IDSA releases guidance on antibiotic selection for gram-negative antimicrobial-resistant bacterial infections

The Infectious Diseases Society of America (IDSA) on Sept. 8 published guidance on treating patients with infections caused by three groups of antimicrobial-resistant bacteria that the CDC have designated as urgent or serious threats.

These gram-negative bacteria include extended-spectrum beta-lactamase-producing (ESBL) Enterobacterales, carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance. U.S. hospitals of all sizes encounter these bacteria, which cause a wide range of serious infections that carry significant morbidity and mortality risks, the guidance said.

Despite approval of new antibiotics, treatment options against these infections are limited. To help guide clinicians in selecting antibiotic therapy for these infections, which are difficult to manage and are not covered by present guidelines, the IDSA developed a specific guidance document rather than comprehensive clinical practice guidelines. The document, which is the first of its kind, was developed by a panel of six practicing infectious diseases subspecialists with clinical and research expertise in treating resistant bacterial infections. Preferred and alternative treatment recommendations were based on a comprehensive (but not necessarily systematic) review of the literature; the document does not include a formal grading of the evidence. The recommendations were made assuming that the causative organism has been identified and that in vitro activity of antibiotics has been demonstrated.

Key recommendations include the following:

• Nitrofurantoin and trimethoprim-sulfamethoxazole are preferred treatment options for uncomplicated cystitis caused by ESBL Enterobacterales.
• Ertapenem, meropenem, imipenem-cilastatin, ciprofloxacin, levofloxacin, or trimethoprim-sulfamethoxazole is the preferred treatment option for pyelonephritis and complicated urinary tract infections (UTIs) caused by ESBL Enterobacterales.
• A carbapenem is preferred for the treatment of infections outside of the urinary tract caused by ESBL Enterobacterales.
• Piperacillin-tazobactam and cefepime should be avoided for the treatment of infections caused by ESBL Enterobacterales, even if susceptibility to these drugs is demonstrated.
• Ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, nitrofurantoin, or a single dose of an aminoglycoside is the preferred treatment option for uncomplicated cystitis caused by CRE.
• Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol are preferred treatment options for pyelonephritis and complicated UTIs caused by CRE resistant to both ertapenem and meropenem.
• Extended-infusion meropenem is the preferred treatment for infections outside of the urinary tract caused by CRE resistant to ertapenem but susceptible to meropenem, when carbapenemase testing results are either not available or negative. In the case of resistance to both ertapenem and meropenem or if carbapenemase production is present, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam are the preferred treatment options.
• Polymyxin B and colistin should be avoided for the treatment of infections caused by CRE, although clinicians may consider colistin as a last resort for uncomplicated CRE cystitis. Combination antibiotic therapy (i.e., the use of a beta-lactam in combination with an aminoglycoside, fluoroquinolone, or polymyxin) is not routinely recommended.
• Ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, cefiderocol, or a single dose of an aminoglycoside is the preferred treatment option for uncomplicated cystitis caused by P. aeruginosa with difficult-to-treat resistance.
• Ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, and cefiderocol are the preferred treatment options for pyelonephritis and complicated UTIs caused by difficult-to-treat P. aeruginosa.
• Ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-cilastatin-relebactam, as monotherapy, are the preferred treatment options for the treatment of infections outside of the urinary tract caused by difficult-to-treat P. aeruginosa.

The expert panel did not consider the cost of agents and did not provide recommendations on empiric treatment or durations of therapy. The guidance will be updated through an iterative review process that will incorporate new evidence-based data, and future versions will expand recommendations to include other problematic gram-negative pathogens, the document said.