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

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On Sep 2018




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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."



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Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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Saraswati Dental College
Lucknow
On Sep 2018




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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.
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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.
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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
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2008 | Month : October | Volume : 2 | Issue : 5 | Page : 1057 - 1064 Full Version

Developing A Protocol For Empirical Antibiotics For Neonatal Sepsis Based On Data On Antibiotic Sensitivity Patterns At Two Tertiary Neonatal Units In Southern India


Published: October 1, 2008 | DOI: https://doi.org/10.7860/JCDR/2008/.356
DIWAKAR KK*, ANANTHEN KS**

Department of Pediatrics, Malankara Orthodox Syrian Church Medical College, Kolenchery , Kochi, Kerala – 682311(India). **Senior Registrar, Department of Neonatology, Malankara Orthodox Syrian Church Medical College, Kolenchery , Kochi, Kerala – 682311(India).

Correspondence Address :
Diwakar KK, MD, FRCPCH (UK)
Head, Department of Neonatology,
Prof. Department of Pediatrics,
Malankara Orthodox Syrian Church
Medical College, Kolenchery , Kochi,
Kerala – 682311, (India).
Email:krishnadiwakar@fulbrightweb.org

Abstract

Sepsis continues to be a major challenge in neonatal care. The choice of first –line antibiotics to be commenced in at-risk neonates has always been a matter of debate.
Objective
To compare the bacteriological profiles of isolates from blood cultures at two neonatal centers situated in different states of India, and evaluate if a common ‘first-line combination’ of antibiotics could be recommended for infants at-risk for sepsis.
Method
Isolates obtained from neonatal blood culture done at the Kasturba Medical College, Manipal, Karnataka (Center A) and the Malankara Orthodox Syrian Church Medical College, Kochi, Kerala (Center B) were retrospectively analyzed. The sensitivity of common antibiotics and their combinations was analyzed in relation to the bacteriological profile and age of onset of sepsis (Early or late).
Results
Six ninety seven isolates from 3077 samples of blood cultures done in at-risk neonates were retrospectively evaluated. Five twenty nine isolates were obtained from Center A and 168 from Center B. Coagulase negative staphylococcus (CONS) constituted the largest group (37.6%) of these isolates. Klebsiella species (18.5%), Pseudomonas (14.1 %), Acinetobacter sp. (7 %), Enterobacter sp. (4.9 %) were the other common isolates. The combination of Ampicillin + Amikacin covered 49% isolates, followed by Ciprofloxacin + Gentamicin (46.4%), Ciprofloxacin + Amikacin (44%) and Ampicillin + Gentamicin (38.6%). The types of isolates and the sensitivity pattern of isolates to combination antibiotics was found to be similar at both the centers (r = 0.81). Addition of a ‘third’ antibiotic Cefotaxime to the combination of Ampicillin + Amikacin did not reveal any significantly increase in the number of isolates covered. The antibiotic sensitivity patterns were similar among EOS and LOS and correlated at r= 0.9 (p<0.01) for individual antibiotics and at r = 0.97 (p < 0.01) for combination antibiotics.
Conclusion
The combination of Ampicillin + Amikacin , covers the maximum numbers of isolates and could be the best first-line antibiotics in neonatal sepsis. Addition of more antibiotics does not necessarily result in wider coverage of isolates. The initial combination of antibiotics could be the same for EOS and LOS. Blood cultures are mandatory in all neonatal sepsis for seeking specific sensitivity patterns and accordingly modifying the antibiotic therapy.

Keywords

Neonatal Sepsis, First-line antibiotics.

Introduction
Infection, till date, continues to be a bugbear in the management of neonates. Commencing antibiotics in at-risk infants has become the norm of neonatal intensive care. Despite the availability of rapid methods of diagnosis and identification, the choice of the primary antibiotic continues to be based on recommendations of literature. The present study was undertaken to determine the ‘first line antibiotics’ that would be optimal to commence in at- risk neonate while awaiting the blood cultures and sensitivity report. The authors postulate that obtaining data from two hospitals separated geographically over 500 km, in different states, could provide comparative information that could facilitate a consensus in choosing the ‘first-line’ antibiotics in neonatal sepsis.

Material and Methods

Isolates obtained from neonatal blood culture done over a 4-year period from January 1999 to December 2002 at the Kasturba Medical College, Manipal, Karnataka (Center A) and over an 18 months period, from March 2004 to August 2005, at the Malankara Orthodox Syrian Church Medical College, Kochi, Kerala (Center B) were retrospectively analyzed. The indications for blood cultures were the same at both centers. Cultures were done for evaluating at risk neonates and in those infants clinically suspected to have sepsis. The age of presentation, identity of isolates, frequency and sensitivity to commonly used antibiotics were evaluated.

The attempt to search for an ideal combination to cover the largest cluster of isolates was performed by evaluating the sensitivity of isolates to any one of the antibiotics of the selected combination. The profile and sensitivity of isolates were also analyzed separately for both the centers, and the coefficient of correlation determined.
Isolates obtained in blood cultures of infants with in 72 hours of life was considered “Early Onset Sepsis” (EOS) and those beyond 72 hours considered as “Late Onset Sepsis” (LOS). Sensitivity pattern of isolates based on the ‘onset of sepsis’ was also evaluated. The principal investigator was the same and was head of the neonatal services at both the centers during the study period. Relevant statistical analysis was done using the SPSS version 7.5 statistical package.

Results

Three thousand seventy seven samples of blood cultures were evaluated (Table/Fig 1).Two thousand five hundred forty five of these were from Center A and 532 were from Center B. Isolates were reported in 697 (22.7%). Coagulase negative staphylococcus (CONS) constituted the largest group (37.6%) of these isolate. This was followed by Klebsiella species (18.5%), Pseudomonas (14.1 %), Acinetobacter sp.(7 %), Enterobacter sp. (4.9 %) and other bacteria in varying percentages. The isolates were similar at both the centers though they varied in their frequency of occurrence (Table/Fig 1). While CONS was the most common isolate at both centers, Enterobacter sp. and Acinetobacter sp. were more common than Klebsiella at Center B.

Contaminants, which included aerobic spore bearing bacilli constituted 6% (42/697) of the total isolates, and were excluded from further analysis (Table/Fig 1).Six hundred fifty five isolates were therefore evaluated for sensitivity to commonly used antibiotics. Five hundred twenty of these were from Center A and 135 from Center B.

The antibiotics sensitivity of individual isolates was evaluated (Table/Fig 2). Gram negative organisms like Enterobacter, Pseudomonas and Klebsiella, were found to be more sensitive to Amikacin. Sensitivity to Ciprofloxacin was seen among both gram negative and gram positive bacteria. The antibiotics sensitivity pattern of identical species of bacteria was found to be different at the two centers (Table/Fig 2). The correlation for antibiotics sensitivity between the two centers was observed to be best for Enterobacter sp. and (r = 0.8, p =0.05) least for COPS (r =0.04, p = 0.9).

Individual antibiotics were then evaluated for their ‘antimicrobial cover’ against the organisms isolated (Table/Fig 3). The largest clusters of isolates were sensitive to Aminoglycosides --. Amikacin (37.7%) followed by Gentamicin (36.6%) and Netilmycin (28.9%). The sensitivity of isolates to aminoglycosides was followed by Ciprofloxacin (23.8%), Cotrimoxozole (23.5%), Cefotaxime (22%) and Ampicillin (18.5%). Comparison of the ‘antimicrobial cover’ of individual antibiotics at Center A and Center B (Table/Fig 3) were not identical and correlated at r = 0.57 (p = 0.07).

Antibiotic combinations commonly used in clinical practice, were assessed for the widest coverage against the isolates (Table/Fig 4). Eg. The combination of Ampicillin and Amikacin was evaluated to see if the isolates were sensitive to either Ampicillin OR Amikacin (Table/Fig 4). Ampicillin + Amikacin covered the largest cluster of bacteria (49%). This was followed by Ciprofloxacin + Gentamicin (46.4%), Ciprofloxacin + Amikacin (44%) and Ampicillin + Gentamicin (38.6%). The three drug combination of Cefotaxime + Ampicillin +Amikacin covered 50.5% while Cefotaxime+Ampicillin+Gentamicin covered 44.9% of the isolates. The numbers of isolates sensitive to the combination Ampicillin + Amikacin was compared to the combinations of other antibiotics and chi square test applied. The numbers of isolates sensitive to Ampicillin + Amikacin was significantly more than Ampicillin + Gentamicin (Chi square = 14.3, p = 0.002), Cefotaxime + amikacin (chi square = 8.7, p = 0.003), and Cefotaxime + Gentamicin (chi square = 3.98, p = 0.046). However, sensitivity of combination of Ampicillin + Amikacin was not significantly different from the combination of Ciprofloxacin + Gentamicin (Chi square = 0.88, p = 0.34). Though a greater percentage of isolates were sensitive to the combination Cefotaxime + Gentamicin than Cefotaxime+Amikacin, the difference was not statistically significant (chi square =0.9, p=0.3).
The differential evaluation of the centers showed that while in center A coverage provided by Ampicillin + Amikacin (51.3%) was followed by Ciprofloxacin + Gentamicin (47.7%), in Center B the combination of Ciprofloxacin + Gentamicin (44.4%) covered a few more isolates than Ampicillin + Amikacin (43%). The percentage of isolates sensitive to combination of antibiotics were similar at both the centers and correlated at r =0.8 (p = 0.008) (Table/Fig 4).

Three hundred eighty nine (59%) isolates were of EOS and 266 (41%) were of LOS. The antibiotic sensitivity patterns of the isolate clusters of EOS and LOS were compared. The sensitivity patterns correlated well for individual antibiotics (r = 0.9, p =<0.01) (Table/Fig 5), as well as for the common combinations of antibiotics (r = 0.97, p = <0.01) (Table/Fig 6).33.6% (220/655) of the isolates were resistant to all the commonly plated antibiotics. (Table/Fig 1). Multi drug resistance was most common amongst Klebsiella, (43%), Pseudomonas (36%) Acinetobacter (30%) and CONS (29%). One hundred twenty five of the 389 isolates of EOS and 87 of the 266 of LOS were resistant to the commonly used antibiotics and their combination. There was no higher risk of resistance in LOS. (Relative Risk= 1.01 (0.91 – 1.12) at 95 % Confidence limits, p= 0.8, ns)

Discussion

The at–risk approach to neonatal sepsis results in higher cost of blood cultures being done in a large number of infants. As is the recommended practice, antibiotics are commenced as soon as blood is drawn for cultures and the drugs stopped if no organism is isolated. In case the cultures show any isolate, the antibiotics are altered based on the sensitivity pattern for drugs. As the clinical symptoms of sepsis are common to many other neonatal diseases, blood cultures still continue to be the golden standard for confirming sepsis. As seen in the present study, such an approach results in a major number of cultures not yielding any isolates.

The choice of primary antibiotics are based on the preferences of the neonatal center and more studies to clarify this have always been sought(1).The presumptive or ‘first-line’ antibiotic therapy is aimed at commencing antibiotics that have a reasonable chance of being effective against the isolate, while awaiting specific sensitivity reports. Needless to say, the ideal combination should be effective against 100% of the isolates. The quest for the widest coverage has resulted in neonatal centers preferring to use varied combinations of antibiotics, often based on anecdotal observations.

The variations in the bacteriological spectrum of sepsis observed by us at the two centers, supports the observations of other workers(2). Though gram negative bacterial infections as a group were more common (3), Coagulase Negative Staphylococcus (CONS) was seen to be the commonest bacteria isolated (Table/Fig 1). The resistance of CONS to multiple drugs including Cloxacillin, reiterates the observations of other workers (4) to the emerging trends of resistance in this common isolate. The observed sensitivity of CONS to aminoglycosides could give some solace. However, its sensitivity to specific aminoglycosides were different at the two centers, with more numbers of CONS at center A being sensitive to Amikacin, while Gentamicin covered more numbers of CONS at Center B. This variation in sensitivity to specific aminoglycosides was observed even amongst CONS isolated from a single center (5). The emergence of Enterobacter sp. as an important cause for neonatal sepsis 6 was supported by the data from Center B.

Aminoglycosides are usually found to be effective against most of the gram negative infections and a large proportion of staphylococci(7). According to our study quinolones follow aminoglycosides in their coverage of the numbers of organisms isolated (Table/Fig 2),(Table/Fig 3).Thus, highlighting a major role for these drugs , in the management of infants at risk for sepsis[ 8], (9).


Over 50% of the Klebsiella, Acinetobacter and Staphylococci isolates were found to be sensitive to Cotrimoxozole (Table/Fig 2). More isolates were found to be sensitive to this drug at Center B than at Center A. However, the non availability of parenteral preparations, and the risk of its sulpha component displacing bilirubin from albumin binding sites, limits the use of Cotrimoxozole in early neonatal sepsis. The role of Cotrimoxozole could nevertheless be considered when neonates have to be managed at the outback community level, where health care is delivered by the community health workers (10).

The differences in the bacteriological profile are quoted as an important reason by clinicians to avoid a uniform approach to ‘first-line’ antibiotic therapy in neonates at-risk of sepsis at various hospitals. The primary objective of the clinician, while awaiting culture and sensitivity reports, is to administer that combination of antibiotics which would cover the widest spectrum of suspected bacteria in neonatal sepsis.

Resistance to Ampicillin and a greater sensitivity to Aminoglycosides have been often reported (11). The isolates obtained in this study were evaluated for their sensitivity to either or any of the drugs in combination. Implying, that, if a combination therapy was to be implemented, there would be a reasonable chance, of at least one of the drugs in the combination being effective against the isolates. Despite, the limited sensitivity to Ampicillin(Table/Fig 3) the combination of Ampicillin + Amikacin was observed to be sensitive for the largest cluster of isolates 49 %, (Table/Fig 4).

Though higher numbers of isolates were sensitive to Cefotaxime than Ampicillin (Table/Fig 3), combining them with Aminoglycosides, yielded varying percentages of sensitivity. The sensitivity being categorized as (Ampicillin + Amikacin) > (Cefotaxime+ Gentamicin) > (Cefotaxime + Amikacin) > (Ampicillin + Gentamicin) . It was observed that despite Amikacin provided a wider coverage than Gentamicin (Table/Fig 3), the combination of ‘Cefotaxime + Gentamicin’ covered more isolates than ‘Cefotaxime + Amikacin’. The difference however was not statistically significant (chi square =0.9, p=0.3). These observations indicate that in the present study, more organisms were sensitive-in-common to the combination of Amikacin and Cefotaxime than to Gentamicin and Cefotaxime. Thus, the overlap in the sensitivity patterns of Cefotaxime and Amikacin narrows the presumptive coverage for this combination. Similarly, the total numbers of isolates sensitive to the combinations of Ampicillin + Amikacin and Ciprofloxacin+ Gentamicin were comparable (p = 0.34, ns).

It was noted that despite the variations in the patterns of bacterial isolates (Table/Fig 1) and varying sensitivity of individual isolates at both the centers (Table/Fig 2), the antimicrobial efficacy of antibiotic combinations (Table/Fig 4) were fairly similar ( r=0.8, p = 0.008).It was also noted that adding more number of antibiotics did not significantly increase the coverage eg. Ampicillin +Amikacin +Cefotaxime yielded only 1.5% increase in coverage as compared to Ampicillin + Amikacin (p =0.6, ns). It is, therefore, high time for clinicians to contemplate if the benefit of empirical addition of more antibiotics to the combination is justifiable, since the risk of toxicity would undoubtedly be higher.

We attempted to evaluate, if a uniform antibiotic policy could be advocated despite the differences in bacteria isolated. This presumption was based on the hypothesis that despite their diversity the different types of bacteria isolated could possibly be sensitive to the same antibiotic/combination of antibiotics. It is therefore, reasonable to surmise that the same antibiotic or combination of antibiotics could cover a wide –though not necessarily identical - cluster of bacterial isolates at different neonatal centers. The isolates of Center A and Center B showed a wider variation in their sensitivity, to individual antibiotics than to combinations of antibiotics r = 0.81, p = 0.008, (Table/Fig 4). Thus reaffirming, that a rational combination of antibiotics could be equally effective at different neonatal centers.

It is often recommended that choice of antibiotics for ‘Late Onset Sepsis’ and ‘Early Onset Sepsis’ should be different as the bacteriologic profiles would differ. In our observations however, we noted that the spectrum of antibiotic sensitivity of both EOS and LOS correlated well with each other(r = 0.9, p < 0.01), for single as well as combination antibiotics. Our study did not reveal any higher risk for resistance to commonly used antibiotics from isolates in LOS than EOS. It could therefore be inferred that, the suggested combination of antibiotics could be initiated in all high-risk neonates or those suspected to have sepsis – irrespective of the age of presentation.

Despite its limitations, ‘Penicillins + Aminoglycoside’ combination continues to be the optimal drug combination for at –risk infants, while awaiting the specific culture-sensitivity reports. Ampicillin + Amikacin was the most optimal combination in the present study. Ampicillin-sulbactum (12) was not assessed in the study.

Ciprofloxacin and an aminoglycoside, was observed to be another promising combination and requires more attention. The poor CSF penetrability of Ciprofloxacin however, limits its value. The fact that nearly 50 % isolates were found to be sensitive to combinations other than Ampicillin + Amikacin , highlights the absolute necessity of obtaining blood cultures in all at risk infants.



Conclusion

This study,therefore concludes that Ampicillin + Amikacin could be a suitable combination as the ‘1st line antibiotics’ in neonatal sepsis, while awaiting blood culture reports. The variations in the bacterial flora of neonatal centers is no indication for substituting the standard ‘first line’ combination of ‘penicillin + aminoglycoside’ with more ‘exotic’ combination in at- risk neonates. A conservative approach while choosing antibiotics is perhaps better than embarking on combinations that include the ‘latest’ antibiotics for the ‘elusive’ 100% cover.

Increasing the numbers of antibiotics in any combination need not yield a proportionate increase in the antimicrobial cover. (Table/Fig 4).The high correlation between their antibiotic sensitivity patterns, and the absence of any greater risk for antibiotic resistance in LOS, seems to justify commencing the same combination of drugs, viz. Ampicillin + Amikacin as initial antibiotics in both early and late onset sepsis.

It can never be reiterated enough that blood cultures are mandatory in neonatal sepsis for rationalizing antibiotic therapy. Empirical cocktails of antibiotics based on anecdotal reports or personal preferences should never supersede the meticulous blood culture and sensitivity reports. Larger studies involving more neonatal centers could perhaps be useful in recommending a uniform drug policy in treating neonates who are at-risk for sepsis.

Limitations
Information on baseline characteristics of the patients (gestational age, birth weight, patients on long lines, TPN etc) were not assessed in the study.

Key Message

* A combination of a penicillin and an aminoglycoside – Ampicillin and Amikacin is a satisfactory combination of antibiotics to commence in all infants suspected or presenting with features of sepsis while awaiting blood culture reports.
* Blood culture is a mandatory investigation in the treatment of neonatal sepsis.

Acknowledgement

Prof. Radhakutty Amma,* Dr. Ramesh Bhat**, Dr. Amita Rao**, Prof. K. S. Seetha*** , Prof. SugandhiRao***.
*Department of Microbiology, Malankara Orthodox Syrian Church Medical College, (Kochi),**Department of Pediatrics Kasturba Medical College, (Manipal),***Department of Microbiology Kasturba Medical College, (Manipal)
Originally published in "Perinatology" and "Neonatology Today". Reprinted with permission. All rights reserved

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