Gaps in antibiotic development: the postmarketing task

Abstract

Antibiotic development is mainly focused on demonstrating clinical efficacy and setting susceptibility breakpoints. However, several issues cannot be addressed at the premarketing stage. Any ecological effects on human microbiota, as well as effects on mixed inocula selecting bacterial populations in species, strains within species, or subpopulations within strains, need to be addressed and can be explored in the laboratory using pharmacodynamic simulator devices as predictors of resistance selection. From the social perspective, relationships between the consumption of a compound and resistance can only be performed postmarketing. Specific resistance phenotypes/genotypes that could not be isolated in enough numbers in clinical trials can be examined in pharmacodynamic devices in the laboratory for comparison with other antibiotics and thereby for determination of the compound that best fits the need to counter the development/emergence and further spread of resistance.

Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults

“…Due to this, H. influenzae has acquired more relevance, and the good activity of cefditoren against this species and its ability to counter diffusion of the fts I gene and the indirect pathogenicity by β-lactamase producing strains, strengths its value within the antibiotic armamentarium. Despite there is a lack of CLSI/EUCAST susceptibility breakpoints, the first decade of the present century has provided a plethora of pharmacodynamic studies with cefditoren, focused not only on activity/efficacy prediction but also on countering selection and diffusion of resistance, which support its role in the treatment of infections caused by respiratory human-adapted pathogens, thus filling the traditional gap remaining in antibiotic development [ 146 ] by an active post-marketing investigational task [ 147 , 148 ].…”

Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults

“…Due to this, H. influenzae has acquired more relevance, and the good activity of cefditoren against this species and its ability to counter diffusion of the ftsI gene and the indirect pathogenicity by β-lactamase producing strains, strengths its value within the antibiotic armamentarium. Despite there is a lack of CLSI/EUCAST susceptibility breakpoints, the first decade of the present century has provided a plethora of pharmacodynamic studies with cefditoren, focused not only on activity/efficacy prediction but also on countering selection and diffusion of resistance, which support its role in the treatment of infections caused by respiratory human-adapted pathogens, thus filling the traditional gap remaining in antibiotic development [146] by an active post-marketing investigational task [147,148].…”

Drug resistance in community-acquired respiratory tract infections: role for an emerging antibacterial

“…These issues will establish differences between the new compound and older antibiotics, and are mainly focused on the pharmacodynamic data needed to predict selection of resistance and of resistant subpopulations in multibacterial niches (simulating the nasopharynx as the specific site for emergence of resistance in respiratory tract isolates), followed in the postmarketing phase by specific surveillance on resistance to core antibiotics to detect emerging resistances and any link with antibiotic consumption in the community. 88 This will define the role of the new antibiotic, not only from the perspective of its therapeutic potential, but also from the ecologic perspective, ie, countering resistances to core antibiotics in the community. The introduction of new antibiotics with documented adequate PK/PD and ecologic potentials might impact antibiotic policies, ie, decreased use of antibiotics with high resistance selection potential.…”