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

From the Guidelines

For gram-negative rod infections, the recommended antibiotics depend on the specific pathogen and infection site, with carbapenems, such as meropenem 1g IV every 8 hours, or piperacillin-tazobactam 4.5g IV every 6 hours, being considered for more resistant organisms, as stated in the 2017 WSES guidelines for management of intra-abdominal infections 1. The choice of empiric antibiotic regimens in patients with intra-abdominal infections (IAIs) should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology, as recommended by Sartelli et al. in the World Journal of Emergency Surgery 1.

• First-line options typically include fluoroquinolones, third-generation cephalosporins, or aminoglycosides, but their use should be guided by local resistance patterns and the specific pathogen involved.
• For more resistant organisms, such as ESBL-producing Enterobacteriaceae, carbapenems or piperacillin-tazobactam may be necessary, as they offer a wide spectrum of antimicrobial activity against gram-positive and gram-negative aerobic and anaerobic pathogens.
• The use of carbapenems should be limited to preserve the activity of this class of antibiotics, due to the concern of emerging carbapenem-resistance, as highlighted in the 2017 WSES guidelines 1.
• New antibiotics, such as ceftolozone/tazobactam and ceftazidime/avibactam, have been approved for the treatment of complicated IAIs, including infections caused by ESBL-producing Enterobacteriaceae and P. aeruginosa, and may be valuable for treating infections caused by MDR gram-negative bacteria, as reported in recent studies 1.
• Treatment duration typically ranges from 7-14 days depending on infection severity and site, and empiric therapy should be broad initially, then narrowed based on culture results, as recommended by the Surgical Infection Society and the Infectious Diseases Society of America 1.
• When treating gram-negative infections, it is essential to consider local resistance patterns, as many gram-negative rods produce beta-lactamases that confer resistance to certain antibiotics, and to monitor for side effects, including nephrotoxicity with aminoglycosides and C. difficile infection with broad-spectrum agents.

From the FDA Drug Label

Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species 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

Antibiotics for Gram-Negative Rods: Gentamicin is effective against various gram-negative rods, including Pseudomonas aeruginosa, Proteus species, Escherichia coli, Klebsiella species, Serratia species, and Citrobacter species.

• Key points:
  • Gentamicin is a bactericidal antibiotic that inhibits protein synthesis in susceptible bacteria.
  • It is effective against a range of gram-negative bacteria, including those that cause serious infections.
  • The decision to use gentamicin should be based on the results of susceptibility tests and the severity of the infection.
  • Gentamicin may be used in combination with other antibiotics, such as penicillins or cephalosporins, to treat certain infections 2, 2.

From the Research

Treatment Options for Gram-Negative Rods

• The treatment of gram-negative rod infections is a challenge due to the increasing problem of multidrug resistance, which limits therapeutic options 3.
• Currently, there are no randomized clinical trials involving the treatment of infections caused by multidrug-resistant gram-negative rods, and published data are limited 3.

Antibiotic Options

• Polymyxins and sulbactam are potential options for the treatment of imipenem-resistant Acinetobacter spp. 3.
• Tigecycline presents a broad spectrum of activity in vitro and may be useful in treating Acinetobacter infections and extended-spectrum beta-lactamase-producing Enterobacteriaceae 3.
• Carbapenems, such as imipenem, have a broad spectrum of activity that includes potential resistant pathogens and may be used in the initial treatment of serious Gram-negative infections 4.
• Ceftolozane/tazobactam and ceftazidime/avibactam are novel β-lactam/β-lactamase inhibitor combination agents that have been shown to retain in vitro activity against selected resistant Gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa 5, 6.

Recent Developments

• Ceftazidime/avibactam has demonstrated consistent activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms 5, 6.
• New antimicrobial treatment options, including β-lactam/β-lactamase inhibitor combinations, eravacycline, plazomicin, and cefiderocol, are being developed to treat severe or multidrug-resistant Gram-negative infections 7.
• The availability of new antibiotics offers an opportunity to improve empiric and definitive treatment of these infections, especially in critically ill and immunocompromised hosts 7.