title: In vitro activity of gallium maltolate against Staphylococci in logarithmic, stationary, and biofilm growth phases: comparison of conventional and calorimetric susceptibility testing methods.
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 microg/ml) than S. epidermidis (94 to 200 microg/ml). Minimal biofilm inhibitory concentrations were 3,000 to >or=6,000 microg/ml (S. aureus) and 94 to 3,000 microg/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 3x MIC and 2.9 log(10) CFU/ml (MSSE) and 4.0 log(10) CFU/ml (MRSE) against S. epidermidis at 10x 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 microg/ml (MSSA), 94 to 1,500 microg/ml (MRSA), and 94 to 375 microg/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.
authors.affiliation: Infectious Diseases, Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Baldoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Steinhuber
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.forename: Andrej
authors.initials: A
authors.lastname: Trampuz
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002151:Calorimetry; D003470:Culture Media; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D007501:Iron / Q000378:metabolism; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D013210:Staphylococcus / Q000187:drug effects* / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development; D013530:Surgical Wound Infection / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D004269:DNA, Bacterial; D009942:Organometallic Compounds; D011753:Pyrones; C512662:gallium maltolate; D007501:Iron