The differential activity of aminoglycoside antibiotics with rifampin explored in a kinetic in vitro model of implant-associated infection (Staphylococcus epidermidis).
Implant-associated infections offer resistance to antibiotic treatment and possibly do so because the causative bacteria which reside on the artificial surface are enclosed in a protective matrix (biofilm) shielding the bacteria against the action of host defenses and antibiotic action. We have investigated in vitro the effect of various antimicrobial agents on biofilms of Staphylococcus epidermidis, which is the main organism responsible for implant-associated infections. Rifampin was found to exert superior activity, albeit incomplete, against S. epidermidis biofilms using an assay system which enabled the determination of the kinetics of antibiotic action over five days. In a large screening study looking for agents capable of completing the action of rifampin, gentamicin was unexpectedly found to be antagonistic to rifampin. The present study was undertaken to investigate further the activity of gentamicin and five other aminoglycoside antibiotics using a wider range of concentrations (2.5-20 micrograms/mL). The main findings were a marked synergy with rifampin demonstrated by streptomycin, producing a bactericidal outcome, which contrasted sharply with the indifference or antagonism shown by the other aminoglycosides. We then studied in further detail the effect of separate combinations of streptomycin and gentamicin with rifampin over a wider concentration range of each agent (1.25-40 micrograms/mL). Streptomycin showed strong rapid synergy with rifampin even at the lowest concentration of each antibiotic. Gentamicin demonstrated a concentration-related antagonism towards rifampin which was independent of rifampin concentration. The data support the conclusion that streptomycin, like cell-wall active antibiotics, exerts a potent synergy with rifampin against S. epidermidis biofilms, and that the other aminoglycosides, predominantly gentamicin, strongly antagonize rifampin action.(ABSTRACT TRUNCATED AT 250 WORDS)
Richards
G K
GK
Department of Laboratories, South Saskatchewan Hospital Center, Regina, Canada.
Morcos
R J
RJ
Gagnon
R F
RF
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology; D066298:In Vitro Techniques; D019736:Prostheses and Implants / Q000009:adverse effects*; D012293:Rifampin / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000209:etiology / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D013307:Streptomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D012293:Rifampin; D013307:Streptomycin