Exclusive Gram-Negative Antibiotics for Treating Susceptible Infections

Primary Exclusive Gram-Negative Agents

• The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) suggests polymyxin as a last-resort therapy for multidrug-resistant gram-negative infections, particularly carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA), with careful dosing and monitoring due to significant nephrotoxicity 1

Predominantly Gram-Negative Agents

• Aminoglycosides are effective against gram-negative bacteria, including P. aeruginosa, but have no activity against anaerobic bacteria, requiring combination with metronidazole for mixed infections 2
• The ESCMID recommends aminoglycosides over tigecycline for complicated UTIs caused by carbapenem-resistant Enterobacterales (CRE) 1
• The ESCMID conditionally recommends aminoglycosides for short-duration therapy in 3rd-generation cephalosporin-resistant Enterobacterales (3GCephRE) without septic shock, when active in vitro 3

Emerging Combination Therapy for Metallo-β-Lactamase Producers

• The ESCMID suggests aztreonam plus ceftazidime-avibactam combination for severe infections caused by CRE carrying metallo-β-lactamases resistant to new antibiotic monotherapies (conditional recommendation, moderate evidence) 1

Clinical Algorithm for Selection

• For empiric therapy when gram-positive coverage is needed, combining aztreonam with an anti-gram-positive agent (vancomycin, daptomycin, or linezolid) is recommended, rather than using aminoglycosides, to avoid aminoglycoside toxicity while maintaining gram-negative coverage 4, 5
• Anaerobic coverage is required for polymicrobial infections, and metronidazole or another anti-anaerobic agent should be added to exclusive gram-negative agents 2