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  • 1
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    356. Risk Assessment of Pneumocystis jirovecii Pneumonia among Hospitalized Patients with Hypoxic Respiratory Failure - A Proposed Multivariable Calculator Based on Previous Prednisone Equivalent Dose
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Corticosteroids increase the risk of Pneumocystis jirovecii pneumonia (PJP). It is unknown how much corticosteroid dose exposure would modify the risk of PJP in different populations. We aim to develop a PJP risk calculator based on the previous dose of corticosteroids and modulated by additional clinical factors. Methods A multicenter retrospective case-control study was performed on patients tested for PJP within the UCHealth system from 2000 to 2021. We developed a model for estimating PJP risk based on previous prednisone equivalent daily dose (PEDD) and adjustable for additional clinical variables. PJP was fit to a generalized additive model (GAM), with a spline for prednisone dose and additive covariates for demographics and risk factors. We used a multicenter federated network to calibrate the model to estimate the PJP prevalence among hospitalized patients with hypoxic respiratory failure. Results We had a complete sample of 199 patients, 104 cases with PJP, and 95 controls. Patients with HIV (OR: 19 CI: 6.3-60.8, p & lt; 0.0001), diabetes (OR: 4.1 CI: 1.2-14.8, p & lt; 0.0288), and autoimmune disease (OR: 5.2 CI: 1.4-19.2, p & lt; 0.0139) were more likely to have PJP. Patients with preexisting lung disease (OR: 0.3 CI: 0.1-0.6, p & lt; 0.0041) and on PJP prophylaxis (OR: 0.06 CI: 0.02-0.2, p & lt; 0.0001) were less likely to have PJP. 36.8% of controls and 49% of cases were on steroids with a mean PEDD of 15 mg/day and 20.4 mg/day, respectively. We found a prevalence of PJP of 0.126% among hospitalized patients with hypoxic respiratory failure. The developed model can estimate the PJP risk based on a previous PEDD in 32 different clinical combinations: e.g., a PEDD of 20 mg/day would give a calculated annual PJP risk of approximately 1.74% (95% CI: [0.39, 7.42]) if a patient has autoimmune disease only but 6.29% (95% CI: [1.34, 24.91] ) if a patient has HIV only (Figure 1). Figure 1.Predicted probability of PJP based on previous prednisone dose among hospitalized patients with hypoxic respiratory failure for three different clinical scenarios Conclusion Previous corticosteroid dose alone is inadequate to inform of an increased risk of PJP. A multivariable calculator incorporating the absence or presence of additional traditional risk factors could optimally stratify the PJP risk. Future directions include validating the findings in external cohorts and modeling PJP risk in the ambulatory setting to inform the need for PJP prophylaxis. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.434
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 2
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    1003. Cytokine Levels in Sepsis and TNFα Association with Mortality but not Sepsis Severity or Infection Source: a Systematic Review and Meta-analysis
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S592-S592
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    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S592-S592
    Abstract: Sepsis is a global health problem associated with significant morbidity and mortality and is attributed to a “cytokine storm.”. However, anti-cytokine therapies have failed to lower sepsis mortality in clinical trials. Linking cytokine excess to sepsis pathogenesis requires quantification of cytokine levels in sepsis. This systematic review and meta-analysis characterizes levels of key cytokines in the circulation of sepsis patients and relates TNFα levels to mortality and patient characteristics. Methods Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched from 1946 to May 2020 for studies in English disclosing cytokine levels in sepsis. Keywords included sepsis, septic shock, purpura fulminans, and tumor necrosis factor (TNF)α. We related cytokine amounts to 28-day mortality. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). This systematic review is registered in PROSPERO under number CRD42020179800. Results A total of 3656 records were identified. After exclusions, 103 studies were included. Among these studies, 72 disclosed TNFα levels, 25 showed interleukin (IL)-1β levels, and 6 presented interferon (IFN)γ levels. The pooled estimate mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% CI, 39.8-85.8 pg.ml; I2 = 99.4%). Pooled estimate means for IL-1α and IFNγ in sepsis patients were 21.8 pg/ml (95% CI, 12.6-37.8 pg.ml; I2 =99.8%) and 63.3 pg/ml (95% CI, 19.4-206.6 pg/ml; I2 = 99.7%), respectively. Elevated TNFα concentrations were associated with increased 28-day mortality (P=0.001). In a subgroup analysis, TNFα levels did not relate to sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score (figure 1). In a metaregression, TNFα associated with age, percentage of females and mortality at 28 days. Figure 1: A: TNFa levels according to sepsis source. B: TNFa levels according to measurement technique. C: TNFa levels according to presence or absence of cardiovascular disease. D: TNFa levels according to presence or absence of malignancy. E: TNFa levels according to sepsis severity. F: TNFa levels in fungal compared to other causes of sepsis (Yes=fungal sepsis; No= Other types of sepsis). G: TNFa levels according to SOFA score. H: TNFa levels and mortality at 28 days. Conclusion We presented levels of TNFα, IL-1β, and IFNγ in human sepsis and showed that TNFα elevations are associated with sepsis mortality. TNFα concentrations did not correlate with sepsis severity. We believe the concept that elevated cytokines cause sepsis should be revisited in the context of these data. Disclosures All Authors: No reported disclosures
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab466.1197
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 3
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    1383. Necrotizing Fasciitis and Streptococcus pyogenes (GAS) Infection Seasonality and Risk Factors for Infection— a Multicenter Research Network Study
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
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    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Streptococcus pyogenes causes acute pharyngitis and type II necrotizing fasciitis. Seasonal variations in the incidence of S. pyogenes infections are not robustly characterized. We aim to identify seasonal variations and risk factors of S. pyogenes infections and all causes of necrotizing fasciitis. Methods From 2010 to 2019, we identified all infectious adult cases of S. pyogenes using ICD-10 diagnoses and lab results (PCR and antigen-based assays) and cases of necrotizing fasciitis using ICD-10 diagnoses within a federated research network. We extracted seasonal (quarterly) incidence rates. We used an autoregressive integrated moving average (ARIMA) model to assess the seasonality of the cases (6-month intervals). Demographic characteristics and 3-month outcomes of S. pyogenes pharyngitis were compared to a cohort of patients with acute upper respiratory illnesses excluding S. pyogenes. Results We identified 238,088 cases of S. pyogenes pharyngitis and 26,931 cases of necrotizing fasciitis in adults. S. pyogenes infection average incidence was higher during the winter than the summer: 0.34 vs. 0.20 cases per 1,000 patients. Necrotizing fasciitis diagnoses were highest during the summer months (average 0.026 per 1000 patients). There was a significant ARIMA seasonal variation in the time series analysis for S. pyogenes infections (p=0.006) (figure 1). However, necrotizing fasciitis was not significant (p=0. 0.79) (Figure 2). Compared to adults with acute respiratory infections other than S. pyogenes, adults with S. pyogenes pharyngitis were more likely to be younger (25.8 ± 14.9 vs. 45.4 ± 19.9 years old, p & lt; 0.0001) and of Hispanic or Latino ethnicity (11% vs. 8%, p & lt; 0.0001). For age-matched outcomes, adults with S. pyogenes pharyngitis had lower rates of hospitalization (0.888% vs. 1.714%, p & lt; 0.0001) and mortality (0.114% vs. 0.174%, p & lt; 0.0001) at three months relative to adults with acute respiratory infections other than S. pyogenes. Figure 1.Seasonal variation of adults with established ICD code or testing for Streptococcus pyogenes (GAS) infectionsFigure 2.Seasonal variation of adults with established ICD code for necrotizing fasciitis Conclusion Peaks in S. pyogenes infections are more likely to occur in the winter months, although spring and fall seasons can display variably high rates of S. pyogenes year over year. Necrotizing fasciitis of any microbiological did not show a significant seasonal variation. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.1212
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 4
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    370. Toxoplasma gondii IgG Seropositivity is Associated with Increased Schizophrenia, Hospitalization, and 1-year Mortality— a Multicenter Research Network Study
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Despite Toxoplasma seropositivity found in about one-third of the global population, we lack information about the clinical outcomes of patients with past exposure to this parasite without the manifested disease. We aim to evaluate 1-year mortality and mental health diagnosis in patients with Toxoplasma IgG seropositivity. Methods We queried a federated national multicenter network to validate mortality risk differences between Toxoplasma IgG seropositive and seronegative patients from 2010 to 2021, excluding patients with active disease. We used propensity score matching to assess independent mental health outcomes and mortality risk 1-year after serology. Results We found 6244 patients with Toxoplasma IgG positivity without toxoplasmosis and 29,179 patients with negative Toxoplasma IgG. Patients with positive Toxoplasma IgG were slightly older (46.1 ± 17 vs. 45±16.5, p & lt; 0.0001) and more likely to be Hispanic (15% vs. 12%, p & lt; 0.0001). Toxoplasma gondii IgG seropositivity was more often present in patients with neoplasms (25% vs 22%, & lt; 0.0001), type 2 diabetes mellitus (13% vs 12%, p=0.0284), and less likely in transplant recipients (7% vs. 8%, p=0.0015), and liver cirrhosis (5% vs 7%, p. & lt; 0.0001). Propensity score matching to 6099 seronegative patients adjusted for age, gender, race, ethnicity, heart disease, transplant, neoplasm, and cirrhosis found that seropositive patients had an increased risk of 1-year mortality (OR: 1.2, CI: 1.06-1.4, p=0.0036) (Figure 1), hospitalization (OR:1.2, CI: 1.1-1.3, p & lt; 0.0001) and schizophrenia (OR: 1.4, CI: 1.01-1.8, p=0.04). An increased risk was not seen with bipolar disorder (OR: 0.86, CI: 0.66-1.15, p=0.3206). Figure 1.Kaplan-Meier survival analysis comparing the survival probability of patients without toxoplasmosis with a positive toxoplasma IgG (purple line) to those with a negative Toxoplasma IgG (green line) Conclusion Toxoplasma IgG seropositivity without clinical disease is associated with an increased risk of one-year mortality, hospitalization, and schizophrenia diagnosis. Further prospective studies are needed to clarify the association of Toxoplasma exposure with schizophrenia and worse outcomes. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.448
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 5
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    472. Corticosteroid Exposure as a Risk Factor for Pneumocystis jirovecii Pneumonia Mortality in HIV-Negative Patients: A Multicenter Retrospective Case-Control Study with a Global Research Network Validation
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: HIV-negative patients have higher mortality from PJP compared to patients with HIV, however, we lack data on predictors of PJP-associated mortality in HIV-negative patients. We aim to characterize the role of previous corticosteroid exposure in PJP-related mortality. Methods A multicenter retrospective case-control study was performed on HIV-negative patients tested for PJP within the UCHealth system from 2000 to 2021. Cox proportional-hazards model was used for survival analysis. We queried TrinetX, a global research network, to validate mortality risk differences among HIV-negative patients with PJP with prior corticosteroid exposure versus those without. We used propensity score matching to assess independent corticosteroid risk of 1-year mortality. Results We identified 105 cases of PJP and 71 controls without PJP. HIV-negative patients with steroid exposure in the previous 6 months were more likely to have a history of malignancy (26.5% vs 11.9%, p=0.026), solid organ transplant (14.8% vs 3.4%, p=0.023), inflammatory disease (27.6% vs 8.5%, p=0.03), or use of other immunosuppressive drugs (83.8% vs 13.6%, p & lt; 0.0001). The median prednisone equivalent dose was higher in patients who died at 7 weeks (33.7 vs. 21.5 mg/d) and 1 year (33.7 vs. 20 mg/d). Adjusted Cox proportional-hazard model found an increased rate of death at 10 weeks (HR: 3.8, CI: 1.6-9.26, p=0.003)(Figure 1) and 1 year (HR: 4.8, CI: 2.2-10.7, p & lt; 0.0001) among patients previously on steroids. A TrinetX-based propensity score matching of 2176 HIV-negative patients found a significantly increased 1-year mortality (OR: 1.9 CI: 1.6-2.2, p & lt; 0.0001) after PJP diagnoses in the group with corticosteroid exposure in the previous year compared to those with PJP without corticosteroid exposure. The mean β-d-glucan (203±154 vs. 82± 35.8 pg/mL, p=0.025) and ferritin levels (1591±5576 vs. 1041± 1300 mcg/L, p=0.02) were higher in those with prior steroid use. Figure 1.Adjusted 70-days mortality among HIV negative patients with PJP by corticosteroid exposure Conclusion HIV-negative patients with PJP and corticosteroid use preceding diagnosis have higher mortality than those without corticosteroid use. A higher fungal burden may influence corticosteroid mediated mortality. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.530
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
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    473. Diabetes Mellitus as a Risk Factor for Cryptococcosis — a Multicenter Research Network Study
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Diabetes mellitus type 2 (DM2) is a common medical condition that increases the risk of bacterial infections, and is often present in patients with cryptococcosis. The role of DM2 as an independent risk factor for cryptococcosis is debatable. We aim to better characterize the natural history of cryptococcosis in patients with DM2 as their only comorbidity. Methods We utilized TrinetX, a federal national network, to identify HIV-negative patients who had cryptococcosis without known risk factors. Demographic characteristics and outcomes were compared between patients with DM2 and those without DM2, who tested positive or had ICD based diagnoses of Cryptococcus infection within five years of diagnosis of DM2. Results Sixty patients with DM2 (as the sole risk factor) and 707 patients without DM2 had cryptococcosis. Patients with DM2 and cryptococcosis were older (61 ± 13.6 years vs. 55.8 ± 16.2 years, p=0.0219), and more likely to be Hispanic or Latino (18% vs. 9%, p=0.023). They had higher rates of hypertension (77% vs 44%, p & lt; 0.0001), cystic fibrosis (18% vs 1%, p & lt; 0.0001), tuberculosis (18% vs 1%, p & lt; 0.0001), and chronic kidney disease (33% vs 18%, p=0.0026). The mean HbA1c among patients with DM2 who developed cryptococcosis was 8.16 (SD 2.62). The most common sites of cryptococcus infection were pulmonary (56% vs 55%, p=0.8930) and cerebral (36% vs 40%, p=0.5589), in both groups. The two groups had similar mortality (20% vs 25.47%, p=0.3676) (Figure 1), and hospitalization rates (20% vs 31.3%, p=0.08). The overall annual cryptococcosis risk among HIV-negative patients with DM2 without any additional risk factors was 0.001%. Conclusion Cryptococcosis occurs rarely in HIV-negative patients with DM2 and without additional risk factors. Hispanic or Latino ethnicity, uncontrolled hyperglycemia, and chronic kidney disease may increase the risk of cryptococcosis among patients with DM2. Cryptococcosis in patients whose only comorbidity is DM2 have as high of mortality as that seen with more established comorbitidies. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.531
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 7
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    Disseminated Cryptococcal Disease in A Patient With Chronic Chylothorax and a Pleurovenous Catheter, a Case Report With Autopsy Findings
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. 6 ( 2021-06-01)
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    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 6 ( 2021-06-01)
    Abstract: Cryptococcus species are ubiquitous in the environment with a global distribution. While causing disease predominantly in immunocompromised hosts such as those with advanced HIV, HIV-uninfected patients are increasingly recognized as being affected. The most common forms of infection are cryptococcal pneumonia and meningitis. HIV-uninfected patients and extrapulmonary infections have worse outcomes, likely due to delayed diagnosis and treatment. Cryptococcus infections involving chylothorax or chyloabdomen have rarely been reported in humans. We describe a case of fulminant disseminated cryptococcosis with fungemia, peritonitis, and empyema in a patient with chronic chylothorax treated with an indwelling pleurovenous shunt. Key autopsy findings included cryptococcal organisms identified on calcified lymphadenopathy, pleural adhesions, and pericardium. We discuss the importance of identifying patients with nontraditional risks factors for cryptococcal disease, such as lymphopenia and hypogammaglobulinemia, and the potential implications of pleurovenous catheters in Cryptococcus dissemination.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab258
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 8
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    Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis
    Oxford University Press (OUP) ; 2024
    In:  Open Forum Infectious Diseases
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP)
    Abstract: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofae115
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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