O01 Antimicrobial resistance and death certification: are we there yet?

TL;DR

The study finds that antimicrobial resistance contributes to deaths more than death certificates show, with intrinsic resistance being a bigger issue than acquired resistance.

Contribution

A new standardized definition for AMR-attributable deaths was applied to death certification in a UK hospital setting.

Findings

4.2% of deaths were attributed to antimicrobial resistance, with intrinsic resistance mechanisms being more common than acquired ones.

Only 62.5% of AMR-attributable deaths had infection recorded on death certificates, and AMR was never listed as a cause of death.

Delays in effective treatment were similar between deaths caused by intrinsic and acquired resistance mechanisms.

Abstract

The impact of antimicrobial resistance (AMR) on death at the patient level remains challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK centre through death certification.

This was a retrospective study of all patients who died in University College London Hospitals NHS Foundation Trust in 2022 (N=758). Clinical records of participants with positive microbiological samples within 28 days of death were reviewed by two independent investigators. AMR-attributable deaths were defined using a newly proposed standardized patient-level definition after consensus agreement between the two investigators. A third investigator acted as a tiebreaker in cases of disagreement.

Overall, infection was the underlying cause of death for 11.7% (89/758) of participants and was implicated in the pathway that led to death in 41.1% (357/758) of cases. The most common infection syndromes leading to death as documented on the medical certificate of confirmation of death (MCCD) were respiratory tract infections, sepsis and COVID-19. In total, 4.2% (32/758) of all deaths were AMR-attributable. AMR-attributable deaths were more commonly recorded in patients admitted under haematology (7.5%, 9/120) and in younger patients (median age 67 versus 72, P=0.01). The median time from the index sample collection until death was 4.5 days (IQR 2–10.5 days). The majority of AMR-attributable deaths (56.3%, 18/32) were caused by treatment failure and subsequent treatment delay caused by intrinsic resistance mechanisms, primarily by Enterococcus faecium (38.9%, 7/18), Enterobacterales carrying repressed chromosomal AmpCs (27.7%, 5/18) and Pseudomonas aeruginosa (22.2%, 4/18). On the contrary, a minority of AMR-attributable deaths (43.7%, 14/32) were caused by acquired resistance mechanisms, primarily derepressed AmpCs (28.6%, 4/14) and ESBLs (21.4%, 3/14). The median time to effective treatment was 32 h 15 min and did not differ significantly between the two groups. Only 62.5% (20/32) of AMR-attributable deaths as judged by study investigators had infection recorded on the MCCD. AMR was not recorded as a cause of death in any of the patients, including the 14 patients who were deemed to have suffered deaths due to acquired resistance by the study investigators.

Infection and AMR were significant causes of death in this cohort, yet there significantly underreported during death certification. In a low incidence setting for AMR, delays in treatment and AMR-attributable mortality due to intrinsic resistance mechanisms (expected phenotypes) were more common compared with acquired resistance mechanisms.