Pneumocystis Carinii Pneumonia Research Articles

Opportunistic Infections, Mortality Risk, and Prevention Strategies in Patients With Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome

Abstract Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a genetic disorder characterized by bone marrow failure and systemic inflammation, putting patients at risk for infections. This study comprehensively examines the prevalence of opportunistic infections in patients with VEXAS, evaluating their impact on clinical outcomes and potential preventive measures. Methods Patients with confirmed VEXAS were included. Survival analysis and logistic regression were used to identify associations between opportunistic infections and mortality. Infection rates (IRs) for Pneumocystis jirovecii pneumonia (PJP) and alphaherpesviruses were calculated over a prospective 8-month observation period in relationship to prophylaxis. Results Of 94 patients with VEXAS, 6% developed PJP; 15% had alphaherpesvirus reactivation, with varicella zoster virus (VZV) being the most common herpesvirus; and 10% contracted a nontuberculous mycobacterial (NTM) infection. Risk of death was significantly increased per month following a diagnosis of PJP (hazard ratio [HR], 72.41 [95% confidence interval {CI}, 13.67–533.70]) or NTM (HR, 29.09 [95% CI, 9.51–88.79]). Increased odds for death were also observed in patients with a history of herpes simplex virus (HSV) reactivation (odds ratio [OR], 12.10 [95% CI, 1.29–114.80]) but not in patients with VZV (OR, 0.89 [95% CI, .30–2.59]). Prophylaxis for PJP (IR, 0.001 vs 0 per person-day, P < .01) and VZV (IR, 0.006 vs 0 per person-day, P = .04) markedly decreased infection rates with a number needed to treat of 4 and 7, respectively. Conclusions Opportunistic infections are common in patients with VEXAS. Patients who develop PJP, HSV, or NTM are at increased risk for death. Prophylaxis against PJP and VZV is highly effective.

A Systematic Review of Maternal Mortality in African Countries

Introduction: The goal of this review is to investigate maternal mortality rates (MMR) in African countries. Because the MMR of Black women in the United States is 3-5x higher than in White women, this study aims to identify if a similar racial disparity is present in Africa where the majority of the birthing population identifies as Black. Methods: Four bibliographic databases were searched - PubMed, Web of Science Core Collection, Scopus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) – and a variety of search terms were identified, including “Maternal Mortality”, “Ethnic Groups”, “Minority Groups”, “Continental Population Groups”, “Medically Underserved Area”, “Race Factors” and “Racial Disparities”. Inclusion criteria were manuscripts with statistics on maternal mortality or severe maternal morbidity in African countries or regions; exclusion criteria included “wrong outcome”, “wrong study type”, and studies only discussing maternal morbidity without mention of mortality. Papers that were not written in or that did not include information about an African country or region were excluded. Results: Overwhelmingly, hypertension-related mortality was identified as a leading cause of death in nearly every study, followed closely by post-partum hemorrhage, often due to over- or underuse of anticoagulation therapy. Unsafe abortion contributed to higher rates of adolescent mortality (37% of adolescents in one study) while accounting for 9-27% of the overall mortality rate. MMR across the continent varied significantly. Countries with the highest average recorded MMRs include Tunisia (1,820/100,000), Sierra Leone (1,800/100,000), Guinea (1,600/100,000), and Somalia (1,600/100,000). The lowest average MMRs found in this study included Tanzania (120/100,000), Egypt (124.5/100,000), Algeria (160/100,000), and Libya (220/100,000). Factors contributing to higher rates of mortality included extremes in maternal age, with the highest rates being in those older than 40 and younger than 20. Educational status played a large role, with up to 68% of mortality in one study occurring in people considered to be illiterate. Low socioeconomic status and being a member of a minority religious and/or ethnic group within a population corresponded with higher mortality rates, in addition to either late or minimal access to antenatal care (up to 28x higher MMR). A common comorbidity related to maternal mortality was patients having an established HIV diagnosis. Though mortality rates were significant in both HIV-positive and HIV-negative patients, most deaths in HIV-positive patients were related to advanced disease as opposed to obstetric complications, with one study finding the MMR of HIV-infected patients to be 6.2 times higher than HIV-negative patients. Among these deaths, tuberculosis, pneumocystis jirovecii pneumonia, and meningitis were among the most common causes. One study investigated the association between antiretroviral (ART) therapy and decreased rates of HIV-positive mortality. The recorded MMR of both HIV-positive and HIV-negative women decreased over the 10 years in this study; however, the HIV-positive MMR in the third time period was still 3.2 times higher than that of HIV-negative women (4.1 times higher in the second period, 7.1 times higher in the first period) with HIV-positive patients making up 33.3% of maternal deaths. One 2021 study focused on the effects of a COVID-19 infection on maternal outcomes – identifying no statistically significant difference in MMR, except that HIV-positive patients were twice as likely to contract COVID than controls. Conclusion: According to US CDC, the 2020 US national MMR was 23.8 per 100,000 live births, compared with the lowest national MMR in this study - Tanzania at 120/100,000; 6-fold higher than the US national average. In this systematic review, multiple factors were found to contribute to higher MMR, including low socioeconomic status, poor access to trained medical professionals, and patients having untreated or severe comorbidities such as HIV or tuberculosis. Two studies used a data collection method called ‘The Sisterhood Method’ which gathered retrospective data via interviewing women about the maternal outcomes of their biological sisters. Though this method of collection is useful for countries and/or regions that have limited access to electronic medical records (EMR) or census data, it relies on the memory and the willingness of interviewees to provide information, which may create recall bias and alter the validity of those studies. Our work identifies a need for further maternal mortality research to identify differences in healthcare systems across countries (both in Africa and worldwide) leading to higher death rates in some nations. Additionally, training programs (such as “Human Resources for Health,” “Pan-African Academy of Christian Surgeons [PAACS]”, “East, Central, and Southern African Health Community [ECSA-HC]”, etc.) should be supported with funding and other resources to address this crisis, while also supporting ongoing initiatives to expand medical education and training in African countries. Efforts should also be made to increase patient education about early signs of obstetric complications. Though maternal mortality rates have trended downward in recent decades, further research is needed to highlight and address disparities across countries and populations to provide equitable care to all.

The Prevalence, Predisposing Factors, and Outcomes of Pneumocystis jirovecii Pneumonia among Pediatric Inpatients, Northeastern Iran

The Prevalence, Predisposing Factors, and Outcomes of Pneumocystis jirovecii Pneumonia among Pediatric Inpatients, Northeastern Iran

Outcome of Pneumocystis pneumonia in transplant and non-transplant HIV-negative immunocompromised patients.

Previous studies showed HIV-negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among HIV-negative immunocompromised patients. In this retrospective cohort study at the University Health Network, we included all HIV-negative immunocompromised patients who fulfilled the European Organization for Research and Treatment of Cancer (EORTC) PCP diagnosis criteria from December 2018 to December 2019. We compared the demographics, comorbidities, course of illness, and PCP outcome (28-day mortality and composite outcome [i.e., death or intensive care unit (ICU) admission]) between solid organ transplant (SOT) and non-SOT patients. Of 160 non-HIV patients with PCP diagnoses, 118 patients fulfilled EORTC criteria (76 males [64.4%], median [range] age: 65.5 [21-87] years). PCP presentation in SOT recipients (n=14) was more severe than non-SOT patients (n=104): acute presentation (onset <7 days before admission: 11/14 [78.6%] vs. 51/104 [56%], p=.037), shortness of breath (100% vs. 75/104 [74.3%], p=.037), median [range] O2 saturation (88% [75%, 99%] vs. 92%[70%, 99%], p=.040), and supplemental O2 requirement (12/14 [85.7%] vs. 59/104 [56.7%], p=.044). The mortality [4/14, (28.6%) vs. 15/104 (14.4%), p=.176], ICU admission (10/14 [71.4%] vs. 18/104 [17.3%], p<.0001), and mechanical ventilation (8/14 [57.1%] vs. 18/104 [17.3%], p=.0007) in SOT patients was different from non-SOT patients. In multivariable analysis, SOT recipients were at greater risk of composite outcome than non-SOT patients (aOR [CI95%]: 12.25 [3.08-48.62], p<.001). PCP presentation and outcomes in SOT recipients are more severe than in non-SOT patients. Further studies are required to explore the biological reasons for this difference.

Pneumocystis jirovecii pneumonia in non-HIV patients: need for a more extended prophylaxis.

Pneumocystis jirovecii pneumonia (PCP) has a significant mortality rate for non-HIV immunocompromised patients. Prevention is primarily based on combined trimethoprim and sulfamethoxazole (TMP-SMX) but guidelines on pneumocystosis prophylaxis are scattered and not consensual. This study aims to describe PCP in non-HIV patients and to review case by case the prior indication of prophylaxis according to specific guidelines.We included patients with confirmed diagnosis of PCP admitted to one university hospital from 2007 to 2020. Prior indication for pneumocystis prophylaxis was assessed according to the specific guidelines for the underlying pathology or treatment. Of 150 patients with a medical diagnosis of PCP, 78 were included. Four groups of underlying pathologies were identified: hematological pathologies (42%), autoimmune diseases (27%), organ transplantation (17%), and other pathologies at risk of PCP (14%). A small subgroup of 14 patients (18%) had received a prior prescription of pneumocystis prophylaxis but none at the time of the episode. Transfer to intensive care was necessary for 33 (42%) patients, and the mortality rate at 3 months was 20%. According to international disease society guidelines, 52 patients (59%) should have been on prophylaxis at the time of the pneumocystis episode. Lowest compliance with guidelines was observed in the hematological disease group for 24 patients (72%) without prescription of indicated prophylaxis. Infectious disease specialists should draw up specific prophylactic guidelines against pneumocystis to promote a better prevention of the disease and include additional criteria in their recommendations according to individual characteristics to prevent fatal cases.

18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency

Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4+ and/or CD8+ cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.

A combined immune and inflammatory indicator predict the prognosis of severe Pneumocystis jirovecii pneumonia patients: a 12-year, retrospective, observational cohort

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.

Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis.

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. 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. 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. 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.

Cutaneous Pneumocystis Jirovecii Infection in an Allogeneic Stem Cell Transplant Recipient.

Extrapulmonary Pneumocystis jirovecii pneumonia (PJP) infection can happen while receiving pentamidine prophylaxis.It is extremely rare to see a cutaneous infection, and no case has been reported in the last two decades.Trimethoprim-sulfamethoxazole (TMP-SMX) remains the first-line treatment for pulmonary and extrapulmonary PJP.

Should We Reconsider Pneumocystis Pneumonia Presentation and Treatment According to Its Underlying Disease?: An Unsupervised Cluster Analysis of a Retrospective Multicenter Study

Should We Reconsider Pneumocystis Pneumonia Presentation and Treatment According to Its Underlying Disease?: An Unsupervised Cluster Analysis of a Retrospective Multicenter Study

Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study.

Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear. This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality. We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048). This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.

Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients

ObjectiveThe lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with pneumocystis pneumonia (PCP) remains poorly understood. MethodsMulti-omics analysis and machine learning were performed on bronchoalveolar lavage fluid to explore interaction between the lung microbiota and host immunity in PCP. Then we constructed a diagnostic model using differential genes with LASSO regression and validated by qPCR. The immune infiltration analysis was performed to explore the landscape of lung immunity in patients with PCP. ResultsPatients with PCP showed a low alpha diversity of lung microbiota, accompanied by the elevated abundance of Firmicutes, and the differential expressed genes (DEGs) analysis displayed a downregulation of MAPK signaling. The MAPK10, TGFB1, and EFNA3 indicated a potential to predict PCP (AUC = 0.86). The lung immune landscape in PCP showed the lower levels of naïve CD4+ T cells and activated dendritic cells. The correlation analysis of the MAPK signaling pathway-related DEGs and the differential microorganisms at the level of phylum showed that the Firmicutes was negatively correlated with these DEGs. ConclusionWe profiled the characteristics of lung microbiota and immune landscape in PCP, which may contribute to elucidating the mechanism of PCP.

Impact of pneumocystis pneumonia on clinical outcomes in patients with lung malignancy compared to other malignancies.

e20001 Background: Pneumocystis pneumonia (PCP) is an opportunistic infection that causes significant morbidity and mortality in cancer patients. Although infrequent in solid malignancies, limited studies suggest that PCP portends a worse outcome in patients with lung cancer. We examined hospitalization outcomes for PCP among patients with lung cancer relative to other malignancies. Methods: A retrospective cohort analysis using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using ICD-9 and ICD-10 codes, cancer patients admitted for PCP were identified and stratified based on their diagnosis of lung cancer versus other cancer types. Primary outcomes were inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included odds of mechanical ventilation, ICU care, bronchoscopy, and palliative care. Statistical analyses were performed using t-tests, univariate and multivariate logistic regression. Results: Among 5,408 hospitalizations for PCP in cancer patients, 10.6% had a diagnosis of lung cancer and 89.4% had other cancer types. Lung cancer patients were older (mean age: 66 vs 62 years; p = 0.001) and had a higher Charlson comorbidity burden (&gt;2) compared to those with other cancers (69.8 vs 34.2%; p&lt;0.001). 31% of lung cancer patients admitted for PCP died compared to 16% of patients with other cancer types ( p&lt;0.001). Multivariate regression analysis showed that hospitalized PCP patients with lung cancer had two-fold higher odds of hospital-associated mortality relative to those with other cancer types (adjusted odds ratio (aOR): 2.2; 95% confidence interval (CI): 1.39-3.37; p = 0.001). Both cohorts had similar LOS (aOR: 0.86; P=0.61; 95% CI: 0.5-1.5) and THC (β -15,377; p=0.113; 95% CI= -34,407-3,653). Among secondary outcomes, lung cancer patients admitted for PCP had higher odds of mechanical ventilation (25.3 vs 17.7%; aOR: 1.61; p = 0.046) and palliative care utilization (24 vs 13%; p=0.002). Conclusions: Pneumocystis pneumonia is associated with significantly higher inpatient mortality among patients with lung cancer compared to other cancers. These patients also had higher rates of mechanical ventilation and palliative care utilization. Health care providers need to maintain a high index of suspicion to facilitate early diagnosis and intervention in order to mitigate adverse outcomes.[Table: see text]

Trainee-led quality improvement (QI) project examining PCP prophylaxis in patients on chronic, high-dose corticosteroids.

e23211 Background: Patients with cancer who develop Pneumocystis pneumonia (PCP) have 30-day mortality rates estimated to be &gt; 50%. Despite consensus guidelines from the American Society of Clinical Oncology (ASCO) and Infectious Diseases Society of America (IDSA), appropriate PCP prophylaxis is reported as low as 3.9% for patients with solid malignancies on chronic, high-dose corticosteroids. In this trainee-led QI initiative, we investigated rates of appropriate PCP prophylaxis at a tertiary care cancer center and surveyed clinicians regarding barriers to prescribing prophylaxis. Methods: An interprofessional, multidisciplinary team consisting of hematology-oncology fellows and cancer-center level QI staff was established. This analysis combined a retrospective chart review and survey at a tertiary care center. Retrospective chart review examined PCP prophylaxis rates among patients with solid malignancies prescribed high dose/duration corticosteroids per ASCO/IDSA guidelines (≥20mg prednisone equivalents daily for ≥1 month) between May 1, 2022 and May 31, 2023. The survey, conducted between December 2022 and May 2023, assessed prescriber knowledge of, and attitudes towards, appropriate PCP prophylaxis prescription. The survey was open to clinicians across oncology specialties. Results: Over the study period, 297 patients met inclusion criteria for PCP prophylaxis (median age 62, 178 (60%) were male, 212 (71%) were White, and 55 (18%) were Black). Fewer than half of eligible patients were prescribed prophylactic antibiotics (n = 140, 47%). There were no sociodemographic differences between patients prescribed prophylaxis and those not prescribed prophylaxis. Survey responses (n = 71) included 33 (46%) attending physicians, 21 (30%) advanced practice providers, 8 (11%) residents/fellows, and 9 (13%) unknown. Thirty participants (42%) had cared for a patient who developed PCP while on corticosteroids. While 62 participants (87%) had experience prescribing PCP prophylaxis, only 18 (25%) accurately identified the dose and duration of corticosteroids at which prophylaxis is needed. Lack of guideline knowledge/education was the most commonly cited barrier to prophylaxis (Table). Conclusions: Our study shows strikingly fewer than half of eligible patients on chronic, high-dose steroids were prescribed PCP prophylaxis. Lack of provider knowledge and systems-related obstacles were noted as primary barriers. Based on these findings, an urgent QI intervention is underway to address each barrier, increase rates of PCP prophylaxis, and reduce rates of PCP incidence towards the broader goal of improving outcomes in this at-risk patient population. [Table: see text]

A phase Ib/II study of an anti-CD137 agonist antibody ADG106 in combination with weekly paclitaxel and dose-dense doxorubicin/cyclophosphamide.

e14507 Background: ADG106 is a fully human agonistic anti-CD137 IgG4 monoclonal antibody which modulates the tumor microenvironment and has demonstrated increased efficacy when added to chemotherapy in preclinical models. We studied the combination of ADG106 with chemotherapy. Methods: We conducted a phase Ib trial in patients with advanced solid tumors to determine the recommended phase 2 dose (RP2D) of ADG106 + weekly P (paclitaxel 80mg/m2) or ddAC (doxorubicin 60mg/m2, cyclophosphamide 600mg/m2 Q2W with pegfilgrastim), followed by a phase II trial of neoadjuvant ADG106 + weekly Px12→ADG106 + ddACx4→surgery in stage I-III HER2 negative breast cancer patients. In phase Ib, one dose of single agent ADG106 was administered followed 2 weeks later by ADG106 + ddAC (Cohort 1) or ADG106 + weekly P (Cohort 2). Dose levels (DL) of ADG106 were 50mg (DL-1), 100mg (DL1), 200mg (DL2). Serial tumor biopsies were performed at baseline, after single agent ADG106 and at disease progression in phase I, and at baseline, after single agent ADG106, after cycle 1 ADG106 + P, and at surgery in phase II for translational studies. Results: 11 patients were enrolled into Phase Ib with median 3 (range 2-11) prior lines of palliative systemic therapy. ADG106 + ddAC (n=2 at DL1) was deemed intolerable with 1 patient experiencing G4 neutropenia and the other G3 infection; thus ADG106 was not added to ddAC in phase II. No DLTs were observed in all patients receiving ADG106 + P (n=6 at DL1; n=3 at DL2); ADG106 RP2D was declared at 200mg + P. In this cohort, the most common all-grade AEs were neutropenia (n=6), peripheral neuropathy (n=6) and fatigue (n=6); significant ≥G3 AEs were infection (n=2) and G3 neutropenia (n=6). 5/11 (45%) patients in phase I achieved clinical benefit (CBR; PR=2, SD=3) which is clinically meaningful as 9/11 (82%) had prior taxane exposure. 18 of the planned 30 patients have been enrolled into Phase II (ADG106+weekly P→ddACx4→surgery); 10 have completed study treatment and 5 have undergone surgery. While on ADG106 + P, 4 patients experienced G3 adverse events (AEs): neutropenia (n=3), hypophosphatemia (n=1), fever (n=1). Most common G1-2 AEs were ALT elevation (n=4), acneiform rash (n=3) and peripheral neuropathy (n=3). While on ddAC alone, all AEs were low grade except for 1 patient who had G3 pneumonitis from Pneumocystis Jiroveci Pneumonia. 26 sets of matched tumor biopsies have been collected (9 in phase I; 17 in phase II) and will be tested for a panel of 40 markers by multiplex IHC, including CD137, PD-L1, and CD3/4/8. Conclusions: ADG106 when combined with ddAC exacerbates neutropenia and is not tolerable despite prophylactic pegfilgrastim. The RP2D of ADG106 in combination with P is 200mg and is safe and tolerable; manageable G3 neutropenia was the most common AE. There are no new safety signals thus far in Phase II. Further efficacy analyses and studies on tumor immune markers are ongoing. Clinical trial information: NCT05275777 .

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation.

The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants. Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4''-O-isovaleryltransferase gene (ist) from streptomyces thermotoleran. Carrimycin has good antibacterial and antiviral effects. However, no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia (SP) after solid organ transplantation. To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment. In March 2022, ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022. When the condition was critical and difficult to control with other drugs, carrimycin was administered. These ten patients' clinical features and treatment protocols were retrospectively analyzed, and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated. All ten patients were included in the analysis. Regarding etiological agent detection, there were three cases of fungal pneumonia, two cases of bacterial pneumonia, two cases of Pneumocystis pneumonia, and three cases of mixed infections. After treatment with carrimycin, the disease in seven patients significantly improved, the course of the disease was significantly shortened, fever was quickly controlled, chest computed tomography was significantly improved, and oxygenation was significantly improved. Finally, the patients were discharged after curing. One patient died of acute respiratory distress syndrome, and two patients discontinued treatment. Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

Impact of Sulfonamide Allergy Label on Clinical Outcomes in Patients with Pneumocystis jirovecii Pneumonia.

The presence of antibiotic allergy labels can have harmful impacts on clinical outcomes, particularly among immunosuppressed patients, in whom there have been associations with increased complications, readmission rates, and mortality. We explore the effects of a sulfonamide allergy label (SAL) on clinical outcomes in adult patients with Pneumocystis jirovecii pneumonia (PJP). In this retrospective matched cohort study, we utilized TriNetX, a multicenter national database, to match 535 adult patients with PJP and SAL to an equal number of controls. We identified cases indexed between 01/01/2010 and 01/01/2023 utilizing ICD-10 codes for PJP and allergy status to sulfonamides and through detection of P. jirovecii antigen with immunofluorescence or PCR. Propensity score matching was performed in a 1:1 fashion for demographics and comorbidities, and our analysis included clinical outcomes that occurred within 30days after the occurrence of the index event. While hospitalization risk tended to be lower among patients with SAL as compared to controls (RR: 0.90; 95% CI 0.81-1.01), there were no major differences in the risk of respiratory failure (RR: 0.94; 95% CI 0.84-1.05), prednisone use (RR: 1; 95% CI 0.91-1.10), intensive level of care requirement (RR: 0.85; 95% CI 0.69-1.06), intubation (RR: 0.85; 95% CI 0.61-1.19), or mortality (RR: 0.98; 95% CI 0.68-1.42). The presence of SAL did however impact antibiotic prescription patterns, with an underutilization of trimethoprim (RR: 0.50; 95% CI 0.43-0.59) and sulfamethoxazole (RR, 0.47; 95% CI 0.40-0.56) and overuse of alternative agents by patients with SAL as compared to controls. Yet, there was no difference in the occurrence of adverse outcomes such as hepatotoxicity (RR: 1.09; 95% CI 0.49-2.45) or acute kidney injury (RR: 0.94; 95% CI 0.78-1.14) between patients with SAL and controls. The presence of SAL alters antibiotic prescription patterns among adults with Pneumocystis infection but has no clinically significant impact on outcomes.

Pneumocystis pneumonia in French intensive care units in 2013-2019: mortality and immunocompromised conditions.

The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are poorly described. We analyzed all adult PCP cases admitted to French ICUs via the French medical database system (PMSI), over the period from 2013 to 2019. French ICUs admitted a total of 4055 adult patients with PCP. Among all hospitalized PCP cases, the proportion requiring ICU admission increased from 17.8 in 2014 to 21.3% in 2019 (P < 0.001). The incidence of severe PCP rose from 0.85 in 2013 to 1.32/100,000 adult inhabitants in 2019 (P < 0.0001), primarily due to the proportion of HIV-negative patients that increased from 60.6% to 74.4% (P < 0.0001). Meanwhile, the annual number of severe PCP cases among patients with HIV infection remained stable over the years. In-hospital mortality of severe PCP cases was 28.5% in patients with HIV infection and 49.7% in patients without. Multivariable logistic analysis showed that patients with HIV infection had a lower adjusted risk of death than patients without HIV infection (Odds Ratio [OR]: 0.30, 95% confidence interval [95CI]: 0.17-0.55). Comorbidities or conditions strongly associated with hospital mortality included the patient's age, Simplified Acute Physiologic Score II, congestive heart failure, coagulopathy, solid organ cancer, and cirrhosis. A vast array of autoimmune inflammatory diseases affected 19.9% of HIV-negative patients. The number of PCP cases requiring ICU admission in France has risen sharply. While the yearly count of severe PCP cases in HIV-infected patients has remained steady, this rise predominantly affects cancer patients, with a recent surge observed in patients with autoimmune inflammatory diseases, affecting one in five individuals.

Predictive models-assisted diagnosis of AIDS-associated Pneumocystis jirovecii pneumonia in the emergency room, based on clinical, laboratory, and radiological data.

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 (> 24bpm), 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.

Mapping the Burden of Fungal Diseases in the United Arab Emirates.

The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE's low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of Pneumocystis pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE's national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE.