Meropenem 

1️⃣ Introduction

Meropenem is a carbapenem antibiotic belonging to the β-lactam class. It is structurally related to imipenem but has improved stability against renal dehydropeptidase-I and does not require cilastatin.


2️⃣ Mechanism of Action

Meropenem:

  • Binds to Penicillin Binding Proteins (PBPs)
  • Inhibits peptidoglycan synthesis
  • Causes bacterial cell wall lysis
  • Bactericidal (time-dependent killing)

Like all β-lactams:

  • Killing depends on %T > MIC
  • Optimal exposure: drug concentration above MIC for ≥40% of dosing interval (severe infections → target ≥100% T>MIC)


3️⃣ Spectrum of Activity

Meropenem is one of the broadest spectrum antibiotics.

 Gram Positive

  • Streptococcus species
  • MSSA
  • Enterococcus faecalis (moderate activity)

 Gram Negative

  • Enterobacteriaceae
  • ESBL producers
  • Pseudomonas aeruginosa
  • Acinetobacter (variable)

 Anaerobes

  • Bacteroides fragilis
  • Clostridium species

1️⃣ What is ESBL?

Extended-Spectrum Beta-Lactamase

These are enzymes produced by certain Gram-negative bacteria that:

  • Hydrolyze extended-spectrum cephalosporins
  • Inactivate penicillins
  • Inactivate aztreonam
  • Are inhibited by β-lactamase inhibitors (clavulanate, tazobactam, sulbactam)


Common ESBL Producing Organisms

1️⃣ Escherichia coli

2️⃣ Klebsiella pneumoniae

3️⃣ Proteus mirabilis

4️⃣ Enterobacter cloacae

5️⃣ Citrobacter freundii


Meropenem Not Effective Against

  • MRSA
  • Enterococcus faecium
  • Stenotrophomonas maltophilia
  • Atypicals (Mycoplasma, Chlamydia)


4️⃣ Pharmacokinetics 

Absorption IV only

Distribution

  • Widely distributed
  • Good lung penetration
  • Excellent intra-abdominal penetration
  • Good CSF penetration (especially inflamed meninges)

Elimination

  • Renal (70% unchanged)
  • Requires dose adjustment in renal failure



5️⃣ Extended & Continuous Infusion 

Since meropenem is time-dependent, prolonged infusion(over 3 hours) or continuous infusion improves target attainment.

Preferred in:

  • Septic shock
  • High MIC organisms
  • Augmented renal clearance
  • CRRT patients



 6️⃣ Clinical Indications

ICU Indications

  • Septic shock
  • Ventilator-associated pneumonia
  • Hospital-acquired pneumonia
  • Intra-abdominal sepsis
  • Complicated UTI
  • CNS infections
  • Febrile neutropenia
  • Necrotizing soft tissue infections


 Resistance Mechanisms 

  1. Carbapenemase production
    • KPC(Klebsiella pneumoniae Carbapenemase)
    • NDM(New Delhi Metallo-β-lactamase)
    • OXA-48(Oxacillinase)
  1. Efflux pumps
  2. Porin loss

Meropenem fails against:

  • Carbapenem-resistant Enterobacteriaceae (CRE)


 Adverse Effects

  • Nausea, diarrhea
  • Rash
  • Transaminitis
  • Thrombocytopenia (rare)
  • Seizures (less than imipenem)

Seizure Risk

  • Higher in:
    • Renal failure
    • CNS pathology
    • High doses


 Meropenem vs Imipenem

Feature

Meropenem

Imipenem

Cilastatin needed

No

Yes

Seizure risk

Lower

Higher

CNS penetration

Better

Moderate

Pseudomonas

Good

Good


 Meropenem in Special Situations

Pregnancy

  • Category B
  • Relatively safe

ICU with Augmented Renal Clearance

  • May require higher doses
  • Extended infusion preferred

ECMO

  • Increased volume of distribution
  • Therapeutic drug monitoring if available


Antibiotic Stewardship Perspective

Meropenem is a last-line broad-spectrum antibiotic.

Principles:

  • Avoid empirical overuse
  • De-escalate once culture available within 48–72 hours
  • Use extended infusion instead of increasing dose unnecessarily
  • Combine if needed for MDR organisms