Usage
Meropenem is a broad-spectrum carbapenem antibiotic prescribed for a wide range of bacterial infections. It is effective against both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. Specific infections meropenem is used to treat include:
- Complicated skin and skin structure infections (cSSSI)
- Complicated intra-abdominal infections (cIAI)
- Bacterial meningitis
- Pneumonia
- Urinary tract infections (UTIs)
- Septicemia
Pharmacological Classification: Antibiotic (Carbapenem)
Mechanism of Action: Meropenem inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). It is resistant to hydrolysis by most beta-lactamases, giving it a broad spectrum of activity.
Alternate Names
Meropenem is the generic name. Several brand names exist, including Merrem IV.
How It Works
Pharmacodynamics: Meropenem exerts its bactericidal action by irreversibly inhibiting PBPs, which are essential for bacterial cell wall synthesis. This leads to cell lysis and bacterial death.
Pharmacokinetics:
- Absorption: Administered intravenously (IV), achieving rapid and complete absorption.
- Distribution: Widely distributed into various body tissues and fluids, including cerebrospinal fluid (CSF), which is crucial for treating meningitis.
- Metabolism: Minimally metabolized, primarily to an inactive metabolite.
- Elimination: Primarily excreted unchanged by the kidneys, with a half-life of approximately 1 hour. Dose adjustments are needed in patients with renal impairment. Hepatic impairment does not significantly affect meropenem pharmacokinetics.
Mode of Action: Meropenem penetrates the bacterial cell wall readily and binds with high affinity to PBPs, specifically PBPs 1, 2, and 3. This binding inhibits the transpeptidation and cross-linking reactions crucial for peptidoglycan synthesis, a key component of the bacterial cell wall. The resulting weakened cell wall makes the bacteria susceptible to osmotic lysis and eventual death.
Receptor Binding/Enzyme Inhibition: Meropenem’s primary mode of action is through the inhibition of PBPs, functioning as a mechanism-based inhibitor. It is stable against most beta-lactamases, which contributes to its broad-spectrum activity.
Elimination Pathways: Predominantly renal excretion.
Dosage
Standard Dosage
Adults:
- cSSSI: 500 mg IV every 8 hours
- cIAI: 1 g IV every 8 hours
- Pseudomonas aeruginosa infections: 1 g IV every 8 hours
Infusion over 15-30 minutes or bolus injection over 3-5 minutes. Maximum dose: Up to 2g every 8 hours for severe infections.
Children (3 months and older):
- cSSSI: 10 mg/kg IV every 8 hours (Maximum: 500 mg/dose)
- cIAI: 20 mg/kg IV every 8 hours (Maximum: 1 g/dose)
- Meningitis: 40 mg/kg IV every 8 hours (Maximum: 2 g/dose)
- Children > 50 kg: Adult dosages apply
Infusion over 15-30 minutes or bolus injection over 3-5 minutes.
Children (less than 3 months): Dosage based on gestational and postnatal age. See below.
Special Cases:
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Elderly Patients: No dose adjustment is necessary in patients with normal renal function. Dose adjustments should be based on creatinine clearance in patients with renal impairment (see below). Extended or continuous infusions may be considered.
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Patients with Renal Impairment: Dosage adjustments required based on creatinine clearance (CrCl):
- CrCl > 50 mL/min: Standard dose
- CrCl 26-50 mL/min: Standard dose every 12 hours
- CrCl 10-25 mL/min: Half the standard dose every 12 hours
- CrCl < 10 mL/min: Half the standard dose every 24 hours
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Patients with Hepatic Dysfunction: No dose adjustment is necessary.
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Patients with Comorbid Conditions: Consider individual patient factors and adjust dosage accordingly. Monitor closely.
Clinical Use Cases
Dosing guidelines for specific medical settings are generally the same as standard dosing guidelines, with adjustments made based on individual patient needs and the severity of the infection. Higher doses (up to 2 g every 8 hours for adults and 40 mg/kg every 8 hours for children) may be necessary for more severe infections, including those caused by less susceptible organisms.
Dosage Adjustments
Renal impairment requires dosage adjustments based on creatinine clearance (see above). No adjustment is needed for hepatic dysfunction. Dosage adjustments are also needed for neonates and infants less than 3 months old. For neonates (less than 3 months):
- < 32 weeks GA and PNA < 2 weeks: 20 mg/kg every 12 hours IV (infusion over 30 minutes).
- < 32 weeks GA and PNA ≥ 2 weeks, or ≥ 32 weeks GA and PNA < 2 weeks: 20 mg/kg every 8 hours IV (infusion over 30 minutes).
- ≥ 32 weeks GA and PNA ≥ 2 weeks: 30 mg/kg every 8 hours IV (infusion over 30 minutes).
Side Effects
Common Side Effects:
- Headache
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Injection site reactions (pain, swelling, redness)
Rare but Serious Side Effects:
- Seizures
- Clostridium difficile-associated diarrhea
- Severe allergic reactions (anaphylaxis)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
Long-Term Effects: Potential for renal toxicity with prolonged use, particularly at higher doses. Superinfections.
Adverse Drug Reactions (ADR):
- Anaphylaxis
- Severe skin reactions (SJS/TEN)
- Pseudomembranous colitis
- Seizures
Contraindications
- Hypersensitivity to meropenem or other carbapenems
- History of anaphylactic reactions to beta-lactam antibiotics
Drug Interactions
- Probenecid: Reduces renal excretion of meropenem, increasing serum levels.
- Valproic acid/Divalproex sodium: Meropenem can decrease valproic acid levels, increasing the risk of seizures.
- Anticoagulants (e.g., warfarin): May enhance the anticoagulant effect.
- Other antibiotics, especially bacteriostatic antibiotics, may have antagonistic activity.
Pregnancy and Breastfeeding
- Pregnancy: Animal studies have not shown adverse effects, but there are limited data in humans. Use only if the potential benefit outweighs the risk to the fetus.
- Breastfeeding: Meropenem is excreted in breast milk in small amounts. Use with caution and monitor the infant for any adverse effects.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.
- Side Effects: Common: Headache, nausea, vomiting, diarrhea, constipation, injection site reactions. Serious: Seizures, C. difficile infection, allergic reactions.
- Contraindications: Hypersensitivity to meropenem or other carbapenems, history of anaphylactic reactions to beta-lactams.
- Drug Interactions: Probenecid, valproic acid, anticoagulants.
- Pregnancy & Breastfeeding: Use with caution in pregnancy. Monitor infants for adverse effects during breastfeeding.
- Dosage: Refer to detailed dosage section above.
- Monitoring Parameters: Renal function (serum creatinine, creatinine clearance), liver function tests, complete blood count (CBC) during prolonged therapy, signs and symptoms of infection, clinical response.
Popular Combinations
Meropenem is often used as monotherapy but can be combined with other antibiotics depending on the infection. For example, it may be combined with vancomycin for suspected methicillin-resistant Staphylococcus aureus (MRSA) infections or with an aminoglycoside for severe Gram-negative infections.
Precautions
- General Precautions: Assess renal function before and during therapy. Monitor for signs of hypersensitivity and superinfections.
- Specific Populations: Use cautiously in pregnancy and breastfeeding (see above). Adjust dose in patients with renal impairment (see above). Dosage adjustments required for neonates and infants.
- Lifestyle Considerations: No specific lifestyle considerations typically apply, but maintain adequate hydration.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Meropenem?
A: See the detailed dosage section above.
Q2: How is Meropenem administered?
A: Intravenously (IV), either by infusion over 15-30 minutes or bolus injection over 3-5 minutes.
Q3: What are the most common side effects of Meropenem?
A: The most common side effects are headache, nausea, vomiting, diarrhea, constipation, and injection site reactions.
Q4: Can Meropenem be used in patients with renal impairment?
A: Yes, but the dosage must be adjusted based on creatinine clearance.
Q5: What are the contraindications to using Meropenem?
A: Known hypersensitivity to meropenem or other carbapenems and a history of anaphylactic reactions to beta-lactam antibiotics.
Q6: Does Meropenem interact with other medications?
A: Yes. Clinically significant interactions can occur with probenecid, valproic acid, anticoagulants, and potentially other antibiotics. See Drug Interactions section for more details.
Q7: Can Meropenem be used during pregnancy and breastfeeding?
A: It should be used cautiously during pregnancy and breastfeeding. Consult the Pregnancy and Breastfeeding section for detailed information.
Q8: What should be monitored during Meropenem therapy?
A: Renal function, liver function tests, complete blood count during prolonged therapy, signs and symptoms of infection, and clinical response.
Q9: How does meropenem differ from other carbapenems?
A: Meropenem is generally well-tolerated and has a lower risk of seizures compared to imipenem. It is also stable against dehydropeptidase-1, meaning it does not need to be co-administered with cilastatin. Its spectrum of activity is similar to other carbapenems, covering a wide range of Gram-positive and Gram-negative bacteria.
Q10: What are the signs of a severe allergic reaction to meropenem?
A: Signs of a severe allergic reaction (anaphylaxis) can include difficulty breathing, swelling of the face, lips, or tongue, hives, rash, itching, and a rapid or weak pulse. Seek immediate medical attention if these occur.
