Pub Date : 2013-11-15DOI: 10.2174/1876518101304010001
Pramod K. Gupta, S. Kulkarni, Ramakrishna Rajan
Curcuma longa commonly known as turmeric has been used in Indian Ayurvedic medicine as a constituent to treat various disorders. It is by now clear that principal curcuminoid of turmeric; curcumin, a yellow pigment, is responsi- ble for these beneficiary activities. The aim of the present study was to evaluate anti-mycobacterial effect of curcumin (CMN) on intracellular growth of MDR clinical isolates of Mycobacterium tuberculosis (MTB). Curcumin was evaluated for its efficacy to inhibit the intracellular growth of MTB H37Rv and two MDR clinical isolates in Raw 264.7 cell line us- ing CFU assay. Resazurin microtiter plate assay (REMA) was used to evaluate its direct anti-mycobacterial activity. Curcumin, though did not show direct anti-mycobacterial activity against three MTB strains, exhibited dose dependent in- hibition of intracellular growth for MTB H37Rv as well as two MDR clinical isolates. These results suggest that CMN could be a potential candidate for future, novel adjunctive anti-TB therapy.
{"title":"Inhibition of Intracellular Survival of Multi Drug Resistant Clinical Isolates of Mycobacterium tuberculosis in Macrophages by Curcumin","authors":"Pramod K. Gupta, S. Kulkarni, Ramakrishna Rajan","doi":"10.2174/1876518101304010001","DOIUrl":"https://doi.org/10.2174/1876518101304010001","url":null,"abstract":"Curcuma longa commonly known as turmeric has been used in Indian Ayurvedic medicine as a constituent to treat various disorders. It is by now clear that principal curcuminoid of turmeric; curcumin, a yellow pigment, is responsi- ble for these beneficiary activities. The aim of the present study was to evaluate anti-mycobacterial effect of curcumin (CMN) on intracellular growth of MDR clinical isolates of Mycobacterium tuberculosis (MTB). Curcumin was evaluated for its efficacy to inhibit the intracellular growth of MTB H37Rv and two MDR clinical isolates in Raw 264.7 cell line us- ing CFU assay. Resazurin microtiter plate assay (REMA) was used to evaluate its direct anti-mycobacterial activity. Curcumin, though did not show direct anti-mycobacterial activity against three MTB strains, exhibited dose dependent in- hibition of intracellular growth for MTB H37Rv as well as two MDR clinical isolates. These results suggest that CMN could be a potential candidate for future, novel adjunctive anti-TB therapy.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77442411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-12-29DOI: 10.2174/1876518101103010053
S. Simoens, J. Verhaegen, P. V. Bleyenbergh, W. Peetermans, M. Decramer
This study aims to analyse antibiotic treatment of respiratory tract infections in ambulatory care in Belgium by: a) mapping antibiotic consumption over time and breaking down antibiotic consumption by infection type; b) discussing antibiotic treatment as recommended by Belgian guidelines; and c) reviewing the current evidence on the cost- effectiveness of antibiotic treatment. IMS Health data showed that the total volume of antibiotic consumption in ambulatory care in Belgium has increased over the years. Antibiotic consumption mainly originated from the use of broad-spectrum penicillins. The volume of fluoroquinolone use remains well controlled. Policy makers need to target the main drivers of inappropriate antibiotic consumption rather than a specific class of antibiotics when they aim to promote better use of antibiotics in ambulatory care. A s-lactam-based therapy for CAP is recommended as first choice in Belgian guidelines and moxifloxacin is advocated for CAP outpatients with comorbid conditions or outpatients in whom infection with atypical pathogens needs to be considered. Because of its high eradicating power against the target organisms and because H. influenzae is the main pathogen to be covered, amoxicillin-clavulanic acid may be a first choice to treat COPD exacerbations, although this choice is subject to debate. Moxifloxacin is recommended in case of IgE-mediated s-lactam allergy or severe intolerance to s-lactam antibiotics for the treatment of COPD exacerbations or for the treatment of upper respiratory tract infections on the rare occasion that antibiotic treatment is warranted. One study supported the cost- effectiveness of first-line treatment of CAP with moxifloxacin in Belgium.
{"title":"Antibiotic Treatment of Respiratory Tract Infections in Ambulatory Care in Belgium","authors":"S. Simoens, J. Verhaegen, P. V. Bleyenbergh, W. Peetermans, M. Decramer","doi":"10.2174/1876518101103010053","DOIUrl":"https://doi.org/10.2174/1876518101103010053","url":null,"abstract":"This study aims to analyse antibiotic treatment of respiratory tract infections in ambulatory care in Belgium by: a) mapping antibiotic consumption over time and breaking down antibiotic consumption by infection type; b) discussing antibiotic treatment as recommended by Belgian guidelines; and c) reviewing the current evidence on the cost- effectiveness of antibiotic treatment. IMS Health data showed that the total volume of antibiotic consumption in ambulatory care in Belgium has increased over the years. Antibiotic consumption mainly originated from the use of broad-spectrum penicillins. The volume of fluoroquinolone use remains well controlled. Policy makers need to target the main drivers of inappropriate antibiotic consumption rather than a specific class of antibiotics when they aim to promote better use of antibiotics in ambulatory care. A s-lactam-based therapy for CAP is recommended as first choice in Belgian guidelines and moxifloxacin is advocated for CAP outpatients with comorbid conditions or outpatients in whom infection with atypical pathogens needs to be considered. Because of its high eradicating power against the target organisms and because H. influenzae is the main pathogen to be covered, amoxicillin-clavulanic acid may be a first choice to treat COPD exacerbations, although this choice is subject to debate. Moxifloxacin is recommended in case of IgE-mediated s-lactam allergy or severe intolerance to s-lactam antibiotics for the treatment of COPD exacerbations or for the treatment of upper respiratory tract infections on the rare occasion that antibiotic treatment is warranted. One study supported the cost- effectiveness of first-line treatment of CAP with moxifloxacin in Belgium.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76010227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-12-29DOI: 10.2174/1876518101103010045
Manisha Debmandal, S. Mandal, N. Pal
The present study investigates the prevalence of antibiotic resistance among bacterial isolates from different environmental samples and determines their resistance patterns. Bacteria were isolated from the Ganges water, the intestine of Labeo rohita, soil samples from agricultural land, and clinical samples of urine, pus, and throat swab. The bacterial isolates were identified on the basis of standard cultural, morphological and biochemical characteristics. Antibiotic susceptibility of the isolates was tested by disc diffusion and agar dilution method. A total of 87 bacteria belonging to 13 different genera were isolated. The percentages of resistance detected were, Ax: amoxycillin (82.75%), Te: tetracycline (49.42%), Tr: trimethoprim (41.37%), Ch: chloramphenicol (39.08%), Nx: nalidixic acid (22.98%), Ci: ciprofloxacin (24.13%), S: streptomycin (9.19%), G: gentamycin (4.59%) and Ak: amikacin (4.59%). A majority of 57 (65.51%) strains were multi-resistant; 77 (88.5%) were resistant to at least one drug. Determination of resistance pattern revealed that 3 water isolates and 1 clinical isolate belonging to Pseudomonas aeruginosa (n=3) and Proteus vulgaris (n=1) were resistant to all the 9 antibiotics tested; a Proteus mirabilis strain was resistant to all the drugs except G. In the seven-drug-resistant group, Klebsiella aerogenes showed AxChTeNxTSCi-resistance and P. mirabilis strain exhibited AxChTeNxTrGCi resistance pattern. The high prevalence of antibiotic-resistant bacteria harboring diverse resistance traits could represent a potential health risk. The study of antibiotic resistance helps predict future emergence and guide the development of strategies to counteract this resistance. Therefore periodic and comprehensive survey of antibiotic resistance in the environmental bacteria is required.
{"title":"Antibiotic Resistance Prevalence and Pattern in Environmental Bacterial Isolates","authors":"Manisha Debmandal, S. Mandal, N. Pal","doi":"10.2174/1876518101103010045","DOIUrl":"https://doi.org/10.2174/1876518101103010045","url":null,"abstract":"The present study investigates the prevalence of antibiotic resistance among bacterial isolates from different environmental samples and determines their resistance patterns. Bacteria were isolated from the Ganges water, the intestine of Labeo rohita, soil samples from agricultural land, and clinical samples of urine, pus, and throat swab. The bacterial isolates were identified on the basis of standard cultural, morphological and biochemical characteristics. Antibiotic susceptibility of the isolates was tested by disc diffusion and agar dilution method. A total of 87 bacteria belonging to 13 different genera were isolated. The percentages of resistance detected were, Ax: amoxycillin (82.75%), Te: tetracycline (49.42%), Tr: trimethoprim (41.37%), Ch: chloramphenicol (39.08%), Nx: nalidixic acid (22.98%), Ci: ciprofloxacin (24.13%), S: streptomycin (9.19%), G: gentamycin (4.59%) and Ak: amikacin (4.59%). A majority of 57 (65.51%) strains were multi-resistant; 77 (88.5%) were resistant to at least one drug. Determination of resistance pattern revealed that 3 water isolates and 1 clinical isolate belonging to Pseudomonas aeruginosa (n=3) and Proteus vulgaris (n=1) were resistant to all the 9 antibiotics tested; a Proteus mirabilis strain was resistant to all the drugs except G. In the seven-drug-resistant group, Klebsiella aerogenes showed AxChTeNxTSCi-resistance and P. mirabilis strain exhibited AxChTeNxTrGCi resistance pattern. The high prevalence of antibiotic-resistant bacteria harboring diverse resistance traits could represent a potential health risk. The study of antibiotic resistance helps predict future emergence and guide the development of strategies to counteract this resistance. Therefore periodic and comprehensive survey of antibiotic resistance in the environmental bacteria is required.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90534903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-11-29DOI: 10.2174/1876518101103010037
I. Gurt, E. Katz
The population of the stock of the Lister strain of vaccinia virus, applied in Israel for immunization against smallpox, was found to be heterogeneous. A middle-size plaque (MP) virus was found to be the most attenuated for mice, out of the three variants which we characterized. Previously we found that C-terminal truncation of the A33R viral envelope protein of vaccinia virus leads to an enhanced release of free virus from the infected cells and to attenuation of the virus for mice. A recombinant of the MP variant with such truncation, was now constructed and found to release more progeny virus from the infected cells and slightly more attenuated for mice than its parent virus. This new recombinant of vaccinia virus may be useful when vaccination against smallpox would be required again, in the future.
{"title":"Pathogenicity for Mice of a Recombinant of Vaccinia Virus and Protection Against Infection with a Lethal Virus","authors":"I. Gurt, E. Katz","doi":"10.2174/1876518101103010037","DOIUrl":"https://doi.org/10.2174/1876518101103010037","url":null,"abstract":"The population of the stock of the Lister strain of vaccinia virus, applied in Israel for immunization against smallpox, was found to be heterogeneous. A middle-size plaque (MP) virus was found to be the most attenuated for mice, out of the three variants which we characterized. Previously we found that C-terminal truncation of the A33R viral envelope protein of vaccinia virus leads to an enhanced release of free virus from the infected cells and to attenuation of the virus for mice. A recombinant of the MP variant with such truncation, was now constructed and found to release more progeny virus from the infected cells and slightly more attenuated for mice than its parent virus. This new recombinant of vaccinia virus may be useful when vaccination against smallpox would be required again, in the future.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81937103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-11-02DOI: 10.2174/1876518101103010030
J. Cleary, K. Wasan
Objective: The binding characteristics of the polyene antifungal amphotericin B (AmB) are still arguably unclear 50 years after the first human treatment. Our purpose was to investigate the dynamic of polyene cell associated binding using an AmB directed antibody. Methods: Ex vivo murine model and in vitro mammalian cells studies were utilized to assess the binding characteristics of AmB at human therapeutic concentrations. Balb/c mice administered a single dose of an AmB formulation were assessed using immunohistochemistry. Human mononuculear cells isolated after phlebotomy were assessed using transmission electron micrography. Results & Conclusions: Ex vivo studies demonstrated diffuse binding of AmB formulations, however, the sensitivity of the technique would not allow delineation of the antifungals' cellular binding. However, transmission electron micrography of in vitro cell cultures allowed apparent discrimination of cell associated binding and suggestions of intracellular trafficking within 2 hours of polyene exposure. One could hypothesize the observed characteristics and previously published literature are suggestive of binding to clathrin type receptors with internalization and processing by endosomes. Further work will be required to substantiate this hypothesis.
{"title":"Amphotericin B: A New Look at Cellular Binding","authors":"J. Cleary, K. Wasan","doi":"10.2174/1876518101103010030","DOIUrl":"https://doi.org/10.2174/1876518101103010030","url":null,"abstract":"Objective: The binding characteristics of the polyene antifungal amphotericin B (AmB) are still arguably unclear 50 years after the first human treatment. Our purpose was to investigate the dynamic of polyene cell associated binding using an AmB directed antibody. Methods: Ex vivo murine model and in vitro mammalian cells studies were utilized to assess the binding characteristics of AmB at human therapeutic concentrations. Balb/c mice administered a single dose of an AmB formulation were assessed using immunohistochemistry. Human mononuculear cells isolated after phlebotomy were assessed using transmission electron micrography. Results & Conclusions: Ex vivo studies demonstrated diffuse binding of AmB formulations, however, the sensitivity of the technique would not allow delineation of the antifungals' cellular binding. However, transmission electron micrography of in vitro cell cultures allowed apparent discrimination of cell associated binding and suggestions of intracellular trafficking within 2 hours of polyene exposure. One could hypothesize the observed characteristics and previously published literature are suggestive of binding to clathrin type receptors with internalization and processing by endosomes. Further work will be required to substantiate this hypothesis.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74447311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-09-28DOI: 10.2174/1876518101103010023
O. Vassallo, S. Castelli, A. Biswas, S. Sengupta, P. Das, I. d’Annessa, F. Oteri, A. Leoni, P. Tagliatesta, H. Majumder, A. Desideri
Conjugated eicosapentaenoic acid inhibits the relaxation activity of purified L. donovani topoisomerase I, with an efficiency higher than that displayed by the corresponding human enzyme. Docking of the acid compound over the 3D structure of the enzyme shows that the complex is stabilized by a large network of interaction between the compound and many residues located in proximity of the active site, including the catalytic tyrosine 222, providing an explanation for its efficient inhibitory effect. The acid has also a strong antiprotozoal activity against L. donovani promastigotes ( EC50= 75 � M) whilst it has no effect against murine macrophages (IC50 � 2 mM). Taken together the results indicate that L. donovani topoisomerase I can be considered an interesting molecular target and that conjugated eicosapentaenoic acid can be taken in consideration as a possible lead compound against leishmaniasis.
{"title":"Conjugated Eicosapentaenoic Acid (cEPA) Inhibits L. donovani TopoisomeraseI and has an Antiproliferative Activity Against L. donovani Promastigotes","authors":"O. Vassallo, S. Castelli, A. Biswas, S. Sengupta, P. Das, I. d’Annessa, F. Oteri, A. Leoni, P. Tagliatesta, H. Majumder, A. Desideri","doi":"10.2174/1876518101103010023","DOIUrl":"https://doi.org/10.2174/1876518101103010023","url":null,"abstract":"Conjugated eicosapentaenoic acid inhibits the relaxation activity of purified L. donovani topoisomerase I, with an efficiency higher than that displayed by the corresponding human enzyme. Docking of the acid compound over the 3D structure of the enzyme shows that the complex is stabilized by a large network of interaction between the compound and many residues located in proximity of the active site, including the catalytic tyrosine 222, providing an explanation for its efficient inhibitory effect. The acid has also a strong antiprotozoal activity against L. donovani promastigotes ( EC50= 75 � M) whilst it has no effect against murine macrophages (IC50 � 2 mM). Taken together the results indicate that L. donovani topoisomerase I can be considered an interesting molecular target and that conjugated eicosapentaenoic acid can be taken in consideration as a possible lead compound against leishmaniasis.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83202049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-09-08DOI: 10.2174/1876518101103010017
M. Ueno, K. Hayashi
Influenza is one of the common infectious diseases caused by influenza virus. Vaccines are the most effective means to fight infectious diseases. While these vaccines are quite effective in young adults, however, they are less for the above high risk group. A currently used influenza vaccine contains aluminum hydroxide as an adjuvant, which sometimes induces the production of IgE antibodies causing an allergic reaction. In order to overcome the drawbacks, artificial membrane vaccines or liposome vaccines have been developed. Liposomes are known to be effective immunoadjuvants. On the other hand, various membrane proteins, including matrix membrane proteins, have been reported to be spontaneously transferrable from living cell membranes to artificial membranes (liposomes). In this article, we introduced a new method to prepare the artificial membrane vaccine, "influenza virosomes", using inter-membrane protein transfer, and discussed the immunreactivity of the virosomes. We concluded that the application of inter-membrane protein transfer technique is a useful method for the preparation of the artificial membrane vaccine, virosomes. The virosomes showed high immunoreactivity especially with MDP (muramyldipeptide) derivatives as an adjuvant or booster treatment.
{"title":"Development of New Vaccine－New Method to Prepare Artificial Membrane Vaccine using Inter-Membrane Protein Transfer","authors":"M. Ueno, K. Hayashi","doi":"10.2174/1876518101103010017","DOIUrl":"https://doi.org/10.2174/1876518101103010017","url":null,"abstract":"Influenza is one of the common infectious diseases caused by influenza virus. Vaccines are the most effective means to fight infectious diseases. While these vaccines are quite effective in young adults, however, they are less for the above high risk group. A currently used influenza vaccine contains aluminum hydroxide as an adjuvant, which sometimes induces the production of IgE antibodies causing an allergic reaction. In order to overcome the drawbacks, artificial membrane vaccines or liposome vaccines have been developed. Liposomes are known to be effective immunoadjuvants. On the other hand, various membrane proteins, including matrix membrane proteins, have been reported to be spontaneously transferrable from living cell membranes to artificial membranes (liposomes). In this article, we introduced a new method to prepare the artificial membrane vaccine, \"influenza virosomes\", using inter-membrane protein transfer, and discussed the immunreactivity of the virosomes. We concluded that the application of inter-membrane protein transfer technique is a useful method for the preparation of the artificial membrane vaccine, virosomes. The virosomes showed high immunoreactivity especially with MDP (muramyldipeptide) derivatives as an adjuvant or booster treatment.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87860247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-08-25DOI: 10.2174/1876518101103010012
P. V. Gawande, N. Yakandawala, K. LoVetri, Srinivasa Madhyastha
Since the traditional methods of treatment have proven ineffective against chronic wounds involving biofilms, the present study evaluates the in vitro efficacy of a novel wound gel comprising an antibiofilm DispersinB ® enzyme and a broad-spectrum antimicrobial triclosan against chronic wound-associated bacteria. The antimicrobial and antibiofilm activity of DispersinB ® -triclosan wound gel was tested against chronic wound-associated bacteria such as Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, coagulase-negative Staphylococci, Acinetobacter baumannii and Klebsiella pneumoniae using a quantitative culture method and a biofilm assay. The DispersinB ® -triclosan wound gel showed more enduring antimicrobial activity against the test organisms compared to commercial wound gels Silver-Sept™ and IODOSORB. When DispersinB ® -triclosan wound gel was tested against preformed biofilm, it showed 2-4 log10 reduction in the biofilm embedded bacterial cells. Furthermore, DispersinB ® - triclosan wound gel compared to IODOSORB was significantly more effective in inhibiting biofilm in MRSA and A. baumannii (P < 0.05). This study indicates the potential application of a broad-spectrum DispersinB ® -triclosan wound gel
{"title":"In Vitro Antimicrobial and Antibiofilm Activity of DispersinB ® -Triclosan Wound Gel against Chronic Wound-associated Bacteria","authors":"P. V. Gawande, N. Yakandawala, K. LoVetri, Srinivasa Madhyastha","doi":"10.2174/1876518101103010012","DOIUrl":"https://doi.org/10.2174/1876518101103010012","url":null,"abstract":"Since the traditional methods of treatment have proven ineffective against chronic wounds involving biofilms, the present study evaluates the in vitro efficacy of a novel wound gel comprising an antibiofilm DispersinB ® enzyme and a broad-spectrum antimicrobial triclosan against chronic wound-associated bacteria. The antimicrobial and antibiofilm activity of DispersinB ® -triclosan wound gel was tested against chronic wound-associated bacteria such as Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, coagulase-negative Staphylococci, Acinetobacter baumannii and Klebsiella pneumoniae using a quantitative culture method and a biofilm assay. The DispersinB ® -triclosan wound gel showed more enduring antimicrobial activity against the test organisms compared to commercial wound gels Silver-Sept™ and IODOSORB. When DispersinB ® -triclosan wound gel was tested against preformed biofilm, it showed 2-4 log10 reduction in the biofilm embedded bacterial cells. Furthermore, DispersinB ® - triclosan wound gel compared to IODOSORB was significantly more effective in inhibiting biofilm in MRSA and A. baumannii (P < 0.05). This study indicates the potential application of a broad-spectrum DispersinB ® -triclosan wound gel","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81616720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-08-15DOI: 10.2174/1876518101103010006
Clara J. Sei, T. Chanturiya, J. Mond, J. Kokai-Kun
Lysostaphin is being developed as a treatment for serious staphylococcal infections. Mice challenged with S. aureus produce inflammatory cytokines including, TNF-� and IL-6, and over-production of these cytokines can lead to shock and contribute to the lethality of staphylococcal infections. Two major components of the staphylococcal cell wall, peptidoglycan and lipoteichoic acid, are known to synergize to induce shock and organ failure in animal models, and we wished to determine whether the rapid lysostaphin-mediated degradation of peptidoglycan during treatment of systemic S. aureus infection could affect shock-associated parameters. We found that lysostaphin treatment of S. aureus-infected mice, which reduces bacteremia and organ infection, also reduced the serum levels of inflammatory cytokines and reversed the symptoms of S. aureus-induced shock. We compared the cytokine response of mice challenged with S. aureus to that of mice challenged with S. aureus and then treated with lysostaphin or nafcillin. Lysostaphin-treated mice, as compared with untreated mice or nafcillin-treated mice, had a blunted cytokine responses to S. aureus challenge. Core body temperature was used as a real time indicator for systemic shock in mice. Mice infected with S. aureus demonstrated a rapid drop in core body temperature, which was reversed by lysostaphin treatment. These studies demonstrated that lysostaphin treatment did not contribute to the induction of shock by rapidly releasing staphylococcal cell wall components, but rather it blunted the inflammatory cytokine response and ameliorated shock related symptoms. Keyword: S. aureus, lysostaphin, shock, cytokine release.
{"title":"Lysostaphin Reduces the Production of Inflammatory Cytokines in Staphylococcus aureus Challenged Mice, and Prevents Systemic Shock","authors":"Clara J. Sei, T. Chanturiya, J. Mond, J. Kokai-Kun","doi":"10.2174/1876518101103010006","DOIUrl":"https://doi.org/10.2174/1876518101103010006","url":null,"abstract":"Lysostaphin is being developed as a treatment for serious staphylococcal infections. Mice challenged with S. aureus produce inflammatory cytokines including, TNF-� and IL-6, and over-production of these cytokines can lead to shock and contribute to the lethality of staphylococcal infections. Two major components of the staphylococcal cell wall, peptidoglycan and lipoteichoic acid, are known to synergize to induce shock and organ failure in animal models, and we wished to determine whether the rapid lysostaphin-mediated degradation of peptidoglycan during treatment of systemic S. aureus infection could affect shock-associated parameters. We found that lysostaphin treatment of S. aureus-infected mice, which reduces bacteremia and organ infection, also reduced the serum levels of inflammatory cytokines and reversed the symptoms of S. aureus-induced shock. We compared the cytokine response of mice challenged with S. aureus to that of mice challenged with S. aureus and then treated with lysostaphin or nafcillin. Lysostaphin-treated mice, as compared with untreated mice or nafcillin-treated mice, had a blunted cytokine responses to S. aureus challenge. Core body temperature was used as a real time indicator for systemic shock in mice. Mice infected with S. aureus demonstrated a rapid drop in core body temperature, which was reversed by lysostaphin treatment. These studies demonstrated that lysostaphin treatment did not contribute to the induction of shock by rapidly releasing staphylococcal cell wall components, but rather it blunted the inflammatory cytokine response and ameliorated shock related symptoms. Keyword: S. aureus, lysostaphin, shock, cytokine release.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78283424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-30DOI: 10.2174/1876518101103010001
G. Rubinstein, B. Bavdaz, S. Bunder, N. Blázquez
The aim of this work was to study and compare macrolide resistance patterns among Streptococcus pneumoniae, Streptococcus agalactiae and Streptococcus pyogenes, to describe the phenotypes of macrolide-lincosamide resistance and to further investigate associations between macrolide resistance and social clustering. Susceptibility data were obtained from 4 clinical microbiology laboratories in Bariloche, Argentina for the period 2002- 2008. Patients were differentiated in two population clusters according to the institution they attended (public or private). A total of 4310 strains were studied: 2615 S. pyogenes, 995 S. agalactiae and 700 isolates of S.pneumoniae. Erythromycin resistance rates over the study period were 1.5% for S. pyogenes, 7.8% for S. agalactiae and 11.3% for S. pneumoniae. For the complete study group, these values differed significantly among species (contingency table 2 = 164.52, p<0.0001). Resistance in S.pyogenes and S. pneumoniae showed irregular trends whilst S. agalactiae showed an increasing tendency during the whole period appearing to be a better indicator of the trends in macrolide resistance. A dual character MLSB phenotype of both inducible and constitutive resistance was observed in S. agalactiae only. Resistance in isolates from the population attending private institutions was significantly higher than those attending the public hospital (S. pyogenes, (1.9 vs. 0.6, 2 = 5.851, p<0.025); S. pneumoniae, 19.1 vs. 7.0 ( 2 = 21.98, p<0.001), and. S. agalactiae, 12.4 vs. 3.8 ( 2 = 24.5, p<0.001)). In conclusion, macrolides resistance rates during 2002-2008 were significantly different for S. pyogenes, S. agalactiae and S.pneumoniae. We also found significant variations in macrolide resistance levels in different population groups.
本研究的目的是研究和比较肺炎链球菌、无乳链球菌和化脓链球菌对大环内酯类药物的耐药模式，描述大环内酯类药物耐药的表型，并进一步探讨大环内酯类药物耐药与社会聚类之间的关系。2002- 2008年期间，从阿根廷巴里洛切的4个临床微生物实验室获得了药敏数据。根据患者就读的机构(公立或私立)将患者分为两类人群。共检出4310株，其中化脓性链球菌2615株，无乳链球菌995株，肺炎链球菌700株。研究期间，化脓性链球菌、无乳链球菌和肺炎链球菌的红霉素耐药率分别为1.5%、7.8%和11.3%。对于整个研究组，这些值在物种之间差异显著(列联表2 = 164.52,p<0.0001)。化脓性链球菌和肺炎链球菌的耐药呈不规则趋势，而无乳链球菌在整个时期呈上升趋势，这是大环内酯类耐药趋势的较好指标。仅在无乳葡萄球菌中观察到诱导型和构成型双性状MLSB表型。私立机构人群中分离株的耐药性显著高于公立医院人群(化脓性链球菌，(1.9 vs. 0.6，2 = 5.851,p<0.025);肺炎链球菌，19.1 vs. 7.0(2 = 21.98,p<0.001);无乳链球菌，12.4比3.8(2 = 24.5,p<0.001)。结论:2002-2008年，化脓性链球菌、无乳链球菌和肺炎链球菌的大环内酯类药物耐药率存在显著差异。我们还发现大环内酯类药物耐药水平在不同人群中存在显著差异。
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