Cocrystallizing and Codelivering Complementary Drugs to Multidrugresistant Tuberculosis Bacteria in Perfecting Multidrug Therapy

Curr Top Med Chem. 2023;23(19):1850-1858. doi: 10.2174/1568026623666230504094521.


Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria.

Keywords: Cell membrane permeability; Cocrystals; Efflux pump; Multidrug-resistant bacteria; Supramolecular synthon; tuberculosis.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacteria / metabolism
  • Bacterial Proteins / metabolism
  • COVID-19*
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Humans
  • Leprostatic Agents / pharmacology
  • Tuberculosis* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / microbiology


  • Bacterial Proteins
  • Leprostatic Agents
  • Anti-Bacterial Agents