ICU infections, stewardship and the immunocompromised

Carbapenem-resistant and MDR Gram-negative infections

Reviewed Nov 2026·5 references
New· views rounded down, updated weekly

Mechanism-directed therapy for CRE (NDM, OXA-48, KPC), CRAB and CRPA following ICMR 2022 and IDSA 2024, with polymyxin dosing and infection control.

Definition
CRE = Enterobacterales resistant to any carbapenem. In India, NDM (metallo-beta-lactamase) and OXA-48-like carbapenemases predominate, often together. CRAB and CRPA are carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.

At the bedside

  1. 1

    Infection or colonisation?

    Treat only clinical infection; Acinetobacter and Stenotrophomonas in respiratory or wound samples are often colonisers.

  2. 2

    Ask the lab for mechanism

    Request carbapenemase testing (phenotypic/PCR: NDM, OXA-48, KPC) and ceftazidime-avibactam + aztreonam synergy testing.

  3. 3

    NDM (± OXA-48) CRE

    First choice: ceftazidime-avibactam 2.5 g q8h + aztreonam 2 g q8h, both over 3 h (after synergy shown). Alternatives: polymyxin + another active agent (tigecycline, aminoglycoside, IV fosfomycin) or high-dose meropenem if MIC < 16.

  4. 4

    OXA-48-like or KPC CRE

    Ceftazidime-avibactam 2.5 g q8h over 3 h (if susceptible). Meropenem-vaborbactam or imipenem-relebactam also options for KPC where available.

  5. 5

    CRAB

    High-dose sulbactam (6-9 g/day; e.g. ampicillin-sulbactam 9 g q8h over 4 h) as backbone plus a second active agent (polymyxin, minocycline 200 mg q12h, tigecycline) for moderate-severe infection.

  6. 6

    CRPA

    Use any susceptible beta-lactam (ceftazidime, cefepime, piperacillin-tazobactam); newer agents (ceftolozane-tazobactam, ceftazidime-avibactam) per susceptibility; polymyxin-based combination only when nothing else works.

  7. 7

    Polymyxin rules

    Always load. Polymyxin B for systemic infections (no renal adjustment); colistin for UTI (renal excretion as active drug). Avoid tigecycline monotherapy for bacteraemia/pneumonia.

  8. 8

    Source control and infection control

    Remove lines, drain collections; contact precautions, cohorting, rectal surveillance per policy, hand hygiene.

NDM CRE (with aztreonam) or OXA-48/KPC (alone)

Ceftazidime-avibactam (± aztreonam)

IV over 3 h
Dose
2.5 g q8h (+ aztreonam 2 g q8h over 3 h for MBL)

CRO when no better option

Polymyxin B

IV
Dose
Load 2.5 mg/kg (25,000 units/kg), then 1.5 mg/kg (15,000 units/kg) q12h
Worked example
70 kg: 17.5 lakh units (175 mg) load over 2 h, then 10.5 lakh units (105 mg) q12h; Indian vial 5 lakh units

1 mg = 10,000 units.

CRO UTI or when polymyxin B unavailable

Colistin (colistimethate sodium)

IV
Dose
9 million units load, then 4.5 million units q12h

CRAB backbone

Ampicillin-sulbactam (high dose)

IV over 4 h
Dose
9 g q8h (sulbactam 9 g/day)

Mechanism-directed therapy (ICMR 2022)

Organism / mechanismFirst choiceOther options
CRE - NDM (MBL) ± OXA-48Ceftazidime-avibactam + aztreonam, prolonged infusion (synergy test)Polymyxin + active agent; high-dose meropenem if MIC < 16
CRE - OXA-48-likeCeftazidime-avibactam (prolonged infusion)Polymyxin + active agent
CRE - KPCCeftazidime-avibactamPolymyxin + active agent
CRABHigh-dose sulbactam + second active agentPolymyxin, minocycline, tigecycline
CRPAAny susceptible beta-lactam/BL-BLIPolymyxin-based combination if pan-resistant
Red flag · call your senior now
Septic shock with known CRE colonisation: empirical regimen must cover CRE until cultures are back.
Pitfall
Using polymyxin B for UTI (low urinary concentration) or colistin without a loading dose.
Pitfall
Empirical ceftazidime-avibactam + aztreonam: national guidance reserves it for targeted therapy.
Pearl
Give ceftazidime-avibactam and aztreonam simultaneously (Y-site) so the inhibitor protects aztreonam at the same time.

References

  1. 1

    Indian Council of Medical Research. Guidance on Diagnosis and Management of Carbapenem Resistant Gram-negative Infections. New Delhi: ICMR; 2022.

  2. 2

    Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 guidance on the treatment of antimicrobial-resistant gram-negative infections. Clin Infect Dis 2024 (online ahead of print).

  3. 3

    Tsuji BT, Pogue JM, Zavascki AP, et al. International consensus guidelines for the optimal use of the polymyxins. Pharmacotherapy 2019;39:10-39.

  4. 4

    Indian Council of Medical Research. Annual Report: Antimicrobial Resistance Research and Surveillance Network, January 2023-December 2023. New Delhi: ICMR; 2024.

  5. 5

    National Centre for Disease Control (DGHS, MoHFW) and Indian Council of Medical Research. National Treatment Guidelines for Antimicrobial Use in Infectious Disease Syndromes, Version 2.0. New Delhi: MoHFW; November 2025.

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