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How to Treat ESBL, CRE, and DTR-Pseudomonas

June 24, 2021

Written by Clay Smith

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For ESBL, non-β-lactam antibiotics – like TMP/SMX or nitrofurantoin – usually work well for cystitis. For CRE or DTR-P. aeruginosa, look it up, call ID, and know this may mean alternative (and often expensive) antibiotics.

Why does this matter?
Antimicrobial resistance is a major problem that costs up to 35,000 lives in the U.S. alone per year. There are three highly resistant organisms that are the focus of this article: extended-spectrum β-lactamase– producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). If you’re like me and are wondering why it’s called Enterobacterales and not Enterobacteriaceae anymore, you must see this epic nerdy comic in the Journal of Clinical Microbiology. For all these recommendations, you have to consider local resistance patterns and culture and sensitivity data on the actual organism in question. But here are general recommendations.



  • ESBL-E have enzymes that inactivate most penicillins, cephalosporins, and aztreonam; non-β-lactam antibiotics usually work fine, unless the organism has additional resistance genes. The following recommendations are largely quoted and only minimally adapted from the IDSA recommendations table.

  • Cystitis – First-line: nitrofurantoin, trimethoprim-sulfamethoxazole; second-line: amoxicillin-clavulanate, single-dose aminoglycosides, fosfomycin (Escherichia coli only); third-line: ciprofloxacin, levofloxacin, ertapenem, meropenem, imipenem-cilastatin

  • Pyelonephritis or complicated urinary tract infection – Ertapenem, meropenem, imipenem cilastatin, ciprofloxacin, levofloxacin, or trimethoprim-sulfamethoxazole

  • Infections outside of the urinary tract – Meropenem, imipenem-cilastatin, ertapenem; Oral step-down therapy to ciprofloxacin, levofloxacin, or trimethoprim-sulfamethoxazole should be considered.

CRE and DTR-P. aeruginosa

  • These gram-negatives are usually nosocomial. An interesting fact about CRE is that it is often resistant to ertapenem but not meropenem.

  • Unlike ESBL, which I have seen several times in ED patients and outpatients, you are less likely to run into CRE and DTR-P in the ED. But if you do, go straight to the IDSA source to get free, full-text, up to date recommendations for treatment, and give your friendly and brilliant ID colleagues a call.

Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis. 2021 Apr 8;72(7):e169-e183. doi: 10.1093/cid/ciaa1478.

What are your thoughts?