RESUMO
In vitro studies demonstrate that oxacillin minimal inhibitory concentrations (MICs) of methicillin-resistant S. aureus (MRSA) strains USA300 and 400 decrease in the presence of cefoxitin. The aim of this study was to characterize the activity of cefoxitin plus ß-lactams against a collection of MRSA isolates. We assessed the in vitro antimicrobial activity of a selection of ß-lactams alone and together with subinhibitory concentrations of cefoxitin against a collection of MRSA, methicillin-susceptible S. aureus (MSSA), and vancomycin-intermediate S. aureus (VISA) isolates using MICs and time kill assays. For community-associated (CA) MRSA strains USA300 and USA400, MICs of nafcillin, cefazolin, cephalexin, cefuroxime, ceftriaxone and cefotaxime decreased by 8- to 64-times in the presence of 10 µg/ml cefoxitin. In contrast, for hospital-associated (HA) strains COLn, N315, and Mu50, there was no change in any ß-lactam MIC in the presence of cefoxitin. When combined with cefoxitin, the cephalexin MIC decreased for eight CA-MRSA and five MSSA sequence types but did not change for seven HA-MRSA sequence types. ß-lactam/cefoxitin combinations were synergistic against CA- but not HA-MRSA strains in time kill assays. Cefoxitin combined with a variety of ß-lactams enhances their activity against CA-MRSA strains in vitro. Further studies of combination ß-lactam therapy may provide insight into ß-lactam biology, penicillin binding protein cooperativity, and novel therapeutic strategies against MRSA.
Assuntos
Cefoxitina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , beta-Lactamas/farmacologia , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Sinergismo Farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade MicrobianaRESUMO
The aim of this experiment was to compare social stress, as measured by social behavior and adrenocortical activity, in young dairy goats during the first week after introduction into a herd of adult goats either during the dry period of the herd (i.e., all goats in the herd being pregnant or dry: PD) or shortly after parturition (i.e., all animals lactating or with their kids: LK). Thirty-two young goats that had had no contact with adult goats from the age of 7 wk were introduced into adult goat groups. Adult goats were kept in 2 groups of 36 animals each. Young goats were introduced (in groups of 4 animals each) into each of these 2 groups either during the PD period (2 repetitions) or during LK (2 repetitions); goats with different rearing experience were balanced over introduction periods. Young goats were more often receivers of agonistic social interactions when introduced during PD than during LK. Irrespective of the period of introduction, young goats had other young goats as neighbors more frequently than expected by chance alone, although this was even more distinct during PD. Cortisol metabolite levels increased markedly from baseline during PD, but not after parturition. Rearing showed an effect only on the nearest neighbors, with mother-reared young goats staying closer together. Our results indicate that young goats experience less social stress when being introduced into a herd of adult dairy goats shortly after parturition and with kids still present rather than during the dry period. Whether this effect is due to the period and lactational stage itself or to the presence of kids needs to be tested in future studies.