In vitro activity of gallium against meticillin-susceptible and meticillin-resistant Staphylococcus aureus and S. epidermidis
Abstract number: O99
Baldoni D., Steinhuber A., Zimmerli W., Trampuz A.
Objectives: Gallium (III) is a semi-metallic element physically similar to iron (III) and competes for iron-binding sites of transporters and enzymes. Since gallium (III) is not reducible like iron (III), it is unable to participate in biologically important redox reactions, which represents the presumed mode of antimicrobial action. We investigated the in vitro anti-staphylococcal activity of gallium maltolate (GaM), an oral formulation with good bioavailability and a favourable safety profile in clinical studies.
Methods: GaM in vitro susceptibility was performed in triplicate by a macrodilution assay with 105 CFU/mL in iron-limited RPMI 1640 for determination of MIC and logarithmic MBC (MBClog) or in PBS for determination of stationary MBC (MBCstat). The following standard strains were tested: S. aureus ATCC 29213 (MSSA), S. aureus ATCC 43300 (MRSA), S. epidermidis 1457 (MSSE) and S. epidermidis B3972 (MRSE). Time-kill studies were performed with GaM at 105 CFU/mL in RPMI 1640 over 24 h (for MSSA) or 48 h (for MSSE) and expressed as reduction of viable counts in log CFU/mL.
Results: GaM MIC/MBClog/MBCstat values were (in mg/mL): 1.5/>6/>6 (for MSSA) and 1.1/6/>6 (for MRSA), 0.10/1.5/4.5 (for MSSE) and 0.14/1.5/1.5 (for MRSE). The ratio MBCstat/MBClog was 3 (for MSSE) and 1 (for MRSE). Figure shows the time-kill curve of MSSE at GaM concentrations at 0.1×, 1×, 10× and 20× MIC. In time-kill studies, GaM at 0, 0.2, 2 and 6 mg/mL reduced after 24 h incubation MSSA bacterial load (in log CFU/mL) of -2.3, -1.5, 0.8 and 1.3, respectively (positive values denote net growth).
Conclusion: GaM inhibits growth of S. epidermidis at considerable lower concentrations than of S. aureus (0.1 vs. 1 mg/mL). Against S. aureus, GaM was only bacteriostatic at concentrations up to 6 mg/mL. In contrast, GaM kills S. epidermidis in both logarithmic and stationary growth phases exhibiting a 3-log CFU reduction at 2 mg/mL GaM in 24 h. GaM is a potential anti-staphylococcal drug and may be especially useful in combination with other antimicrobials to prevent development of resistance.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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