Antimicrobial resistance in ICU: ESBL, CRE, MRSA, VRE management

Also known as VRE · MDR-GNB · Carbapenemase · KPC · NDM · OXA-48 · CTX-M · Antibiotic stewardship

Antimicrobial resistance (AMR) in ICU: resistant organisms limit antibiotic options, increase mortality. KEY organisms: (1) ESBL (Extended-Spectrum Beta-Lactamase) — E. coli, Klebsiella — resistant to penicillins, cephalosporins. Treat: carbapenem (meropenem). (2) CRE (Carbapenem-Resistant Enterobacteriaceae) — resistant to carbapenems. Treat: polymyxin/colistin, ceftazidime-avibactam, meropenem-vaborbactam. (3) MRSA — resistant to beta-lactams. Treat: vancomycin, linezolid, daptomycin. (4) VRE (Vancomycin-Resistant Enterococcus) — treat: linezolid, daptomycin. Prevention: antibiotic stewardship, infection control, surveillance, isolation. CRE mortality 40-50%.

high22 referencesUpdated 20 Aug 20268 min readVerification in progress

The one-line answer

Four resistant organisms dominate the ICU, and the enzyme or gene decides the drug. ESBL Enterobacterales need a carbapenem — in MERINO, meropenem beat piperacillin-tazobactam on 30-day mortality (4 versus 12 percent) in ceftriaxone-resistant E. coli and Klebsiella bacteraemia. CRE are the most urgent threat — bacteraemia mortality exceeded 40 percent in the INCREMENT cohort — and the Ambler class of the carbapenemase dictates therapy: serine enzymes (KPC, OXA-48) fall to ceftazidime-avibactam, which cut hospital mortality to 9 versus 32 percent for colistin in CRACKLE; metallo-enzymes (NDM, VIM, IMP) need aztreonam plus ceftazidime-avibactam. MRSA (mecA) needs vancomycin targeting AUC/MIC 400 to 600, linezolid for pneumonia, or daptomycin (never for pneumonia — surfactant inactivates it). VRE needs linezolid or high-dose daptomycin (at least 10 mg/kg daily). Stewardship and isolation are non-negotiable.^[7]^[16]^[11]^[21]^[17]^[9]^[8]^[20]^[18]

Meet the patient

A 67-year-old man is transferred from an overseas hospital in septic shock, ventilated, on noradrenaline. Blood cultures grow Klebsiella pneumoniae resistant to all beta-lactams including the carbapenems, with a positive modified Hodge test. The isolate is susceptible only to colistin and tigecycline. His INCREMENT-CPE score is 8.^[3]

This is the scenario every ICU fears. The resistance mechanism decides the drug, and the wrong empiric choice is, on its own, a predictor of death. The questions are: what carbapenemase is this, what is the single best active agent, and is this patient sick enough to need combination therapy?^[3]

References22Show

[1]Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis Lancet Infect Dis, 2018.PMID 29276051
[2]Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Machuca I, Pascual A. Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae Clin Microbiol Rev, 2018.PMID 29444952
[3]Tzouvelekis LS, Markogiannakis A, Piperaki E, Souli M, Daikos GL. Treating infections caused by carbapenemase-producing Enterobacteriaceae Clin Microbiol Infect, 2014.PMID 24890393
[4]Holmes AH, Moore LSP, Sundsfjord A, et al. Understanding the mechanisms and drivers of antimicrobial resistance Lancet, 2016.PMID 26603922
[5]Rhee C, Kadri SS, Dekker JP, et al. Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use JAMA Netw Open, 2020.PMID 32297949
[6]Timsit JF, Bassetti M, Cremer O, et al. Rationalizing antimicrobial therapy in the ICU: a narrative review Intensive Care Med, 2019.PMID 30659311
[7]Harris PNA, Tambyah PA, Lye DC, et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial JAMA, 2018.PMID 30208454
[8]Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study Clin Infect Dis, 2012.PMID 22247123
[9]Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists Clin Infect Dis, 2020.PMID 32658968
[10]Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, et al. A Predictive Model of Mortality in Patients With Bloodstream Infections due to Carbapenemase-Producing Enterobacteriaceae Mayo Clin Proc, 2016.PMID 27712635
[11]Yahav D, Giske CG, Grāmatniece A, et al. New β-Lactam-β-Lactamase Inhibitor Combinations Clin Microbiol Rev, 2020.PMID 33177185
[12]Paul M, Daikos GL, Durante-Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial Lancet Infect Dis, 2018.PMID 29456043
[13]Tamma PD, Heil EL, Justo JA, et al. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections Clin Infect Dis, 2024.PMID 39108079
[14]Kaye KS, Bhowmick T, Metallidis S, et al. Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial JAMA, 2018.PMID 29486041
[15]Duplessis C, Crum-Cianflone NF. Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA) Clin Med Rev Ther, 2011.PMID 21785568
[16]Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, et al. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study Lancet Infect Dis, 2017.PMID 28442293
[17]Falcone M, Daikos GL, Tiseo G, et al. Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales Clin Infect Dis, 2021.PMID 32427286
[18]Cairns KA, Udy AA, Peel TN, et al. Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections Clin Microbiol Rev, 2023.PMID 37067406
[19]Luther MK, Timbrook JT, Caffrey AR, et al. Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis Crit Care Med, 2018.PMID 29088001
[20]Silverman JA, et al. Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact J Infect Dis, 2005.PMID 15898002
[21]van Duin D, Lok JJ, Earley M, et al. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae Clin Infect Dis, 2018.PMID 29020404
[22]Bassetti M, Echols R, Matsunaga Y, et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial Lancet Infect Dis, 2021.PMID 33058795

Antimicrobial resistance in ICU: ESBL, CRE, MRSA, VRE management

Also known as VRE · MDR-GNB · Carbapenemase · KPC · NDM · OXA-48 · CTX-M · Antibiotic stewardship

high22 referencesUpdated 20 Aug 20268 min readVerification in progress

Meet the patient

References22Show

[1]Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis Lancet Infect Dis, 2018.PMID 29276051
[2]Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Machuca I, Pascual A. Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae Clin Microbiol Rev, 2018.PMID 29444952
[3]Tzouvelekis LS, Markogiannakis A, Piperaki E, Souli M, Daikos GL. Treating infections caused by carbapenemase-producing Enterobacteriaceae Clin Microbiol Infect, 2014.PMID 24890393
[4]Holmes AH, Moore LSP, Sundsfjord A, et al. Understanding the mechanisms and drivers of antimicrobial resistance Lancet, 2016.PMID 26603922
[5]Rhee C, Kadri SS, Dekker JP, et al. Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use JAMA Netw Open, 2020.PMID 32297949
[6]Timsit JF, Bassetti M, Cremer O, et al. Rationalizing antimicrobial therapy in the ICU: a narrative review Intensive Care Med, 2019.PMID 30659311
[7]Harris PNA, Tambyah PA, Lye DC, et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial JAMA, 2018.PMID 30208454
[8]Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study Clin Infect Dis, 2012.PMID 22247123
[9]Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists Clin Infect Dis, 2020.PMID 32658968
[10]Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, et al. A Predictive Model of Mortality in Patients With Bloodstream Infections due to Carbapenemase-Producing Enterobacteriaceae Mayo Clin Proc, 2016.PMID 27712635
[11]Yahav D, Giske CG, Grāmatniece A, et al. New β-Lactam-β-Lactamase Inhibitor Combinations Clin Microbiol Rev, 2020.PMID 33177185
[12]Paul M, Daikos GL, Durante-Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial Lancet Infect Dis, 2018.PMID 29456043
[13]Tamma PD, Heil EL, Justo JA, et al. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections Clin Infect Dis, 2024.PMID 39108079
[14]Kaye KS, Bhowmick T, Metallidis S, et al. Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial JAMA, 2018.PMID 29486041
[15]Duplessis C, Crum-Cianflone NF. Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA) Clin Med Rev Ther, 2011.PMID 21785568
[16]Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, et al. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study Lancet Infect Dis, 2017.PMID 28442293
[17]Falcone M, Daikos GL, Tiseo G, et al. Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales Clin Infect Dis, 2021.PMID 32427286
[18]Cairns KA, Udy AA, Peel TN, et al. Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections Clin Microbiol Rev, 2023.PMID 37067406
[19]Luther MK, Timbrook JT, Caffrey AR, et al. Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis Crit Care Med, 2018.PMID 29088001
[20]Silverman JA, et al. Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact J Infect Dis, 2005.PMID 15898002
[21]van Duin D, Lok JJ, Earley M, et al. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae Clin Infect Dis, 2018.PMID 29020404
[22]Bassetti M, Echols R, Matsunaga Y, et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial Lancet Infect Dis, 2021.PMID 33058795