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American Journal of Transplantation :... Apr 2024Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort...
Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.
Topics: Female; Humans; Middle Aged; Europe; Glucocorticoids; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Transplant Recipients; Male; Aged
PubMed: 37977229
DOI: 10.1016/j.ajt.2023.11.003 -
Antimicrobial Agents and Chemotherapy Mar 2024cyst life forms contain abundant β-glucan carbohydrates, synthesized using β-1,3 and β-1,6 glucan synthase enzymes and the donor uridine diphosphate (UDP)-glucose....
cyst life forms contain abundant β-glucan carbohydrates, synthesized using β-1,3 and β-1,6 glucan synthase enzymes and the donor uridine diphosphate (UDP)-glucose. In yeast, phosphoglucomutase (PGM) plays a crucial role in carbohydrate metabolism by interconverting glucose 1-phosphate and glucose 6-phosphate, a vital step in UDP pools for β-glucan cell wall formation. This pathway has not yet been defined in . Herein, we surveyed the and genomes, which predicted a homolog of the major PGM enzyme. Furthermore, we show that PjPgm2p and PmPgm2p function similarly to the yeast counterpart. When both homologs are heterologously expressed in cells, both genes can restore growth and sedimentation rates to wild-type levels. Additionally, we demonstrate that yeast cell lysates expressing the two transcripts individually can restore PGM activities significantly altered in the yeast strain. The addition of lithium, a competitive inhibitor of yeast PGM activity, significantly reduces PGM activity. Next, we tested the effects of lithium on viability and found the compound displays significant anti- activity. Finally, we demonstrate that a para-aryl derivative (ISFP10) with known inhibitory activity against the PGM protein and exhibiting 50-fold selectivity over the human PGM enzyme homolog can also significantly reduce Pmpgm2 activity . Collectively, our data genetically and functionally validate phosphoglucomutases in both and and suggest the potential of this protein as a selective therapeutic target for individuals with pneumonia.
Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Phosphoglucomutase; Saccharomyces cerevisiae; Lithium; Pneumocystis; beta-Glucans; Phosphates; Glucose; Uridine Diphosphate
PubMed: 38259086
DOI: 10.1128/aac.00756-23 -
Chest Jun 2024Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical... (Observational Study)
Observational Study
BACKGROUND
Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated.
RESEARCH QUESTION
Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease?
STUDY DESIGN AND METHODS
In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality.
RESULTS
Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010).
INTERPRETATION
Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.
Topics: Humans; Pneumonia, Pneumocystis; Male; Female; Retrospective Studies; Middle Aged; Prognosis; Aged; Pneumocystis carinii; Immunocompromised Host; Risk Factors
PubMed: 38215935
DOI: 10.1016/j.chest.2024.01.015 -
Medical Mycology Dec 2023Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary... (Observational Study)
Observational Study
Bronchial aspirate obtained during bronchoscopy yields increased fungal load compared to bronchoalveolar lavage fluid in patients at risk of invasive aspergillosis and Pneumocystis pneumonia.
Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary aspergillosis (IPA). However, procedural variations exist across medical centers and wards. This study aimed to compare the diagnostic potential of BALF and bronchial aspirate (BA) obtained during bronchoscopy in 173 patients suspected of fungal infections. A prospective observational study was conducted from April 2020 to November 2021. BALF and BA were collected during bronchoscopy and subjected to direct examination, fungal culture, Aspergillus fumigatus qPCR (AfqPCR), and Pneumocystis jirovecii qPCR (PjqPCR). Galactomannan detection was performed on BALF. Patients were classified based on established European Organization for Research and Treatment of Cancer (EORTC) criteria. Out of 173 patients, 75 tested positive for at least one test in BA or BALF. For Aspergillus, proportion of positive AfqPCR (14.5% vs. 9.2%; P < 0.0001) and fungal loads (Cq of 31.3 vs. 32.8; P = 0.0018) were significantly higher in BA compared to BALF. For Pneumocystis, fungal loads by PjqPCR was also higher in BA compared to BALF (Cq of 34.2 vs. 35.7; P = 0.003). BA only detected A. fumigatus and P. jirovecii in 12 (42.9%) and 8 (19.5%) patients, respectively. BA obtained during a BAL procedure can be a suitable sample type for increased detection of P. jirovecii and A. fumigatus by qPCR. The use of BA in diagnostic algorithms requires further investigation in prospective studies.
Topics: Humans; Bronchoalveolar Lavage Fluid; Pneumonia, Pneumocystis; Bronchoscopy; Prospective Studies; Sensitivity and Specificity; Aspergillosis; Invasive Pulmonary Aspergillosis; Pneumocystis carinii; Mannans
PubMed: 37996394
DOI: 10.1093/mmy/myad120 -
International Journal of Clinical... Apr 2024An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs). (Review)
Review
BACKGROUND
An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs).
AIM
This umbrella analysis aimed to assess the potential risk of bias in existing SRs and to summarize the published diagnostic values of NGS in different IDs.
METHOD
We searched PubMed, Embase, and the Cochrane Library until September 2023 for SRs assessing the diagnostic validity of NGS for IDs. Two investigators independently determined review eligibility, extracted data, and evaluated reporting quality, risk of bias, methodological quality, and evidence certainty in the included SRs.
RESULTS
Eleven SRs were analyzed. Most SRs exhibited a moderate level of reporting quality, while a serious risk of bias was observed in all SRs. The diagnostic performance of NGS in detecting pneumocystis pneumonia and periprosthetic/prosthetic joint infection was notably robust, showing excellent sensitivity (pneumocystis pneumonia: 0.96, 95% CI 0.90-0.99, very low certainty; periprosthetic/prosthetic joint infection: 0.93, 95% CI 0.83-0.97, very low certainty) and specificity (pneumocystis pneumonia: 0.96, 95% CI 0.92-0.98, very low certainty; periprosthetic/prosthetic joint infection: 0.95, 95% CI 0.92-0.97, very low certainty). NGS exhibited high specificity for central nervous system infection, bacterial meningoencephalitis, and tuberculous meningitis. The sensitivity to these infectious diseases was moderate. NGS demonstrated moderate sensitivity and specificity for multiple infections and pulmonary infections.
CONCLUSION
This umbrella analysis indicates that NGS is a promising technique for diagnosing pneumocystis pneumonia and periprosthetic/prosthetic joint infection with excellent sensitivity and specificity. More high-quality original research and SRs are needed to verify the current findings.
PubMed: 38570474
DOI: 10.1007/s11096-024-01704-2 -
Annals of Medicine Dec 2023To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori...
AIM
To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-β-d-Glucan (BG) assay.
METHODS
52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed.
RESULTS
The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS ( < .001). The combination of mNGS with serum BG statistically outperformed mNGS or serum BG alone in the areas under the receiver operating characteristic curves (AUCs, = .0013 and = .0015, respectively). Notably, all the blood samples showing positive mNGS for came from PCP patients. The leading co-pathogens among patients with PCP were cytomegalovirus, Epstein-Barr virus and Torque teno virus.
CONCLUSIONS
mNGS shows superiority over several common clinical methods in the diagnosis of suspected PCP. Serum BG in conjunction with mNGS further improved the diagnostic efficacy of mNGS.
Topics: Humans; Pneumonia, Pneumocystis; Epstein-Barr Virus Infections; Sensitivity and Specificity; Herpesvirus 4, Human; High-Throughput Nucleotide Sequencing; Respiratory System
PubMed: 37403381
DOI: 10.1080/07853890.2023.2232358 -
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 -
European Journal of Internal Medicine Sep 2023
Topics: Humans; Dapsone; Pneumonia, Pneumocystis; Anemia, Hemolytic; Methemoglobinemia
PubMed: 37169635
DOI: 10.1016/j.ejim.2023.04.030 -
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 -
PLoS Neglected Tropical Diseases Sep 2023Fungal diseases are associated with high morbidity and mortality, yet their epidemiology and burden are not well addressed. While deaths probably exceed 1.5 million per...
Fungal diseases are associated with high morbidity and mortality, yet their epidemiology and burden are not well addressed. While deaths probably exceed 1.5 million per year, many cases remain undiagnosed and underreported. Estimating the burden of these diseases is needed for prioritization and implementation of effective control programs. Here we used a model based on population at risk to estimate the burden of serious fungal infections in Sudan. The prevalence of the susceptible population including HIV, TB, cancer, asthma, and COPD was obtained from the literature. Incidence and prevalence of fungal infections were calculated using local data when applicable and if not available then regional or international figures were used. In total, the estimated number of Sudanese suffering from fungal disease is 5 M (10% of the total population). Tinea capitis, recurrent vulvovaginitis and keratitis are estimated to affect 4,127,760, 631,261, and 6,552 patients, respectively. HIV-related mycosis is estimated to affect 5,945 oral candidiasis, 1,921 esophageal candidiasis, 571 Pneumocystis pneumonia, and 462 cryptococcal meningitis cases. Aspergillus infections are estimated as follow: 3,438 invasive aspergillosis, 14,950 chronic pulmonary aspergillosis, 67,860 allergic bronchopulmonary aspergillosis cases, while the prevalence of severe asthma with fungal sensitization and fungal rhinosinusitis was 86,860 and 93,600 cases, respectively. The neglected tropical disease eumycetoma was estimated to affect 16,837 cases with a rate of 36/100,000. Serious fungal infections are quite common in Sudan and require urgent attention to improve diagnosis, promote treatment, and develop surveillance programs.
Topics: Female; Humans; Sudan; Mycoses; Candidiasis; Asthma; HIV Infections
PubMed: 37656764
DOI: 10.1371/journal.pntd.0011464