scholarly journals Efficacy of Fosfomycin in Experimental Osteomyelitis Due to Methicillin-ResistantStaphylococcus aureus

2010 ◽  
Vol 55 (2) ◽  
pp. 931-933 ◽  
Author(s):  
W. Poeppl ◽  
S. Tobudic ◽  
T. Lingscheid ◽  
R. Plasenzotti ◽  
N. Kozakowski ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Treatment Period ◽  
Bacterial Culture ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Experimental Osteomyelitis ◽  
Development Of Resistance ◽  
Bone Cultures

ABSTRACTThe activity of fosfomycin was evaluated in an experimental methicillin-resistantStaphylococcus aureus(MRSA) osteomyelitis model. Eighteen rats were treated for 4 weeks with 150 mg of fosfomycin/kg of body weight intraperitoneally once daily or with saline placebo. After treatment, animals were euthanized and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were positive for methicillin-resistantS. aureusin all 9 (100%) untreated controls and in 2 of 9 (22.2%) fosfomycin-treated rats. Thus, fosfomycin treatment was significantly more efficacious than placebo. No development of resistance was observed after the 4-week treatment period.

scholarly journals Daptomycin plus Fosfomycin, a Synergistic Combination in Experimental Implant-Associated Osteomyelitis Due to Methicillin-Resistant Staphylococcus aureus in Rats

2014 ◽  
Vol 59 (2) ◽  
pp. 859-863 ◽  
Author(s):  
Tilman Lingscheid ◽  
Wolfgang Poeppl ◽  
Dominik Bernitzky ◽  
Luzia Veletzky ◽  
Manuel Kussmann ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Bacterial Counts ◽  
Content Type ◽  
Bacterial Cultures ◽  
Development Of Resistance ◽  
Bacterial Inoculum ◽  
Titanium Wire ◽  
Mrsa Infection

ABSTRACTThe aim of this study was to evaluate the combination of daptomycin and fosfomycin in experimental chronic implant-associated osteomyelitis due to methicillin-resistantStaphylococcus aureus(MRSA). Infection was induced in the tibiae of rats by the insertion of a bacterial inoculum (1 to 5 × 108CFU/ml) of a clinical MRSA isolate and a titanium wire. Four weeks after infection, each animal was assigned to a treatment group: daptomycin monotherapy at 60 mg/kg of body weight once daily (n= 10), fosfomycin monotherapy at 40 mg/kg once daily (n= 10), or daptomycin and fosfomycin combined at 60 mg/kg and 40 mg/kg, respectively, once daily (n= 9). Ten animals were left untreated. After a 3-week treatment period, the animals were euthanized, and the infected tibiae and implants were processed for quantitative bacterial cultures. The bacterial cultures from bones were positive for MRSA in all animals in the untreated group, the daptomycin group, and the fosfomycin group, with median bacterial counts of 2.34 × 106CFU/g bone, 1.57 × 106CFU/g bone, and 3.48 × 102CFU/g bone, respectively. In the daptomycin-fosfomycin group, 6 out of 9 animals were positive for MRSA, with a median count of 7.92 CFU/g bone. Bacterial cultures derived from the titanium wires were negative in the fosfomycin- and daptomycin-fosfomycin-treated groups. Based on bacterial counts in bones, treatment with daptomycin-fosfomycin was statistically significantly superior to all that of the other groups (P≤ 0.003). Fosfomycin was superior to daptomycin and no treatment (P< 0.0001). No development of resistance was observed in any treatment arm. The combination of daptomycin and fosfomycin demonstrated synergism against MRSA in experimental implant-associated osteomyelitis.

scholarly journals In Vivo Activity of Evernimicin (SCH 27899) against Methicillin-Resistant Staphylococcus aureus in Experimental Infective Endocarditis

2001 ◽  
Vol 45 (1) ◽  
pp. 208-211 ◽  
Author(s):  
Helen W. Boucher ◽  
Claudie Thauvin-Eliopoulos ◽  
David Loebenberg ◽  
George M. Eliopoulos
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Infusion Therapy ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Treatment Groups ◽  
Potential Efficacy ◽  
Mrsa Infection ◽  
The Difference

ABSTRACT Currently, there exist few satisfactory alternatives to vancomycin for therapy of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. We employed a rat model of aortic valve endocarditis to assess the potential efficacy of evernimicin (SCH 27899) compared with vancomycin against infection with a strain susceptible to both agents (MICs of 0.25 and 0.50 μg/ml, respectively). Infected animals were assigned to one of three groups: controls (no treatment), evernimicin at 60 mg/kg of body weight by intravenous (i.v.) infusion once daily, or vancomycin at 150 mg/kg of body weight per day by continuous i.v. infusion. Therapy was administered for 5.5 days. At the start of therapy, colony counts in vegetations were 6.63 ± 0.44 log10 CFU/g. In both treatment groups, bacterial density within vegetations was significantly reduced in comparison with control animals that had not been treated. Final colony counts were as follows (mean ± standard deviation): controls, 10.12 ± 1.51 log10 CFU/g of vegetation; evernimicin, 7.22 ± 2.91 log10 CFU/g of vegetation; vancomycin, 5.65 ± 1.76 log10 CFU/g of vegetation. The difference between the evernimicin and vancomycin groups was not significant. These results confirmed the bacteriostatic activity of evernimicin in vivo in an experimental model of severe MRSA infection.

scholarly journals Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model

2011 ◽  
Vol 55 (11) ◽  
pp. 4999-5003 ◽  
Author(s):  
W. Poeppl ◽  
S. Tobudic ◽  
T. Lingscheid ◽  
R. Plasenzotti ◽  
N. Kozakowski ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rat Model ◽  
Antagonistic Effect ◽  
Combination Group ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Bacterial Counts ◽  
Content Type ◽  
Development Of Resistance

ABSTRACTThein vivoactivities of daptomycin, fosfomycin, and a combination of both antibiotics against a clinical isolate of methicillin-resistantStaphylococcus aureus(daptomycin MIC, 0.25 μg/ml; fosfomycin MIC, 0.5 μg/ml) were evaluated in a rat model of osteomyelitis. A total of 37 rats with experimental osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once daily, a combination of both drugs, or a saline placebo. After the completion of treatment, animals were euthanized, and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were found to be positive for methicillin-resistantS. aureusin 9 of 9 (100%) animals of the placebo group, in 9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin-treated rats, and in 1 of 9 (22.2%) rats comprising the combination group. Results of bacterial counts in the bone samples were expressed as log10CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's multiple-comparison test. Based on bacterial counts, treatment with daptomycin was significantly superior to placebo, although it remained inferior to treatment with fosfomycin. No synergistic or antagonistic effect was observed for the combination therapy. No development of resistance against daptomycin or fosfomycin was observed after the 4-week treatment period.

scholarly journals In VitroPharmacodynamics of Human Simulated Exposures of Ceftaroline and Daptomycin against MRSA, hVISA, and VISA with and without Prior Vancomycin Exposure

2013 ◽  
Vol 58 (2) ◽  
pp. 672-677 ◽  
Author(s):  
Amira A. Bhalodi ◽  
Mao Hagihara ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Sequential Therapy ◽  
Free Drug ◽  
Pharmacodynamic Model ◽  
Prior Exposure ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Infection

ABSTRACTThe effects of prior vancomycin exposure on ceftaroline and daptomycin therapy against methicillin-resistantStaphylococcus aureus(MRSA) have not been widely studied. Humanized free-drug exposures of vancomycin at 1 g every 12 h (q12h), ceftaroline at 600 mg q12h, and daptomycin at 10 mg/kg of body weight q24h were simulated in a 96-hin vitropharmacodynamic model against three MRSA isolates, including one heteroresistant vancomycin-intermediateS. aureus(hVISA) isolate and one VISA isolate. A total of five regimens were tested: vancomycin, ceftaroline, and daptomycin alone for the entire 96 h, and then sequential therapy with vancomycin for 48 h followed by ceftaroline or daptomycin for 48 h. Microbiological responses were measured by the changes in log10CFU during 96 h from baseline. Control isolates grew to 9.16 ± 0.32, 9.13 ± 0.14, and 8.69 ± 0.28 log10CFU for MRSA, hVISA, and VISA, respectively. Vancomycin initially achieved ≥3 log10CFU reductions against the MRSA and hVISA isolates, followed by regrowth beginning at 48 h; minimal activity was observed against VISA. The change in 96-h log10CFU was largest for sequential therapy with vancomycin followed by ceftaroline (−5.22 ± 1.2,P= 0.010 versus ceftaroline) and for sequential therapy with vancomycin followed by ceftaroline (−3.60 ± 0.6,P= 0.037 versus daptomycin), compared with daptomycin (−2.24 ± 1.0), vancomycin (−1.40 ± 1.8), and sequential therapy with vancomycin followed by daptomycin (−1.32 ± 1.0,P> 0.5 for the last three regimens). Prior exposure of vancomycin at 1 g q12h reduced the initial microbiological response of daptomycin, particularly for hVISA and VISA isolates, but did not affect the response of ceftaroline. In the scenario of poor vancomycin response for high-inoculum MRSA infection, a ceftaroline-containing regimen may be preferred.

scholarly journals Novel Antibiotic Combinations of Diverse Subclasses for Effective Suppression of Extensively Drug-Resistant Methicillin-Resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shumyila Nasir ◽  
Muhammad Sufyan Vohra ◽  
Danish Gul ◽  
Umm E Swaiba ◽  
Maira Aleem ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clavulanic Acid ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Development Of Resistance ◽  
Amoxicillin Clavulanic Acid ◽  
Combination Antibiotics ◽  
Time Kill

The emergence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), the chief etiological agent for a range of refractory infections, has rendered all β-lactams ineffective against it. The treatment process is further complicated with the development of resistance to glycopeptides, primary antibiotics for treatment of MRSA. Antibiotic combination therapy with existing antimicrobial agents may provide an immediate treatment option. Minimum inhibitory concentrations (MICs) of 18 different commercially available antibiotics were determined along with their 90 possible pairwise combinations and 64 triple combinations to filter out 5 best combinations. Time-Kill kinetics of these combinations were then analyzed to find collateral bactericidal combinations which were then tested on other randomly selected MRSA isolates. Among the top 5 combinations including levofloxacin-ceftazidime; amoxicillin/clavulanic acid-tobramycin; amoxicillin/clavulanic acid-cephradine; amoxicillin/clavulanic acid-ofloxacin; and piperacillin/tazobactam-tobramycin, three combinations were found to be collaterally effective. Levofloxacin-ceftazidime acted synergistically in 80% of the tested clinical MRSA isolates. First-line β-lactams of lower generations can be used effectively against MRSA infection when used in combination. Antibiotics other than glycopeptides may still work in combination.

scholarly journals Efficacy of Fosfomycin Compared to Vancomycin in Treatment of Implant-Associated Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

2014 ◽  
Vol 58 (9) ◽  
pp. 5111-5116 ◽  
Author(s):  
Wolfgang Poeppl ◽  
Tilman Lingscheid ◽  
Dominik Bernitzky ◽  
Uwe Y. Schwarze ◽  
Oliver Donath ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Drug Control ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Content Type ◽  
Titanium Wire ◽  
Experimental Rat Model ◽  
Vancomycin Group ◽  
Emergence Of Resistance

ABSTRACTFosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistantStaphylococcus aureus(MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1 × 108to 5 × 108CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n= 11) or 75 mg/kg fosfomycin intraperitoneally once daily (n= 10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29 × 106CFU/g of bone) and the vancomycin group (median, 3.03 × 105CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42 × 102and 1.51 × 103CFU/g of bone). Vancomycin was superior to the no-drug control (P= 0.002), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). The cultures from the wires were positive in all untreated animals (median, 2.5 × 103CFU/implant), in 10 animals in the vancomycin group (median, 1.15 × 103CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P= 0.324), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

scholarly journals Combination of Tedizolid and Daptomycin against Methicillin-Resistant Staphylococcus aureus in an In Vitro Model of Simulated Endocardial Vegetations

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Jordan R. Smith ◽  
Juwon Yim ◽  
Seth Rice ◽  
Kyle Stamper ◽  
Razie Kebriaei ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Treatment Options ◽  
Antagonistic Activity ◽  
Exact Nature ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vitro Model

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for health care-associated infections, and treatment options are limited. Tedizolid (TZD) is a novel oxazolidinone antibiotic with activity against MRSA. Previously, daptomycin (DAP) has demonstrated synergy with other antibiotics against MRSA. We sought to determine the efficacy of the combination of TZD and DAP against MRSA in an in vitro model of simulated endocardial vegetations (SEVs). TZD simulations of 200 mg once daily and DAP simulations of 6 mg/kg of body weight and 10 mg/kg once daily were tested alone and in the combinations TZD plus DAP at 6 mg/kg or DAP at 10 mg/kg against two clinical strains of MRSA, 494 and 67. These regimens were tested in SEV models over 8 days to determine the antibacterial activity of the regimens and whether synergy or antagonism might be present between the agents. Against both strains 494 and 67 and at both DAP dose regimens, the combination of TZD and DAP was antagonistic at 192 h. In all cases, DAP alone was statistically superior to DAP plus TZD. When the combination was stopped after 96 h, transitioning to DAP at 6 mg/kg or DAP at 10 mg/kg alone resulted in better antibacterial activity than either of the TZD-plus-DAP combinations, further demonstrating antagonistic effects. Against MRSA, we demonstrated that TZD and DAP have antagonistic activity that hinders their overall antimicrobial efficacy. The exact nature of this antagonistic relationship is still undetermined, but its presence warrants further study of the potentially harmful grouping of the two antibiotics in clinical use.

scholarly journals Efficacy of LY333328 against Experimental Methicillin-Resistant Staphylococcus aureus Endocarditis

1998 ◽  
Vol 42 (4) ◽  
pp. 981-983 ◽  
Author(s):  
Glenn W. Kaatz ◽  
Susan M. Seo ◽  
Jeffrey R. Aeschlimann ◽  
Heather H. Houlihan ◽  
Renee-Claude Mercier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Rabbit Model ◽  
Glycopeptide Antibiotic ◽  
In Vivo Efficacy ◽  
Methicillin Resistant ◽  
Therapeutic Alternative ◽  
Staphylococcus Aureus Endocarditis

ABSTRACT The in vivo efficacy of LY333328, a new glycopeptide antibiotic, was compared with that of vancomycin by using the rabbit model of left-sided methicillin-resistant Staphylococcus aureusendocarditis. Animals received LY333328 or vancomycin (25 mg/kg of body weight every 24 or 8 h, respectively) for 4 days. These drugs were equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and tissues. We conclude that in this model, LY333328 was microbiologically effective and may be a therapeutic alternative to vancomycin.

scholarly journals Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

1996 ◽  
Vol 40 (5) ◽  
pp. 1219-1224 ◽  
Author(s):  
B Fantin ◽  
J Pierre ◽  
N Castéla-Papin ◽  
L Saint-Julien ◽  
H Drugeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Limiting Factor ◽  
High Dose ◽  
Methicillin Resistant

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

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