8/31/2023 0 Comments Gram negative bacteria antibiotics![]() However, a variety of β-lactamases that are capable of hydrolyzing these antibiotics, including imipenemase (IMP), Verona integron-encoded MBL (VIM), K. In the 1990 s, the pharmaceutical industry introduced carbapenems, which are extremely stable to degradation by β-lactamases. The further selection of resistant mutants led to the appearance of extended-spectrum β-lactamases (ESBLs) that now compromise the use of even third-generation cephalosporins. For example, the rapid increase in resistance to the widely-used ampicillin in the early 1960 s turned out to be due to a plasmid-mediated β-lactamase, one of the first described in Gram-negative bacteria, known as TEM (the TEM 1 enzyme was originally found in Eschericihia coli isolated from a patient named Temoniera, hence named TEM). However, resistance has been heavily influenced over the years by the widespread administration of these antibiotics in clinical practice. ![]() The origin of β-lactamases is presumably ancient and their development evolved to combat natural β-lactams. Β-lactamase-mediated resistance is the most important and efficient method of β-lactam resistance for Gram-negative bacteria. The profile of resistance to currently used antimicrobial agents and the development of new anti-Gram-negative agents, with a particular attention to cephalosporins, β-lactamase inhibitors and carbapenems will be discussed. Recently, the IDSA supported an initiative of developing 10 new systemic antibacterial drugs through the discovery of new drug classes, as well as exploring possible new molecules from existing classes of antibiotics (the "10 × '20" initiative, endorsed by the American Academy of Pediatrics, American Gastro-enterological Association, Trust for America's Health, Society for Healthcare Epidemiology of America, Pediatric Infectious Disease Society, Michigan Antibiotic Resistance Reduction Coalition, National Foundation for Infectious Diseases, and European Society of Clinical Microbiology and Infectious Diseases). In 2007, the IDSA and the FDA repeated their call for an increase in new antibacterial research to develop next-generation drugs. In fact, in 2004 the Infectious Diseases Society of America (IDSA) issued their report, "Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates, A Public Health Crisis Brews," which proposed incentives to reinvigorate pharmaceutical investment in antibiotic research and development. Since 2001, different agencies and societies have tried to draw attention to the significant lack of new antibiotics for Gram-negative pathogens. Among new antibacterials active against Gram-negative microorganisms that are already on the market, tigecycline, the first Food and Drug Administration (FDA)-approved representative of the glycylcyclines, and doripenem, a new carbapenem, seem the most promising. New antibiotics that have been discovered and introduced into clinical practice in the last few years are active mostly against Gram-positive organisms, whereas when targeting resistant Gram-negative bacteria, clinicians are forced to rediscover old drugs, such as polymixins and fosfomycin. ![]() In particular, the pharmaceutical pipeline of antibiotics active against MDR Gram-negative bacteria is very limited. ![]() Numerous classes of antimicrobials are currently available for physicians to use in the treatment of patient with infections however, the pace of antibiotic drug development has slowed during the last decade (Figure 1). Resistance to the current library of antibacterial drugs is a serious problem in all parts of the world including the Asia-Pacific region, Latin America, Europe, and North America. Some authors have summarized this phenomenon with the word 'ESKAPE', to include the most frequent MDR microorganisms: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. The World Health Organization (WHO) has identified antimicrobial resistance as one of the three most important problems for human health. In recent years, infections caused by multi-drug resistant (MDR) pathogens have become a serious problem, especially in the nosocomial setting. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |