title: Will new antimicrobials overcome resistance among Gram-negatives?
abstract: The spread of resistance among Gram-positive and Gram-negative bacteria represents a growing challenge for the development of new antimicrobials. The pace of antibiotic drug development has slowed during the last decade and, especially for Gram-negatives, clinicians are facing a dramatic shortage in the availability of therapeutic options to face the emergency of the resistance problem throughout the world. In this alarming scenario, although there is a shortage of compounds reaching the market in the near future, antibiotic discovery remains one of the keys to successfully stem and maybe overcome the tide of resistance. Analogs of already known compounds and new agents belonging to completely new classes of antimicrobials are in early stages of development. Novel and promising anti-Gram-negative antimicrobials belong both to old (cephalosporins, carbapenems, β-lactamase inhibitors, monobactams, aminoglycosides, polymyxin analogues and tetracycline) and completely new antibacterial classes (boron-containing antibacterial protein synthesis inhibitors, bis-indoles, outer membrane synthesis inhibitors, antibiotics targeting novel sites of the 50S ribosomal subunit and antimicrobial peptides). However, all of these compounds are still far from being introduced into clinical practice. Therefore, infection control policies and optimization in the use of already existing molecules are still the most effective approaches to reduce the spread of resistance and preserve the activity of antimicrobials.
authors.affiliation: Division of Infectious Diseases, Santa Maria della Misericordia University Hospital, Udine, Italy. mattba@tin.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Bassetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Ginocchio
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Mikulska
authors.forename: Lucia
authors.initials: L
authors.lastname: Taramasso
authors.forename: Daniele Roberto
authors.initials: DR
authors.lastname: Giacobbe
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000627:therapeutic use; D015780:Carbapenems / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D017053:Infection Control / Q000458:organization & administration; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000008:administration & dosage / Q000627:therapeutic use; D011113:Polymyxins / Q000008:administration & dosage / Q000627:therapeutic use; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D001618:beta-Lactamases / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D015780:Carbapenems; D007211:Indoles; D008997:Monobactams; D011113:Polymyxins; D011500:Protein Synthesis Inhibitors; D001618:beta-Lactamases