Protocol based Surgical Antimicrobial Prophylaxis in Endo-Urologic Surgeries: An Attempt to Convince the Surgeons to Follow the Guidelines

Surgical antibiotic prophylaxis (SAP) prevents infectious complications during surgery by administering an effective antimicrobial agent before surgery. There is, however, lack of adherence to the standard SAP administration protocol. We reviewed 576 surgeries and find that cefuroxime/cefazolin was used as SAP in less than 31% of surgeries followed by ceftriaxone and cefoperazone. In 61% of cases, SAP was continued for more than 24 hours and in 2/3rd more than one SAP was prescribed, we noted the best SAP compliance was for the timing of pre-operative dosage. We then selected a unit of urology and applied the recommended SAP protocol, and monitored the patient’s outcome. All the surgeries were endoscopic urological procedures and our protocol was effective in 97.7% of patients. Out of 89, 78(87.6%) surgeries went uneventful, whereas 11 (12.4%) had post-operative complications. Two out of 89 (2.2%) cases had UTI post-operatively which was considered as surgical site infection. following the EAU guidelines for antibiotic prophylaxis reduced antibiotic use without increasing postoperative infection rates and SAP should be followed as per the standard guidelines in other units also. This small study is a way forward for our HICC team to motivate other surgeons to follow the guidelines and become antimicrobial stewardship champions. Our study demonstrates the feasibility of developing and successfully implementing such protocols.


INTRODUCTION
Surgical site infection (SSI) is defined as an infection occurring at the incision site or deep to it within 30 days of surgery. 1 SSI are one of the most common nosocomial infections and account for 20% of all infections occurring in hospital inpatients. 2,3There is a 2-to 11-fold increase in mortality risk, with 75 percent of SSI-related deaths directly attributable to the SSI. 4 Out of all hospital-acquired infections mortality rate for SSI is 8%; however, mortality associated with SSI varies according to the surgical procedure. 5Surgical antibiotic prophylaxis (SAP) prevents infectious complications during surgery by administering an effective antimicrobial agent before surgery. 1 However, lack of adherence to follow protocol for SAP is among one of the factors for irrational use. 6,7acteria that become resistant to multiple antibiotics are often the result of incorrect or prolonged antibiotic use. 830% to 50% of antibiotics prescribed in hospitals are for postsurgical prophylaxis, and almost 30% to 90% of these regimens are unnecessary. 9The Hospital Infection Control Committee's (HICC) most difficult task is to persuade surgeons to adhere to the antimicrobial prophylaxis guidelines.The majority of surgeons used antibiotics of their own choosing as prophylaxis and are unwilling to adhere to a standard procedure.Choosing a broad-spectrum antimicrobial for prophylaxis is generally taken as an alternative to infection prevention practices and to avoid taking the risk of infection transmission.Other than the choice of antibiotic, another reason for the establishment of antibiotic resistance is failure to follow surgical prophylactic protocols.These can be in the form of incorrect timing and duration of the prophylactic therapy. 6,10urgical antimicrobial prophylaxis lacks sufficient information and recommendations in India; hence there is an unmet need to collect baseline data.The purpose of this study was to examine the trend in the prescription of antimicrobial prophylaxis in various surgical specialties and apply the recommended SAP in a selected unit of surgery, and observe the outcomes of patients in that unit.

MATERIALS AND METHODS
A prospective observational study was conducted in Jawaharlal Nehru medical college, Aligarh from December 2019 to March 2020, with prior approval from the institutional ethics committee.A review of the surgical prophylaxis given in various surgical specialties was done as a routine HICC activity.To convince the other surgical teams, we chose one unit i.e. the urology unit to follow the prescribed guidelines of SAP and assess the outcomes of the patients.Detailed clinical history, indication for surgery, details of the surgery performed and prophylaxis given, and the presence of co-morbidities were recorded.Patients were followed up to a period of 30 days after the surgery to assess the SSI.The research was carried out as part of our center's antibiotic stewardship program.
The European Association of Urology (EAU) guidelines for perioperative antibiotic prophylaxis strongly recommend obtaining a urine culture prior to all urological surgeries.It is recommended that patients who will be undergoing contaminated surgeries (a positive urine culture) have their bacteriuria under control prior to surgery, and they should also consider a prolonged regimen (with no specific duration in mind).The WHO guidelines 1 were used to design the protocol for antibiotic prophylaxis.Whereas the European Association of urology guidelines were also utilized. 11ll surgical operations were divided into clean, clean-contaminated, and contaminated.According to the EAU criteria, 11  The following protocol as shown in Table 1 was suggested for urological surgeries.Single-dose 1.5-g intravenous cefuroxime was administered for clean and clean-contaminated surgeries that was discontinued within 24 hours after the surgery.Antibiotics were given for 48 hours for the patients with risk factors such as morbid obesity, diabetes, malnutrition, and chronic renal disease.Patients with positive urine culture were given antibiotics according to the culture report and their indwelling tubes and catheters were replaced/removed to try to sterilize the urine.They were then operated on under antibiotic cover.
This protocol was followed for all elective endourological surgeries, as well as the postoperative course and complications were recorded by following the patients up to a period of 30 days and the results were evaluated.Adherence to the prophylaxis protocol without additional antibiotic use or change and an uneventful postoperative course were both considered indicators of effectiveness.

RESULTS
As a routine protocol of HICC, 576 surgeries were reviewed over a period of three months (Figure 1).A total of 1036 antibiotic doses were given for SAP pre-operatively (Figure 1).Cefuroxime/cefazolin was used as SAP in less than 180/576 (31.3%) of the surgeries performed, of which it was used as a sole agent in only 80/576 (13.9%) cases and was used in combination with other antimicrobials in the 100/576 (17.4%).There was non-uniformity in the choice of antibiotic used for prophylaxis.Apart from cefazolin/cefuroxime, the antibiotics used for SAP were ceftriaxone 140/576 (24.3%), cefoperazone 130/576 (22.6%), metronidazole 92/576 (16%), piperacillin-tazobactam 90/576 (15.6%), cefoperazone-sulbactam 84/576 (14.6%), amoxicillin-clavulanic acid 75/576 (13%), amikacin 67 (11.6%), cefotaxime 62/576 (10.8%), ceftazidime 40/576 (6.9%) and even meropenem and vancomycin each 38/576 (6.6%).The best compliance amongst the practices regarding SAP was for the timing of pre-operative dosage, which was given within 60 min prior to surgery, except for the cases of paediatric surgery where there was a breach in dosage timings in majority i.e 45 out of 65 cases (69.2%)Table 2.However, while considering the discontinuation of SAP, compliance was very poor and the SAP was discontinued within 24 hours in only 100 (17.4%) cases Figure 2. On observing the compliance to stop the SAP within 24 hours, it was noted that only 100/576 surgeries (17.4%) discontinued SAP at 24 hours, with the obstetrics and gynaecology surgeries showing best compliance.In majority of surgeries (63.5%, 366/576) (40.1%, 231/576) antibiotic was continued upto 48-72 hours.In more than half of the surgeries audited i.e., 340/576 (59%) more than one antibiotic was used in prophylaxis, while in a few even 3 antibiotics were given as SAP 60/576 (10.4%).(Table 3) To ensure the compliance and evaluate the challenges in following the guidelines we analysed a total of 89 (70 male & 19 female)

DISCUSSION
It is critical to select and administered antimicrobials correctly in pre and post-surgical conditions as well as to assess and monitor the preoperative environment, which may influence the development of SSI.An antimicrobial prophylaxis's primary goal is to reduce surgical site infection (SSI) and other avoidable periprocedural infections, with the secondary goal of avoiding the use of antibiotics. 12Despite the availability of national and international guidelines, there is hesitation among surgeons to follow these guidelines.It is a challenge for the Hospital Infection Control Unit of the Hospital to convince the surgeons to follow the prescribed guidelines.The HICC first evaluated the data of the compliance of SAP in various surgical units.In 180 (31.3%) cases either cefazolin or cefuroxime were prescribed alone (13.9%) or in combination (17.4%) which are the recommended prophylactic drug in all procedures (except in patients with a serious beta-lactam allergy).Similar results were seen in Hasibi F et al, study where cefuroxime was used in (31.63%) of cases. 13Cefazolin was most commonly prescribed antibiotic (90.3%) in Hassan et al. 14 study and administered in 47.9% cases in study of Fatima et al. 15 Ampicillin were used as most frequent prescribed antibiotic (43.8%) in Bunduki et al study. 16The goal is to administer the drug with a moderate spectrum of activity, which may target only the suspected surgical pathogens and thus curtail the development of antimicrobial resistance. 16However, the choice of antibiotic as noted was based on the surgeon's decision.It varied from Amoxycillin-clavulanic acid to meropenem-vancomycin combination.It was observed that more the complicated the surgery was, higher the class of antibiotic chosen for the surgery, similarly, the duration of SAP was also found to be dependent upon the complexity of the surgery performed.Therefore, as seen in our study, SAP was continued even beyond 7 days in 83.3% of neurosurgery (due to complexity of surgery and the risk involved), 50% plastic surgery cases (due to the higher risk of contamination and risk of rejection of grafts due to infection) and 32.8% of orthopaedic surgery cases (higher blood loss, implants, and dirty wounds).Similar study shows that SAP was continued for more than 24 hours in 80% of surgeries. 15Study in Pakistan also shows in 43.3% of cases SAP was continued for more than 24 hours. 17Prophylaxis was continued for more than 48 hours in 100% of cases in study in congo. 18he majority 340 (59%) of the patients had prescribed two antibiotics and in 60 cases  19 where 56% of the patients were prescribed more than two antibiotics perioperatively, however similar study shows that only single antibiotic is used as prophylaxis in 95.92% of cases. 13AU8 recommends use of a single antibiotic as a prophylaxis perioperatively.However, the surgeons use more antimicrobials to give broad spectrum coverage to all sorts of pathogens that might infect the patient.In our study, we found that most of the patients 531 (92.1%) had received the first dose of perioperative antibiotic within 60 minutes prior to surgery.A study done by Shah et al. 19 reported that 63% of patients receive prophylaxis 30 minutes prior to surgery.A similar study in India found that preoperative doses were administered at varying times, with some beginning as early as six hours before surgery. 20Study in Italy found only moderate compliance with this recommendation. 18Whereas 86% adherence to timing of administration prior to incision was noted in study of Berrondo et al. 21.SAP was administered 90 min in Bertschi D et al., 22 De Jong et al. 23 study, and was administered 60 minutes before surgery in Kasatpibal et al. 24 and Zhang X et al. 25 study, In our study non-compliance in pre-op dose timing was seen in only one unit, that was due to some administrative issues and was later on resolved.Overall, as seen in this study, compliance to SAP was very poor.Poor adherence to antibiotic prophylaxis recommendations has been shown in other studies with similar results. 26,27We tried to evaluate the reasons for non-compliance and it was noted that knowledge gaps, overcautious attitude of the surgeons, fear of losing faith by the patients, and non-availability of the desired drug in the hospital inventory were few of the reasons for the same.One of the most critical reasons noted was the lack of local evidence from the hospital.Majority of surgeons wanted the HICC to prove that if they switch to a narrower spectrum, it is not going to harm their patients.Thus, to convince our surgeons, we chose a unit that had previous experience of using the recommended antimicrobials.
Out of a total of 89 patients included in the study from a chosen unit 78.7% were males and 21.3% were females.Out of 89, 78(87.6%)surgeries went uneventful, whereas 11 (12.4%) had postoperative complications.Postoperative complications included erythema, blister, and de-squamation of skin in 11 cases.These local reactions occurred in the initial part of the study as were a setback to HICC, since the participating unit was then hesitant to continue the study.However, the HICC reviewed these cases and events that occurred during the surgery and it was then found that there was a change of OT staff, which led to concentrated dilutions of chlorhexidine being used in part preparation. 27Two out of 89 (2.2%) cases had UTI post-operatively which was considered as surgical site infection.
It is critical to select and administered antimicrobials correctly in pre and post-surgical conditions as well as to assess and monitor the preoperative environment, which may influence the development of SSI.An antimicrobial prophylaxis's primary goal is to reduce surgical site infection (SSI) and other avoidable periprocedural infections, with the secondary goal of avoiding the use of antibiotics. 12Despite the availability of national and international guidelines, there is hesitation among surgeons to follow these guidelines.It is a challenge for the Hospital Infection Control Unit of the Hospital to convince the surgeons to follow the prescribed guidelines.
The HICC first evaluated the data of the compliance of SAP in various surgical units.
In 180 (31.3%) cases either cefazolin or cefuroxime were prescribed alone (13.9%) or in combination (17.4%) which are the recommended prophylactic drug in all procedures (except in patients with a serious beta-lactam allergy).Similar results were seen in Hasibi F et al, study where cefuroxime was used in (31.63%) of cases. 13Cefazolin was most commonly prescribed antibiotic (90.3%) in Hassan et al. 14 study and administered in 47.9% cases in study of Fatima et al. 15 Ampicillin were used as most frequent prescribed antibiotic (43.8%) in Bunduki et al. study. 16The goal is to administer the drug with a moderate spectrum of activity, which may target only the suspected surgical pathogens and thus curtail the development of antimicrobial resistance. 16However, the choice of antibiotic as noted was based on the surgeon's decision.It varied from Amoxycillin-clavulanic acid to meropenem-vancomycin combination.It was observed that more the complicated the surgery was, higher the class of antibiotic chosen for the surgery, similarly, the duration of SAP was also found to be dependent upon the complexity of the surgery performed.Therefore, as seen in our study, SAP was continued even beyond 7 days in 83.3% of neurosurgery (due to complexity of surgery and the risk involved), 50% plastic surgery cases (due to the higher risk of contamination and risk of rejection of grafts due to infection) and 32.8% of orthopaedic surgery cases (higher blood loss, implants, and dirty wounds).Similar study shows that SAP was continued for more than 24 hours in 80% of surgeries15.Study in Pakistan also shows in 43.3% of cases SAP was continued for more than 24 hours17.SAP was continued for more than 48 hours in 100% of cases in study in congo. 18he majority 340 (59%) of the patients had prescribed two antibiotics and in 60 cases (10.4%) three antimicrobials were given for SAP.Similar results were seen in study of Shah et al. 19 , where 56% of the patients were prescribed more than two antibiotics perioperatively, however similar study shows that only single antibiotic is used as prophylaxis in 95.92% of cases. 13AU11 recommends use of a single antibiotic as a prophylaxis perioperatively.However, the surgeons use more antimicrobials to give broad spectrum coverage to all sorts of pathogens that might infect the patient.In our study, we found that most of the patients 531 (92.1%) had received the first dose of perioperative antibiotic within 60 minutes prior to surgery.A study done by Shah et al. 19 reported that 63% of patients receive prophylaxis 30 minutes prior to surgery.A similar study in India found that preoperative doses were administered at varying times, with some beginning as early as six hours before surgery. 20Study in Italy found only moderate compliance with this recommendation. 21Whereas 86% adherence to timing of administration prior to incision was noted in study of Berrondo et al. 22 SAP was administered 90 min in Bertschi D et al23, De Jong et al. 24 study, and was administered 60 minutes before surgery in Kasatpibal et al. 25 and Zhang X et al. 26 study, In our study non-compliance in pre-op dose timing was seen in only one unit, that was due to some administrative issues and was later on resolved.
Overall, as seen in this study, compliance to SAP was very poor.Poor adherence to antibiotic prophylaxis recommendations has been shown in other studies with similar results. 22,27We tried to evaluate the reasons for non-compliance and it was noted that knowledge gaps, overcautious attitude of the surgeons, fear of losing faith by the patients, and non-availability of the desired drug in the hospital inventory were few of the reasons for the same.One of the most critical reasons noted was the lack of local evidence from the hospital.Majority of surgeons wanted the HICC to prove that if they switch to a narrower spectrum, it is not going to harm their patients.Thus, to convince our surgeons, we chose a unit that had previous experience of using the recommended antimicrobials.
Out of a total of 89 patients included in the study from a chosen unit 78.7% were males and 21.3% were females.Out of 89, 78(87.6%)surgeries went uneventful, whereas 11 (12.4%) had postoperative complications.Postoperative complications included erythema, blister, and de-squamation of skin in 11 cases.These local reactions occurred in the initial part of the study as were a setback to HICC, since the participating unit was then hesitant to continue the study.However, the HICC reviewed these cases and events that occurred during the surgery and it was then found that there was a change of OT staff, which led to concentrated dilutions of chlorhexidine being used in part preparation. 28Two out of 89 (2.2%) cases had UTI post-operatively which was considered as surgical site infection.

CONCLUSION
Surgical Antimicrobial Prophylaxis is an important part of the SSI prevention bundle and also of Antimicrobial Stewardship program.However, convincing the surgeons for implementing the recommended antimicrobials is a challenge.Small and consistent efforts do show impact and we need to create our own local data to persuade those in practice to follow the recommendations.
We thus conclude that following the EAU guidelines for antibiotic prophylaxis reduced antibiotic use without increasing postoperative infection rates and SAP should be followed as per the standard guidelines in other units also.This small study is a way forward for our HICC team to motivate other surgeons to follow the guidelines and become antimicrobial stewardship champions.This study provides an analysis of the surgical antibiotic prophylaxis (SAP) done in one Indian institution and demonstrates that it is feasible to improve SAP by little means.Thus, it could serve as an example for other similar centres.These protocols are likely to reduce antibiotic resistance as well as treatment costs.

Limitations of study
The major limitation of our study is that it only includes elective endoscopic cases of a single unit i.e urology, emergency cases were not included in this study.

Figure 1 .
Figure 1.Prescribed prophylaxis of choice for various surgical procedures

Table 2 .
Timing of antibiotic administration before surgery for prophylaxis ENT= Ear Nose and Throat, CTVS= Cardiothoracic and Vascular Surgery

Table 3 .
Number of antibiotics used as SAP in various specialities for surgery

Table 5 .
Outcome of our modified antibiotic prophylaxis protocol according to the type of surgery

Table 4 .
Demographic data and type of surgical approach Variable