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

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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 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 : 2022 | Month : September | Volume : 16 | Issue : 9 | Page : FC15 - FC19 Full Version

Prescription Pattern for Antimicrobials and the Potential Predictors for Antibiotics among Patients with COVID-19: A Retrospective Observational Study


Published: September 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/56961.16874
Chaitali Ashish Chindhalore, Ganesh Natthuji Dakhale, Snehalata Vijayanand Gajbhiye, Ashish V Gupta

1. Assistant Professor, Department of Pharmacology, AIIMS, Nagpur, Maharashtra, India. 2. Professor and Head, Department of Pharmacology, AIIMS, Nagpur, Maharashtra, India. 3. Assistant Professor, Department of Pharmacology, AIIMS, Nagpur, Maharashtra, India. 4. Senior Resident, Department of Pharmacology, AIIMS, Nagpur, Maharashtra, India.

Correspondence Address :
Dr. Chaitali Ashish Chindhalore,
503, Yashwantapt, Golden Park, Manewada Besa Road, Nagpur, Maharashtra, India.
E-mail: drchaitali@aiimsnagpur.edu.in

Abstract

Introduction: Long-term repercussions of Coronavirus Disease-2019 (COVID-19) on antimicrobial resistance have been raised as a grave concern due to the rampant use of antibiotics in the management of COVID-19. As per meta-analysis, the prevalence of antibiotic prescribing was 74.6% which was significantly higher than the estimated prevalence of bacterial co-infection. World Health Organisation (WHO) recommended that antibiotic therapy should not be used in patients with mild/moderate COVID-19 unless there is any bacterial suspicion. Also, the guidelines laid down by the Ministry of Health and Family Welfare, Government of India, does not recommend systematic empiric antibiotic therapy in patients hospitalised with COVID-19. Despite not being recommended, antimicrobials are still given in clinical practice.

Aim: To analyse prescriptions for antimicrobials and to identify potential predictors for antibiotic prescription.

Materials and Methods: A retrospective observational study was conducted at a tertiary care teaching institute. Data (demographic profile, co-morbidities, disease category, prescribed antimicrobials, laboratory investigations, and duration of hospital stay) were collected from case files of patients with laboratory-confirmed Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection. These patients were admitted in the institute from January 2021 to May 2021. Logistic regression was used to analyse factors associated with the empirical use of antimicrobial agents.

Results: A total of 184 case files were analysed. The mean age of patients was 55.84±15.72 years, with a male preponderance (70.10%). Among antimicrobials, antivirals were prescribed in 159 (86.41%) patients, and antibiotics in 152 patients (82.6%). Antivirals prescribed include Remdesivir [109(68.55%)] and Favipiravir [70(44.02%)]. Ceftriaxone was found to be the highest prescribed antibiotic, with a median duration of administration of six days. An association was found between disease severity and CRP level with antibiotic prescription. On multivariable analysis, the odds of receiving antibiotics were 6.7 times higher in patients with severe disease.

Conclusion: More than 80% of COVID-19 patients received antibiotics. Duration of hospital stay was similar among patients whether they received antibiotics or not. Disease severity and raised CRP level were strong predictors for prescribing antibiotics for COVID-19.

Keywords

Antibiotic prescription, Coronavirus disease-2019, C-reactive protein, Disease severity

COVID-19 pandemic with millions of cases and a high mortality rate has had an instantaneous and devastating impact on the health sector globally. Despite limited evidence regarding efficacy, several drugs were tried and still are in use for treating COVID-19. As a result of drug repositioning, several drugs have been repurposed, including antimicrobials with potential activity against SARS-CoV-2, like lopinavir/ritonavir, remdesivir, favipiravir, ivermectin, doxycycline, azithromycin, etc (1). In addition to this, high susceptibility to secondary bacterial infection due to invasive procedures and the inability to discern COVID-19 severe inflammatory reaction from bacterial co-infection contributes to higher use of antibiotics (2). The long-term repercussions of COVID-19 on antimicrobial resistance have been raised as a grave concern due to the rampant use of antibiotics in the management of COVID-19 (3),(4).

According to a recent meta-analysis by Langford BJ et al., the prevalence of bacterial co-infection and secondary infection in COVID-19 is relatively low at 3.5% and 14.3%, respectively (5). A review article which analysed statistics from 19 studies involving 2,834 patients concluded that the mean rate of antibiotic use was 74.0% though only 17.6% of patients had secondary infections in COVID-19 management (6). Various other studies also reported that the estimated prevalence of bacterial and fungal co-infection is less than 10% in COVID-19 patients (7),(8). A series of reports from China from January to April 2020, revealed that 72% of patients received broad-spectrum antimicrobials (9). In another meta-analysis, 154 studies were included, antibiotic data were available from 30,623 patients. The prevalence of antibiotic prescribing was 74.6%. Prescribing was significantly higher than the estimated prevalence of bacterial co-infection (10).

Since the beginning of the pandemic, prescribing antibiotics for optimal management of patients with COVID-19 was a matter of dispute. The WHO recommended that antibiotic therapy or prophylaxis should not be used in patients with mild/moderate COVID-19 unless it is justifiable (11). The guidelines laid down by the Ministry of Health and Family Welfare, Government of India, does not recommend systematic empiric antibiotic therapy in patients hospitalised with COVID-19 (12). Interestingly, Adebisi YA et al., conducted a rapid review of national treatment guidelines for COVID-19 in 10 African countries and found that some countries still recommended the use of antibiotics in the management of mild COVID-19 cases (13).

Irrational, over, and misuse of antibiotics arise as a global concern in both hospital and community settings and lead to adverse events including antimicrobial resistance, associated health problems, amplified hospital stay, and cost (4). The prescription analysis is a powerful exploratory tool that describes drug use patterns, provides early signals of irrational drug use, and suggests interventions to make medical care more rational and cost-effective (14). Limited data regarding antimicrobial use in the management of COVID-19 is available from India (15). A study reported increased sale and consumption of antibiotics particularly azithromycin in India during this pandemic (16). But data from systematic studies for antimicrobial use in COVID-19 are meagre (17). Prediction research explores the ability of various markers to predict future outcomes. The potential predictor provides information on an associated dependent variable regarding a particular outcome. It is helpful in assessing the predictive properties of patient characteristics, tests, markers, or combinations of variables (18). The factors that determine why clinicians prescribe antimicrobials are important to understand. Despite not being recommended, antimicrobials still are given in clinical practice.

Hence, the present study was conducted to assess the overall pattern of antimicrobial drug use in COVID-19 patients with emphasis on antibiotics, to identify predictors for antibiotic prescribing, and to explore whether prescribing antibiotics influences the duration of hospital stay in central India.

Material and Methods

The present retrospective observational study was conducted in AIIMS Nagpur, Maharashtra, India. The approval of the Institutional research cell and Institutional Ethics Committee (IEC) [IEC/Pharmac/2021/267 date 28/07/2021] was obtained. The institute has dedicated facilities for COVID-19 management including Outpatient Department (OPD) services, triage, and an indoor facility. The institution has an inpatient capacity of 350 to treat patients suffering from COVID-19 of any severity. Case files of admitted patients for the duration of January 2021 to May 2021 were collected from the medical record section of the institute, and analysed during the period from August 2021 to October 2021.

Inclusion criteria: For analysis, only those case files were included if the patient's age was more than 18 years, had positive SARS-CoV-2, and had an inpatient stay lasting more than 24 hours.

Exclusion criteria: Case files of patients were excluded from analysis if any data was missing, or patients were discharged against medical advice.

Data related to demographic profile, co-morbidities, disease category, prescribed antimicrobials, laboratory investigations, and duration of hospital stay were collected from case files of admitted patients with laboratory-confirmed SARS-CoV-2 infection.

Data related to antibiotics prescribed were analysed for number of patients who received particular antibiotic, duration, route of administration and Category as per WHO AWaRe (Access, Watch, and Reserve) classification of antibiotics, 2021 (19).

Statistical Analysis

Results were summarised using frequency and percentage for categorical data and either means and Standard Deviation (SD) or median and Interquartile Range (IQR) for continuous data wherever applicable. Mann-Whitney U test was used to compare the effect of antibiotic prescription on the duration of hospital stay. Logistic regression was used to analyse factors associated with the empirical use of antimicrobial agents. The stepwise selection was used to determine which variables went into the multivariable model, where p=0.20 was the cut-off. Statistical analysis was done using Graph pad prism version 9.0.0 (121) and International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) statistics version 25.0. The p<0.05 was considered statistically significant.

Results

A total of 324 case files were evaluated. Among 324 case files, data entry was missing in 98 case files, 13 patients had hospital stay less than 24 hours, and 29 patients were discharged against medical advice. The remaining 184 case files were analysed.

The mean age of patients was 55.84±15.72 years, ranging from 18-96 years, with a male preponderance (70.1%). Out of 184 patients, 125 (67.93%) patients had suffered from one or more co-morbidity, with the highest prevalence of hypertension 84 (45.65%) (Table/Fig 1).

Among antimicrobials, a total of 179 antivirals were prescribed in 159 (86.41%) patients, whereas a total of 232 antibiotics were prescribed in 152 patients (82.6%). Antivirals prescribed included Remdesivir [109 (68.55%)] by intravenous route and Favipiravir [70 (44.02%)] by oral route. Ivermectin, by oral route, was the only antiparasitic prescribed for treating COVID-19 (Table/Fig 2).

Among antibiotics, ceftriaxone, a third-generation cephalosporin was found to be the highest prescribed antibiotic with a median duration of administration of six days. Most commonly prescribed antibiotics include ceftriaxone (66.44%) followed by cefixime (42.76%) and piperacillin/tazobactum (21.05%). All three antibiotics belongs to ‘Watch’ category as per WHO AWaRe classification of antibiotics, 2021. Doxycycline (9.21%), amoxycillin/clavulanic acid (1.97%) and amikacin (2.63%) belongs to ‘Access’ category and linezolid (3.28%) included in ‘Reserve’ category (Table/Fig 3). (Table/Fig 4) describes antibiotics prescribed for different patient characteristics.

On univariate analysis, factors found to be associated with antibiotic use included age, disease severity, co-morbidity, raised CRP, LDH, Ferritin, and D-Dimer levels. However, on multivariable analysis, disease severity and CRP level were associated with antibiotic prescribing. The odds of receiving antibiotics were 6.7 times higher in patients with severe disease. Similarly, patients with raised CRP levels were 14.66 times more likely to receive antibiotics than those with normal CRP levels (Table/Fig 5).

(Table/Fig 6) shows that the duration of hospitalisation did not significantly differ among those who received antibiotics as compared to those who did not. Prescribing antibiotics did not affect the duration of the hospital stay.

Discussion

Antimicrobial resistance is a hidden threat prowling behind the COVID-19 pandemic attributed to the irrational use of antibiotics which has facilitated the emergence and spread of resistant pathogens. The present study assessed the utilisation pattern of antimicrobials in general and antibiotics in particular among COVID-19 patients admitted to the tertiary care teaching institute in central India. The present study also analysed predictors for prescribing antibiotics and the effect of antibiotic administration on the length of hospital stay.

The present study observed that 41.85% patients were elderly. A retrospective analysis by Buetti N et al., reported that median age of patient was 66.5 year (IQR 61-70) (20). In a study by Stevens RW et al., 62.8% patients had age more than 60 years (21). The majority of patients were suffering from co-morbidity. The most common co-morbidity was hypertension which was in accordance with a previous study which described that 55.4% patients were hypertensive (21).

The present study found that the majority (82.6%) of the study population received antibiotics, which was in agreement with the study conducted in France where 174 (78%) out of 222 patients received antibiotic therapy (22). One of the reasons for overprescribing antibiotics may be the difficulty in distinguishing viral from bacterial aetiology based on only clinical criteria. For patients who are critically ill and hospitalised, the diagnosis of a potential bacterial co-infection is uncertain. So physicians tend to use broad-spectrum antibiotics to manage such patients (23).

Though, WHO does not recommend antibiotic use in mild/moderate COVID-19, national guidelines in some countries recommend antibiotic use in mild to moderate cases also (13). In India, Ministry of health and family welfare released guidelines that stated antibiotics should not be prescribed routinely unless there is clinical suspicion of a bacterial infection (12). However, the Maharashtra COVID-19 task force recommends the use of antibiotics in COVID-19 from stage IC onwards (24). Discrepancies in guidelines by various regulatory authorities also might be responsible for the overuse of antibiotics.

However, in a retrospective study by Stevens RW et al., antibiotics were prescribed to only 37.9% of the study cohort. The author explained that the lower rate of antibiotic prescribing was due to the implementation of passive and active antimicrobial stewardship techniques like prospective audits with intervention and feedback using real-time alerts during the study period (21).

The current study observed that the most commonly prescribed antibiotic was ceftriaxone followed by cefixime. A study by Stevens RW et al., showed that ceftriaxone followed by cefepime was most commonly prescribed with a median length of antibiotic therapy was five days (21). In a meta-analysis of 28 studies by Langford BJ, the most common antibiotic classes prescribed were fluoroquinolones (20.0%) (10). Whereas, in a study by Buetti N et al., and Morettoa F et al., the most frequently used antibiotic was amoxicillin-clavulanic acid (68%) (20),(22).

The AWaRe classification of antibiotics was developed in 2017 by the WHO Expert Committee and classified antibiotics into three groups, Access, Watch, and Reserve, taking into account the potential for antimicrobial resistance (19). The present study observed that majority of the antibiotics prescribed were from the "watch" (antibiotics that have higher resistance potential) and "reserve" categories. This is worrisome since it contributes further to antimicrobial resistance.

On univariate analysis, factors associated with antibiotic prescribing include elderly patients, co-morbidity, disease severity, and raised blood levels of CRP, LDH, Ferritin, and D-Dimer. However, the multivariable analysis of the current study revealed that disease severity and raised CRP level were significantly associated with empirical antibiotic use. Patients with higher disease severity are more prone to complications and fatal outcomes. They are more prone to mechanical ventilation and fatal infection. So antibiotic prescribing is highly common in patients suffering from severe diseases. Similar findings have been reported in another study where antibiotic prescribing was highest in the ICU setting (86.4%) and patients in maximum three quartiles requiring mechanical ventilation (80.6%) (10).

Studies had observed that CRP is usually increased on presentation in patients with COVID-19. Serial CRP measurement over time may help to diagnose or rule out nosocomial bacterial infections and will be helpful for appropriate use of antibiotic therapy (25). A study by Guan W et al., from China mentioned that 81.5% patients with severe diseases had CRP level >10 mg/L as compared to 56.4% patients suffering from mild disease. However author had not mentioned exact CRP level of patients (26). In a study by Pink I et al., CRP level on admission in patient with secondary bacterial infection, was 130.6 mg/L (68.8-186.65) which was increased further upto 292.5 mg/L (183-341.8) in contrast to patients without secondary bacterial infection in whom CRP level increased from 73.4 mg/L (31.2-119.5) to 93.9 mg/L (50-171). Receiver Operating Characteristic (ROC) analysis of CRP yielded Area Under Curve (AUC) of 0.86 (p<0.001) for all patients. At a cut-off of 172 mg/L, CRP had a sensitivity of 81% and a specificity of 76% for the detection of secondary bacterial infection. Thus, CRP measurement on admission and during disease progression in patients with COVID-19 may help identify secondary bacterial infections and guide the use of antibiotic therapy (27).

The odds of receiving antibiotics were four-times higher in elderly patients and patients with raised LDH level. These findings have clinical significance though not significant statistically. Though serum LDH level is not a biomarker for infection, elevated LDH levels signify tissue hypoperfusion indicating the severity of the disease. Studies reported that raised LDH was associated with a six-fold increase in odds of developing severe disease and a 16-fold increase in odds of mortality in patients with COVID-19 (28),(29).

Though present study findings stated that older age, co-morbidity, raised level of ferritin and D-dimer were not associated with increased frequency of antibiotic prescribing, some previous studies documented that disease severity, presence of co-morbidity, and older age group were associated with empirical antibiotic use (10),(21). The present study observed no significant difference in the duration of hospital stay among patients receiving antibiotics as compared to those who did not receive antibiotics. Also, a study by Beutti N et al., concluded that early administered antibiotics do not impact mortality in critically ill patients with COVID-19 (20).

Thus, the present study findings reiterate the need to apply antimicrobial stewardship strategies, such as prospective audits with intervention and feedback, multidisciplinary approaches, and training, to curb antimicrobial overuse in COVID-19. As there is significant diagnostic uncertainty in identifying bacterial infection in patients with COVID-19, uniform regulatory guidelines can advocate appropriate empiric antibiotics for patients who derive the greatest benefit, and in which patients the risks of antibacterial therapy exceed the benefits. At the same time, lack of access to antibiotics could also be dangerous if there is diagnostic uncertainty. Therefore, it is advised to use a correct and speedy diagnostic test like culture-independent rapid technologies which can be used for point of care use in settings such as emergency, Intensive Care Unit (ICU), or even OPD.

Limitation(s)

The present study analysed data from a single institution with a limited sample size which limits the external validity of the findings.

Conclusion

Finally, to conclude, more than 80% of COVID-19 patients received antibiotics during their hospital stay. Duration of hospital stay was similar among patients whether they received antibiotics or not. Disease severity and raised CRP level were strong predictors for prescribing antibiotics for COVID-19.

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DOI and Others

DOI: 10.7860/JCDR/2022/56961.16874


Date of Submission: Apr 07, 2022
Date of Peer Review: May 13, 2022
Date of Acceptance: Jun 21, 2022
Date of Publishing: Sep 01, 2022

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? No
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Apr 12, 2022
• Manual Googling: Jun 17, 2022
• iThenticate Software: Aug 15, 2022 (21%)

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