Antibiotic Restriction Might Facilitate the Emergence of Multi-drug Resistance

High antibiotic resistance frequencies have become a major public health issue. The decrease in new antibiotics' production, combined with increasing frequencies of multi-drug resistant (MDR) bacteria, cause substantial limitations in treatment options for some bacterial infections. To diminish overall resistance, and especially the occurrence of bacteria that are resistant to all antibiotics, certain drugs are deliberately scarcely used—mainly when other options are exhausted. We use a mathematical model to explore the efficiency of such antibiotic restrictions. We assume two commonly used drugs and one restricted drug. The model is examined for the mixing strategy of antibiotic prescription, in which one of the drugs is randomly assigned to each incoming patient. Data obtained from Rabin medical center, Israel, is used to estimate realistic single and double antibiotic resistance frequencies in incoming patients. We find that broad usage of the hitherto restricted drug can reduce the number of incorrectly treated patients, and reduce the spread of bacteria resistant to both common antibiotics. Such double resistant infections are often eventually treated with the restricted drug, and therefore are prone to become resistant to all three antibiotics. Thus, counterintuitively, a broader usage of a formerly restricted drug can sometimes lead to a decrease in the emergence of bacteria resistant to all drugs. We recommend re-examining restriction of specific drugs, when multiple resistance to the relevant alternative drugs already exists.Author Summary: Methods for minimizing antibiotic resistance are becoming more important as antibiotic resistance frequencies are rising, coupled with low discovery rates of new antibiotics. In this work we examined the practice of restricting specific drugs to be used only as 'last resort'. The goal of such restrictions is to maintain low resistance levels to certain drugs, and prevent the creation of bacteria resistant to all available treatment options. We used a mathematical model to study the impact of such restrictions, when some resistance to the unrestricted drugs is already present. We estimated the resistance frequencies of common bacteria from hospital data. We find that restricting drugs leads to increased rates of incorrect treatment, and might simultaneously lead to increased emergence of multidrug resistant bacteria. We conclude that restricting specific antibiotics should be done with caution. In some cases lifting restrictions might even delay MDR emergence.