Researchers at the Yale School of Public Health have developed a new mathematical model to help predict the optimal dosing of antibiotics.
Although antibiotics were first introduced more than 70 years ago, substantial uncertainty remains about how the drugs should be used by patients to ensure recovery, while minimizing toxic side effects and the risk of developing antibiotic resistance.
“To date, antibiotic treatment recommendations have been arrived at by trial-and-error or with complex models of drug distribution and action, and it is not possible in most cases to know whether the recommended dose, frequency and length of most treatment regimens are appropriate,” said Ted Cohen, M.D., M.P.H, D.Ph., associate professor at Yale School of Public Health and senior author of the study in the journal Science Translational Medicine.
While current mathematical models predict the effect of antibiotics on bacteria in specific settings, these models fail to reliably predict treatment efficacy across a range of biologically relevant scenarios.
In their study, Pia Abel zur Wiesch, postdoctoral fellow at Yale School of Public Health and lead author, Cohen and a team of international colleagues describe a model that uses information about how antibiotics bind to bacterial target molecules to predict how these drugs will affect individual bacterial cells and populations of bacteria. The model suggests that the apparent complexity of antibiotic action may be explained by the simple chemical kinetics of antibiotics binding to bacterial targets. Accordingly, the new model offers an alternative explanation for the mechanisms that are responsible for complex antibiotic actions.
Abel zur Wiesch said that the complexity of antibiotic action has traditionally been ascribed to various biological phenomena. For example, it is not well understood why very long treatment courses are needed to eradicate some bacterial infections. One common explanation has been that some bacteria are “asleep” and not susceptible to antibiotics, but can then “wake up” after therapy is discontinued and cause patients to suffer a relapse.
The authors hope the model may eventually help inform the design of more effective antibiotic dosing regimens based on chemical kinetic properties of antibiotics alone. Furthermore, the model may be useful for speeding the development of new antibiotics by identifying favorable chemical kinetic characteristics of new drug compounds.
In the future, the authors plan to extend this model to understand how chemical kinetics of antibiotics influence the risk of drug resistance, particularly for diseases of global health importance such as tuberculosis. “While we are excited about the promise of this modeling framework for explaining antibiotic effects, additional work is needed to evaluate whether this simple modeling framework can be used to inform the design of regimens for diseases requiring complex multidrug treatments,” said Abel zur Wiesch.
Publication: Pia Abel zur Wiesch, et al., “Classic reaction kinetics can explain complex patterns of antibiotic action,” Sci Transl Med 13 May 2015: Vol. 7, Issue 287, p. 287ra73; DOI: 10.1126/scitranslmed.aaa8760
Image: Yale University
Anti-biotics are chemical warfare against bacteria. After all they have no limbs to war against us and can only produce chemicals and enzymes for their survival against the attacks. The efficacy of the drug is to first tear its skin. Then it accommodates by forming a very thick skin or shell around them to protect against the chemicals. This is a struggle for existence. It will also closely pack the spores on the membrane, which they cannot altogether stop making because it is needed for their phagocytosis and exocytosis. Simply it means that they require inlets and outlets for their food intake and excreta. If we improve the molecule to enter its pore even now and attack its nucleus, then it knows the way to keep a copy of the DNA separately in a capsule which can be passed on to the next bacteria for progeny by sexual transmission. i.e., transmission by a separate rod developed by them to inject into the other bacteria for survival. Please note that bacteria can produce both asexually and sexually but keeps its DNA formula intact. The new traits of forming formidable skin and satelite nucleus and also certain enzymes to dissolve the molecules attacking them are formulated in their modified DNA. Thus bacteria becomes more and more resistant to the drugs discovered. As long as it can rewrite the formula for its life with these nuances and new techniques our war will continue.They cannot to adapt to grow limbs which are not needed for mobility but enzyme production is more advanced in them to be successful against the chemicals. We know how nicely E-Coli bacteria are used by animals to digest the straw which they eat because of the enzymes produced by the gut bacteria. For us also enzymes of the gut bacteria are useful for digestion and in fact we derive more benefit from bacterial enzymes in our body than the harm which they do to us. In fact human insulin is produced by the E-coli modified in the laboratory to help us. Since you cannot make every patient in the world to consume adequate doses of anti-biotic to eradicate completely , the adaptation of the remaining bacteria will continue and they will only thrive giving us more and more headache. After all they are going to last on earth much longer than human race and they were much earlier also, which makes them a prodigy in the art of survival techniques. Our war with the bacteria with anti-biotics improved will be a never ending process. Thank You.