From the Guidelines
Meropenem has limited effectiveness against tuberculosis when used alone but may have a role in treating multidrug-resistant tuberculosis (MDR-TB) as part of a combination regimen, as suggested by the World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update 1.
Key Points
- Meropenem is not a first-line TB drug and should only be used when standard options fail due to resistance.
- For MDR-TB treatment, meropenem is typically administered at 1 gram intravenously every 8 hours, always combined with clavulanate (usually as amoxicillin-clavulanate) and other active anti-TB medications based on susceptibility testing.
- Treatment duration for MDR-TB regimens containing meropenem typically ranges from 18-24 months.
- The rationale for meropenem's activity against TB is that it inhibits cell wall synthesis by binding to penicillin-binding proteins, but Mycobacterium tuberculosis produces beta-lactamases that can degrade carbapenems.
- Adding clavulanate inhibits these beta-lactamases, enhancing meropenem's effectiveness.
- Side effects include gastrointestinal disturbances, headache, rash, and rarely seizures, particularly in patients with CNS disorders or renal impairment, so dosage adjustment is necessary in renal dysfunction.
Evidence-Based Recommendations
The use of meropenem in MDR-TB treatment is supported by the World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update 1, which suggests that meropenem can be used as part of a combination regimen for the treatment of MDR-TB. Additionally, the American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America treatment guidelines for drug-resistant tuberculosis also mention the use of meropenem as an alternative agent for the treatment of MDR-TB 1.
Important Considerations
- Meropenem should only be used under the guidance of a healthcare professional with expertise in the treatment of MDR-TB.
- Patients with MDR-TB should be closely monitored for adverse events and treatment outcomes.
- The use of meropenem in combination with other anti-TB medications should be based on susceptibility testing to ensure the most effective treatment regimen.
- The treatment of MDR-TB requires a comprehensive approach, including the use of multiple anti-TB medications, close monitoring, and supportive care.
From the Research
Effect of Meropenem on Partially Resistant Tuberculosis
- The study 2 investigated the early bactericidal activity of meropenem plus clavulanate (with or without rifampin) for tuberculosis, which may be relevant to partially resistant tuberculosis.
- The results showed that meropenem had bactericidal activity against tuberculosis, with a greater effect at higher doses.
- However, the tolerability of intravenous meropenem, with amoxicillin/clavulanate, was poor at all doses, which may limit its utility in second-line regimens for partially resistant tuberculosis.
- Other studies 3, 4, 5, 6 discussed the treatment of tuberculosis, including the use of first-line and second-line drugs, but did not specifically address the effect of meropenem on partially resistant tuberculosis.
Mechanism of Action and Resistance
- The study 3 reviewed the mechanisms of action and resistance of anti-tuberculosis drugs, including first-line and second-line agents.
- The study 4 discussed the pharmacodynamics of tuberculosis drugs, including the area under the curve (AUC) divided by the minimal inhibitory concentration (MIC), which may be relevant to understanding the effect of meropenem on partially resistant tuberculosis.
Clinical Implications
- The study 2 suggested that meropenem may be a useful option for the treatment of partially resistant tuberculosis, but its poor tolerability may limit its use.
- The study 6 emphasized the importance of individualized treatment regimens for patients with multidrug-resistant tuberculosis, which may include the use of meropenem in certain cases.