What antibiotics are effective against gram-negative infections?

From the Guidelines

The most effective antibiotics against gram-negative infections are carbapenems, such as meropenem 1g every 8 hours, and fourth-generation cephalosporins, such as cefepime 1-2g every 12 hours, as recommended by the 2017 WSES guidelines for management of intra-abdominal infections 1. The choice of antibiotic depends on the specific infection site, severity, and local resistance patterns. For severe infections, combination therapy may be necessary, and treatment duration typically ranges from 7-14 days depending on the infection type and clinical response. These antibiotics work by targeting different bacterial structures - carbapenems disrupt cell wall synthesis, while fourth-generation cephalosporins inhibit cell wall synthesis and have a broader spectrum of activity. Gram-negative bacteria have a thinner peptidoglycan layer but possess an outer lipopolysaccharide membrane that makes them resistant to many antibiotics effective against gram-positive organisms. Renal function should be monitored with certain antibiotics, such as aminoglycosides, and drug allergies must be considered before prescribing. Antibiotic stewardship is important to prevent resistance development, as highlighted in the guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia 1. Other options include fluoroquinolones, aminoglycosides, and piperacillin-tazobactam, but their use should be guided by local resistance patterns and patient-specific factors, as recommended by the 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer 1 and the 2010 guidelines for the diagnosis and management of complicated intra-abdominal infection in adults and children 1.

Some key points to consider when choosing an antibiotic for gram-negative infections include:

• Local resistance patterns: The choice of antibiotic should be guided by local resistance patterns to ensure effective treatment.
• Severity of infection: Severe infections may require combination therapy or broader-spectrum antibiotics.
• Patient-specific factors: Renal function, drug allergies, and other patient-specific factors should be considered when choosing an antibiotic.
• Antibiotic stewardship: Antibiotic use should be guided by principles of antibiotic stewardship to prevent resistance development.

Overall, the choice of antibiotic for gram-negative infections should be guided by a combination of factors, including local resistance patterns, severity of infection, patient-specific factors, and principles of antibiotic stewardship. The use of carbapenems and fourth-generation cephalosporins, as recommended by the 2017 WSES guidelines, is a reasonable approach for the treatment of gram-negative infections, but should be tailored to the individual patient and local resistance patterns 1.

From the FDA Drug Label

The ceftazidime component of AVYCAZ is a cephalosporin antibacterial drug with in vitro activity against certain gram-negative and gram-positive bacteria. AVYCAZ demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA). AVYCAZ also demonstrated in vitro activity against P aeruginosa in the presence of some AmpC beta-lactamases, and certain strains lacking outer membrane porin (OprD). Gentamicin, an aminoglycoside, binds to the prokaryotic ribosome, inhibiting protein synthesis in susceptible bacteria. It is bactericidal in vitro against Gram-positive and Gram-negative bacteria. Ceftazidime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftazidime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria

Antibiotics that cover gram-negative infections:

• AVYCAZ (ceftazidime and avibactam): effective against certain gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.
• Gentamicin: bactericidal against Gram-positive and Gram-negative bacteria.
• Ceftazidime: has activity against Gram-negative bacteria, including Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa. 2, 3, 4

From the Research

Antibiotics Effective Against Gram-Negative Infections

• The following antibiotics have been found to be effective against gram-negative infections:
  • Ceftriaxone
  • Ciprofloxacin
  • Ceftazidime
  • Piperacillin-tazobactam
  • Meropenem 5
• Carbapenems, tigecycline, piperacillin-tazobactam, cefepime, ceftazidime, ceftolozane-tazobactam, and ceftazidime-avibactam are also treatment options for resistant gram-negative infections 6
• Novel agents such as ceftolozane/tazobactam and ceftazidime/avibactam have been shown to be effective against multidrug-resistant gram-negative bacteria, including Pseudomonas aeruginosa 7, 8

Specific Infections and Antibiotic Use

• For complicated intra-abdominal infection and complicated urinary tract infection, ceftolozane/tazobactam and ceftazidime/avibactam have been approved as treatment options 7, 8
• Ceftazidime/avibactam is also active against carbapenem-resistant Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases 7
• Empirical therapy with novel agents should be considered in patients with risk factors for difficult-to-treat gram-negative infections and severe clinical presentation of acute infection 9

Antibiotic Stewardship

• Antimicrobial stewardship is essential to preserve the activity of these agents and reduce selective pressure for antimicrobial resistance 9, 7
• Empirical treatment with novel agents should be continued only for a few hours, until de-escalation, modification, or confirmation is made possible by the results of rapid diagnostic tests 9