Introduction and geographic availability of new antibiotics approved between 1999 and 2014

Abstract

BackgroundDespite the urgent need for new, effective antibiotics, few antibiotics of value have entered the market during the past decades. Therefore, incentives have been developed to stimulate antibiotic R&D. For these incentives to be effective, geographic availability for recently approved antibiotics needs to be better understood. In this study, we analyze geographic availability and market introduction of antibiotics approved between 1999 and 2014.Material and methodWe identified antibiotics, considered new chemical entities (NCEs) for systemic use approved globally between 1999 and 2014, from national medicine agencies’ lists of approved drugs, and data from the WHO Collaborating Center for Drug Statistics. Geographic availability was mapped using sales data from IQVIA, and analyzed with regards to class, indication, safety, and origin.ResultsOf the 25 identified NCEs, only 12 had registered sales in more than 10 countries. NCEs with the widest geographic availability had registered sales in more than 70 countries within a ten-year timeframe and 30 countries within a three-year timeframe, spreading across five different geographic regions and three country income classes. Half (52%) of the NCEs had an indication for infections caused by antibiotic- resistant bacteria, little diversity was seen regarding target pathogen and indication. Antibiotics originated from and/or marketed by companies from the US or Europe had greater geographic availability compared to Japanese antibiotics, which seldom reached outside of Asia. For 20 NCEs developers chose to fully or partially sublicense marketing rights to a number of companies of different sizes.ConclusionOur findings show great variation in geographic availability of antibiotics, indicating that availability in multiple regions and country income classes is possible, but rarely seen within a few years of market authorization. Sublicensing agreements between multiple companies was common practice. Moreover, differences were seen between countries regarding benefit/risk evaluations and company behavior. These findings could be a potential source of uncertainties, and create barriers to assure that working antibiotics are developed and made available according to public health needs.

Design and Preclinical Development of a Phage Product for the Treatment of Antibiotic-Resistant Staphylococcus aureus Infections

“…It is a significant problem in many clinical settings and the antibiotic-resistant forms are classified as a “High Priority” pathogen by the World Health Organization (WHO) [6] and a “Serious Threat” by the U.S. Centers for Disease Control and Prevention (CDC) [7]. Since 1999, nine antibiotics targeting methicillin-resistant S. aureus (MRSA) have been approved (linezolid, daptomycin, tigecycline, ceftobiprole, telavancin, ceftaroline, dalbavancin, oritavancin, tedizolid) [8]. Of these, only the oxazolidinones, now nearly 20 years old, were a completely new class [9].…”

“…Side effects such as renal toxicity and cross-resistance (e.g. among glyo- and lipoglycopeptides) can limit clinical use [8]. Moreover, many antibiotics have reduced efficacy against Staphylococcus spp.…”

Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)

“…Researchers and clinicians are faced with the urgent need to develop novel scaffolds and effective antibacterial drugs to overcome AMR emergence and spreading of MDR strains [5,6]. The opportunistic human pathogens that exhibit multidrug resistance, like Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., known as ESKAPE pathogens, are considered as a serious global health issue [7,8]. Among them, methicillin-resistant Staphylococcus aureus (MRSA) represents the leading cause of nosocomial and community-acquired infections, being recognized by the World Health Organisation (WHO) as the antibiotic-resistant pathogen of high priority.…”

Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins

“…), are frequently isolated in hospital environments, where they are responsible for the majority of nosocomial infections [5]. In particular, Gram-positive bacteria have predominantly developed resistance to all the available antibiotics and pose a serious problem not only in hospitals but also for the general population [6,7]. Infections of methicillin-resistant Staphylococcus aureus (MRSA) are of particular concern [8].…”