What are the recommended antibiotics for treating gram-negative bacilli infections?

Recommended Antibiotics for Gram-Negative Bacilli Infections

Carbapenems are the first-line treatment for severe gram-negative bacilli infections, particularly for multidrug-resistant strains, due to their broad spectrum of activity and high efficacy. 1

First-Line Options Based on Severity and Resistance Patterns

For Susceptible Gram-Negative Bacilli

• Carbapenems (imipenem, meropenem, ertapenem) are the most effective agents with >98.7% susceptibility rates against Enterobacteriaceae 1, 2
• Third-generation cephalosporins (cefotaxime, ceftriaxone) plus metronidazole for mild infections 1
• Piperacillin/tazobactam remains effective for many gram-negative infections including those with anti-Pseudomonas coverage 1
• Aminoglycosides (gentamicin) are effective against Pseudomonas aeruginosa but require combination with metronidazole for anaerobic coverage 1, 3

For Third-Generation Cephalosporin-Resistant Enterobacteriaceae (3GCephRE)

• Carbapenems (imipenem or meropenem) are strongly recommended for bloodstream infections and severe infections 1
• Ertapenem may be used for bloodstream infections without septic shock 1
• Piperacillin-tazobactam, amoxicillin/clavulanic acid or fluoroquinolones can be considered for low-risk, non-severe infections 1
• Aminoglycosides or IV fosfomycin are recommended for complicated urinary tract infections without septic shock 1

For Carbapenem-Resistant Enterobacteriaceae (CRE)

• Meropenem-vaborbactam or ceftazidime-avibactam if active in vitro 1
• Polymyxin combination therapy is recommended over monotherapy for patients requiring polymyxin treatment 1
• Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam have potent activity against Klebsiella pneumoniae carbapenemase producers 4

For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)

• Ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relabactam and cefiderocol have potent activity 1, 4
• Combination therapy with two in vitro active drugs is suggested for severe infections 1
• Monotherapy chosen from drugs active in vitro for non-severe infections 1

For Carbapenem-Resistant Acinetobacter baumannii (CRAB)

• Ampicillin-sulbactam for CRAB susceptible to sulbactam with HAP/VAP 1
• Polymyxin or high-dose tigecycline if active in vitro for sulbactam-resistant CRAB 1
• Combination therapy including two in vitro active antibiotics for severe infections 1
• Cefiderocol, plazomicin and eravacycline may play important roles in management 4

Special Considerations

Combination Therapy

• Polymyxin-carbapenem combination may be suggested for CRGNB if meropenem MIC is ≤8 mg/L for CRE or ≤32 mg/L for CRAB 1
• Polymyxin combination with rifampin or fosfomycin has been studied but shows conflicting results 1
• Cell wall-active agents with aminoglycosides often result in synergism 5

Antibiotic Stewardship Considerations

• Carbapenems should be used judiciously to preserve activity and prevent emergence of resistance 1
• Stepdown therapy should be considered once patients are stabilized, using narrower-spectrum agents based on susceptibility 1
• MIC testing should be performed for commonly used antimicrobial agents for treating CRGNB infections 1

Monitoring and Safety

• Monitor renal function during polymyxin treatment 1
• Therapeutic drug monitoring is encouraged for polymyxins and aminoglycosides 1, 3
• Avoid combining ototoxic and nephrotoxic drugs with polymyxins 1
• Prothrombin time monitoring may be needed with cephalosporins in patients with renal/hepatic impairment 6

Algorithm for Empiric Treatment of Gram-Negative Infections

1. Assess infection severity:

   • Severe (septic shock, ICU): Start with carbapenems or piperacillin/tazobactam 1
   • Non-severe: Consider narrower spectrum options based on local resistance patterns 1

2. Consider local epidemiology and resistance patterns:

   • High prevalence of ESBL: Use carbapenems 1, 7
   • High prevalence of CRE: Consider newer agents (ceftazidime-avibactam) 1

3. Adjust based on source of infection:

   • Urinary source: Aminoglycosides or fosfomycin may be appropriate 1
   • Intra-abdominal: Ensure anaerobic coverage with metronidazole if using cephalosporins 1
   • Pneumonia: Follow pathogen-specific recommendations 1

4. De-escalate therapy once culture results available:

   • Switch to narrowest effective therapy based on susceptibility testing 1
   • Consider oral step-down when appropriate 1

Remember that resistance patterns vary geographically, so local antibiograms should guide empiric therapy choices, and susceptibility testing should direct definitive therapy 1.