What is the recommended antimicrobial coverage for E. coli bacteremia and Enterobacterales infections?

From the Guidelines

For E. coli bacteremia and Enterobacterales infections, the recommended antimicrobial coverage typically includes ceftazidime/avibactam 2.5 g IV q8h or meropenem/vaborbactam 4 g IV q8h, as these are the most recent and highest quality recommendations for treating these infections, especially in cases of carbapenem-resistant Enterobacterales (CRE) 1.

Key Considerations

• The choice of antimicrobial therapy should be based on the severity of the infection, the presence of resistant organisms, and local epidemiology 1.
• For severe infections or in areas with high resistance rates, combination therapy with an aminoglycoside or fluoroquinolone may be considered, but the use of these agents should be guided by susceptibility testing and local resistance patterns 1.
• The treatment duration typically ranges from 7-14 days, depending on the infection source, severity, and clinical response, and should be individualized based on the patient's condition and response to therapy 1.

Recommended Antimicrobial Regimens

• Ceftazidime/avibactam 2.5 g IV q8h or meropenem/vaborbactam 4 g IV q8h are recommended for the treatment of bloodstream infections and complicated intra-abdominal infections caused by CRE 1.
• Imipenem/cilastatin/relebactam 1.25 g IV q6h or tigecycline 100 mg IV loading dose, then 50 mg IV q12h may also be considered for the treatment of complicated intra-abdominal infections 1.

Important Notes

• The use of carbapenems should be limited to preserve their activity against multidrug-resistant organisms 1.
• Local antibiogram data should guide therapy, and susceptibility testing should be performed to ensure the chosen antimicrobial regimen is effective against the isolated organism 1.
• Source control through drainage of abscesses or removal of infected devices is essential when applicable, and therapy should be narrowed based on culture and susceptibility results once available to reduce selection pressure for resistance development 1.

From the FDA Drug Label

The recommended adult and pediatric dosages and routes of administration are outlined in the following table Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli, K. pneumoniae, or P. mirabilis 0.5 to 1 g IV/IM Every 12 hours 7 to 10 Severe Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli or K. pneumoniae 2 g IV Every 12 hours 10 Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by E coli, viridans group streptococci, P. aeruginosa, K. pneumoniae, Enterobacter species, or B. fragilis 2 g IV Every 8 to 12 hours 7 to 10

Antimicrobial Coverage for E. coli Bacteremia and Enterobacterales Infections:

• E. coli bacteremia: The recommended dose for severe uncomplicated or complicated urinary tract infections, including pyelonephritis, due to E. coli is 2 g IV every 12 hours for 10 days.
• Enterobacterales infections: The recommended dose for complicated intra-abdominal infections caused by Enterobacter species is 2 g IV every 8 to 12 hours for 7 to 10 days. 2

From the Research

Antimicrobial Coverage for E. coli Bacteremia and Enterobacterales Infections

• The recommended antimicrobial coverage for E. coli bacteremia and Enterobacterales infections is a crucial aspect of treatment, with various studies suggesting different approaches:
  • A study published in 2020 3 found that ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intra-abdominal infections caused by ESBL-producing Enterobacterales species.
  • Another study from 2018 4 compared piperacillin-tazobactam with meropenem for the treatment of bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae, and found that definitive treatment with piperacillin-tazobactam did not result in a noninferior 30-day mortality.
• The inoculum effect of antibiotics against CTX-M-extended-spectrum β-lactamase-producing Escherichia coli was investigated in a 2014 study 5, which found that meropenem is the most active compound against serious infections caused by Escherichia coli producing ESBLs.
• A 2021 study protocol 6 outlined a multicentre, open-label randomised non-inferiority trial comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales.
• An earlier study from 2006 7 assessed the clinical correlation of the CLSI susceptibility breakpoint for piperacillin-tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species, and found that treatment was successful in 10 of 11 nonurinary infections from susceptible strains.

Key Findings

• Ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intra-abdominal infections caused by ESBL-producing Enterobacterales species 3.
• Meropenem is the most active compound against serious infections caused by Escherichia coli producing ESBLs 5.
• Piperacillin-tazobactam may not be a suitable alternative to meropenem for the treatment of bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae 4.
• Ceftolozane-tazobactam is being investigated as a potential alternative to meropenem for the treatment of bloodstream infection caused by ESBL or AmpC-producing Enterobacterales 6.