Descrição
Background. Previous studies examining synergistic effects of antibiotics against
CoNS biofilms often relied on drug concentrations higher than the peak serum (PS)
concentration, as determined by MIC assays, therefore having little clinical
applicability. Other studies investigated synergistic effects of a wide range of
antibiotics, however many are not routinely used in a clinical setting. Dicloxacillin is
the major antibiotic used in Portugal to treat staphylococci infections, and we
evaluated the synergistic effect of antibiotics with different mechanisms of action
combined with dicloxacillin and other cell wall synthesis inhibitors.
Methods. We used combinations of 5 antibiotic agents (cefazolin, vancomycin,
dicloxacillin, tetracycline and rifampicin) at the PS concentration of each agent, and
evaluated the killing rate over a 24 h period using biofilms made by 10 CoNS clinical
isolates. Results from all of the assays were compared using ANOVA.
Results. Among all of the combinations tested there was an increase in the killing
rate of the antibiotics when compared to the killing rates when only one antibiotic
was used. However, only the combination of dicloxacillin with rifampicin resulted in a
true synergistic effect for most CoNS strains. When tetracycline was used in
combination with any other antibiotic, a decrease in the killing rate was obtained.
Conclusions. Our results indicate that dicloxacillin could be useful against CoNS
biofilms when combined with a small amount of rifampicin (10 μg/ml). Antibiotics
highly effective against planktonic cells, like vancomycin, were minimally effective
against cells in biofilms, even after adding more antibiotics with distinct mechanisms
of action. Also, except for dicloxacillin, adding more antibiotics to the biofilm did not
result in an increase in killing efficiency, and there were even antagonistic in some
instances. Screening for synergistic effects of different combinations of antibiotics
might be a useful tool to determine a therapeutic approach to infections involving
CoNS biofilms.