title: Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection.
abstract: The aim of this study was to determine whether Galleria mellonella larvae can be used (i) as an in vivo infection model for Pseudomonas aeruginosa and (ii) for evaluating the pharmacokinetics and efficacy of antipseudomonal antibiotics. Two strains of P. aeruginosa were employed, NCTC 10662 (antibiotic-susceptible) and NCTC 13437 (multidrug-resistant). Larvae were infected with increasing doses of either P. aeruginosa strain to investigate the effect of inoculum size on survival. Subsequently, infected larvae were treated with a range of antibiotics to examine whether these agents were effective against P. aeruginosa infection in vivo and whether the efficacy of these drugs matched the known susceptibilities of each bacterial strain. Larval burden of P. aeruginosa was also determined after infection and treatment with cefotaxime. Pharmacokinetic properties of the antibiotics tested were measured using a well diffusion assay to determine the concentration of antibiotics in larval haemolymph over time. Galleria mellonella larvae were sensitive to P. aeruginosa infection, and increasing inoculum doses of live cells resulted in greater larval mortality. Heat-killed bacteria had no detrimental effect on survival. Antibiotic efficacy against P. aeruginosa-infected G. mellonella correlated with the measured in vitro sensitivities of the two strains tested. The therapeutic benefit arising from administration of cefotaxime correlated with a reduced burden of bacteria present in the haemolymph. There was a clear correlation between measured antibiotic pharmacokinetics and the therapeutic effect. This study strongly supports future application of the G. mellonella infection model to initial studies of novel antipseudomonal treatments.
authors.affiliation: Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews, Fife KY16 9ST, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Hill
authors.affiliation: Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews, Fife KY16 9ST, UK.
authors.forename: Neyme
authors.initials: N
authors.lastname: Veli
authors.affiliation: Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews, Fife KY16 9ST, UK. Electronic address: pjc5@st-andrews.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Coote
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006458:Hemolymph / Q000737:chemistry; D006801:Humans; D007814:Larva / Q000382:microbiology; D007915:Lepidoptera / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents
keywords: Cystic fibrosis; Gram-negative infection; Hospital-acquired infection; Insect infection model; Resistance