Exposure to oxacillin subinhibitory concentrations and in vitro induction of resistance expression in heteroresistant and non-heteroresistant oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA)

Resistance expression can occur as a consequence of irrational use of antibiotics, since this implies dissemination of subinhibitory concentration (sub-MICs) in different environments and generates a selective pressure. The study aimed to evaluate the in vitro influence of selective pressure on antibiotic resistance expression in two oxacillin-susceptible mecA -positive Staphylococcus aureus (OS-MRSA), through exposure to oxacillin sub-MICs. One heteroresistant OS-MRSA strain and a non-heteroresistant strain, both isolated from nasal colonization were exposed to two-fold serial dilutions of oxacillin (0,125 a 256 μg/mL) during seven consecutive days. Disc diffusion test was used to determine the susceptibility to several antibiotics and population analysis profile (PAP) was used to evaluate the expression of oxacillin resistance before and after antibiotic exposure. Susceptibility to non-β-lactam antibiotics was not altered but changes in phenotypic expression of penicillin and oxacillin resistance were observed. Both OS-MRSA strains began to express homoresistance (oxacillin MIC = 256 μg/mL) and had no penicillin zone inhibition after induction, different from that was observed before oxacillin exposure, which suggested increased in β-lactamase production. In vitro selective pressure with oxacillin stimulated β-lactamase production and led phenotypic expression of oxacillin resistance in heteroresistant and non-heteroresistant OS-MRSA, which became homoresistant. This reinforces the impact that irrational use of antibiotics has on individuals colonized by S. aureus and on the population, emphasizing that the emergence and spread of resistance to antibiotics represent a process of evolution in response to selective antimicrobial pressure. ### Competing Interest Statement The authors have declared no competing interest.