Meropenem + Tazobactam

Usage

Meropenem + Tazobactam is an antibiotic combination prescribed for the treatment of various bacterial infections. Tazobactam is a beta-lactamase inhibitor, while Meropenem is a carbapenem antibiotic. This combination is effective against a broad spectrum of gram-negative and gram-positive bacteria, including some resistant strains. It is used to treat complicated intra-abdominal infections, complicated skin and soft tissue infections, complicated urinary tract infections, and pneumonia (including hospital-acquired and ventilator-associated pneumonia). It’s classified as a carbapenem antibiotic, in combination with a beta-lactamase inhibitor. Meropenem inhibits bacterial cell wall synthesis, leading to bacterial cell death. Tazobactam protects meropenem from degradation by bacterial beta-lactamases, thereby extending its effectiveness against a wider range of bacteria.

Alternate Names

While “Meropenem + Tazobactam” is the standard generic name, specific brand names may exist depending on the manufacturer and region. One example found is MERODUKE TAZO.

How It Works

Pharmacodynamics: Meropenem exerts its bactericidal action by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), which are crucial for the final step of peptidoglycan synthesis in bacterial cell walls. This binding disrupts the cross-linking of peptidoglycans, weakening the cell wall and eventually leading to cell lysis and death. Tazobactam, a beta-lactamase inhibitor, protects meropenem by binding and inactivating beta-lactamase enzymes produced by certain bacteria. These enzymes normally break down beta-lactam antibiotics like meropenem, rendering them ineffective. By inhibiting these enzymes, tazobactam extends the spectrum of activity of meropenem.

Pharmacokinetics: Both drugs are administered intravenously. Meropenem is well-absorbed, reaching peak plasma concentrations rapidly after administration. It is widely distributed in body tissues and fluids, including cerebrospinal fluid, making it effective against central nervous system infections. Meropenem is primarily eliminated through renal excretion, with about 70% of the dose excreted unchanged in the urine. Tazobactam is also primarily eliminated renally. The half-life of both drugs is around 1 hour, requiring frequent dosing to maintain therapeutic levels. Dosing adjustments are necessary in patients with renal impairment.

Dosage

Standard Dosage

Adults: The standard dose is 1 to 2 grams intravenously, usually every 8 hours depending on the severity of the infection. It can also be administered via intravenous infusion over a 3-hour period for 1 gram dose. For pneumonia, peak levels of 7-8 mg/dL are targeted, while for systemic gram-negative infections and cystitis the target peak level is 6-8 mg/dL and 3-4 mg/dL, respectively. Irrespective of indication, the trough level target is <1 mg/L.

Children: Dosage is based on weight (mg/kg) and the specific infection being treated. Pediatric safety considerations include monitoring for adverse reactions and adjusting the dose in case of renal impairment.

Special Cases: Dosage adjustment is necessary in patients with renal impairment, and depends on the creatinine clearance (CrCl) rate. Similar adjustments may be necessary for patients with hepatic dysfunction and for the elderly, based on the individual case and clinical judgement. For patients with a CrCl > 40 mL/min a 3.375 g IV dose every 6 hours is indicated, for a CrCl between 20 and 40 mL/min without hemodialysis, 2.25 g IV every 6 hours are indicated. For patients with a CrCl < 20 mL/min without hemodialysis, 2.25 g IV are indicated every 8 hours, while on hemodialysis 2.25 g IV every 12 hours are indicated. Additionally, a dose of 0.75g of Meropenem/ Tazobactam are indicated after every dialysis period on hemodialysis days. No structured procedure for dose adjustments following concentration measurements outside the target range was pre-specified. For all prolonged or continuous infusions, a loading dose of 1 g meropenem or 4 g piperacillin/0.5 g tazobactam was recommended.

Clinical Use Cases The dosage is determined by the specific indication and the patient’s condition. Doses may be higher and more frequent in severe infections or critical care settings. For prolonged or continuous infusions, a loading dose of 1g meropenem or 4g piperacillin/0.5g tazobactam is recommended.

Dosage Adjustments Dosage should be adjusted for renal and hepatic function, age, body weight and other relevant factors.

Side Effects

Common Side Effects: Headache, nausea, vomiting, diarrhea, pain and inflammation at the injection site are common side effects.

Rare but Serious Side Effects: Seizures, allergic reactions (including anaphylaxis), severe diarrhea (pseudomembranous colitis), hearing changes, mental/mood changes, and signs of kidney problems.

Long-Term Effects: Long-term effects are rare but can include antibiotic-associated colitis and the development of resistant bacteria.

Contraindications

Known hypersensitivity to meropenem, tazobactam, or any component of the formulation, or any other carbapenem or beta-lactam antibiotic.

Drug Interactions

Probenecid, valproic acid, and drugs that affect renal function can interact with Meropenem + Tazobactam.

Pregnancy and Breastfeeding

Meropenem + Tazobactam should be used during pregnancy and breastfeeding only if clearly needed, and the potential benefits outweigh the potential risks to the fetus or infant.

Drug Profile Summary

• Mechanism of Action: Meropenem inhibits cell wall synthesis, while Tazobactam protects Meropenem from degradation by bacterial beta-lactamases.
• Side Effects: Common side effects include headache, gastrointestinal upset, and injection site reactions. Serious side effects can include seizures and allergic reactions.
• Contraindications: Hypersensitivity to carbapenems or beta-lactam antibiotics.
• Drug Interactions: Probenecid, valproic acid.
• Pregnancy & Breastfeeding: Use only if the potential benefits outweigh the potential risks.
• Dosage: Varies depending on the patient, the infection, and renal function.
• Monitoring Parameters: Renal function, liver function, complete blood count, signs and symptoms of infection.

Popular Combinations

While Meropenem and Tazobactam are typically administered together, other combinations may be used depending on the specific infection and the patient’s clinical condition.

Precautions

Standard precautions for antibiotic use apply, including assessment of allergies, renal function, and potential drug interactions. Monitoring for adverse effects is crucial.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Meropenem + Tazobactam?

A: The dosage varies depending on the type and severity of infection, the patient’s age, weight, and renal function. Consult the dosage section for specific guidelines and adjustments.

Q2: What are the most common side effects?

A: Common side effects include headache, nausea, vomiting, diarrhea, and injection site reactions.

Q3: What are the serious side effects to watch for?

A: Seizures, allergic reactions, Clostridium difficile colitis, and signs of kidney problems are serious side effects that require immediate attention.

Q4: Can it be used during pregnancy and breastfeeding?

A: Use during pregnancy and breastfeeding should be carefully considered, weighing the benefits against the potential risks. Consult a specialist if necessary.

Q5: How does tazobactam enhance the effectiveness of meropenem?

A: Tazobactam inhibits beta-lactamase enzymes produced by bacteria, preventing the degradation of meropenem and thus broadening its spectrum of activity.

Q6: What are the key drug interactions?

A: Co-administration with probenecid may increase meropenem plasma concentrations. Concurrent use with valproic acid may increase the risk of seizures.

Q7: How should the dose be adjusted for patients with renal impairment?

A: The dose needs to be reduced in patients with renal impairment based on creatinine clearance.

Q8: What are the main contraindications?

A: Hypersensitivity to meropenem, tazobactam, or any beta-lactam antibiotics is a contraindication.

Q9: What monitoring is recommended during therapy?

A: Monitor renal function, complete blood count, and signs and symptoms of the infection, as well as be vigilant for adverse reactions.

Q10: Are there any dietary restrictions while taking Meropenem + Tazobactam?

A: No specific dietary restrictions are associated with this medication. However, maintaining a healthy diet and hydration is always recommended.