In vitro activities of ciprofloxacin and rifampin alone and in combination against growing and nongrowing strains of methicillin-susceptible and methicillin-resistant Staphylococcus aureus

Abstract

We characterized the effects of ciprofloxacin and rifampin alone and in combination on Staphylococcus aureus in vitro. The effects of drug combinations (e.g., indifferent, antagonistic, or additive interactions) on growth inhibition were compared by disk approximation studies and by determining the fractional inhibitory concentrations. Bactericidal effects in log-phase bacteria and in nongrowing isolates were characterized by time-kill methods. The effect of drug combinations was dependent upon whether or not cells were growing and whether killing or growth inhibition was the endpoint used to measure drug interaction. Despite bactericidal antagonism in time-kill experiments, our in vitro studies suggest several possible explanations for the observed benefits in patients treated with a combination of ciprofloxacin and rifampin for deep-seated staphylococcal infections. Notably, when growth inhibition rather than killing was used to characterize drug interaction, indifference rather than antagonism was observed. An additive bactericidal effect was observed in nongrowing bacteria suspended in phosphate-buffered saline. While rifampin antagonized the bactericidal effects of ciprofloxacin, ciprofloxacin did not antagonize the bactericidal effects of rifampin. Each antimicrobial prevented the emergence of subpopulations that were resistant to the other.

Tigecycline in combination with other antimicrobials: a review of in vitro, animal and case report studies

“…In fact, the addition of rifampicin to tigecycline resulted in antagonism for two (both rifampicin-susceptible) of the four tested S. aureus isolates [46]. Rifampicin frequently resulted in antagonism in vitro when combined with other classes of antibacterials, includ- K. pneumoniae TKA 1 CST Petersen et al [44] K. pneumoniae ing ␤-lactams, vancomycin and ciprofloxacin, against S. aureus [59][60][61]. However, no antagonism was reported for the tigecycline/rifampicin combination in a model of MRSA osteomyelitis in rabbits (see below) [22].…”

Northern Hemisphere temperature patterns in the last 12 centuries

“…Rifampin is attractive as an adjunctive agent as it is bactericidal, 87 has activity against cells in stationary growth phase, 88 and is better able to penetrate cells, 89 110 The median duration of bacteremia was longer in the combination arm (9 vs. 7 days) and rates of treatment failure were similar. Similarly, Riedel et al determined in a retrospective cohort of 84 patients with S. aureus native valve infective endocarditis (IE) that the addition of rifampin was associated with longer duration of bacteremia and increased mortality compared with controls.…”

Daptomycin combinations as alternative therapies in experimental foreign-body infection caused by meticillin-susceptible Staphylococcus aureus

“…LVX (at high doses of 750-1000 mg/day) plus RIF is currently considered the optimal treatment for acute MSSA PJI; its efficacy has been previously described by our own and other groups against experimental staphylococcal FBI [13,15,[24][25][26]. However, alternative therapies have insufficient evidence to support their use in cases where clinical failure occurs or these drugs cannot be administered due to intolerance, allergy or pharmacokinetic interactions [1,2,4].…”