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\def\RunningAuthor{Muhas C et al.}
\firstPage{2595}
\articleType{Original Article}
\receivedDate{12 Oct 2021}
\acceptedDate{17 Nov 2021}
\revisedDate{15 Nov 2021}
\journalVolume{2021, 12}
\journalIssue{4}
\journalDoi{ijrps.v12i4.4911}
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\title{\textbf{Prescription Pattern of Antimicrobial Agents in Various Dental Clinics at Malabar Region of Kerala, South India}}
\author{Muhas~C\textsuperscript{*}\textsuperscript{1},  
            Mohamed~Saheer~K\textsuperscript{2},  
            Syed~Altafuddin~Quadri\textsuperscript{2},  
            Naseef~P~P\textsuperscript{3},  
            Abdul~Khader~P~M\textsuperscript{4}, 
            Muhammed~Elayadeth-Meethal\textsuperscript{5}~\\[5pt]{\textsuperscript{1}Department of Pharmacy Practice, KTN College of Pharmacy, Chalavara, Palakkad-679505, Kerala, India}~\\{\textsuperscript{2}Department of Dental Technology, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia}~\\{\textsuperscript{3}Department of Pharmaceutics, Moulana College of Pharmacy, Perintalmanna, Malappuram-679321, Kerala, India}~\\{\textsuperscript{4}MDC Denta care, KK Tower, Edavanappara, Malappuram, Kerala, India}~\\{\textsuperscript{5}Department of Animal Breeding and Genetics, College of Veterinary and Animal Sciences, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad, Kerala, India}}

\begin{abstract}
Antimicrobial agents (AMAs) are among the most commonly prescribed drugs in dental practice. However inappropriate prescribing and irrational use of antimicrobial agents without prior culture and sensitivity tests, inadequate duration, dosing etc. have been identified as major factors contributing to the emergence of antibiotic resistance, which is an ongoing challenge in all over the world. A total of 1900 patients were screened and out of which 1748 patients were selected based on the inclusion and exclusion criteria for the study after taking consent. This study shows that the majority of patients attended in these clinics were female, 1020 (58.35\%) and majority of patients (717) comes under age group 21-40 (41.02\%) followed by age group by \ensuremath{\leq } 20 (32.43\%).  This study established that most commonly recommended antimicrobial agents were amoxicillin, followed by amoxicillin-clavulanate and metronidazole. The antimicrobial agents like Ciprofloxacin, Cefixime, Tetracyclines, Azithromycines were also used but in less extent. This study also revealed that the selection of antimicrobials was not confirmed with culture and sensitivity tests in all cases, which may negatively influence bacterial resistance profile. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Antimicrobial Agents,\newline Prescription Pattern,\newline Amoxicillin,\newline Drug Utilization,\newline Dental Practice
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Muhas~C~\\ Phone:\ 9947786738~\\  Email:\ drmuhasc@gmail.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
        \textsc{DOI:}\ \href{https://doi.org/10.26452/\@journalDoi}{\textcolor{blue}{\underline{\smash{https://doi.org/10.26452/\@journalDoi}}}}\par%
        \vspace*{-11pt}\hrulefill\\{\fontsize{9.12}{10.12}\selectfont Production and Hosted by}\par{IJRPS |~\href{www.ijrps.com}{www.ijrps.com}}\par%
        \vspace*{-2pt}{\fontsize{9.12}{10.12}\selectfont\textcopyright\ \@copyrightYear\ $|$ All rights reserved.}\par%
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        \makeatother
        
    
\section{Introduction}
Antimicrobial agents (AMAs) are among the most commonly prescribed drugs, accounting for 30 {\textendash} 50\% of medicine prescriptions \unskip~\citep{1281092:23774167}. These antimicrobial agents are also very commonly used in dental practice and use of these agents takes an important part in dental care \unskip~\citep{1281092:23774196}.

Dentists are regularly prescribing antimicrobial agents for prophylactic or therapeutic indication to treat oral and dental infections \unskip~\citep{1281092:23774289}. Dentists usually start antimicrobial therapy in oral conditions such as periodontal abscess, acute ulcerative gingivitis and pericoronitis \unskip~\citep{1281092:23774292}. However inappropriate prescribing and irrational use of antimicrobial agents without prior culture and sensitivity tests, inadequate duration, dosing etc. have been identified as major factors contributing to the emergence of antibiotic resistance, which is an ongoing challenge in all over the world \unskip~\citep{1281092:23774293,1281092:23774511}. There are also other issues by the usage of antimicrobial agents such as possible adverse events and additional cost of prescribing etc \unskip~\citep{1281092:23774522}.

In recent years, dental practitioners have reported a shift from narrow spectrum to broad spectrum antimicrobials prescription due to excessive antimicrobial resistance \unskip~\citep{1281092:23774566}. The data available on antimicrobial agents use in most of the low and middle income countries are scanty and inadequate. Distinctively, information on antimicrobials use in dental practice sector is widely unavailable \unskip~\citep{1281092:23774579}. So the evaluation of prescribing pattern in these dental care facilities is of very important to identify problems related with rational drug use and to propose interventions \unskip~\citep{1281092:23774643}.

So this study was conducted to find out the prescription pattern of antimicrobial agents in North Malabar region of Kerala to analyze the nature of prescription habits and to improve the rational use of these antimicrobial agents \unskip~\citep{1281092:23774661}.
    
\section{MATERIALS AND METHODS\ensuremath{^{}}}
This is a cross-sectional, observational study was carried out for a period of 6 months from October 2020 to March 2021 at various dental clinics in Malappuram district, which is located in North Malabar region of Kerala. A total of 1900 patients who visited in these dental clinics were screened and out of which 1748 patients were included based on the inclusion and exclusion criteria.

\textbf{Inclusion Criteria}


  
  \begin{enumerate}
  \item \relax Both genders.
  \item \relax Patients of any age.
  \item \relax Prescription containing any antimicrobial agent.
  \end{enumerate}
  \textbf{Exclusion Criteria}


  
  \begin{enumerate}
  \item \relax Patients with ineligible and incomplete prescription.
  \item \relax Patients with oral cancer.
  \item \relax Patients who is not willing to participate.
  \end{enumerate}
  A structured questionnaire was prepared and explained in a simple language to patients by our team members. Patient's demographic data, detailed medical history, comorbidities, various features like dental conditions for which antibiotics were recommended, duration, dose, dosage, number of antibiotics in each prescription were recorded in the study proforma. The patient's details were allocating a code for recognition and the patient data entered into an approved excel spreadsheet. The secrecy and anonymity of the patient's details will be preserved during and after the study. The institution ethics committee approval was obtained and also collected the written informed consent from all the participants.

\textbf{Statistical Analysis}

In this study, the data were scrutinized using Microsoft excel 2007 and the collected data is expressed in the percentile form.
    
\section{RESULTS}
In this study, a total of 1900 patients who visited various dental clinics were screened and out of which 1748 patients were selected. The majority of patients attended in these clinics were females, 1020 (58.35\%) (Figure~\ref{f-365cd1ae7e3b}). These patients were further categorized based on their age. In case of male subjects, most of the patients presents in age group of 21-40 (41.35\%) followed by \ensuremath{\leq } 20 (28.85) and only 07.69\% of subjects constitutes above 60 years of age group. In case of female patients; 43.72\% patients were present in 21-40 age group and followed by \ensuremath{\leq } 20 (32.05\%). Totally majority of patients (717) comes under age group 21-40 (41.02\%), followed by age group by \ensuremath{\leq } 20 (32.43\%) (Table~\ref{tw-dc220b6bc490}).


\bgroup
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\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/a4f17f7e-a395-4d17-9646-03d01f5554aa-upicture1.png}{\includegraphics{images/a4f17f7e-a395-4d17-9646-03d01f5554aa-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Gender Based Distribution}}
\label{f-365cd1ae7e3b}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/220cefab-f915-4a73-9412-6a9b86569e88-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/220cefab-f915-4a73-9412-6a9b86569e88-upicture2.png}{\includegraphics{images/220cefab-f915-4a73-9412-6a9b86569e88-upicture2.png}}{}
\makeatother 
\caption{\boldmath {Relationship Between Gender and Number of Drugs in Prescription}}
\label{f-dc7fa3dbfee9}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/335496bb-8b3b-466d-b1c9-905025e0e09b-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/335496bb-8b3b-466d-b1c9-905025e0e09b-upicture3.png}{\includegraphics{images/335496bb-8b3b-466d-b1c9-905025e0e09b-upicture3.png}}{}
\makeatother 
\caption{\boldmath {Relationship Between Age and Number of Drugs in Prescription}}
\label{f-dea1156315ee}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/781942cd-723d-496a-9d11-5687037c4d91-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/781942cd-723d-496a-9d11-5687037c4d91-upicture4.png}{\includegraphics{images/781942cd-723d-496a-9d11-5687037c4d91-upicture4.png}}{}
\makeatother 
\caption{\boldmath {Frequency Distribution of the Conditions for which Antimicrobial was Prescribed}}
\label{f-289410d5a4ec}
\end{figure}
\egroup

\bgroup
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\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/d8ef0648-6442-4f7f-8798-de48185abf6b-upicture5.png}{\includegraphics{images/d8ef0648-6442-4f7f-8798-de48185abf6b-upicture5.png}}{}
\makeatother 
\caption{\boldmath {Percentage of Antibiotic Classes of Prescription}}
\label{f-36447e9da2ae}
\end{figure}
\egroup

\begin{table*}[!htbp]
\caption{\boldmath {Study Subjects Based on Age} }
\label{tw-dc220b6bc490}
\def\arraystretch{1.1}
\ignorespaces 
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\begin{tabulary}{\linewidth}{p{\dimexpr.1425\linewidth-2\tabcolsep}p{\dimexpr.218\linewidth-2\tabcolsep}p{\dimexpr.218\linewidth-2\tabcolsep}p{\dimexpr.2072\linewidth-2\tabcolsep}p{\dimexpr.2143\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Sl. No. & \cAlignHack Age group & \cAlignHack Male (\%) & \cAlignHack Female (\%) & \cAlignHack Total (\%)\\
\tblmidrule 
\cAlignHack 1. &
  \cAlignHack \ensuremath{\leq } 20 &
  \cAlignHack 210 (28.85) &
  \cAlignHack 327 (32.05) &
  \cAlignHack 567 (32.43)\\
\cAlignHack 2. &
  \cAlignHack 21 {\textendash} 40 &
  \cAlignHack 301 (41.35) &
  \cAlignHack 446 (43.72) &
  \cAlignHack 717 (41.02)\\
\cAlignHack 3. &
  \cAlignHack 41 {\textendash} 60 &
  \cAlignHack 161 (22.11) &
  \cAlignHack 205 (20.10) &
  \cAlignHack 366 (20.94)\\
\cAlignHack 4. &
  \cAlignHack {\textgreater}60 &
  \cAlignHack 56 (07.69) &
  \cAlignHack 42 (04.11) &
  \cAlignHack 98 (05.60)\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Incidence of Polypharmacy} }
\label{tw-7ed97f03a1e8}
\def\arraystretch{1.1}
\ignorespaces 
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\begin{tabulary}{\linewidth}{p{\dimexpr.321\linewidth-2\tabcolsep}p{\dimexpr.41519999999999996\linewidth-2\tabcolsep}p{\dimexpr.2638\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Number of Drugs & \cAlignHack Number of patients, n=1748 & \cAlignHack Percentage\\
\tblmidrule 
\cAlignHack 1. &
  \cAlignHack 95 &
  \cAlignHack 05.43\\
\cAlignHack 2. &
  \cAlignHack 686 &
  \cAlignHack 39.24\\
\cAlignHack 3. &
  \cAlignHack 529 &
  \cAlignHack 30.26\\
\cAlignHack 4. &
  \cAlignHack 406 &
  \cAlignHack 23.22\\
\cAlignHack 5. &
  \cAlignHack 32 &
  \cAlignHack 01.83\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Monotherapy and Combination Therapy of Antibiotics in a Prescription} }
\label{tw-38279c08e0a0}
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\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3121\linewidth-2\tabcolsep}p{\dimexpr.4712\linewidth-2\tabcolsep}p{\dimexpr.2167\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Number of Antibiotics & \cAlignHack Number of patients, n=1748 & \cAlignHack Percentage\\
\tblmidrule 
\cAlignHack 1. &
  \cAlignHack 1293 &
  \cAlignHack 73.97\\
\cAlignHack 2. &
  \cAlignHack 455 &
  \cAlignHack 26.03\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Utilization Pattern of Antimicrobial Agents} }
\label{tw-9ebc76560256}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1484\linewidth-2\tabcolsep}p{\dimexpr.5249999999999999\linewidth-2\tabcolsep}p{\dimexpr.3266\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Sl.no & \cAlignHack Drugs & \cAlignHack Number of times prescribed\\
\tblmidrule 
\cAlignHack 1. &
  \cAlignHack Amoxicillin &
  \cAlignHack 797\\
\cAlignHack 2. &
  \cAlignHack Amoxicillin + Clavulanic acid &
  \cAlignHack 670\\
\cAlignHack 3. &
  \cAlignHack Metronidazole &
  \cAlignHack 646\\
\cAlignHack 4. &
  \cAlignHack Ciporofloxacin &
  \cAlignHack 36\\
\cAlignHack 5. &
  \cAlignHack Cefixime &
  \cAlignHack 13\\
\cAlignHack 6. &
  \cAlignHack Doxycycline &
  \cAlignHack 12\\
\cAlignHack 7. &
  \cAlignHack Azithromycin &
  \cAlignHack 09\\
\cAlignHack 8. &
  \cAlignHack Erythromycin &
  \cAlignHack 08\\
\cAlignHack 9. &
  \cAlignHack Tetracycline &
  \cAlignHack 06\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Patients on Monotherapy} }
\label{tw-72817b2a3b26}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3255\linewidth-2\tabcolsep}p{\dimexpr.4443999999999999\linewidth-2\tabcolsep}p{\dimexpr.2301\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Drugs & \cAlignHack Number of times prescribed, n=1293 & \cAlignHack Percentage\\
\tblmidrule 
\cAlignHack \textbf{Penicillins} &
  \cAlignHack  &
  \cAlignHack \\
\cAlignHack Amoxicillin &
  \cAlignHack 604 &
  \cAlignHack 46.71\\
\cAlignHack Amoxicillin + Clavulanic acid &
  \cAlignHack 408 &
  \cAlignHack 31.55\\
\cAlignHack \textbf{Nitroimidazole} &
  \cAlignHack  &
  \cAlignHack \\
\cAlignHack Metronidazole &
  \cAlignHack 197 &
  \cAlignHack 15.23\\
\cAlignHack \textbf{Fluroquinolones} &
  \cAlignHack  &
  \cAlignHack \\
\cAlignHack Ciporofloxacin &
  \cAlignHack 36 &
  \cAlignHack 02.78\\
\cAlignHack Cephalosporins &
  \cAlignHack  &
  \cAlignHack \\
\cAlignHack Cefixime &
  \cAlignHack 13 &
  \cAlignHack 01.01\\
\cAlignHack \textbf{Tetracyclines} &
  \cAlignHack  &
  \cAlignHack \\
\cAlignHack Doxycycline &
  \cAlignHack 12 &
  \cAlignHack 00.93\\
\cAlignHack Tetracycline &
  \cAlignHack 06 &
  \cAlignHack 00.46\\
\cAlignHack \textbf{Macrolides} &
  \cAlignHack  &
  \cAlignHack \\
\cAlignHack Azithromycin &
  \cAlignHack 09 &
  \cAlignHack 00.69\\
\cAlignHack Erythromycin &
  \cAlignHack 08 &
  \cAlignHack 00.61\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
Prescription pattern of the 1748 prescriptions were assessed and in which total 4838 drugs were used for the treatment of the patients. The average number of drugs per prescription was 2.77.

Table~\ref{tw-7ed97f03a1e8}  indicated that only 95 patients (05.43\%) were receiving monotherapy and 686 (39.24\%) patients were receiving two drug therapy and 529 (30.26\%) patients receiving three-drug therapy and 406 (23.22\%) patients taking four drugs in their prescriptions. Only 32 (01.83\%) patients were receiving 5 drugs through their prescriptions. Figure~\ref{f-dea1156315ee}  indicated that age significantly affected the number of drugs in each prescription, however, effect of gender and the interaction effect (gender x number of drugs in the prescription) were not significant (Figure~\ref{f-dc7fa3dbfee9}). 

Total number of antibiotics prescribed was 2203 and average number of antibiotics per prescription was 1.26. Out of antibiotics prescribed 73.97\% of patients receiving monotherapy and 26.03\% of patients were receiving two drug therapy (Table~\ref{tw-38279c08e0a0}). In patients with two drug therapy, mainly they received either Amoxicillin + Metronidazole or Amoxiclav + Metronidazole.

The most common dental problems for which antimicrobial agents were prescribed include dental infections (38.84\%), root canal treatment (30.26\%), extraction (20.59\%), scaling (05.09\%), perio surgery (02.12\%), fracture (02.06\%) and oral ulcer (01.03\%). Majority of patients receiving antimicrobial agent therapy for dental infections, root canal treatment and extraction (Figure~\ref{f-289410d5a4ec}). 

Table~\ref{tw-9ebc76560256}  showed that the prescribing pattern of antimicrobial agents and the most commonly prescribed antimicrobial agents to treat above mentioned conditions were amoxicillin which was followed by Amoxicillin + clavulanic acid and Metronidazole. The antimicrobial agents like Ciprofloxacin, Cefixime, Tetracyclines, Azithromycines were not frequently used. Table~\ref{tw-72817b2a3b26}  described that Amoxicillin was prescribed most frequently, 604 times (46.71\%) followed by Amoxicillin + Clavulanic acid (31.55\%), and Metronidazole (15.23\%). Figure~\ref{f-36447e9da2ae}  showed that those patients receiving single antimicrobial agent, penicillin was the most common class of antibiotics administered (78.26\%) followed by nitroimidazole class (15.23\%), fluoroquinolones (02.78\%), Tetracyclines (01.39\%), Macrolides (01.30\%) and Cephalosporins (01.01\%).
    
\section{DISCUSSION}
Appropriate diagnosis of a dental problems and its treatment with proper drugs and dental procedure take part in the crucial role in dental care \unskip~\citep{1281092:23774703}. This study was carried out to find the prescription pattern of antimicrobial agents in various dental clinics at North Malabar region of Kerala, South India.

In our study, majority of the patients visiting inn the dental clinics were females (58.35\%) and the same report were also found by another study conducted in Malappuram district of Kerala \unskip~\citep{1281092:23774703}. In this study, most of the dental cases were related to dental problems such as dental infections, dental abscesses, root canal treatment, post dental extraction etc. for which antimicrobial agents were recommended, which was in concordance to the study carried out in different places of North and South India \unskip~\citep{1281092:23774703,1281092:23774735}.

This study established that most commonly recommended antimicrobial agents was amoxicillin, followed by amoxicillin-clavulanate and metronidazole. These findings were in line with the antibiotics prescribing guidelines, which recommends amoxicillin or metronidazole as first choice agents for the treatment of different dental infections \unskip~\citep{1281092:23774764,1281092:23774814}. The same report was also exhibited by some different studies \unskip~\citep{1281092:23774579,1281092:23774735}. Other studies from England and Iran also advocated that amoxicillin as first choice drug in dental practice. Another rationale behind this extensive use of amoxicillin may be due to its comparative clinical effectiveness to other antimicrobials, appropriate dosage, cost effectiveness and tolerability \unskip~\citep{1281092:23774831,1281092:23774862}.\ensuremath{^{}} In contrast, in the USA amoxicillin was prescribed only by 27.5\% of members of American association of endodontists \unskip~\citep{1281092:23774952,1281092:23774963}.

The use of antimicrobial agents for minor infections or in some cases in patients without infections could be major supporter to the development of antibiotic resistance. In this study, it was also found that only a few culture sensitivity tests were accomplished before the commencement of antimicrobial therapy \unskip~\citep{1281092:23775088}.
    
\section{Conclusion}
This study was exhibit to analyse the prescription pattern of antimicrobial agents in North Malabar region of Kerala, South India. Our findings demonstrated that dental infections were the most commonly reported conditions followed by root canal treatment and extraction for which antimicrobial therapy were recommended in this region. Among the antimicrobial agents, Amoxicillin was prescribed most frequently followed by Amoxicillin + Clavulanic acid and Metronidazole. This study also revealed that the selection of antimicrobials was not confirmed with culture and sensitivity tests in all cases, which may negatively influence bacterial resistance profile. There is a crucial need to uplift public and professional awareness with respect to the risks of antimicrobial use in dentistry.

\textbf{Funding Support}

This study was supported by the Deanship of Scientific Research of King Khalid University, Abha, Saudi Arabia, through research group program under grant no: RGP:2/191/42. We also acknowledge those patients who participated in this study.

\textbf{Conflict of Interest}

The authors declare that there is no conflict of interest.
    

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