What is Meropenem (Carbapenem antibiotic)?

From the Guidelines

Meropenem is recommended as a first-line treatment option for severe infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-susceptible Enterobacterales, particularly in patients with bloodstream infections and severe infections 1. The typical adult dose is 1 gram administered intravenously every 8 hours, though this may be adjusted to 500 mg every 8 hours for less severe infections or increased to 2 grams every 8 hours for certain severe infections like meningitis.

Key Considerations

• Treatment duration typically ranges from 7-14 days depending on the infection site and severity.
• Dose adjustments are necessary for patients with renal impairment, with reductions based on creatinine clearance.
• Meropenem works by inhibiting bacterial cell wall synthesis by binding to penicillin-binding proteins, resulting in cell death.
• It has activity against many gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa, and anaerobes, making it valuable for complicated intra-abdominal infections, complicated skin infections, pneumonia, and meningitis.

Side Effects and Monitoring

• Common side effects include headache, diarrhea, nausea, and injection site reactions.
• Patients should be monitored for allergic reactions, especially those with penicillin allergies, though cross-reactivity is less common than with other beta-lactams.

Resistance and Combination Therapy

• The use of meropenem in combination with other antibiotics, such as vaborbactam, may be considered for the treatment of CRE infections, particularly in patients with severe infections or those who are at high risk of treatment failure 1.
• The choice of empiric antibiotic regimens in patients with intra-abdominal infections should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.

Special Considerations

• In patients with non-severe infections or among patients with low-risk infections, under the consideration of antibiotic stewardship, the use of monotherapy chosen from among the in vitro active old drugs, on an individual basis and according to the source of infection, is considered good clinical practice 1.
• For patients with severe infections caused by CRE carrying metallo-b-lactamases and/or resistant to all other antibiotics, including ceftazidime-avibactam and meropenem-vaborbactam, treatment with cefiderocol may be conditionally recommended 1.

Overall, meropenem is a valuable treatment option for serious bacterial infections, particularly those caused by multi-drug resistant organisms, and its use should be guided by local resistance patterns, patient-specific factors, and antibiotic stewardship principles.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Meropenem Overview

• Meropenem is a broad-spectrum antibacterial agent of the carbapenem family, used for empirical therapy prior to the identification of causative organisms, or for disease caused by single or multiple susceptible bacteria in both adults and children with a broad range of serious infections 2.
• It has a broad spectrum of in vitro activity against Gram-positive and Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae 2, 3.

Indications and Efficacy

• Meropenem is approved for use in complicated intra-abdominal infection (cIAI), complicated skin and skin structure infection (cSSSI) and bacterial meningitis (in paediatric patients aged > or = 3 months) in the US, and in most other countries for nosocomial pneumonia, cIAI, septicaemia, febrile neutropenia, cSSSI, bacterial meningitis, complicated urinary tract infection (UTI), obstetric and gynaecological infections, in cystic fibrosis patients with pulmonary exacerbations, and for the treatment of severe community-acquired pneumonia (CAP) 2.
• Meropenem has similar efficacy to comparator antibacterial agents, including imipenem/cilastatin, clindamycin plus tobramycin or gentamicin, cefotaxime plus metronidazole, cefepime and ceftazidime plus amikacin, and ceftazidime, clarithromycin plus ceftriaxone or amikacin 2, 3.
• Meropenem showed greater efficacy than ceftazidime or piperacillin/tazobactam in febrile neutropenia, and greater efficacy than ceftazidime plus amikacin or tobramycin in patients with nosocomial pneumonia 2.

Pharmacokinetics and Pharmacodynamics

• Meropenem undergoes primarily renal elimination; therefore, dosage adjustment is required for patients with renal impairment 4.
• Meropenem has time-dependent bactericidal activity; thus, the percentage of time that free-drug concentrations are higher than the MIC (%T>MIC) best characterizes the drug's pharmacodynamic profile (bactericidal target of approximately 40%T>MIC) 4.
• Pharmacodynamic modeling can identify regimens with the greatest probability of attaining this target, and probabilities can be compared with clinical and microbiological responses in patients 4.

Safety Profile

• Meropenem is well tolerated and has an acceptable safety profile, with the most common adverse events reported being diarrhoea, rash, and nausea/vomiting 5.
• The incidence of seizures considered by investigators to be related to meropenem treatment was 0.07% in infections other than meningitis 5.
• Meropenem has good CNS and gastrointestinal tolerability when used for the treatment of serious bacterial infections in a wide range of adult and paediatric patient populations 5.

Optimizing Meropenem Therapy

• Prolonged and continuous infusion regimens of meropenem have shown some clinical benefit, especially in cases involving multidrug-resistant gram-negative bacteria and in specific patient populations 6.
• Personalized dosing of meropenem for critical infections should be guided by real-time therapeutic drug monitoring (TDM) 6.
• There is a notable lack of sufficient data, highlighting the necessity for large-scale, multi-center clinical trials to validate the safety and effectiveness of meropenem in treating severe infections 6.