Michael Vicchiarelli
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View article: Evaluation of a potent LpxC inhibitor for post-exposure prophylaxis treatment of antibiotic-resistant <i>Burkholderia pseudomallei</i> in a murine infection model
Evaluation of a potent LpxC inhibitor for post-exposure prophylaxis treatment of antibiotic-resistant <i>Burkholderia pseudomallei</i> in a murine infection model Open
LPC-233 (a.k.a. VB-233) is a potent antibiotic targeting the essential enzyme LpxC in Gram-negative bacteria. We present herein the pharmacokinetics and pharmacodynamics data of LPC-233 for treating murine infections caused by Burkholderia…
View article: Population pharmacokinetics and humanized dosage regimens matching the peak, area, trough, and range of amikacin plasma concentrations in immune-competent murine bloodstream and lung infection models
Population pharmacokinetics and humanized dosage regimens matching the peak, area, trough, and range of amikacin plasma concentrations in immune-competent murine bloodstream and lung infection models Open
Amikacin is an FDA-approved aminoglycoside antibiotic that is commonly used. However, validated dosage regimens that achieve clinically relevant exposure profiles in mice are lacking. We aimed to design and validate humanized dosage regime…
View article: Individual Components of Polymyxin B Modeled via Population Pharmacokinetics to Design Humanized Dosage Regimens for a Bloodstream and Lung Infection Model in Immune-Competent Mice
Individual Components of Polymyxin B Modeled via Population Pharmacokinetics to Design Humanized Dosage Regimens for a Bloodstream and Lung Infection Model in Immune-Competent Mice Open
Polymyxin B is a “last-line-of-defense” antibiotic approved in the 1960s. However, the population pharmacokinetics (PK) of its four main components has not been reported in infected mice. We aimed to determine the PK of polymyxin B1, B1-Il…
View article: Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get
Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get Open
Dose range studies for polymyxin B (PMB) regimens of 0.75 to 12 mg/kg given every 12 h (q12h) were evaluated for bacterial killing and resistance prevention against an AmpC-overexpressing Pseudomonas aeruginosa and a bla KPC-3 -harboring K…
View article: Emergence of Resistance to Ceftazidime-Avibactam in a Pseudomonas aeruginosa Isolate Producing Derepressed <i>bla</i> <sub>PDC</sub> in a Hollow-Fiber Infection Model
Emergence of Resistance to Ceftazidime-Avibactam in a Pseudomonas aeruginosa Isolate Producing Derepressed <i>bla</i> <sub>PDC</sub> in a Hollow-Fiber Infection Model Open
Ceftazidime (CAZ)-avibactam (AVI) is a β-lactam/β-lactamase inhibitor combination with activity against type A and type C β-lactamases. Resistance emergence has been seen, with multiple mechanisms accounting for the resistance. We performe…
View article: Developing New Drugs for Mycobacterium tuberculosis Therapy: What Information Do We Get from Preclinical Animal Models?
Developing New Drugs for Mycobacterium tuberculosis Therapy: What Information Do We Get from Preclinical Animal Models? Open
Preclinical animal models of infection are employed to develop new agents but also to screen among molecules to rank them. There are often major differences between human pharmacokinetic (PK) profiles and those developed by animal models o…
View article: The Combination of Fosfomycin plus Meropenem Is Synergistic for Pseudomonas aeruginosa PAO1 in a Hollow-Fiber Infection Model
The Combination of Fosfomycin plus Meropenem Is Synergistic for Pseudomonas aeruginosa PAO1 in a Hollow-Fiber Infection Model Open
Treating high-density bacterial infections is a challenging clinical problem. We have a paucity of new agents that can address this problem.
View article: Clinical Regimens of Favipiravir Inhibit Zika Virus Replication in the Hollow-Fiber Infection Model
Clinical Regimens of Favipiravir Inhibit Zika Virus Replication in the Hollow-Fiber Infection Model Open
Zika virus (ZIKV) infection is associated with serious, long-term neurological manifestations. There are currently no approved therapies for the treatment or prevention of ZIKV infection.
View article: Utility of a Novel Three-Dimensional and Dynamic (3DD) Cell Culture System for PK/PD Studies: Evaluation of a Triple Combination Therapy at Overcoming Anti-HER2 Treatment Resistance in Breast Cancer
Utility of a Novel Three-Dimensional and Dynamic (3DD) Cell Culture System for PK/PD Studies: Evaluation of a Triple Combination Therapy at Overcoming Anti-HER2 Treatment Resistance in Breast Cancer Open
Background: Emergence of Human epidermal growth factor receptor 2 (HER2) therapy resistance in HER2-positive (HER2+) breast cancer (BC) poses a major clinical challenge. Mechanisms of resistance include the over-activation of the PI3K/mTOR…
View article: Erratum for Drusano et al., “Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia”
Erratum for Drusano et al., “Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia” Open
View article: Determination of the Dynamically Linked Indices of Fosfomycin for Pseudomonas aeruginosa in the Hollow Fiber Infection Model
Determination of the Dynamically Linked Indices of Fosfomycin for Pseudomonas aeruginosa in the Hollow Fiber Infection Model Open
Fosfomycin is the only expoxide antimicrobial and is currently under development in the United States as an intravenously administered product. We were interested in identifying the exposure indices most closely linked to its ability to ki…
View article: Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia
Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia Open
Ventilator-associated bacterial pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent guidelines of the Infectious Diseases Society of America an…
View article: Fosfomycin (FOS) Plus Meropenem (MER) Suppresses Resistance Emergence Against P. aeruginosa (PA) PAO1 in the Hollow Fiber Infection Model (HFIM)
Fosfomycin (FOS) Plus Meropenem (MER) Suppresses Resistance Emergence Against P. aeruginosa (PA) PAO1 in the Hollow Fiber Infection Model (HFIM) Open
FOS (ZTI-01, fosfomycin for injection) is an epoxide antibiotic that covalently binds MurA, an earlier step in cell wall synthesis inhibition. FOS has demonstrated synergistic killing with other classes of agents, including carbapenems. PA…