PhilSPEN Online Journal of Parenteral and Enteral Nutrition

(Article 144 | POJ_0136 | 2020-2021)

Original Clinical Investigation

The efficacy of administration of probiotics and antibiotics versus antibiotics alone in elective surgery in the reduction of risk of surgical site infections – a systematic review

Abstract | Introduction | Methodology | Results | Discussion | Conclusion | References | Back to Total Name and Codes page2

Submitted: | Posted:

Authors:

Rafael Luis C. Encarnacion MD

Co-Authors: Danilo D. del Rosario MD and Domingo S. Bongala MD

Institution where research was conducted:

Department of Surgery, University of the East Ramon Magsaysay Memorial Medical Center

 

ABSTRACT: | Back

Background:

Probiotics became a new adjunct of therapy for administration of antibiotics in surgical site infections. The question then occurs: how effective is it when we compare placement of antibiotics alone versus antibiotic and probiotic therapy in elective surgery cases?    

Objective:

To find out if there is a difference between administration of antibiotics alone or with concomitant administration of probiotics in patients with surgical site infections.

Methodology:

A literature search was conducted where the words PROBIOTICS OR PROBIOTIC OR SYNBIOTIC AND OPERATION OR “SURGERY” OR SURGICAL PROCEDURE AND “SURGICAL SITE INFECTION” OR SURGICAL INFECTION were included. Only randomized studies in English were included which amounted to five studies on surgical site infections. Funnel plots were used to assess the results.

Results:

Patients receiving probiotics before elective surgery had a lower occurence rate of surgical site infections. Of the 422 patients receiving probiotics before elective surgery, 92 (21.80%) patients had occurrence of infection compared to the 144 (32.58%) of 442 patients who did not receive any probiotic therapy.

Conclusion:

The administration of probiotics has a beneficial effect in terms of SSI incidence amongst patients undergoing elective surgeries by as much as 21.8% compared to those without probiotic therapy which was a 32.8% difference.

 

KEYWORDS: Surgical Site Infection, antibiotics, probiotics

 

INTRODUCTION | Back

Surgical Site Infections (SSIs) are defined as the infections of either in the surgical incision, or the organ, or the space, that occur after a surgical intervention. SSIs contribute to patient morbidity, mortality, and overall cost of treatment. 1 SSIs have been traditionally ascribed to improper techniques in infection control, e.g. inadequate preoperative asepsis-antisepsis technique, breaches in the sterile operative field, or transmission of contaminants or pathogens from the environment or the healthcare worker; this line of thinking reflects to the concept that complete decontamination will eliminate the possibility of SSIs.

Antibiotic prophylaxis is one of the measures used to prevent the possibility of SSIs. 2 However, poor management of antibiotic use runs the risk of antibiotic resistance; even short-term antibiotic use can lead to stabilization of resistant bacteria in the human intestinal microbiome that can persist for years. 3The human microbiota contributes to the overall host resistance to infection; the intestinal microbiota, in particular contribute tonic stimulation to local immune cells, resulting an increased drive in systemic immunity. The maintenance of the normal intestinal microbiota throughout the hospitalization period contributes in the prevention of life-threatening infections. 4Probiotics are live micro-organisms that, when ingested, are known to provide beneficial effects on the maintenance of normal intestinal barrier functions, lowering the risk of postoperative bacteremia, and hastening the return of normal gut function postoperatively. Multiple Randomized Controlled Trials (RCTs) have been done that have analyzed the effect of prophylactic probiotics in combination antibiotics. The objective of this systematic review is to analyze these RCTs and provide a summary of their applications. These are the objectives of the study:

  1. To compare the effects of the administration of probiotics in the prevention of SSIs
  2. To determine if the administration of probiotics in patients undergoing elective surgery would have a beneficial effect in terms of SSI incidence.

Surgical Site Infection

There are a number of measures recommended in terms of prevention of SSI. Antibiotics should be administered only when indicated based on clinical practice guidelines and timed so as to establish a bactericidal concentration is established in the serum and tissues at the time of incision. Topical antimicrobial agents should not be applied to the surgical incision for the prevention of SSI. Triclosan-coated sutures can be considered for the prevention of SSI. Blood glucose levels should be maintained below 200 mg/dL, whether or not the patient has diabetes mellitus. Perioperative normothermia and adequate volume status should be maintained in order to optimize tissue oxygen delivery. Patients are advised to bathe full-body with either an antimicrobial and non-antimicrobial agent at least the night before the operative.  Alcohol based antiseptic agents are recommended unless contraindicated. Antimicrobial plastic drapes have no role in SSI prevention. Intraoperative irrigation of deep or subcutaneous tissues with aqueous iodophor solution for the prevention of SSI can be considered. Intraperitoneal lavage with an aqueous iodophor solution in contaminated or dirty abdominal procedures is not necessary. 2 1

Probiotics

Probiotics are live bacteria that add to or replace lost beneficial bacteria that are normally present in the gastrointestinal tract. Probiotics come in many forms as food and dietary supplements; These products have a variety of bacteria at different concentrations with little standardization. The administration of pro-biotic bacteria promotes cytokine activation, releases factors that mediate inflammatory responses, and inhibits pathogenic bacterial strains competitively. Probiotics can inhibit bacterial translocation and adherence as well as stimulate epithelial growth, motility, and mucous secretion. There is also some evidence that they may enhance host immunity via stimulating immunoglobulin (IgA) and interleukin 8 (IL-8), which leads to migration of neutrophils to the mucosa and decreasing inflammatory cytokines. The administration of probiotic, prebiotic, and/or synbiotic therapies reduce POCs such as SSI, UTI, pneumonia, and sepsis. individual studies often failed to identify the best choice of probiotic, prebiotic, and synbiotic therapies to reduce POCs. 4


METHODOLOGY | Back

A systematic Literature Search of PubMed, Cochrane, and Google Scholar was done using a broad search string ((“PROBIOTICS” OR PROBIOTIC OR SYNBIOTIC) AND (OPERATION OR “SURGERY” OR SURGICAL PROCEDURE) AND (“SURGICAL SITE INFECTION” OR SURGICAL INFECTION)). Papers written in the English language, from 2000-2020 were included. The studies that were included in this review will be randomized controlled trials that deal with the administration of probiotics. RCTs were included if they satisfied the following criteria: the study population consisted of patients who will undergo elective surgery; the intervention group received prophylactic probiotics or synbiotics in combination to antibiotics preoperatively; the study included randomization to pro/synbiotic versus placebo/standard care. Studies that were non-randomized were excluded. The primary outcome was the incidence of SSI. All potential papers were selected for eligibility according to the criteria specified. The primary author conducted the search and review the trials. Data abstraction was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

The odds ratio (OR) was the primary measure of treatment effect or adverse events, and 95 per cent confidence intervals (CI) for OR will be calculated. Heterogeneity was assessed by Q-square (v2) and I-square statistics (I2). The I2 statistic indicated the percentage variability due to between-study or inter-study variability. An I2 value greater than 50 per cent was classified as a substantial presence of heterogeneity. Reporting bias was assessed by visual judgment of a funnel plot.

 

Figure 1. PRISMA flowchart used in the systematic review

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Study

Population

Number of patients

Probiotic Content

Probiotic Dosage

Duration of therapy

Control

Antibiotic Therapy

Outcome

Aisu, 2015

Patients who underwent elective colorectal surgery

156

Enterococcus faecalis T110/Clostridium butyricum TO-A/Bacillus mesentericus TO-A

2/10/10 mg per tablet, 6 tablets/day

3-15 days preoperatively

No intervention

1 g cefmetazole sodium 30 min. prior to the surgery, with
additional administration every 3 hours during the surgery

Incidence of SSIs up to 30 days after surgery

Flesch, 2017

Patients with
histologically proven colorectal adenocarcinoma with
indication of elective and potentially curative colorectal resection

91

Lactobacillus acidophilus NCFM,
Lactobacillus rhamnosus HN001,
Lactobacillus paracasei Lactobacillus
plantarum c-37, Bifidobacterium lactis
HN019; Prebiotic: FOS

109 per strain per 6 g sachet,
2 sachets twice a day

5 days preoperatively, 14 days postoperatively

Placebo (96% maltodextrin 100% (6g))

IV
gentamicin and metronidazole one hour before surgery

Incidence of SSIs up to 30 days after surgery

Komatsu, 2015

Patients scheduled to undergo elective laparoscopic
colorectal surgery

362

Lactobacillus casei Strain
Shirota; Prebiotic: GOS,
Bifidobacterium breve Strain Yakult

4 × 1010 per 80 mL bottle,
2.5 g, 1 ×
1010 per 100 mL bottle, one bottle each, once a day

7-11 days preoperatively, 6 days postoperatively

No intervention

IV cephalosporin within 1 hour before operation.

Incidence of SSIs up to 30 days after surgery

Sadahiro, 2014

Patients scheduled to undergo elective colon cancer operations between May 2008 and October
2011, in whom curative resection was
considered feasible

195

Bifidobacterium bifidum; Prebiotic:
multooligossacharide

1 × 109 per tablet, 3 tablets thrice a day

7 days preoperatively, 11 days postoperatively

No intervention

IV 1g
infusion of flomoxef 1 hour before incision, with additional administration of 1g flomoxef if OR time exceeded 3 hours

Incidence of SSIs up to 30 days after surgery

Zhang, 2012

Patients diagnosed
with pathologically documented colorectal adenocarcinoma
and intended to undergo elective radical CRC resection with
laparotomy

60

Bifidobacterium longum, Lactobacillus
acidophilus, Enterococcus faecalis

0.21 g (108
CFU/g) per capsule, 3 capsules thrice a day

3 days preoperatively

Placebo

IV 3g cefuroxime prior to infusion

Incidence of SSIs during the entire postoperative hospitalization period

 

 

 

Characteristics of the randomized controlled trials included in the study

RESULTS | Back

Five (5) randomized controlled trials were included in this study, all of which dealt with the occurrence of surgical site infections among patients receiving probiotics before elective surgery. 864 cases were included.

For the analysis of rate of surgical site infections, patients receiving probiotics before elective surgery had a lower occurence rate. Of the 422 patients receiving probiotics before elective surgery, 92 (21.80%) patients had occurrence of surgical site infection, compared to the 144 (32.58%) of 442 patients who did not receive probiotic therapy. Heterogeneity was at 52%; fixed effects was used, with an overall odds ratio of 0.58 (95% Confidence Interval, 0.42, 0.80, p = 0.0009). The funnel plot for the primary outcome of Surgical Site Infection revealed no apparent asymmetry.

Table 1. List of Included Studies

Author

Year

Country

Number of Patients

Study design

Aisu

2015

Japan

156

RCT

Flesch

2017

Brazil

91

RCT

Komatsu

2015

Japan

379

RCT

Sadahiro

2014

Japan

310

RCT

Zhang

2012

China

60

RCT

Table 2. Surgical Site Infection occurrence among patients subjected to probiotic nutritional adjuncts

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Figure 1. Funnel plot of prophylactic probiotics in combination with antibiotics group versus antibiotics alone for prevention of surgical site infection

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DISCUSSION: | Back

Surgical Site Infections still remain as a significant problem, leading to extended hospital stay, increased admission cost, and reduced quality of patient life. Alongside the implementation of effective infection prevention practices, the administration of probiotics with or without prebiotics may be a good choice of agents to prevent SSIs in postoperative surgical patients. 1 2 5
All of the RCTs dealt with the administration of probiotics in patients undergoing elective colorectal surgery. The study by Aisu et al. in 2015 demonstrated that patients receiving probiotics had a lower incidence of SSIs (10.29 %) as compared to the control group (32.79%). They concluded that the administration of probiotics induced a decrease in superficial incisional SSI incidence and an increase in CD4+ ATP activity. Probiotic administration therefore appears to result in the perioperative enhancement of the host immune function. 5

The study by Flesch et al. in 2017 demonstrated that patients receiving probiotic therapy also had a lower SSI incidence (2.08 %) compared to the control group (27.27%); they concluded that the perioperative administration of symbiotics in patients submitted to elective surgery for colorectal cancer significantly reduced the rates of postoperative infection. 6

The study by Komatsu et al. in 2015 demonstrated that patients receiving probiotics had a 57.01% SSI incidence rate versus the 84.76% incidence rate of the control group; however the authors claimed that their findings cannot be regarded as clinically relevant from a surgical point of view. The authors also claimed that a possibility of type 2 error cannot be excluded in their study. 7

The study by Sadahiro et al. in 2014 demonstrated that patients receiving probiotics had a 28.20% SSI incidence rate versus the 30.13% SSI rate in the control group; the study concluded that the preventive effect of probiotics on SSI incidences could not be confirmed. 8

The study by Zhang et al. in 2012 demonstrated that patients receiving probiotics had a 3.45% SSI incidence rate compared to the 15.38% SSI incidence rate in the control group; the study concluded that preoperative oral bifid triple viable probiotics could minimize the postoperative occurrence of infectious complications possibly because of their inhibitory effects on intestinal overgrowth of E coli. The study also claimed that the administration of probiotics maintained microbial colonization resistance and restricted bacterial translocation from the intestine, concluding that it was a result of the enhancement of systemic/ localized immunity and concurrent attenuation of systemic stress response. 9

It has been demonstrated that probiotics can improve the intestinal microbial environment and activate host immune function, leading to the prevention of infectious complications; Modulation of the intestinal microbiota by probiotic microorganisms occurs through a mechanism called “competitive exclusion.” 10

Perioperative administration of probiotics can reinforce the immune function of the host and increase the resistance to infections, leading to a reduction in the incidence of superficial incisional SSI. Furthermore, since the perioperative administration of probiotics reduced the postoperative inflammatory response, it could lead to a decrease in the length of the hospital stay. The present results suggest that systemic inflammatory responses can be favorably modified by probiotics. 10 11

This systematic review presents with a number of limitations. This review did not expound on the benefitis of each specific strain that was used. The RCTs used in this review differed in terms of probiotic strains used; some RCTs added a prebiotic in the form of galactooligosaccharides or fructooligosaccharides; some RCTs only gave probiotics preoperatively whilst others chose to administer probiotics preoperatively and postoperatively. The duration of the prebiotic administration varies from one RCT to another. Different preoperative antibiotics were also used; it was not within the scope to this review to factor in the type of antibiotics given preoperatively. Other factors that were also not accounted for were the OR time, blood loss, the presence of comorbidities, and BMI.


CONCLUSION: | Back

The administration of probiotics has a beneficial effect in terms of Surgical Site Infection incidence amongst patients undergoing elective surgeries by as much as 21.8%. Compared to those without probiotic therapy there was a 32.8% difference. Further studies are needed to draw detailed protocols to evaluate particular probiotic strains and optimal duration of their supplementation in patients undergoing surgical procedures.

 

REFERENCES: | Back

1. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surgery. 2017;152(8).

2. Ban KA, Minei JP, Laronga C, et al. American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg. 2017;224:59-74.

3. Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 2010;156:3216–3223.

4. Guyton K, Alverdy JC. The gut microbiota and gastrointestinal surgery. Nat Rev Gastroenterol Hepatol. 2017;14(1):43-54.

5. Aisu N, Tanimura S, Yamashita Y, et al. Impact of perioperative probiotic treatment for surgical site infections in patients with colorectal cancer. Experimental and Therapeutic Medicine. 2014;10:966-972.

6. Flesch A, Tonial S, Contu P, Damin D. Perioperative synbiotics administration decreases postoperative infections in patients with colorectal cancer: a randomized, double-blind clinical trial. Rev Col Bras Cir. 2017;44(6):567-573.

7. Komatsu S, Sakamoto E, Norimizu S, et al. Efficacy of perioperative synbiotics treatment for the prevention of surgical site infection after laparoscopic colorectal surgery: a randomized controlled trial. Surg Today. 2016;46(4):479-490.

8. Sadahiro S, Suzuki T, Tanaka A, et al. Comparison between oral antibiotics and probiotics as bowel preparation for elective colon cancer surgery to prevent infection: Prospective randomized trial. Surgery. 2014;155(3):493-503.

9. Zhang J, Du P, Gao J, Yang B, Fang W, Ying C. Preoperative Probiotics Decrease Postoperative Infectious Complications of Colorectal Cancer. Am J Med Sci. 2012;343(3):199-205.

10. Yang Y, Xia Y, Chen H, et al. The effect of perioperative probiotics treatment for colorectal cancer: short-term outcomes of a randomized controlled trial. Oncotarget. 2016 ;7(7):8432-8440.

11. Wu XD, Xu W, Liu MM, et al. Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials. J Surg Oncol. 2018;117(7):1394-1404.

12. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Medicine. 2009;6(7).

13. Siddharthan R, Chapek M, Warren M, Martindale R. Probiotics in Prevention of Surgical Site Infections. Surg Infect (Larchmt). 2018;19(8):781-784.

14. Reddy BS, MacFie J, Gatt M, Larsen CN, Jensen SS, Leser TD. Randomized clinical trial of effect of synbiotics, neomycin and mechanical bowel preparation on intestinal barrier function in patients undergoing colectomy. British Journal of Surgery. 2007;94:546-554.

 

 

Abstract | Introduction | Methodology | Results | Discussion | References | Back to Total Name and Codes page2