AMR in focus: Deep dive into mortality associated with carbapenem-resistant gram-negative infections

Globally there are major concerns regarding the spread of carbapenemase-producing Enterobacterales, particularly because of the limited options for treatment of infections due to these bacteria, potential delays in initiating appropriate treatment, and caution with overuse of broad-spectrum or newer antimicrobials. These concerns are also exacerbated by a lack of detailed knowledge about the impact and outcomes of these infections, particularly serious infections such as bloodstream infections (BSI). It is therefore extremely timely that two multi-center studies have recently been published on this topic, one from researchers in Italy and the other from the United Kingdom, and these give extremely valuable information that will be helpful for decision-making and planning.

This edition of the “Deep Dive” blog series will briefly review some of the findings from these studies. This prospective multi-center study from 19 hospitals in Italy, performed between 2018 and 2020, followed up all patients in the study institutions with gram-negative bacterial infections. Primary outcomes were 30-day mortality and attributable mortality. The study included over 1200 patients and the results showed that while overall 30-day mortality in the carbapenem-susceptible group was 13.7%, mortality was higher in all the carbapenem-resistant groups, for example, 26.6% in KPC-producing gram negatives, 36.4% in metallo-betalactamase (MBL) producing Enterobacterales, and 43.2% in carbapenem-resistant Acinetobacter baumannii. Attributable mortality rates were highest for MBLs, at 35%.

The study from Anton-Vazquez and colleagues took a different approach to assess this problem by reporting a retrospective observational study of patients with carbapenemase-producing Enterobacterales bloodstream infection over a ten-year period from 2011 to 2021 in six hospitals in the United Kingdom. The study included an analysis of overall mortality and a multi-variate analysis of factors predicting 30-day mortality. The results showed 84 episodes of CPE BSI, 44% due to OXA-48, 42% due to MBLs, and 14% to KPC. 30-day case fatality rate was 38% and both sepsis and septic shock were associated with death. It is well known hat trying to find associations between specific types of antibiotic resistance and mortality is fraught with difficulty, particularly because patients with resistant organisms may well have more severe underlying diseases necessitating longer stays in hospital with more opportunities for acquisition of such organisms, nevertheless, it is striking that both studies gave similar estimates of mortality despite being performed in different countries and over different time periods.

Future studies looking in detail at the impact on mortality of some of the newer antimicrobial agents with activity against carbapenem-resistant organisms would be of great interest.

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Author: Dr. Beryl Oppenheim Dr. Beryl Oppenheim is a Senior Director of Medical Affairs at Cepheid. Beryl is a medically qualified microbiologist who has worked in the National Health Service in England for many years, leading laboratories and infection control teams. Dr. Oppenheim has published widely with more than 100 peer-reviewed publications, and her main research interests include healthcare-associated infections (HAIs), antimicrobial resistance, and infections in the critically ill and immunocompromised host.

References

I. Falcone M, Tiseo G, Carbonara S, Marino A, Di Caprio G, Carretta A, Mularoni A, Mariani MF, Maraolo AE, Scotto R, Dalfino L, Corbo L, Macera M, Medaglia AA, d'Errico ML, Gioè C, Sgroi C, Del Vecchio RF, Ceccarelli G, Albanese A, Buscemi C, Talamanca S, Raponi G, Foti G, De Stefano G, Franco A, Iacobello C, Corrao S, Morana U, Pieralli F, Gentile I, Santantonio T, Cascio A, Coppola N, Cacopardo B, Farcomeni A, Venditti M, Menichetti F; Advancing knowledge on Antimicrobial Resistant Infections Collaboration Network (ALARICO Network). Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results from a Nationwide Study in Italy (ALARICO Network). Clin Infect Dis. 2023 Jun 16;76(12):2059-2069.

II. Anton-Vazquez V, Evans TJ, Fernando S, Somasunderam D, David K, Melzer M, Hawkins L, Morris-Jones S, Arias M, Drazho B, Dall'Antonia M, Planche T. Clinical, microbiological characteristics, and predictors of mortality in patients with carbapenemase-producing Enterobacterales bloodstream infections: a multicentre study. Infect Prev Pract. 2023 Jul 8;5(3):100298