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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

38738190
10.5005/jp-journals-10071-24701
Letter to the Editor
Author Response
Vijayakumar M 1https://orcid.org/0000-0001-6866-4709

Selvam Velmurugan 2https://orcid.org/0000-0002-9495-2293

Renuka MK 3https://orcid.org/0000-0002-7412-2989

Rajagopalan Ram E 4https://orcid.org/0000-0001-9486-3285

1–4 Department of Critical Care Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
Vijayakumar M, Department of Critical Care Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India, Phone: +91 9642599067, e-mail: vijay092@gmail.com
5 2024
30 4 2024
28 5 515515
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: Vijayakumar M, Selvam V, Renuka MK, Rajagopalan RE. Author Response. Indian J Crit Care Med 2024;28(5):515.

Keywords

Carbapenem-resistant enterobacterales
Ceftazidime-avibactam
Critically ill patients
Sequential organ failure assessment
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pmcWe thank Salotagi S et al.1 for their interest in our study. We have noted the reader's concerns regarding antibiotic selection and are hereby addressing their queries. It's essential to clarify that although a single dose of aminoglycosides or fosfomycin is conventionally reserved for managing uncomplicated lower urinary tract infections (UTIs), our study uniquely focused on patients admitted to the intensive care unit, manifesting signs of severe sepsis and septic shock. Furthermore, the severity of illness among these patients was underscored by a mean sequential organ failure assessment (SOFA) score was 7, indicative of a higher risk of ICU mortality estimated at around 30%.

In our study, samples exhibiting carbapenem resistance underwent testing using the VITEK 2 automated system, adhering to ISO standards to determine minimum inhibitory concentrations (MICs). The GeneXpert system, utilizing PCR technology detects the presence of carbapenem-resistant (CARBA-R) genes, including NDM, OXA-48, Imipenemase (IMP-1), and KPC. The interaction between CAZ-AVI and AZT was evaluated through a double-disk sandwich diffusion method. However, it's important to note that the genotypic and phenotypic correlation of CARBA-R Enterobacteriaceae falls outside the scope of our study's objectives.2 We acknowledge the viewpoint expressed by our readers regarding the reserved use of ceftazidime-avibactam with aztreonam as a last-resort treatment for severe invasive infections. Notably, none of our patients received this combination therapy as an empirical option. Approximately 50% of patients were administered ceftazidime-avibactam with aztreonam as early targeted therapy following CARBA-R results, while the remainder received it after the final sensitivity report.3,4

The main study outcomes included evaluating clinical success on day 14 and the microbiological response. Clinical success was a composite outcome defined by various factors including patient survival, hemodynamic stability, and improvement in SOFA score. To analyze this composite outcome, a cox multivariate regression model was employed, adjusting for baseline SOFA score and existing comorbidities. Unlike univariate methods, the cox model enables simultaneous assessment of multiple factors, providing a thorough evaluation of their influence on survival time.5

Despite the promising results, it's crucial to acknowledge the limitations of our study, including the influence of clinician discretion in antibiotic selection and the potential for bias in patient allocation. We agree with the readers’ suggestion that a well-structured randomized controlled trial would provide more robust evidence to address these limitations and offer clearer insights into treatment outcomes. Moving forward, further research is warranted to explore optimal treatment strategies for CARBA-R Enterobacteriaceae infections, taking into account factors such as infection severity, antibiotic resistance patterns, and individual patient characteristics. By continuing to advance our understanding of these complex infections, we can enhance patient outcomes and contribute to the global effort in combating antimicrobial resistance.

Orcid

Vijayakumar M https://orcid.org/0000-0001-6866-4709

Velmurugan Selvam https://orcid.org/0000-0002-9495-2293

Renuka MK https://orcid.org/0000-0002-7412-2989

Ram E Rajagopalan https://orcid.org/0000-0001-9486-3285

Source of support: Nil

Conflict of interest: None
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References

1. 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 38738202
2. Baran I Aksu N Phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Turkey Ann Clin Microbiol Antimicrob 2016 15 20 10.1186/s12941-016-0136-2 27048322
3. Falcone M Daikos GL Tiseo G Bassoulis D Giordano C Galfo V et al. Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by metallo-β-lactamase–producing enterobacterales Clin Infect Dis 2021 72 11 1871 1878 10.1093.cid/ciaa586 32427286
4. Shaw E Rombauts A Tubau F Padullés A Càmara J Lozano T et al. Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M-15-producing Klebsiella pneumoniae infection J Antimicrob Chemother 2018 73 4 1104 1106 10.1093/jac/dkx496 29272413
5. Deo SV Deo V Sundaram V Survival analysis-part 2: Cox proportional hazards model Indian J Thorac Cardiovasc Surg 2021 37 2 229 233 10.1007/s12055-020-01108-7 33642726
