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Dr Ron Daniels

Antimicrobial Resistance and the Burden of Sepsis

Posted on 18/11/2020 by Dr Ron Daniels

Sepsis is a devastating condition resulting from a dysregulated immune system response to infection, which can lead to organ failure and death. Each year, sepsis affects close to 50 million people globally, of whom more than 40% are children under age 5 particularly in low- and middle-income countries. Sepsis remains also a leading cause of death in high-income countries, where the burden is primarily among the adult population. In the U.S., sepsis is the most expensive condition treated annually, consuming over $60 billion each year[1]. Overall, sepsis causes or contributes to over 11 million deaths each year. However, the majority of deaths due to sepsis are preventable and can be treated with prompt response and appropriate therapy, including antimicrobial stewardship.

Acting quickly BUT safely

Timely and targeted antimicrobial stewardship in the context of appropriate urgent therapy represents the cornerstone of effective sepsis therapy. Adult patients who receive antimicrobials within three hours of sepsis recognition have increased chances of survival. Similarly, in children with sepsis and septic shock, several cohorts report substantially better outcomes in those who receive timely intravenous antibiotics. We remain mindful that antimicrobial resistance represents a serious threat: it has been estimated that AMR contributes to at least 10% of sepsis deaths worldwide.

The 2017 WHA 70.7 Resolution urges governments to integrate prevention, diagnosis and treatment of sepsis in national health systems. Sepsis plans must include, amongst other measures, public awareness, the implementation of basic hygiene practices, infection prevention and control measures, and training of professionals.  The resolution also encourages governments “to continue in their efforts to reduce antimicrobial resistance and promote the appropriate use of antimicrobials“, while at the same time acknowledging that “ineffective or incomplete antimicrobial therapy for infections, including sepsis, may be a major contributor to the increasing threat of antimicrobial resistance“.


Better targeting antibiotics to sepsis treatment

Over the past years, a stimulating controversy on the use of antibiotics in sepsis treatment has perhaps overlooked that the aims of sepsis campaigns in fact closely align with the global agenda on antimicrobial stewardship: delivering the right antimicrobial for the right patient, and stopping antibiotics where they are no longer necessary.

The Surviving Sepsis Campaign recommends, in fact, initiating sepsis treatment with broad-spectrum antibiotics covering the main likely pathogens, followed by narrowing to targeted therapy if a pathogen or source is identified, and stopping antimicrobial therapy if bacterial or fungal infection is felt unlikely to be the cause. Indiscriminate administration of early antibiotics is not only unnecessary, but may also lead to increased costs and adverse effects on the patients or their community, such as the spread of increased antimicrobial resistance.

Screening and speeding up delivery of the right antibiotics

In England’s NHS from 2016 to 2019 hospitals were incentivized to prioritize patients with sepsis, including measurement of the rates of screening for sepsis and the rates of delivery of rapid antibiotics (within 1 hour) for patients suspected to have sepsis. Not only did screening improve markedly, but also rates of rapid antibiotic delivery improved steadily from a baseline of 32% of patients in 2016 to more than 80% in April 2019, with most antibiotic prescriptions starting in EDs. However, total hospital consumption of antibiotics remained unchanged – it is compatible to incentivize rapid treatment of sepsis without adverse consequence on hospital antibiotic usage.

Diagnostics lead to better outcomes

As highlighted in the AMR Industry Alliance 2020 Progress report, diagnostics have become increasingly important to ensure that the use of antimicrobials can achieve the best outcomes, including reducing the incidence of sepsis and reducing the inappropriate prescription of antimicrobials.

The Global Sepsis Alliance welcomes the work of the AMR Industry Alliance for their contribution to slowing the emergence of resistance. We will keep on supporting such efforts that will contribute to a balanced and effective use of antimicrobials, in view of reaching the ambitious Sepsis Declaration’s goals on sepsis incidence reduction.

Dr. Ron Daniels, member of the GSA Executive Committee, and Executive Director of the UK Sepsis Trust.

[1] Buchman, Timothy G. PhD, MD1,2; Simpson, Steven Q. MD1,3; Sciarretta, Kimberly L. PhD1; Finne, Kristen P. BA4; Sowers, Nicole MPP5; Collier, Michael BA5; Chavan, Saurabh MBBS, MPH5; Oke, Ibijoke MPA5; Pennini, Meghan E. PhD1; Santhosh, Aathira MA5; Wax, Marie MBA1; Woodbury, Robyn PhD1; Chu, Steve JD6; Merkeley, Tyler G. MS, MBA1; Disbrow, Gary L. PhD1; Bright, Rick A. PhD1; MaCurdy, Thomas E. PhD5,7,8,9; Kelman, Jeffrey A. MD, MMSc6 Sepsis Among Medicare Beneficiaries: 3. The Methods, Models, and Forecasts of Sepsis, 2012–2018*, Critical Care Medicine: March 2020 – Volume 48 – Issue 3 – p 302-318. doi: 10.1097/CCM.0000000000004225