scholarly journals Early empirical TB treatment in HIV-positive patients admitted to hospital in South Africa: an observational cohort study

2021 ◽  
Author(s):  
Carolin Bresges ◽  
Douglas Wilson ◽  
Katherine Fielding ◽  
Elizabeth L Corbett ◽  
Fabrizia Del-Greco ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hospital Mortality ◽  
South African ◽  
Observational Cohort Study ◽  
Hiv Positive ◽  
Rapid Diagnostics ◽  
Tb Treatment ◽  
Competing Risks Analysis ◽  
Observational Cohort ◽  
The Impact

Abstract Background Empirical TB treatment in HIV-positive inpatients is common and may undermine the impact of new diagnostics. We sought to describe empirical TB treatment and compare characteristics and outcomes with patients treated for TB after screening. Methods Retrospective observational cohort study of HIV-positive inpatients treated empirically for TB prior to TB screening. Data on clinical characteristics, investigations and outcomes were collected from medical records. Comparison cohorts with microbiologically-confirmed or empirical TB treatment after TB screening with Xpert MTB/RIF and urine lipoarabinomannan assays were taken from South African STAMP trial site. In-hospital mortality was compared using a competing-risks analysis adjusted for age, sex and CD4 count. Results Between January 2016 and September 2017, 100 patients excluded from STAMP were treated for TB empirically prior to TB screening. After enrolment in STAMP and TB screening, 240/1177 (20.4%) patients received TB treatment, of whom 123 had positive TB tests and 117 were treated empirically. Characteristics were similar among early empirically treated patients and those treated after TB screening. 50% of early empirical TB treatment was based on radiological investigations, 22% on cerebrospinal or pleural fluid testing, and 28% on clinical features alone. Only 11/100 empirically treated patients had subsequent microbiological confirmation. In-hospital mortality was lower in patients with microbiologically-confirmed TB compared to those treated empirically (adjusted sub-distribution HR 0.5, 95% CI 0.3-0.9). Conclusions Empirical TB treatment remains common in severely ill HIV-positive inpatients. These patients may benefit from TB screening using existing rapid diagnostics, both to improve confirmation of TB disease and reduce over-treatment for TB.

scholarly journals Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured Versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 557
Author(s):  
Matthias Gijsen ◽  
Erwin Dreesen ◽  
Ruth Van Daele ◽  
Pieter Annaert ◽  
Yves Debaveye ◽  
...  
Keyword(s):  
Renal Function ◽  
Cohort Study ◽  
Protein Binding ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Observational Cohort Study ◽  
Target Attainment ◽  
Binding Model ◽  
Observational Cohort ◽  
The Impact

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

scholarly journals Relevance of prediction scores derived from the SARS-CoV-2 first wave, in the UK COVID-19 second wave, for early discharge, severity and mortality: a PREDICT COVID UK prospective observational cohort study

2021 ◽  
Author(s):  
Hakim Ghani ◽  
Alessio Navarra ◽  
Phyoe K Pyae ◽  
Harry Mitchell ◽  
William Evans ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hospital Mortality ◽  
Observational Cohort Study ◽  
Single Site ◽  
Urgent Care ◽  
Prognostic Scores ◽  
Prospective Observational Cohort Study ◽  
Observational Cohort ◽  
The Uk ◽  
Second Wave

Objective: Prospectively validate two prognostic scores, pre-hospitalisation (SOARS) and hospitalised mortality prediction (4C Mortality Score), derived from the coronavirus disease 2019 (COVID-19) first wave, in the evolving second wave with prevalent B.1.1.7 and parent D614 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, in two large United Kingdom (UK) cohorts. Design: Prospective observational cohort study of SOARS and 4C Mortality Score in PREDICT (single site) and multi-site ISARIC (International Severe Acute Respiratory and Emerging Infections Consortium) cohorts. Setting: Protocol-based data collection in UK COVID-19 second wave, between October 2020 and January 2021, from PREDICT and ISARIC cohorts. Participants: 1383 from single site PREDICT cohort and 20,595 from multi-site ISARIC cohort. Main outcome measures: Relevance of SOARS and 4C Mortality Score derived from the COVID-19 first wave, determining in-hospital mortality and safe discharge in the UK COVID-19 second wave. Results: Data from 1383 patients (median age 67y, IQR 52-82; mortality 24.7%) in the PREDICT and 20,595 patients from the ISARIC (mortality 19.4%) cohorts showed both SOARS and 4C Mortality Score remained relevant despite the B.1.1.7 variant and treatment advances. SOARS had AUC of 0.8 and 0.74, while 4C Mortality Score had an AUC of 0.83 and 0.91 for hospital mortality, in the PREDICT and ISARIC cohorts respectively, therefore effective in evaluating both safe discharge and in-hospital mortality. 19.3% (231/1195, PREDICT cohort) and 16.7% (2550/14992, ISARIC cohort) with a SOARS of 0-1 were potential candidates for home discharge to a virtual hospital (VH) model. SOARS score implementation resulted in low re-admission rates, 11.8% (27/229), and low mortality, 0.9% (2/229), in the VH pathway. Use is still suboptimal to prevent admission, as 8.1% in the PREDICT cohort and 9.5% in the ISARIC cohort were admitted despite SOARS score of 0-1. Conclusion: SOARS and 4C Mortality Score remains valid, providing accurate prognostication despite evolving viral subtype and treatment advances, which have altered mortality. Both scores are easily implemented within urgent care pathways with a scope for admission avoidance. They remain safe and relevant to their purpose, transforming complex clinical presentations into tangible numbers, aiding objective decision making. Trial registration: NHS HRA registration and REC approval (20/HRA/2344, IRAS ID 283888).

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