Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Archana Dambal

"Journal of clinical and diagnostic research is a welcome change in publishing practices. It aims to reach out to the grass-root level researchers who do not lack in experience, clinical material and ideas, but lack in their knowledge in English language and statistics. The journal achieves it's aim by supporting in these exact domains.
It also gives due credit to all research designs like descriptive and qualitative studies while many journals ignore these important study designs. The rigorous review process does not allow any compromise in quality
It is indexed in many indexing agencies and the articles are available under creative commons licence free of cost
The frequency of publication supports many aspiring authors from India and other countries.
It's wide scope welcomes articles across various specialities in medicine. In an era when there is an unscientific insistence on speciality specific research by regulatory bodies in medical education, JCDR supports collaborative research across specialities. I wish the publisher all the best in his future endeavors."



Dr. Archana Dambal
Department of General Medicine,
Belgaum Institute of Medical Sciences,Belgaum, Karnataka,INDIA,
On 30 Nov 2018




Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Original article / research
Year : 2011 | Month : December | Volume : 5 | Issue : 8 | Page : 1559 - 1563

Invitro Activity of Tigecycline Against Gram Positive and Gram Negative Isolates in a Tertiary Care Hospital

Shanthi M., Uma Sekar

1. MBBS,MD, Assistant Professor Department of Microbiology, Sri Ramachandra Medical college and Research Institute, Sri Ramachandra University, Porur, Chennai-600116 Tamil Nadu 2. MBBS, DCP, MD, Professor and Head Department of Microbiology, Director, Sri Ramachandra Laboratory services Sri Ramachandra Medical college and Research Institute , Sri Ramachandra University Porur, Chennai-600116 Tamil Nadu

Correspondence Address :
Uma Sekar, MBBS, DCP, MD,
Professor and Head, Department of Microbiology
Director ,Sri Ramachandra Laboratory services
Sri Ramachandra Medical College and Research Institute
Sri Ramachandra University, Porur,
Chennai-600116. India.
Phone: +91 98408 37632
E-mail: umasekar02@yahoo.co.in

Abstract

Background: Resistance to multiple anti-microbial agents among gram positive and gram negative pathogens is high worldwide. Tigecycline, a glycylcycline antibiotic is a promising advancement in the treatment of infections caused by multidrug resistant organisms.

Objectives: To evaluate the invitro activity of tigecycline against a spectrum of Gram positive and Gram negative pathogens Materials and Methods: A total of 195 non -repetitive, clinically significant isolates obtained from various clinical specimens from hospitalised patients were included in the study. The organisms isolated include methicillin resistant Staphylococcus aureus (MRSA) (n=40), Enterococcus fecalis (n=15), Streptococcus pneumoniae (n=10), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli(n=40), ESBL producing Klebsiella pneumoniae (n=40), ESBL producing Enterobacter spp (n=15), Serratia marcesens (n=5), Acinetobacter baumannii (n=25) and Haemophilus influenzae (n=5). Minimum inhibitory concentrations (MIC) were determined for various classes of anti-microbial agents including tigecycline using broth microdilution methodology as defined by the Clinical laboratory Standards Institute (CLSI) using Microscan panels. Interpretation of the anti-microbial susceptibility testing was done as per CLSI criteria. For tigecycline, interpretative criteria was as per the United States Food and Drug Administration breakpoints. MRSA and ESBL screening were performed in accordance with CLSI guidelines.

Results: Tigecycline exhibited good activity against all the isolates tested in the study. The three most active agents in vitro against MRSA and Enterococcus fecalis isolates in this study were tigecycline, vancomycin and linezolid with 100 % susceptibility. In the case of ESBL producing Enterobacteriaceae, meropenem and tigecycline were the most active agents. Tigecycline was the most effective anti-microbial agent against the multidrug resistant Acinetobacter baumannii including the meropenem resistant isolates.

Conclusion: Tigecycline is an alternative option for the treatment of multi-drug resistant pathogens causing complicated skin and soft tissue and intra-abdominal infections.

Keywords

Anti-microbial resistance, Tigecycline, In vitro susceptibility

How to cite this article :

Shanthi M., Uma Sekar. INVITRO ACTIVITY OF TIGECYCLINE AGAINST GRAM POSITIVE AND GRAM NEGATIVE ISOLATES IN A TERTIARY CARE HOSPITAL. Journal of Clinical and Diagnostic Research [serial online] 2011 December [cited: 2019 Apr 24 ]; 5:1559-1563. Available from
http://jcdr.net/back_issues.asp?issn=0973-709x&year=2011&month=December&volume=5&issue=8&page=1559-1563&id=1795

INTRODUCTION
Treatment of serious life threatening infections due to multi-drug resistant (MDR) pathogens presents a difficult challenge due to limited therapeutic options. Increased resistance to anti-bacterial agents among clinically important organisms, particularly nonfermentative Gram negative bacilli (including Acinetobacter spp. and Pseudomonas aeruginosa), extended spectrum beta lactamase (ESBL) producing Enterobacteriaceae and Gram positive organisms such as Staphylococcus aureus and Enterococcus spp is of great concern (1). Infections caused by these organisms leads to prolonged hospitalisation, high treatment cost, increased morbidity and mortality (2). With the emergence and spread of carbapenem resistance among Pseudomonas aeruginosa, Acinetobacter spp and members of Enterobacteriaceae, the only available treatment options remaining is the polymyxin group of antibiotics. Methicillin resistant Staphylococcus aureus (MRSA)and vancomycin resistant Enterococcus (VRE) spp are also on rise in many parts of the world (3).

In Intensive care units (ICU) carbapenems and vancomycin are used as the last resort in the treatment of MDR Gram negative and Gram positive infections respectively. Currently, carbapenem resistance is increasingly reported among Gram negative bacteria. The prevalence of vancomycin intermediate Staphylococcus aureus (VISA) strains in India is reported to be 6.3% (3),(4). Clearly there is a need for new anti-microbial agents with novel mechanisms of actions to keep in pace with the emergence and spread of MDR pathogens.

Tigecycline, a newer semi-synthetic gylcylcycline derived from minocycline is a promising molecule in the treatment of infections caused by MDR organisms. Tigecycline is a bacteriostatic agent and has potent invitro activity against several Gram positive andGram negative aerobic and anaerobic bacteria including MRSA, VRE, Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxaella catarrhalis, Haemophilus influenzae, ESBL producing Enterobacteriaceae and carbapenem resistant Acinetobacter spp. Furthermore, it is not affected by the known mechanisms of resistance to tetracycline and minocycline such as efflux pumps and ribosomal protective mechanisms. In addition it does not present cross resistance with other antibiotics such as beta lactams, aminoglycosides and fluoroquinolones. However it is affected by the intrinsic multidrug pumps of Pseudomonas aeruginosa and Proteae and it is not useful to treat infections caused by them (5),(6),(7). Because of this promising microbiological, pharmacodynamics and pharmacokinetic profile, tigecycline is a good alternative to treat infections due to MDR pathogens. As of now, tigecycline is approved for the treatment of complicated skin and soft tissue and intra-abdominal infections (8).

We evaluated the invitro activity of tigecycline against a spectrum of Gram positive and Gram negative pathogens.

Material and Methods

Bacterial isolates:
The study was conducted in a 1600 bedded university teaching hospital from August 2007- May 2008. A total of 195 non-repetitive, clinically significant isolates from hospitalised patients were included in the study. The source of these isolates included pus (n=58), blood (n=42), bronchoalveolar lavage [BAL] (n=29)urine (n=25), wound swab (n=23), sputum (n=11), ear swab (n=2), cerebrospinal fluid [CSF] (n=2), bile (n=1), pleural fluid (n=1), and peritoneal fluid (n=1). The organisms were identified either by conventional methods or Microscan walkway system (Dade Behring Inc., USA) using Gram negative and Gram positive panels. The organisms which were tested included MRSA (n=40), Enterococcus fecalis (n=15), Streptococcus pneumoniae (n=10), ESBL producing Escherichia coli (n=40) , ESBL producing Klebsiella pneumoniae (n=40), ESBL producing Enterobacter spp (n=15), Serratia marcesens (n=5) ,Acinetobacter baumannii (n=25) and Haemophilus influenzae (n=5).

Anti-microbial susceptibility testing:
Minimum inhibitory concentrations (MIC) were determined using broth microdilution methodology as defined by the CLSI using Microscan panels (9). The test panel for Gram negative isolates included (concentration given in μg/ml): amikacin (0.5-64), amoxicillin-clavulanic acid (0.12/0.06- 32/16), ampicillin (0.5-32), cefepime (0.5-32) ceftazidime (8-32), cefotaxime (0.06-64), levofloxacin (0.008-8) meropenem (0.06-16), minocycline (0.5-16), piperacillin-tazobactam (0.06/4-128/4) and tigecycline (0.008-16).The gram positive organisms were tested against the following anti-microbials: amoxicillin-clavulanic acid (0.03/0.0015-8/4), ampicillin (0.06-16), penicillin (0.06-8), linezolid (0.5-8), cefotaxime (0.03-64), levofloxacin (0.06-32), minocycline (0.25-8) ,vancomycin (0.12-32) and tigecycline (0.008-16). MIC determination was carried out using freshly prepared cation adjusted Mueller-Hinton broth to prevent oxidative degradation of tigecycline in aqueous solution (10). For Streptococcus pneumoniae and Haemophilus influenzae Mueller Hinton broth with 3% lysed horse blood was used. Broth microdilution panels inoculated with Gram negative organisms were incubated in ambient air at 35°C for 16-20 hours. Staphylococcus aureus and Enterococcus spp were incubated in ambient air at 35ºC for 24 hours. Panels with Streptococcus pneumoniae and Haemophilus influenzae were incubated at 35ºC for 16-20 hours in CO2 incubator. Quality control strains were used in the study of E.coli ATCC 25922Staphylococcus aureus ATCC 29213 and Enterococcus fecalis ATCC 29212. Interpretation of the anti-microbial susceptibility testing was done as per CLSI criteria (9). Since there were no CLSI recommended interpretative criteria for tigecycline, the United States Food and Drug Administration (FDA) breakpoints: Staphylococcus aureus (susceptible ≤0.5 μg/ml), Enterococcus (susceptible ≤0.25 μg/ml), Enterobacteriaceae (susceptible ≤ 2μg/ ml, intermediate 4μg/ml, resistant ≥8μg/ml) were used. The FDA had not established breakpoints for Acinetobacter baumannii, therefore MIC interpretation was done using the breakpoints criteria listed for Enterobacteriaceae as per previous studies done in centers in India and other countries in the world (2),(9),(11),(12).

Anti-bacterial resistance determination:
Methicillin resistance in Staphylococcus aureus was detected using cefoxitin (30μg) (Himedia laboratories, Mumbai, India) disc by diffusion method and interpreted in accordance with CLSI criteria (9).

The presence of ESBL among E.coli, K. pneumoniae and Enterobacter spp was detected according to CLSI methodology for which cefotaxime 30 μg, cefotaxime–clavulanic acid (30/10μg), ceftazidime (30 μg) and ceftazidime-clavulanic acid (30/10 μg) discs (Himedia laboratories, Mumbai, India ) were used. An increase of ≥ 5 mm in inhibition zone on the combination disc was compared to the cephalosporin alone indicated ESBL production (9).

Results

Bacterial isolates:
Gram positive (n=65): The MRSA (n=40) isolates were from pus (n=17), wound swab (n=9), blood (n=9), BAL (n=2), ear swab ( n=2) and peritoneal fluid (n=1). Streptococcus pneumoniae (n=10) were from sputum (n=8), BAL (n=1) and pleural fluid (n=1). Enterococcus fecalis (n=15) were isolated from pus (n=5), urine (n=4), wound swab (n=3) and blood (n=3).

Gram negative (n=130):
ESBL producing Escherichia coli (n=40) were isolated from pus (n=16) , blood (n=8), urine (n=6) wound swab (n=5) BAL (n=4) and bile (n=1).The source for ESBL producing Klebsiella pneumoniae (n=40) were pus (n=15), blood (n=11),BAL (n=6), wound swab (n=5) and urine (n=3). Acinetobacter baumannii included in the study were isolated from BAL (n=14), blood (n=6), urine (n=2), CSF (n=1) wound swab (n=1) and pus (n=1). Out of the 15 Enterobacter spp, 8 were from urine, 4 from blood, 2 from BAL and 1from pus. There were 3 Serratia marcesens isolated from pus and 2 from urine specimens. Five isolates of Haemophilus influenzae were tested, which were obtained from sputum (n=3), blood (n=1) and CSF (n=1).

Susceptibility to tigecycline:
All MRSA were susceptible with MIC ranging from 0.03-0.25μg/ml. The ESBL producing K. pneumoniae, E.coli and the Enterobacter species were all susceptible to tigecycline. Among the A. baumannii isolates (n=25), 20 were susceptibile to tigecycline and in 5 isolates the MIC was in intermediate range.

Susceptibility to other classes of Antimicrobial agents: (Table/Fig 1) shows the susceptibility pattern, the MIC50 and MIC90 values of the Gram positive isolates included in the study.

All the MRSA isolates were susceptible to tigecycline, minocycline, vancomycin and linezolid. Among the E. fecalis and Streptococcus pneumoniae isolates, there was uniform susceptibility to tigecycline, vancomycin and linezolid.

The susceptibility profile of Gram negative isolates is shown in (Table/Fig 2).

The ESBL producing E.coli and Enterobacter spp, were susceptible to amikacin, piperacillin– tazobactam, meropenem and tigecycline. Levofloxacin and cefepime showed poor activity against these organisms. In the case of ESBL producing K. pneumoniae, meropenem and tigecycline were the most active agents. Amikacin, pipercillin-tazobactam, cefepime and levofloxacin exhibited high MIC in most of the isolates tested in the study.

With the exception of Ampicillin and Amoxycillin clavulanic acid, Serratia marcesens isolates were susceptible to all the antimicrobial agents in the panel.

Haemophilus influenzae isolates were susceptible to all the antimicrobials tested in the study.

Among the A. baumannii (n=25), amikacin, levofloxacin, cefepime and piperacillin-tazobactam showed poor activity with only few isolates being susceptible. Meropenem resistance was encountered in 8/25 isolates. Tigecycline was the most effective anti-microbial agent against the multidrug resistant Acinetobacter baumannii including the meropenem resistant isolates.

Discussion

Bacterial resistance to the commonly used anti-microbial agents is increasing and it is a matter of concern, particularly in patients with serious and complicated nosocomial infections. Emergence and spread of methicillin resistance among Staphylococcusaureus, ESBL production in Enterobacteriaceae and carbapenem resistance among Gram negative bacteria have led to the limited therapeutic options, resulting in increased morbidity and mortality. The development of new ant-imicrobial agents with novel modes of action is critically needed to keep in pace with the development and spread of drug resistance mechanisms among bacteria (11).

Tigecycline is a glycylcycline compound with broad spectrum of bacteriostatic activity against gram positive pathogens including MRSA, VISA (Vancomycin intermediate Staphylococcus aureus)VRE and penicillin resistant Streptococcus pneumoniae; against Gram negative organisms like ESBL producing Enterobacteriaceae, Multidrug resistant Acinetobacter species including the carbapenem resistant isolates, anaerobes such as Bacteriodes fragilis group, atypical organisms like Mycoplasma spp, Chlamydia spp and rapidly growing Mycobacteria (5). It acts by inhibiting the protein synthesis in the bacterial cell by binding to the 30S subunit of the ribosome. In comparison with tetracycline, tigecycline exhibits its bacteriostatic effects by binding to corresponding ribosomal sites with greater affinity and irrespective of the mutations that confer resistance to tetracycline and also it evades the tetracycline efflux pumps. Tigecycline does not exhibit co-resistance with known mechanisms of resistance. Its capacity to penetrate into various tissues, makes it useful in the treatment of infections of the skin and soft tissues as well as intra -abdominal infections, whereas its low serum concentrations compromise its use in bloodstrinfections. It is not useful in the treatment of nosocomial pneumonia as indicated by poor results in the study of ventilator associated pneumonia (13), (14).

This study was done to evaluate the invitro activity of tigecycline against MRSA, ESBL producing Enterobacteriaceae, multi-drug resistant Acinetobacter baumannii by determining their MIC to tigecycline. The other organisms tested were Streptococcus pneumoniae and Haemophilus influenzae.

MRSA is a global problem with treatment options limited to glycopeptides (vancomycin, teicoplanin), oxazolidinones (linezolid), streptograminins (quinupristin-dalfopristin), and polycyclic compounds (tetracycline, tigecycline).The prevalence of MRSA from several centres in India as reported ranges from 20-80%. Emergence of vancomycin and linezolid resistance among Staphylococcus aureus is an alarming threat. The prevalence of vancomycin intermediate Staphylococcus aureus (VISA) strains in India is reported to be 6.3% (4). Later there were sporadic reports of vancomycin resistant Staphylococcus aureus (VRSA) from India (15),(16). More recently, a study conducted in a tertiary care centre to identify the emergence of vancomycin resistance in south India, reported 4.46% of VISA and 1.95% of VRSA (17). The three most active agents in vitro against MRSA isolates in this study are tigecycline, vancomycin and linezolid with 100% susceptibility. Hence tigecycline plays a very important role in the treatment of infections caused by MRSA and is currently the drug of choice against the VISA and VRSA isolates (13),(15).

Tigecycline demonstrated excellent activity against the Streptococcus pneumoniae, Haemophilus influenzae isolates. In India till date multi-drug resistance is not a significant problem in these pathogens. Hence tigecycline is not an optimal choice for the management of infections caused by Streptococcus pneumoniae and Haemophilus influenzae.

Tigecyline was highly active against the ESBL producing Enterobacteriaceae. Although carbapenems are widely regarded as the drugs of choice for treatment of infections caused by ESBL producing organisms, production of beta lactamases capable of hydrolyzing carbapenems have been reported from Enterobacteriaceae (19). The available alternative treatment options in such infections are the tigecycline and the polymyxin B. However in this study, we did not encounter carbapenem resistance in the Enterobacteriaceae. In a multi-centric study from India, regardless of the presence or absence of ESBL, tigecycline exhibited good activity against Enterobacteriaceae (11).

A baumannii is one of the commonly isolated nosocomial pathogen, mainly from the patients in the ICU. These isolates are resistant to multiple anti-microbial agents including the carbapenems .Treatment options for carbapenem resistant Acinetobacter baumannii are limited to polymyxin and tigecycline. In the study isolates tigecycline demonstrated good activity against the Acinetobacter baumannii with MIC ≤2μ/ml in 80% (n=20) and in the remaining 20% (n=5) the MIC was in intermediate range (4μ/ml). A tigecycline susceptibility report from a tertiary care hospital in India reported a low rate of susceptibility (42%) to tigecycline among Acinetobacter species, where the organisms were totally unexposed to tigecycline and also to the tetracycline group of antibiotics (2). In another study from India, 70.6% of MDR Acinetobacter species were susceptible to tigecycline (11). In a study on 224 urine isolates from complicated urinary tract infections, the overall resistance to tigecycline in Acinetobacter spp was 14.2% and among the carbapenemresistant isolates, 32% were resistant to tigecycline (20). Hence the use of tigecycline should be strictly monitored to prevent the development and dissemination of resistance against tigecycline, which is the last resort in the treatment of MDR Acinetobacter baumannii infections.

To conclude, the present study shows tigecycline is a potent antimicrobial agent against MRSA, ESBL producing Enterobacteriaceae and multi-drug resistant Acinetobacter baumannii. Due to its long half-life and large volume of distribution, it can be an important lifesaving agent in the treatment of polymicrobial intra-abdominal, skin and soft tissue infections. It is not useful in bloodstream infections and nosocomial pneumonia. In view of its excellent activity against MDR pathogens, it is prudent to reserve tigecycline for life threatening infections when other options fail. This will minimise the emergence of resistance to tigecycline.

Key Message

Tigecycline is a potent anti-microbial agent against MRSA,VISA,ESBL and carbapenem resistant Gram negative pathogens Useful in the treatment of complicated skin and soft tissue and intra-abdominal infections

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