Archive for September 24, 2014

Alternative Screening Approaches for Discovery of Middle East Respiratory Syndrome Coronavirus Inhibitors

Antimicrobial Agents and Chemotherapy AUG  2014 V.58 N.8 P.4251-4252

Robert L. LaFemina

Editor, Antimicrobial Agents and Chemotherapy, Schwenksville, Pennsylvania, USA

Two coronaviruses causing severe respiratory disease and high mortality rates emerging within the past dozen years reinforces the need for clinically efficacious antivirals targeting coronaviruses.

Alternative screening approaches for antivirals against the recently emergent Middle East respiratory syndrome coronavirus (MERS-CoV) may provide lead compounds to address this need.

Two Antimicrobial Agents and Chemotherapy (AAC) papers screened libraries of approved compounds that may potentially be repurposed as MERS-CoV antivirals.

A third AAC paper showed that a previously described severe acute respiratory syndrome coronavirus (SARS-CoV) helicase inhibitor also has activity against MERS-CoV.

PDF

http://aac.asm.org/content/58/8/4251.full.pdf+html

September 24, 2014 at 8:16 pm

Effectiveness of Antimicrobial Peptide Immobilization for Preventing Perioperative Cornea Implant-Associated Bacterial Infection

Antimicrobial Agents and Chemotherapy Sept 2014 V.58 N.9 P.5229-5238

Xiao Wei Tana, Tze Wei Goha, P. Saraswathib, Chan Lwin Nyeina, Melina Setiawana, Andri Riaua, R. Lakshminarayananb,e, Shouping Liub,e, Donald Tanc,d,e, Roger W. Beuermanb,c,f and Jodhbir S. Mehtaa,b,d,e

aTissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore

bAntimicrobials Group, Singapore Eye Research Institute, Singapore

cYong Loo Lin School of Medicine, National University of Singapore, Singapore

dSingapore National Eye Centre, Singapore

eDuke-NUS Graduate Medical School, Singapore

fDuke-NUS SRP Neuroscience and Behavioral Disorders, Singapore

Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization may improve the bactericidal effect of the Ti substrate.

In this study, we tested the bactericidal efficacy of a functionalized Ti surface in a rabbit keratitis model. A corneal stromal pocket was created by a femtosecond laser.

The Ti films were then inserted into the pocket, and Staphylococcus aureus or Pseudomonas aeruginosa was inoculated into the pocket above the implant films.

The corneas with Ti-AMP implants were compared with the corneas implanted with unprotected Ti by slit lamp observation and anterior segment optical coherence tomography (AS-OCT). Inflammatory responses were evaluated by bacterium counting, hematoxylin-eosin staining, and immunostaining.

There was a lower incidence and a lesser extent of infection on rabbit corneas with Ti-AMP implants than on those with unprotected Ti implants.

The bactericidal effect of AMP against S. aureus was comparable to that of postoperative prophylactic antibiotic treatment; hence, SESB2V AMP bound to the Ti implant provided functional activity in vivo, but its efficacy was greater against S. aureus than against P. aeruginosa.

This work suggests that SESB2V AMP can be successfully functionalized in a rabbit keratitis model to prevent perioperative corneal infection.

PDF

http://aac.asm.org/content/58/9/5229.full.pdf+html

September 24, 2014 at 8:14 pm

Revised Reference Broth Microdilution Method for Testing Telavancin: Effect on MIC Results and Correlation with Other Testing Methodologies

Antimicrobial Agents and Chemotherapy Sept 2014 V.58 N.9 P.5547-5551

David J. Farrell, Rodrigo E. Mendes, Paul R. Rhomberg and Ronald N. Jones

JMI Laboratories, North Liberty, Iowa, USA

The reference broth microdilution (BMD) antimicrobial susceptibility testing method for telavancin was revised to include dimethyl sulfoxide (DMSO) as a solvent and diluent for frozen-form panel preparation, following the CLSI recommendations for water-insoluble agents.

Polysorbate 80 (P-80) was also added to the test medium to minimize proven drug losses associated with binding to plastic surfaces.

Four hundred sixty-two Gram-positive isolates, including a challenge set of organisms with reduced susceptibilities to comparator agents, were selected and tested using the revised method for telavancin, and the MIC results were compared with those tested by the previously established method and several Sensititre dry-form BMD panel formulations.

The revised method provided MIC results 2- to 8-fold lower than the previous method when tested against staphylococci and enterococci, resulting in MIC50 values of 0.03 to 0.06 μg/ml for staphylococci and 0.03 and 0.12 μg/ml for Enterococcus faecium and Enterococcus faecalis, respectively.

Less-significant MIC decreases (1 to 2 log2 dilution steps) were observed when testing streptococci in broth supplemented with blood, which showed similar MIC50 values for both methods.

However, Streptococcus pneumoniae had MIC50 results of 0.008 and 0.03 μg/ml when tested by the revised and previous methods, respectively.

Highest essential agreement rates (≥94.0%) were noted for one candidate dry-form panel formulation compared to the revised test. The revised BMD method provides lower MIC results for telavancin, especially when tested against staphylococci and enterococci.

This is secondary to the use of DMSO for panel production and the presence of P-80, which ensure the proper telavancin testing concentration and result in a more accurate MIC determination.

Moreover, earlier studies where the previous method was applied underestimated the in vitro drug potency.

PDF

http://aac.asm.org/content/58/9/5547.full.pdf+html

September 24, 2014 at 8:12 pm


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