; Simian Acquired Immunodeficiency Syndrome; Coinfection; Simian Immunodeficiency Virus; Immunocompromised Host; Vaccines, Synthetic; Primates; Adjuvants, Immunologic; Macaca
PubMed: 36561749
DOI: 10.3389/fimmu.2022.1036658 -
Antimicrobial Agents and Chemotherapy Aug 2022A3IS (Mycosinate) is a synthetic product which only contains ingredients found naturally within honey. A3IS is a broad-spectrum antimicrobial product which produces a...
A3IS (Mycosinate) is a synthetic product which only contains ingredients found naturally within honey. A3IS is a broad-spectrum antimicrobial product which produces a sustained release of hydrogen peroxide at low but therapeutic levels. The product elicits this release through an enzymatic reaction between glucose oxidase and the substrate glucose once the product is hydrated. As medical uses for different honeys are being re-evaluated, the purpose of this study was to evaluate the effects of A3IS against a comprehensive panel of human pathogens, including Pneumocystis species, providing a unique assessment against a panel of eukaryotic pathogens. Without exception, A3IS exhibited significant efficacy at 50% and 100% inhibitory concentrations against a broad spectrum of human pathogens including yeasts, molds (both hyaline and dematiaceous), and dimorphic fungi. Notably, A3IS was effective against fungal strains with a high level of resistance to fluconazole or voriconazole. The 50% inhibitory concentrations for Pneumocystis carinii and P. murina (surrogates for ) were considered "Marked" and "Moderate" on an established rank scale, and would be considered for studies, based on an established pipeline. These results indicate that A3IS is a novel anti-fungal agent against an extensive range of human fungal pathogens.
Topics: Antifungal Agents; Fluconazole; Fungi; Humans; Microbial Sensitivity Tests; Pneumocystis; Pneumonia, Pneumocystis; Voriconazole
PubMed: 35852368
DOI: 10.1128/aac.00521-22 -
Trends in Parasitology Oct 2021The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the...
The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the pandemic era. We discuss the concern of Pneumocystis jirovecii and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfection, their similarities, and the impact of immunosuppression, with a suggested diagnostic pathway for their suspected coinfection.
Topics: COVID-19; Coinfection; Humans; Immunosuppression Therapy; Pandemics; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 34364804
DOI: 10.1016/j.pt.2021.07.010