<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">JASMI</journal-id><journal-title-group><journal-title>Journal of Analytical Sciences, Methods and Instrumentation</journal-title></journal-title-group><issn pub-type="epub">2164-2745</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/jasmi.2020.101001</article-id><article-id pub-id-type="publisher-id">JASMI-98054</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Chemistry&amp;Materials Science</subject></subj-group></article-categories><title-group><article-title>
 
 
  Effective Antibiotic Stewardship Program: Controlling Antibiotic Resistance and Optimizing Drug Use in Ahmadi Hospital
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Saud</surname><given-names>M. Alajmi</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Wadha</surname><given-names>N. Almarri</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Ahmadi Hospital, Kuwait Oil Company, Ahmadi, Kuwait</addr-line></aff><aff id="aff2"><addr-line>Infection Prevention and Control Unit, Ahmadi Hospital, Kuwait Oil Company, Ahmadi, Kuwait</addr-line></aff><pub-date pub-type="epub"><day>21</day><month>01</month><year>2020</year></pub-date><volume>10</volume><issue>01</issue><fpage>1</fpage><lpage>11</lpage><history><date date-type="received"><day>15,</day>	<month>December</month>	<year>2019</year></date><date date-type="rev-recd"><day>19,</day>	<month>January</month>	<year>2020</year>	</date><date date-type="accepted"><day>22,</day>	<month>January</month>	<year>2020</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  An Antimicrobial Stewardship Program (ASP) is established to promote cost effective and safe use of antimicrobial agents. Basically, this approach directs the management of antimicrobials in terms of selection of appropriate drugs, determination of administration routes and standardization of both medication dosage and treatment duration. The program involves, but is not limited to, Hospital Staff Education, Pharmacodynamics Dose Optimization, Computer-Assisted Decision Support Programs, Pharmacist-Driven Intravenous to Oral Switch Programs, Pharmacy Dosing Programs and Antibiotic Cycling. A study was conducted to determine effectiveness of the ASP in significantly improving patient outcomes (e.g. decrease morbidity and mortality from infection). This was undertaken by collecting restrospective data on patient length of hospital stay, bed turnover rate and antibiotic consumption over a period of 2 years since the ASP was initiated. Periodic data were then compared and interpreted based on its clinical, quality and financial implications in order to measure effectiveness of the program implementation.
 
</p></abstract><kwd-group><kwd>Antibiotics</kwd><kwd> Antibiotic Stewardship</kwd><kwd> Drug Resistance</kwd><kwd> Infectious Disease</kwd><kwd> Kuwait</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>In addition to saving lives, antibiotics have played significant role in understanding major advances in medicine and surgery [<xref ref-type="bibr" rid="scirp.98054-ref1">1</xref>]. They have treated infections that require chemotherapy treatments, have chronic diseases including diabetes, or rheumatoid arthritis, end-stage renal disease, or require complex surgeries such as organ transplants, joint replacements, or cardiac surgery [<xref ref-type="bibr" rid="scirp.98054-ref1">1</xref>]. Antibiotics have extended the expected life span by treating bacterial infections [<xref ref-type="bibr" rid="scirp.98054-ref2">2</xref>] [<xref ref-type="bibr" rid="scirp.98054-ref3">3</xref>]. The first antibiotic-penicillin—was very successful in treating the deathly infectious diseases. However, soon penicillin resistance emerged that threatened the advantages of penicillin [<xref ref-type="bibr" rid="scirp.98054-ref4">4</xref>]. To tackle the threatening diseases new beta-lactams were introduced that restored confidence of treating bacterial diseases [<xref ref-type="bibr" rid="scirp.98054-ref5">5</xref>]. This was followed by emergence of Methicillin resistance in Staphylococcus aureus (MRSA), development of Vancomycin for treating MRSA and then identification of Vancomycin-resistant cases [<xref ref-type="bibr" rid="scirp.98054-ref5">5</xref>].</p><p>Despite efforts to stem the upward trend of antibiotic resistance, the spread of multidrug-resistant organisms (MDROs) and MDRO-associated infections are continuously increasing in the hospital patients [<xref ref-type="bibr" rid="scirp.98054-ref6">6</xref>]. MDRO-associated infections has resulted in deterioration in clinical results, increase in health associated cost and risk of death. Cephalosporin-resistant Enterobacter infection has resulted in increase in hospital charges, length of stay and mortality [<xref ref-type="bibr" rid="scirp.98054-ref7">7</xref>].</p><p>Epidemiological studies have shown positive relationship among the antibiotic usage and evolution of antibiotic resistance bacterial strains [<xref ref-type="bibr" rid="scirp.98054-ref8">8</xref>]. Mutations, horizontal gene transfer and acquisition of plasmids provide multi-drug resistance to bacteria. The usage of antibiotics results in decimation of antibiotic susceptible bacteria, but antibiotic resistant bacteria grow and reproduce as a result of natural selection. The surviving bacteria share their genetic material to other strains making them resistant too. Diverse inheritance pattern and adaptive capabilities of the bacteria make them resistant whether antibiotics are used appropriately or inappropriately. This shed light on their careful and prudent use in order to slow down the process of antibiotic resistance development. It has been observed innumerable times that a bacteria that was resistant to an antibiotic acquires resistance [<xref ref-type="bibr" rid="scirp.98054-ref9">9</xref>]. Studies have suggested that more than 50% of antibiotic usage is inappropriate [<xref ref-type="bibr" rid="scirp.98054-ref10">10</xref>]. Even warning regarding development of resistant bacteria due to overuse or misuse of antibiotics has not resulted in decrease or appropriate use of antibiotic prescription [<xref ref-type="bibr" rid="scirp.98054-ref11">11</xref>]. In addition to overuse, inappropriate use of antibiotics has also resulted in speeding up the process of antibiotic resistance [<xref ref-type="bibr" rid="scirp.98054-ref12">12</xref>].</p><p>The terms which are used for antimicrobial stewardship programs may vary significantly such as antibiotic policies, antibiotic control program and antibiotic management programs. All these terms in general refer to a principal program with which emphasizes on change and controlled use of antimicrobial agents at any health care institution, it may use multiple strategies [<xref ref-type="bibr" rid="scirp.98054-ref13">13</xref>].</p><p>An ASP is established to control and regulate the cost effective and safe use of antimicrobial means and agents. Basically, this approach directs the appropriate management and selection of antimicrobials, administration routes, dosages of medicine and duration of treatment and therapy [<xref ref-type="bibr" rid="scirp.98054-ref14">14</xref>]. The ASP emphasizes on the use of right drug for appropriate time duration in right amount. In addition, above mentioned program controls the development of multidrug-resistant organisms (MDROs), adversarial drug events, length of stay at hospital, collateral damages e.g. Clostridium difficile colitis development as well as reduces health care costs [<xref ref-type="bibr" rid="scirp.98054-ref15">15</xref>]. ASP plays a crucial role in controlling antimicrobial resistance because microbes perpetually become resistant due to the extensive exposure to antimicrobial agents. There are multiple strategies for improving the diagnosis of severe infections. Multidrug-resistant organisms are the main focus of this program which provides guidance about proper use of broad-spectrum therapies as well as avoiding unnecessary exposure to antibiotics. These diagnostic approaches result in rapid and immediate identification of causal organisms as well as improves the specificity of sepsis diagnosis. Antibiotic stewardship program has successfully been reported to reduce the incidence and colonization of C. difficile [<xref ref-type="bibr" rid="scirp.98054-ref16">16</xref>].</p><p>Optimum antimicrobial stewardship comprises choosing the most suitable drug at its best dosage and period of therapy to eliminate an infection while curtailing side effects and pressures of resistant strains adaptation [<xref ref-type="bibr" rid="scirp.98054-ref17">17</xref>]. The decision matrix utilized by physicians to advice antibiotics can guide as a conceptual framework. Making a suitable antibiotic option begins with awareness of infectious diseases and the organisms implicated in different infections, as well as identifying which species are resistant to a specific antibiotic and whether that antibiotic can enter the infection site. Therefore, in taking these decisions, both pharmacodynamic and pharmacokinetic awareness is vital [<xref ref-type="bibr" rid="scirp.98054-ref18">18</xref>]. Overall clinical experience, including renal function, drug reactions, and use of concurrent medications that can end in drug interactions are imperative concerns that must be taken into account in the decision to pick and use an antibiotic. Another important factor is the availability of a particular antibiotic in hospital setting. Microbiological surveillance or screening of susceptibility may play a key role in improving antibiotic selection. Empirical therapy usually involves the use of broad-spectrum medications, but it is important to move to a narrower-activity medicine when the effects of available culture test indicate that such an approach is acceptable [<xref ref-type="bibr" rid="scirp.98054-ref19">19</xref>].</p><p>Antibacterial stewardship has 2 main methods, however, the best strategy is to apply both of them. The front-end or pre prescription approach that uses restrictive prescriptive authority. There are certain antimicrobials that are considered restricted and need earlier authorization for usage by all practitioners except a selected group of clinicians. Clinicians that are lacking the authority to prescribe a particular drug are required to contact the nominated antimicrobial steward and request for approval for that particular antimicrobial. The front-end approach provides advantage of targeting some antimicrobials depending on local resistance patterns and the hospital formulary [<xref ref-type="bibr" rid="scirp.98054-ref20">20</xref>] [<xref ref-type="bibr" rid="scirp.98054-ref21">21</xref>].</p><p>The back-end or postprescription approach to stewardship utilizes feedback and review. The antimicrobial steward reviews existing antibiotic orders and is responsible for recommending clinicians to continue, adjust, change, or discontinue the antibiotic usage depending upon the availability of microbiological results and specific clinical features of a particular case. Studies that used this approach have demonstrated a decrease in antimicrobial usage and decrease in number of antimicrobials based prescription [<xref ref-type="bibr" rid="scirp.98054-ref22">22</xref>] [<xref ref-type="bibr" rid="scirp.98054-ref23">23</xref>]. The back-end approach provides a benefit in providing capability to emphasis on de-escalation, a factor that is very critical in appropriate antimicrobial usage. De-escalation is amendment of the initial empiric antimicrobial depending upon information from culture test, laboratory results, and patient’s clinical status. De-escalation contains altering a broad-spectrum antibiotic to the one with narrower coverage, moving from combined therapy to single therapy, or even stemming antibiotic medication completely as soon as it is evident that these antimicrobial drugs are no more required.</p><p>A study was conducted to determine effectiveness of the ASP in significantly improving patient outcomes (e.g. decrease morbidity and mortality from infection). This was undertaken by collecting restrospective data on patient length of hospital stay, bed turnover rate and antibiotic consumption over a period of 2 years since the ASP was initiated. Periodic data was then compared and interpreted based on its clinical, quality and financial implications in order to measure effectiveness of the program implementation.</p></sec><sec id="s2"><title>2. Materials and Methods</title><p>An ASP was initiated in Ahmadi Hospital to assess antimicrobial usage, suitability of antibiotic selection and appropriateness of utilization. Different clinical departments and multi-disciplinary experts were involved and a complete set-up of ASP was designed.</p><p>Hospital-wide ASP educational sessions and campaigns were facilitated. Core contributors in the ASP such as doctors, pharmacists, infection preventionists, medical technologists, nurses and Information Technology (IT) specialists were prioritized in the engagement sessions which focused on the prudent and appropriate use of antibiotics.</p><p>Available data on antibiotic prescriptions were analyzed. Following this, a rationalization was applied in the process of ordering each type of antibiotic for all clinical specialties to control prescriptions and prevent inappropriate use. A specialty-specific antibiotic policy was then implemented for each clinical department to comply with. This policy specified antibiotics to be used for each type of infection, clinical condition and pathogen. Antibiotics were selected based on the annual hospital antibiogram report.</p><p>An infection control surveillance was also activated to look into the efficacy, side effects, dosage adjustment and alteration of antibiotics. Special focus was given to the development of antibiotic-induced Clostridium difficile infection in inpatients.</p><p>Data on average length of stay and bed turnover were collected. These were gathered over a period of 2 years (2018-2019) in two same quarters, April to June. In addition to this, antibiotic consumption data was also obtained from the pharmacy. Data was categorized into 1) no. of antibiotic prescriptions per specialty and 2) No. of antibiotic prescriptions by drug name and type. All data collected were analyzed using SPSS-23 and correlated to evaluate changes in trends during the ASP implementation.</p></sec><sec id="s3"><title>3. Results</title><sec id="s3_1"><title>3.1. Hospital-Related Results</title><sec id="s3_1_1"><title>3.1.1. Average Length of Stay (ALOS)</title><p>The Average Length of Stay (ALOS) was calculated by dividing the sum of lengths of stay for all discharged patients (including deaths) into the total number of discharges (including deaths) and is expressed as hospital or calendar days. Comparing the data from 2018 to 2019, it can be inferred that there is an increase on the ALOS from 4.4 to 5.1 hospital days. <xref ref-type="fig" rid="fig1">Figure 1</xref> shows ALOS in 2019 was higher in all three months compared to the same period in 2018. There is a marginal difference between the ALOS on the month of May of the years in comparison, from 4.3 to 5.4 hospital days making it the month with the most significant change in trend. Though also increased by 0.5 days, April remained with the minimal ALOS in all three months.</p></sec><sec id="s3_1_2"><title>3.1.2. Bed Turnover Rate (BTR)</title><p>Bed Turnover Rate (BTR) was calculated by dividing the number of discharges (including deaths) in a given period and the hospital bed count during the period. The result is then expressed as cycles or discharges per bed per period. <xref ref-type="fig" rid="fig2">Figure 2</xref> shows a change in the trend pattern between 2018 and 2019. Bed turnover in April was nearly twice as the rate in the preceding year. It also illustrates</p><p>a change in the trend with the month of May decreasing to 2.38 in 2018 from 2.7 in 2019. The turnover rate in June, on the other hand, increased from 2.0 to 2.42. Overall, the median BTR is at 2.0 in 2018 and 2.5 in 2019.</p></sec></sec><sec id="s3_2"><title>3.2. Antibiotic Consumption</title><sec id="s3_2_1"><title>3.2.1. Antibiotic Prescription per Clinical Specialty</title><p>Data on the total number of antibiotics prescribed by each specialty was gathered and analyzed by bar plots. From August to December of 2018 (5-month period), a total no. of 4837 prescriptions were noted, averaging 32 prescriptions per day, as illustrated in <xref ref-type="fig" rid="fig3">Figure 3</xref>. By March to August of 2019 (6-month period): 5324 prescriptions were recorded, averaging 29 prescriptions per day, as shown in <xref ref-type="fig" rid="fig4">Figure 4</xref>. In both time periods, medical physicians prescribed the most antibiotics. Medical doctors averaged at 14.8 in 2018 which lowered to 12.1 prescriptions in 2019. The surgeons, on the other hand, initially averaged at 4.76 in 2018 and improved at 4.05 the succeeding year. The pediatricians, however, remained on an average of 4.21 prescriptions for both observation periods. The specialty with the least number of prescribed antibiotics were the dentists.</p></sec><sec id="s3_2_2"><title>3.2.2. Antibiotic Consumption per Medication</title><p>Both time periods in <xref ref-type="fig" rid="fig5">Figure 5</xref> and <xref ref-type="fig" rid="fig6">Figure 6</xref> show that Ceftriaxone and Piperacillin/Tazobactam were the most frequently prescribed antibiotics. Ceftriaxone tallied to more than a thousand prescriptions followed by Piperacillin/Tazobactam with about half as many as the latter. Other antibiotics that are mostly ordered for patients were Tavanic (Levofloxacin), Metronidazole, Meronem (Meropenem) and Dalacin-C (Clindamycin).</p></sec></sec></sec><sec id="s4"><title>4. Discussion</title><p>In this study, ALOS has increased in 2019 as compared to 2018 (<xref ref-type="fig" rid="fig1">Figure 1</xref>). This implies that patients are staying in the hospital for a longer period of time as compared to the previous year. Indications of higher ALOS are slow recovery of the patients and slow decimation of the disease-causing organisms. This may be due to microbes developing resistance and requiring longer exposure to the antibiotics for full recovery from the disease. Hence, resulting in longer inpatient admissions, various studies have concluded increase in resistance to several</p><p>antibiotics such as Piperacillin [<xref ref-type="bibr" rid="scirp.98054-ref24">24</xref>]. This antibiotic has been majorly used in our institution (<xref ref-type="fig" rid="fig5">Figure 5</xref> and <xref ref-type="fig" rid="fig6">Figure 6</xref>). This implicates avoidance of inappropriate usage of antibiotics in the future to prevent drug resistance.</p><p>An increase in the median bed turnover rates (<xref ref-type="fig" rid="fig2">Figure 2</xref>) may have been brought about by the facility transition. This occurred in the next two years following mobilization of old patients and admission of new cases due to the increase in bed capacity. Similarity in the patterns of admissions, discharges and BTR validates the concept that as the number of admissions and discharges are increasing, a high turnover rate is expected. Corresponding facilities and services are enhanced to tackle the increasing number of inpatients. This happened as a result of starting of a systematic antibiotic stewardship plan in the hospital [<xref ref-type="bibr" rid="scirp.98054-ref14">14</xref>].</p><p>Several studies have suggested decreasing antibiotic usage in the children by parents awareness and interventions in the provision of antibiotics [<xref ref-type="bibr" rid="scirp.98054-ref25">25</xref>]. In our setting, pediatricians are among the top three physician specialties with the most number of prescriptions (<xref ref-type="fig" rid="fig3">Figure 3</xref> and <xref ref-type="fig" rid="fig4">Figure 4</xref>). Prudent use implies minimal possible use of antibiotics especially in children [<xref ref-type="bibr" rid="scirp.98054-ref26">26</xref>].</p><p>Studies have demonstrated that increased usage of Ceftriaxone has resulted in resistance, giving rise to Penicillin-resistant Streptococcus pneumonia. The increased usage of Ceftriaxone has resulted in several alterations in the penicillin-binding targets in S. pneumonia [<xref ref-type="bibr" rid="scirp.98054-ref27">27</xref>]. In our setting, Ceftriaxone has maximum usage among all the antibiotics listed with a big marginal difference (<xref ref-type="fig" rid="fig5">Figure 5</xref> and <xref ref-type="fig" rid="fig6">Figure 6</xref>). Several other antibiotics that are oftenly used in our hospital are Tavanic (Levofloxacin), Metronidazole, Meronem (Meropenem) and Dalacin-C (Clindamycin) (<xref ref-type="fig" rid="fig5">Figure 5</xref> and <xref ref-type="fig" rid="fig6">Figure 6</xref>). Several studies have suggested resistance against these agents [<xref ref-type="bibr" rid="scirp.98054-ref28">28</xref>] [<xref ref-type="bibr" rid="scirp.98054-ref29">29</xref>]. There is dire need for the appropriate use of these antibiotics to stem the mechanism of antibiotic resistance evolution.</p><p>Commitment and cooperation of several hospital departments is paramount to the smooth execution of the ASP. Strategies include proper education, working in collaboration with pharmacists and medicine experts, and optimizing dosage of the antibiotic, which are all interdependently important.</p></sec><sec id="s5"><title>Funding Information</title><p>No funding was received for this study. S. M. A. and W. N. A. are full-time employees of Ahmadi Hospital and preparation of this manuscript was entirely self-funded.</p></sec><sec id="s6"><title>Conflicts of Interest</title><p>All authors declared no competing interests for this work.</p></sec><sec id="s7"><title>Cite this paper</title><p>Alajmi, S.M. and Almarri, W.N. (2020) Effective Antibiotic Stewardship Program: Controlling Antibiotic Resistance and Optimizing Drug Use in Ahmadi Hospital. Journal of Analytical Sciences, Methods and Instrumentation, 10, 1-11. https://doi.org/10.4236/jasmi.2020.101001</p></sec></body><back><ref-list><title>References</title><ref id="scirp.98054-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Gould, I.M. and Bal, A.M. (2013) New Antibiotic Agents in the Pipeline and How They Can Help Overcome Microbial Resistance. Virulence, 4, 185-191. 
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