Pathogen virulence does not alter antibiotic efficacy under growth-matched in vivo conditions

Abstract

Whether pathogen virulence influences antibiotic efficacy independently of bacterial growth dynamics has not been directly tested under controlled in vivo conditions. Here, we used the Galleria mellonella larval infection model to address this question. We first compared Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus across a wide range of inoculum sizes, revealing pronounced pathogen-specific differences in virulence. Despite these differences, all pathogens followed a similar infection trajectory characterised by an initial reduction in bacterial burden followed by successful proliferation within the host. Focusing on P. aeruginosa and E. coli, which differ markedly in virulence but display comparable in vivo growth rates (doubling times of approximately 30 minutes), we assessed antibiotic efficacy under experimentally controlled, growth-matched conditions. Treatment with ciprofloxacin or gentamicin at defined multiples of the MIC reduced bacterial loads, prevented host death, and cleared infections to an indistinguishable extent for both pathogens. These findings demonstrate that pathogen virulence does not determine antibiotic efficacy when bacterial growth is comparable in vivo, and support the predictive value of MIC-based susceptibility testing during active infection.