Mini-CAT Spring 2018

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PICO Search Assignment Worksheet                    Name____________________


Brief description of patient problem/setting (summarize the case very briefly)


67 yo F with PMH of C-section, HTN, HLD undergoes laparoscopic cholecystectomy after presenting with mild leukocytosis, persistent RUQ pain and N/V. During the prior to the surgery the patient is wondering if prophylactic antibiotics would help reduce inflammation and infection post-surgery.


Search Question (including outcomes or criteria to be tracked)


Does prophylactic antibiotics prevent/ reduce post-operative infection in patients undergoing laparoscopic cholecystectomy?


What kind of question is this? (boxes now checkable in Word)


☐Prevalence              ☐Screening                ☐Diagnosis

☒Prognosis                ☒Treatment               ☒Harms



PICO search terms


Laparoscopic cholecystectomy Prophylactic antibiotics No Antibiotic Risk post-operative infection
Elective cholecystectomy prophylactic intravenous antibiotics Placebo Hospital duration
Adult Preventative Antibiotics   Risk of surgical site infection
Gallbladder removal     Mortality
Laparoscopy     Incidence of abdominal infection


Search tools and strategy used:

[Please indicate what data bases/tools you used, provide a list of the terms you searched together in each tool, and how many articles were returned using those terms]:



Initial search terms : “antibiotic cholecystectomy” – 1033 results

Limited search terms – 5 years- 209 results

Search terms:  “ prophylactic antibiotics laparoscopic cholecystectomy” – 54 results

Limited search terms – 5 years — 16 results

Limit search terms – systematic review, meta-analysis –6 results



Initial searched terms “cholecystectomy” – 168  results

Filters applied- prophylactic antibiotics —  2 results


TRIP database

Initial searched terms-“ prophylactic antibiotics laparoscopic cholecystectomy” – 4089 results

Filters applied-Systematic review and randomized control trial – 5 results

Google Scholar

Initial Search term: “Prophylactic antibiotic cholecystectomy” -17,500 results

Filter applied: Since 2018 -588 results



Initial Search term “Cholecystectomy” – 2910 results

Filters applied “ prophylactic antibiotic” – 530 results

Years- 2018 (9), 2017 (28) , 2016 (20)


Articles Chosen (3-5) for Inclusion (please copy and paste the abstract with link):

Please pay attention to whether the articles actually address your question and whether they are the highest level of evidence available.  If you cannot find high quality articles, be prepared to explain the extensiveness of your search and why there aren’t any better sources available. 



  1. Sanabria A, Dominguez LC, Valdivieso E, Gomez G. Antibiotic prophylaxis for patients undergoing elective laparoscopic cholecystectomy. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No.: CD005265. DOI: 10.1002/14651858.CD005265.pub2.





Cholecystectomy is a common surgical procedure. In the open cholecystectomy area, antibiotic prophylaxis showed beneficial effects, but it is not known if its benefits and harms are similar in laparoscopic cholecystectomy. Some clinical trials suggest that antibiotic prophylaxis may not be necessary in laparoscopic cholecystectomy.



To assess the beneficial and harmful effects of antibiotic prophylaxis versus placebo or no prophylaxis for patients undergoing elective laparoscopic cholecystectomy.


Search methods

We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2010), MEDLINE (1985 to August 2010), EMBASE (1985 to August 2010), SCI-EXPANDED (1985 to August 2010), LILACS (1988 to August 2010) as well as reference lists of relevant articles.


Selection criteria

Randomised clinical trials comparing antibiotic prophylaxis versus placebo or no prophylaxis in patients undergoing elective laparoscopic cholecystectomy.


Data collection and analysis

Our outcome measures were all-cause mortality, surgical site infections, extra-abdominal infections, adverse events, and quality of life. All outcome measures were confined to within hospitalisation or 30 days after discharge. We summarised the outcome measures by reporting odds ratios and 95% confidence intervals (CI), using both the fixed-effect and the random-effects models.


Main results

We included eleven randomised clinical trials with 1664 participants who were mostly at low anaesthetic risk, low frequency of co-morbidities, low risk of conversion to open surgery, and low risk of infectious complications. None of the trials had low risk of bias. We found no statistically significant differences between antibiotic prophylaxis and no prophylaxis in the proportion of surgical site infections (odds ratio (OR) 0.87, 95% CI 0.49 to 1.54) or extra-abdominal infections (OR 0.77, 95% CI 0.41 to 1.46). Heterogeneity was not statistically significant.


Authors’ conclusions

This systematic review shows that there is not sufficient evidence to support or refute the use of antibiotic prophylaxis to reduce surgical site infection and global infections in patients with low risk of anaesthetic complications, co-morbidities, conversion to open surgery, and infectious complications, and undergoing elective laparoscopic cholecystectomy. Larger randomised clinical trials with intention-to-treat analysis and patients also at high risk of conversion to open surgery are needed.



  1. Prophylactic antibiotics at the time of elective cholecystectomy are effective in reducing the post-operative infective complications: a systematic review and meta-analysis.

Sajid MS, Bovis J, Rehman S, Singh KK.

Transl Gastroenterol Hepatol. 2018 Apr 28;3:22. doi: 10.21037/tgh.2018.04.06. eCollection 2018.

PMID: 29780900





The objective of this article is to evaluate the role of prophylactic antibiotics in preventing the infective complications in patients undergoing elective laparoscopic cholecystectomy (ELC).



A systematic review of the literature on the published randomized, controlled reporting the role of prophylactic antibiotics in preventing the infective complications in patients undergoing ELC was undertaken using the principles of meta-analysis.



Twenty-five RCTs on 6,138 patients evaluating the infective complications in patients undergoing ELC were systematically analysed. There were 3,099 patients in antibiotics group and 3,039 patients in no-antibiotics group. The risk of surgical site infection (SSI) [odds ratio (OR), 0.75 (95% CI, 0.52-1.07), P=0.11], distant infection [OR, 0.66 (95% CI, 0.21-2.14), P=0.49] and residual abscess [OR, 0.93 (95% CI, 0.23-3.81), P=0.92] was lower in the antibiotics group but statistical significance was not reached. However, the risk of overall all type of infective complications was statistically lower [OR, 0.69 (95% CI, 0.50-0.95), P=0.02] in the antibiotics group. Subsequently, this was reflected into the reduced length of hospitalization [standardized mean difference (SMD), -0.32 (95% CI, -0.54–0.10), P=0.004] in the antibiotics group.



Use of prophylactic antibiotics at the time of induction in patients undergoing ELC has clinically proven advantage of reducing the post-operative infective complications.


  1. Reappraisal of previously reported meta-analyses on antibiotic prophylaxis for low-risk laparoscopic cholecystectomy: an overview of systematic reviews.

Matsui Y, Satoi S, Hirooka S, Kosaka H, Kawaura T, Kitawaki T.

BMJ Open. 2018 Mar 16;8(3):e016666. doi: 10.1136/bmjopen-2017-016666.

PMID: 29549197





Many researchers have addressed overdosage and inappropriate use of antibiotics. Many meta-analyses have investigated antibiotic prophylaxis for low-risk laparoscopic cholecystectomy with the aim of reducing unnecessary antibiotic use. Most of these meta-analyses have concluded that prophylactic antibiotics are not required for low-risk laparoscopic cholecystectomies. This study aimed to assess the validity of this conclusion by systematically reviewing these meta-analyses.



A systematic review was undertaken. Searches were limited to meta-analyses and systematic reviews. PubMed and Cochrane Library electronic databases were searched from inception until March 2016 using the following keyword combinations: ‘antibiotic prophylaxis’, ‘laparoscopic cholecystectomy’ and ‘systematic review or meta-analysis’. Two independent reviewers selected meta-analyses or systematic reviews evaluating prophylactic antibiotics for laparoscopic cholecystectomy. All of the randomised controlled trials (RCTs) analysed in these meta-analyses were also reviewed.



Seven meta-analyses regarding prophylactic antibiotics for low-risk laparoscopic cholecystectomy that had examined a total of 28 RCTs were included. Review of these meta-analyses revealed 48 miscounts of the number of outcomes. Six RCTs were inappropriate for the meta-analyses; one targeted patients with acute cholecystitis, another measured inappropriate outcomes, the original source of a third was not found and the study protocols of the remaining three were not appropriate for the meta-analyses. After correcting the above miscounts and excluding the six inappropriate RCTs, pooled risk ratios (RRs) were recalculated. These showed that, contrary to what had previously been concluded, antibiotics significantly reduced the risk of postoperative infections. The rates of surgical site, distant and overall infections were all significantly reduced by antibiotic administration (RR (95% CI); 0.71 (0.51 to 0.99), 0.37 (0.19 to 0.73), 0.50 (0.34 to 0.75), respectively).



Prophylactic antibiotics reduce the incidence of postoperative infections after elective laparoscopic cholecystectomy.

  1. Antibiotic Prophylaxis in Elective Laparoscopic Cholecystectomy: a Systematic Review and Network Meta-Analysis

Gomez-Ospina, J.C., Zapata-Copete, J.A., Bejarano, M. et al. J Gastrointest Surg (2018) 22: 1193.



To determine the effectiveness and harms of using antibiotic prophylaxis (ABP) versus placebo/no intervention in patients undergoing elective laparoscopic cholecystectomy (eLCC) to prevent surgical site infection (SSI).



We searched MEDLINE (OVID), EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to October 2017. We included clinical trials which involved adults at low risk undergoing eLCC and compared ABP versus placebo/no intervention. The primary outcome was SSI and secondary outcomes were other infections and adverse effects. Cochrane Collaboration tool was used to assess the risk of bias. We performed the statistical analysis in R and reported information about risk difference (RD) with a 95% confidence interval (CI). Heterogeneity was evaluated using the I2 test. We produced network diagrams to show the amount of evidence available for each outcome and the most frequent comparison.



We included 18 studies in qualitative and quantitative analysis. The antibiotics most commonly studied were cefazolin and cefuroxime. We found high risk of detection bias in one study and attrition bias in another. Unclear risks of selection, performance, and detection bias were frequent. For SSI, we found no heterogeneity I2 = 0% and no inconsistency p = 0.9780. No significant differences were found when compared ABP versus placebo/no intervention. Cefazolin had a RD of − 0.00 (95% CI − 0.01 to 0.01). We found no differences in regular meta-analysis, with a RD of − 0.00 (95% CI − 0.01 to 0.01) as well as for intra-abdominal and distant infections. Adverse effects were only assessed in one study, without any case reported.



This systematic review demonstrated no differences between ABP versus placebo/no intervention when using to prevent SSI and intra-abdominal and distant infections in patients at low risk undergoing eLCC.




Author (Date) Level of Evidence Sample/Setting

(# of subjects/ studies, cohort definition etc. )

Outcome(s) studied Key Findings Limitations/Bases
Article #1:

Sanabria (2010)

Low-Moderate Systematic Review of RCTs 11 RCTs studies

1664 participants

adult patients >17 years old, undergoing laparoscopic cholecystectomy with preoperative clinical diagnosis of cholelithiasis without acute cholecystitis or other benign non-acute inflammatory disease of the gallbladder.



Jaundiced patients

Primary outcome:

-Assess the beneficial and harmful effect of antibiotics in patients undergoing laproscopic cholecystectomy


– All-cause mortality


-Surgical Site infection (defined by CDC )

– Extra-abdominal infection (defined by CDC)


-Adverse events(defined as allergic reaction to antibiotics


-Quality of life

-In 11 trials, 900 in the prophylaxis group and 764 in the no-prophylaxis group.

Rate of conversion to open surgery was from 2.4 % to 8.4%

All-cause mortality

Mortality was not reported in any of the trials.

Surgical Site Intervention:

Prophylaxis group: 24 of 900 (2.7%) had a surgical site infection

No-prophylaxis group: 25 of 764 (3.3%).

OR was 0.87, 95% CI (0.49 to 1.54).

No statistically significant differences or heterogeneity were observed

Extra-abdominal infection:

Seven trial reported infectious events different from surgical site infection

Prophylaxis group: 7 of 657 (1.0%) patients

No-Prophylaxis: 22 of 531 (1.8%)

OR was 0.66 (95% CI 0.25 to 1.74). No statistically significant differences or heterogeneity were observed

Adverse events

Information about adverse events was not given in any of the trials.

Quality of life

None of the trials reported on the quality of life.

Conductance of more clinical trials with low risk of bias must be considered in order to increase the sample size and to surpass methodological weaknesses.


Risk of bias criteria were not clearly reported, we cannot be sure that bias did not have an effect in the trials.


Assess individual risk of the patients


Lack of intention-to-treat analysis in all but one of the analysed trials. This is important to stress because trials with no intention-to- treat analyses tend to produce misleading results

Article #2:

Sajid (2016)

Systematic Review and Meta-analysis -25 RCT


-6,138 patients


-3,099 patients in antibiotics group -3,039 patients in no-antibiotics group


Patients: all patients with cholecystitis, cholelithiasis, gallstones.

❖ Intervention/comparator: intravenous antibiotics at the time of induction.

❖ Outcomes: length of stay in hospital, all infective complications, superficial SSI, deep SSI, distant infections and deep space infection.

Primary outcome:

-adverse effects


-postoperative infective



-Superficial and deep wound


-Distant infection


-Duration of hospital stay

postoperative infective complication

random effects model analysis (OR, 0.69; 95% CI, 0.50–0.95; Z=2.27; P=0.02), the risk of developing postoperative infective complications was statistically lower in patients receiving prophylactic antibiotics

-Superficial and deep wound

Random effects model analysis (OR, 0.75; 95% CI, 0.52–1.07; Z=1.61; P=0.11), the risk of developing superficial and deep wound SSI was lower in antibiotics group but it could not reach the statistical significance

Distant Infection

In the random effects model analysis (OR, 0.66; 95% CI, 0.21–2.14; Z=0.68; P=0.49), the risk of developing distant infections was lower in antibiotics group but it could not reach the statistical significance

Hospital Duration:

OR, −0.32; 95% CI, −0.54–−0.10; Z=2.85; P=0.004), the duration of hospital stay was statistically shorter in patients who received prophylactic antibiotic

Confounding factors which might have influenced the final outcome of the postoperative infective complications include the use of variable number and size of ports for ELC; type, duration and dosage of antibiotics; use of extraction endo-bag at surgeons’ discretion; and use of placebo versus no-placebo in non-antibiotics group.
Article #3:

Matusi (2018)

Systematic Review and Meta-analysis -7 meta-analysis that encompassed 28 RCT


-7065 patients,


– postoperative infective complication


-Superficial and deep wound


-Distant infection

Surgical Site Infection (Distant and overall infection:

(RR (95% CI); 0.71 (0.51 to 0.99), 0.37 (0.19 to 0.73), 0.50 (0.34 to 0.75), respectively).

Administration of prophylactic antibiotics to patients undergoing low-risk cholecystectomy is not recommended because of the modest risk of developing an SSI and healthcare costs.

There is little evidence regarding reducing medical costs and microbial resistance by eliminating antibiotic prophylaxis.

One limitation of this study is such ‘super-analysis of analyses’ is also open to bias and error because, even in a ‘super-analysis’, it is impossible to completely remove all bias inherent in the assessed meta-analyses and in their original RCTs.


RCTs included in these meta-analyses were performed in many countries with different life environments and health care systems, drawing definitive conclusions about the effects of antibiotic prophylaxis is problematic

Article #4:

Gomez-Ospina (2018)

Systematic Review  and Network  Meta-Analysis -18 qualitative and quantitative analysis

-4087 patients with a mean of 227 patients per study


Preoperative diagnosis of cholelithiasis or other benign diseases of the gallbladder


Should include at least 1-week follow-up.



pregnant or breast-feeding women, antibiotic allergy, antibiotic therapy within 48 h to 7 days prior to surgery, clinically active infection at the moment of surgery, and evidence or suspicion of common bile duct stones

Primary Outcome

– Surgical site infection (SSI) defined as CDC and Prevention’s National Healthcare Safety Network classification


Secondary Outcome

– distant infection (defined as any infection remote from the surgical site)


-Intra-abdominal infection (affecting intra-abdominal organs, peritonitis, or intra-abdominal abscesses)


-Adverse effects

Most Common antibiotics used in the study was cefazolin and cefuroxime. Other abx include: ciprofloxacin, cefotetan, ceftazidime, cefotazime, ceftriaxone, ampicillin-sulbactam/


Placebo was use in 11 studies and no antibiotics in 7 studies, n=1967 (control group)


Surgical Site infection:

No significant differences for mixed comparisons. ABP versus placebo/no intervention; 2122 and 1967 patients were included in each branch, respectively; we found no differences, with a RD of − 0.00 (95% CI − 0.01 to 0.01).


Intrabdominal Infection

no significant differences for mixed comparisons when cefazolin, cefotaxime, ceftriaxone, and cefuroxime were each compared versus placebo for intra-abdominal infection

Distant infection

no significant differences for mixed comparisons when cefazolin, cefotaxime, ceftriaxone, and cefuroxime were each compared versus placebo for distant infection


Adverse effects were only assessed in one study, without any case reported.

-High risk of detection bias in 1 study, High risk of attrition bias in 1 study.


adverse effects in the studies included in their meta-analysis were poorly reported


Cholecystectomy is the most common abdominal surgical procedure that performed in the US and other developed countries. About 90% of cholecystectomies performed are performed laparoscopically in the US and is considered the gold standard for surgical treatment of gallstone disease. Laparoscopic procedure provides less postoperative pain, better cosmesis, and shorter hospital stays. Laparoscopic Cholecystectomy is indicated in patients who have symptomatic cholelithiasis (with or without complications), asymptomatic cholelithiasis, acalculous cholecystitis, gallbladder polyps, and porcelain gallbladder. When preparing for this procedure, literature indicated controversy of initiating prophylactic antibiotics especially in patients undergoing elective procedure with low risk for infection.

Matsui et al and Sajjid et al demonstrated that the use of prophylactic antibiotics reduced surgical site infection (SSI) and decreased hospitalization, reduced costs. Sanabria et al, indicated that prophylactic antibiotics did reduce post-operative infection and surgical site infection; however, the reduction is statistically negligible. Furthermore, the article reported 1% of the prophylactic group and 1.8% of the non-prophylactic group had a extra-abdominal infection. This study does not refute that prophylactic antibiotics reduces the risk of infection. Gomez-Ospina et al found that there no significant difference in surgical site infection, distant infection and intraabdominal infection and thus, concluded that patient  do not require antibiotic prophylaxis for surgical intervention to prevent infection. All the studies indicated no adverse events from use of prophylactic antibiotics.


Clinical bottom line:

Based off evidence from the articles, it is important to understand the role of antibiotics in the management of post-operative laparoscopic cholecystectomy. Literature has been shifting toward considering antibiotic prophylaxis unnecessary in patients with elective cholecystectomy and low risk of infection. This is since surgical site infection following laparoscopic procedure in comparison to an open procedure is relatively low. According to UptoDate, infection rates in laparoscopic procedure is 0 – 4% without antimicrobial prophylaxis and 0-7% with prophylaxis. Furthermore, global campaign to reduce inappropriate use of antibiotics administration to decrease microbial resistance. Matusi et al stated that microbial resistance may be caused by administering large amounts of therapeutic antibiotics for long period of time rather than a short course of prophylactic antibiotic. Thus, the use of prophylactic antibiotic can prevent post-operative infection by reducing antibiotics post-operatively. In the clinical setting, hospitals tend to practice “defensive medicine” to help cover all basis and protect the provider. Therefore, many surgeons will administer antibiotic prophylaxis to make sure that the possibility of infection is reduced. Furthermore, it important to be aware of the confounding factors in laparoscopic surgeries such as use of variable number and size of ports for ELC; type, duration and dosage of antibiotics; use of extraction endo-bag at surgeons’ discretion which, might have influenced the final outcome of the postoperative infective complications. My patient may benefit from prophylactic antibiotics due to her presentation prior to elective cholecystectomy and reduce her hospitalization.