Tozzi A. 2017. Bacteria may produce resistance to antibiotics... although never exposed to them. BMJ, https://www.bmj.com/content/358/bmj.j3418/rr-9. Response to: Llewelyn MJ, Fitzpatrick JM, Darwin E, Tonkin-Crine S, Gorton C, et al. 2017. The antibiotic course has had its day. BMJ, 358:j3418.
Llewelyn et al. are concerned about antibiotic resistance caused by drug misuse. However, studies suggest that bacteria do not need exposure to antibiotics to gain resistance. Indeed, Bhullar et al. (2012) discovered bacteria at the bottom of a 1,000 feet deep cave (Lechuguilla Cave, New Mexico) that, although isolated from humans and antibiotic drugs for four million years, are resistant to 14 different commercially available antibiotics. This finding negates the theory that bacteria only develop resistance to antibiotics when directly exposed to them. Therefore, antibiotic resistance did not evolve in the clinic just through our use, rather is natural, ancient and hard wired in the microbial pangenome. Environmental organisms as reservoirs of resistance genes that can be vehicled to other bacteria through simple horizontal transmission.
Bhullar K, Waglechner N, Pawlowski A, Koteva K, Banks ED, et al. Antibiotic Resistance Is Prevalent in an Isolated Cave Microbiome. PLoS One. 2012; 7(4): e34953. doi: 10.1371/journal.pone.0034953.