- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Pharmaceutical and Antibiotic Environmental Impacts
- Antimicrobial Resistance in Staphylococcus
- Antibiotic Use and Resistance
- Bacterial Identification and Susceptibility Testing
- Pneumonia and Respiratory Infections
- Bacterial biofilms and quorum sensing
- Cancer therapeutics and mechanisms
- Vibrio bacteria research studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Malaria Research and Control
- Diabetic Foot Ulcer Assessment and Management
- Synthesis and Biological Evaluation
- Bacteriophages and microbial interactions
- Wound Healing and Treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Complementary and Alternative Medicine Studies
- bioluminescence and chemiluminescence research
- Neutropenia and Cancer Infections
- Antimicrobial Peptides and Activities
- Synthesis and Catalytic Reactions
- Drug-Induced Adverse Reactions
- Pressure Ulcer Prevention and Management
- Tuberculosis Research and Epidemiology
California Northstate University
2016-2024
University at Buffalo, State University of New York
2014-2017
Center for Excellence in Education
2015
ABSTRACT Acinetobacter baumannii is emerging with resistance to polymyxins. In 24-h time-kill experiments, high-dose ampicillin-sulbactam in combination meropenem and polymyxin B achieved additivity or synergy against 10 8 CFU/ml of two clinical A. isolates resistant all three drugs (maximum reductions, 1.6 3.1 logs). a 14-day hollow-fiber infection model, (8/4 g every h, respectively) (2 h) (1.43 mg/kg body weight 12 h loading dose) resulted rapid (96 eradication .
Objectives: The emergence of polymyxin resistance threatens to leave clinicians with few options for combatting drug-resistant Acinetobacter baumannii. objectives the current investigation were define in vitro and identify a combination regimen capable eradicating A. baumannii no apparent drug susceptibilities. Methods: Two clonally related, paired, isolates collected from critically ill patient who developed colistin while receiving methanesulfonate clinical population pharmacokinetic study...
Administering polymyxin antibiotics in a traditional fashion may be ineffective against Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Here, we explored increasing the dose intensity of B two strains baumannii hollow-fiber infection model. The following dosage regimens were simulated for (t1/2 = 8 h): non-loading (1.43 mg/kg body weight every 12 h [q12h]), loading...
KPC-producing Klebsiella pneumoniae are an emerging public health problem around the globe. We defined combinatorial pharmacodynamics and ability to suppress resistance of two 'old' antibiotics, fosfomycin colistin, in time-kill experiments hollow-fibre infection models (HFIM).
The pharmacodynamics of polymyxin/carbapenem combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) are largely unknown. Our objective was to determine whether intensified meropenem regimens in combination with polymyxin B enhance killing and resistance suppression CRAB.Time-kill experiments for were conducted three B-susceptible (MIC = 0.5 mg/L) CRAB strains varying MICs (ATCC 19606, N16870 03-149-1; MIC 4, 16 64 mg/L, respectively) at 108 cfu/mL. A hollow-fibre infection...
Polymyxin combination therapy is increasingly used clinically. However, systematic investigations of such combinations are a relatively recent phenomenon. The emerging pharmacodynamic (PD) and pharmacokinetic (PK) data on CMS/colistin polymyxin B suggest that caution required with monotherapy. Given this situation, has been suggested as possible way to increase bacterial killing reduce the development resistance. Considerable in vitro have generated support view, particularly studies...
The manuscripts contained in this special edition of Antibiotics represent a current review the polymyxins as well highlights from 3rd International Polymyxin Conference, which was held Madrid, Spain, 25 to 26 April 2018. role polymyxin antibiotics has evolved over time based on availability alternative agents. After high rates nephrotoxicity caused drug class fall out favor, were once against utilized 21st century combat drug-resistant pathogens. However, introduction safer agents with...
We sought to determine if Acinetobacter baumannii is capable of altering the pharmacodynamics an antistaphylococcal β-lactam. Two strains methicillin-susceptible Staphylococcus aureus (MSSA) and two A. isolates were studied in 24-h static time-killing experiments under monoculture or coculture conditions. Bacterial killing meropenem was described using empirical pharmacokinetics/pharmacodynamics model that developed Hill functions. A mechanism-based pharmacodynamic also used describe effect...
Combining the hybridization and repurposing strategies, six compounds from our in-house library having a designed hybrid structure of MBX-1162, pentamidine MMV688271 were repurposed as potential antibacterial agents. Among,
Staphylococcus aureus small-colony variants (SCVs) often persist despite antibiotic therapy. Against a 10(8)-CFU/ml methicillin-resistant S. (MRSA) (strain COL) population of which 0%, 1%, 10%, 50%, or 100% was an isogenic hemB knockout (Ia48) subpopulation displaying the SCV phenotype, vancomycin achieved maximal reductions 4.99, 5.39, 4.50, 3.28, and 1.66 log10 CFU/ml over 48 h. Vancomycin at ≥16 mg/liter shifted from 50% cells 0 h to h, well characterized by Hill-type model (R2>0.90).
Staphylococcus aureus possesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined vitro evolution S. response escalating vancomycin exposure by evaluating bacterial killing progression resistance. A hollow-fiber infection model was utilized simulate human doses increasing from 0.5 4 g every 12 h (q12h) versus high inoculum (10(8) CFU/ml) methicillin-resistant (MRSA) USA300 USA400. Host-pathogen interactions using Galleria mellonella...
The impact of quorum sensing on polymyxin and azithromycin pharmacodynamics was assessed in Pseudomonas aeruginosa PAO1 an isogenic rhlR/lasR double knockout. For B, greater killing against the knockout than observed at 108 CFU/ml (polymyxin B half-maximal effective concentration [EC50], 5.61 versus 12.5 mg/liter, respectively; P < 0.005). Polymyxin combined with (256 mg/liter) synergistic each strain, significantly reducing respective EC50 compared to those monotherapy (P 0.005), is a...
The optimal selection of antibacterials during polymicrobial infections is poorly defined. objective the current investigation was to quantify pharmacodynamics relevant antimicrobials co-culture Pseudomonas aeruginosa with two separate Staphylococcus aureus phenotypes.Time-kill experiments were conducted against co-cultures P. strain PA01 paired either normal phenotype (NP) MRSA isolate COL or small colony variant (SCVP) Ia48. killing by levofloxacin, gentamicin, clindamycin, vancomycin and...
The continuing need for the discovery of potent antibacterial agents against antibiotic-resistant pathogens is driving force many researchers to design and develop such agents. Herein, we report design, synthesis, biological evaluation amidine derivatives as new Compound 13d was most active in this study a wide range antibiotic-resistant, susceptible, Gram-positive, Gram-negative bacterial strains. Time–kill assay experiments indicated that compound an effective bactericidal tested organisms...
ABSTRACT Despite a dearth of new agents currently being developed to combat multidrug-resistant Gram-negative pathogens, the combination ceftolozane and tazobactam was recently approved by Food Drug Administration treat complicated intra-abdominal urinary tract infections. To characterize activity product, time-kill studies were conducted against 4 strains Escherichia coli that differed in type β-lactamase they expressed. The four investigational included 2805 (no β-lactamase), 2890 (AmpC...
Enterococcus faecalis commonly produce aminoglycoside-modifying enzymes (AMEs) and are implicated in polymicrobial infections.To determine if AME-producing E. is capable of protecting Enterobacteriaceae Pseudomonas aeruginosa from gentamicin exposure.Two Klebsiella pneumoniae isolates, two Escherichia coli isolates were investigated monoculture time-kill experiments, each Gram-negative organism was also evaluated during co-culture with either or AME-deficient faecalis. A...
Our objective was to study the pharmacodynamics of daptomycin in presence varying concentrations human serum (HS) vitro quantify fraction that is 'active'. Time kill experiments were performed with (0 256 mg/L) against two MRSA strains at log-phase growth, HS (0%, 10%, 30%, 50%, 70%) combined Mueller-Hinton broth. Daptomycin ≥ 2 mg/L achieved 99.9% within 8 h all concentrations; early killing activity slightly attenuated higher concentrations. After 1 h, bacterial reduction USA300 upon...