What are the treatment options for a hospital-acquired Urinary Tract Infection (UTI) caused by Extended-Spectrum Beta-Lactamase (ESBL) producing bacteria?

From the Guidelines

For a hospital-acquired urinary tract infection (UTI) caused by Extended-Spectrum Beta-Lactamase (ESBL)-producing organisms, carbapenems are the first-line treatment option, with meropenem and ertapenem being preferred due to their efficacy and stability against ESBL enzymes, as supported by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1. The treatment of hospital-acquired UTIs caused by ESBL-producing bacteria requires careful consideration of the antibiotic regimen to ensure effective treatment and minimize the risk of resistance.

• The ESCMID guidelines recommend carbapenems, such as meropenem and ertapenem, as the first-line treatment option for ESBL-producing organisms 1.
• Specifically, meropenem 1g IV every 8 hours or ertapenem 1g IV daily for 7-10 days are recommended regimens.
• For patients with carbapenem allergies, fosfomycin 3g orally every 48 hours for 3 doses or amikacin 15mg/kg IV daily (with therapeutic drug monitoring) can be considered.
• It is essential to obtain urine cultures before starting antibiotics and adjust therapy based on susceptibility results, as ESBL-producing bacteria are resistant to most penicillins, cephalosporins, and aztreonam due to their ability to hydrolyze the beta-lactam ring in these antibiotics.
• Carbapenems remain stable against ESBL enzymes due to their unique molecular structure, making them an effective treatment option.
• For prevention of recurrence, ensuring adequate hydration, completing the full antibiotic course, and implementing infection control measures, including proper catheter care if present, are crucial.
• Hospital antibiogram data should guide empiric therapy choices, as resistance patterns vary by institution 1.

From the FDA Drug Label

5 grams (ceftazidime 2 grams and avibactam 0.5 grams) intravenously every 8 hours or the best available intravenous therapy (BAT) for 5 to 21 days of treatment. Among Gram-negative uropathogens from both arms of Trial 2, genotypic testing identified certain ESBL groups (e.g., TEM-1, SHV-12, CTX-M-15, CTX-M-27, KPC-2, KPC-3, OXA-48) and AmpC beta-lactamases expected to be inhibited by avibactam in isolates from 273/281 (97.2%) patients in the mMITT population.

The treatment options for a hospital-acquired Urinary Tract Infection (UTI) caused by Extended-Spectrum Beta-Lactamase (ESBL) producing bacteria include:

• Avibactam (in combination with ceftazidime) 5 grams (ceftazidime 2 grams and avibactam 0.5 grams) intravenously every 8 hours for 5 to 21 days of treatment 2
• Best available therapy (BAT), which may include carbapenem antibacterial drugs such as meropenem, imipenem, doripenem, and colistin 2 Key points:
• Avibactam has been shown to inhibit certain ESBL groups and AmpC beta-lactamases in 97.2% of patients in the mMITT population 2
• Clinical and microbiological cure rates with avibactam were similar to the overall results in the subset of patients with ESBL-producing bacteria 2

From the Research

Treatment Options for Hospital-Acquired UTI caused by ESBL-producing Bacteria

• The treatment options for UTIs due to ESBLs-producing Enterobacteriales include:
  • Oral options: nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin for ESBL-E coli, and pivmecillinam, fosfomycin, finafloxacin, and sitafloxacin for ESBL-Klebsiella pneumoniae 3, 4
  • Parenteral options: piperacillin-tazobactam (for ESBL-E coli only), carbapenems including meropenem/vaborbactam, imipenem/cilastatin-relebactam, and sulopenem, ceftazidime-avibactam, ceftolozane-tazobactam, aminoglycosides including plazomicin, cefiderocol, fosfomycin, sitafloxacin, and finafloxacin 3, 5
• Piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome 6
• Initiation of narrow-spectrum antibiotics in septic UTI with ESBL-E might not deteriorate the clinical outcome if promptly escalated on clinical deterioration or with ESBL-E culture results 7

Considerations for Treatment

• Knowledge of the common uropathogens and local susceptibility patterns is essential in determining appropriate empiric antibiotic therapy of UTIs 3, 5
• The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance 3, 5
• Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options 3, 5