tedizolid-phosphate and Pneumonia--Staphylococcal

tedizolid-phosphate has been researched along with Pneumonia--Staphylococcal* in 3 studies

Reviews

1 review(s) available for tedizolid-phosphate and Pneumonia--Staphylococcal

ArticleYear
Use of pharmacokinetic/pharmacodynamic systems analyses to inform dose selection of tedizolid phosphate.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014, Volume: 58 Suppl 1

    In the Staphylococcus aureus neutropenic murine thigh-infection model, the ratio of the free area under the 24-hour concentration-time curve to the minimum inhibitory concentration (fAUC/MIC) was found to be the pharmacodynamic index most closely linked to bacterial effect, with a ratio of approximately 50 producing a static effect. Further work was undertaken in neutropenic versus non-neutropenic animals. The presence of granulocytes increased the activity of tedizolid considerably, 25-fold on average, and maximal effect was achieved at an exposure equivalent to approximately 200 mg tedizolid phosphate per day in humans (dosing regimen used in phase 2 and 3 clinical trials). The fAUC/MIC was also found to be the pharmacodynamically linked variable in the S. aureus neutropenic murine pneumonia model; the fAUC/MIC ratio required for a static effect was approximately 20. Pharmacokinetic (PK) data demonstrate that tedizolid penetrates well into the epithelial lining fluid (ELF) of the lung. Data from the pneumonia infection model and ELF penetration PK study support exploring its use in pneumonia.

    Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Disease Models, Animal; Humans; Microbial Sensitivity Tests; Organophosphates; Oxazoles; Pneumonia, Staphylococcal; Staphylococcal Skin Infections; Staphylococcus aureus

2014

Other Studies

2 other study(ies) available for tedizolid-phosphate and Pneumonia--Staphylococcal

ArticleYear
Antimicrobial and immunomodulatory effects of tedizolid against methicillin-resistant Staphylococcus aureus in a murine model of hematogenous pulmonary infection.
    International journal of medical microbiology : IJMM, 2016, Volume: 306, Issue:6

    Tedizolid (TZD) is a second-generation oxazolidinone and demonstrates potent in-vitro activity against multidrug-resistant Gram-positive bacteria. Phase III studies in patients with acute bacterial skin and skin structure infections (ABSSSI) have demonstrated the non-inferiority of TZD to linezolid (LZD). However, there are only a few studies that show the effect of TZD in pulmonary infections. In this study, we investigated the effect of TZD in a murine model of hematogenous pulmonary infection caused by methicillin-resistant Staphylococcus aureus (MRSA). The mice were treated either twice daily with saline (control), 25mg/kg of vancomycin (low-VAN), 110mg/kg of vancomycin (high-VAN), 120mg/kg of LZD or once daily with 20mg/kg of TZD. As compared to the control, the low- and high-VAN treatment groups, LZD and TZD significantly improved the survival rate, reduced the bacterial count in the lungs. Furthermore, TZD decreased the area of central bacterial colony zone (CBCZ) at 36h post-inoculation, compared with the control. In addition, we investigated the immunomodulatory effect of TZD by evaluating the plasma concentrations of the inflammatory cytokines. Although there were no significant differences in the bacterial count in the lungs amongst the drugs at 26h post-inoculation, TZD and LZD significantly improved the plasma concentrations of TNF-alpha, IL-6 and MIP-2, in comparison with the control. In this study, both TZD and LZD demonstrated antimicrobial and immunomodulatory efficacy in a murine model of hematogenous pulmonary infection caused by MRSA.

    Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Cytokines; Disease Models, Animal; Immunologic Factors; Lung; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Organophosphates; Oxazoles; Plasma; Pneumonia, Staphylococcal; Survival Analysis; Treatment Outcome

2016
Comparative pharmacodynamics of the new oxazolidinone tedizolid phosphate and linezolid in a neutropenic murine Staphylococcus aureus pneumonia model.
    Antimicrobial agents and chemotherapy, 2012, Volume: 56, Issue:11

    Tedizolid phosphate (TR-701) is a novel oxazolidinone prodrug (converted to the active form tedizolid [TR-700]) with potent Staphylococcus aureus activity. The current studies characterized and compared the in vivo pharmacokinetic/pharmacodynamic (PD) characteristics of TR-701/TR-700 and linezolid against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in the neutropenic murine pneumonia model. The pharmacokinetic properties of both drugs were linear over a dose range of 0.625 to 40 mg/kg of body weight. Protein binding was 30% for linezolid and 85% for TR-700. Mice were infected with one of 11 isolates of S. aureus, including MSSA and community- and hospital-acquired MRSA strains. Each drug was administered by oral-gastric gavage every 12 h (q12h). The dosing regimens ranged from 1.25 to 80 mg/kg/12 h for linezolid and 0.625 to 160 mg/kg/12 h for TR-701. At the start of therapy, mice had 6.24 ± 0.40 log(10) CFU/lungs, which increased to 7.92 ± 1.02 log(10) CFU/lungs in untreated animals over a 24-h period. A sigmoid maximum-effect (E(max)) model was used to determine the antimicrobial exposure associated with net stasis (static dose [SD]) and 1-log-unit reduction in organism relative to the burden at the start of therapy. The static dose pharmacodynamic targets for linezolid and TR-700 were nearly identical, at a free drug (non-protein-bound) area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) of 19 and 20, respectively. The 1-log-unit kill endpoints were also similar, at 46.1 for linezolid and 34.6 for TR-700. The exposure targets were also comparable for both MSSA and MRSA isolates. These dosing goals support further clinical trial examination of TR-701 in MSSA and MRSA pneumonia.

    Topics: Acetamides; Administration, Oral; Animals; Anti-Bacterial Agents; Area Under Curve; Blood Proteins; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Linezolid; Lung; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Organophosphates; Oxazoles; Oxazolidinones; Pneumonia, Staphylococcal; Prodrugs; Protein Binding; Staphylococcus aureus

2012