Current Status of Carbapenem Antibiotics

Mohammed      I. El-Gamal; Chang-Hyun      Oh

Abstract

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.

Keywords: Carbapenems, β-lactams, β-lactamases, carbapenemases, nosocomial infections, community-acquired infections, multidrug resistance, polymicrobial infections, Carbapenem, Lactam antibiotics, antibacterial agents, Gram-positive, Gram-negative bacteria, broad-spectrum, thienamycin, imipenem/cilastatin, panipenem/betamipron, biapenem, tebipenem, tebipenem pivoxil, meropenem, ertapenem, doripenem, lenapenem, tomopenem, lactams, lactamases, aerobic and anaerobic bacteria, ventilator-associated pneumonia, urinary tract infections, intra-abdominal infections, penicillins, cephalosporins, penicillin-binding proteins, metallo--lacta-mases, 1--methyl group, Trans-1-Hydroxyethyl Substituent, aspar-gine-132, hydrogen-bonding interaction, DHP-I spe-cific inhibitor, amine or amidine moieties, Carbapenems lacking 1-methyl group, 1--Methylcarbapenems lacking pyrrolidin-3-ylthio moiety, 1--Methylcarbapenems containing pyrrolidin-3-ylthio moiety, olivanic acids, carpetimycins, asparenomycins, pluracidomycins, N-acetyl derivative, N-formimidoyl derivative, plasmid-mediated IMP-type carbapenemases, OprD porins, febrile neutropenia, hepatic transaminases, aspartate transa-minase, alanine transaminase, faropenem, human renal DHP-I, MK-0826, AmpC -lactamase resistance mechanisms, meta-substituted benzoic acid substituent, carboxylic acid moiety, complicated intra-abdominal infections, complicated skin and skin-structure infections, cystic fibrosis, ami-kacin, levofloxacin, daptomycin, line-zolid, Alkaline phosphatase, Aspartate transaminase, Dehydropeptidase-I