Discovery and market approval of antibacterial drugs is a process that is riddled with several critical milestones and challenges. The fact is that with the rise in bacterial resistance against the available antibiotics, the pressure for innovation in the development of antibacterial drugs has never been so strong. This article explains a few of the most common challenges that arise during antibacterial drug development and strategic approaches to overcome them effectively.
Discovery of new targets
Pathogenesis of bacteria
The first challenge in antibacterial drug development is identifying novel targets. This requires a detailed understanding of the pathogenesis of bacteria. It is, therefore, upon the researcher to explore the genetic and biochemical pathways of the bacteria to point out potential vulnerabilities that can be targeted by new drugs.
Advances in Genomic Technologies
Genomic technologies are of importance in this endeavor. These include technologies like high-throughput sequencing and CRISPR-Cas systems which are powerful tools expected to quickly and efficiently enable the dissection of bacterial genomes thus identifying essential genes that can be the targets of drugs.
Enhancing Drug Efficacy
Optimizing Pharmacokinetics and Pharmacodynamics
Once a target is identified, developing a molecule that can interact effectively with the target is the next step. This involves studying the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug. PK studies show how the body interacts with the drug following its administration. This includes absorption, distribution, metabolism, and excretion of the drug. On the other hand, PD studies show how the body is affected by the drug, and more particularly how the drug kills or inhibits bacterial multiplication.
Addressing the Minimum Bactericidal Concentration (MBC)
For the enhancement of the antibacterial drugs’ efficacy, minimum concentration of antibacterial required to kill a specific bacterium must be determined. Based on the MBC, researchers must design drugs that achieve the lowest possible MBCs without inducing high levels of resistance or toxicity.
Addressing the Minimum Inhibitory Concentration (MIC)
The MIC test provides the lowest concentration of the antibacterial agent required to suppress the visible growth of a bacterium following an overnight incubation. MIC is a very essential parameter to be included in the early stages of antibacterial drug development because it allows the evaluation of the potency of a new antibacterial agent across a spectrum of bacteria.
Addressing the Zone of Inhibition (ZOI)
The ZOI test is conducted with agar diffusion techniques, such as the Kirby-Bauer disk diffusion test. It measures the effectiveness of an antibacterial agent by observing the clear zones that surround a disk impregnated with the drug, where the growth of bacteria is inhibited.
The results obtained with these tests can help the researchers assess the efficacy of drug formulations and if required change the formulations to improve the efficacy.
Overcoming Resistance
Mechanisms of Resistance
Drug resistance represents one of the most important and ongoing problems in antibacterial drug development. There are several mechanisms by which bacteria can gain resistance, including genomic mutation or acquisition of resistance genes from other bacteria. Appropriate knowledge of these mechanisms is essential in the development of drugs that would be less prone to resistance.
Innovative Drug Combinations
New drug combinations could also be used to get over such resistance. Combining drugs with different mechanisms of action may lower the probability of bacteria developing resistance against all mechanisms at once.
Regulatory Challenges
Adhering to Regulatory Standards
Another critical challenge is navigating the regulatory landscape. The safety and efficacy of the new antibacterial drugs has to be supported with evidence in the form of data in order to pass the standards set by the regulatory bodies.
Accelerated Approval Pathways
Early engagement with the regulatory bodies in the early steps of antibacterial drug development and availing of accelerated approval pathways will make the whole process more streamlined. These mechanisms are purposefully designed to expedite the development and review of drugs that address unmet medical needs in treating serious conditions.
Enhancing Clinical Trials
Designing Effective Trials
Clinical trials are the basis for the approval of an antibacterial drug. Effective trial designs incorporate appropriate doses, schedules, and selection of suitable patient groups. It is essential that the drug shows effectiveness against bacteria in an actual clinical environment.
Flexible Trial Designs
Adaptive trial designs offer flexibility in the trial process and allow for modifications according to the interim results. This adaptive nature provides flexibility in responding to unforeseen challenges during the trial—for example, changes in bacterial resistance.
Role of MIS
At Microbe Investigations Switzerland, we understand the hurdles that drug developers face in creating effective antibacterial treatments. Leveraging our expertise in microbial testing, including critical assessments like MIC, ZOI, and MBC, we provide insightful data and strategic support to help develop an effective drug. Our advanced testing services are designed to assess drug efficacy and speed up the development process, ensuring you stay ahead in the competitive pharmaceutical landscape.
To learn more about our MBC, MIC or ZOI tests or to receive a quote, please contact our experts today.
