Meropenem is Highly Effective Against Gram-Negative Bacilli
Meropenem is strongly recommended as a first-line treatment for infections caused by gram-negative bacilli, particularly in severe infections due to third-generation cephalosporin-resistant Enterobacterales. 1
Mechanism of Action and Spectrum of Activity
Meropenem is a carbapenem antibiotic that works by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). It specifically:
- Binds to PBPs 2,3, and 4 of Escherichia coli and Pseudomonas aeruginosa 2
- Penetrates the cell wall of most gram-positive and gram-negative bacteria 2
- Exhibits bactericidal activity at concentrations typically 1-2 times the bacteriostatic concentrations 2
Gram-Negative Coverage
Meropenem demonstrates excellent activity against numerous gram-negative pathogens, including:
- Enterobacterales (E. coli, Klebsiella pneumoniae, Proteus mirabilis)
- Pseudomonas aeruginosa
- Haemophilus influenzae
- Neisseria meningitidis 2
Clinical Applications and Recommendations
Severe Infections Due to Resistant Gram-Negative Bacteria
For patients with bloodstream infections (BSI) and severe infections due to third-generation cephalosporin-resistant Enterobacterales (3GCephRE), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) strongly recommends a carbapenem (imipenem or meropenem) as targeted therapy. 1
For less severe infections:
- Ertapenem may be used for BSI without septic shock 1
- For low-risk, non-severe infections, alternatives like piperacillin-tazobactam, amoxicillin/clavulanic acid, or quinolones may be considered 1
Carbapenem-Resistant Infections
For carbapenem-resistant Enterobacterales (CRE) infections:
- Meropenem-vaborbactam or ceftazidime-avibactam are suggested for severe infections if active in vitro 1
- For CRE with meropenem MIC ≤8 mg/L, high-dose extended-infusion meropenem may be used as part of combination therapy 1
Dosing Considerations
- Standard dosing: 1 gram IV every 8 hours 2
- For severe infections or resistant pathogens: 2 grams IV every 8 hours as 3-hour infusion 3
- Dose adjustment required in renal impairment 2
Advantages Over Other Carbapenems
Meropenem offers several advantages:
- Lower potential for seizure induction compared to imipenem 4
- Does not require co-administration with cilastatin (a renal dehydropeptidase inhibitor) 5
- Excellent tissue penetration, including cerebrospinal fluid in the presence of inflammation 4
Combination Therapy Considerations
- For patients with CRE infections susceptible to and treated with newer agents like ceftazidime-avibactam or meropenem-vaborbactam, combination therapy is not recommended 1
- For severe CRPA (carbapenem-resistant Pseudomonas aeruginosa) infections treated with polymyxins, aminoglycosides, or fosfomycin, treatment with two in vitro active drugs is suggested 1
Common Pitfalls and Caveats
Resistance mechanisms: Be aware of potential resistance mechanisms including decreased outer membrane permeability, reduced affinity of target PBPs, increased efflux pump expression, and production of carbapenemases 2
Not effective against: Meropenem does not have activity against methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE) 2
Dosing in renal impairment: Dosage adjustment is necessary in patients with reduced renal function as meropenem is predominantly renally excreted 4
Pharmacokinetic monitoring: For critically ill patients, therapeutic drug monitoring is recommended to optimize dosing, particularly when treating resistant pathogens 6
In conclusion, meropenem is a highly effective broad-spectrum carbapenem antibiotic with excellent activity against gram-negative bacilli, making it an important option for the empirical and targeted treatment of serious bacterial infections, particularly those caused by resistant gram-negative pathogens.