title: In vitro and in vivo evaluations of the activities of lauric acid monoester formulations against Staphylococcus aureus.
abstract: Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are needed. Lauric acid monoesters combined with lactic, mandelic, malic, or benzoic acid are being evaluated as possible alternatives. We determined the in vitro activity of 13 lauric acid monoester (LAM) formulations and mupirocin against 30 methicillin-susceptible S. aureus (MSSA) isolates and 30 methicillin-resistant S. aureus (MRSA) isolates. We then used a murine model of MRSA nasopharyngeal colonization to compare the in vivo activity of mupirocin with three LAM formulations. MSSA and MRSA MIC(90) values were 0.25 microg/ml for mupirocin and </=4 microl/ml for all LAM formulations tested. Hsd:ICR mice were challenged with 10(8) CFU/naris MRSA. Five days later, S. aureus colonization was documented by culture. Treatment with bland, mupirocin, or one of three LAM ointments was then administered unblinded thrice daily for 2 days. Three days after treatment, both anterior nares were cultured for S. aureus. Administration of 128774-49E or 128774-53A was associated with greater eradication of MRSA carriage (24/34 [71%] or 33/40 [83%]) of animals, respectively) than bland ointment (12/38 [32%]) (P < 0.005). 128774-53A administration resulted in greater MRSA carriage eradication than mupirocin (19/38 [50%]) (P < 0.005) in this model. LAM formulations warrant evaluation for S. aureus nasal decolonization in humans.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Rouse
authors.forename: Margalida
authors.initials: M
authors.lastname: Rotger
authors.forename: Kerryl E
authors.initials: KE
authors.lastname: Piper
authors.forename: James M
authors.initials: JM
authors.lastname: Steckelberg
authors.forename: Matthew
authors.initials: M
authors.lastname: Scholz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Andrews
authors.forename: Robin
authors.initials: R
authors.lastname: Patel
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002353:Carrier State / Q000382:microbiology; D004195:Disease Models, Animal; D004952:Esters / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007850:Lauric Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests / Q000592:standards; D016712:Mupirocin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D009305:Nasopharynx / Q000382:microbiology; D009824:Ointments; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004952:Esters; D007850:Lauric Acids; D009824:Ointments; C030358:lauric acid; D016712:Mupirocin; D008712:Methicillin