RESUMO
Arbekacin is an aminoglycoside used in Japan for treating infections caused by gentamicin and oxacillin-resistant S. aureus (ORSA). The objective of this study was to determine the in vitro antimicrobial activity of arbekacin against 454 clinical isolates of ORSA. The isolates were consecutively collected between January and July, 2000, from patients hospitalized in 8 Brazilian medical centers. The antimicrobial susceptibility testing was performed by disk diffusion method according to NCCLS recommendations. The vast majority of the isolates, 453 strains (99.8%), were considered susceptible to arbekacin based on the criteria proposed by the Requirements for Antibiotic Products of Japan. Only 1 isolate (0.2%) was classified as resistant. On the other hand, high rates of resistance were demonstrated for other aminoglycosides, such as gentamicin (97.6% resistance) and amikacin (97.0% resistance). Resistance rate was also high for ciprofloxacin (98.0%). All isolates were considered susceptible to vancomycin. The excellent in vitro antimicrobial activity of arbekacin demonstrated in this study indicates that this antimicrobial agent may play an important role in the treatment of severe ORSA infections, especially those that show poor clinical response with vancomycin monotherapy. Since the aminoglycosides should not be used as monotherapy to treat Gram positive infections, further studies evaluating in vitro and in vivo synergistic activity of arbekacin combinations are necessary to clarify the clinical role of this aminoglycoside.
Assuntos
Aminoglicosídeos , Antibacterianos/farmacologia , Dibecacina/análogos & derivados , Dibecacina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Brasil , Resistência Microbiana a Medicamentos , Hospitais , Humanos , Testes de Sensibilidade Microbiana , Oxacilina/farmacologia , Resistência às Penicilinas , Penicilinas/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificaçãoRESUMO
In spontaneously beating sinus venosus of the frog Caudiverbera caudiverbera the effects of bekanamycin and dibekacin, two aminoglycoside antibiotics, on action potentials of cardiac primary pacemaker cells were studied by intracellular recording. Bekanamycin and dibekacin induced a concentration-dependent decrease of the amplitude, overshoot and the rate of rise of the action potential. Both also flattened the slow diastolic depolarization leading to a marked decrease in beat rate. At the highest concentration used (1 x 10 3 M), the aminoglycosides produced a compete inhibition of primary cells action potentials. It was preceded by the appearance of subthreshold oscillations of the membrane potential which were observed for a few minutes until the electrical activity of pacemaker cell ceased. During absence of impulse initiation a stable membrane potential about -40 mV was observed. Aminoglycoside effects, excepting those on SCL, were completely supressed when external calcium was increased to.3.6 mM. The results support the conclusion that bekanamycin and dibekacin depress the electrical activity of pacemaker cells. It is suggested that this effect is induced by amminoglycosides blockade of the slow calcium current involved in both upstroke and slow diastolic depolarization and through modification of potassium outward current. Bekanamycin at a lower concentration than that needed to induce electrophysiological effects potentiated verapamil 1 x 10 8 effects on cardiac pacemaker cells