Identification of predictive factors for surgical site infections in gastrointestinal surgeries: A retrospective cross-sectional study in a resource-limited setting

Background Surgical site infection (SSI), albeit infrequent, drastically impacts the quality of care. This article endeavors to investigate the predictive factors of SSIs following surgical interventions that involve the gastrointestinal (GI) tract within a single institution in a resource-limited setting. Methods Over seven years from June 2015 to June 2022, patients who underwent GI surgery and developed SSI were retrospectively matched with an unaffected case-control cohort of patients. Standardized techniques for wound culture, laboratory evaluation of bacterial isolates, and antibiotic susceptibility tests were employed. Logistic regression analysis was utilized to investigate the predictive factors associated with 30-day postoperative SSI occurrence. Results A total of 525 patients who underwent GI surgical procedures were included, among whom, 86 (16.4%) developed SSI and the majority of SSIs were superficial (74.4%). Escherichia coli was the most commonly isolated bacterium (54.4%), and a high percentage of multidrug-resistant organisms were observed (63.8%). In multivariate Cox regression analysis, illiteracy (Odds ratio [OR]:40.31; 95% confidence interval [CI]: 9.54-170.26), smoking (OR: 21.15; 95% CI: 4.63-96.67), diabetes (OR: 5.07; 95% CI: 2.27-11.35), leukocytosis (OR: 2.62; 95% CI: 1.24-5.53), hypoalbuminemia (OR: 3.70; 95% CI: 1.35-10.16), contaminated and dirty wounds (OR: 6.51; 95% CI:1.62-26.09), longer operation duration (OR: 1.02; 95% CI: 1.01-1.03), emergency operations (OR: 12.58; 95% CI: 2.91-54.30), and extending antibiotic prophylaxis duration (OR: 3.01; 95% CI: 1.28-7.10) were the independent risk factors for SSI (all p < 0.05). Conclusions This study highlights significant predictors of SSI, including illiteracy, smoking, diabetes, leukocytosis, hypoalbuminemia, contaminated and dirty wounds, longer operative time, emergency operations, and extending antibiotic prophylaxis duration. Identifying these risk factors can help surgeons adopt appropriate measures to reduce postoperative SSI and improve the quality of surgical care, especially in a resource-limited setting with no obvious and strict policy for reducing SSI.


Introduction
A surgical site infection (SSI) is a frequently encountered nosocomial infection that typically develops within 30 days of surgery.In cases where an implant is used, the timeframe for SSI occurrence can extend up to one year. 1The estimated incidence of SSI is 0.5% to 3% worldwide, with a higher incidence reported in low-income countries, where SSI is estimated to be the most common healthcare-associated infection. 2,3In addition to the socioeconomic status, surgeries that involve the gastrointestinal (GI) appear to have a higher SSI incidence, with reports indicating a 12%-30% incidence rate of such cases.The associated expenditure of increased hospitalization (7-11 folds), mortality, and morbidity (2-11 folds) force a higher emphasis on detecting such patients earlier in the course of their illness and identifying patients with a higher risk of developing SSI to improve the quality of care and minimize the cost. 4,5rious factors have been studied concerning SSI, which can extend from socioeconomic status to preoperative settings and surgical approaches. 6Certain non-modifiable risk factors include age, gender, immunosuppression, diabetes mellitus, obesity, or active smoking.4][5] SSI can be attributed to microorganisms that are derived from the patient's skin flora or the surrounding environment. 1In either scenario, the adherence of microorganisms to the surgical instruments can contaminate the incision.Contaminated surgical procedures pose an increased risk, particularly when multidrug-resistant microorganisms are involved. 6evious monocentric and retrospective studies in Yemen reported SSI rates of 2.2% and 31.7%. 7,8However, there is limited information available about the extent of SSI and its predictive factors in low-income countries, such as Yemen. 7,8his study aimed to investigate the SSI rate and its predictive factors among Yemeni patients who underwent GI surgeries in a resource-limited setting.

Study design
A retrospective cross-sectional study was conducted to investigate the SSI rate in patients who underwent gastrointestinal surgery at Al-Thora Hospital, Ibb University, IBB, Yemen, between June 2015 and October 2022.We included 525 patients, from whom written informed consent was obtained.The study was approved by the Ethics Research Committees of Ibb University [ID: IBBUNI.AC.YEM.2023.75, on 03/03/2023].

Inclusion criteria
Adult patients (≥18 years old), who had undergone either elective or emergency GI surgery at general surgery wards were included.

Exclusion criteria
Exclusion criteria were pregnancy, anticoagulation, incomplete or concealing data, non-bowel-related surgeries (e.g., hernia), postoperative complications within more than 30 days of surgery, or admission to another hospital.

Data collection
The study enrolled all eligible patients in consecutive order and utilized organized questionnaires to gather applicable information.This included demographics, including age, gender, educational level, body mass index (BMI), and place of residence, as well as health habits such as cigarette smoking and Khat chewing.In addition, comorbid conditions such as diabetes mellitus (DM), hypertension, chronic kidney, lung, and liver disease, history of malignancy, and preoperative blood transfusions were also documented.The American Society of Anesthesiologists (ASA) categorization system was used to measure preoperative physical state.Other information collected included the operative date, duration, wound nature, type, duration, anesthesia type, using the safety checklists, the urgency of surgery, readmission, reoperation, hair removal time, and details of preoperative antimicrobial administration (injection of amoxicillin and clavulanic acid 1.2 g for clean wounds and injection of ceftriaxone 1 g and metronidazole 500 mg for clean-contaminated wounds).Laboratory-collected data were white blood cell (WBC) counts, neutrophile percentage, and albumin levels.

REVISED Amendments from Version 2
All reviewer comments were responded and most of them were acted on in revised manuscript.The revised manuscript only includes minor changes as the reviewer suggested including a revision in organisms responsible in Table 3, a paragraph regarding steps to reduce SSIs overall in gastrointestinal procedures, and a few suggestions by reviewers.
The study documented surgery-related complications (e.g., SSI, fistula) in addition to non-surgical complications such as pneumonia, urinary tract infection (UTI), sepsis, and myocardial infarction (MI).Culture results and antibiotic sensitivities were also recorded, with wound swabs and pus specimens collected using standard microbiological techniques and transported to the laboratory for sensitivity analysis.Additionally, we collected the National Nosocomial Infections Surveillance (NNIS) index for each patient.

Definitions
Based on the depth of infection, these SSIs were subsequently categorized into superficial (affecting the skin and subcutaneous tissue), deep (involving muscle and fascia), and organ space infections. 6Wounds were classified into four categories depending on their level of contamination: clean, clean-contaminated, contaminated, or dirty-infected.The ASA score, which reflects the patient's physical condition before the surgery, was determined through evaluation by the anesthesiologist using the ASA classification system. 9The NNIS index considers three risk variables, each of which is worth one point: contaminated or dirty-infected surgical wound, ASA scores greater than 2, and operation length greater than T (where T is defined as the 75th percentile of the normal time for a surgical procedure). 9The gastrointestinal cases were sorted into four categories (small bowel, large bowel, biliary, and pancreatic). 10Leukocytosis was defined as a WBC count greater than 100 Â 10 9 /L and hypoalbuminemia was defined as an albumin <3.5 g/dL.

Study outcomes
The primary outcome was the prevalence of postoperative SSIs determined by assessing culture-positive results which were assessed by infection prevention and control staff diagnosis, according to the criteria set forth by the United States Center for Disease Control (CDC).This definition included infections affecting the superficial, deep, and organ space tissues of the surgical incision.The incidence of SSI was determined by evaluating and following up on all patients for 30 days following their surgery, by systematic visits, starting from the date of the operation. 9It is important to note that medical complications such as pneumonia, MI, and UTI were separately documented and reported, and were not included in the definition of SSI or postoperative surgical complications.The secondary outcome was investigating the predictive factors for SSIs.

Variables and measures
The outcome variable was SSI expressed as a binary variable: yes and no.Independent variables included Age (<60 years and ≥60 years), Sex (male and female), ASA score (Low [1 or 2] and High [3 or 4]), NNIS index (No risk, Low risk, Moderate risk, High risk), Surgical sites (Large bowel and Other gastrointestinal sites), Hospital stays (<5 days and ≥5 days), BMI (<30 kg/m 2 and ≥30 kg/m 2 ), Residency (Urban and Rural), Educational level (Educated and Illiterate), the Antibiotic time before surgery (<1 h and ≥1 h), hair removal time (<24 hours and ≥24 hours), WBC (<10Â10 9 /L and ≥10Â10 9 /L), Albumin (≥3.5 mg/dL and <3.5 mg/dL), Operative type (Elective and Emergency), Blood loss (<200 mL and ≥200 mL), Anesthesia type (Spinal and General), Wound class (I and II and III and IV), Temperature (<38°C and ≥38°C), and Operation duration (min).Additionally, Khat chewing, Smoking, History of hypertension, History of diabetes, History of chronic renal failure, History of chronic liver disease, History of lung disease, Perioperative blood transfusion, History of malignancy, Safety checklist used, and Drain insertion were presented as "yes" and "no".

Statistical analysis
IBM SPSS version 22 software (IBM Corp., Armonk, New York) was used for statistical analyses.Quantitative variables were presented as means and standard deviations, while qualitative variables were reported as frequencies and percentages.The normality of the data was confirmed using the Kolmogorov-Smirnov test.Statistical tests were used to compare qualitative and quantitative variables, including the independent samples t-test or Mann-Whitney test for quantitative variables, and the Chi-square or Fisher's exact test for qualitative variables.All the continuous variables were converted into categorical variables for a better presentation of the nomogram.
Univariate analysis was conducted to identify the statistically significant variables associated with the development of SSIs.First, we did univariate logistic regression to determine the potential variables for SSI.When the P-value<0.05,the corresponding variable would be considered statistically significant.Second, Spearman's rank correlation coefficient was used to analyze the correlations between statistically significant variables.If correlation coefficients>0.700between different variables, the strongly correlated variables would be removed.To detect collinearity, the variance inflation factor (VIF) was calculated.If VIF>3.000 or tolerance<0.100,the corresponding variable would be removed.Next, we conducted a multivariate logistic regression analysis of all the statistically significant variables to examine their independence.The links between each risk factor and SSI were presented as an odds ratio (OR) and confidence interval (CI).A p-value of less than 0.05 was judged statistically significant.The ROC curve (receiver operating characteristic curve) was utilized to evaluate the risk adjustment prediction performance of the previous NNIS risk index and the Author's model for post-gastrointestinal SSI, which contains the significant factors in multivariate analysis. 9

Characteristics and presentation of patients
This study included a total of 525 patients, comprising 295 (56%) male patients and 230 (44%) female patients, with a mean age of 52.9AE16.9.Table 1 provides a summary of the patients' characteristics and presentation.The postoperative 30-day SSI occurred in 86 (16.4%) patients.A total of 193 (36.8%) of patients had ASA Class One.The operative case distribution was 206 (39.2%) in the small bowel, 182 (34.7%) in the large bowel, 124 (23.6%) in the biliary system, and 13 (2.5%) in the pancreatic system.The mean operation duration was 76.4AE28.2minutes.General complications were UTI and pneumonia in 5.5%, high-grade fever in 5.1%, and MI in 1% of patients.Laboratory and operative characteristics of patients are mentioned in Table 2.

Causative pathogens
Pathogens linked with SSI were identified from all SSI patient wounds.Escherichia coli (51.2%),Enterococcus spp.(17.4%),Bacteroides species (9.3%), and Clostridium perfringens (8.1%) were the most commonly isolated microorganisms, with more than half of pathogenicity (63.8%) being multidrug-resistant organisms and the majority (70.1%) being extended-spectrum β-lactam producers (Table 3).The majority of SSIs were superficial infections 64 (74.4%), while deep SSI infection was presented in 14 (16.3%), and organ-specific SSI infection was seen in 8 (9.3%) of cases.The relationship between variables and SSI occurrences The relationship between the independent factors and the dependent variable was explored using univariate and multivariate Cox regression analysis.On univariate analysis, Khat chowing, high ASA class (3 or 4), smoking, hypertension, diabetes, hypoalbuminemia, illiterate, contaminated and dirty wounds, higher temperatures ≥38°C, leukocytosis, neutrophile ≥85%, longer operation duration, blood loss more than 200 mL, biliary and pancreatic cases, longer hospital stay, hair removal ≥24 hours of surgery, presence of NNIS risk index, and emergency surgery were statistically significant associations with SSI occurrence (all p<0.05) (Table 4).5).The prediction model's total ROC curve was 0.946, which was much higher than the NNIS score (0.660) (Figure 1).

Discussion
The improved access to healthcare, increased population age, and increased complexity of surgical interventions and patients' conditions shed light on the importance of managing post-operative complications.Despite the precautions and the hygienic approach implemented to limit the incidence of SSI, it still represents one of the most common post-operative complications.Such infections result in an increased healthcare expenditure, and worsened mortality and morbidity. 10his predicament can be especially disadvantageous for low-income nations, where providing healthcare is already a daunting task due to constrained resources, indigent communities, and elevated levels of antimicrobial resistance. 11ong the 525 enrolled patients, the incidence of SSI within 30 days after surgery was 16.4%, which is in line with previous reports from developing countries, such as Saudi Arabia, with a rate of 16.3%. 14However, earlier studies showed much higher rates of SSI affecting up to one-third of the patients in Yemen. 8In contrast, more recent reports from Yemen have demonstrated a lower incidence of SSI, with a rate of 12.7% among patients who underwent gastrointestinal procedures. 8Our findings, which showed a slightly higher rate of SSI, could be partially attributed to the larger number of complicated cases or complex oncological procedures performed at our tertiary teaching hospital.
Several studies have been conducted to evaluate the link between putative risk variables and SSI in GI surgical operations.However, there is a large range of variation in the variables analyzed and the proportional effect of these factors on individual outcomes.To address this issue, we comprehensively studied the preoperative and operational risk variables  6,12 This study found that illiteracy, current smoking status, DM, leukocytosis, hypoalbuminemia, contaminated and dirty wounds, longer operation duration, emergency operations, and longer time between administering antibiotics and operation were predictors for the development of SSI.Most of the potential predictive factors included have been previously reported as risk factors in other studies with a variety of reports and different levels. 6,12e relationship between age and SSI risk is complex and not well understood.While some studies have reported an increased rate of infection in older patients, others have observed a favorable trend with increasing age.For instance, Kaye et al. demonstrated a 1.2% decrease in SSI risk for each additional year after 65 years of age. 13Nevertheless, these findings were demonstrated consistently, as a higher rate of SSI was observed in the older population. 14,15Typically, with increasing age, there is an accumulated risk of developing comorbidities and immune dysfunction, which may lead to an increased likelihood of SSI.However, our study's findings revealed no association between age and the development of SSI.This divergence may be attributed to variations in age categorization, as the majority of patients (67%) in this study were younger than 65 years.
The present study reveals a significant association between the level of literacy and the incidence of SSI.Specifically, illiterate patients were 40 times more susceptible to SSIs than educated patients.These results are in accordance with previous research conducted by Mezemir et al. and Baker et al. 16,17 Notably, a high prevalence of limited health literacy among adults in our country may adversely impact health outcomes.For example, patients with limited health literacy may experience difficulty in comprehending complex health information, may exhibit non-compliance with postoperative instructions, and may not adequately prepare for surgery.These factors may increase the risk of SSIs and other adverse outcomes, highlighting the potential health inequality in providing care and education for illiterate patients.Therefore, it is critical to improve health literacy among patients, particularly those with limited education, to potentially reduce the incidence of SSIs and enhance surgical outcomes.
This study did not find a significant association between unmodifiable risk factors, such as gender, BMI, residency, number of comorbidities (hypertension, history of malignancy, CRF, liver and lung diseases), perioperative blood transfusion, and SSIs in multivariate analysis.Although these social determinants are important factors that may contribute to patient outcomes, there is a lack of consensus on their association with SSI occurrence in the literature.For example, Marzoug et al. found that male sex and a greater number of comorbidities were associated with SSI occurrence. 18Additionally, Li et al. reported that ascites, bleeding diathesis, history of lung disease, radiotherapy, chemotherapy, chronic steroid use, and weight loss were associated with SSI occurrence. 19In contrast, Mezemir et al. did not find an association between gender, BMI, and SSI occurrence, which was similar to our study. 16These discrepancies may be attributed to sample size and demographics variation across studies, as well as variations in the documentation and management of patient comorbidities.The use of more objective measures, such as preoperative laboratory and radiologic values, may provide a better understanding of the association between comorbidities and SSI occurrence.Distinctly, in this study, DM and hypoalbuminemia had 5-and 3.7 times higher chances of developing SSIs, respectively.This association was observed in prior studies, 11,20 as hyperglycemia has been shown to impair WBC functions, leading to decreased immunity. 21On the other hand, reduced serum albumin levels are often associated with malnutrition or chronic wasting diseases. 11However, the glucose levels were not available for the included patients and the albumin level was converted into categorical variables for a better presentation of the nomogram.
Our study revealed that smoking was strongly associated with a 21-fold increased risk of developing SSIs compared to non-smokers.The vasoconstrictive and toxic effects of smoking are known to impede tissue oxygen delivery and hinder the healing process, thus contributing to the development of SSIs.These findings align with previous reports by Mawalla et al. and Billoro et al. 22,23 Regarding Khat (Catha edulis) chewing, its role in SSI occurrence remains uncertain.Our study observed a 1.99-fold increase in SSI occurrence among Khat chewers, although this association was not statistically significant.Currently, there is a lack of published studies specifically investigating the relationship between SSI and Khat chewing.However, Misha et al. found no association between Khat chewing and SSI occurrence in their regression analysis. 3Nevertheless, Khat chewing has been linked to various gastric issues (e.g., intestinal obstruction, and gastritis). 24Furthermore, long-term Khat consumption poses a risk of developing severe complications including hepatitis, hepatic fibrosis, and cirrhosis in advanced stages. 25Future prospective and more inclusive studies are recommended to investigate this issue, particularly in our country where the traditional use of these plants is widespread.
The settings of operation can significantly impact the development of SSI.Prior research has suggested that the degree of intraoperative wound contamination is indicative of SSI occurrence. 26,277][28] In this study, no statistically significant difference in SSI occurrence between colorectal procedures and other GI site procedures.However, most large-bowel SSIs were deep SSI types (8/31 in large bowel procedures vs., 3/25 in biliary and pancreatic procedures vs., 3/30 in small bowel procedures).According to data published by the National Healthcare Safety Network, rates of SSI following bile duct, liver, or pancreatic surgery are as high as 10 per 100 procedures.Rates of SSI following colon surgery are approximately 5 per 100 procedures, and rates of SSI following gallbladder surgery are 0.7 per 100 procedures. 29Bozzay et al. study, the incisional SSI rates were higher following small bowel and gastrostomy closure procedures than for colorectal procedures and 66.1% of the cumulative incisional SSI burden from all procedures was attributable to 3 procedure groups (gastrostomy: 27.5%, small bowel: 22.9%, colorectal: 15.7%). 30wever, our findings were inconsistent with the literature documenting pancreatic and biliary leaks as independent risk factors for SSI occurrence. 27This discrepancy could be attributed to the low number of cases involving biliary and pancreatic procedures, with most of them undergoing simple operations.Therefore, further prospective studies with a larger number of cases are necessary to clarify this issue.
Our study also found that emergency operations were 12.58 times more likely to result in SSI, consistent with other studies. 6,11In addition, leukocytosis was found to be a predictor for the development of SSI, which aligns with previous research. 31Additionally, prolonged operation duration was recognized as an independent factor for SSI development in other studies, as it increases the risk of infection due to extensive surgical procedures and incisions, prolonged anesthesia, blood loss, and weaning antimicrobial prophylaxis concentration. 6,32Furthermore, administering antibiotics one hour before operation has been reported as a predictor for SSI in previous studies. 23,33In this study, it was observed that longer operation durations and administration of antibiotics more than one hour before the operation increased the likelihood of SSI by 1.02 times and 3.01 times, respectively.These findings are consistent with previous studies that showed the importance of re-dosing when this duration reaches the half-life of the administered antibiotic and guidelines recommend it. 23,32 this study, the time for hair removal was not statistically significant in multivariate analysis.This was in line with a recently published systematic review by Tanner et al. who mentioned that hair removal with clippers or depilatory cream may reduce the risk of SSIs, but not fewer than shaving with a razor.Moderate-certainty evidence suggests clippers or creams may reduce SSIs and complications.Hair removal on the day of surgery may also reduce risk. 33 the other hand, Zhang et al. reported that patients undergoing hair removal (the day of surgery or the night before surgery) had lower SSI incidence compared with those without hair removal. 34n this study, we investigated the microorganisms responsible for SSIs and their susceptibility to commonly prescribed prophylactic antibiotics.We found that the most common organisms isolated from infected wounds were Gram-negative bacteria, with extended-spectrum β-lactamase-producing E. coli being the most prevalent.Mawalla et al. reported a different outcome compared to this finding, as their studies indicated a higher presence of Gram-positive bacteria, including Staphylococcus aureus. 22In contrast, studies have reported similar findings to ours, demonstrating a higher occurrence of Gram-negative bacteria in infected abdominal wounds. 26,35Furthermore, our findings revealed a high prevalence of multi-resistant pathogens in relation to commonly prescribed prophylactic antibiotics, which may serve as an explanation for the elevated rate of deep SSI observed in our study.Hence, there is a need to consider appropriate prophylactic antibiotics, especially for high-risk patients.Additionally, strict adherence to surgical site infection prevention techniques Such as disinfection and sterilization of medical and surgical tools to avoid the spread of infectious germs need to get more attention.Healthcare rules should specify whether cleaning, disinfection, or sterilization is required based on the item's intended usage.
The NNIS risk index is a widely recognized framework for assessing and predicting the likelihood of SSI. 9 Within our study, two elements of the NNIS exhibited statistical significance (operation duration and wound class).However, upon conducting multivariate analysis, the overall NNIS model did not yield statistical significance.Moreover, when comparing the predictive accuracy, our developed model outperformed the NNIS model.Acutely, the performance of the NNIS model in this study showed poor predictive performance for the SSI occurrence as determined by the ROC curve.These results align with previous findings reported by Zhang et al. 11 Surgical site infections can be prevented by a variety of techniques, including improved preoperative surgical site preparation, good infection control management during procedures, careful adherence to prophylactic antibiotics administration, and a variety of preventive measures aimed at neutralizing the threat of bacterial, viral, and fungal contamination posed by operative staff, the operating room environment, and the patient's endogenous skin flora.Glucose-level control, improved oxygen supply, and normothermia maintenance are three new areas that have the potential to lower the incidence of SSIs even further.Continuous study into the biology of SSIs, as well as rigorous adherence to the use of evidence-based proven techniques to minimize SSIs, can help to further reduce the health and cost repercussions of SSIs. 6,12udy limitations There are several limitations to consider in this study.First, the retrospective nature of the study may introduce an unintended bias to the study.In addition, it was conducted at a single tertiary teaching hospital, which may limit the generalizability of the findings to other healthcare settings.Furthermore, the study relied on clinical documentation to identify SSI, which could lead to underreporting or misclassification of cases.Moreover, the study focused on a specific geographic region, and the findings may not apply to other populations with different demographics or healthcare systems.Although the study took into account certain potential confounding variables (e.g., the use of prophylactic antibiotics), other potential confounding variables are difficult to assess with the retrospective nature of the study (e.g., surgical techniques and intra-operative maintenance of sterile technique, among others).Finally, the study did not explore long-term outcomes or evaluate the impact of interventions aimed at reducing surgical site infections.Based on our findings, further research needs to be validated in a large prospective cohort study with a long-term post-procedural follow up and the use of local coordinators may minimize these potential biases.

Conclusions
This study highlights significant predictors of SSI, including illiteracy, active smoking, DM, leukocytosis, hypoalbuminemia, contaminated and dirty wounds, longer operation duration, emergency operations, and extending antibiotic prophylaxis duration.Escherichia coli was the most common pathogen and had a high rate of multidrug-resistant strains.Identifying these risk factors can help surgeons adopt appropriate measures to reduce SSI and improve the quality of surgical care, especially in a resource-limited setting with no obvious and strict policy for reducing SSI.

Natale Calomino
University of Siena, Siena, Italy The aim of the work is to investigate the possibility of predicting surgical site infection.The abstract induces the curiosity to read the article in its entirety.in the introduction we focus on the fact that surgical site infection is nosocomial.This concept needs to be described better, in fact it is nosocomial because it happens in hospital, or it is nosocomial because the contaminating bacteria are of nosocomial origin, for example we can notice that in a smaller ward the patients have wounds infected by the same bacterial strains.We absolutely agree on the factors that induce infections.The study design and methods are well orchestrated with the right inclusion and exclusion criteria.We also agree on the approval of the ethics committee.We learn without having to add anything about the results.In the discussion we absolutely agree on what was said regarding the socio-economic factors and the clinical conditions with which patients present themselves in hospital.I liked what was said about hair removal, to this I would add the shower before each operation and antibiotic prophylaxis, in this regard I recommend an article already the subject of numerous citations [ref 1 ], to be cited in the bibliography.We agree on the conclusions.Great digression on limitations.English worth reviewing, good iconography, even if the images are a bit small.The bibliography is a good basis for the article.

If applicable, is the statistical analysis and its interpretation appropriate? Yes
Are all the source data underlying the results available to ensure full reproducibility?Yes

Are the conclusions drawn adequately supported by the results? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: generale surgery, oncological surgery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Version 2
Reviewer Report 26 April 2024 https://doi.org/10.5256/f1000research.161396.r258951 © 2024 Sasmal P.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Prakash Kumar Sasmal AIIMS, Bhubaneswar, India
Dear authors, This retrospective study aims to determine prediction factors for surgical site infection in a developing country after gastrointestinal surgery.SSIs are very common and distressing not only to the patients but also to the surgeons.Time and again, it is clear that SSIs after surgery are caused by several factors and not a single factor correction will ever decrease the rate.However, a few points need to be clarified to understand the readers better, as recall bias is more expected in a retrospective study.As multiple variables are taken to correlate only the associations, it becomes challenging to point out a particular cause to rectify.
1-As far as I can interpret in the study, the authors have put leucocytosis and high neutrophils as one of the factors for SSIs.Is leucocytosis the cause or effect of SSIs?
2-The prolonged hospital stays >5 days were the cause of SSIs or the effect of the infection, for Reviewer Expertise: Gastrointestinal and Metabolic surgery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 25 May 2024

Faisal Ahmed
APPROVED WITH RESERVATIONS Dear authors, This retrospective study aims to determine prediction factors for surgical site infection in a developing country after gastrointestinal surgery.SSIs are very common and distressing not only to the patients but also to the surgeons.Time and again, it is clear that SSIs after surgery are caused by several factors, and not a single factor correction will ever decrease the rate.However, a few points need to be clarified to understand the readers better, as recall bias is more expected in a retrospective study.As multiple variables are taken to correlate only the associations, it becomes challenging to point out a particular cause to rectify.
As far as I can interpret in the study, the authors have put leucocytosis and high neutrophils as one of the factors for SSIs.Is leucocytosis the cause or effect of SSIs?Answer: Thank you very much.
Leukocytosis was a predictive factor for SSI occurrence and not the cause. 1.
The prolonged hospital stays >5 days were the cause of SSIs or the effect of the infection, for which the patients were not discharged.Answer: Thank you very much.Prolonged hospital stays >5 days were a predictive factor for SSI occurrence and not the cause.

2.
The Khat chewing, as mentioned in Table 5, has spelling errors.Answer: Thank you very much.It was revised as you mentioned.

3.
The type of organ-specific SSIs in case of bowel, biliary, and pancreatic surgery need to be specified whether there was a documented leak in those cases.Especially in pancreatic cases, whether preop stenting was done or not.Answer: Thank you very much.Unfortunately, the data on postoperative leaks is not available for all cases.a future study focused on SSI occurrence and specific postoperative complications in specific organs is planned.

4.
The organisms responsible need to be subclassified according to the bowel, biliary, or pancreatic surgery, as the readers will benefit from knowing the common bacteria involved.
Answer: Thank you very much.Reviewer Expertise 1.
Gastrointestinal and Metabolic surgery 2.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however, I have significant reservations, as outlined above.

If applicable, is the statistical analysis and its interpretation appropriate? Yes
Are all the source data underlying the results available to ensure full reproducibility?Yes

Are the conclusions drawn adequately supported by the results? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Healthcare associated infections, clinical infectious diseases.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
The abstract mentions a SSI rate of 15% (79/525), whereas the results section and the discussion state 16.4% (86/525).

1.
The abstract states that the majority of SSI were superficial but detailed results on the depth of SSI (superficial, deep, organ/space) are not provided in the results section.These data would be interesting by type of surgery.

2.
The inclusion criteria state that all eligible patients between June 2015 and October 2022 were included, reaching 525 patients in about 7 years.Knowing the number of patients excluded would be of interest.

3.
Precisions on how SSI were detected would be of interest.Was the diagnosis made by surgeons or infection control personnel?Were all the patients followed-up after discharge?If yes, by systematic visits?All SSI were microbiologically documented.Was it because samples were taken from all patients with a clinically diagnosed SSI or because positive lab results were used to identify patients with SSI?

4.
Operations are grouped in four categories (small bowel, large bowel, biliary, and pancreatic) in the description of the population analyzed.More details would be interesting to know which operations were included in these four categories, e.g.how many cholecystectomies were included in biliary surgery?Were appendectomies included in large bowel surgery or only colon surgery?Did large bowel surgery include rectal surgery?

5.
These operations are then grouped in two categories (small bowel and others) in the statistical analyses.Although small bowel surgery represents the highest number of included operations, grouping large bowel surgery with biliary surgery appears counterintuitive, especially if cholecystectomies, which are much less at risk than colon surgery, represent the majority of biliary surgery.Could the results have been different and reached statistical significance if the comparison had been made between large bowel and others rather than between small bowel and others?6.
Some continuous variables such as age, hospital stay, BMI or temperature were stratified into binomial variables for the statistical analyses.Did it imply a loss of power for detecting risk factors and perhaps better determine a cut-off for the prediction?This applies particularly for age which could have been considered as an ordinal variable and stratified first in ten-year categories.

7.
The timing of shaving was found significant but shaving is not recommended by international guidelines and may constitute a risk factor for SSI (cf.for example reference 2 in the present paper).Is shaving systematically done in this hospital?Avoiding it accordingly with guidelines could constitute a simple mean for decreasing SSI rates that could be mentioned in the discussion.

8.
It is stated that variables with a p value <0.2 in univariate analysis were fitted for logistic regression but "antibiotic timing" and "operative type", which had both higher p values in univariate analysis (p=0.454 and p=0.506, respectively, as presented in table 4) are nevertheless part of the multivariable model (table 5).More details would be useful for a better understanding.

9.
Do all the operations performed in digestive surgery in this hospital correspond to open surgery?Since operations done with a laparoscope have been shown to be less at risk for SSI, information would be of interest about it in the methods and in the discussion.

10.
It is stated that "pathogens linked with SSI were identified from all SSI patient wounds".The total number of pathogens in table 3 amounts to 86 for 86 patients.This would mean that only one pathogen was identified from every patient with SSI.Were no patients suffering from a polymicrobial SSI detected (which is relatively frequent in colon surgery)?Were no other pathogens identified than the seven presented in table 3? For example, Enterobacter spp.streptococci or Candida spp.?

11.
More details would be of interest on resistance patterns of the isolated bacteria: proportion of ESBL producers in E. coli and Klebsiella respectively, presence or not of carbapenemaseproducing Enterobacteriaceae, resistance profile of Pseudomonas aeruginosa, resistance to vancomycine in enterococci.

12.
Mentioning the substances usually administered for antibiotic prophylaxis in these operations would help better realizing the magnitude of the problem of antibiotic resistance in this setting.

13.
Were only the significant variables in the multivariable analysis used for calculating the performance of the model for predicting SSI? Please specify.

14.
Discussion, paragraph 6. Mentioning whether glucose levels were not available for the included patients together with albumin levels or were available but not analyzed would be of interest since, irrespective of a history of diabetes, this could constitute, as stated, a risk factor for SSI.

15.
Discussion, paragraph 9.The following sentence is hard to understand: "Furthermore, our study revealed that the prevalence of SSI in large, pancreatic, and biliary surgeries was lower than in intestinal procedures; although this association was not statistically significant."Does "large" mean large bowel?Then "intestinal" might mean small bowel.Please clarify.In addition, please refer to comments 5 and 6 above for possible modifications in the discussion about this result.

16.
Discussion, paragraph 10.It is stated that a long duration may induce weaning prophylactic antibiotic concentration.Studies have shown the importance of re-dosing when this duration reach the half-life of the administered antibiotic and guidelines recommend it.This could be mentioned here and cited as a mean to lower SSI rates.17.
Discussion, paragraph 11.Please refer to comments 11, 12, and 13 above and possibly take them into account for extending the discussion about antibiotic resistance in this paragraph.

18.
Limitations, 3 rd sentence.Does "clinical identification" mean that no radiological or laboratory markers were used to help for the diagnosis of SSI?If yes, this should be specified in the methods.If not, underreporting might be due to interobserver variability if persons with different backgrounds did it (e.g.surgeons, infectious diseases physicians, infection control nurses).

19.
Limitations, 4 th sentence.Internal and external validation on other datasets or prospectively should be mentioned as a mean to consolidate these findings.

21.
Terminology.The same words should be used through the different tables (e.g."surgical status" in table 1 instead of "operative type" in tables 4 and 5).Consider using "operation duration" instead of "operative time".

22.
References 13 and 14 are identical.Reference 18 corresponds to a correction: please mention the original publication.

23.
(The source data are available but the corresponding file could not be opened.)

Is the study design appropriate and is the work technically sound? Yes
Are sufficient details of methods and analysis provided to allow replication by others?Partly

If applicable, is the statistical analysis and its interpretation appropriate? Partly
Are all the source data underlying the results available to ensure full reproducibility?Yes

Are the conclusions drawn adequately supported by the results? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Healthcare associated infections, clinical infectious diseases.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
The inclusion criteria state that all eligible patients between June 2015 and October 2022 were included, reaching 525 patients in about 7 years.Knowing the number of patients excluded would be of interest.

1.
Answer: Thank you.Unfortunately, the total number of patients was not accurately calculated.For that, we avoided mentioning the total patient numbers.
Precisions on how SSIs were detected would be of interest.Was the diagnosis made by surgeons and infection control personnel?Were all the patients followed up after discharge?If yes, by systematic visits?All SSIs were microbiologically documented.Was it because samples were taken from all patients with a clinically diagnosed SSI or because positive lab results were used to identify patients with SSI? 1.
Answer: Thank you.
Regarding infection control personnel, it was corrected.
Regarding patients followed up: yes.As they were operated, it is usually to have a regular follow-up.Additionally, we mentioned that they underwent systematic visits.Regarding microbiology documentation, all patients had culture and we mentioned it in the data collection section.The main causes of sample collection are the patient symptoms and the SSI suspected.
Operations are grouped into four categories (small bowel, large bowel, biliary, and pancreatic) in the description of the population analyzed.More details would be interesting to know which operations were included in these four categories, e.g.how many cholecystectomies were included in biliary surgery?Were appendectomies included in large bowel surgery or only colon surgery?Did large bowel surgery include rectal surgery? 1.
Answer: Thank you.
We did not collect the data regarding These operations are then grouped into two categories (small bowel and others) in the statistical analyses.Although small bowel surgery represents the highest number of included operations, grouping large bowel surgery with biliary surgery appears counterintuitive, especially if cholecystectomies, which are much less at risk than colon surgery, represent the majority of biliary surgery.Could the results have been different and reached statistical significance if the comparison had been made between Large bowel and others rather than between small bowel and others? 1.
Answer: Thank you.We revised it as you mentioned.However, it was not statistically significant as we mentioned in table 4.
Some continuous variables such as age, hospital stay, BMI or temperature were stratified into binomial variables for the statistical analyses.Did it imply a loss of power for detecting risk factors and perhaps better determine a cut-off for the prediction?This applies particularly for age which could have been considered as an ordinal variable and stratified first in ten-year categories.Answer: Thank you.All the continuous variables were converted into categorical variables for a better presentation of the nomogram.This statement was mentioned.
The timing of shaving was found significant but shaving is not recommended by international guidelines and may constitute a risk factor for SSI (cf.for example reference 2 in the present paper).Is shaving systematically done in this hospital?Avoiding it according with guidelines could constitute a simple means for decreasing SSI rates that could be mentioned in the discussion. 1.
Answer: Thank you.This item was revised to be Hair removal.We mentioned this issue in the discussion section.
It is stated that variables with a p value <0.2 in univariate analysis were fitted for logistic regression but "antibiotic timing" and "operative type", which had both higher p values in univariate analysis (p=0.454 and p=0.506, respectively, as presented in table 4) are nevertheless part of the multivariable model (table 5).More details would be useful for a better understanding. 1.
Answer: Thank you.
To better understand, we revised the Statistical analysis section.
10. Do all the operations performed in digestive surgery in this hospital correspond to open surgery?Since operations done with a laparoscope have been shown to be less at risk for SSI, information would be of interest about it in the methods and in the discussion.Answer: Thank you.Unfortunately, the laparoscopic equipment is not available in our hospital.For that, we avoided mentioning the laparoscopic procedures.

11.
It is stated that "pathogens linked with SSI were identified from all SSI patient wounds".The total number of pathogens in table 3 amounts to 86 for 86 patients.This would mean that only one pathogen was identified from every patient with SSI.Were no patients suffering from a polymicrobial SSI detected (which is relatively frequent in colon surgery)?Were no other pathogens identified than the seven presented in Table 3?For example, Enterobacter spp.streptococci or Candida spp.? Answer: Thank you.This was the result reported by the laboratory.

12.
More details would be of interest on resistance patterns of the isolated bacteria: proportion of ESBL producers in E. coli and Klebsiella respectively, presence or not of carbapenemase-producing Enterobacteriaceae, resistance profile of Pseudomonas aeruginosa, resistance to vancomycin in enterococci.Answer: Thank you.We did not collect the data regarding the antibiotic sensitivity or resistance.

13.
Mentioning the substances usually administered for antibiotic prophylaxis in these operations would help better realize the magnitude of the problem of antibiotic resistance in this setting.Answer: Thank you. it was mentioned in the data collection section.
14. Were only the significant variables in the multivariable analysis used for calculating the performance of the model for predicting SSI? Please specify .Answer: Thank you.

Figure 1 .
Figure 1.The receiver operating characteristic curve of the prediction model compared with the National Nosocomial Infections Surveillance risk index in the validation cohort.Abbreviations: AUROC: Area under the receiver operating characteristic curve; NNIS: National Nosocomial Infections Surveillance.

○○○○
Thank you very much.○ All mentioned comments were responded to and included in the revised manuscript.○ Is the study design appropriate and is the work technically sound?Thank you very much.All mentioned comments were responded to and included in the revised manuscript.○ Are sufficient details of methods and analysis provided to allow replication by others? 1. Yes ○ Answer: Thank you very much.○ If applicable, is the statistical analysis and its interpretation appropriate?1. Yes ○ Answer: Thank you very much.○ Are all the source data underlying the results available to ensure full reproducibility?

Table 1 .
Patient characteristics of 525 patients who underwent gastrointestinal procedures.

Table 4 .
Univariate analysis of risk factors associated with surgical site infection.

Table 3 .
Distribution of pathogens identified in surgical site infections.

Table 5 .
Multivariate analysis of risk factors associated with surgical site infection.

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