Antimicrobial Resistant Gram-Negative Infections

Guideline Reference: IDSA 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections (July 18, 2023)

Guideline Scope: This guideline focuses on ESBL Enterobacterales, AmpC ESBL, CPE, MDR Pseudomonas, Carbapenem-resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia.

ESBL-E

ESBLs are enzymes that inactivate most penicillins, cephalosporins, and aztreonam. EBSL-E generally remain susceptible to carbapenems. ESBLs do not inactivate non–β-lactam agents (eg, ciprofloxacin, trimethoprim-sulfamethoxazole, gentamicin). However, organisms carrying ESBL genes often harbor additional genes or mutations in genes that mediate resistance to a broad range of antibiotics.

ESBL-Enterobacterales is growing in community prevalence in the USA. Any gram-negative organism has the potential to harbor ESBL genes; however, they are most prevalent in Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis.

Infection	Recommended Regimen
Uncomplicated Cystitis	Nitrofurantoin, TMPSMX. Less preferred are cipro, levoflox, and carbapenems. Single dose aminoglycosides and oral fosfomycin are also alternatives.
Pyelonephritis and complicated UTI	TMP-SMX, ciprofloxacin, or levofloxacin are preferred treatment options. Ertapenem, meropenem, imipenem are second-line. Aminoglycosides for a full treatment course are an alternative. Fosfomycin and nitrofurantoin do not achieve adequate concentrations in the renal parenchyma and are therefore not recommended.

Antibiotic Dosing