scholarly journals In Vitro Activity of Expanded-Spectrum Pyridazinyl Oxime Ethers Related to Pirodavir: Novel Capsid-Binding Inhibitors with Potent Antipicornavirus Activity

2004 ◽  
Vol 48 (5) ◽  
pp. 1766-1772 ◽  
Author(s):  
D. L. Barnard ◽  
V. D. Hubbard ◽  
D. F. Smee ◽  
R. W. Sidwell ◽  
K. G. W. Watson ◽  
...  
Keyword(s):  
Common Cold ◽  
The United States ◽  
Neutral Red ◽  
In Vitro Activity ◽  
Oral Agent ◽  
Uptake Assay ◽  
The Common ◽  
Orally Bioavailable ◽  
Neutral Red Uptake Assay

ABSTRACT Picornaviruses (PV) include human rhinovirus (HRV), the primary cause of the common cold, and the enteroviruses (EV), which cause serious diseases such as poliomyelitis, meningoencephalitis, and systemic neonatal disease. Although no compounds for PV infections have been approved in the United States, pirodavir was one of the most promising capsid-binding compounds to show efficacy in human clinical trials for chemoprophylaxis of the common cold. Susceptibility to hydrolysis precluded its use as an oral agent. We have developed orally bioavailable pyridazinyl oxime ethers that are as potent as pirodavir. Compounds BTA39 and BTA188 inhibited a total of 56 HRV laboratory strains and three clinical isolates as determined by neutral red uptake assay. At concentrations of <100 nM, BTA39 inhibited 69% of the HRV serotypes and isolates evaluated, BTA188 inhibited 75%, and pirodavir inhibited 59% of the serotypes and isolates. The 50% inhibitory concentrations (IC50s) for the two compounds ranged from 0.5 nM to 6,701 nM. The compounds also inhibited EV, including coxsackie A and B viruses (IC50 = 773 to 3,608 nM) and echoviruses (IC50 = 193 to 5,155 nM). BTA39 only inhibited poliovirus strain WM-1 at 204 nM, and BTA188 only inhibited poliovirus strain Chat at 82 nM. EV 71 was inhibited by BTA39 and BTA188, with IC50s of 1 and 82 nM, respectively. Both compounds were relatively nontoxic in actively growing cells (50% cytotoxic doses, ≥4,588 nM). These data suggest that these oxime ethers warrant further investigation as potential agents for treating selected PV infections.

scholarly journals Evaluation of Cytotoxicity and Genotoxicity ofAcacia aromaLeaf Extracts

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
C. M. Mattana ◽  
M. A. Cangiano ◽  
L. E. Alcaráz ◽  
A. Sosa ◽  
F. Escobar ◽  
...  
Keyword(s):  
Ethanolic Extract ◽  
Neutral Red ◽  
Genotoxic Effect ◽  
Cellular Damage ◽  
Native Plant ◽  
San Luis ◽  
Uptake Assay ◽  
Healing Of Wounds ◽  
Neutral Red Uptake Assay

Acacia aroma, native plant from San Luis, Argentina, is commonly used as antiseptic and for healing of wounds. The present study was conducted to investigate thein vitrocytotoxicity and genotoxicity of hot aqueous extract (HAE) and ethanolic extract (EE) ofA. aroma. The cytotoxic activity was assayed by neutral red uptake assay on Vero cell. Cell treatment with a range from 100 to 5000 μg/mL of HAE and EE showed that 500 μg/mL and 100 μg/mL were the maximum noncytotoxic concentrations, respectively. The CC50was 658 μg/mL for EE and 1020 μg/mL for HAE. The genotoxicity was tested by the single-cell gel electrophoresis comet assay. The results obtained in the evaluation of DNA cellular damage exposed to varied concentrations of the HAE showed no significant genotoxic effect at range of 1–20 mg/mL. The EE at 20 mg/mL showed moderate genotoxic effect related to the increase of the DNA percentage contained in tail of the comet; DNA was classified in category 2. At concentrations below 5 mg/mL, the results of cytotoxicity and genotoxicity of aqueous and ethanolic extracts ofAcacia aromaguarantee the safety at cell and genomic level. However further studies are needed for longer periods including animal models to confirm the findings.

Cold, Cough, and Allergy Medications: Uses and Abuses

1996 ◽  
Vol 17 (1) ◽  
pp. 12-17
Author(s):  
Murray L. Katcher
Keyword(s):  
Otitis Media ◽  
Common Cold ◽  
Symptomatic Relief ◽  
Respiratory Illness ◽  
The United States ◽  
Upper Respiratory Infection ◽  
Common Diagnosis ◽  
Associated Symptoms ◽  
The Common ◽  
Upper Respiratory

Separately or in combination, antihistamines, decongestants, antitussives, and expectorants are used to treat the cough and rhinitis symptoms of the common cold and of allergies. Each year, Americans spend 1 to 2 billion dollars on cough and cold remedies and lose more than 26 million school days and 23 million work days because of rhinitis and associated symptoms. Studies have shown that antihistamines and decongestants are efficacious in the treatment of allergy symptoms, but the results of studies are mixed regarding their efficacy in the treatment of symptoms of the common cold, and studies show no effect in prevention or treatment of otitis media. Some review articles and consensus opinions do not recommend the use of these drugs in the common cold (especially in preschool children), although some studies have demonstrated symptomatic relief, and physicians continue to prescribe or recommend these drugs for respiratory illness more than 36 million times annually. The Common Cold More than 200 million cases of acute upper respiratory infection (URI) occur each year in the United States, and more than 75 million are seen by physicians. URIs account for 23 million missed work days and 26 million missed school days. This is the second most common diagnosis made by office-based pediatricians, second only to otitis media.

Ethanol in Over-the-Counter Drugs

1996 ◽  
Vol 17 (10) ◽  
pp. 342-343
Keyword(s):  
United States ◽  
National Health ◽  
Common Cold ◽  
National Health Interview Survey ◽  
The United States ◽  
Over The Counter ◽  
Health Interview Survey ◽  
Health Interview ◽  
Interview Survey ◽  
The Common

The use of over-the-counter (OTC) medications among children in the United States is extensive. More than 800 OTC medications are available for treatment of the common cold, with almost 2 billion dollars spent annually on cough and cold medications alone. In 1994, Kogan et al determined that more than 50% of 3-year-old children in the United States had been given OTC medications in the 30 days prior to the study survey. Cough and cold preparations and acetaminophen were reported to be the medications used most frequently (66.7%). The use of cough and cold medications has not decreased when compared with findings from a 1981 National Health Interview Survey, despite increasing evidence that these medications are not effective and, in some circumstances, even may be harmful to children.

scholarly journals In Vitro Activity of Imipenem and Colistin against a Carbapenem-ResistantKlebsiella pneumoniaeIsolate Coproducing SHV-31, CMY-2, and DHA-1

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Hung-Jen Tang ◽  
Yee-Huang Ku ◽  
Mei-Feng Lee ◽  
Yin-Ching Chuang ◽  
Wen-Liang Yu
Keyword(s):  
Outer Membrane ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Hip Infection ◽  
Outer Membrane Porin ◽  
The Common ◽  
Inoculum Effect ◽  
Time Kill

We investigated the synergism of colistin and imipenem against a multidrug-resistantK. pneumoniaeisolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the commonβ-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. TheblaSHV-31,blaCMY-2, andblaDHA-1were detected. Outer membrane porin genes analysis revealed loss ofompK36and frame-shift mutation ofompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L) and 1x MIC of imipenem (8 mg/L) was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistantK. pneumoniaeinfections.

scholarly journals Evaluation of In Vitro Activity of Ceftaroline Tested against Streptococcus pneumoniae Isolates from United States Hospitals: Results from 7 Years of the AWARE Surveillance Program (2010–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S378-S378
Author(s):  
Michael A Pfaller ◽  
Rodrigo E Mendes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Helio S Sader
Keyword(s):  
United States ◽  
The United States ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Amoxicillin Clavulanate ◽  
Infection Types ◽  
Research Grant

Abstract Background Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. pneumoniae (SPN), including multidrug-resistant (MDR) strains. CPT fosamil is approved for clinical use in the United States (US) to treat community-acquired bacterial pneumonia (CABP). The AWARE Program monitors the in vitro activity of CPT against clinical bacteria from various infection types. We evaluated the activity of CPT against isolated SPN clinical isolates from US hospitals collected in 2010 through 2016. Methods A total of 8,768 isolates were consecutively collected (1 per patient) from 47 medical centers in 2010–2016 and tested for susceptibility (S) to CPT and comparator agents using CLSI broth microdilution methods. Resistant subgroups included isolates that were nonsusceptible (NS) to penicillin (PCN), ceftriaxone (CRO), amoxicillin-clavulanate (AMC), erythromycin (ERY), clindamycin (CM), and levofloxacin (LEV) as well as MDR (NS to ≥3 classes of agents) and extensively drug resistant (XDR; NS to ≥5 classes). Results CPT inhibited 99.99% of SPN isolates at ≤0.5 mg/L (only 1 isolate had a CPT MIC of 1 mg/L) and remained active against all SPN-resistant (R) subgroups, including PCN-NS (8.7% at ≥4 mg/L), CRO-NS (6.9% at ≥2 mg/L), MDR (21.7%), and XDR (8.4%) strains. CPT activity remained stable against all R subgroups each year. MDR and XDR frequency decreased from 25.0% and 14.1% in 2011 to 17.8% and 3.2% in 2015, respectively; and S to PCN, CRO, AMC, CM, trimethoprim-sulfamethoxazole (TMX), and tetracycline (TET) increased in the same period (Table). The CPT-NS isolate had multiple substitutions in the penicillin binding proteins (PBP), mainly PBP2x, when compared with reference sequences, and showed 31 amino acid alterations in MurM. For MDR isolates, CPT (99.9%S), tigecycline (99.9%S), linezolid (100.0%S), and vancomycin (100.0%S) were the most active agents. Conclusion CPT demonstrated potent and consistent (2010–2016) activity against SPN, including several R phenotypes and the less S serotypes. SPN S to many antibiotics increased from 2011 to 2015, but remained stable in 2015–2016. Increases in S rates could be related to the anti-pneumococcal vaccine PVC-13 introduced in 2010. Disclosures M. A. Pfaller, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; H. S. Sader, Allergan: Research Contractor, Research grant

scholarly journals ARGONAUT II Study of the In Vitro Activity of Plazomicin against Carbapenemase-Producing Klebsiella pneumoniae

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Michael R. Jacobs ◽  
Caryn E. Good ◽  
Andrea M. Hujer ◽  
Ayman M. Abdelhamed ◽  
Daniel D. Rhoads ◽  
...  
Keyword(s):  
United States ◽  
16S Rrna ◽  
Klebsiella Pneumoniae ◽  
Great Lakes ◽  
The United States ◽  
Great Lakes Region ◽  
In Vitro Activity ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC50 and MIC90 values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF-, rmtB-, or armA-encoded 16S rRNA methyltransferases in all except 1 isolate.

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