Issues beyond resistance: inadequate antibiotic therapy and bacterial hypervirulence

ABSTRACT The administration of antibiotics while critical for treatment, can be accompanied by potentially severe complications. These include toxicities associated with the drugs themselves, the selection of resistant organisms and depletion of endogenous host microbiota. In addition, antibiotics may be associated with less well-recognized complications arising through changes in the pathogens themselves. Growing evidence suggests that organisms exposed to antibiotics can respond by altering the expression of toxins, invasins and adhesins, as well as biofilm, resistance and persistence factors. The clinical significance of these changes continues to be explored; however, it is possible that treatment with antibiotics may inadvertently precipitate a worsening of the clinical course of disease. Efforts are needed to adjust or augment antibiotic therapy to prevent the transition of pathogens to hypervirulent states. Better understanding the role of antibiotic-microbe interactions and how these can influence disease course is critical given the implications on prescription guidelines and antimicrobial stewardship policies. While antibiotic resistance remains a major clinical problem, there are several other issues associated with inadequate antibiotic therapy including the promotion of undesirable qualities leading to hypervirulent organisms.