What are the appropriate antibiotics for treating Gram-negative (Gram negative) rod infections?

From the Guidelines

Gram-negative rod infections are typically treated with beta-lactams, such as piperacillin/tazobactam, or carbapenems, such as meropenem, with consideration of local resistance patterns and patient factors, including allergies and kidney function, as recommended by the 2017 WSES guidelines for management of intra-abdominal infections 1.

Treatment Options

• Beta-lactams: piperacillin/tazobactam (4.5g IV every 6-8 hours) or cefepime (1-2g IV every 12 hours)
• Carbapenems: meropenem (1g IV every 8 hours) or imipenem/cilastatin
• Fluoroquinolones: ciprofloxacin (400mg IV or 500-750mg oral twice daily) or levofloxacin, although their use is limited due to increasing resistance rates 1
• Aminoglycosides: gentamicin (5-7mg/kg IV daily) or tobramycin, for suspected infections by gram-negative bacteria, but with caution due to their toxic side effects
• Polymyxins: colistin (2.5-5mg/kg IV daily in divided doses) for multidrug-resistant organisms

Considerations

• Local resistance patterns: selection of empiric antibiotic therapy should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1
• Patient factors: allergies, kidney function, and severity of infection
• Infection site: intra-abdominal infections may require broader-spectrum antibiotics, such as piperacillin/tazobactam or carbapenems
• Treatment duration: typically ranges from 7-14 days, depending on infection severity and site, but may be shorter (3-5 days) for uncomplicated intra-abdominal infections with adequate source control 1

Resistance Mechanisms

• Gram-negative bacteria have a thin peptidoglycan layer and an outer membrane containing lipopolysaccharides, making them naturally resistant to many antibiotics
• Efflux pumps and beta-lactamase enzymes provide additional resistance mechanisms
• Increasing resistance rates to fluoroquinolones and carbapenems have been reported, highlighting the need for careful selection of empiric antibiotic therapy and consideration of local resistance patterns 1

From the FDA Drug Label

Colistimethate for Injection, USP is indicated for the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli. It is particularly indicated when the infection is caused by sensitive strains of Pseudomonas aeruginosa. This antibiotic is not indicated for infections due to Proteus or Neisseria Colistimethate for Injection, USP has proven clinically effective in treatment of infections due to the following gram-negative organisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa

The antibiotic Colistin (IV) is effective against certain gram-negative rods, including:

• Pseudomonas aeruginosa
• Enterobacter aerogenes
• Escherichia coli
• Klebsiella pneumoniae 2

From the Research

Antibiotics for Gram-Negative Rods

• Gram-negative rods are a type of bacteria that can cause serious infections, and treatment options are limited due to increasing resistance to antibiotics 3.
• Meropenem is a broad-spectrum antibacterial agent that has been shown to be effective against Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae 4.
• Other antibiotics that have been shown to be effective against Gram-negative rods include ceftolozane/tazobactam and ceftazidime/avibactam, which are combination agents that combine a beta-lactam antibiotic with a beta-lactamase inhibitor 5.
• The treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections is challenging, and requires careful consideration of the patient's medical history and local microbiological epidemiology 6.
• New treatment options, such as ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, plazomicin, and eravacycline, have become available in recent years, but their optimal use must be guaranteed to delay the emergence and diffusion of resistance to novel agents 6.

Mechanisms of Resistance

• Gram-negative rods can develop resistance to antibiotics through various mechanisms, including the production of beta-lactamases, which can break down beta-lactam antibiotics 3.
• The use of beta-lactamase inhibitors, such as tazobactam and avibactam, can help to overcome resistance to beta-lactam antibiotics 5.
• The development of new antibiotics that are active against Gram-negative rods is critical to addressing the growing problem of antibiotic resistance 7.

Treatment Considerations

• The treatment of Gram-negative rod infections requires careful consideration of the patient's underlying disease and the appropriateness of therapy 7.
• The use of broad-spectrum antibiotics, such as meropenem, can be effective in treating serious infections caused by Gram-negative rods, but may also contribute to the development of resistance 4.
• The optimization of dosages and treatment duration is critical to ensuring the effective treatment of Gram-negative rod infections, while also minimizing the risk of resistance 6.