Pharmacodynamic Evaluation of Omadacycline against Staphylococcus aureus in the Neutropenic Mouse Pneumonia Model.

Omadacycline is an effective therapy for community-acquired bacterial pneumonia (CABP). Given its potent activity against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA), we sought to determine the pharmacodynamic activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with a therapeutic effect in the neutropenic mouse pneumonia model against 10 MSSA/MRSA strains. The area under the concentration-time curve (AUC)/MIC associated with 1-log kill was noted at 24-h epithelial lining fluid (ELF) and plasma AUC/MIC exposures of ∼2 (ELF range, <0.

Pharmacodynamics of Omadacycline against Staphylococcus aureus in the Neutropenic Murine Thigh Infection Model.

Omadacycline is a novel aminomethylcycline antibiotic with potent activity against , including methicillin-susceptible (MSSA) and methicillin-resistant (MRSA). We investigated the pharmacodynamic activity of omadacycline against 10 MSSA/MRSA strains in a neutropenic murine thigh model. The median 24-h area under the concentration-time curve (AUC)/MIC values associated with net stasis and 1-log kill were 21.

APX001 Pharmacokinetic/Pharmacodynamic Target Determination against in an Model of Invasive Pulmonary Aspergillosis.

APX001, the prodrug of APX001A, is a first-in-class antifungal agent that has a potent activity against The goal of current study was to determine the pharmacodynamic (PD) index and target of APX001 in an immunocompromised murine model of invasive pulmonary aspergillosis against 6  isolates. Minimum effective concentration (MEC) values ranged from 0.03 to 0.

Pharmacodynamic Characterization of a Novel Odilorhabdin Antibiotic, NOSO-502, against Escherichia coli and Klebsiella pneumoniae in a Murine Thigh Infection Model.

NOSO-502 is a novel odilorhabdin antibiotic with potent activity against The goal of these studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) indices and magnitude best correlated with efficacy in the murine thigh infection model. Six and 6 isolates were utilized. MICs were determined using CLSI methods and ranged from 1 to 4 mg/liter.

Pharmacokinetics and Pharmacodynamics of APX001 against Candida spp. in a Neutropenic Disseminated Candidiasis Mouse Model.

APX001 is the prodrug of APX001A, which is a first-in-class small molecule with a unique mechanism of action that inhibits the fungal enzyme Gwt1 in the glycosylphosphatidylinositol (GPI) biosynthesis pathway. The goal of the present study was to determine which pharmacokinetic/pharmacodynamic (PK/PD) index and magnitude best correlated with efficacy in the murine disseminated candidiasis model for ( = 5), ( = 5), and ( = 4). MIC values ranged from 0.

Pharmacodynamic Target Assessment of Eravacycline against Escherichia coli in a Murine Thigh Infection Model.

Eravacycline is a novel fluorocycline antibiotic with potent activity against a broad range of pathogens, including strains with tetracycline and other drug resistance phenotypes. The goal of the studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter and magnitude best correlated with efficacy in the murine thigh infection model. Six isolates were utilized for the studies.

Pharmacodynamic Evaluation of Omadacycline (PTK 0796) against Streptococcus pneumoniae in the Murine Pneumonia Model.

Omadacycline is a novel aminomethylcycline antibiotic in clinical development for community-acquired bacterial pneumonia (CABP). We used a neutropenic murine pneumonia infection model to characterize the pharmacodynamic activity of omadacycline against Four strains with various phenotypic resistances to other antimicrobials, including tetracyclines, were utilized. Drug concentration measurements were performed in the plasma and epithelial lining fluid (ELF) after administration of 0.

In Vivo Pharmacodynamic Evaluation of an FtsZ Inhibitor, TXA-709, and Its Active Metabolite, TXA-707, in a Murine Neutropenic Thigh Infection Model.

Antibiotics with novel mechanisms of action are urgently needed. Processes of cellular division are attractive targets for new drug development. FtsZ, an integral protein involved in cell cytokinesis, is a representative example.

Isavuconazole (BAL4815) pharmacodynamic target determination in an in vivo murine model of invasive pulmonary aspergillosis against wild-type and cyp51 mutant isolates of Aspergillus fumigatus.

Invasive pulmonary aspergillosis (IPA) continues to rise in concert with increasing numbers of immune suppression techniques to treat other medical conditions and transplantation. Despite these advances, morbidity and mortality rates remain unacceptably high. One strategy used to optimize outcomes is antifungal pharmacodynamic (PD) examination.

Isavuconazole pharmacodynamic target determination for Candida species in an in vivo murine disseminated candidiasis model.

Pharmacodynamic (PD) studies with triazoles in the neutropenic murine disseminated candidiasis model have been performed extensively for Candida albicans. They have consistently shown that the pharmacodynamic index most closely correlated with efficacy is the ratio of the 24-h area under the concentration-time curve (AUC) to the MIC, and a target 24-h free-drug AUC/MIC ratio near 25 is associated with 50% of maximal microbiologic efficacy. We utilized this model to investigate the pharmacodynamics of isavuconazole.

Impact of in vivo triazole and echinocandin combination therapy for invasive pulmonary aspergillosis: enhanced efficacy against Cyp51 mutant isolates.

Previous studies examining combination therapy for invasive pulmonary aspergillosis (IPA) have revealed conflicting results, including antagonism, indifference, and enhanced effects. The most commonly employed combination for this infection includes a mold-active triazole and echinocandin. Few studies have evaluated combination therapy from a pharmacodynamic (PD) perspective, and even fewer have examined combination therapy against both wild-type and azole-resistant Cyp51 mutant isolates.