METHODS: The D-PRISM study was a multinational, survey-based investigation to assess the diagnosis and treatment of pneumonia in the ICU. A self-administered online questionnaire was distributed to intensive care clinicians from 72 countries between September to November 2022. The questionnaire included sections on professional profiles, current clinical practice in diagnosing and managing CAP, HAP, and VAP, and the availability of microbiology diagnostic tests. Multivariable analysis using multiple regression analysis was used to assess the relationship between reported antibiotic duration and organisational variables collected in the study.

RESULTS: A total of 1296 valid responses were collected from ICU clinicians, spread between low-and-middle income (LMIC) and high-income countries (HIC), with LMIC respondents comprising 51% of respondents. There is heterogeneity across the diagnostic processes, including clinical assessment, where 30% (389) did not consider radiological evidence essential to diagnose pneumonia, variable collection of microbiological samples, and use and practice in bronchoscopy. Microbiological diagnostics were least frequently available in low and lower-middle-income nation settings. Modal intended antibiotic treatment duration was 5-7 days for all types of pneumonia. Shorter durations of antibiotic treatment were associated with antimicrobial stewardship (AMS) programs, high national income status, and formal intensive care training.

METHODS: Using rapid evaluation methods, we will use four data collection methods: 1) registry embedded indicators to assess quality of care processes and their associated outcomes; 2) process mapping to provide a preliminary framework to understand gaps between current and desired care practices; 3) structured observations of processes of interest identified from the process mapping and; 4) focus group discussions with stakeholders to identify barriers and enablers influencing the gap between current and desired care practices. We will also collect self-assessments of readiness for quality improvement. Data collection and analysis will be led by local stakeholders, performed in parallel and through an iterative process across eight countries: Kenya, India, Malaysia, Nepal, Pakistan, South Africa, Uganda and Vietnam.

METHODS: An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee selected an international panel of clinicians and researchers with expertise in sepsis management. A Delphi process based on an iterative approach was used to obtain the final consensus statements.

RESULTS: A stable consensus was achieved for 30 (94%) of the statements by 41 experts after four survey rounds. These include consensus on managing patients with sepsis outside a designated critical care area, triggers for escalating clinical management and criteria for safe transfer to another facility. The experts agreed on the following: in the absence of serum lactate, clinical parameters such as altered mental status, capillary refill time and urine output may be used to guide resuscitation; special considerations regarding the volume of fluid used for resuscitation, especially in tropical infections, including the use of simple tests to assess fluid responsiveness when facilities for advanced hemodynamic monitoring are limited; use of Ringer's lactate or Hartmann's solution as balanced salt solutions; epinephrine when norepinephrine or vasopressin are unavailable; and the administration of vasopressors via a peripheral vein if central venous access is unavailable or not feasible. Similarly, where facilities for investigation are unavailable, there was consensus for empirical antimicrobial administration without delay when sepsis was strongly suspected, as was the empirical use of antiparasitic agents in patients with suspicion of parasitic infections.

CLINICAL QUESTION: What is the role of drugs in the treatment of patients with covid-19?

CONTEXT: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics.

WHAT IS NEW?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19.

ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.