Abstract
Since the 1940s β-lactam antibiotics have been used to treat bacterial infections. However, emergence and dissemination of β-lactam resistance has reached the point where many marketed β-lactams no longer are clinically effective. The increasing prevalence of multidrug-resistant bacteria and the progressive withdrawal of pharmaceutical companies from antibiotic research have evoked a strong reaction from health authorities, who have implemented initiatives to encourage the discovery of new antibacterials. Despite this gloomy scenario, several novel β-lactam antibiotics and β-lactamase inhibitors have recently progressed into clinical trials, and many more such compounds are being investigated. Here we seek to provide highlights of recent developments relating to the discovery of novel β-lactam antibiotics and β-lactamase inhibitors.
Highlights
The emergence and spread of resistance to antibiotics always has accompanied their clinical use.During the past 20 years, physicians have experienced a worrisome situation, described by Shlaes [1] and by Pendleton [2], involving a significant increase in morbidity and mortality due to bacterial infections in both community and hospital settings
In this review we report recent progress in the discovery and development of novel β-lactam antibiotics [5,6] and β-lactamase inhibitors, including β-lactamase inhibitors lacking a β-lactam ring [7,8]
Widespread use of β-lactam antibiotics derives from their efficacy and safety profile, but emergence of new, more aggressive β-lactamases is obliging clinicians to resort to drugs with lower therapeutic windows, such as polymyxins and tigecycline
Summary
The emergence and spread of resistance to antibiotics always has accompanied their clinical use. Two types of strains have compromised the clinical utility of currently available antibiotics and underscored the need for new compounds: Antibiotics 2014, 3. The bacteria that constitute the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter spp.) are responsible for about 30%–35% of nosocomial infections, including the vast majority of MDR and XDR strains, leaving physicians with limited therapeutic options [3,4]. In this review we report recent progress in the discovery and development of novel β-lactam antibiotics [5,6] and β-lactamase inhibitors, including β-lactamase inhibitors lacking a β-lactam ring [7,8]
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