scholarly journals Activity of Tedizolid in Methicillin-Resistant Staphylococcus epidermidis Experimental Foreign Body-Associated Osteomyelitis

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Kyung-Hwa Park ◽  
Kerryl E. Greenwood-Quaintance ◽  
Audrey N. Schuetz ◽  
Jayawant N. Mandrekar ◽  
Robin Patel
Keyword(s):  
Foreign Body ◽  
Combination Therapy ◽  
Rat Model ◽  
Staphylococcus Epidermidis ◽  
Steel Wire ◽  
Clinical Strain ◽  
Methicillin Resistant ◽  
Infection Period ◽  
Treatment Groups ◽  
All Treatment

ABSTRACT We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia, and a stainless steel wire with a precolonized MRSE biofilm was implanted. Following a 1-week infection period, 92 rats received either no treatment (n = 17) or 14 days of intraperitoneal tedizolid (n = 15), tedizolid plus rifampin (n = 15), rifampin (n = 15), vancomycin plus rifampin (n = 15), or vancomycin (n = 15). Quantitative bone and wire cultures were performed after treatment completion and also 1 week after infection in a separate group of five rats. The median quantity of staphylococci in bone after the 1-week infection period was 4.89 log10 CFU/g bone (interquartile range, 3.83 to 5.33 log10 CFU/g bone); staphylococci were recovered from all associated wires. A median quantity of staphylococci of 3.70 log10 CFU/g bone was detected in bones of untreated control rats after 3 weeks. Quantities of staphylococci in bones of all treatment groups except the group receiving vancomycin alone (2.78 log10 CFU/g) were significantly lower than those for untreated controls, with no staphylococci being detected in the groups receiving rifampin monotherapy, tedizolid-plus-rifampin combination therapy, and vancomycin-plus-rifampin combination therapy. Quantities of staphylococci on wires from all treatment groups that included rifampin were significantly lower than those for untreated controls. No resistance to rifampin, tedizolid, or vancomycin was detected. Tedizolid combined with rifampin was active in a rat model of MRSE foreign body-associated osteomyelitis.

scholarly journals Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant Staphylococcus epidermidis Osteitis without Implant

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
S. Albac ◽  
D. Labrousse ◽  
D. Hayez ◽  
N. Anzala ◽  
D. Bonnot ◽  
...  
Keyword(s):  
Rat Model ◽  
Staphylococcus Epidermidis ◽  
Bacterial Load ◽  
Clinical Strain ◽  
Bacterial Reduction ◽  
Methicillin Resistant ◽  
Content Type ◽  
Infection Period ◽  
Antibiotic Effect ◽  
The Mean

ABSTRACT We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteitis without implant to compare the efficacy of vancomycin, linezolid, daptomycin, ceftaroline, and rifampin either alone or in association with rifampin. A clinical strain of MRSE was inoculated into the proximal tibia. Following a 1-week infection period, rats received either no treatment or 3, 7, or 14 days of human-equivalent antibiotic regimen. Quantitative bone cultures were performed throughout the 14-day period. The mean ± SD quantity of staphylococci in the bone after a 1-week infection period was 4.5 ± 1.0 log10 CFU/g bone, with this bacterial load remaining stable after 3 weeks of infection (4.9 ± 1.4 log10 CFU/g bone). Vancomycin monotherapy was the most slowly bactericidal treatment, whereas ceftaroline monotherapy was the most rapidly bactericidal treatment. The addition of rifampin significantly increased the bacterial reduction for vancomycin, linezolid, and daptomycin. All tibias were sterilized after 2 weeks of treatment except for animals receiving vancomycin or daptomycin alone (66.6% and 50% of sterilization, respectively). These results show that ceftaroline and linezolid alone remain good options in the treatment of MRSE osteitis without implant. The combination with rifampin increases the antibiotic effect of vancomycin and daptomycin lines.

scholarly journals Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis

2020 ◽  
Vol 222 (9) ◽  
pp. 1498-1504
Author(s):  
Melissa J Karau ◽  
Suzannah M Schmidt-Malan ◽  
Mariana Albano ◽  
Jayawant N Mandrekar ◽  
Christina G Rivera ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Rat Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Kirschner Wire ◽  
Methicillin Resistant ◽  
Joint Infections ◽  
Single Animal ◽  
K Wires

Abstract Background 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. Methods 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. Results 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 P ≤ .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. Conclusions 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.

scholarly journals Treatment with Linezolid or Vancomycin in Combination with Rifampin Is Effective in an Animal Model of Methicillin-ResistantStaphylococcus aureusForeign Body Osteomyelitis

2010 ◽  
Vol 55 (3) ◽  
pp. 1182-1186 ◽  
Author(s):  
Paschalis Vergidis ◽  
Mark S. Rouse ◽  
Gorane Euba ◽  
Melissa J. Karau ◽  
Suzannah M. Schmidt ◽  
...  
Keyword(s):  
Animal Model ◽  
Foreign Body ◽  
Proximal Tibia ◽  
Bacterial Load ◽  
Control Group ◽  
Treatment Groups ◽  
Titanium Wire ◽  
Experimental Rat Model ◽  
Rifampin Resistance ◽  
All Treatment

ABSTRACTRifampin monotherapy was compared to the combination of linezolid or vancomycin with rifampin in an experimental rat model of methicillin-resistantStaphylococcus aureus(MRSA) chronic foreign body osteomyelitis. MRSA was inoculated into the proximal tibia, and a titanium wire was implanted. Four weeks after infection, rats were treated intraperitoneally for 21 days with rifampin alone (n= 16), linezolid plus rifampin (n= 14), or vancomycin plus rifampin (n= 13). Thirteen animals received no treatment. At completion of treatment, qualitative cultures of the wire and quantitative cultures of the bone (reported as median values) were performed. Quantitative cultures from the control, rifampin monotherapy, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups revealed 4.54, 0.71, 0.10, and 0.50 log10CFU/gram of bone, respectively. The bacterial load was significantly reduced in all treatment groups compared to that in the control group. Rifampin resistance was detected in isolates from 10, 2, and 1 animal in the rifampin, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups, respectively. Cultures of the removed wire revealed bacterial growth in 1 and 2 animals in the rifampin and linezolid-plus-rifampin groups, respectively, with no growth in the vancomycin-plus-rifampin group and growth from all wires in the untreated group. In conclusion, we demonstrated that combination treatment with linezolid plus rifampin or vancomycin plus rifampin is effective in an animal model of MRSA foreign body osteomyelitis in the context of retention of the infected foreign body.

scholarly journals A novel rat model of foreign body osteomyelitis for evaluation of antimicrobial efficacy

2019 ◽  
Vol 3 (1) ◽  
pp. 7-14
Author(s):  
Cassandra L. Brinkman ◽  
Suzannah M. Schmidt-Malan ◽  
Melissa J. Karau ◽  
Robin Patel
Keyword(s):  
Foreign Body ◽  
Animal Models ◽  
Rat Model ◽  
Staphylococcus Epidermidis ◽  
Foreign Bodies ◽  
Infected Animal ◽  
Infection Site ◽  
Aureus Infection ◽  
Novel Model ◽  
A Current

The most common organism-type causing orthopedic foreign body infection is the staphylococci, of which Staphylococcus aureus and Staphylococcus epidermidis are especially common. These organisms form biofilms on orthopedic foreign body surfaces, rendering such infections challenging and time consuming to treat. Our group evaluates novel therapeutics for orthopedic foreign body infection in animal models. A current limitation of most animal models is that that they only allow for the removal of one sample per animal, at the time of sacrifice. Herein, we describe a novel rat model of foreign body osteomyelitis that allows removal of foreign bodies at different time points, from the same infected animal. We demonstrate that this model can be used for both S. aureus and S. epidermidis orthopedic foreign body infection, with 3.56, 3.60 and 5.51 log10 cfu/cm2 S. aureus recovered at four, five and six weeks, respectively, after infection, and 2.08, 2.17 and 2.62 log10 cfu/cm2 S. epidermidis recovered at four, five and six weeks, respectively, after infection. We evaluated the model with S. aureus infection treated with rifampin 25 mg/kg twice daily for 21 days. Using quantitative cultures, we were no longer able to detect bacteria as of the 14th day of treatment with bacteria becoming detectable again 7 days following the discontinuation of rifampin a period. This novel model allows monitoring of evolution of infection at the infection site in the same animal.

scholarly journals Inflammasome Regulation at the Level of Cellular and Molecular Function affect by Recombinant Tissue Plasminogen Activator and Exosomes Treatment in Ischemic Stroke Animal Model

2021 ◽  
Author(s):  
Mohsen Safakhil ◽  
Mina Ramezani ◽  
Azadeh Mohamadgholi
Keyword(s):  
Animal Model ◽  
Cell Death ◽  
Combination Therapy ◽  
Functional Recovery ◽  
Therapy Group ◽  
Neuronal Cell ◽  
Cresyl Violet ◽  
Treatment Groups ◽  
Cresyl Violet Staining ◽  
All Treatment

Abstract In the current research, neuroprotection and performance improvement have been investigated in MCAO animal model treated with exosomes combined with rt-PA. Middle cerebral artery occlusion (MCAO) was induced in 25 adult male Wistar rats. Rats received rt-PA with a dose of 100 µg/kg in a single dose or drived-exosome from bone marrow MSCs. The Garcia scoring system and elevated body test were employed as behavioral tests for the functional recovery assessment. Cresyl violet staining was applied to evaluate the cell death degree in brain tissues. Immunohistochemical analysis was performed for the detection of GFAP and IBA1-positive cells. Results Cresyl violet staining revealed that the population of dark cells was significantly reduced in all treatment groups. A considerable increase (P ≤ 0.05) in catalase enzyme was observed in the combination therapy group compared whit the MCAO group (P ≤ 0.05). The amount of GPX despite the increase in all treatment groups compared to MCAO group was not statistically significant (P ≥ 0.05). Our conclusion was approved by the Nlrp1 and Nlrp3 downregulation during combination therapy in MCAO model by reduction in cell death rate. The Density of GFAP-positive cells Showed a decrease in the exosome with or without rt-PA experimental groups in comparison with the MCAO group (P < 0.05). Our observation indicated that exosomes, in combination with rt-PA, resulted in the noticeable functional recovery, neuronal regeneration, and reduction of neuronal cell death after a 7-day period of the MCAO induction. This novel therapeutic strategy could provide a better treatment option for those patients suffered from stroke.

scholarly journals Polycationic Peptides as Prophylactic Agents against Methicillin-Susceptible or Methicillin-Resistant Staphylococcus epidermidis Vascular Graft Infection

2000 ◽  
Vol 44 (12) ◽  
pp. 3306-3309 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Luigi Goffi ◽  
Federico Mocchegiani ◽  
...  
Keyword(s):  
Rat Model ◽  
Staphylococcus Epidermidis ◽  
Subcutaneous Tissue ◽  
Bacterial Species ◽  
Graft Infection ◽  
Prosthetic Graft ◽  
Control Group ◽  
Vascular Graft Infection ◽  
Agar Culture ◽  
Methicillin Resistant

ABSTRACT Several polycationic peptides isolated from animals, plants, and bacterial species possess a broad spectrum of antimicrobial activity. A rat model was used to investigate the efficacies of two peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infections. The effect of peptide-soaked collagen-sealed Dacron was compared to that of rifampin-soaked collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible rifampin-susceptible Staphylococcus epidermidis and methicillin-resistant rifampin-susceptible S. epidermidis. Graft infections were established in the back subcutaneous tissue of 240 adult male Wistar rats by implantation of 1-cm2 Dacron prostheses, followed by topical inoculation with 2 × 107 CFU of S. epidermidis. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups to which perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg of body weight) was administered, six contaminated groups that received a peptide- or rifampin-soaked graft, and six contaminated groups that received a peptide- or rifampin-soaked graft and perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Overall, the efficacies of the polycationic peptides against the methicillin-susceptible and methicillin-resistant strains were not significantly different from that of rifampin. Nevertheless, the combinations of ranalexin- and buforin II-coated grafts with cefazolin treatment demonstrated efficacies significantly higher than that of the combination of rifampin-coated grafts and cefazolin treatment against the methicillin-resistant strain.

scholarly journals Activity of Tedizolid in Methicillin-Resistant Staphylococcus aureus Experimental Foreign Body-Associated Osteomyelitis

2016 ◽  
Vol 60 (11) ◽  
pp. 6568-6572 ◽  
Author(s):  
Kyung-Hwa Park ◽  
Kerryl E. Greenwood-Quaintance ◽  
Jayawant Mandrekar ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Rat Model ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
Methicillin Resistant ◽  
Trough Concentrations ◽  
Rifampin Resistance

ABSTRACTWe compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistantStaphylococcus aureus(MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n= 14), tedizolid plus rifampin (n= 11), rifampin (n= 16), or vancomycin plus rifampin (n= 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.

scholarly journals Activity of Omadacycline in Rat Methicillin-Resistant Staphylococcus aureus Osteomyelitis

2021 ◽  
Author(s):  
Melissa J. Karau ◽  
Suzannah M. Schmidt-Malan ◽  
Scott A. Cunningham ◽  
Jayawant N. Mandrekar ◽  
Bobbi S. Pritt ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bacterial Load ◽  
Potential Treatment ◽  
Combination Therapies ◽  
Treatment Groups ◽  
Experimental Rat Model ◽  
Rifampin Resistance ◽  
All Treatment

Omadacycline, vancomycin and rifampin as well as rifampin combination therapies were evaluated in an experimental rat model of MRSA osteomyelitis. All treatment groups had less MRSA recovered than saline-treated animals. Emergence of rifampin resistance was observed in 3 of 16 animals with rifampin monotherapy, and none with rifampin combination therapy. After treatment, the median tibial bacterial load was 6.04, 0.1, 4.81 and 5.24 log 10 cfu/g for saline-, rifampin-, vancomycin- and omadacycline-treated animals. Omadacycline or vancomycin administered with rifampin yielded no detectable MRSA. Omadacycline, administered with rifampin, deserves evaluation in humans as a potential treatment for osteomyelitis.

scholarly journals Metabolic Activity of Staphylococcus epidermidis Is High during Initial and Low during Late Experimental Foreign-Body Infection

2004 ◽  
Vol 186 (8) ◽  
pp. 2236-2239 ◽  
Author(s):  
Stefaan Johan Vandecasteele ◽  
Willy Eduard Peetermans ◽  
An Carbonez ◽  
Johan Van Eldere
Keyword(s):  
Foreign Body ◽  
16S Rrna ◽  
Antibiotic Treatment ◽  
Metabolic Activity ◽  
Rat Model ◽  
Staphylococcus Epidermidis ◽  
Exponential Growth Phase ◽  
Active Process

ABSTRACT Foreign-body infection (FBI) is notoriously resistant to eradication by antibiotic treatment. It is hypothesized that reduced bacterial metabolic activity contributes to this resistance. We examined the metabolic activity of Staphylococcus epidermidis in 204 samples recovered during in vitro foreign-body colonization and in 424 samples recovered during in vivo FBI in a rat model. Metabolic activity was measured by determining the amount of 16S rRNA per genome by quantitative PCR. The initial foreign-body-associated growth proved to be a metabolically active process, both in vitro and in vivo. The initial 16S rRNA content was similar to that observed during in vitro exponential-growth phase. However, during late in vivo FBI, a 114-fold (P ≪ 0.0001) decrease in the 16S rRNA content was observed, indicating that there was markedly decreased metabolic activity. This decreased metabolic activity during late FBI can explain at least in part why such infections are so difficult to eradicate with conventional antibiotic treatment.

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