| 2020 | Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis. | J Infect Dis | Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without Vancomycin, in a rat model of foreign body osteomyelitis.Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with Vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively.Rifampin, rifabutin or rifapentine administered with Vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or Vancomycin alone (4.64 log10 CFUs/g) (both Pā
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.02). The K-wires of animals receiving no treatment or Vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with Vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group.Rifabutin or rifapentine with Vancomycin were as active as rifampin with Vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections. |
| 1998 | In vitro susceptibilities of aerobic and facultative non-spore-forming gram-positive bacilli to HMR 3647 (RU 66647) and 14 other antimicrobials. | Antimicrob Agents Chemother | The comparative in vitro activity of the ketolide HMR 3647 (RU 66647) and those of structurally related macrolide-lincosamide-streptogramin compounds (erythromycin, roxithromycin, azithromycin, clarithromycin, josamycin, lincomycin, pristinamycin, and quinupristin-dalfopristin) as well as those of benzylpenicillin, doxycycline, Vancomycin, teicoplanin, levofloxacin, and rifapentine against 247 aerobic and facultative non-spore-forming gram-positive bacilli were determined by an agar dilution method. The ketolide was active against most organisms tested except Corynebacterium striatum, coryneform CDC group 12, and Oerskovia spp. The frequency of resistance to erythromycin and other macrolides as well as that to lincomycin was high. Pristinamycin and, to a lesser extent, quinupristin-dalfopristin were very active, but resistance to these agents was present in some strains of Rhodococcus equi, Listeria spp., C. striatum, Erysipelothrix rhusiopathiae, and Oerskovia spp. HMR 3647 was very active against all erythromycin-sensitive and many erythromycin-nonsusceptible strains, especially Corynebacterium minutissimum, Corynebacterium pseudodiphtheriticum, Corynebacterium amycolatum, and Corynebacterium jeikeium. In vitro resistance to benzylpenicillin was common, but doxycycline, Vancomycin, and teicoplanin were very active against most organisms tested except E. rhusiopathiae, against which glycopeptide antibiotics were not active. The in vitro activity of levofloxacin was remarkable, but resistance to this agent was common for C. amycolatum, Corynebacterium urealyticum, C. jeikeium, and Oerskovia spp. strains. Rifapentine was also very active in vitro against many organisms, but resistance to this agent was always present in E. rhusiopathiae and was very common in C. striatum and C. urealyticum. |
| 1989 | The activity of rifampin and analogs against Staphylococcus epidermidis biofilms in a CAPD environment model. | Am J Nephrol | Rifampin has been noted to exhibit exceptional antimicrobial activity against Staphylococcus epidermidis biofilms as compared to commonly used antibiotics. To further explore this unique effect of rifampin, we evaluated the antimicrobial activity of three commercially available preparations of rifampin, two rifampin analogs (CGP29861 and rifapentine) and the parent compound rifamycin SV. These were tested against standardized S. epidermidis biofilms in various milieus. All six members of the rifamycin group tested demonstrated marked antimicrobial activity but with minor foci of resisters when tested in a peptone water environment. The microscopy of the exposed biofilms showed profound lysis and morphological distortion of the remaining cells. The synergistic elimination of the foci of resistance was achieved in an environment of fresh peritoneal dialysis (PD) solution or by the addition of Vancomycin. Neither Vancomycin nor fresh PD solution demonstrated significant antimicrobial activity when tested alone with biofilm preparations. Spent PD fluid markedly antagonized the activity of the rifamycins with the exception of the rifampin analogs, an effect primarily of pH. The synergistic effect of Vancomycin with the rifamycins was not affected either by protein content or pH, leaving the antagonistic properties of spent PD fluid unexplained. The variable activity of the different members of the rifamycin group underlines the importance of structural differences in determining their interaction with bacterial biofilms. Further precision of the nature of these structural interactions is seen to have considerable potential for therapeutic advancement of catheter-associated sepsis. |
| 1987 | Comparative in vitro activity of CI934, a new fluoroquinolone, alone and in combination with coumermycin, against gram-positive bacteria. | Drugs Exp Clin Res | The in vitro activity of Cl934, a new quinolone antimicrobial agent, was studied against 314 strains of Gram-positive bacteria representing 6 genera: Staphylococcus aureus, Streptococcus faecalis, S. agalactiae, S. pyogenes, S. pneumoniae, S. milleri, viridans streptococci, Listeria monocytogenes, Corynebacterium JK, Mycobacterium fortuitum and Bacillus spp.; and compared with that of enoxacin, ciprofloxacin, penicillin G, ampicillin, coumermycin, oxacillin, Vancomycin, teicoplanin, rifampin, rifapentine, LM 427, erythromycin, minocycline, tetracycline and clindamycin. The agar dilution method was used. Cl934 was very active in vitro, with MIC90 less than or equal to 0.5 mg/l against most species tested, except for S. faecalis and M. fortuitum. It was usually 2 to 8-fold more active than ciprofloxacin. Cl934 was also tested by the killing curve method, alone and in combination with coumermycin. It was rapidly bactericidal against most species tested, including S. faecalis. A synergistic interaction was observed with coumermycin against S. aureus, S. agalactiae, S. milleri and S. faecalis. The only antagonistic interaction occurred against L. monocytogenes exposed to 8 X MIC of Cl934 with 2 X MIC of coumermycin. |
| 1985 | In vitro activities of rifapentine and rifampin, alone and in combination with six other antibiotics, against methicillin-susceptible and methicillin-resistant staphylococci of different species. | Antimicrob Agents Chemother | The antistaphylococcal activity of rifapentine, a new rifamycin SV derivative, was evaluated in vitro and compared with that of rifampin. A total of 313 staphylococcal strains freshly isolated from clinical material and including representatives of all currently recognized Staphylococcus species of human origin were used. The susceptibility to methicillin of all the test strains was determined preliminarily. Despite minor differences with some species, the MICs of rifapentine were found to be substantially similar to those of rifampin. Methicillin-resistant strains of all species were most resistant to rifapentine and rifampin than were their methicillin-susceptible counterparts. For most strains tested, the MBCs of both rifamycins exceeded by twofold the respective MICs. Both the checkerboard dilution and time-kill methods were used to determine the interactions of rifapentine or rifampin with six different antibiotics: cefamandole, Vancomycin, teicoplanin, gentamicin, erythromycin, and fusidic acid. No significant differences between the two rifamycins in the combinations were observed against either methicillin-susceptible or methicillin-resistant strains. Minor differences were noted depending on the second antibiotic tested or the staphylococcal species examined. Antagonism was never observed, and indifference was the prevalent response. Cases of synergism were observed occasionally with the checkerboard method and slightly more often with the time-kill method. |