Risk Factors for Treatment Resistant Postoperative Surgical Site Infections

Introduction

Every surgeon tries to perform surgery in the best way possible without causing any complications or harm to the patient. However, despite all possible efforts, perioperative or postoperative complications that increase patient morbidity may occur in any surgery. Surgical site infections (SSI) are just one of these complications1. SSI is the most common complication after gynecologic surgeries2 and it has been shown that SSI develops at a rate of 2.7% after hysterectomy3. SSIs are superficial or deep infections that occur in the surgical area within one-month postoperatively4. Thus, predictors of post-operative SSI after gynecological surgery are of clinical benefit. This will also help when preparing guidelines for future reference1.

Although defining risk factors for SSI is complex and difficult, there are numerous published studies concerning the risk factors1,2,5,7. However, the number of studies examining predictive factors for SSIs resistant to treatment in gynecologic surgery is quite low. When looking at the literature, modifiable factors, such as preoperative anemia, malnutrition, smoking, obesity, hypertension (HT), type 2 diabetes mellitus (DM) and unmodifiable predisposing factors such as age and malignancy have been identified for SSI4. If these factors are controlled as well as possible in the preoperative period, the risk of SSI may be reduced. If anemia is present, iron supplementation (or blood transfusion if time is limited), identifying and resolving the cause of malnutrition and applying total parenteral nutrition pre- and postoperatively if necessary, reducing or smoking cessation, ensuring weight loss if body mass index (BMI) is high, controlling HT and DM, using prophylactic antibiotics, and ensuring tissue oxygenation and normothermia in the intraoperative period have been shown to reduce the occurrence rate of SSI4,8. In obese patients, it is also recommended not to leave subcutaneous dead space and, if necessary, to use a negative pressure drain in this area9.

The resistance of SSIs to antibiotics has been less well investigated, Therefore, we aimed to examine and identify the risk factors for patients who develop resistance to treatment which results in higher morbidity and mortality rates compared to patients who respond to treatment. If it is known which reasons cause resistance to treatment in patients who develop SSI, the success of the treatment can be achieved by correcting the modifiable factors or increasing attention in the presence of these factors.

Materials and Methods

This study was approved by the Kocaeli University non-invasive ethics committee (KU GOKAEK-2024/277). All patients between the ages of 18 and 90 years who underwent elective surgery for benign or malignant gynecological reasons between January 2021 and December 2023 in the Department of Obstetrics and Gynecology, Kocaeli University Hospital, Türkiye, were retrospectively screened for the presence of SSI. Patients who underwent wound culture after developing SSI findings and only those in whom growth was detected were included in the study. In our clinic, 1 g of cefamezin is routinely given to all patients preoperatively and control cultures are routinely taken from patients who are given appropriate antibiotic therapy after SSI. Demographic, obstetric and perioperative data of patients with positive control culture (study group) and patients with negative control culture (control group) were compared.

Demographic, obstetric and perioperative data of all patients

BMI: Body mass index; LMWH: low-molecular-weight heparins; p<0.05 is significant.

Patients who had local or systemic infectious symptoms, such as redness, increased temperature, and itching in the area where surgery would be performed before the operation, patients who had a culture taken because of infection in the wound area in the postoperative period but were using antibiotics at the time, and patients who were found to have developed SSI but no positive cultures were found were not included in the study.

The patients' age, BMI, indications for surgery, obstetric and gynecological history, menopause status, comorbidities, medications used, surgical approach types (Pfannenstiel, lower midline incision, midline incision, vaginal and laparoscopic approach), whether postoperative low molecular weight heparin (LMWH) was administered, surgery duration, amount of blood transfusion if administered, whether pathology results were benign or malignant, number of days of hospitalization, wound culture results, and whether secondary suture was required were recorded.

According to the culture results, single, double, triple or quadruple antibiotic combinations were selected according to their antibiograms and based on indicated sensitivities and were used in all patients.

Statistical evaluation was performed using IBM SPSS, version 29.0 (IBM Corp., Armonk, NY, USA). The normal distribution test was evaluated using Shapiro-Wilk and Kolmogorov-Smirnov tests. Numerical variables are given as Mean ± standard deviation, median (25th-75th percentile) and frequency (percentages). Differences between groups/materials were compared using Student's t test, One-way analysis of variance and Tukey's multiple comparison test for numerical variables with normal distribution and Mann Whitney U Test, Kruskal Wallis test and Dunn's multiple comparison test for numerical variables without normal distribution. Fisher's exact chi-square test, Yates' chi-square test and Monte Carlo chi-square test were used for categorical variables to evaluate the differences between groups. The relationship between numerical variables was evaluated using Spearman or Pearson correlation analysis, as appropriate. Logistic regression analysis was performed to determine risk factors for treatment-resistant wound infections. A p<0.05 was considered sufficient for statistical significance in two-sided tests.

The growth percentages of the agents in the wound culture of all patients are given.

* Other agents included Proteus mirabilis, Morganella morgagni, Streptococcus agalactiae, Serratia marcescens, Klebsiella aeroginosa.

Results

Demographic, obstetric and perioperative data of the patients are given in Table 1. A total of 144 patients who developed postoperative SSI and had positive wound cultures were identified. The median (range) age of the patients was 53 (40-65) years, ranging from 22-89 years old. The median BMI was 34.75 (29.85-41.45) kg/m2 and 105 (72.9%) of the patients were obese (BMI ≥30 kg/m2). More than half were postmenopausal (n=81, 56.3%). The number of patients with both cultures positive was 49 (34%). Table 2 shows the percentage of growth of the agents in the wound culture of the patients.

The types of operations performed on the patients are shown in Table 3. The most common operation was hysterectomy ± unilateral/bilateral salpingooophorectomy ± bilateral pelvic paraaortic lymph node dissection (BPPALND) ± omentectomy due to malignancy. Histopathological reports confirmed that 67 (46.5%) of the patients were operated on for malignant causes. The median operation time was 95 (75-133.75) minutes.

Types of operations performed on patients in both groups.

BPPLND: bilateral pelvic and paraaortic lymph node dissection.

Comparison of demographic, obstetric and medical history data of the patients between the two groups.

OAD: Oral antidiabetics; BMI: Body mass index; p<0.05 is significant.

Demographic, obstetric and history data of the patients are compared between the two groups in Table 4. While the number of patients with growth in only the first culture was 95 (66%), the number of patients with growth in both cultures was 49 (34%). No significant difference was found in terms of age, BMI, obstetric data, presence of menopause, HT and DM diagnoses between these two groups. However, there was a significant difference between the groups in terms of chronic drug use (p=0.002).

Table 5 compares the data of the groups in the preoperative and postoperative follow-ups. No significant difference was found in terms of surgical approach. No significant difference was found in terms of being operated on due to malignancy, operation times, blood transfusion requirements and postoperative LMWH use. The median hospital stay before the development of SSI was significantly longer in the study group (p=0.017). A significant difference was found in the number of antibiotics used in the treatment of SSI between the two groups (p=0.027). The use of triple and quadruple antibiotic regimens was more common in the study group. No significant difference was found in terms of the need for secondary sutures.

Comparison of peroperative and postoperative follow-up data between the two groups.

LMWH: Low-molecular-weight heparins; p<0.05 is significant.

Discussion

SSI, which affects surgical treatment outcomes, is the most common hospital-acquired infection2. The incidence of SSI after obstetric and gynecologic surgery is between 4.6% and 10.3%1,2. However, defining risk factors for SSI is complex and difficult. Current findings in the literature on risk factors are generally limited due to small sample sizes and poor statistical power2.

In the present study, and unlike in other studies examining infection risk factors, all patients who had already had growth were included, but the risk factors of patients who had growth in the second culture despite appropriate treatment according to identified antibacterial sensitivities were investigated. In a meta-analysis including 13 articles for SSI in gynecology, BMI ≥24, malignant lesions, ≥60 minutes of surgery, ≥300 mL of intraoperative bleeding, urinary catheter retention time and ≥3 vaginal digital examinations were reported as independent risk factors for SSI in obstetric and gynecological surgery2. Our findings support these data with nearly three-quarters of our cohort being obese, more than half were operated for malignant reasons and the median surgery time was longer than one hour. However, only 18 (12.5%) patients required blood transfusion. In a study including 206 Caesarean section operations, controlling BMI, shortening the operation time, good bleeding control, and reducing the duration of urinary catheterization were found to be beneficial in preventing SSI5.

In gynecological operations, incisions are usually applied to the skin, vulva, vagina, umbilical region and other areas where many microorganisms are found. These incisional surgical approaches are significant in terms of infection2. The operations with the lowest SSI rate are laparoscopy and sterilization (tubal ligation) surgeries. The highest infection rate was seen in radical and extended hysterectomies. In addition, it has been suggested that vaginal hysterectomy (1%) has a lower SSI incidence than abdominal surgery (5.7%)10. Abdominal distension frequently occurs in the early postoperative period and therefore the wound layers are subjected to significant tension. From this perspective, it has been suggested that more frequent use of transverse incisions will greatly reduce the incidence of both hernia and wound infection complications10. We also added the types of abdominal incisions applied to the patients and the vaginal approach rates to the study for comparison. However, we found that these differences were not a risk factor in terms of the development of resistance to treatment in SSIs.

The immune system is generally at risk in patients with malignant tumors and SSIs are frequently seen in these patients2. However, in the present study, malignancy was not found to be a risk factor for resistance to treatment. It has been reported that HT is not a risk factor for SSI1,6. Our results support this as HT was not a risk factor for resistance to treatment. While DM is considered a risk factor for SSI in many studies11-15, such a finding was not reported others1,2,6,7,16. Our findings also suggest that that DM was not a risk factor for SSIs in the study group. When we compared the BMIs and the number of obese patients between the two groups, there was no significant difference and that SSIs were not a risk factor for resistance to treatment. Other studies have also found that high BMI was not a risk factor for SSI16. However, the meta-analysis of SSI in gynecological surgery reported that BMI ≥24 kg/m2 conferred a 2.5 greater risk of SSI, BMI ˃28 a 16-fold increase in risk and and BMI ˃30 a 7-fold increase in risk2. In addition to its anti-inflammatory and hyperglycemic effects, single-dose dexamethasone administration did not increase the risk of SSI (p=0.19)18. However, in our study, it was found that chronic prednisolone and oral antidiabetic use was significantly more common in the group that developed treatment-resistant SSI.

The duration of surgery (˃1 hour or ˃1.5 hours) has been identified as a risk factor for SSI in several studies (1,2,5,10). In the present study, the median duration of surgery was calculated as around 1.5 hours. However, when we evaluated the resistance to treatment in SSI by comparing the two groups, no significant difference was found. The hemoglobin value of all patients who underwent surgery was above 10 mg/dL. However, it was observed that some patients had to be transfused with erythrocyte suspension, varying from 1-5 units, in the postoperative period. When the two groups were compared, no significant difference was found in terms of transfusion requirement. When the literature was examined, the need for blood transfusion was given as a risk factor for SSI1,2, and the need for blood transfusion is common in women with SSI (23.75%)10. However, another study stated that the need for blood transfusion was not a risk factor for SSI16.

Infection is associated with increased hospital stay and therefore increased healthcare costs2. Studies have shown that a longer duration of hospitalization is associated with SSI that occurs later19,20. Our findings support this in the group that developed treatment-resistant SSI. It has been reported that the proportion of patients who required secondary sutures after SSI was high at 87.7%4. In the present study, secondary sutures were needed in only 14 patients and no significant difference was detected between the two groups for this procedure. This suggests that the presence of resistant SSI does not predict the need for secondary sutures.

Conclusion

In the present study, chronic drug use, multiple antibiotic treatment and long hospital stay before the development of SSI were evaluated as risk factors for treatment-resistant SSI. Clinicians should consider the possible risk of treatment-resistant infection in SSI patients who have a history of chronic drug use, especially steroids and oral anti-diabetic therapies, having long-term hospital stay pre-operatively and/or with a history of multiple antibiotic treatment regimens

Statement of ethics

This study was approved by the Ethics Committee of Kocaeli University non-invasive ethics committee (KU GOKAEK-2024/277)The study was performed according to the Declaration of Helsinki.

Source of Finance

The authors declare that they have received no financial support for this study

Conflict of interest statement

The authors declare that they have no conflict of interest.

Availability of data and materials

The data supporting the conclusion of this article will be available by the authors without undue reservation.

Author contributions

All authors contributed to the article.