Clinical Infectious Diseases最新文献

Background: An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed.

Methods: A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24).

Results: A total of 497 participants, ages 6-83, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95%CI 28-37) when compared to Xpert MTB/RIF Ultra, 29% (95%CI 25-34) when compared to a bacteriological confirmation, and 22% (95%CI 18-26) when compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95%CI 74-89) when compared to Xpert MTB/RIF Ultra, 84% (95%CI 75-90) when compared to a bacteriological confirmation, and 54% (95%CI 44-64) when compared to a composite clinical diagnosis.

Conclusions: While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.

Background: Integrase strand transfer inhibitor (InSTI)-based antiretroviral therapies have been associated with greater weight gain in people living with HIV versus on protease inhibitor (PI)-based regimens. The DEFINE study investigated whether switching from an InSTI- to a PI-based regimen could mitigate/reverse weight gain.

Methods: DEFINE (NCT04442737) was a randomized, 48-week, open-label, prospective, phase 4 study in virologically suppressed adults with HIV-1 and ≥10% weight gain on InSTI+tenofovir alafenamide (TAF)/emtricitabine (FTC) (<36 months pre-screening). Participants either switched immediately to darunavir/cobicistat/emtricitabine/TAF (D/C/F/TAF) or continued InSTI+TAF/FTC during Weeks 0-24 then switched to D/C/F/TAF for Weeks 24-48. The primary endpoint was least squares (LS) mean (95% confidence interval [CI]) percent weight change from baseline to Week 24.

Results: Overall, 103 adults were randomized (D/C/F/TAF, n=53; InSTI+TAF/FTC, n=50); 30% female; 61% Black/African American. No significant difference in weight change was observed at Week 24 (LS mean change: D/C/F/TAF, 0.63% [95%CI: -0.44, 1.70] vs InSTI+TAF/FTC, -0.24% [-1.35, 0.87]; p=0.24); however, a trend towards weight loss was observed with extended time post-ARV switch to D/C/F/TAF (baseline to Week 48, -0.36% [-1.77, 1.06]), particularly in subgroups at higher weight gain risk (eg, females, Black/African Americans). Metabolic endpoints paralleled weight change over time. D/C/F/TAF was well tolerated, with comparable virologic efficacy between arms.

Conclusions: While no significant change in body weight was observed at 24 weeks after switching from InSTI+TAF/FTC to D/C/F/TAF among adults with weight gain, a trend towards weight loss emerged with longer time post-ARV switch, supporting further investigation of antiretroviral selection/switch for weight management.

Background: Corticosteroids appears to be beneficial for severe Mycoplasma pneumoniae pneumonia in children but data in adults are limited. This study investigated effects of adjunctive corticosteroids in hypoxemic adults with M. pneumoniae pneumonia.

Methods: Adults admitted 2013-2017 with verified M. pneumoniae pneumonia and hypoxemia (SpO2<93% or oxygen treatment) were included in a cohort. Treatment was defined as receipt of at least one glucocorticoid dose.Primary outcome was time to regression of hypoxemia, analysed with a multivariable Cox regression. Secondary outcomes included fever duration, length of stay, and complications.

Results: Corticosteroids were given to 31% (122/388) during hypoxemia. Median age was 44 (IQR 34-57) years. Median time to start of corticosteroid treatment was 1.9 (IQR 0.6-3.6) days from admission. Median cumulative dose was equivalent to 15 (IQR 10-19) mg betamethasone. Treatment duration was 5 (IQR 3-6) days. Patients treated with corticosteroids had more severe respiratory disease, longer symptom duration and were more often treated with fluoroquinolones.Time to regression of hypoxemia (HR 0.92 [95% CI 0.72-1.19], P = 0.53) and length of stay (HR 0.91 [95% CI 0.71-1.16], P = 0.44) were not significantly different between corticosteroid treated and controls. Corticosteroid treatment was associated to shorter fever duration (HR 1.44 [95% CI 1.00-2.06], P = 0.046). Complications did not differ significantly between treatment groups.

Conclusion: Adjunctive corticosteroids were not associated with reduced time to regression of hypoxemia in adults with M. pneumoniae pneumonia. However, duration of fever was shorter and no increase in complications was seen.

Background: The 2019 ATS/IDSA community-acquired pneumonia (CAP) guidelines recommend that clinicians prescribe empiric antibiotics for MRSA or P. aeruginosa only if locally validated risk factors (or 2 generic risk factors if local validation is not feasible) are present. It remains unknown how implementation of this recommendation would influence care.

Methods: This cross-sectional study included adults hospitalized for CAP across 50 hospitals in the Premier Healthcare Database from 2010-2015 and sought to describe how the use of extended-spectrum antibiotics (ESA) and the coverage for patients with CAP due to restraint organisms would change under the two approaches described in 2019 ATS/IDSA guidelines. To do this, the proportion of ESA use in patients with CAP and the proportion of ESA coverage among patients with infections resistant to recommended CAP therapy were measured.

Results: In the 50 hospitals, 19%-75% of patients received ESA, and 42%-100% of patients with resistant organisms received ESA. The median number of risk factors identified per hospital was 9 (interquartile range [IQR], 6-12). Overall, treatment according to local risk factors reduced the number of patients receiving ESA by 38.8 percentage points and using generic risk factors by 47.5 percentage points. However, the effect varied by hospital. The use of generic risk factors always resulted in less ESA use and less coverage for resistant organisms. Using locally validated risk factors resulted in a similar outcome in all but one hospital.

Conclusion: Future guidelines should explicitly define the optimal trade-off between adequate coverage for resistant organisms and ESA use.

In a commercial claims database analysis, <0.5% of patients with inflammatory bowel disease or rheumatoid arthritis developed an IFI within one year of initiating TNF-alpha therapy. Histoplasmosis was the most common IFI type. Overall IFI incidence varied based on region, underlying conditions, and use of certain immunosuppressive medications.

Objective: Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy is limited. We evaluated metabolic markers in pregnant women with HIV after starting TAF- vs TDF-based ART.

Methods: We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC+DTG; n=217) or TDF/FTC+DTG (n=215). We measured non-fasting plasma concentrations of glucose, total-cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), lipoprotein (a), and triglycerides from samples collected eight weeks after enrollment. We employed linear regression models to estimate by-arm mean differences.

Results: 219 participants enrolled in the DTG arms in Zimbabwe and Uganda: 109 in the TAF/FTC+DTG and 110 in the TDF/FTC+DTG arms. At study entry, mean gestational age was 22.6 weeks, median HIV-1 RNA was 711 copies/mL, and mean age was 25.8 years. By eight weeks, mean total cholesterol was 12 mg/dL higher in women randomized to TAF/FTC+DTG versus TDF/FTC+DTG (95% CI 3.8, 21.1). Pregnant women in the TAF/FTC+DTG arm had higher mean LDL-C (7.1 mg/dL, 95% CI 0.2, 14.0), triglycerides (12.3 mg/dL, 95% CI 1.8, 22.7), lipoprotein (a) (7.3 mg/dL, 95% CI 1.1, 13.6), and lower mean HDL-C (2.8 mg/dL, 95% CI 0.1, 5.6) compared to the TDF/FTC+DTG arm.

Conclusion: Pregnant women randomized to start TAF/FTC+DTG had higher lipids than those randomized to TDF/FTC+DTG within eight weeks of ART initiation. However, lipid levels were within normal reference ranges.