What is the first-line treatment for suspected or confirmed infections caused by Escherichia coli (E. coli) or Klebsiella?

From the Guidelines

The first-line treatment for suspected or confirmed infections caused by Escherichia coli (E. coli) or Klebsiella typically involves beta-lactam antibiotics, with specific choices depending on infection severity, site, and local resistance patterns. For uncomplicated urinary tract infections, oral options include trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3-5 days), nitrofurantoin (100 mg four times daily for 5-7 days), or fosfomycin (3 g single dose) 1. For more severe infections like pyelonephritis or bacteremia, intravenous therapy with a third-generation cephalosporin such as ceftriaxone (1-2 g daily) or an extended-spectrum penicillin with beta-lactamase inhibitor like piperacillin-tazobactam (3.375-4.5 g every 6-8 hours) is recommended 1. For suspected ESBL-producing strains, carbapenems like meropenem (1 g every 8 hours) may be necessary 1. Treatment duration typically ranges from 7-14 days depending on infection severity and site. These recommendations target the cell wall synthesis of these gram-negative bacteria, with drug selection balancing spectrum of activity, tissue penetration, and resistance concerns. Antibiotic susceptibility testing should guide definitive therapy once available, as resistance patterns vary significantly by region. Some key points to consider in the management of these infections include:

• Local resistance patterns should be considered when selecting empirical antimicrobial therapy 1
• The use of individual-level predictors of resistance can be helpful in guiding empirical antimicrobial choice 1
• Combination therapy may be necessary for suspected or proven infection with MDR Pseudomonas aeruginosa or carbapenemase-producing Klebsiella pneumoniae 1
• Clinical response should guide the continuation or modification of antibiotic therapy, rather than solely following a predetermined protocol 1

From the FDA Drug Label

1. 1 Complicated Skin and Skin Structure Infections Tigecycline for injection is indicated in patients 18 years of age and older for the treatment of complicated skin and skin structure infections caused by susceptible isolates of Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis.

2. 2 Complicated Intra-abdominal Infections Tigecycline for injection is indicated in patients 18 years of age and older for the treatment of complicated intra-abdominal infections caused by susceptible isolates of Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

The first-line treatment for suspected or confirmed infections caused by Escherichia coli (E. coli) or Klebsiella is not explicitly stated in the provided drug label as the first-line treatment. However, tigecycline is indicated for the treatment of complicated skin and skin structure infections and complicated intra-abdominal infections caused by susceptible isolates of E. coli and Klebsiella 2.

• Key points:
  • Tigecycline is an option for the treatment of infections caused by E. coli and Klebsiella.
  • The choice of antibiotic should be guided by the severity and site of the infection, the patient’s clinical and bacteriological progress, and local epidemiology and susceptibility patterns.
  • Tigecycline should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

From the Research

First-Line Treatment for E. coli and Klebsiella Infections

The first-line treatment for suspected or confirmed infections caused by Escherichia coli (E. coli) or Klebsiella depends on various factors, including the type of infection, patient's health status, and local susceptibility patterns.

• For acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females, the recommended first-line empiric antibiotic therapy includes:
  • A 5-day course of nitrofurantoin
  • A 3-g single dose of fosfomycin tromethamine
  • A 5-day course of pivmecillinam 3
• High rates of resistance to trimethoprim-sulfamethoxazole and ciprofloxacin preclude their use as empiric treatment of UTIs in several communities, particularly if patients were recently exposed to them or are at risk of infections with extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriales 3

Treatment Options for ESBL-Producing E. coli and Klebsiella

For UTIs due to ESBL-producing E. coli or Klebsiella pneumoniae, treatment options include:

• Oral options: nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin 3
• Parenteral options: piperacillin-tazobactam (for ESBL-E coli only), carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, aminoglycosides, and fosfomycin 3
• Amikacin has been shown to be an effective and safe alternative treatment option for lower UTIs caused by ESBL-producing E. coli or Klebsiella pneumoniae that are resistant to all oral antibiotics 4

Clinical Efficacy of Piperacillin-Tazobactam vs Meropenem

A randomized clinical trial compared the effectiveness of piperacillin-tazobactam and meropenem in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E. coli or K. pneumoniae. The results showed that piperacillin-tazobactam was not noninferior to meropenem in terms of 30-day mortality 5