Carbapenem-hydrolyzing gram-negative bacteria: current options for treatment and review of drugs in development.
Multidrug resistant gram-negative bacteria are an increasing therapeutic challenge. The beta-lactamases are a group of enzymes that confer resistance to the beta-lactam antibiotics. The carbapenems have been in wide use to treat beta-lactamase producing, multidrug resistant gram-negative bacterial infections. However, the emergence of carbapenemases, enzymes capable of hydrolyzing the carbapenems, has limited our therapeutic options. In the recent years, there has been some development in the discovery of new agents such as boronic acid derivatives, ME1071 and Ca-EDTA that may enhance the activity of existing antibiotics, CTC-96 which reverses antibiotic resistance and polymyxin derivatives with decreased renal toxicity. While global efforts towards new drug development should continue, appropriate use of currently available antibiotics is equally important. In this review, we will discuss the general characteristics of carbapenemases, recent patents with drugs under development and current treatment options.
Division of Infectious Diseases, Department of Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA.
Foad I
FI
Abandeh
Mark E
ME
Drew
Madhuri M
MM
Sopirala
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D015780:Carbapenems / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D006868:Hydrolysis; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D001618:beta-Lactamases