Rajaa Dabour, Tomer Meirson, Abraham O Samson, 2016
Antibiotic resistance is an ancient bacterial survival mechanism that pre-dates modern medicine. In local settings, such as hospitals, antibiotic resistance rises and falls in a cyclic pattern. Here we investigate whether antibiotic resistance is also governed by a cyclic pattern in global settings. To this end, we counted the yearly occurrence of the word combination ‘antibiotic’ and ‘resistance’ in the scientific literature. For example, for ampicillin resistance in 1986, we counted the number of papers containing the word-pair ‘ampicillin resistance’ as indexed by PubMed in that year. We repeated this procedure for 300 generic antibiotics, and for all years between 1986 and 2015. Finally, we fit the data of antibiotic resistance to a periodic function. Of the 300 generic antibiotics, ca. 150 were marketed after 1986 and as such were excluded from the study. Of the 150 remaining antibiotics, most presented 0.8) with experimental data published by the US Centers for Disease Control and Prevention (CDC). While costly CDC data are incomplete, and until more experimental data become available, our inexpensive theoretical data could serve as a trend line for antibiotic resistance. Periodic antibiotic resistance adheres to Darwin’s principle of natural selection. At first, antibiotic resistance is an uncommon and sporadic trait. Then, following worldwide use of the antibiotic, survival of resistant bacteria is favoured, which in turn gives rise to the antibiotic resistance. Then, as resistance increases, the antibiotic becomes less used. Finally, as antibiotic use declines, natural selection diminishes and resistance decreases. Strikingly, the periodic frequency of antibiotics acting through the same mechanism is quite similar (i.e. penicillin and ampicillin). On the other hand, the periodic frequency of antibiotics acting through different mechanism is considerably different. The relative periodic frequency is correlated with spectrum width and frequency of usage, and widely used broad-spectrum antibiotics (i.e. cefacetrile, tetracycline and chloramphenicol) have higher frequencies than less-used narrow-spectrum antibiotics (i.e. neomycin, gentamicin and penicillin). Finally, antibiotic resistance is sometimes governed by more than one principal frequency (i.e. cefoperazone). As shown here, most antibiotic resistance is governed by a periodic function. This observation is clinically relevant and supports antibiotic cycling favouring antibiotic use during the rise phase of resistance, and disfavouring use once the resistance peak is reached. Finally, these data show that most antibiotics are sustainable in the long run.