The Infectious Diseases Society of America (IDSA) has released updated guidelines for the treatment of antimicrobial-resistant Gram-negative (AMR) infections. The updated guidelines were published in Clinical infectious diseases.
The updated guidelines cover preferred and alternative treatment options for 6 AMR Gram-negative infections, as follows:
- Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E);
- AmpC β-lactamase-producing Enterobacteriaceae (AmpC-E);
- Carbapenem-resistant Enterobacteriaceae (CRE);
- Pseudomonas aeruginosa with difficult to treat resistance (DTR-P. aeruginosa);
- Carbapenem resistant Acinetobacter baumannii (CRAB); And
- Stenotrophomonas maltophilia.
A panel of infectious disease specialists with expertise in the management of AMR infections was assembled to suggest preferred and alternative therapeutic approaches for each pathogen group. They based their suggestions on therapeutic issues commonly encountered in clinical practice. Each AMR Gram-negative infection examined was designated as an urgent or serious threat by the Centers for Disease Control and Prevention (CDC).
ESBL-E infections
Simple cystitis
- Preferred agents include nitrofurantoin and trimethoprim-sulfamethoxazole (TMP-SMX).
- Alternative agents include ciprofloxacin and levofloxacin.
Piperacillin-tazobactam (TZP) and cefepime are only recommended if initiated as empiric therapy, although the panel advises monitoring patients closely for clinical response if this approach is selected.
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The field of AMR is dynamic and rapidly evolving, and the treatment of antimicrobial-resistant infections will continue to pose a challenge to clinicians.
Pyelonephritis and complicated urinary tract infection (cUTI)
- Preferred agents include TMP-SMX, ciprofloxacin, and levofloxacin.
- Alternative agents include ertapenem, meropenem, and imipenem-cilastatin.
Infections outside the urinary tract
- Preferred agents include meropenem, imipenem-cilastatin, and ertapenem.
For patients who respond to preferred agents, a transition to oral agents such as TMP-SMX, ciprofloxacin, and levofloxacin should be considered if sensitivity is observed.
Combinations of β-lactam-β-lactamase inhibitors such as ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam and cefiderocol are preferentially reserved for carbapenem-resistant ESBL-E infections outside the urinary tract.
AmpC-E infections
Infections caused by Complex E cloacae, Klebsiella aerogenes, And Citrobacterium freundii with clinically significant ampC production
- Preferred agents include cefepime, if the minimum inhibitory concentration is at least 4 mcg/mL.
- Alternative agents include carbapenems, if sensitivity is demonstrated.
Carbapenem-resistant infections
- Preferred agents include ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol.
Ceftolozane-tazobactam is recommended only in patients at risk of polymicrobial infection.
Simple cystitis
- Preferred agents include non-β-lactam therapy such as nitrofurantoin or TMP-SMX.
- Alternative agents include aminoglycosides.
Other alternatives include TMP-SMX and fluoroquinolones for invasive infections, and ceftriaxone if sensitivity is demonstrated.
CRE infections
Infections sensitive to meropenem and imipenem without carbapenemase production or sensitivity to ertapenem
- Preferred agents include meropenem extended infusion and imipenem-cilastatin.
Simple cystitis
- Preferred agents include nitrofurantoin, TMP-SMX, ciprofloxacin, and levofloxacin.
- Alternative agents include single-dose aminoglycosides, colistin, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol.
Other alternative agents include oral fosfomycin for infections in which Escherichia coli is the causative pathogen.
Pyelonephritis and ITUC
- Preferred agents include TMP-SMX, ciprofloxacin, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol.
- Alternative agents include aminoglycosides (reserved for patients who can tolerate nephrotoxicity).
The committee also noted that levofloxacin may be considered if sensitivity is demonstrated.
DTR-P. aeruginosa Infections
Multidrug-resistant infections sensitive to β-lactams or non-carbapenems
- Preferred agents include TZP, ceftazidime, cefepime, and aztreonam.
Severe infections resistant to carbapenems
- Preferred agents include ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-cilastatin-relebactam.
Uncomplicated cystitis, pyelonephritis and IVCU
- Preferred agents include ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam and cefiderocol.
Infections outside the urinary tract
- Preferred agents include ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-cilastatin-relebactam.
- Alternative agents include cefiderocol.
CRAB infections
Although there is no established standard antibiotic regimen for the treatment of CRAB infections, the general approach is high-dose ampicillin-sulbactam in combination with at least 2 other agents, including polymyxin B, minocycline, tigecycline and cefiderocol.
Combination therapy with cefiderocol should be limited to infections refractory to other antibiotics or if other agents cannot be tolerated.
S maltophilia Infections
- Preferred agents include TMP-SMX, minocycline, tigecycline, and cefiderocol.
Combination therapy with ceftazidime-avibactam and aztreonam is recommended for patients with severe disease and those unresponsive to preferred agents.
Looking forward
IDSA plans to provide additional updates to this guidance annually.
According to the guideline authors, “the field of AMR is dynamic and rapidly evolving, and treatment of this disease antimicrobial resistant infections will continue to challenge clinicians.
Disclosure: Several study authors have declared affiliations with pharmaceutical, biotechnology, and/or device companies. Please see the original reference for a complete list of disclosures.
