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ANTIBIOTSKA PROFILAKSA U ABDOMINALNOJ HIRURGIJI - USAGLAŠENOST PREPORUKA I PRAKSE ANTIBIOTIC PROPHYLAXIS IN ABDOMINAL SURGERY – COMPLIANCE WITH INTERNATIONAL GUIDELINES

Introduction. Antibiotic prophylaxis (AP) in surgery is an important measure that contributes to prevention of surgical International and national guidelines provide clear recommendations for the proper implementation of antibiotic prophylaxis. However, many studies indicate poor compliance in many health care centers. Aim: Our study aimed to determine the level of compliance in the application of antibiotic prophylaxis in abdominal surgery with the guidelines. Materials and methods: the presence of drug allergies. The collected data were analyzed by descriptive and analytical statistics (χ2 test). Results: During the study period, 270 patients were operated on at the Clinic for Digestive Surgery, of whom 227 (84.1%) received antibiotic prophylaxis. Cefazolin, an antibiotic recommended for most abdominal surgeries, was administered to only 17 (6.3%) patients. The majority of patients (64.4%) received antibiotic prophylaxis within 30 minutes of the beginning of surgery. The duration of antibiotic prophylaxis of up to 24 hours after the operation was applied in 13.1% of patients. Conclusion: Compliance with the guidelines was low, while full compliance with the recommendations for antibiotic prophylaxis was achieved only with regards to the route of antibiotic administration.


INTRODUCTION
Antibiotic prophylaxis (AP) in surgery is an efficient method for preventing and reducing the risk of surgical site infection. According to the Centers for Disease Control and Prevention (CDC), surgical site infections are considered an important global problem [1]. They are connected with a longer duration of treatment, the need for additional surgical procedures, and a higher mortality rate [2]. International guidelines and the Serbian National Good Clinical Practice Guideline provide clear recommendations for the proper implementation of antibiotic prophylaxis in surgery [3,4]. However, data from literature indicate insufficient compliance with these guidelines, in many healthcare institutions [5,6]. Irrational and inadequate use of antibiotics represents one of the main drivers of bacterial resistance development and may be accompanied by the occurrence of many adverse effects of antibiotics and increased overall treatment costs [1,2].
The choice of the antibiotic mostly depends on the region of the body where the surgical procedure is performed. However, based on the majority of recommendations from international guidelines and clinical practice guides, first generation cephalosporins (cefazolin) are the medicaments of first choice in the prevention of surgical site infections in abdominal surgery. Intravenous administration of antibiotics is recommended. For most antibiotics in surgical antibiotic prophylaxis, the application of antibiotics within 60 minutes of the beginning of the surgical procedure is considered appropriate [3]. Administering one more dose of the antibiotic should always be considered in procedures lasting longer than two drug elimination half-lives, as well as in cases where there was more than 1,500 ml of blood loss. In patients with proven penicillin allergy, administration of beta-lactam antibiotics should be avoided. In such cases, the alternative antibiotic proposed in the guidelines should be administered. It is believed that a single dose of antibiotic is sufficient for effective antibiotic prophylaxis in most surgical procedures and that it should be completed within 24 hours [3,4].
The aim of our study was to investigate the level of compliance of antibiotic prophylaxis application in abdominal surgery with international guidelines and the recommendations from the National Guide.

MATERIALS AND METHODS
This retrospective study of the method of antibiotic prophylaxis application in abdominal surgery included 270 patients, who were surgically treated at the Clinic for Digestive Surgery of the University Clinical Center of Serbia (UCCS), in the period January -March 2019. Patients undergoing emergency surgery, those with a previously antibiotska profilaksa u abdominalnoj hirurgijiusaglašenost preporuka i prakse antibiotic prophylaxis in abdominal surgerycompliance with international guidelines proven infection who had already been on antibiotic therapy, as well as patients undergoing invasive diagnostic procedures were excluded from the study (56 patients). Data on applied antibiotic prophylaxis, the type of antibiotic, the mode of administration, the time of administration of the first dose, the need for redosing, the length of antibiotic application, and the presence of drug allergies, were obtained from medical records (anesthesia records and hospital medication charts).
The data were analyzed using the methods of descriptive and analytical statistics. Depending on the type of marker being observed, the data have been presented as the median (interquartile range) or number (percentage). The compliance of the obtained results with the recommendations was tested in relation to the Serbian National Good Clinical Practice Guideline for Rational Antibiotic Use and the ASHP Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery of the American Society of Health-System Pharmacists (AHSP) ( Table 1).
In creating the database and in data processing, the software -IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY), was used.

Source of recommendations: references 3 and 4 n -Number of patients in whom prophylaxis was administered according to guidelines; N -Number of patients who were given prophylaxis; IQR -Interquartile range
antibiotska profilaksa u abdominalnoj hirurgijiusaglašenost preporuka i prakse antibiotic prophylaxis in abdominal surgerycompliance with international guidelines AP was applied in 84.1% patients, which confirms the estimations that prophylactic administration accounts for 30% -50% of the overall intrahospital antibiotic consumption [7]. Data found in literature indicate that the coverage of surgical patients with AP is very high in most developed countries, amounting to over 95% [8].
In our study, antibiotics, as prophylaxis, were least used in the group of patients who underwent hernia repair surgery (69.2%). Elective inguinal hernia surgery is a typical example of 'clean' surgery, which does not require AP. Although results of randomized studies do not offer a clear conclusion regarding the efficiency of antibiotic prophylaxis in the decrease of wound infection frequency, guides recommend that the antibiotic should be applied as prophylaxis when prosthetic material (mesh) implantation is planned, as well as in cases of complex hernia repair, especially in medical centers where there is less experience in this type of surgery [9].
Low-risk laparoscopy does not indicate prophylactic antibiotic use, according to the recommendations of the national and international guides. The fact that it is sometimes difficult to preoperatively define the risk in laparoscopy has probably resulted in a relatively [7]. Podaci iz literature ukazuju da je obuhvat hirurških bolesnika antibiotskom profilaksom u većini razvijenih zemalja visok i iznosi preko 95% [8].
In our study, a huge variability in the selection of antibiotics or combinations of antibiotics used as prophylaxis has been shown. Although recommendations suggest the application of cefazolin for most operations in abdominal surgery, this drug was only the fifth most frequent drug used and was administered to only 17 (6.3%) patients. The most frequently applied antibiotic regimens were the following: ceftriaxone and metronidazole (24.8%), ceftriaxone (21.9%), metronidazole (13.7%), and ciprofloxacin (10.7%). Fourteen different antibiotic regimens were applied as antibiotic prophylaxis.
A study including 14 hospitals in Germany has shown that as many as 29 antibiotic regimens were used as antibiotic prophylaxis, and that variations in clinical practice and deviation from recommendations was especially prominent in abdominal surgery [10]. This study showed significant use of broad-spectrum antibiotics and of socalled reserve antibiotics, which was also the case in our study. It is surprising that in our environment ciprofloxacin was used to a great extent, despite the recommendation that quinolones, due to adverse effects, should be used only for treating life-threatening infections.
The reasons for poor compliance of the choice of AP with recommendations offered in the guides have not completely been elucidated. It is possible that a relatively high frequency of self-reported allergies to antibiotics has contributed to this state of affairs. A previous study carried out in this health center has shown that almost 40% of patients report a drug allergy prior to surgery, wherein the alleged allergy to penicillin is the one most commonly reported [11]. Yet, clindamycin was not used as AP in a single case, even though it is the first recommended alternative for cefazoline in patients allergic to beta-lactam antibiotics, and therefore, the overall compliance with the guidelines with respect to antibiotic choice was a only 22.6%.
All of the patients in our study received the antibiotic intravenously, which is in keeping with the guidelines. Other authors have reported similar results, especially in the domain of abdominal surgery [12].
The timing of antibiotic administration for surgical prophylaxis is significant, since the goal is to achieve the highest concentration of the drug in the blood at the time of the greatest exposure to potential causative agents of wound infection. In our study, this aspect of AP application had the lowest compliance with the guidelines, since the timeline for antibiotic application was observed in only 8 (3.0%) patients. This is far lower than the results reported by other authors, where in 45% to 94% of the cases, AP was applied at the appropriate time, as recommended by the guidelines [13]. primenjenih za profilaksu. Iako preporuke sugerišu primenu cefazolina za većinu operacija u abdominalnoj hirurgiji, ovaj lek je bio tek na petom mestu po učestalosti primene, a dobilo ga je 17 (6,3%) bolesnika. Najčešće primenjivani antibiotski režimi bili su: ceftriakson i metronidazol (24,8%), ceftriakson (21,9%), metronidazol (13,7%) i ciprofloksacin (10,7%). Kao AP, primenjeno je ukupno 14 različitih antibiotskih režima.
Vreme davanja antibiotika za hiruršku profilaksu je od značaja, jer je cilj da se postigne najviša koncentracija leka u plazmi u vreme najveće izloženosti potencijalnim uzročnicima infekcije rane. Ovaj aspekt primene antibiotske profilakse imao je najnižu usaglašenost sa smernicama u našem istraživanju, jer je kod samo 8 (3,0%) bolesnika ispoštovana satnica za davanje doze antibiotika. To je neuporedivo niže u odnosu na rezultate drugih autora, gde je 45% do 94% slučajeva antibiotske profilakse bilo primenjeno u pravilno vreme, u skladu sa preporukama [13]. Mogući uzroci ovako niske usaglašenosti sa smernicama u našem istraživanju leže u organizacionim razlozima, jer operacioni blok na Klinici za digestivnu hirurgiju nema prostor u kome bi bolesnici mogli da dobiju lek venskim putem. Takođe, česte izmene programa otežavaju da bolesnik dobije lek pravovremeno na odeljenju, već se sa ordiniranim antibiotikom upućuje u operacionu salu gde procedure antibiotska profilaksa u abdominalnoj hirurgijiusaglašenost preporuka i prakse antibiotic prophylaxis in abdominal surgerycompliance with international guidelines The possible causes of such a low compliance with the guidelines, in our study, may be attributed to organizational issues, since the surgical suite at the Clinic for Digestive Surgery does not have a space/room where the patients could receive the antibiotic intravenously. Also, frequent changes in the operating schedule make it more difficult for the patient to receive the antibiotic in a timely fashion while still on the ward, rather the patients are prescribed the antibiotic and then transferred to the operating theatre, where anesthesia procedures are often given priority. This is why the greatest number of patients in our study (174; 64.4%) received AP within 30 minutes of the beginning of the operation.
Prolonged antibiotic prophylaxis is one of the frequent mistakes made in many healthcare facilities. Although guides clearly emphasize that only one dose should be administered or that antibiotic application should be finished within 24 hours, studies report that this recommendation is observed in 5.8% -91.4% cases [14]. The fact that the appropriate duration of prophylaxis was achieved in 13.1% of the cases may be explained by the surgeons' concern that infections may develop after major, clean-contaminated surgeries, in situations when drains remain in place for a number of days. It remains unclear, why the length of prophylaxis was observed only in one patient who underwent laparoscopic cholecystectomy, for which, in most cases, antibiotic prophylaxis is unnecessary.
It is possible that the conditions for good clinical practice in the application of antibiotic prophylaxis are developed during medical studies, when knowledge and understanding in this area is obtained. A study carried out in a hospital in Qatar showed that 51% of surgical residents, who were performing surgery independently, were aware of the principles of antibiotic prophylaxis application [15]. Aside from theoretical knowledge, clinical practice is shaped by other factors as well, which were not the subject of this study. The results from earlier studies indicate the importance of feedback related to the application of antibiotics, obtained through the health information system, as well as the importance of periodical internal professional supervision, for improving the compliance of clinical practice with AP application guides [16,17].

CONCLUSION
The compliance of clinical practice with recommendations from guides on AP in abdominal surgery was poor at the tertiary health institution for abdominal surgery observed in our study. The fact that this is the era of extensive surgery development, but also the development of multi-drug resistance in bacteria causing intrahospital infections, necessitates the need for certain oko uvođenja u anesteziju često imaju prioritet. Zato je najveći broj bolesnika (174; 64,4%) antibiotsku profilaksu primio unutar 30 minuta od početka operacije.

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antibiotska profilaksa u abdominalnoj hirurgijiusaglašenost preporuka i prakse antibiotic prophylaxis in abdominal surgerycompliance with international guidelines measures and procedures, with the aim of achieving a more rational use of antibiotics. It is necessary to implement measures at the institutional level, so as to raise the awareness of clinicians on the importance of this problem; support antibiotic management teams in hospitals; introduce checklists, in order to establish supervision of different aspects of AP application; and enhance the study of medicine, in the sense of emphasizing the significance of this issue. Promoting the National Guide and developing local recommendations are also some of the measures that may contribute to a more effective and efficient application and administration of antibiotic prophylaxis in surgery.