Is meropenem effective against Gram-Negative Rods (GNR)?

Meropenem Effectively Covers Gram-Negative Rods (GNR)

Yes, meropenem provides excellent coverage against gram-negative rods (GNR) and is a highly effective carbapenem antibiotic for treating serious infections caused by these organisms. 1, 2

Spectrum of Activity Against GNR

• Meropenem has broad-spectrum activity against gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacteriaceae 2
• The bactericidal activity of meropenem results from inhibition of cell wall synthesis by binding to penicillin-binding proteins (PBPs) in gram-negative bacteria, specifically PBPs 2,3, and 4 of Escherichia coli and Pseudomonas aeruginosa 1
• Meropenem demonstrates activity against numerous clinically important gram-negative rods, including:
  • Escherichia coli 1
  • Klebsiella pneumoniae 1
  • Pseudomonas aeruginosa 1
  • Proteus mirabilis 1
  • Haemophilus influenzae 1
  • Neisseria meningitidis 1

Effectiveness Against Resistant GNR

• Meropenem is particularly valuable for treating infections caused by gram-negative bacilli that produce extended-spectrum β-lactamases or those that may hyperproduce lactamases (i.e., Enterobacter species, Citrobacter species, or Serratia marcescens) 3
• For carbapenem-resistant gram-negative bacilli (CRGNB), newer formulations like meropenem-vaborbactam are recommended for severe infections due to carbapenem-resistant Enterobacteriaceae (CRE) if active in vitro 3
• In patients with meningitis caused by gram-negative isolates resistant to standard therapy, meropenem may be the preferred treatment option 3

Clinical Applications for GNR Infections

• Meropenem has demonstrated similar or superior efficacy compared to other antibiotics in treating serious GNR infections:
  • Similar efficacy to imipenem/cilastatin in complicated intra-abdominal infections, complicated skin and skin structure infections, and other serious infections 2, 4
  • Greater efficacy than ceftazidime or ceftazidime plus aminoglycosides in patients with nosocomial pneumonia caused by GNR 2, 4
  • Effective as empirical monotherapy for serious infections in both adult and pediatric intensive care patients 4

Dosing Considerations for GNR Coverage

• For optimal treatment of gram-negative infections in critically ill patients, dosing should be adjusted based on:
  • Renal function 5
  • Pathogen identification and susceptibility 5
  • Site of infection 5
• For necrotizing infections involving GNR, meropenem can be dosed at 1 g every 8 hours intravenously 3

Advantages Over Other Antibiotics for GNR

• Meropenem has several advantages when treating GNR infections:
  • More active against most gram-negative pathogens than imipenem, though less active against gram-positive organisms 4
  • Lower seizure potential than imipenem, making it suitable for treating bacterial meningitis 2, 6
  • Does not require co-administration with a renal dehydropeptidase inhibitor like imipenem does 7
  • Excellent tissue penetration, including cerebrospinal fluid (with inflammation), respiratory tract, and urinary tract 6

Limitations and Resistance Considerations

• Resistance mechanisms to meropenem in GNR include:
  • Decreased outer membrane permeability due to diminished porin production 1
  • Reduced affinity of target PBPs 1
  • Increased expression of efflux pump components 1
  • Production of carbapenemases and metallo-β-lactamases 1
• Meropenem is not effective against methicillin-resistant Staphylococcus aureus (MRSA) 1
• For carbapenem-resistant GNR carrying metallo-β-lactamases, newer agents like cefiderocol or combination therapies may be needed 3

In clinical practice, meropenem remains a cornerstone antibiotic for treating serious GNR infections due to its broad spectrum, favorable safety profile, and effectiveness against many resistant strains.