2010-01-01·Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates)4区 · 医学
Current status of carbapenem antibiotics
4区 · 医学
作者: El-Gamal, Mohammed I. ; Oh, Chang-Hyun
β-Lactam antibiotics are the most prescribed antibacterial agents. They comprise more than half of all antibiotics. They are considered as the cornerstone of the antibiotic armamentarium. By inhibiting bacterial cell wall biosynthesis, they are highly effective against Gram-positive and Gram-negative bacteria. Antibiotic resistance among Gram-negative pathogens in hospitals represents a dangerous threat to public health. Since many bacteria have developed resistance to older agents, new β-lactam antibiotics have been continuously developed. In the late 1970s, a new class of exceptionally broad-spectrum non-traditional β-lactams, carbapenems, was developed. This review article focuses on the new developments related to the field of carbapenems for treatment of bacterial infections, especially those caused by Gram-negative bacteria. The structural features, principal characteristics, and clinical implications of carbapenems including thienamycin, imipenem/cilastatin, panipenem/betamipron, biapenem, tebipenem, tebipenem pivoxil, meropenem, ertapenem, doripenem, lenapenem, and tomopenem are discussed herein.
2002-12-01·Journal of Infection and Chemotherapy4区 · 医学
Alterations of susceptibility of Pseudomonas aeruginosa by overproduction of multidrug efflux systems, MexAB-OprM, MexCD-OprJ, and MexXY/OprM to carbapenems: Substrate specificities of the efflux systems
Overproduction of multidrug efflux systems MexAB-OprM, MexCD-OprJ, and MexXY/OprM of Pseudomonas aeruginosa caused reduction of susceptibility of the mutant, which lacked AmpC and all three systems to panipenem, meropenem, S4661 and DU6681a; meropenem, S4661 and DU6681a; and BO2727, panipenem, meropenem, S4661 and DU6681a, respectively, but not reduction of the susceptibility to imipenem and biapenem. Thus, we determined substrate specificities of these efflux systems to carbapenems.
2002-04-01·Expert Opinion on Investigational Drugs2区 · 医学
Recent developments in carbapenems
2区 · 医学
作者: Bonfiglio, Giovanni ; Russo, Giovanni ; Nicoletti, Giuseppe
Carbapenems are beta-lactam antibiotics characterised by the presence of a beta-lactam ring with a carbon instead of sulfone in the 4-position of the thyazolidinic moiety. The first carbapenem to be utilised in therapy was imipenem, the N-formimidoyl derivative of thienamycin. Imipenem is coadministered with cilastatin, an inhibitor of human renal dehydropeptidase I, as imipenem is hydrolysed by this enzyme. Meropenem was the first carbapenem with a 1-beta-methyl group and 2-thio pyrrolidinyl moiety, which renders this antibiotic stable to renal dehydropeptidase I. Other carbapenems for parenteral administration later discovered include biapenem, panipenem, ertapenem, lenapenem, E-1010, S-4661 and BMS-181139. Carbapenems which are orally administered include sanfetrinem, DZ-2640, CS-834 and GV-129606. Carbapenems have an ultra-broad spectrum of antibacterial activity and stability to almost all clinically relevant beta-lactamases. This differentiates them from all other currently available classes of beta-lactam antibiotics. However, Class B beta-lactamases, along with some rare Class A and D enzymes, are able to hydrolyse these antibiotics. Although Class B enzymes are generally chromosomally-encoded (isolated from Stenotrophomonas maltophilia, Aeromonas spp., Bacillus cereus, Bacteroides fragilis, Flavobacterium spp. and Legionella gormanii), plasmid-metallo-beta-lactamases now are appearing in B. fragilis, Pseudomonas aeruginosa, Acinetobacter baumannii and members of Enterobacteriaceae such as Serratia marcescens and Klebsiella pneumoniae. The number of these enzymes compared to the number of other beta-lactamase types is still low, however, it is likely that they will spread due to the increased selective pressure of carbapenem use. The very broad spectrum of antimicrobial activity associated with a good clinical efficacy and a favourable safety profile makes the carbapenems valuable as 'first-line' antibiotics in initial empirical therapy for the treatment of severe infections.