title: Evaluation of antibiotic efficacy against infections caused by planktonic or biofilm cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae in Galleria mellonella.
abstract: The lack of novel antibiotics for more than a decade has placed increased pressure on existing therapies to combat the emergence of multidrug-resistant (MDR) bacterial pathogens. This study evaluated the Galleria mellonella insect model in determining the efficacy of available antibiotics against planktonic and biofilm infections of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae strains in comparison with in vitro minimum inhibitory concentration (MIC) determination. In general, in vitro analysis agreed with the G. mellonella studies, and susceptibility in Galleria identified different drug resistance mechanisms. However, the carbapenems tested appeared to perform better in vivo than in vitro, with meropenem and imipenem able to clear K. pneumoniae and P. aeruginosa infections with strains that had bla(NDM-1) and bla(VIM) carbapenemases. This study also established an implant model in G. mellonella to allow testing of antibiotic efficacy against biofilm-derived infections. A reduction in antibiotic efficacy of amikacin against K. pneumoniae and P. aeruginosa biofilms was observed compared with a planktonic infection. Ciprofloxacin was found to be less effective at clearing a P. aeruginosa biofilm infection compared with a planktonic infection, but no statistical difference was seen between K. pneumoniae biofilm and planktonic infections treated with this antibiotic (P>0.05). This study provides important information regarding the suitability of Galleria as a model for antibiotic efficacy testing both against planktonic and biofilm-derived MDR infections.
authors.affiliation: Public Health England, Microbiology Services Division, Porton Down, Salisbury, Wiltshire SP4 0JG, UK; College of Life and Environmental Sciences, University of Exeter, Exeter, Devon EX4 4QD, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Benthall
authors.affiliation: Public Health England, Microbiology Services Division, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Touzel
authors.affiliation: Public Health England, Microbiology Services Division, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Charlotte K
authors.initials: CK
authors.lastname: Hind
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Exeter, Devon EX4 4QD, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.affiliation: Public Health England, Microbiology Services Division, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Sutton
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Exeter, Devon EX4 4QD, UK.
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Thomas
authors.affiliation: Public Health England, Microbiology Services Division, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. Electronic address: matthew.wand@phe.gov.uk.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Wand
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018441:Biofilms / Q000254:growth & development; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000502:physiology; D007915:Lepidoptera / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents
keywords: Antibiotic resistance; Galleria mellonella; Klebsiella pneumoniae; Pseudomonas aeruginosa; Virulence