In Vitro Activity of Gallium Maltolate against Staphylococci in Logarithmic, Stationary, and Biofilm Growth Phases: Comparison of Conventional and Calorimetric Susceptibility Testing Methods

Abstract

ABSTRACT Ga 3+ is a semimetal element that competes for the iron-binding sites of transporters and enzymes. We investigated the activity of gallium maltolate (GaM), an organic gallium salt with high solubility, against laboratory and clinical strains of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and methicillin-resistant S. epidermidis (MRSE) in logarithmic or stationary phase and in biofilms. The MICs of GaM were higher for S. aureus (375 to 2000 μg/ml) than S. epidermidis (94 to 200 μg/ml). Minimal biofilm inhibitory concentrations were 3,000 to ≥6,000 μg/ml ( S. aureus ) and 94 to 3,000 μg/ml ( S. epidermidis ). In time-kill studies, GaM exhibited a slow and dose-dependent killing, with maximal action at 24 h against S. aureus of 1.9 log 10 CFU/ml (MSSA) and 3.3 log 10 CFU/ml (MRSA) at 3× MIC and 2.9 log 10 CFU/ml (MSSE) and 4.0 log 10 CFU/ml (MRSE) against S. epidermidis at 10× MIC. In calorimetric studies, growth-related heat production was inhibited by GaM at subinhibitory concentrations; and the minimal heat inhibition concentrations were 188 to 4,500 μg/ml (MSSA), 94 to 1,500 μg/ml (MRSA), and 94 to 375 μg/ml (MSSE and MRSE), which correlated well with the MICs. Thus, calorimetry was a fast, accurate, and simple method useful for investigation of antimicrobial activity at subinhibitory concentrations. In conclusion, GaM exhibited activity against staphylococci in different growth phases, including in stationary phase and biofilms, but high concentrations were required. These data support the potential topical use of GaM, including its use for the treatment of wound infections, MRSA decolonization, and coating of implants.