New antibiotic development: barriers and opportunities

Abstract

Antibiotic resistance represents a serious threat to public health worldwide, leading to increased healthcare costs, prolonged hospital stays, treatment failures and deaths. To address the emergency of multidrug-resistance, the major international societies of infectious diseases and public health have developed strategies and guidelines to reduce unnecessary antimicrobial use as well as to incite the development of new antibiotics targeting multidrug-resistant pathogens. Even though pharmaceutical companies have been developing new antibiotics since 2010, the global situation is still worrisome. Indeed, the currently available data regarding new antibiotics are limited to microbiological activity and pharmacokinetic profile and their use for the treatment of life-threatening infections (i.e., sepsis) is often off-label. The aim of this article is to present the antibiotic molecules recently commercialized and with which clinicians will deal quite often in next years. We describe ceftolozane/tazobactam, ceftazidime/avibactam, eravacycline, plazomicin, dalbavancin, oritavancin and tedizolid in terms of mechanism of action, antimicrobial spectrum, trials behind the approval and possible indications for the future. In last few years, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved many new antibiotic molecules but, unfortunately, they lack in biological innovation and in wide clinical indications. These agents show appealing properties for off-label use, as we propose in the article, but caution is still needed considering that high-quality clinical data are limited.

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“…Thus, it is necessary to produce scaffolds to develop new leads for further therapeutic purposes. In fact, the new drug development approach has been carried out with various procedures, such as combining existing drugs [4], use of natural ingredients [5], synthesis of new compounds [6,7], and the development of environmentally friendly synthesis (green chemistry) [8]. The multicomponent reaction (MCR) is an approach to achieve the efficient synthesis.…”