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Indian J Crit Care Med
Indian J Crit Care Med
IJCCM
Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine
0972-5229
1998-359X
Jaypee Brothers Medical Publishers

10.5005/jp-journals-10071-24639
Letter to the Editor
Eternal Hunt: Unravelling the Challenge of CRE, the Quest for Perfection Continues!
Salotagi Siddannagoud 1https://orcid.org/0009-0005-8832-5532

Kannan Abinaya 2https://orcid.org/0000-0002-2340-5495

Jindal Atul 3https://orcid.org/0000-0002-0504-1077

1–3 Department of Pediatrics, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
Atul Jindal, Department of Pediatrics, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India, Phone: +91 8224014667, e-mail: dratuljindal@gmail.com
5 2024
30 4 2024
28 5 513514
Copyright © 2024; The Author(s).
2024
https://creativecommons.org/licenses/by-nc/4.0/ © The Author(s). 2024 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
How to cite this article: Salotagi S, Kannan A, Jindal A. Eternal Hunt: Unravelling the Challenge of CRE, the Quest for Perfection Continues! Indian J Crit Care Med 2024;28(5):513–514.

Keywords

Carbapenem-resistant enterobacteriaceae
Hospital-acquired infections
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pmc Dear Editor,

The article titled “The Comparative Efficacy of Ceftazidime–Avibactam with or without Aztreonam vs Polymyxins for Carbapenem-resistant Enterobacteriaceae Infections: A Prospective Observational Cohort Study” by Vijayakumar M et al. was read with great interest.1 We appreciate the authors’ research and want to express our views about the article.

Carbapenem-resistant Enterobacteriaceae (CRE) refers to organisms displaying resistance to either Meropenem or Imipenem or those Enterobacterales isolates producing carbapenemase enzymes.2 Infections caused by these organisms are associated with high mortality rates among hospitalized patients, up to 50% in some studies.3 Ceftazidime-Avibactam (CZT-AVI), Meropenem–Vaborbactam, Imipenem–Cilastatin–Sulbactam, Polymyxins, and Cefiderocol are preferred treatment options for invasive infections.2 This study compared Ceftazidime–Avibactam with or without Aztreonam (AZT) vs Polymyxins for treating CRE.

Despite its demonstrated efficacy against NDM (New Delhi Metalloproteinase)-producing CRE, Ceftazidime-Avibactam with Aztreonam is typically reserved as a last-resort treatment for severe invasive infections.4 This study did not discuss the degree of infection, especially regarding non-bloodstream diseases. In cases of urinary tract infections, it is uncertain whether they are upper or lower UTIs, and whether they are complicated. Uncomplicated lower UTIs due to CRE can be treated with a single dose of Colistin, Aminoglycosides, or Fosfomycin.2

Researchers did not mention the genotypic and phenotypic correlation of Carbapenem-resistant Enterobacteriaceae. Though studies have proven the role of Ceftazidime–Avibactam with Aztreonam in NDM subtypes, it is not 100%.5 Hence, the summary of the sensitivity profile along with minimum inhibitory concentrations and genotype for both antibiotic groups would have clarified it. This study mentioned clinician discretion in choosing antibiotics based on the results of culture sensitivity testing and the specific Carbapenemase gene. Out of a total of 89 patients included in the study 2/3rd of patients received CAZ–AVI ± AZT, and only 1/3rd received Polymyxin. The study did not mention the reason for the difference in sample size of the groups.

This study had multiple primary outcomes, in our opinion, it should have considered a single composite primary outcome. There was mention of the duration of antibiotics and extension if needed. However, there was no mention of antibiotic policy in case there is no response or worsening despite in vitro sensitive antibiotics.6 In ICU, it is common to have hospital-acquired infections and antibiotics need to be modified in case of any. There was no mention of such episodes of new HAI during antibiotic therapy and the antibiotic modifications if any.

It has been stated that CAZ–AVI ± AZT was used in patients with NDM infections, but 19 patients in the CAZ–AVI ± AZT group harbored both NDM and OXA 48 genes. The use of AZT in these patients is unclear because the overall number of NDM infections in the CAZ-AVI + AZT group does not equal the number of NDM infections in the CAZ-AVI ± AZT group.

We appreciate the efforts of the researchers in conducting this study. An ideal approach would be to use the genomics of bacteria to choose antibiotics,5 and this is something that this study has used. However, its availability and affordability are an issue in India. We also emphasize that the site of infection, severity, and MIC of sensitive antibiotics should also be considered while choosing antibiotics despite bacterial genomics. High-end antibiotics like the one used in this study should be reserved for severe invasive multi-drug resistant infections. Further studies for genotype-phenotype correlation, site and severity-specific usage of antibiotics, and their efficacy are needed for multidrug-resistant organisms like CRE.

Orcid

Siddannagoud Salotagi https://orcid.org/0009-0005-8832-5532

Abinaya Kannan https://orcid.org/0000-0002-2340-5495

Atul Jindal https://orcid.org/0000-0002-0504-1077

Source of support: Nil

Conflict of interest: None
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References

1. Vijayakumar M Selvam V Renuka MK Rajagopalan RE The comparative efficacy of ceftazidime–avibactam with or without aztreonam vs polymyxins for carbapenem-resistant Enterobacteriaceae Infections: a prospective observational cohort study Indian J of Crit Care Med: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine 2023 27 12 923 10.5005/jp-journals-10071-24577
2. Tamma PD Aitken SL Bonomo RA Mathers AJ van Duin D Clancy CJ Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections Clin Infect Dis 2023 ciad428 10.1093/cid/ciad428 37463564
3. Soontaros S Leelakanok N Association between carbapenem-resistant Enterobacteriaceae and death: A systematic review and meta-analysis Am J Infect Control 2019 47 10 1200 1212 10.1016/j.ajic.2019.03.020 31072673
4. Larcher R Laffont-Lozes P Roger C Doncesco R Groul-Viaud C Martin A et al. Last resort beta-lactam antibiotics for treatment of New-Delhi Metallo-Beta-Lactamase producing Enterobacterales and other Difficult-to-Treat Resistance in Gram-negative bacteria: A real-life study Front Cell Infect Microbiol 2022 5 12 1048633 10.3389/fcimb.2022.1048633
5. Sun S Chen K Kong X Tian W Niu S Genetic diversity and in vitro activity of aztreonam/avibactam and ceftazidime/avibactam against carbapenem-resistant Enterobacterales: A multi-centre study in Southwest China Infect Drug Resist 2022 1 2243 2251 10.2147/IDR.S357396
6. Lu G Tang H Xia Z Yang W Xu H Liu Z et al. In vitro and in vivo antimicrobial activities of ceftazidime/avibactam alone or in combination with aztreonam against carbapenem-resistant Enterobacterales Infect Drug Resist 2022 1 7107 7116 10.2147/IDR.S385240
