Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies versus Pseudomonas aeruginosa infection.

The aim of the study was to determine if 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 anti-pseudomonal antibiotics. Two strains of P. aeruginosa were employed, NCTC10662 (antibiotic susceptible) and NCTC13437 (multi-drug 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 infections in vivo and if 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. G. 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 versus 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 reduced burden of bacteria present in the haemolymph. There was clear correlation between the measured antibiotic pharmacokinetics and the therapeutic effect. This study strongly supports the future application of the G. mellonella infection model to initial studies of novel anti-pseudomonal treatments.