Antibiotics · Antibiotics epteber 2 ... Resistance in bacteria to carbapenems is due to the...

Volume 6 Issue 4J Drug Metab Toxicol 2015

ISSN: 2157-7609, JDMT an open access journalAntibiotics 2015

September 14-16, 2015

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September 14-16, 2015 Las Vegas, USA

World Congress and Exhibition on

AntibioticsLiquid chromatography mass spectrometry based rapid secondary metabolite profiling of marine Pseudoalteromonas sp. M2Woo-Jung and KimGyeonggi Institute of Science and Technology Promotion (GSTEP), Korea

The ocean is a rich resource of flora, fauna and food. A wild-type bacterial strain showing confluent growth on marine agar with antibacterial activity was isolated from marine water, identified using 16S rDNA sequence analysis as Pseudoalteromonas

sp., and was designated as strain M2. This strain was found to produce various secondary metabolites including quinolone alkaloids. Using high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis, we identified 9 secondary metabolites of 4-hydroxy-2-alkylquinoline (pseudane-III, IV, V, VI, VII, VIII, IX, X, and XI). Additionally, this strain produced 2 novel closely related compounds, 2-isopentylqunoline-4-one and 2-(2,3-dimetylbutyl)qunoline-4-(1H)-one, which have not been previously reported from marine bacteria. From the metabolites produced by Pseudoalteromonas sp. M2, 2-(2,3-dimethylbutyl)quinolin-4-one, pseudane-VI and pseudane-VII inhibited melanin synthesis in melan-a cells by 23.0%, 28.2% and 42.7%, respectively, wherein pseudane-VII showed highest inhibition at 8 µg/mL. The results of this study suggest that liquid chromatography (LC)-MS/MS-based metabolite screening effectively improves efficiency of novel metabolite discovery. Additionally, these compounds are promising candidates for further bioactivity development.

BiographyWoo Jung Kim received the PhD degree from the Catholic University of Korea in Biotechnology. He is currently Gyeonggi Institute of Science and Technology Promotion (GSTEP) in Korea. His research interests include structure and bioactivities of polysaccharides and oligosaccharides and related enzymology. He has published more than 22 papers in journals and been a member of the Korean Society for Glycoscience and The Korean Society for Applied Biological Chemistry.

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Woo-Jung et al., J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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Antibiotics

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Antibacterial activities of metabolites from Platanus occidentalis (American Sycamore) against fish pathogenic bacteriaKevin K SchraderUniversity of Mississippi, USA

One approach to the management of common fish diseases in aquaculture is the use of antibiotic-laden feed. However, there are public concerns about the use of antibiotics in agriculture and the potential development of antibiotic resistant

bacteria. Therefore, the discovery of other environmentally safe natural compounds as alternatives to antibiotics would benefit the aquaculture industries. Four natural compounds, commonly called platanosides, [kaempferol 3-O-α-L-(2”,3”-di-E-p-coumaroyl)rhamnoside(1), kaempferol 3-O-α-L-(2”-E-p-coumaroyl-3”-Z-p-coumaroyl)rhamnoside (2), kaempferol 3-O-α-L-(2”-Z-p-coumaroyl-3”-E-p-coumaroyl)rhamnoside (3) and kaempferol 3-O-α-L-(2”,3”-di-Z-p-coumaroyl)rhamnoside (4)] isolated from the leaves of the American sycamore (Platanus occidentalis) tree were evaluated using a rapid bioassay for their antibacterial activities against common fish pathogenic bacteria including Flavobacterium columnare, Edwardsiella ictaluri, Aeromonas hydrophila and Streptococcus iniae. The four isomers and a mixture of all four isomers were strongly antibacterial against isolates of F. columnare and S. iniae. Against F. columnare ALM-00-173, 3 and 4 showed the strongest antibacterial activities, with 24-h 50% inhibition concentration (IC50) values of 2.13±0.11 and 2.62±0.23 mg/L, respectively. Against S. iniae LA94-426, 4 had the strongest antibacterial activity, with 24-h IC50 of 1.87±0.23 mg/L. Neither a mixture of the isomers nor any of the individual isomers were antibacterial against isolates of E. ictaluri and A. hydrophila at the test concentrations used in the study. Several of the isomers appear promising for the potential management of columnaris disease and streptococcosis in fish.

BiographyKevin K Schrader completed his PhD in 1995 from Auburn University, AL, and Postdoctoral studies with Mississippi State University in 1996-1997. He is a Research Microbiologist at the USDA, ARS, Natural Products Utilization Research Unit, National Center for Natural Products Research. He has authored and co-authored more than 80 papers in peer-reviewed journals, one U.S. patent, an edited book, and over 10 invited book chapters, and he has been serving as an Editorial Board Member of repute.

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Kevin K Schrader, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsEfficacy of ceftriaxone-sulbactam-EDTA combination in immuno compromised patients in a tertiary care cancer centreSanjay Biswas, Vivek Bhatt and Rohini KelkarTata Memorial Centre, India

Introduction: The resistance to the antimicrobials has been increasing over the years and is varying from country to country. Among the causes of β-lactam antibiotic resistance, the production of ESBLs appeared to be most common. The ESBLs are plasmid mediated and can be easily transmitted among members of Enterobacteriaceae, thus facilitating the dissemination of resistance, not only to β-lactam, but to other commonly used antibiotics including aminoglycosides and quinolone. To overcome ESBLs resistance, carbapenem drugs have been introduced in clinical settings, although carbapenems resistance has been reported increasingly worldwide. Resistance in bacteria to carbapenems is due to the production of carbapenem hydrolyzing enzymes called carbapenemases, which is encoded by KPC, VIM and IMP genes. The aim of the present study was to compare the susceptibility pattern of ceftriaxone-sulbactam-EDTA(CSE) combination with other routinely used antibiotics in immunocompromised patients.

Materials and Methods: A total of 33930 clinical samples were received in the Dept. of Microbiology in 2014. All the samples were processed as per standard microbiological methods. Antimicrobial susceptibility testing of cefoperazone-sulbactam, ceftriaxone-sulbactam-EDTA, piperacillin-tazobactam, imipenem and meropenem of 195 Gram negative isolates, included in this study, were carried out by disc diffusion methodas per CLSI guidelines. ATCC strains were used as standards. Interpretative criteria of Ceftriaxone were used for interpretation of CSE.

Results: Of the 33930 samples received, only 195 Gram negative isolates, from different clinical samples, were included in this study. Blood was the most common isolate followed by broncho- alveolar lavages, wound swabs and drain fluids. Escherichia coli was the commonest isolate followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Carbapenems were the most sensitive antimicrobial followed by cefoperazone-sulbactam, ceftriaxone-sulbactam-EDTA and piperacillin-tazobactam.

Conclusions: Results obtained in the current study clearly demonstrates the good in-vitro activity of ceftriaxone plus sulbactam plus EDTA as compared to other beta-lactam beta-lactamase inhibitor combinations. The enhanced susceptibility of ceftriaxone+EDTA+sulbactam against different clinical isolates is likely to be associated with synergistic activity of ceftriaxone+sulbactam+EDTA. EDTA chelates the divalent ions, thus enhancing the susceptibility of ceftriaxone plus EDTA plus sulbactam towards different microorganisms. The EDTA also enhances the susceptibility by altering the outer membrane permeability, which in turn increased penetration of drugs inside the bacterial cells.

BiographySanjay Biswas is a Professor & Microbiologist in the Dept of Microbiology in Tata Memorial Hospital, Mumbai, and completed his MBBS in Sambalpur University 1992 and MD (Microbiology) at Bombay University in October 1998.

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Sanjay Biswas et al., J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003






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Systemic antibiotic consumption in a population of South Korea between 2009 and 2013Juhee Park and Soo-Ok LeeHealth Insurance Review and Assessment Service, South Korea

Background: This study was conducted to investigate overall systemic antibiotic consumption levels and specific patterns using standardized Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology.

Methods: The administrative data from South Korean Health Insurance Review & Assessment (HIRA) were used to examine trends in antibiotic consumption. Main outcome measures are DDD (Defined Daily Dose) by ATC (Anatomical Therapeutic Chemical classification) class. Antibiotic usage data were collected for systemic antibacterial (ATC category J01). Detailed information on indications and seasonal variations, age and institutional determinants on antibiotic consumption were also explored.

Results: Total consumption was slightly increased from 25.8 DID (the number of DDD per 1,000 inhabitants per day) to 26.7DID from 2009 to 2013 slightly. These values are higher than the average (21.2 DID) of OECD 2012. Consumption figures under 10 years of age (44.8 DID and 51.5 DID in 2009 and 2013, respectively) were even higher than figures in aged 60-69 (34.0 DID and 33.4 DID in 2009 and 2013, respectively) especially the measure of average in aged 2-5 was very high (65 DID). The most frequently prescribed antibiotic was combinations of penicillins, incl. beta-lactamase inhibitors (J01CR, 24.32%, in 2013), followed by second-generation cephalosporins (J01DC, 18.24%) and macrolides (J01FA, 13.82%). 49.4% (6.6 DID) among the outpatients of acute upper respiratory infections and 54.6% (5.8 DID) among the outpatients of other acute upper respiratory infections were prescribed antibiotics.

Conclusions: Overall antibiotic prescription usage has increased slightly. However, use of cephalosporins is gradually increasing, except first-generation cephalosporins and the amount of antibiotics in children is still a high level, which can affect to antibiotic resistance. In South Korea, using various policies, it is intended to inhibit the use of antibiotics. During 2000s, antibiotic prescriptions for acute respiratory tract infection (RTI) decreased due to various program including Evaluation Project on Appropriate Prescribing (EPAP) which is analyzing prescribing pattern and providing physicians’ feedback began in 2001. Efforts to increase prudent antibiotic use, especially for upper respiratory system infections and for younger children, should be made to decrease antibiotic use.

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Juhee Park et al., J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003






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The potential of endophytic actinomycetes of Amphipterygium adstringens as producers of novel antibioticsKarol Rodríguez-Peña, Martha Lydia Macías Rubalcava and Sergio SánchezUniversidad Nacional Autónoma de México, México

Endophytes are microorganisms that inhabit plants without causing apparent damage. It has been found that the interaction between the host plant and endophyte is based on both physical and chemical mechanisms. The secondary metabolism

of these microorganisms which allows them to defend themselves or communicate with their host, as well as their unique habitat make them a very interesting source of new molecules with biological activity. Actinomycetes are a group of Gram-positive bacteria that have been extensively studied for their ability to produce a variety of secondary metabolites, especially the genus Streptomyces. However, it has recently been found by genome mining studies among some others, that other genera of actinomycetes that have hardly been studied are also capable of producing a large number of compounds. In this study, endophyte isolation was made from the medicinal plant Amphipterygium adstringens. Four actinomycetes were isolated: one of the genus Streptomyces and three others closest to the genus Actinoplanes. Phylogenetic studies place the latter three strains as potential new species. Sequential extracts were conducted, first with dichloromethane (DCM) and then with ethyl acetate (EtAc). The minimum inhibitory concentration was determined with Gram-positive, Gram-negative and a yeast. Extracts from the strain NF3 showed significant activity against the Gram-positive bacteria tested at 0.1μg/mL with DCM and 6.3 μg/mL with EtAc, making it a very attractive strain for further elucidation of bioactive molecules. The extracts from strain TFC3 meanwhile, showed activity against Bacillus subtilis with 200 μg/mL in both DCM and EtAc. These same extracts were tested against cancer cell lines MCF7 and HeLa, as well as with with HaCaT as a healthy cell line. The extract from the NF3 strain produced mortality higher than 80% with 0.4 μg/mL in MCF7, 0.8 μg /mL for HeLa and 1.6 μg/mL for HaCaT. The putative Actinoplanes extracts had moderate activity only at 200 μg/mL with different cell lines. However, genomic studies of closely related strains indicate that these strains have enormous potential due to the large number of clusters that encode various cryptic secondary metabolite pathways.

BiographyKarol Rodríguez-Peña is a PhD student in Biomedical Sciences at UNAM. He has 40 years experience leading the Industrial Microbiology Laboratory at the Biomedical Research Institute at UNAM. He carried out his Postdoctoral studies at MIT in Cambridge MA. He is Member of the American Academy of Microbiology and has published more than 150 papers in reputed journals. He is the Editorial Board Member of Applied Microbiology and Biotechnology and Editor in Chief of Biotechnology.

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Karol Rodríguez-Peña et al., J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsblaNDM-1 possessing Escherichia coli and Klebsiella pneumoniae isolates exhibiting multidrug-resistant and pandrug-resistant phenotypes in Northeast IndiaArijit BoraGauhati University, India

Increasing reports on New Delhi metallo-β-lactamase-1 (NDM-1) producing Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae constitute a serious threat to global health. Although, NDM-1 was first reported in 2009

in a Swedish patient previously admitted to an Indian hospital, till the data on the NDM-1 producing Enterobacteriaceae in Indian hospital is limited due to constrained resources. Therefore, the present study was designed to evaluate the incidence of blaNDM-1 gene in E. coli and K. pneumoniae isolates at a tertiary care referral hospital in Northeast India. A total of 412 consecutive, non-duplicate isolates of E. coli (n=221) and K. pneumoniae (n=191) were recovered from various clinical samples. On the basis of their reduced susceptibility to meropenem or ertapenem, 55 (24.88%) E. coli and 52 (27.22%) K. pneumoniae were screened for detection of blaNDM-1 by PCR. All screened isolates were found to be positive for blaNDM-1. Each of the blaNDM-1 possessing isolates of E. coli and K. pneumoniae was also found to be positive for one or more additional bla genes, such as blaTEM, blaSHV, blaCTX-M and blaAmpC. All the blaNDM-1 possessing isolates were “multidrug-resistant” as well as 56.36% E. coli 63.46% of K.pneumoniae isolates with blaNDM-1 were “pandrug- resistant”. In addition, few of the blaNDM-1 positive isolates showed reduced susceptibility to tigecycline and colistin, which extremely limits the treatment options for infections cause by NDM-1-positive isolates.

BiographyArijit Bora has completed his PhD from Department of Biotechnology, Gauhati University, Assam, India in association with Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. He has more than 10 years of academic and laboratory experiences in the field of Medical Microbiology. Presently, he is working as a scientific officer in the Department of Applied Sciences, GUIST, Gauhati University, Assam, India. He has published 09 papers in reputed journals and presented his research works in two international conferences.

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Arijit Bora, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003






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Review of antibiotic use/overuse legislation: Time to actSara ImanpourTexas A&M University, USA

Introduction: Antibiotic resistance poses a considerable challenge to local, national and global health. The major cause of antibiotic resistance stems from the overuse/misuse of the antibiotic. While details regarding the development of antibiotic resistance is complicated and often depends on many different components, one concept is clear: the extension of antibiotic resistance is increasing by the enormous use of antibiotic. Therefore, the USA needs policy and legislation to cope with the antibiotic resistance problem.

Method: To identify all eligible studies we will search the CINAHL, Scopus, and Medline (Pubmed) from 1990-2014. Studies had included if they met the paper’s goals.

Result: Antibiotic resistance can spread all over the world and cause serious problems, such as increasing hospital costs, increasing length of hospitalization, and growing mortality rates due to various infectious diseases. Despite the fact that congress has periodically released reports regarding the issue of antibiotic overuse, no significant action has been taken to regulate the use of antibiotics. Essentially all of the bills, which were introduced in different times either in Congress or Senate, were targeting antibiotic usage in animals or agriculture, but not human.

Discussion: Physician’s over-prescription, lack of awareness among patients, and lack of financial support for health care facilities is the most important reason of increasing antibiotic resistance; therefore it is time to act and save people’s lives as well as reduce health care facilities’ cost.

BiographySara Imanpour is doing PhD in health services reserach at Texas A&M school of public health. She recieved her MBA in 2012 from Azad University, Tehran, Iran.

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Sara Imanpour, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003

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Antimicrobial resistance of Escherichia coli isolated from piglets in South Eastern AustraliaL K Van Breda, A N Ginn, O Dhungyel, J R Iredell and M P WardThe University of Sydney, Australia

Introduction: The Australian pig industry commonly uses antimicrobials for prevention of diarrheal diseases in neonatal and weaner piglets caused by Escherichia coli. E. coli is ubiquitous in both humans and animals. Surveillance of E. coli resistance from both healthy and diseased piglets is necessary to anticipate any potential threat to both animal and public health. The aim of this study was to assess resistance to antimicrobials used in human medicine in E. coli isolated from healthy and clinically sick piglets.

Methods: A snapshot survey of 22 commercial piggeries located in South Eastern Australia: New South Wales n=9; Victoria n=10; and South Australia n=3 was conducted from September 2013 to May 2014. Faecal samples were collected from each herd (10 from pre-weaned and 40 from post-weaned piglets). Each sample was categorised according to a simple faecal consistency score (1 = firm and shaped, 2 = soft and shaped, 3 = loose, 4 = watery) and according to detection of β-haemolytic E. coli. A total of 325 E. coli isolates were tested for resistance to 27 antimicrobials using the BD Phoenix Automated Microbiology System (BD Diagnostics).

Results & Discussion: The highest prevalence of resistance was to tetracycline (72%), with moderate prevalence of resistance to trimethoprim-sulfamethoxazole (45%) and chloramphenicol (37%). Resistance to cefazolin (8%), cefoxitin (5%) and ceftriaxone (3%) was less frequent, although continued monitoring for emerging resistance to these antimicrobials is essential, considering their importance in human therapeutics.

Implications: Multi-drug resistant isolates (including drugs important for human health) observed in this study require further investigation. Surveillance of E. coli resistance from both healthy and diseased piglets is necessary to anticipate any potential threat to both animal and public health. In addition, monitoring of pigs at slaughter and pork products is needed to develop an integrated public health surveillance system.

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L K Van Breda et al., J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsThe role of predatory bacteria towards the control of microbial resistanceElufisan Temidayo OluyomiInstituto Politecnicio Nacional, Mexico

The continuous emergence of resistance microorganisms from the Hospital and the community still remain a serious global threat to health care delivery and contributes largely to the rate of death, long duration of hospital stay and increase cost

of care delivery. Exacerbating this situation are the quick ability of microorganism to circumvent other strategies that have been tried to combat microbial resistance. Several strategies have been put in place to avert high rate if microbial resistance to antimicrobial agent such as modification of existing antibiotics, introduction of new antibiotics, the use of phage among others but the abiltiy of microorganisms to quickly evade this strategy makes high incidence of microbial resistance to drug persist. Recently the role of probiotics and other microbial agent is being considered for the treatment of resistant bacteria or microbes but a more recent and of future significance are the predatory bacteria with the possible ability of preying on other bacteria. These bacteria group pose a better alternative for combating resistance in bacteria because of their intrinsic ability to prey on other which are also a form of adaptation in them. Several predatory bacteria have been discussed in literature such as the Balos (Bdellovibrio and Like organisms) and some of them have been exploited for this purpose in laboratory research. Of recent are the Stenotrophomonas species which have a high ability to mutuate and can quickly learn to survive in a wide range of condition. This ability pose on them the potential to be predatory as some of them has been found in endosymbiotic association where they help their host to destroy other pathogen. It thus become pertinent that intensified effort be put into the research of predatory bacteria as they could provide an alternative route of escape from multi-resistant microbes. In this light we have decided to research into the predatory role of Stenotrophomonas species in the control of resistant bacteria.

BiographyElufisan Temidayo Oluyomi is a PhD student at the Instituto Politecnicio Nacional Mexico and has worked as a Research Officer at the National Centre for Technology Management (An agencies of the Federal Ministry of Science and Technology Nigeria). He holds a Master’s degree in Pharmaceutical Microbiology from the University of Ibadan Nigeria and has over 10 publications in reputable Journals. He is an International Member of American Society of Microbiologist.

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Elufisan Temidayo Oluyomi, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsClinical and socio econonomic determinants of antibiotic usage and prescription prior admission for clinical severe pneumonia in children under five years of age in Rabat, MoroccoJroundi ImaneUniversity Mohamed V, Morocco

Scarce data is available regarding antibiotic usage and prescription in children with respiratory tract infections in the Kingdom of Morocco, a middle-income country in Northwestern Africa. A National survey in 2006, showed that

in ambulatory setting, almost 35 percent of children under five visiting the primary heath care centers receive antibiotics for non severe acute respiratory infection. We hereby present data on antibiotic usage prior the admission and antibiotic susceptibility of major circulating respiratory pathogens in children under five years of age admitted to the Hôpital d’Enfants de Rabat, Morocco, with a diagnosis of clinical severe pneumonia (using World Health Organization (WHO) standardized case definitions) during a period of 14 months (November 2010–December 2011), as part of a larger hospital-based surveillance study designed to understand the etiology and epidemiology of severe pneumonia cases among children. Data were collected through a questionnaire administered to the parents and from the medical record. Seven hundred children were recruited after obtaining parental consent. The mean age was 21.5 months (SD 14.6). 29.4% (206/700) received antibiotics two weeks previous their admission. 86.5% (166/192) of antibiotics were prescribed by a physician, (21/192; 10.9%) obtained directly the antibiotics from the pharmacy and 5 (2.6%) by self-medication. The multivariates analysis, showed that the use of antibiotics in pre admission was associated with a symptom duration of more than seven days (adjusted OR 3.98, 95% CI 2.17 to 7.31), with fever (aOR 1.52, 95% CI 1.2 to 2.28 ) and incomplete vaccination status(aOR 1.89, 95% CI 1.11 to 3.23). The bacterial susceptibility to the antibiotics used showed a good susceptibility rate to most antibiotics used for ARI. A good understanding of the determinants of the pre-admission usage of antibiotics in children with severe respiratory infections linked with an adequate surveillance of the antibiotic susceptibility from circulating pathogens could help policy makers improve their recommendations on management of respiratory infections.

BiographyJroundi Imane is MD, MPH, and a PhD candidate in the University of Barcelona. She is an Assistant Research Professor at the unit of training and research on public health and community health at the School of Medicine and pharmacy of Rabat, University Mohamed V in Morocco. Her field of research is about the determinants of respiratory infection among children under five in Morocco. She has published 20 papers in reputed journals and has is serving as volunteer in remoted areas for community projects for preventing and controling respiratory infections.

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Jroundi Imane, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsPhotodynamic therapy for diabetic foot infectionJoão Paulo TardivoFaculdade de Medicina do ABC, Brazil

Antibiotic therapy and debridement are the most used practices to manage infectious diabetic foot and usually culminate with some amputation. When infection is associated with vascular disease, the clinical pictures are more serious. The chance

of healing without surgical intervention is quite remote. Antibiotics are necessary but diabetic nephropathy is usually present and antibiotics can worsen the clinical condition. It is clearly necessary to develop novel treatment strategies for this health problem. Photodynamic therapy (PDT) is a treatment modality that uses light to generate in-situ reactive oxygen species and to cause death in any type of cell, including bacteria. Therefore, foot infections can be treated with PDT. Several characteristics of PDT favor it uses to treat diabetic feet: It is a very efficient antimicrobial agent, even against resistant microorganisms, avoiding development of resistance; it is applied locally avoiding systemic drug toxicity; it can be applied in outpatient regimens. We performed a clinical study to verify if PDT is an effective method to avoid amputation of infected diabetic feet. An inexpensive PDT protocol was developed and applied to 18 patients with osteomyelitis, classified as Grade 3 on the Wagner scale. Only one of these patients suffered amputation. In the control group, of 16 patients, all of them ended up suffering amputation. The rate of amputation in the PDT group was 0.029 times the rate in the control group and the difference is clearly statistically significant (p=0.002). Another study group with 65 diabetic patients with foot infections allowed the development of the Tardivo algorithm to access amputation risk. Three parameters were more important: tissue oxygenation, location of infection in the foot and progression of the sickness accessed by Wagner classification. We showed that the combined use of the algorithm and of the low-cost PDT protocol can decrease substantially the amputation frequency in diabetic patients.

BiographyJoão Paulo Tardivo has completed his PhD from Faculdade de Medicina do ABC. He is the Director of Diabetic Foot Institute. He has published more than 13 papers in reputed journals about photodynamic therapy and its application in diabetic foot.

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João Paulo Tardivo, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsCross-reactivity of synthetic corticosteroids on cortisol serum levels: A comparison between three different immunoassaysYannick WoutersKatholieke Universiteit Leuven, Belgium

Immunoassays are widely used in clinical laboratories as they have high specificity and are easy in use. A downside of these assays is cross-reactivity with structurally similar molecules to the analyte, which could lead to false clinical interpretation.

Due to structural similarity between methyl prednisolone and prednisolone and the analyte, falsely elevated cortisol levels have been reported with cortisol immunoassays. This study made a comparison between a manual radio immunoassay (RIA) and two automated cortisol assays on Cobas® 8000 (Cortisol I) and Modular® E170 (Cortisol II). Patient’s serum samples were pooled to obtain two concentration levels: A lower cortisol concentration of 5μg/dl and a higher concentration in normal range of 15μg/dl. Serum samples were spiked with different concentrations of prednisolone and methylprednisolone corresponding to commonly used oral doses of synthetic corticosteroid, ranging from 1 mg to 1000 mg (2000 mg) prednisolone (methylprednisolone), as found in literature. Serum was also spiked with a single concentration of dexamethasone, corresponding to a supra-therapeutic dosage of 800 mg per OS, which was expected to have no cross-reactivity with either assay. In one volunteer, serum cortisol levels were measured at different time intervals after the intake of 32 mg Medrol®, the next day after a late-night intake of 2 mg dexamethasone. Differences in elevated cortisol levels by each assay could be indicative for the interference of in vivo metabolites of methylprednisolone.

BiographyYannick Wouters started at the University of Antwerp studying Biochemical Sciences, which he later on extended with a degree in drug development (Pharmacist). As of his great interest in biochemical markers he was given the opportunity to start a 5 year medical residency at the Catholic University of Leuven for the recognition as Clinical Biologist. In his current position he works as an Intern in Microbiology at the clinical laboratory in H-Hartziekenhuis Lier. He is also active as a Board Member of Farmant VZW, which organizes study courses for pharmacists in the field.

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Yannick Wouters, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsTreating multidrug-resistant bacterial infections with bacterial viruses (Bacteriophages)Andrzej GórskPolish Academy of Sciences, Poland

Reputed experts, international organizations and leading biomedical journals warn that the greatest risk to human health comes in the form of antibiotic-resistant bacteria. World Health Organizaton declared that the “post-antibiotic age” is

on the horizon while UK chief medical officer recently pointed out that antimicrobial resistance presents a threat as grave as climate change. There has been a growing search for alternative remedies and bacteriophages (phages) have been in the center of interest. In 2005 the first center of phage therapy in the European Union was established at our Institute which has been treating patients with a wide range of bacterial infections resistant to antibiotics therapy. Our results suggest that phage therapy can achieve good results in approx. 40% of patients with untreatable infections and is very well tolerated. Phage administration may affect patients’ immunity but its alterations are unlikely to mediate the effects observed. Although phage may elicit antibodies that can neutralize phage antibacterial activity in vitro there appears no correlation between antibody responses and the clinical outcome of phage therapy. Our recent hypothesis on phages specifically targeting infected tissues may further improve the results and open new perspectives for phage therapy.

BiographyAndrzej Górsk is currently Vice president, at Polish Academy of Sciences, Head of Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw and also Professor of Medicine/Immunology, The Medical University of Warsaw.

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Andrzej Górsk, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsDetermination the frequency of blaNDM, blaPER, blaVEB, blaIMP, and blaVIM type genes among A. baumannii isolates from hospitalized patientsFatemeh FallahShahid Beheshti University of Medical Sciences, Iran

The aim of this study was to determine the frequency of blaNDM, blaPER, blaVEB, blaIMP, and blaVIM type genes among A. baumannii isolates from hospitalized patients in two hospitals in Tehran, Iran. Antibiotic susceptibility tests were performed

by Kirby-Bauer disc diffusion and Broth microdilution methods. The frequency of MBL (metallo-beta-lactamase) and ESBL (extended-spectrum-beta-lactamase) producers was evaluated by CDDT. The β-lactamases genes were detected by PCR and sequencing methods. We found the resistance of A. baumannii isolates against some antibiotic such as ceftazidime, cefotaxime, cefepime, imipenem, meropenem, amikacin, piperacillin, ciprofloxacin, piperacillin/tazobactam, ampicillin/sulbactam, co-trimoxazole, tetracycline, and 1 (1.8%) to colistin. The prevalence of blaPER-1, blaVEB-1, blaIMP-1, and blaVIM-1 genes was 71 (78.03%), 36 (39.5%), 3 (3.48%), and 15 (17.44%), respectively. We concluded the prevalence of ESBLs and MBLs-producing A. baumannii strains detected in this study is a major concern and highlights the need of infection control measures.

BiographyFatemeh Fallah has completed her DVM from Tehran University and Postdoctoral studies in clinical microbiology from Shahid Beheshti University School of Medicine. She has passed fellowship in Mycobacterium from Bradford University School of Pharmacy, UK. She is faculty member of School of Medicine and deputy of Pediatric Infection Research Center. She has published more than 50 papers in reputed journals and has been serving as an Editorial Board Member of repute.

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Fatemeh Fallah, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003






AntibioticsStudy of antibiotic prescription pattern and associated risk factors in the ICUKashvi GuptaManipal University, India

Background: Critically ill patients admitted to the intensive care unit are highly vulnerable to infections and are treated by empiric broad spectrum antibiotics based on the physician’s priorexperience. Inappropriate and/or prolonged treatment increases mortality and antimicrobial resistance alongside increasing the duration of hospital stay and costs. Studies on drug utilization in the ICU along with associated risk factors are necessary to detect early signs of irrational drug usage and to propose interventions for improving the standard of clinical practice.

Subjects and Methods: A prospective observational study was conducted in the ICU of KMC Hospital Jyoti circle Mangalore for duration of 1 month. Data was collected using a proforma on patient demographics, date and reason for admission to the ICU, outcome of ICU stay and antibiotics prescribed–dosage, frequency and route of administration. It was compiled and univariate analysis was performed. Antibiotics were classified using anatomical therapeutic chemical (ATC) classification system to measure drug usage. Unit price for each antibiotic was obtained from the hospital pharmacy.

Results: Out of 85 patients analyzed during the study period, 58 patients (68%) were prescribed antibiotics during their stay in the ICU. Mean age of the population under study was 53 years and the distribution between males and females was 59:26. 64 patients (75%) could be discharged after treatment while 21 patients (25%) died in the ICU due to their illness. The average duration of stay was found to be 8 days and the most frequent indication for admission was related to infections of the respiratory system followed by sepsis. Most patients received only one antibiotic (62%) and combination therapy of more than three antibiotics was seen in less than 10% of patients. A total of 378 antibiotics were prescribed and the most frequently prescribed antibiotics are depicted in Figure 1. Ceftrixone, a third generation cepahlosporin (116 units) followed by Piperacillin and Tazobactum (105 units) were maximally consumed. On univariate analysis, patients who were prescribed higher number of antibiotics were further linked to poorer ICU outcomes and use of carbapenems like Meropenem and Imipenem, but no co-relation could be established between the number of antibiotics prescribed and the gender or duration of ICU stay of the patient. The total cost incurred on antibiotics was Rs. 2,43,715.66 in the group while the median expenditure was Rs. 1120.89. The cost of antibiotics ranged from Rs. 11.95 for Metronidazoleto Rs. 1835 for Teicoplanin. On univariate analysis it was found that the cost ofantibiotics increased with the number of antibiotics prescribed and age of the patient(p=0.005).

Conclusion: In conclusion, antibiotics are frequently prescribed to intensive care unit patients. The study reveals that elderly patients and those with respiratory infections were found to be at a greater risk for combination therapy of more than three antibiotics which was further associated with poorer ICU outcome. Carbapenems are being increasingly used as a rescue drug when there is no response to the empiric treatment. The appropriateness of antibiotic prescription is imperative to avoid the development of resistant organisms and to reduce the burden of treatment costs for patients especially in developing countries. This requires an urgent multidisciplinary effort for the formulation of antibiotic prescription guidelines so as to aid the clinicians in making the right antibiotic choices.

BiographyKashvi Gupta is in final year of Bachelor of Medicine in Kasturba Medical College, Mangalore, India. She has written seven research papers in various departments from Microbiology to Pharmacology. She has presented her work in international research conferences such as MEDICON 2013 held in Delhi (where she also won the best poster presentation award) and British Pharmacology Society Conference 2013 held in London. She completed a surgical elective at the Royal College of Surgeons in January 2015. She has also attended many research workshops and has published one of her papers in a reputed journal.

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Kashvi Gupta, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsAntibiotic therapy for pelvic inflammatory disease (PID). A meta analysisSavaris R FUniversidae Federal do rio Grande do Sul, Brazil

PID is a common cause of morbidity in young women and affects between 4% to 12% of young women. The main intervention for acute PID is the use of broad-spectrum antibiotics which cover C. trachomatis, N. gonorrhoeae and anaerobic bacteria,

administered either intravenously or orally. Both routes have been considered effective. However, optimal treatment strategy for PID is unclear. We determined the effectiveness and harms of antibiotic regimens used to treat pelvic inflammatory disease and will also share our experience with alternative drug regimen with clindamycin. We retrieved a total of 2057 references published between January 1946 and Januray 2015 from different databses. We considered 85 reports for this review. Overall, no treatment guideline showed superiority to alternative treatment (CDC - RR 1.01, 95% CI 0.98 to 1.03; IUSTI/BASHH - RR 1.01, 95% CI 0.95 to 1.07). There was no difference in PID rates of cure between regimens that used or not antibiotics with cover against anaerobic bacteria (RR 0.99, 95% CI 0.96 to 1.03). Regimens using azithromycin were superior to alternative regimens using doxycycline (RR 1.07, 95% CI 1.02 to 1.14), but a significant heterogeneity among groups was identified (I2=81%). There is no evidence that rates of cure of PID are higher in regimens using metronidazole or other antibiotics with cover against anaerobic bacteria. Regimens with azithromycin were superior than those using doxycycline in mild-moderate cases of PID, but due to heterogeneity among studies, this finding should be interpreted with caution.

BiographySavaris R F his PhD from the University Federal do Rio Grande do Sul, respectively. He had his Postdoctoral studies at University of California, San Francisco (2007), and at the University of North Carolina, Chapel Hill (2013). He is an Associate Professor from the Univ. Federal do Rio Grande do Sul, in the ObGyn Department and co-ordinator on the Cochrane Review on Pelvic Inflammatory Disease. He has published more than 40 papers in reputed journals.

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Savaris R F, J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsClofazimine biocrystals and immunomodulationGi Sang Yoon, Rahul K Keswani, Sudha Sud, Theodore J Standiford, Kathleen A Stringer and Gus R RosaniaUniversity of Michigan, USA

Clofazimine (CFZ) is a clinically useful antibiotic on the WHO’s list of essential medicines for the treatment of leprosy. Since it’s initial use in 1969, CFZ has cured over 16 million leprosy patients with no reports of drug resistance. Therefore, with the

global emergence of drug-resistant microbials, CFZ has received renewed interest. In mice, as in humans, orally administered CFZ is actively sequestered as a mechanism of drug detoxification by tissue resident macrophages, where it is mostly found as intracellular crystal-like drug inclusions (CLDIs). Although there have been several reports of CFZ immunomodulatory action, the underlying mechanism for this property is mainly unknown. With the purpose of elucidating immunomodulatory mechanisms, our studies have shown that CLDI’s possess functions that include the downregulation of Toll-like receptor expression and pro-inflammatory pathways, while upregulating anti-inflammatory pathways in macrophages without exhibiting toxicity. Furthermore, with the use of well-established animal injury models (lung and foot) we have shown that CLDI’s are associated with increased IL-1RA production, leading to profound systemic anti-inflammatory activity. In light of new knowledge on the safety and activity of CLDIs, we are currently researching into the reformulation and repurposing of CFZ as synthetic CLDIs for the treatment of inflammatory disorders such as COPD and rheumatoid arthritis.

BiographyGi Sang Yoon has completed his PhD from Wayne State University in Cell Biology and Anatomy. He is currently investigating the mechanisms of drug sequestration and accumulation, and elucidating drug mechanisms of action with the goal of reformulating and repurposing clinically successful drugs as part of his postdoctoral studies at the University of Michigan College of Pharmacy. He has published numerous papers in reputed journals and has been serving as a reviewer for two journals.

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Gi Sang Yoon et al., J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003




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AntibioticsDeveloping a lead compound for the inhibition of bacterial DNA GyraseUsman Khan1,2 and Donald Weaver1,2

1University of Toronto, Canada2University Health Network, Canada

Purpose: As reported by the Centers of Disease Control (CDC), multi-drug resistance bacteria have an estimated cost of $40 billion on health-care systems globally. In the past 20 years, developments of therapeutics aimed at killing infectious strains of bacteria have been very limited. Bacterial DNA gyrase is a complex enzyme that is used to relieve strain from DNA unwinding and introduces supercoils for various cellular processes including DNA compaction, replication and transcription. Inhibition of bacterial DNA gyrase provides an avenue to develop compounds that can be optimized for clinical applications. The present study focuses on using computational predictions, synthetic chemistry and in vitro enzymatic activity assays to search for a lead compound.

Methods: The rationale for the study employs molecular dynamic simulations and binding energy calculations to predict potential lead compounds from a library containing 800 substituted pyrrole and thiophene analogues. The cumulative binding energy predictions and ligand interactions with binding pocket residues were used to select 25 compounds. These compounds were then tested in in vitro DNA supercoiling assays.

Results: In silico predictions demonstrated favorability of compounds to interact with the ATPase binding site of Gyrase subunit B. Ligand binding scores suggested a preference for tetrazole-substituted thiophenes that adopted pi-stacking interactions with hydrophobic side chains and formed hydrogen bonds with donor side chains. In vitro DNA supercoiling assays indicated dose-dependent reduction of supercoiling activity of DNA gyrase at a concentration of 80 µM for compounds 0599, 0607 and 0608.

Conclusions: Molecular modeling predictions were able to select compounds that inhibit bacterial DNA gyrase in vitro. Computational chemistry and synthetic approaches are being used to optimize analogues of top compounds.

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Usman Khan et al., J Drug Metab Toxicol 2015, 6:4http://dx.doi.org/10.4172/2157-7609.C1.003

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