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

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Dr Mohan Z Mani

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Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
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
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 : 2023 | Month : December | Volume : 17 | Issue : 12 | Page : DC26 - DC30 Full Version

Diagnostic Value of Routine Biomarkers in Predicting Septicaemia in Hospitalised Patients: A Cross-sectional Study


Published: December 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/62941.18846
Bhagwati Chundawat, Sakshee Gupta, Alka Meena

1. Associate Professor, Department of Microbiology, JNUIMSRC, Jaipur, Rajasthan, India. 2. Assistant Professor, Department of Microbiology, JNUIMSRC, Jaipur, Rajasthan, India. 3. Assistant Professor, Department of Biochemistry, SMS Medical College, Jaipur, Rajasthan, India.

Correspondence Address :
Dr. Sakshee Gupta,
Assistant Professor, Department of Microbiology, JNUIMSRC, Jaipur-302017, Rajasthan, India.
E-mail: saksheegupta@gmail.com

Abstract

Introduction: Sepsis is a potentially fatal condition that leads to alterations in coagulation, immunosuppression, and multiorgan failure. Predicting the risk of septicaemia before the onset of organ dysfunction poses a challenge. Prompt diagnosis, coupled with triaged management, is crucial in determining disease outcomes.

Aim: To assess the role of routinely employed biomarkers in the early identification of septicaemia in patients.

Materials and Methods: A cross-sectional study was conducted on 564 blood samples from Jaipur National University Institute of Medical Sciences and Research Centre (JNUIMSRC) in Jaipur, Rajasthan, India, over a period of six months (July 2019-December 2019). Blood culture, identification, and antimicrobial sensitivity testing were performed for all the samples following the Clinical and Laboratory Standards Institute (CLSI- M100) guidelines. Standard septic markers, such as Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Serum Glutamic Pyruvic Transaminase (SGPT), Serum Glutamic Oxaloacetic Transaminase (SGOT), serum urea, serum creatinine, Haemoglobin (Hb), and Total Lymphocyte Count (TLC), were studied. The culture-positive patients were compared with a negative control group. The t-test and logistic regression were used for analysis.

Results: Out of 564 patients suspected of sepsis, 135 (23.94%) were culture positive, with a male-to-female ratio of 1.41. No significant differences were found in septic markers {TLC (p-value=0.261), ESR (p-value=0.186), SGPT (p-value=0.336), SGOT (p-value=0.264), Hb (p-value=0.179), serum urea (p-value=0.350), and serum creatinine (p-value=0.155)} between the culture-positive group (135/564, 23.93%) and the culture-negative group (429/564, 76.06%), except for CRP (p-value=0.006). The results of logistic regression also showed that CRP was a significant predictor of septicaemia (p-value=0.009). Amikacin, doxycycline, and piperacillin-tazobactam were found to be sensitive.

Conclusion: Currently used blood markers do not provide sufficient evidence for the prediction of septicaemia, although CRP may be preliminarily useful. There is an urgent need to combine them with novel markers for the early detection of septicaemia.

Keywords

Antibiogram, Blood culture, C-reactive protein, Routine blood markers, Septicaemia

Sepsis is a leading cause of mortality, ranging from 30-63% (1), increased hospital stay, and readmissions worldwide, with 18 million new sepsis cases reported each year (2). “Sepsis” involves multiorgan dysfunction caused by a deregulated host response to infection, whereas “septic shock” is associated with circulatory and cellular/metabolic dysfunction, as per the consensus definition of Sepsis-3 (3). Since a high proportion of critically ill patients present with Systemic Inflammatory Response Syndrome (SIRS), clinicians are faced with the challenge of accurately distinguishing between both.

Laboratory biomarkers help physicians monitor therapeutic decisions and plan treatment accordingly (4). More than 100 sepsis biomarkers have been proposed and documented in the literature. However, they have limitations in distinguishing sepsis from other inflammatory conditions and predicting outcomes. Hence, no ideal marker has been found to date, owing to the complex pathobiology of the disease. According to the Surviving Sepsis Guidelines 2021, sepsis biomarkers were not found to have a definitive role in clinical evaluation (5).

International guidelines for the management of sepsis have given a weak recommendation regarding the use of serum lactate as an adjunctive test to pretest sepsis in suspected sepsis cases (3). CRP and ESR are markers of inflammation that poorly correlate with clinical measures of disease severity (6). Many authors have studied that bacteraemia may be predicted by an increase in Total Leukocyte Count (TLC) with fever (7), D-dimer (8), lactate, Prothrombin Time/International Normalised Ratio (PT/INR) (9), eosinophil count (10), interleukin-6 and 8 (IL-6 and IL-8) (11), and Procalcitonin (PCT) (11). PCT has been extensively studied and incorporated into practice. Pro-vasopressin (pro-AVP)/proadrenomedullin (ProADM) (12), resistin level (13), biomarkers of complement proteins, activated neutrophils, and monocytes can also complement diagnosis. According to Camacho CH and Losa J, novel markers of bloodstream infections like soluble Triggering Receptor on Myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen receptor (suPAR), proadrenomedullin (ProADM), and presepsin appear promising because of acceptable sensitivity and specificity (14). It is the need of the hour to identify novel sepsis biomarkers conducive to the respective laboratory set-up of each hospital and incorporate them into clinical practice (15),(16). The present study was undertaken to assess the utility of currently employed septic markers (CRP, ESR, TLC, SGOT, SGPT, Hb, serum urea, and creatinine) in predicting the risk of septicaemia in hospitalised patients.

The antibiotic susceptibility pattern of the isolates from Intensive Care Unit (ICU) and wards is helpful to commence empirical treatment before laboratory results are available. Commonly isolated organisms from blood culture, such as Acinetobacter spp., Enterobacter spp., Pseudomonas spp., Staphylococcus spp., Coagulase-negative Staphylococcus, etc., may present with plasmid-mediated or chromosomally acquired resistance (17). Hospitals are now emphasising the preparation of unit-wise antibiograms for effective patient management. Hence, the sensitivity pattern of the culture isolates was analysed for the study population. Due to the lack of advanced infrastructure in resource-limited settings (primary/community healthcare centres and remote areas), prompt administration of empirical therapy becomes challenging (17). Literature probing into the role of conventional biomarkers in the early prediction of sepsis is also scarce in developing countries. Hence, the novelty of present study lies in the assessment of the utility of currently available markers in ICU and hospital settings, in culture-positive/negative controls, and the assessment of the antibiogram. The aim of the study was to assess the role of routinely employed biomarkers in the early identification of septicaemia in patients.

Material and Methods

A cross-sectional study was conducted between July 2019 and December 2019 (six months) to study the conventional biomarkers of sepsis, such as TLC, Hb levels, ESR, SGOT, SGPT, CRP, serum urea, and serum creatinine, in the Department of Microbiology, JNUIMSRC, Jaipur, Rajasthan, India. Consent forms were filled out by the patients participating in the study after approval from the ethical and research committee of the institution (JNUIMSRC/IEC/2020/192).

Inclusion criteria: All significant bacterial isolates obtained by blood culture were included in the study.

Exclusion criteria: Contaminants/commensals, yeasts, and anaerobes were excluded from the study.

Sample size: The calculation of the sample size was done by the Department of Statistics based on data on the prevalence of septicaemia in resource-limited settings (1).

n=Z2p(1-p)/d2

Where n is the sample size, Z is the level of confidence taken as 1.96, P prevalence is 6.0% (Chatterjee S et al.), and d is the precision taken as ±5% (95% confidence interval). Blood samples were procured from 564 patients with signs and symptoms of septicaemia reporting at the hospital. Sepsis was diagnosed by the consultant physician based on the clinical condition of the patient and laboratory evidence.

For blood culture, one set of bottles (paired aerobic and anaerobic bottles, each containing 10 mL of blood) was received by the laboratory after bedside sample collection from the hospital. Cultures were incubated at 37°C in an automated BACTEC blood culture system (Becton Dickinson and Company, Sparks, MD, USA). Bottles were monitored for five days and subcultured on MacConkey agar, blood agar, and chocolate agar if flagged positive by the instrument. The rest of the bottles were discarded on the 6th day. A sample was categorised as “culture positive” when a pathogen was isolated and identified after subculture. The samples yielding clinically “insignificant” pathogens/negative by the blood culture instrument were considered “culture negative”. Data of culture-positive patients were compared with the culture-negative control group.

Identification and antibiotic sensitivity were performed as per CLSI guidelines (M100), 30th edition (18). Preliminary tests (catalase, coagulase, oxidase, hanging drop, etc.) and biochemical tests (Sulphur, Indole, Motility (SIM), Oxidation-Fermentation (OF), indole, citrate, urease, sugar fermentation tests, Methyl Red (MR), Voges-Proskauer (VP), etc.) were performed for the identification of gram-positive and gram negative isolates. Standard disks (Hi Media Labs) were used for antimicrobial sensitivity testing for gram-positive and gram negative bacterial isolates as per CLSI (18). The following antibiotics were tested: Amikacin (AK) (30 μg), Amoxicillin/Clavulanic Acid (AMC) (30 μg), Azithromycin (AZM) (15 μg), cefepime (FEP) (30 μg), Ceftazidime (CAZ) (30 μg), Ceftriaxone (CRO) (30 μg), Cefuroxime (CXM) (30 μg), Ciprofloxacin (CIP) (5 μg), Clindamycin (DA) (2 μg), Colistin (C) (5 μg), Trimethoprim/Sulfamethoxazole (SXT) (25 μg), Doxycycline (DO) (30 μg), Erythromycin (E) (15 μg), Gentamicin (CN) (10 μg), Imipenem (IMI) (10 μg), Levofloxacin (LEV) (5 μg), Linezolid (LZD) (30 μg), Meropenem (MEM) (10 μg), Moxifloxacin (MX) (10 μg), Piperacillin/Tazobactam (TZP) (110 μg), Teicoplanin (TEI) (10 μg), Tobramycin (TOB) (10 μg), and Vancomycin (VA) (30 μg).

E. coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Staphylococcus aureus (ATCC 29213) were used as reference strains following CLSI M100 guidelines.

Blood samples were analysed for routinely used septic markers, including ESR, CRP, SGPT, SGOT, serum urea, serum creatinine, haemoglobin, and TLC (19). Serum urea, creatinine, SGOT, and SGPT were analysed using an automated RX Imola biochemical analyser (RANDOX Laboratories Ltd.). TLC was performed using the Yumizen H550 automated system (Horiba ABX SAS), and ESR was measured using the Westergren tube method, with values >25 mm/h considered abnormal (6). CRP was determined using a latex agglutination card test (19).

Statistical Analysis

The data were presented as median values with a 95% confidence interval due to the skewed distribution of most variables. Univariate analysis, using Analysis of Variance (ANOVA), was performed to compare the conventional septic markers used in the present study and derive Odds Ratios (OR). A p-value ≤0.01 was considered significant. All analyses were performed using Statistical Package for Social Sciences (SPSS) version 21.0 (SPSS, Chicago, IL, USA).

Results

Out of the total 564 samples, 135/564 (23.94%) were culture-positive, with a mean age of 42.5±15 years and a male-to-female ratio of 1.41. Among the 135 culture-positive patients, 56/135 (41.48%) were females, most 48.21% (27/56) of which were in their reproductive age group (21-50 years), and 49/135 (36.29%) were elderly patients (age 51-75 years).

On comparative analysis, all septic markers had insignificant p-values, such as TLC (p-value=0.261), ESR (p-value=0.186), SGPT (p-value=0.336), SGOT (p-value=0.264), haemoglobin (p-value=0.179), serum urea (p-value=0.350), and serum creatinine (p-value=0.155), except for CRP (p-value=0.006), which was significant. The CRP levels were higher in culture-positive patients compared to the culture-negative control group (Table/Fig 1).

The culture positivity rate was comparable between the wards and ICUs with 77/319 (24.13%) and 58/245 (23.67%) positive cultures (p-value=0.31) respectively (Table/Fig 2).

The results of the logistic regression analysis showed that CRP was significantly associated with prediction of septicaemia among the study population compared to other biomarkers such as TLC, ESR, SGOT, SGPT, Hb, serum urea, and creatinine (OR=1.134, p-value <0.01) (Table/Fig 3).

Upon culture, 76/135 (56.30%) isolates were found to be gram-positive, and 59/135 (43.70%) were gram negative. Among gram-positive cocci, the maximum number of isolates were Methicillin-Resistant Staphylococcus aureus (MRSA) (32/135, 23.70%), followed by Coagulase-Negative Staphylococci (CONS) (30/135, 22.22%), including 6/30 (20%) methicillin-sensitive and 24/30 (80%) methicillin-resistant strains. Enterococci accounted for 8/135 (5.9%) of isolates, and Methicillin-Sensitive Staphylococcus aureus (MSSA) accounted for 6/135 (4.44%) of isolates. Among gram negative organisms, Acinetobacter spp. accounted for 18/135 (13.33%) of isolates, followed by Pseudomonas spp. and Escherichia coli with 14/135 (10.37%) each, Enterobacter spp. with 5/135 (3.7%), Klebsiella spp. and Shigella spp. with 4/135 (2.9%) each.

Antibiotic sensitivity testing revealed that more than 67% of strains were sensitive to amikacin, >40% were sensitive to doxycycline, and >53% were sensitive to piperacillin-tazobactam. 75-100% of gram negative bacteria were found to be sensitive to colistin. None of the strains were found to be resistant to vancomycin and linezolid (Table/Fig 4). Out of the 564 patients suspected of sepsis, 429 (76.06%) tested negative for blood culture.

Discussion

The diagnosis of sepsis is associated with a high rate of in-hospital mortality (27.6%) and multidrug resistance (20). A higher percentage of males, 79/135 (58.52%), in the present study was consistent with a study from the US (21), which suggested that the incidence of bloodstream infections increases with age and is significantly higher in males. Septicaemia was found to be more frequent in young females of reproductive age, as the immunological and cardiovascular adaptations during pregnancy might impair their ability to respond to infection (22).

The culture positivity rates were comparable between the wards {77/319 (24.13%)} and the ICUs {58/245 (23.67%)} (p-value=0.31). Studies (23) have shown that the ICUs and emergency departments had significantly higher positivity rates compared to general wards {11.2% versus 5.7% (p-value <0.001)}. Since ICUs and wards are prone to infections, it is relevant to study septic markers, antibiograms, and other parameters of hospital-acquired infections in both settings.

Blood culture and antimicrobial sensitivity testing are recommended prior to deciding on antimicrobial therapy according to the Surviving Sepsis campaign’s international sepsis guidelines (24). Therefore, blood culture is the cornerstone of antibiotic stewardship programs (25). Resource-limited settings face additional challenges, such as low recovery rates (30-40%) of pathogens from blood cultures. This can be due to various reasons, including discrepancies in sample collection, prior antibiotic administration, transportation delays, deviations from standard protocols in Standard Operating Procedures (SOPs) by untrained laboratory technicians, and lack of automation (26). A recent study from the US has demonstrated that more than 89% of patients with signs and symptoms of sepsis were identified as culture-negative, similar to the findings of the present study. This emphasises the urgent need for novel biomarkers in the definitive diagnosis of sepsis in culture-negative samples (27).

A standard diagnostic tool is currently unavailable to predict bacteraemia at an early stage, as definitive culture results typically take atleast 48-72 hours. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores are being used as predictors of fatal outcomes in critically ill patients. However, the roles of most clinical and laboratory biomarkers in the management of septic patients have not been well defined, as suggested by current literature (16).

In the present study, the levels of routinely used biomarkers in culture-positive samples were compared with a culture-negative group. It was found that CRP was significantly higher (p-value=0.006; p-value >0.05) in culture-positive patients. Similarly, Woodworth from the USA (28) reported that CRP accurately predicts sepsis and its severity in ICU patients. This finding was in line with other international (29) as well as Indian studies (19), although some authors have reported contradictory results (6). However, this study did not find any significant differences (p-value >0.001) in the other routine biomarkers such as TLC, ESR, SGOT, SGPT, Hb, serum urea, and creatinine between the culture-positive and negative groups. According to a Japanese study, the mean WBC and ESR levels are significantly lower in culture-negative patients (30). Due to the varying findings in different studies, the definitive association of biomarkers with septicaemia has not been established till date (16),(31).

Univariate analysis suggested that routinely used biomarkers were not significant predictors of septicaemia, except for CRP (OR 1.134, p=0.009). The authors have discussed the role of biomarkers such as WBC (cut-off of 10,000/mm3) (7), ESR, and CRP in predicting sepsis (29). Hassan HR et al., studied that m-ESR was significantly associated with culture-proven sepsis (32), but a study from the USA (6) stated otherwise. Many have suggested that PCT is a more specific predictor of bacteraemia than CRP and ESR (33),(34). The serum PCT level rises and returns back to the normal range faster than CRP levels, making it a better biomarker for sepsis (34). A recent report summarised that the combination of IL-6, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and INR may serve as a potential predictor of 28-day mortality in critically ill patients with sepsis or septic shock (9). Factors such as lack of sensitivity specificity and the complexity of inflammatory processes limit the role of several currently used biomarkers in stratifying patients for treatment (31). It was emphasised that currently targeted biomarkers provide insufficient evidence for treatment decisions. CRP can be helpful in combination with other clinical and laboratory parameters. Hence, positive cultures remain the gold standard for laboratory confirmation of sepsis.

All gram-positive isolates were sensitive to vancomycin (100%), followed by doxycycline (88%). Gram negative isolates were sensitive to Piperacillin/Tazobactam (PIT) (53-92%) and Gentamicin (GEN) (47-75%), similar to an Indian study (PIT-22-60%; GEN-25-100%) (35). Levofloxacin provided comprehensive coverage for both gram-positive and gram negative bacteria, while penicillins and cephalosporins were ineffective (35). In this study, 32/76 (42.10%) of GPCs were found to be MRSA, which was lower as compared to other studies (17). The antibiotic sensitivity profile presented in this study raises an alarm for the decreased sensitivity to colistin among gram negative bacilli. The drug of choice may be amikacin, doxycycline, and piperacillin/tazobactam in susceptible isolates. Although resistance to vancomycin and linezolid was not encountered in this study, hospitals must strictly adhere to the antibiotic policy as Vancomycin-Resistant Staphylococcus aureus (VRSA), Vancomycin-Resistant Enterococci (VRE), and Linezolid-Resistant Enterococci (LRE) have been reported from hospitals (17). Preparation of an antibiogram for each setting will be helpful in the administration of empirical antibiotics in critically ill patients and the prevention of multidrug resistance.

imitation(s)

Although multiple biomarkers were considered in the present study, data for PCT, lactate, IL-6, and D-dimer couldn’t be presented due to infrastructure limitations. In-depth studies with control groups, a significant study population, evaluation by appropriate statistical parameters, and validation are required. It is important to study the biological plausibility of biomarkers and alterations in their levels with the change in the pathobiology of infections.

The present study also emphasises that the diagnostic value of the existing biomarkers is not well established. Hence, rigorous efforts are needed to investigate the role of inflammatory markers in predicting sepsis, along with their combination with novel ones, rather than relying on a single biomarker for rapid diagnosis and prognosis.

Conclusion

With the increasing cases of multidrug-resistant organisms, predicting septicaemia in the present scenario poses a challenge. The results indicate that elevated CRP may serve as an early indicator of sepsis. It is crucial to develop a standardised methodology to assess the usefulness of currently available and novel sepsis biomarkers, which can offer valuable and clinically relevant information.

Acknowledgement

Authors would like to acknowledge JNUIMSRC for providing resources and infrastructure for conducting this study.

References

1.
Chatterjee S, Bhattacharya M, Todi SK. Epidemiology of adult-population sepsis in India: A single center 5 year experience. Indian J Crit Care Med. 2017;21(9):573-77. [crossref][PubMed]
2.
Slade E, Tamber PS, Vincent JL. The surviving sepsis, campaign, raising awareness to reduce mortality. Crit Care. 2003;7(1):01-02. [crossref][PubMed]
3.
Singer M, Deutschman CS, Seymour CW, Hari MS, Annane MSD, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-81. [crossref][PubMed]
4.
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89-95. [crossref][PubMed]
5.
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: Intensive Care Med. 2021;47(11):1181-1247. Doi: https://doi.org/10.1097/ CCM.0000000000005337.
6.
Keenan RT, Swearingen CJ, Yazici Y. Erythrocyte sedimentation rate and C-reactive protein levels are poorly correlated with clinical measures of disease activity in rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis patients. Clin Exp Rheumatol. 2008;26(5):814-19.
7.
Jaffe DM, Fleisher GR. Temperature and total white blood cell count as indicators of bacteremia. Pediatrics. 1991;87(5):670-74. [crossref]
8.
Rodelo JR, De la Rosa G, Valencia ML, Ospina S, Arango CM, Gomez CI, et al. D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. Am J Emerg Med. 2012;30(9):1991-99. [crossref][PubMed]
9.
Liu J, Bai C, Li B, Shan A, Shi F, Yao C, et al. Mortality prediction using a novel combination of biomarkers in the first day of sepsis in intensive care units. Nature Research. 2021;11:1275. https://doi.org/10.1038/s41598-020-79843-5. [crossref][PubMed]
10.
Ho KM, Towler SC. A comparison of eosinopenia and C-reactive proteinas a marker of bloodstream infections in critically ill patients: A case-control study. Anaesth Intensive Care. 2009;37(3):450-56. [crossref][PubMed]
11.
Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, et al; Geneva Sepsis Network. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164(3):396-402. Doi: 10.1164/ajrccm.164.3.2009052. PMID: 11500339. [crossref][PubMed]
12.
Guignant C, Voirin N, Venet F, Poitevin F, Malcus C, Bohé J, et al Assessment of pro-vasopressin and pro-adrenomedullin as predictors of 28-day mortality in septic shock patients. Intensive Care Med. 2009;35(11):1859-67. [crossref][PubMed]
13.
Koch A, Gressner OA, Sanson E, Tacke F, Trautwein C. Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients. Crit Care. 2009;13(3):R95. [crossref][PubMed]
14.
Camacho CH, Losa J. Biomarkers of sepsis. BioMed Res Int. 2014;2014:547818. [crossref][PubMed]
15.
Vallés J, Calbo E, Anoro E. Bloodstream infections in adults: Importance of healthcare-associated infections. J Infect. 2008;56(1):27-34. [crossref][PubMed]
16.
Pierrakos C, Velissaris D, Bisdorff M, Marshall JC, Vincent JL. Biomarkers of sepsis: Time for a reappraisal. Critical Care. 2020;24:287. [crossref][PubMed]
17.
Gohel K, Jojera A, Soni S, Gang S, Sabnis R, Desai M. Bacteriological profile and drug resistance patterns of blood culture isolates in a tertiary care nephrourology teaching institute. BioMed Res Int. 2014;2014:153747. [crossref][PubMed]
18.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, 30th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute, Wayne, PA 2020.
19.
Narayanakar P, Metgud SC, Bhandankar M. Utility of hematological parameters and C-reactive protein levels in early diagnosis of neonatal sepsis. J Scientific Soc. 2019;46(1)14-19. [crossref]
20.
Hammond NE, Kumar A, Kaur P, Tirupakuzhi Vijayaraghavan BK, Ghosh A, Grattan S, et al. Sepsis in India Prevalence Study (SIPS) Investigator Network. Estimates of sepsis prevalence and outcomes in adult patients in the ICU in India: A cross-sectional study. Chest. 2022;161(6):1543-54. Doi: 10.1016/j.chest.2021.12.673. Epub 2022 Jan 31. PMID: 35092747. [crossref][PubMed]
21.
Uslan DZ, Crane SJ, Steckelberg JM, Cockerill FR, Sauver JL, Wilson WR, et al. Age and sex associated trends in bloodstream infections: A population based study in olmsted County. Minnesota Arch Intern Med. 2007;167(8):834-39. [crossref][PubMed]
22.
Greer O, Shah NM, Sriskandan S, Johnson MR. Sepsis: Precision-based medicine for pregnancy and the puerperium. Int J Mol Sci. 2019;20(21):5388. Doi: 10.3390/ijms20215388. PMID: 31671794; PMCID: PMC6861904. [crossref][PubMed]
23.
Nannan Panday RS, Wang S, van de Ven PM, Hekker TAM, Alam N, Nanayakkara PWB. Evaluation of blood culture epidemiology and efficiency in a large European teaching hospital. PLoS ONE. 2019;14(3):e0214052.[crossref][PubMed]
24.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. 2013. Surviving sepsis campaign: International guideline for management of severe sepsis and septic shock. Crit Care Med. 2013;41(2):165-228. [crossref][PubMed]
25.
Standiford HC, Chan S, Tripoli M, Weekes E, Forrest GN. Antimicrobial stewardship at a large tertiary care academic medical center: Cost analysis before, during and after a 7-year programme. Infect Control Hosp Epidemiol. 2012;33(4):338-45. [crossref][PubMed]
26.
Schmitz R, Keller PM, Baier M, Hagel S, Pletz MW, Brunkhorst FM. Quality of blood culture testing-a survey in intensive care units and microbiological laboratories across four European countries. Crit Care. 2013;17(5):R248. [crossref][PubMed]
27.
Sigakis MJG, Jewell E, Maile MD, Cinti SK, Bateman BT, Engoren M. Culture-negative and culture-positive sepsis: A comparison of characteristics and outcomes. Anesth Analg. 2019;129(5):1300-09. Doi: 10.1213/ANE.0000000000 004072. PMID: 30829670; PMCID: PMC7577261. [crossref][PubMed]
28.
Woodworth A, Thompson MA, Rice T, Bissonnett S. Biochemical and hematological markers of inflammation accurately predicts sepsis and its severity in ICU patients. Sysmex J Int. 2019;29(1):01-07.
29.
Miettinen AK, Heinonen PK, Laippala P, Paavonen J. Test performance of erythrocyte sedimentation rate and C-reactive protein in assessing the severity of acute pelvic inflammatory disease. Am J Obstet Gynecol. 1993;169(5):1143-49. [crossref][PubMed]
30.
Watanabe S, Kobayashi N, Tomoyama A, Choe H, Yamazaki E, Inaba Y. Clinical characteristics and risk factors for culture-negative periprosthetic joint infections. J Orthop Surg Res. 2021;16(1):292. Doi: 10.1186/s13018-021-02450-1. PMID: 33941220; PMCID: PMC8091510. [crossref][PubMed]
31.
Samraj SR, Zingarelli B, Wong HR. Role of biomarkers in sepsis care. Shock. 2013;40(5):358-65. [crossref][PubMed]
32.
Hassan HR, Gohil JR, Desai R, Mehta RR, Chaudhary VP. Correlation of blood culture results with the sepsis score and sepsis screen in the diagnosis of early-onset neonatal septicemia. J Clin Neonatol. 2016;5(3):193-98. [crossref]
33.
Müller B, Harbarth S, Stolz D, Bingisser R, Mueller C, Leuppi J, et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10. [crossref][PubMed]
34.
Standage SW, Wong HR. Biomarkers for paediatric sepsis and septic shock. Expert Rev Anti-Infect Ther. 2011;9(1):71-79. [crossref][PubMed]
35.
Sarkar SK, Bhattacharya A, Paria K, Mandal SM. A retrospective study on bacteria causing blood stream infection: Antibiotics resistance and management. Indian J Pharm Sci. 2018;80(3):547-51.[crossref]

DOI and Others

DOI: 10.7860/JCDR/2023/62941.18846

Date of Submission: Jan 20, 2023
Date of Peer Review: Mar 20, 2023
Date of Acceptance: Oct 26, 2023
Date of Publishing: Dec 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jan 27, 2023
• Manual Googling: May 19, 2023
• iThenticate Software: Oct 13, 2023 (12%)

ETYMOLOGY: Author Origin

EMENDATIONS: 8

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