From the Guidelines
Meropenem is not recommended as a primary treatment for tuberculosis, and its use should be limited to specific cases of extensively drug-resistant TB (XDR-TB) under specialist guidance and after drug susceptibility testing. While meropenem has some activity against Mycobacterium tuberculosis, particularly when combined with clavulanate, it is never used as monotherapy for TB 1. Tuberculosis requires a multi-drug regimen typically consisting of isoniazid, rifampin, ethambutol, and pyrazinamide for the initial phase, followed by isoniazid and rifampin for the continuation phase. The standard first-line regimen lasts 6 months total.
Key Considerations
- Meropenem may occasionally be included in regimens for XDR-TB as part of a combination therapy, but only under specialist guidance and after drug susceptibility testing 1.
- The reason for multi-drug therapy is that TB bacteria can rapidly develop resistance to single agents.
- Meropenem's mechanism against TB involves inhibition of cell wall synthesis, but its limited penetration into TB lesions, need for intravenous administration, and high cost make it impractical for routine TB treatment.
Treatment Guidelines
- The American Journal of Respiratory and Critical Care Medicine recommends using at least five drugs in the intensive phase of treatment and four drugs in the continuation phase of treatment for MDR-TB 1.
- The guideline suggests an intensive-phase duration of treatment of between 5 and 7 months after culture conversion and a total treatment duration of between 15 and 21 months after culture conversion 1.
- In patients with pre–XDR-TB and XDR-TB, the guideline suggests a total treatment duration of between 15 and 24 months after culture conversion 1.
Specialist Guidance
If TB is suspected, proper diagnostic testing should be performed and treatment should follow established multi-drug protocols under the guidance of specialists in infectious diseases or pulmonology.
From the Research
Effectiveness of Meropenem in Treating Tuberculosis
- Meropenem, in combination with clavulanate, has shown promising results in treating extensively drug-resistant tuberculosis (XDR-TB) 2, 3.
- A study published in 2018 found that the meropenem-clavulanate combination had a successful outcome rate of 83.3% and a mortality rate of 11.1% in XDR-TB patients, with no relapses observed after a median follow-up of 4 years 2.
- Another study published in 2019 explored the use of meropenem in combination with a β-lactamase inhibitor and found that it may be beneficial for the treatment of difficult-to-treat TB cases 4.
- The clinical use of meropenem-clavulanate for XDR-TB has been reported, with encouraging preliminary data 3.
- A randomized, phase 2A clinical trial published in 2022 evaluated the early bactericidal activity of meropenem plus clavulanate (with or without rifampin) for tuberculosis and found that bactericidal activity was greater with the World Health Organization-recommended total daily dose of 6 g daily than with a lower dose of 3 g daily 5.
Limitations and Adverse Events
- The use of meropenem for tuberculosis treatment is still being researched, and more studies are needed to fully understand its effectiveness and potential limitations 2, 4, 3, 5.
- Adverse events, such as gastrointestinal adverse events, have been reported in patients treated with meropenem 5.
- The tolerability of intravenous meropenem, with amoxicillin/clavulanate, was found to be poor at all doses, which may limit its utility in second-line regimens 5.
Comparison to Other Treatments
- The rate of sustained successful treatment outcome observed with meropenem-clavulanate is higher than that observed in the 2014 World Health Organization XDR-TB cohort 2.
- Meropenem may be an alternative approach for drug-resistant tuberculosis, particularly when used in combination with other drugs or inhibitors 4, 5.