According to data published in the February issue of the journal Science, the combination of the antibiotic carbapenem meropenem with an inhibitor of clavulanic acid beta-lactamase has a synergistic bactericidal effect against the super-resistant strains of Mycobacterium tuberculosis.

Meropenem and clavulanic acid (commonly used in combination with amoxicillin) are approved and used in many countries to treat various bacterial infections caused by susceptible pathogens.

In addition, both drugs have a favorable safety profile and can be used in different categories of patients, including children, from 3 months. However, neither meropenem nor clavulanic acid has traditionally been considered as drugs for the treatment of tuberculosis.

The emergence and widespread resistance to first-, second- and third-line anti-tuberculosis drugs in M. tuberculosis strains greatly limits the possibilities for effective treatment of tuberculosis, greatly increasing the likelihood of unfavorable outcome in patients infected with such strains of super-resistant mycobacteria.

Beta-lactams are generally inactive against M. tuberculosis, because mycobacteria have the natural ability to produce beta-lactamase (BlaC), which effectively destroys the antibiotic molecule. However, as the researchers discovered, clavulanic acid irreversibly inhibits BlaC and meropenem is not very sensitive to hydrolysis by this beta-lactamase and is able to suppress its activity.

When these two drugs were added to the actively growing aerobic culture M. tuberculosis, complete sterilization of the culture medium was observed after 12 days of incubation. In addition, this combination of antimicrobials also reduced the viability of the M. tuberculosis culture under anaerobic conditions in the persistent and non-replicative phase.

In tests, the combination of meropenem with clavulanic acid was also effective against 12 super-resistant clinical strains of Mycobacterium tuberculosis, as well as against sensitive strains.

The revealed synergy and the strong activity detected in vitro of meropenem with clavulanic acid against sensitive and super resistant clinical strains M. tuberculosis suggests that this combination could be effective in the treatment of tuberculosis, including the treatment of patients with the current incurable form of the disease caused by strains of super-resistant mycobacteria.