Preventing surgical site infection after cholecystitis by postoperative antibiotic: A randomized controlled trial study

doi:10.21203/rs.3.rs-1842111/v2

Download PDF

Research Article

Preventing surgical site infection after cholecystitis by postoperative antibiotic: A randomized controlled trial study

https://doi.org/10.21203/rs.3.rs-1842111/v2

This work is licensed under a CC BY 4.0 License

Version 2

posted

You are reading this latest preprint version

Purpose: Surgical site infection is one of the most common complications of surgical procedures and the best method for its risk reduction is prevention. The main purpose of this study is to assess the prophylactic role of postoperative antibiotics in reducing the incidence of surgical site infection.

Methods: We conducted a prospective, randomized trial at Sina Hospital, Tehran, Iran from 2019 to 2021 to compare the postoperative incidence of surgical site infection and deep wound infection, in patients with mild or moderate cholecystitis who underwent elective cholecystectomy in patients receiving prophylactic antibiotics to those who did not receive antibiotics.

Results: The postoperative antibiotics do not associated with a significant decrease in postoperative surgical site infection (P>0.05).

Conclusion: Through this study, we demonstrated that postoperative antibiotics did not have a prophylactic role in the prevention of surgical site infection.

Surgical site infection (SSI)

mild or moderate cholecystitis

postoperative antibiotics

Acute cholecystitis (AC), inflammation of the gallbladder, divided into calculus and acalcalus [1]. Acalculus cholecystitis is multifactorial necroinflammation of gallbladder that usually occurred in the certain patients (e.g, immunosuppressed patients) [2]. Nowadays, laparoscopic cholecystectomy (LC) is the gold standard and surgical procedure of choice for AC [3], introduced in 1980 [4]. One of the main reasons for the superiority of this technique over open cholecystectomy (OC) is the lower incidence of surgical site infection (SSI) (0.3–3.4% after LC versus 1.1–8.4% after OC) [5]. However, the longer operating time is a serious risk factor [6]. According to the literature, in addition to imposing a significant economic burden on the healthcare system because of prolonged hospitalization and re-admission, SSI affects the patient’s quality of life [7, 8]. On the other hand, AC is one of the most common surgical problems treated by surgery [9]. The incidence of SSI is higher in gastrointestinal surgeries compared to other operations [10, 11] and prevention must be considered. In this regard, two strategies have been proposed namely preoperative prophylaxis and postoperative antibiotics. Preoperative and intraoperative antibiotic prophylaxis is known as a reasonable approach in these patients[12, 13], whereas, there is controversy concerning using or not using antibiotics in the postoperative period [14, 15]. Thus, the main purpose of this study was to assess the efficacy of postoperative antibiotics for reducing SSI and deep wound infection in patients undergoing LC or OC.

Study design & population

This prospective randomized controlled trial (RCT) was carried out at the Department of Surgery of Tehran University Hospital, Tehran, Iran during 2019-2021. Patients were randomly and anonymously assigned to intervention (case) and control groups. Randomization was conducted by means of sealed envelopes in the recovery room after surgery. It was stratified with respect to postoperative antibiotic.

This study was approved by the Medical Ethics Committee of Tehran University of Medical Sciences. The ethical code is IR.TUMS.MEDICINE.REC.1398.112. As well, this study was confirmed in the Iranian randomized clinical trial system identified by IRCT20201023049120N1 as the trial number. Patients entered the study voluntarily following signing informed consent.

The inclusion criteria entailed: patients (≥18 years old) undergoing elective cholecystectomy (laparoscopic or open) due to mild or moderate AC based on Tokyo guidelines 2018 [16].

The exclusion criteria were: 1) age under 18 years; 2) pregnant and lactating patients; 3) acute pancreatitis, cholangitis, or hepatobiliary cancers; 4) common bile duct stones; 5) patients dissatisfaction; 6) primary or secondary immune deficiency; 7) sensitivity to beta-lactam antibiotics and 8) delay ≥96 h from diagnosis to surgery.

Preoperative and postoperative management

All patients received preoperative antibiotics prophylaxis (Ceftriaxone 1gr IV and Metronidazole 500 mg IV) and underwent LC, or OC during 96 h of diagnosis, if needed. The surgery was performed by an expert surgeon and his team.

After surgery, the participants were randomly divided into two groups (postoperative antibiotic treatment group or case group) and (without postoperative antibiotic therapy or control group). In the case group, ciprofloxacin and metronidazole were administrated for 5 days orally. Otherwise, antibiotics were infused until they had oral tolerance.

Data collection and follow-up

The collected demographic, clinical, and para-clinical data included age, gender, associated comorbidity, the severity and grading of AC, demographic Murphy's sign, liver function test (LFT), complete blood count, the type of surgery, and the rates of SSI and deep wound infection.

The SSI is a skin or subcutaneous tissue infection that occurs within the first 30 days after surgery. It is diagnosed by at least one of the following criteria:

1. purulent discharge

2. organism growth in aseptic samples of wound culture

3. signs and symptoms of infection (e.g: pain or tenderness of the wound, localized swelling, erythema or warmth)

4. clinical diagnosis of wound infection by an expert surgeon

Deep wound infection is a facial or muscle tissue infection that leads to abscess formation in the gallbladder bed during the first 30 days after surgery. Deep wound infection is diagnosed based on at least one of the criteria including:

purulent discharge from the depths of the incision not related to another organ or space.
localized pain or tenderness
fever (T≥38) and the clinical diagnosis of wound infection or abscess by an expert surgeon

A total of 60 patients with AC that had undergone elective cholecystectomy, followed by postoperative antibiotics in the case group, were included in this study. All patients were evaluated daily during postoperative hospitalization and one, and four weeks postoperatively as outpatients. Patients were assessed for SSI by a special resident.

All the patients were evaluated for postoperative SSI in two groups.

Statistical analysis

The data of this study were statistically analyzed by SPSS software version 22 (IBM, US). Chi-Square test and Fisher's exact test were used to analyze the qualitative data between the two groups. In addition, the t-test (according to the results of the Kolmogorov-Smirnov test) was used to compare quantitative data of the two groups. The statistical significance level was considered 0.05.

Out of 60 patients with AC included in the present study, 30 (50%) were in the control group and 30 (50%) were in the case group.

Demographic, clinical and paraclinical data of patients

We observed that 19 cases (31.7%) were male and 41 (68.3%) were female, who were similarly distributed in the two groups (P>0.05). The mean age of the participants was 48.33±15.2 and 48.5±12.2 years in the case and control groups, respectively. Moreover, the mean interval from diagnosis to surgery was (2.38±1.49 and 2.79±1.75 day), respectively; but there is no significant difference (P>0.05). There was no significant difference between the two groups in this regard. The two study groups were not significantly different in demographic data (age, gender), clinical findings (comorbidity), and laboratory results, such as liver function tests (LFTs), and white blood cell count (WBC) (P-value>0.05). Two patients in the case group and one in the control group developed SSI within 7 days after surgery, revealing no significant difference between the groups (P>0.05). Two SSI patients had undergone open surgery, and a patient had laparoscopic surgery. Furthermore, the severity of cholecystitis was mild in two patients while moderate in other patient. Related data are summarized in Table 1.

Patient follow-up was performed on an outpatient basis in the clinic on the days 7 and 30 after surgery, and no significant difference was found between the two groups (P>0.05).

We assessed the association of SSI with the grade of cholecystitis and found no significant correlation between SSI, the severity of cholecystitis, and the type of surgery (P>0.05), as shown in Table 2.

The SSI is still a serious problem that results in morbidity and even mortality in the postoperative period. Therefore the best management is prevention. Several techniques have been utilized to decrease SSI incidence, such as a perioperative prophylactic antibiotic or postoperative antibiotic. The administration of perioperative antibiotics has been confirmed. However there is controversy about the use of postoperative antibiotics. For instance, a study by Ravinder et al. showed that antibiotics are useful in preventing SSI [17]. Another study demonstrated that prophylactic antibiotic is effective in reducing of superficial SSI but not in preventing deep SSI in low-risk patients and elective LC [18]. In the present study, we assessed superficial and deep wound infections and deep SSI did not occur either groups.

Despite the oldness of this subject we investigated the role of postoperative antibiotics in reducing the incidence of SSI due to the importance of the subject and diversity in the opinion of surgeons. Our results showed that post-operative antibiotic treatment was not associated with a lower incidence of SSI or deep wound infection after cholecystectomy for mild or moderate AC. We did not observe any benefit for postoperative antibiotic treatment in the infections of patients with mild or moderate AC based on Tokyo guideline 2018.

Lau st al. compared two postoperative antibiotic regimens in 203 patients with AC. All patients received cefamandole preoperatively [19]. After surgery, patients were randomly divided into two groups of short and long antibiotic treatment courses. Finally, these authors reported that the longer course of treatment was not associated with a significantly lower SSI incidence [20].

Several other studies performed by Regimbeau et al. [20], Loozen et al. [9], Jaffar et al. [21], and Kim et al. [18], showed that postoperative antibiotic treatment did not reduce the SSI rate, which is similar to our study.

Only one research that prospectively compared the antibiotic regimen and duration treatment on 287 patients with moderate AC found that postoperative antibiotic treatment longer than 4 days did not affect the SSI rate [22]. However Rodriguez et al. indicated that postoperative antibiotics effectively reduced SSI [22].

One of the strengths of our study was the randomized design of this research.

However, the current study had several limitations. First we only considered elective cholecystectomy. Second the number of patients was relatively small.

Our findings demonstrated that postoperative antibiotic treatment in patients with mild or moderate AC according to Tokyo guideline 2018 did not result in a lower incidence of SSI or deep wound infection. Consequently, postoperative antibiotics following uncomplicated AC do not seem necessary.

Source of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was approved by the ethical committee of Tehran University of Medical Sciences. The ethical code is IR.TUMS.MEDICINE.REC.1398.112. As well, this study was confirmed in the Iranian randomized clinical trial system identified by IRCT20201023049120N1 as the trial number.

Acknowledgments

Thanks to the patients who consented to participation in this study.

Authors' contributions: HZM conceived and designed the study, conducted research. HZM and HT provided research materials. HA, ER, and RH analyzed and interpreted data and collected and organized data.RAK wrote the initial and final draft of the article and provided logistic support. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.

Gomes CA, Junior CS, Di Saveiro S, Sartelli M, Kelly MD, Gomes CC, Gomes FC, Corrêa LD, Alves CB, de Fádel Guimarães S. Acute calculous cholecystitis: Review of current best practices. World journal of gastrointestinal surgery. 2017 May 27;9(5):118.
Huffman JL, Schenker S. Acute acalculous cholecystitis: a review. Clinical Gastroenterology and Hepatology. 2010 Jan 1;8(1):15-22.
Yang J, Gong S, Lu T, Tian H, Jing W, Liu Y, et al. Reduction of risk of infection during elective laparoscopic cholecystectomy using prophylactic antibiotics: a systematic review and meta-analysis. Surgical Endoscopy. 2021 Aug 9:1-6.
Richards C, Edwards J, Culver D, Emori TG, Tolson J, Gaynes R, National Nosocomial Infections Surveillance (NNIS) System. Does using a laparoscopic approach to cholecystectomy decrease the risk of surgical site infection?. Annals of surgery. 2003 Mar;237(3):358.
Warren DK, Nickel KB, Wallace AE, Mines D, Tian F, Symons WJ, et al. Risk factors for surgical site infection after cholecystectomy. InOpen forum infectious diseases 2017 (Vol. 4, No. 2, p. ofx036). US: Oxford University Press.
Fahrner R, Malinka T, Klasen J, Candinas D, Beldi G. Additional surgical procedure is a risk factor for surgical site infections after laparoscopic cholecystectomy. Langenbeck's archives of surgery. 2014 Jun;399(5):595-9.
De Lissovoy G, Fraeman K, Hutchins V, Murphy D, Song D, Vaughn BB. Surgical site infection: incidence and impact on hospital utilization and treatment costs. American journal of infection control. 2009 Jun 1;37(5):387-97.
Hassan RS, Osman SO, Aabdeen MA, Mohamed WE, Hassan RS, Mohamed SO. Incidence and root causes of surgical site infections after gastrointestinal surgery at a public teaching hospital in Sudan. Patient Safety in Surgery. 2020 Dec;14(1):1-7.
Loozen CS, van Santvoort HC, van Geloven AA, Nieuwenhuijzen GA, de Reuver PR, Besselink MH, et al. Perioperative antibiotic prophylaxis in the treatment of acute cholecystitis (PEANUTS II trial): study protocol for a randomized controlled trial. Trials. 2017 Dec;18(1):1-7.
Aga E, Keinan-Boker L, Eithan A, Mais T, Rabinovich A, Nassar F. Surgical site infections after abdominal surgery: incidence and risk factors. A prospective cohort study. Infectious Diseases. 2015 Nov 2;47(11):761-7.
Li Z, Li H, Lv P, Peng X, Wu C, Ren J, et al. Surgical Site Infection After Emergency Abdominal Surgery in China: A Multicenter Prospective Study.
Shaffer EA. Epidemiology of gallbladder stone disease. Best practice & research Clinical gastroenterology. 2006 Jan 1;20(6):981-96.
Orlando R, Russell JC, Lynch J, Mattie A. Laparoscopic cholecystectomy: a statewide experience. Archives of Surgery. 1993 May 1;128(5):494-9.
Peters JH, Ellison EC, Innes JT, Liss JL, Nichols KE, Lomano JM, et al. Safety and efficacy of laparoscopic cholecystectomy. A prospective analysis of 100 initial patients. Annals of surgery. 1991 Jan;213(1):3.
Club SS. A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl j Med. 1991;324:1075-8.
Yokoe M, Hata J, Takada T, Strasberg SM, Asbun HJ, Wakabayashi G, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos). Journal of Hepato‐biliary‐pancreatic Sciences. 2018 Jan;25(1):41-54.
Vohra RS, Hodson J, Pasquali S, Griffiths EA. Effectiveness of antibiotic prophylaxis in non-emergency cholecystectomy using data from a population-based cohort study. World journal of surgery. 2017 Sep;41(9):2231-9.
Kim SH, Yu HC, Do Yang J, Ahn SW, Hwang HP. Role of prophylactic antibiotics in elective laparoscopic cholecystectomy: A systematic review and meta-analysis. Annals of hepato-biliary-pancreatic surgery. 2018 Aug 1;22(3):231-47.
Lau WY, Yuen WK, Chu KW, Chung KK, Li AKC. SYSTEMIC ANTIBIOTIC REGIMENS FOR ACUTE CHOLECYSTITIS TREATED BY EARLY CHOLECYSTECTOMY. Australian and New Zealand Journal of Surgery. 1990;60(7):539-43.
Regimbeau JM, Fuks D, Pautrat K, Mauvais F, Haccart V, Msika S, et al. Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: a randomized clinical trial. Jama. 2014;312(2):145-54.
Jaafar G, Persson G, Svennblad B, Sandblom G. Outcomes of antibiotic prophylaxis in acute cholecystectomy in a population-based gallstone surgery registry. The British journal of surgery. 2014;101(2):69-73.
Rodriguez-Sanjuan JC, Casella G, Antolin F, Castillo F, Fernandez-Santiago R, Riano M, et al. How long is antibiotic therapy necessary after urgent cholecystectomy for acute cholecystitis? Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2013;17(11):1947-52.

Table 1

Demographic, clinical and paraclinical data

Control group

Case group

P-value

Age

(mean±SD)

48.50±12.82

48.33±15.20

>0.05

Gender(number)

Female: 41

Male: 19

19 (63.3%)

11 (36.7%)

22 (73.3%)

8 (26.7%)

>0.05

Comorbidity

Positive

Negative

9 (30%)

21 (70%)

8 (26.7%)

22 (73.3%)

>0.05

Type of surgery

Laparoscopy

Open

19 (63.3%)

11 (36.7%)

18 (60%)

12 (40%)

>0.05

Admission to surgery interval (day)

2.79±1.75

2.38±1.49

>0.05

Leukocytosis

Positive

Negative

13 (43.3%)

17 (56.7%)

14 (46.7%)

16 (53.3%)

>0.05

Abnormal LFT

Positive

Negative

1 (3.3%)

29 (96.7%)

2 (6.7%)

28 (93.3%)

>0.05

Ultrasound Morphy sign

Positive

Negative

11 (36.7%)

19 (63.3%)

14 (46.7%)

16 (53.3%)

>0.05

Grade of cholecystitis

Mild

Moderate

22 (73.3%)

8 (26.7%)

18 (60%)

12 (40%)

>0.05

Severity of cholecystitis

Mild

Moderate

19 (63.3%)

11 (36.7%)

16 (53.3%)

14 (46.7%)

>0.05

SSI

Positive

Negative

1 (3.3%)

29 (96.7%)

2 (6.7%)

28 (93.3%)

Deep wound infection

Positive

Negative

Emergency visit (<1week)

Yes

1 (3.3%)

29 (96.7%)

4 (13.3%)

26 (86.7%)

0.353

Ultrasound results

Normal

Abnormal

28 (93.3%)

2 (6.7%)

30 (100%)

0.492

^{SD=Standard Deviation}

^{SSI=Surgical Site Infection}

Table 2

Association between SSI and type of surgery, grade and severity of cholecystitis

		SSI in control group	SSI in case group	P-value
Type of surgery	Laparoscopy Open	0 1	1 1	>0.05
Grade of cholecystitis	Mild Moderate	1 0	1 1	>0.05
Severity of cholecystitis	Mild Moderate	1 0	1 1	>0.05

No competing interests reported.

Download PDF

Version 2

posted

You are reading this latest preprint version

Preventing surgical site infection after cholecystitis by postoperative antibiotic: A randomized controlled trial study

Status:

Version 2

Abstract

Introduction

Methods

Results

Discussion

Declarations

References

Tables

Additional Declarations

Status:

Version 2