Review of the Appropriateness of Surgical Antimicrobial Prophylaxis

Aim: This review aims to describe the appropriateness of surgical antimicrobial prophylaxis during the last decade. Methodology: The review included a searching web of science for articles focused on “the appropriateness of surgical antimicrobial prophylaxis”. The searching process was conducted on 29 Nov 2020 and included original articles so the review articles were excluded. Results: The review included 57 articles; 38 articles were published after 2015 and the rest before 2015. Most of the articles that were included in the review showed a high rate of inappropriate surgical prophylaxis and showed inappropriate duration and time of the antibiotics used. Conclusion: It can be concluded that the rate of surgical prophylaxis inappropriateness was high and the main cause for this result was inappropriate timing and duration. Numerous interventions including educational interventions such as one-time seminars and online e-learning modules are needed to improve the adherence to the guidelines. Review Article Ahmed et al.; JPRI, 33(23B): 81-92, 2021; Article no.JPRI.66551 82


INTRODUCTION
Antimicrobial resistance is considered one of the worldwide threats for both economic development and human health [1]. Resistant microorganisms are the main causative agents of healthcare-associated infections (HAIs) in both high-income and low-income countries. The most reported and surveyed type of HAIs are surgical site infections (SSIs) and account for up to 20% of all hospital-acquired infections [2]. Surgical site infections are defined as postoperative infections that occur within 30 days from a surgical procedure or within 1 year from a permanent implant [3].
Once occurred, surgical site infections are associated with an increased risk of mortality. In addition, they are also connected to a prolonged hospital stay [1,4,5]. Moreover, SSIs cause an increase in healthcare costs that are driven by prolonged hospitalization, additional diagnostic tests, treatment, and re-operations [6]. The prevention of these infections is complex and requires the integration of a range of measures that should be implemented before, during, and after surgery [7]. Of note, 2016 guidelines by the World Health Organization (WHO) highlighted the risk of unnecessary prolongation of surgical antibiotic prophylaxis (SAP) in causing adverse events and developing antimicrobial resistance [7]. One way to minimize this risk is by the implementation of antimicrobial stewardship programs. Positive effects of antimicrobial stewardship interventions in low-and middleincome countries have been previously reported [8,9]. Measures for assessing the effectiveness of antimicrobial stewardship programs (ASPs) are either process measures such as change in antibiotic use, compliance with hospital-specific guidelines, or outcome measures. This review aims to describe the appropriateness of surgical antimicrobial prophylaxis during the last decade [10].

METHODOLOGY
The review included a searching web of science for articles focused on "the appropriateness of surgical antimicrobial prophylaxis". The searching process was conducted on 29 Nov 2020 and included original articles so the review articles were excluded.
The searching process resulted in 86 articles about the topic. After that we limit the search to the last 10 years; 25 articles were excluded and 61 articles were included in the study. After that, we further limit the search to include human research only so another 4 articles were excluded. So, 57 articles were included in the present study. Furthermore, we add several articles that were cited by the included studies.
The inclusion criteria include original articles that were conducted in the last 10 years about the appropriateness of surgical antimicrobial prophylaxis and the exclusion criteria include review articles, articles that were conducted on animals and articles that were conducted before more than 10 years.
The flow diagram for a literature search is shown in Fig. 1. Moreover, the authors of these articles, the year of publications, and the name of the published journals are shown in Table 1 and  Table 2. Most of the articles that were included in the review showed a high rate of inappropriate surgical prophylaxis. Ierano et al. found that the antimicrobials for surgical prophylaxis were poorly prescribed in Australian hospitals with a low rate of the appropriateness of antimicrobials surgical prophylaxis prescription [11,12]. Segala et al. reported that the adherence to perioperative prophylaxis guidelines before the implementation of antimicrobial stewardship was only 36.6% and increased after their intervention [13]. Moreover, Anandalwar et al. reported that regarding the use of surgical antibiotic prophylaxis in general pediatric surgery, 44% of the cases received inappropriate prophylaxis, of which 42% were considered overtreatment and 58% were considered undertreatment [14]. Karaali et al. found that in the pre-intervention phase of their study, the rate at which all stages of surgical prophylaxis were adhered to was found to be low [15].
Osowicki et al. reported that among surgical patients, 65 of 187 antimicrobial prescriptions (35%) were deemed inappropriate and that the common reason for this was excessive prophylaxis duration [16]. Additionally, Cotta et al. found that the rate of the appropriateness of antimicrobials prescribed for surgical prophylaxis was 40.6% and that prolonged duration (>24 hours) was the main reason for inappropriate surgical prophylaxis prescriptions [17]. Gül et al stated that inappropriate antibiotic usage rates in surgical wards were high [18]. They also stated that the inappropriate usage was especially related to prophylaxis and that it is necessary for surgeons to be educated regarding prophylactic antibiotic usage and to stick to the surgical prophylaxis guidelines [18].
Abdel Jalil et al. reported that the overall compliance with the surgical anti microbial prophylaxis guidelines in cesarean deliveries was poor; nevertheless, certain components showed high compliance rates, such as indication and choice of antibiotics [19]. Kara et al. reported that the inappropriate antimicrobial usage rate was 57.1% in surgical wards [20]. Moreover, Degli Atti reported that regarding surgical antibiotic prophylaxis in children the overall appropriateness of antibiotic choice, timing, and duration was 8% [21].
Oshikoya et al. stated that among the 303 surgical pediatric patients, 97.7% received surgical antimicrobial prophylaxis and complete compliance was poor (5.6%) and that timing, redosing, and duration of antimicrobial use were the most violated [22]. Gil et al. found that the overall compliance to antibiotic prophylaxis protocol in breast surgery was very high and the low rate of non-compliance was caused mainly due to the inappropriate timing and inappropriate choice of antibiotic [23]. Alonso-García et al. reported that the antibiotic prophylaxis appropriateness was high in patients who underwent renal surgery with an overall compliance rate of 90.6% [24].
Deelen et al. reported that for most prescriptions there was a protocol about antimicrobial prophylaxis outside the operating theatre and that the adherence to the protocols was high [25]. Quattrocchi et al. found overall low compliance to perioperative antibiotic prophylaxis in 2 hospitals in Italy; mainly regarding antibiotic choice and the total duration of prophylaxis [26]. Conaty et al. stated that regarding surgical antimicrobial prophylaxis (SAP) prescribing in orthopedic surgery, the prescribing appropriateness was low (20%) but it was improved 78% after the implementation of their interventions [27]. Dimopoulou et al. found that the percentage of patients receiving appropriate perioperative antibiotic prophylaxis improved from 6.2% to 77.1% after the educational intervention [28]. Bozkurt et al. stated that both in 2011 and 2012, inappropriate antibiotic use was found to be significantly higher in surgical clinics in comparison to the internal diseases clinics and the ICU [29]. This was caused by the high rates of inappropriate perioperative antimicrobial prophylaxis observed in surgical clinics [29].
Abu-Gharbieh and Fahmy reported that the adherence to international antimicrobial prophylaxis guidelines for cardiac surgery was found to be suboptimal in the study hospital in Dubai [30]. Snyder et al. stated that a high  [34]. They found also that inappropriate use of antimicrobial for surgical prophylaxis is widespread and that antibiotics continue to be prescribed at discharge [34].
McMullan et al. stated that surgical prophylaxis was inappropriate in 59% of prescriptions [35].
Dona et al. found that the appropriateness of antimicrobial prophylaxis was low 48.9 % but it was increased in the post-intervention period from 48.9% to 60.0% [36]. Napolitano et al. stated that perioperative antibiotic prophylaxis was appropriate in 18.1% of cases only and that educational interventions are needed to improve perioperative appropriate antibiotic prophylaxis [37]. Rangel et al. reported that a significant variation exists in the use of AP in the pediatric surgical population [38]. They found that children may receive antibiotics when there is no indication and that numerous children do not receive antimicrobial prophylaxis when indicated [38]. Artoisenet et al. stated that 40 % of intravenous amoxicillin/clavulanate prescriptions that were used for surgical prophylaxis were inappropriate [39].

INAPPROPRIATE INDICATION
The first basic parameter of antimicrobial prophylaxis in surgery is the indication. Segala

INAPPROPRIATE SELECTION AND DOSING
In addition to indication, parameters of antimicrobial prophylaxis in surgery include antimicrobial selection and dosing. Khan et al. stated that only 9.5% of the surgeons adhered to guidelines concerning correct choice [33]. Ramcharan et al. stated that cefuroxime or cefazolin is used commonly as a prophylactic agent and the rate of appropriateness is high [56]. Eisner et al. reported that the most commonly used antibiotics for surgical prophylaxis were cephalosporins and in their study the most frequently used antibiotics were cefuroxime [57]. They stated that the use of cefuroxime was inappropriate due to high percentage of bacterial resistance [57].
Segala et al stated that the adherence to guidelines regarding the selection and dosing of antimicrobial was 58.5 and was improved to 80.6% after the implementation of their interventions [13]. Dimopoulou et al. reported that regarding perioperative antimicrobial prophylaxis, the correct antimicrobial agent was used in 28.7% of the surgeries only [28]. Moreover, Giordano stated that the guidelines of Surgical Antibiotic Prophylaxis for appropriate drug choice were followed in 5.7% of cases and that the guidelines of Surgical Antibiotic Prophylaxis for appropriate drug choice were followed for dose in 91.5% of cases [45]. reported that out of 2059 elective surgical procedures, the dose was appropriate with a rate of 69.7% and that the choice of antibiotic was appropriate with a rate of 78.4% [40]. In addition, Oshikoya et al. stated that most antimicrobials used by pediatric patients were underdosed (44.5%) or overdosed (31.5%) [22]. Toba et al. also stated that due to the inappropriate antibiotic dose it is important to follow the dosing regimens according to the guidelines because this would be useful to reduce the complications associated with antibiotics, reduce antibiotic medicine costs and prevent resistant bacteria [60]. Khan et al. stated that about 40% of the surgeons adhered to guidelines concerning timing [33]. Ierano et al. stated that when procedural Surgical Antibiotic Prophylaxis was clinically indicated but considered inappropriate, the most common reason for inappropriateness was timing (49.5%) [12]. Giordano stated that the adherence rate to guidelines of Surgical Antibiotic Prophylaxis for timing was 48.6% [45]. Napolitano et al. stated that the appropriateness of the timing of prophylactic antibiotic administration was observed in 53.4% of the procedures [37].

INAPPROPRIATE TIMING
Ierano et al. found that the most common reason for inappropriate procedural use was incorrect timing [11]. Segala et al. stated that the adherence to guidelines regarding timing was improved from 92.4 before the implementation of antimicrobial stewardship interventions to 97.6% after the implementation [13]. Abubakar et al. stated that excessive and inappropriate use of antibiotic prophylaxis was observed in women who had obstetrics and gynecology surgeries and that timing of antibiotic prophylaxis was optimal in only 16.5% of surgeries [61]. Pittalis et al. stated that there was a high percentage of inappropriateness in the timing and duration of antibiotic prophylaxis in the Latium region of Italy [62]. Ierano et al. found that duration greater than 24 hours was the most common reason for inappropriate postprocedural surgical antimicrobial prophylaxis [11]. Turnidge et al. found that the rate of surgical antimicrobial prophylaxis exceeding the benchmark of 24 hours was high (36%) [63]. Abu-Gharbieh and Fahmy reported that 93.5% of the patients received the right antibiotic dose while the total duration of all antimicrobial agents used for prophylaxis was concordant with the guidelines in only 67.4% of the patients [30]. Akalin et al. stated that unnecessarily prolonged antimicrobial prophylaxis was observed in 56.9% of the procedures [55]. Giordano et al. stated that the guidelines of surgical antibiotics for the duration were followed in 14.5% of cases [45].

INAPPROPRIATE DURATION
Segala et al. stated that the adherence to guidelines regarding duration was 71% and was improved to 80.1% after their intervention [13]. Arnoldo et al. stated that the appropriateness of duration of surgical prophylaxis was poor but after the implementation of the recommended protocol it is increased significantly [64]. Moreover, Ierano et al. found that prolonged duration was the most common reason for inappropriateness for all surgical procedure groups [12]. Abubakar  Komagamine et al. stated that more than twothirds of the antimicrobial drugs used for surgical prophylaxis were administered for durations longer than 1 day, whereas the duration of antimicrobial drugs for surgical prophylaxis of 1 day or less has been found to be sufficient in most cases [68]. An unnecessarily long duration of surgical antimicrobial prophylaxis was also found to be common in past studies investigating the antimicrobial drug use for surgical prophylaxis [69][70][71][72][73]. The continuation of prophylactic antibiotic treatment postoperatively on surgical wards is of major concern, as no benefit has been demonstrated in previous studies [74][75][76][77][78]. Ciofi et al. highlighted several areas of improvement, such as actions for screening patients in case of occurrence of multidrug resistant bacteria, antimicrobial stewardship programs, and implementation of policies targeting antibiotic prescriptions for therapeutic purposes and medical prophylaxis [79]. Broom et al. stated that the interventions that are implemented to optimize surgical prophylaxis are more likely to be effective in enacting sustained change if they consider the interpersonal and social contexts, including issues of familiarity and cohesiveness, hierarchical patterns, and sense of place within a team

CONCLUSION
It can be concluded that the rate of surgical prophylaxis inappropriateness was high and the main cause for this result was inappropriate timing and duration. Numerous interventions including educational interventions such as onetime seminars and online e-learning modules are needed to improve the adherence to the guidelines. Numerous approaches should be used to encourage adherence to clinical guidelines on surgical antibiotic use, especially on the duration of treatment.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.

ACKNOWLEDGMENT
This Publication was supported by the Deanship of Scientific Research at Prince Sattam bin Abdulaziz University.

COMPETING INTERESTS
Authors have declared that no competing interests exist.