What antibiotics are used to treat infections caused by Gram-negative rods?

Antibiotics for Gram-Negative Rod Infections

Carbapenems are the preferred first-line antibiotics for serious infections caused by gram-negative rods, particularly for suspected or confirmed extended-spectrum beta-lactamase (ESBL) producers or multidrug-resistant organisms. 1

First-Line Options

For Suspected or Confirmed ESBL-Producing Organisms:

• Carbapenems: Meropenem, imipenem, doripenem, or ertapenem
  • Meropenem is particularly recommended for critically ill patients 1
  • Group 1 carbapenems (ertapenem) have activity against ESBL-producing pathogens but not against Pseudomonas and Enterococcus 2
  • Group 2 carbapenems (imipenem/cilastatin, meropenem, doripenem) are active against non-fermentative gram-negative bacilli 2

For Carbapenem-Resistant Gram-Negative Rods:

• Newer β-lactam/β-lactamase inhibitor combinations:

  • Ceftazidime-avibactam: For KPC-producing and OXA-48-like organisms 1, 2
  • Ceftolozane-tazobactam: For ESBL-producing Enterobacteriaceae and multidrug-resistant P. aeruginosa 2
  • Meropenem-vaborbactam: For KPC-producing organisms 1
  • Imipenem-relebactam: For KPC-producing organisms 1

• Polymyxins (colistin/polymyxin E):

  • Active against Enterobacter aerogenes, E. coli, K. pneumoniae, and P. aeruginosa 3
  • Often used in combination therapy for carbapenem-resistant organisms 2

Alternative Options

For Less Severe Infections or Carbapenem-Sparing Strategies:

• Aminoglycosides (gentamicin, amikacin):

  • Active against many gram-negative bacteria including Citrobacter, Enterobacter, E. coli, Klebsiella, Proteus, Serratia, and P. aeruginosa 4
  • Can be used in combination therapy for synergistic effect 1
  • Not effective against anaerobes 2

• Tigecycline:

  • Effective against ESBL-producers and some carbapenem-resistant Enterobacteriaceae 2
  • Not active against P. aeruginosa or Proteus species 2
  • Poor plasma concentrations limit use in bacteremia 2

• Fosfomycin:

  • Redeveloped in intravenous formulation 5
  • Used for multidrug-resistant gram-negative infections 2

Organism-Specific Considerations

For Acinetobacter baumannii:

• Sulbactam-containing combinations are suggested for CRAB (carbapenem-resistant A. baumannii) infections 2
• Tigecycline or polymyxin-based combinations are recommended for CRAB pulmonary infections 2

For Pseudomonas aeruginosa:

• Ceftolozane-tazobactam: Higher activity against MDR P. aeruginosa 2
• Carbapenems: Resistance often due to modification of outer membrane protein OprD 6
• Polymyxins: For carbapenem-resistant strains 2

For Carbapenemase-Producing Enterobacteriaceae:

• KPC producers: Ceftazidime-avibactam or meropenem-vaborbactam 1
• MBL producers: Ceftazidime-avibactam plus aztreonam or cefiderocol 1
• OXA-48-like producers: Ceftazidime-avibactam 1

Treatment Approach Algorithm

1. Assess severity and risk factors:

   • For critically ill patients with sepsis/septic shock → Carbapenem (preferably meropenem)
   • For stable patients → Consider carbapenem-sparing options

2. Consider local resistance patterns:

   • High ESBL prevalence → Carbapenems or newer β-lactam/β-lactamase inhibitors
   • High carbapenem resistance → Polymyxins, tigecycline, or newer agents based on susceptibility

3. Adjust based on culture results:

   • De-escalate to narrower spectrum when possible
   • For carbapenem-resistant organisms → Use targeted therapy based on susceptibility

Common Pitfalls to Avoid

1. Overreliance on carbapenems can promote carbapenem resistance. Use carbapenem-sparing strategies when appropriate 2

2. Inappropriate use of tigecycline for bacteremia or P. aeruginosa infections can lead to treatment failure 2

3. Monotherapy for carbapenem-resistant infections may be insufficient; combination therapy is often needed for severe infections 2

4. Failure to adjust dosing based on renal function, particularly for aminoglycosides and polymyxins, can lead to toxicity 1

5. Delayed effective therapy for ESBL or carbapenem-resistant infections increases mortality 1

The emergence of multidrug-resistant gram-negative bacteria has made antibiotic selection increasingly challenging. Appropriate empiric therapy followed by targeted treatment based on susceptibility testing is crucial for optimal outcomes.