Antibiotic use in gastrointestinal surgery patients at a Vietnamese national hospital

We conducted a descriptive cross-sectional study in all inpatients aged 18 years and older, who underwent invasive gastrointestinal surgery between January 2020 and December 2020 at Thong Nhat Hospital, a National Hospital in South Vietnam. Patients who underwent more than one surgery during hospitalization were excluded from the study. We reviewed patients’ medical records and analyzed the following data: patient characteristics, antimicrobial therapy, and treatment outcomes including postoperative infections and length of hospitalization.

Data for the patients were recorded using a data collection form for each study subject. This form was used to collect the basic data, including age, gender, initial estimated glomerular filtration rate (eGFR, mL/min/1.73 m²), comorbidities. We also collected data pertaining to surgical procedures such as indication, surgical procedure, surgical classification. In addition, we recorded data relating to preoperative antibiotic used (indication, selection, dose, timing of the initial administration, and intraoperative re-dosing and duration) and postoperative ones (selection and dose).

Surgical classification was categorized into four groups—clean, clean-contaminated, contaminated, and dirty/infected. A clean surgery is defined as an incision in which no infection, inflammation and sterile error is encountered, and during which the respiratory, alimentary, and genitourinary tracts are not entered. A clean-contaminated surgery is an incision that entered the respiratory, alimentary or genitourinary tract under controlled conditions and encountered no contamination. A contaminated surgery is an incision undertaken during an operation in which there is a major break in sterile technique or gross spillage from the gastrointestinal tract, or an incision in which acute, non-purulent inflammation is encountered. Open traumatic wounds that are more than 12–24 h old also fall into this category. Dirty or infected surgery is an incision undertaken during an operation in which the viscera are perforated or when acute inflammation with pus is encountered during the operation (for example, emergency surgery for fecal peritonitis), and for traumatic wounds where treatment is delayed, and there is fecal contamination or devitalized tissue present [12, 13].

The sign of postoperative infections included purulent discharge from the incision site, positive results on microbiological culture indicated by discharge of fluid from a closed incision, surgery at sites with at least one clinical manifestation of inflammation (such as swelling, heat, redness, pain), positive culture results, or an infection diagnosed by the surgeon based on the Center of Disease Control (CDC) criteria [13].

The treatment outcomes were the rate of postoperative infections and the length of hospitalization.

We evaluated the appropriateness of prophylactic antibiotic therapy in patients with clean or clean- clean-contaminated surgery with regard to the choice of antibiotic (antibiotic indication), type, dosage, timing, additional dosage, and duration of administration. Criteria for appropriateness of antibiotic administration included physician adherence to guideline-recommended antimicrobials from the 2015 Vietnamese national guideline [14]. We evaluated the appropriateness of postoperative antibiotic treatment with regard to the type and dosage of administration in all patients. The criterion for the appropriateness of antibiotics was physician adherence to antimicrobial usage guidelines from the 2015 Vietnamese national guideline of antibiotic usage [14]. Postoperative antibiotic usage was defined as the appropriate type and dosage of antibiotic.

Patients’ mean age was 59.7 ± 17.2 years (62.5% were men). Most patients had stable renal function with an estimated glomerular filtration rate > 60 mL/min/1.73 m² (86.6%). Patients were mainly hospitalized for cancer (42.0%), and laparoscopic surgery was the procedure indicated in most patients, with laparoscopic colectomy being the predominant operation (35.7%). Most patients underwent clean or clean-contaminated surgery (94.7%) (Table 1).

We assessed the appropriateness of prophylactic antibiotics in 106 patients, who underwent clean or clean- clean-contaminated surgery (Table 2). The appropriateness of prophylactic antibiotic indication in our study was 97.2%. Cefoxitin (64.2%) and metronidazole (21.7%) were the most common antibiotics administered for prophylaxis in this study. No patient had a history of allergy to β-lactam antibiotics. Most of the 97 patients who were prescribed prophylactic antibiotics received monotherapy (76.3%). Cefoxitin is the most commonly used as monotherapy antibiotic (49.5%). The percentage of antibiotics dosage that differed from the recommended dosage is 23.6%. We observed that 100% prophylactic antibiotics were used within 30–60 min before creation of the skin incision.

Notably, no patient received any intraoperative antibiotic. The mean surgical time was 116.5 ± 40.5 min, and no severe intraoperative blood loss (> 1500 mL) was observed. The duration of surgery did not exceed the time required to repeat the dose of the prophylactic antibiotic selected for each patient. Prophylactic antibiotic administration was continued, despite the lack of any sign of infection, over 24 h postoperatively in 12.4% of patients. Of the 106 patients who underwent clean and clean-contaminated surgery, antibiotic administration was justifiably indicated in 103 patients, among whom 6 patients from the clean surgery group did not require prophylactic antibiotic administration, and 97 patients from the clean-contaminated surgery group used only one prophylactic antibiotic. The overall appropriate rate of prophylactic antibiotic was 54.7% (Table 3).

The median duration of postoperative antibiotic use was 9 (7–12) days; the most prolonged duration of antibiotic use was 28 days. β-lactam and fluoroquinolone were the most common antibiotic groups prescribed (Table 4). The overall rate of appropriateness of antibiotic treatment was 38.5%.

In this study, 39 patients (34.8%) developed at least one sign of infection; 14 patients were diagnosed with superficial surgical site infection and 25 patients with one sign of surgical site infection. The median length of hospitalization was 14 (10–20) days (maximum duration 36 days). Our results show that old age was associated with a high risk of postoperative infection and longer length of hospitalization (Tables 5 and 6).

The appropriateness of prophylactic antibiotic indication in our study was 97.2%, which is higher than that reported by Malavaud et al. [17], Durando et al. [18], and Pittalis et al. [19], who observed rates of 88.1%, 70.3% and 95%, respectively. This finding may be attributable to the increasing prevalence of nosocomial infections and drug resistance in Vietnam and the greater attention to postoperative infectious complications and the use of preoperative antibiotic therapy. Most patients in our study received prophylactic cefoxitin (64.2%) and metronidazole (21.7%). Cefoxitin is a 2nd generation broad-spectrum cephalosporin with a wide range of anaerobic coverage and is therefore commonly indicated for prophylaxis in gastrointestinal procedures, such as cholecystectomy, colorectal surgery, and operations for small bowel obstruction [21, 22]. Metronidazole and cefazolin combination therapy is recommended for operations with a high risk of anaerobic bacterial contamination, such as biliary tract surgery, laparoscopy, laparoscopic appendectomy, operations for small bowel obstruction, and colon surgery [23]. Statistical evidence suggests that cefoxitin and metronidazole constitute a high percentage of prophylactic antibiotics administered for gastrointestinal surgery. Most patients were prescribed a single prophylactic antibiotic (76.3%). Commonly used prophylactic antibiotics include cefoxitin (49.5%), ceftriaxone (6.2%), and cefazolin (9.3%).

We observed that the choice of antibiotics used was appropriate in 68.6% of patients in this study. This rate is lower than that reported by Malavaud et al. [17] (91.9%) and Pittalis et al. [19] (84.5%), which is attributable to the differences in hospital practices and policies adopted in our study and those followed by the hospitals included in the aforementioned studies. In fact, prophylactic combination therapy using cefoxitin and metronidazole is widely used during gastrointestinal surgery for effective coverage against anaerobic bacteria, although this combination is not reasonable [24‐26]. A systematic review of 18 studies that investigated adherence to guidelines for antibiotic prophylaxis observed that the rates of appropriateness of antibiotic prophylaxis ranged from 22 to 95% [27].

We observed that prophylactic antibiotic usage was 100% within 30–60 min before creation of the skin incision. Current guidelines recommend that prophylactic antibiotics should be administered within 60 min preoperatively and close to the time of creation of the skin incision (120 min for vancomycin and fluoroquinolones) [28, 29]. The timing of administration is an important determinant of successful antibiotic prophylaxis. Microbes that cause postoperative infection primarily invade the body during surgery (between the time of creation of the skin incision and wound closure) [28]. In a study performed by Koch et al. [22], the postoperative infection rate was lower in those who received prophylactic antibiotics within 60 min before the skin incision than in those who received prophylactic antibiotics later than 60 min before the skin incision. Several studies have reported that the effectiveness of antibiotic prophylaxis is maximum when administered during the 60-min period before creation of the skin incision [23, 24]. A study by Weber et al. [23] showed that the postoperative infection rate was higher in those who received prophylactic antibiotics between 0 and 30 min before the skin incision than in those who received prophylactic antibiotics over approximately 30–60 min prior to creation of the skin incision. In contrast, Steinberg et al. [24] observed no difference in the postoperative infection rate in patients who received prophylactic antibiotics within 0–30 min or 30–60 min.

No patient in our study received additional doses intraoperatively. Based on the clinical practice guidelines for antimicrobial prophylaxis in surgery, patients in whom the surgical time is > 2 times the T_1/2 of the drug and those with intraoperative blood loss > 1500 mL in adults tend to require additional antibiotic prophylaxis to ensure adequate blood and tissue antibiotic concentrations [4, 20]. In our study, we observed that the surgical time did not exceed 120 min in patients who received cefoxitin; therefore, the interval between repeat doses of cefoxitin was not exceeded. Moreover, repeat dose intervals of ceftriaxone (6 h), cefazolin (4 h), and metronidazole (6 h) were longer than the surgical time. Additionally, intraoperative blood loss > 1500 mL did not occur in any patient in our study (based on patients’ surgical record). Therefore, repeat doses of prophylactic antibiotics were not required. The rate of appropriate dose supplementation in this study was 100%, which was higher than the rates reported by Goede et al. [25] (54.9%).

Prophylactic antibiotic usage beyond 24 h after treatment completion was observed in 52.6% of patients, of which 12.4% patients continued treatment without a justifiable indication. A study performed across 9 provincial and central hospitals in 2009 reported that 94.6% of patients received prolonged postoperative prophylactic antibiotics [26], which may have been due to the notion prevalent among surgeons regarding the need for long-term administration of antibiotics to prevent postoperative infections. However, per recommendations, most routine surgeries usually require administration of only a prophylactic dose. Antibiotic prophylaxis is not required beyond 24 h postoperatively for most surgeries (or beyond 48 h for cardiac surgery) [20]. The appropriateness of the rate of prolonged antibiotic prophylaxis in our study was 87.6%, which was higher than that reported by Pittalis et al. [19] (48%). Gouvea et al. [21] showed that the reasonable rate of duration of antibiotic prophylaxis ranged from 5.8 to 91.4%.

The overall rate of appropriateness of antibiotic prophylaxis in our study was 54.7%, which is similar to that reported by Malavaud et al. [17] (58.3%). The similarity in results may be attributed to the fact that the types of surgeries performed and the criteria for criteria for antibiotic selection were nearly identical between our study and the study performed by Malavaud et al. [17].

Surgical site infection is one of the most common infections associated with health care. Therefore, there are many studies to investigate postoperative infection, including surgical site infection after gastrointestinal surgery. In this study, 34.8% of patients had at least one sign of infection, which is higher than that reported by Bhangu et al. [30], Wang et al. [31], Alkaaki et al. [16], who reported rates of 2–5%, 5.2% and 16.3%, respectively. This difference can be explained as follow, we recorded cases of patients with at least one sign of infection, while other studies recorded the proportion of patients with accurate diagnosis of surgical site infection.

The median length of hospitalization was 14 (10–20) days, which is similar to that reported by Jakobson et al. [32] (14.5 ± 10 days) and higher than that reported by Alkaaki et al. [16], the median postoperative hospital stay was 2 days for patients without SSI, compared to 13 days for those with SSI.

We observed that increasing age increased the risk of postoperative, which is similar to findings reported by Neumayer et al. [27], who observed a higher risk of postoperative infection in patients aged over 40 years old than in those aged under 40 years. A study performed in the United States showed that the risk of postoperative infection increased 1.2-fold with every 1-year increase in age among patients aged above 65 years [28].

Furthermore, we observed that advanced age was associated with longer length of hospitalization; this result is similar to that reported by Chong et al. [29], who observed that advanced age was associated with the longer length of hospitalization in patients who underwent laparoscopic cholecystectomy.

Following are the limitations of this study: (a) This retrospective observational study was based on data obtained from patients’ medical records; therefore, we did not consider all potential confounders that may have affected our results. (b) Owing to the small sample size and single-center study design, our findings may not accurately reflect the effect of prophylactic and therapeutic antibiotics in patients who undergo gastrointestinal surgery. Further large-scale studies are warranted to gain a deeper understanding of this subject.