title: Prospects for the next anti-Pseudomonas drug.
abstract: Pseudomonas aeruginosa is one of the most dreaded Gram-negative bacterial pathogens in hospitals. Not only it is among the most frequently isolated Gram-negative organisms in bloodstream and wound infections, pneumonia, intra-abdominal-sepsis and urogenital-sepsis, but also it is frequently found in patients with comorbid illnesses and compromised by in-dwelling catheters, tubes and surgery where mortality rates of more than 60% have been reported. Besides its intrinsic resistance to a number of widely used antibiotics, Pseudomonas also managed to acquire resistance via additional mechanisms, including target mutations, increased expression of efflux pumps and of antibiotic-degrading enzymes. Taken together, the increased incidence in certain types of infections, the increased use of invasive devices in the hospital as well as the increased frequency of multi-resistant Pseudomonas strains, have clearly led to a shortage of treatment options for nosocomial Pseudomonas infections. Even the recommended combination therapy of an antibiotic of the beta-lactam class together with an aminoglycoside or a fluoroquinolone, is no longer always successful and sometimes a polymyxin has to be given as last resort. Despite growing concerns of clinicians and medical societies about the very limited number of novel drugs in the pipeline to fight multi-resistant Pseudomonas strains, only a very small number of novel anti-Pseudomonas drugs are currently in late stage of pre-clinical or clinical development. However, and possibly as a reflection of the magnitude of the problem, quite a variety of approaches are being pursued. Among these are next-generation analogues of successful antibiotic classes (e.g. novel beta-lactams and combinations of novel beta-lactamase inhibitors with known penicillins or cephalosporins), antibodies, phages and selective peptides. It is to be hoped that a number of these novel drugs will show clinical utility and reach the market over the next 6-10 years.
authors.affiliation: Basilea Pharmaceutica International AG, Grenzacherstrasse 487, CH-4005 Basel, Switzerland. malcolm.page@basilea.com
authors.forename: Malcolm G P
authors.initials: MG
authors.lastname: Page
authors.forename: Jutta
authors.initials: J
authors.lastname: Heim
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D015507:Drugs, Investigational / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015507:Drugs, Investigational