What antibiotics have coverage for Gram-negative rods?

From the Guidelines

The most effective antibiotics for coverage of Gram-negative rods include ceftolozane/tazobactam and ceftazidime/avibactam, which are newer cephalosporin/beta-lactamase inhibitor combinations that have strong activity against Gram-negative multidrug-resistant organisms (MDROs), including ESBL-producing Enterobacteriaceae and Pseudomonas aeruginosa 1. These antibiotics are particularly useful in settings with high incidence of carbapenem-resistant Gram-negative bacteria, where carbapenem-sparing treatment is recommended 1. Other options for Gram-negative coverage include fluoroquinolones (ciprofloxacin, levofloxacin), aminoglycosides (gentamicin, tobramycin, amikacin), carbapenems (meropenem, imipenem, ertapenem), third and fourth generation cephalosporins (ceftriaxone, cefepime), piperacillin-tazobactam, and polymyxins (colistin) 1. For empiric coverage of common Gram-negative infections, a third-generation cephalosporin like ceftriaxone (1-2g IV daily) or a fluoroquinolone like ciprofloxacin (400mg IV q12h or 500-750mg PO q12h) is often used. The choice of antibiotic should be guided by the suspected organism, site of infection, local resistance patterns, and patient factors. Some key points to consider when choosing an antibiotic for Gram-negative coverage include:

• Local epidemiology and resistance patterns
• Patient characteristics, such as renal function and allergy history
• Site and severity of infection
• Need for broad-spectrum coverage versus targeted therapy
• Potential for antibiotic resistance and the need for carbapenem-sparing treatment. It's also important to note that Gram-negative bacteria have an outer membrane containing lipopolysaccharide that acts as a barrier to many antibiotics, which is why specific agents that can penetrate this barrier or target unique aspects of Gram-negative cell walls are needed for effective treatment. In general, the use of antibiotics should be guided by a thorough understanding of the underlying microbiology and resistance patterns, as well as careful consideration of the potential benefits and risks of each antibiotic option.

From the FDA Drug Label

Gentamicin has been shown to be active against most of the following bacteria, both in vitro and in clinical infections... Gram-Negative Bacteria: Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Proteus species, Serratia species, Pseudomonas aeruginosa

Levofloxacin has in vitro activity against Gram-negative and Gram-positive bacteria... Gram-Negative Bacteria: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Antibiotics with coverage for Gram-negative rods:

• Gentamicin 2
• Levofloxacin 3

Key points:

• Gentamicin is active against various Gram-negative bacteria, including Citrobacter, Enterobacter, Escherichia coli, Klebsiella, Proteus, Serratia, and Pseudomonas species.
• Levofloxacin has in vitro activity against Gram-negative bacteria, including Enterobacter, Escherichia coli, Haemophilus, Klebsiella, Legionella, Moraxella, Proteus, Pseudomonas, and Serratia species.

From the Research

Antibiotics with Coverage for Gram-Negative Rods

The following antibiotics have been identified as having coverage for Gram-negative rods:

• Ceftazidime/avibactam: active against KPC and OXA-48 producers 4, 5, 6
• Ceftolozane/tazobactam: active against multidrug-resistant Gram-negative bacteria, including Pseudomonas aeruginosa 5, 6, 7
• Cefiderocol: active against carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa 4, 7, 8
• Meropenem/vaborbactam: active against KPC producers 4
• Plazomicin: a next-generation aminoglycoside with in vitro activity against CRE 4, 8
• Eravacycline: a tetracycline class antibacterial with in vitro activity against CRE 4, 8
• Imipenem/relebactam: a potential anti-CRE antibiotic in development 4

Mechanism of Action and Resistance

These antibiotics work through various mechanisms, including:

• β-lactam/β-lactamase inhibitor combinations: inhibit cell wall synthesis and resist β-lactamase degradation 5, 6
• Aminoglycosides: inhibit protein synthesis 4, 8
• Tetracyclines: inhibit protein synthesis 4, 8
• Novel modes of action: such as darobactins, which inhibit the outer membrane protein BamA 7

Clinical Use and Efficacy

These antibiotics have been approved for various indications, including:

• Complicated intra-abdominal infections 5, 6
• Complicated urinary tract infections 5, 6
• Ventilator-associated and nosocomial pneumonia 5
• Severe Gram-negative infections 8