Indian consensus on the management of CRE infection in critically ill patients (ICONIC) — India

ABSTRACT

Background: The increasing burden of carbapenem-resistant Enterobacteriaceae (CRE) carriage and infection in different patient settings in India has created an acute need for guidance for clinicians regarding optimal strategies for the management of CRE infection in critically ill patients.

Research design and methods: A multidisciplinary panel of 11 Indian experts in CRE infection assembled for comprehensive discussion and consensus development. The experts developed clinical statements through a systematic review of key literature.

Main outcome measures: The panel voted anonymously on 60 clinically relevant questions, through a modified Delphi process.

Results: Forty-six key clinical consensus statements (CCS) were proposed. The panel reached a consensus on several important issues, providing recommendations on surveillance, diagnosis, prevention, pharmacokinetic challenges, combination therapy, and cornerstone molecules in CRE infections. The panel also proposed a treatment algorithm for NDM-prevalent settings.

Conclusion: These consensus statements may offer clinicians expert guidance on the management of CRE infections. There is a dearth of high-/moderate-level evidence on managing CRE infections; the recommendations presented herein are based on expert opinion.

KEYWORDS:

• Carbapenem-resistant Enterobacteriaceae (CRE)
• critically ill
• consensus statements
• combination therapy
• NDM

Article highlights

• New Delhi metallo-β–lactamase (NDM) and coproduction of NDM with Oxacillinase-48 like (OXA-48–like) enzymes are the most predominant mechanisms of carbapenem-resistant Enterobacteriaceae (CRE) infections in India.

• Strict contact isolation and hand hygiene is crucial in the prevention and treatment of CRE infection.

• A point-of–care (POC) test may become a powerful tool in guiding early appropriate therapy in CRE infections.

• Role of gentamicin and polymyxins for gut decontamination in CRE carriers is strongly discouraged due to the risk of emergence of further resistance to targeted organisms.

• The mortality risk prediction in patients with CRE infections using a scoring system may help to triage the available treatment options.

• Augmented renal clearance (ARC) is frequently encountered as an early (3–4 days) phenomenon in critically ill patients, and four-hourly estimation of glomerular filtration rate (GFR) would help as a surrogate marker for identifying underlying ARC.

• Empiric combination therapy with NDM coverage should be considered for the management of CRE infection in patients with high mortality risk.

• Polymyxins are the current cornerstone molecule for empirical therapy for CRE infections in India.

Hypernatremia is a potential dose-limiting adverse event for the optimal use of intravenous fosfomycin.

Author contributions

S Rajeev, B Veeraghavan, H Ashit, J Prakash, M Yatin, N Vasant, R Camilla, Singh R. K, S Subramanian, T Subhash and V Subhash provided substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. All authors were responsible for drafting the work or revising it critically for important intellectual content, the final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments

We would like to thank BioQuest Solutions for editorial assistance.

Declaration of interest

P Saiprasad and B Hanmant are employees of Glenmark Pharmaceuticals Ltd. who contributed toward literature search and manuscript writing. The design or procedure of the consensus and the content of the paper are in no way influenced by the grant provider. R Soman has served on the advisory of Cipla, Glenmark and MSD. S Todi has served on the advisory of Cipla, Pfizer, MSD. V Nagvekar has served on the advisory of Cipla, Pfizer, Astellas, Glenmark, Fusion, Mylan. RK Singh has served on the advisory of Cipla, Pfizer, MSD, Glenmark, Fusion, Sanofi, Astra Zeneca. A Hegde has served on the advisory of Pfizer, Glenmark, Fusion, Cipla. C Rodrigues has served on the advisory of Cipla, Pfizer, MSD, Sanofi, Novartis, Astra Zeneca. S Swaminathan has served on the advisory of Mylan, Pfizer, Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by Glenmark Pharmaceuticals Ltd.