Meropenem

Meropenem exerts its bactericidal effect by binding to penicillin-binding proteins (PBPs), disrupting peptidoglycan cross-linking in the bacterial cell wall, leading to cell lysis. Its broad spectrum covers many aerobic and anaerobic Gram-positive and Gram-negative pathogens, including Pseudomonas aeruginosa, Acinetobacter species, and Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs). Unlike imipenem, meropenem is stable to dehydropeptidase-1, so it is administered without cilastatin. It has modest activity against Stenotrophomonas maltophilia and Enterococcus faecium, which are often resistant. Its efficacy in central nervous system infections is enhanced by good penetration into the cerebrospinal fluid, particularly when meninges are inflamed.¹

Meropenem is indicated for complicated intra-abdominal infections, community-acquired and hospital-acquired pneumonia, complicated urinary tract infections, and bacterial meningitis in adults and children. It is also used empirically in febrile neutropenia and for infections caused by multidrug-resistant organisms. The drug is administered intravenously, typically as a 500 mg to 2 g dose every 8 hours, with dose adjustments for renal impairment. Prolonged or extended infusions (e.g., over 3 hours) have been studied to optimize pharmacokinetic/pharmacodynamic targets, especially in critically ill patients. In severe infections, combination therapy with other agents may be considered, though evidence is limited.²

Common adverse effects include nausea, diarrhea, rash, and injection-site reactions; more serious effects include seizures, particularly in patients with renal impairment or underlying neurological disorders, though meropenem is considered less epileptogenic than imipenem. Hypersensitivity reactions, including anaphylaxis, can occur, especially in penicillin-allergic patients. Resistance to meropenem is increasingly reported, primarily due to carbapenemase production (e.g., KPC, NDM, OXA-48) and porin loss combined with efflux pumps. The spread of carbapenem-resistant Enterobacteriaceae (CRE) poses a significant public health threat, limiting therapeutic options. Antimicrobial stewardship programs are crucial to preserve meropenem's efficacy.³

Meropenem has been studied for its potential anti-inflammatory effects independent of antibacterial activity, including modulation of cytokine release. It is also used in the treatment of Nocardia infections, though not FDA-approved for this indication. In veterinary medicine, meropenem is used off-label for severe infections in dogs and horses, but its use is restricted in some countries to preserve human drug efficacy. The drug's stability in various intravenous solutions and its compatibility with other medications are important for clinical practice; for instance, it should not be mixed with valproic acid, as it reduces valproate levels, increasing seizure risk. Meropenem has been used in continuous renal replacement therapy with specific dosing recommendations. Its role in the treatment of Mycobacterium abscessus infections is emerging, though data are limited.⁴

Carbapenem

A class of beta-lactam antibiotics with a broad spectrum of activity, resistant to many beta-lactamases.

Penicillin-binding proteins (PBPs)

Enzymes involved in bacterial cell wall synthesis; targets of beta-lactam antibiotics.

Extended-spectrum beta-lactamases (ESBLs)

Enzymes that confer resistance to penicillins, cephalosporins, and aztreonam.

Carbapenemase

Enzymes that hydrolyze carbapenems, leading to resistance.