How to treat an infection with Gram-negative rods?

Treatment of Infections Caused by Gram-Negative Rods

For infections caused by Gram-negative rods, carbapenems (imipenem or meropenem) are the recommended first-line treatment for severe infections, while less severe infections can be treated with carbapenem-sparing options based on susceptibility patterns. 1

Treatment Based on Infection Severity

Severe Infections/Bacteremia

• For patients with severe infections or bloodstream infections due to Gram-negative rods, particularly third-generation cephalosporin-resistant Enterobacterales (3GCephRE), carbapenems (imipenem or meropenem) are strongly recommended as targeted therapy 1
• For patients with bacteremia without septic shock, ertapenem may be used instead of imipenem or meropenem 1
• For carbapenem-resistant organisms, treatment should be guided by susceptibility testing, with polymyxins (colistin), tigecycline, or newer β-lactam/β-lactamase inhibitor combinations as options 1

Non-Severe Infections

• For low-risk, non-severe infections due to Gram-negative rods, carbapenem-sparing options include:
  • Piperacillin-tazobactam 1
  • Amoxicillin/clavulanic acid 1
  • Fluoroquinolones (if susceptible) 1
• For complicated urinary tract infections without septic shock:
  • Aminoglycosides (e.g., gentamicin) for short durations when active in vitro 1, 2
  • IV fosfomycin 1
  • Cotrimoxazole may be considered for non-severe urinary tract infections 1

Special Considerations for Specific Pathogens

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

• For CRAB susceptible to sulbactam, ampicillin-sulbactam is suggested, particularly for hospital-acquired/ventilator-associated pneumonia 1
• For CRAB resistant to sulbactam, polymyxins or high-dose tigecycline can be used if active in vitro 1

Pseudomonas aeruginosa

• For carbapenem-resistant Pseudomonas aeruginosa (CRPA), options include:
  • Ceftolozane/tazobactam (in combination with metronidazole for mixed infections) 1
  • Polymyxins (colistin) for resistant strains 1

Extended-Spectrum Beta-Lactamase (ESBL) Producers

• For ESBL-producing Enterobacterales, carbapenems are the most reliable option for severe infections 1
• In settings with high incidence of carbapenem-resistant Klebsiella pneumoniae, carbapenem-sparing treatment should be considered 1
• Ceftolozane/tazobactam and ceftazidime/avibactam are newer options for ESBL producers 1

Antibiotic Stewardship Considerations

• Extended use of cephalosporins should be discouraged in settings with high incidence of ESBL-producing Enterobacterales 1
• Fluoroquinolones should be used judiciously due to selection pressure for resistant organisms (ESBLs and MRSA) 1
• Step-down therapy following carbapenems once patients are stabilized is good clinical practice, using:
  • Beta-lactam/beta-lactamase inhibitors
  • Quinolones
  • Cotrimoxazole
  • Other antibiotics based on susceptibility patterns 1

Treatment Duration and Monitoring

• For most Gram-negative infections, treatment duration is typically 7-14 days 1
• For catheter-related bloodstream infections caused by Gram-negative bacilli, catheter removal is generally recommended 1
• Follow-up cultures are recommended in case of treatment failure, especially for carbapenem-resistant Gram-negative bacteria, to detect resistance development 1

Common Pitfalls and Caveats

• Tigecycline performs poorly in bacteremic patients and should not be considered first-line therapy in patients with healthcare-associated pneumonia and bacteremia 1
• For pan-resistant Gram-negative bacteria, optimal source control is crucial in addition to antibiotic therapy 1
• Resistance to commonly used antibiotics is increasing, particularly concerning is increased resistance to beta-lactams, trimethoprim, and quinolones 3
• Inappropriate use of carbapenems should be avoided to reduce selective pressure and association with the increase in carbapenem-resistant Enterobacteriaceae 1
• For infections with multidrug-resistant Gram-negative organisms, combination therapy may be considered, though evidence for improved outcomes is limited 1, 4

Remember that treatment should be guided by local antibiogram data and adjusted based on culture and susceptibility results when available. Source control (e.g., drainage of abscesses, removal of infected foreign bodies) remains a critical component of management alongside appropriate antibiotic therapy 4.