Which antibiotics are typically active against extensively drug‑resistant uropathogenic Escherichia coli (XDR UPEC)?

XDR UPEC Antibiotic Sensitivity

For extensively drug-resistant (XDR) uropathogenic E. coli, fosfomycin and nitrofurantoin remain the most consistently active oral agents, while carbapenems, polymyxins, tigecycline, and novel β-lactam-β-lactamase inhibitor combinations represent the primary parenteral options.

First-Line Agents with Preserved Activity

Oral Options

• Fosfomycin demonstrates the highest sensitivity rates among oral agents for MDR and XDR UPEC strains, maintaining activity even when resistance to fluoroquinolones, trimethoprim-sulfamethoxazole, and extended-spectrum cephalosporins is present 1, 2.

• Nitrofurantoin retains low resistance rates and remains highly effective against multidrug-resistant UPEC isolates, including those resistant to extended-spectrum cephalosporins and fluoroquinolones 3, 2.

Parenteral Options for Severe Infections

• Carbapenems remain the cornerstone treatment for MDR UPEC urosepsis, though their overreliance has contributed to emerging carbapenem resistance 1.

• Novel β-lactam-β-lactamase inhibitor combinations provide alternatives for carbapenem-resistant strains, including ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam 1.

• For metallo-β-lactamase producers (NDM, IMP-4), the combination of ceftazidime-avibactam with aztreonam has demonstrated efficacy 1.

Emerging and Alternative Agents

• Cefiderocol represents a novel siderophore cephalosporin with activity against carbapenem-resistant UPEC 1.

• Polymyxins (colistin, polymyxin B) serve as last-resort options for extensively resistant strains 1.

• Tigecycline and aminoglycosides may retain activity against some XDR strains, though their use requires careful consideration of pharmacokinetics and toxicity 1.

Critical Clinical Caveats

Avoid relying on traditional first-line agents for XDR UPEC, as resistance rates to trimethoprim-sulfamethoxazole (68%) and fluoroquinolones (63%) are extremely high in MDR populations 2.

Extended-spectrum cephalosporin resistance is strongly associated with co-resistance to aztreonam (84.6%), trimethoprim-sulfamethoxazole (84.6%), and fluoroquinolones (81.5%), making these agents unreliable 2.

β-lactam-β-lactamase inhibitor combinations (amoxicillin-clavulanic acid) show variable regional resistance (5.3-37.6% in Europe), but may still have utility in select MDR cases that are not XDR 3, 1.

Practical Algorithm

1. For uncomplicated XDR cystitis: Use fosfomycin or nitrofurantoin as first-line oral therapy 3, 2

2. For complicated UTI or pyelonephritis with XDR UPEC: Initiate carbapenem therapy pending susceptibility results 1

3. For carbapenem-resistant XDR UPEC: Consider novel β-lactam combinations, cefiderocol, or polymyxins based on available susceptibilities 1

4. For metallo-β-lactamase producers: Use ceftazidime-avibactam plus aztreonam combination 1

Always obtain culture and susceptibility testing before finalizing therapy, as XDR patterns vary significantly by geographic region and individual strain characteristics 1, 4.