antibiotics discovery

Topics: Antibiotic resistance, Bacteria, Microbiology Pages: 56 (8806 words) Published: November 4, 2013
Cent. Eur. J. Biol. • 8(10) • 2013 • 943-957
DOI: 10.2478/s11535-013-0209-6

Central European Journal of Biology

New perspectives on antibacterial drug research
Review Article

Joanna Ziemska, Aleksandra Rajnisz, Jolanta Solecka*
Laboratory of Biologically Active Compounds,
National Institute of Public Health - National Institute of Hygiene, 00-791 Warsaw, Poland
Received 14 March 2013; Accepted 10 May 2013

Abstract: Bacterial resistance to commonly used antibiotics is constantly increasing. Bacteria particularly dangerous for human life are methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and fluoroquinolone-resistant Pseudomonas aeruginosa. Hence, there is an incessant need for developing compounds with new modes of action and seeking alternate drug targets. In this review, the authors discuss the current situation of antibacterial medicines and present data on new antibiotic targets. Moreover, alternatives to antibiotics, such as bacteriophages, antimicrobial peptides and monoclonal antibodies, are presented. The authors also draw attention to the valuable features of natural sources in developing antibacterial compounds. The need to prevent and control infections as well as the reasonable use of currently available antibiotics is also emphasized. Keywords: Bacterial resistance • Antibacterial compound • Drug discovery • Target • Antimicrobial peptides © Versita Sp. z o.o.

1. Introduction
The use of antibiotics, especially the excessive and
indiscriminative use, both in medicine and veterinary
science has contributed to the emergence of drug
resistant organisms. Antimicrobial drug resistance
constitutes a growing problem worldwide [1]. Infections
caused by resistant pathogens result in increased
mortality and morbidity among human and animal
populations. In addition, pathogenic microorganisms,
including Staphylococcus aureus, Streptococcus
pneumoniae and Clostridium difficile, contribute to
many hospital-acquired infections. Gram-negative
bacteria are traditionally more difficult to destroy
than Gram-positive bacteria as they contain an
outer membrane that constitutes an extra barrier for
antibacterial compounds. The latest reports from the
American and European disease associations claim
that there are only a few antibiotics in the clinical
pipeline that are more effective in targeting Gramnegative bacteria than existing pharmaceuticals on the market [1]. In the surveillance report titled
“Antimicrobial resistance surveillance in Europe” made
by the European Centre for Disease Prevention and
Control, the authors show a general, Europe-wide
increase in antimicrobial resistance in Gram-negative
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pathogens (Escherichia coli, Klebsiella pneumoniae,
Pseudomonas aeruginosa) [2].
In this review, the authors will discuss the present
status of bacterial resistance to antibiotics, especially
of bacterial species that cause serious hospital and
community-acquired infections. Furthermore, the
review presents antibiotics that are currently on the
market and summarizes novel promising discoveries in
drug development. The authors will also refer to new
antibacterial targets and other alternatives to antibiotics.

2. How antibiotics became outdated?
The lack of new and effective antibacterial compounds
is due to several factors. First of all, it is difficult to find new antibacterial compounds with good pharmacological
profiles and low toxicity for the host. Furthermore, from
an economic point of view, pharmaceutical companies
are more interested in developing drugs for chronic
conditions than for short-term treatments. Moreover, it
is preferable when antibiotics target multiple species.
In addition, bacteria tend to develop resistance to
antimicrobials which restricts their use and consequently
causes drug sales decline [3]. Finally, the chemical
structures of antibiotics, especially those derived from...

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