Iranian Journal of Clinical Infectious Diseases

2010;5(1):3-8 ORIGINAL ARTICLE

©2010 IDTMRC, Infectious Diseases and Tropical Medicine Research Center

Infections after laparoscopic and open cholecystectomy: ceftriaxone

versus placebo; a double blind randomized clinical trial
Mohammad Mozafar*, Mohammad Reza Sobhiyeh, Leili Hafezi Moghadam
Cancer Research Center, Shahid Beheshti University, M.C., Tehran, Iran

ABSTRACT
Background: Gallstone disease is one of the most common gastrointestinal diseases requiring surgery with probable
postoperative infection. The role of prophylactic antibiotics (AB) in prevention of infection is controversial. This study
aimed to compare the manifestations, complications and outcomes of two groups of patients, those receiving
prophylactic AB versus placebo, in order to determine whether antibiotic therapy is required.
Patients and methods: In this double blind randomized clinical trial, we studied 130 patients with symptomatic
cholelithiasis or polyps of gallbladder admitted in Shohada-e-Tajrish Hospital, Tehran, Iran for cholecystectomy
between 2006 and 2008. Patients were randomly assigned in two subgroups: the first group received 1gr ceftriaxone
during induction of anesthesia and the second group received 10mL of isotonic sodium chlorides solution as placebo. All
patients were followed for 4 weeks after surgery.
Results: The study population included 61 males and 69 females with the mean age of 49.3±9.6 and 51.8±9.9 years in
treatment and placebo group, respectively. Of 130 bile culture results, 83 were negative. Escherichia coli, Klebsiella and
Staphylococcus aureus were the most common cultured bacteria. There was no statistically significant difference in
culture results between the patients received AB and placebo (NS). The surgical technique (open versus laparoscopic)
did not influence the culture results.
Conclusion: It can be concluded that prophylactic antibiotics do not have any preventive effect on wound infection in a
double blind setting. According to our findings, routine antibiotic prophylaxis as recommended for biliary surgery (open
or laparoscopic cholecystectomy) is now questionable.

Keywords: Antibiotic, Cholecystectomy, Infection, Prophylaxis.

(Iranian Journal of Clinical Infectious Diseases 2010;5(1):3-8).

INTRODUCTION
1
Gallstone disease is one of the most common gallstones (1-5). Cholecystectomy is one of the
gastrointestinal conditions requiring surgery. In the most common treatments of gallbladder disease,
United States about 750,000 patients (10% of adult which can be performed by either an open or
population) experience cholelithiasis and 500,000 laparoscopic approach. It is also one of the main
cholecystectomies are performed annually. In causes of surgical site infection (SSI) (4-11).
Europe, 18.8% of women and 9.5% of men have Compared to open cholecystectomy (OC),
laparoscopic cholecystectomy (LC) results in less
Received: 17 August 2009 Accepted: 29 December 2009 pain, lower rates of nosocomial infection and SSI,
Reprint or Correspondence: Mohammad Mozafar, MD. shorter surgery time and hospital stay, reduced
Department of General Surgery, Shohada-e-Tajrish Hospital,
Tajrish Square, Tehran, Iran. treatment costs, and a markedly lower death rate
E-mail: [email protected]

Iranian Journal of Clinical Infectious Disease 2010;5(1):3-8

4 Antibiotic therapy in cholecystectomy

but higher rates of gallbladder and common bile following signs; abdominal pain in the upper right
duct injuries and 3-5% conversion rate to open quadrant, Murphy’s sign, leukocytosis
surgery. It has also been suggested that longer time >10000/mm³, and rectal temperature >38°C or
between diagnoses and treatment increases the risk <36.5°C as well as cholecystolithiasis
of having complications (12-16). (stones/sludge) or sonographic signs of
Main complications of LC are major bleeding, cholecystitis (thickening and triple layer formation
wound infection, and biliary leakage or injury of the gall bladder wall) were included. Pregnant
which is mostly seen in developing countries (11, women, patients with jaundice at the time of
17-19). Surgeons' experience and patient selection diagnosis, coagulopathy, coledocholithiasis, portal
are important determinants for complications (20). hypertension, diabetes mellitus,
Among surgical patients, SSIs account for 38% immunosuppressive disorders, previous biliary
of nosocomial infections. It is estimated that SSIs surgery, biliary pancreatitis, history of antibiotic
develop in 2 to 5 percent of more than 30 million consumption within one week prior to surgery,
patients undergoing surgical procedures annually allergic reaction/anaphylaxis to penicillin or
(2,11,17). Age, wound classes 3 and 4, ASA cephalosporins, any acute emergency interventions,
(American Society of Anesthesiology) score 3,4 any contraindications for LC (previous history of
and 5, surgery duration of >2 hours and complexity abdominal surgery, choledocolithiasis),conversion
of surgery are main risk factors for SSI which can from LC to OC and patients who did not agree with
be reduced by minimally invasive procedures terms of study were excluded.
including LC (21,22). Although bile cultures are Having explained surgical methods and study
positive for bacteria in 50-75% of cases, bacterial protocol, patients were assigned in two groups by a
proliferation may be a result of cholecystitis and table of random numbers among the patients' name
not the precipitating factor but this matter is not list. First group received 1gr ceftriaxone during
clearly established (23). induction of anesthesia and the second group
This double blind randomized trial was received 10ml of isotonic sodium chlorides
conducted to compare the manifestations, solution as placebo. Laboratory tests (complete
complications and outcomes of cholecystectomy in blood count/diff, aspartate and alanine
two groups of patients, those who received AB and aminotranferase, serum billirubin, and alkaline
the other group that received placebo. Both groups phosphatase) were checked before surgery. All
were subdivided into two subgroups based on surgeries were performed with the same surgical
surgical technique (OC and LC). The ultimate goal team who were expert in both approaches. In each
of this study was to evaluate the role of bile group patients were randomly divided into two
infection in SSI and determine whether antibiotic subgroups: Group A underwent OC and group B
therapy is needed in patients with gallstone. had LC. None of the patients received extra dosage
of antibiotics (AB) during or after surgery. Both
patients and questioners were blind to surgical
PATIENTS and METHODS approach and administered drugs.
In this randomized clinical trial, 196 patients In OC, we removed the gall bladder after right
with symptomatic cholelithiasis or polyps of subcostal incision. In patients with previous history
gallbladder admitted in Shohada-e-Tajrish of icter, liver function tests elevation and serum
Hospital, Tehran, Iran for cholecystectomy amylase or common bile duct diameter >10mm,
between 2006 and 2008, were studied. Patients common bile duct exploration and T-tube drainage
with acute cholecystitis based on three of the was achieved. LC was performed by Angelo-

Iranian Journal of Clinical Infectious Disease 2010;5(1):3-8

 Mozafar M. et al 5

American method with reusable tools. Gall bladder Table 1. Demographic and disease characteristics of
was dissected with electro cauterization. No routine patients undergoing open/laparoscopic cholecystectomy
with/without prophylactic antibiotic
interaoperative cholangiography was performed OC(n=63) LC(n=67)
during laparoscopy. Bile secretion was cultured in AB Placebo AB Placebo
Characteristics* (n=32) (n=31) (n=34) (n=33)
all patients.
Age (yr) 49.2 51.9 49.3 51.6
We followed all patients for four weeks after Sex
surgery. The bile culture results were compared Female 17(27) 17(27) 18(26.9) 17(25.3)
between groups. In cases with wound infection we Male 15(23.8) 14 (22.2) 16 (23.9) 16 (23.9)
Body weight (kg) 62.3 62.1 62.6 62.2
compared the site of surgery and infection, class of Gallstone 24 20 23 21
infection and treatment. Data were analyzed using Gallbladder polyp 8 11 11 12
ASA score
SPSS (version 16.0, Chicago, Illinois, USA). T- 1 16 14 17 15
test, chi square, and Fisher's exact test were used, 2 12 12 13 13
3 4 5 5 5
when appropriate. P values less than 0.05 were
Cholecystitis
considered significant. Acute 8 7 9 8
Chronic 17 14 19 16
Empyema 5 6 4 6
2 4 2 3
RESULTS Hydropse
OC: open cholecystectomy; LC: laparoscopic cholecystectomy;
Totally, 196 patients enrolled of whom 66 were AB: antibiotic; ASA: American Society of Anesthesiology
* No statistically significant difference was noted between groups.
excluded. Of 130 studied patients, 66 received
prophylactic antibiotic and 64 received placebo.
Table 2. Complications and outcome of surgery in
Meanwhile, 32 patients of treatment group and 31 patients undergoing open/laparoscopic cholecystectomy
of placebo group underwent OC. with/without prophylactic antibiotic
OC(n=63) LC(n=67)
The study population included 61 males and 69
AB Placebo AB Placebo
females with the mean age of 49.3±9.6 and Complications* (n=32) (n=31) (n=34) (n=33)
51.8±9.9 years in treatment and placebo group, Infected bile 11 12 12 13
Intraoperative rupture 8 6 9 7
respectively. Female to male ratio in the treatment of gallbladder
Spillage of bile/ 7 6 8 6
and placebo group was 35/31 and 34/30, gallstone
respectively. Table 1 represents the demographic Subhepatic drain 5 4 6 5
Surgical site infection
features of patients of both groups. As shown, ASA Subhepatic fluid 1 0 1 0
score, body weight, duration of surgery, surgical Infection of incision 0 1 1 1
Operation time (min) 71.4 72.7 69.3 68.4
complications (rupture of bladder, bile or stone Hospital stay (day) 3.46 3.53 4.54 3.57
spillage, wound infection, biloma, intra abdominal * No statistically significant difference was noted between groups.
OC: open cholecystectomy; LC: laparoscopic cholecystectomy;
abscess, portal herniation and post operative icter), AB: antibiotic.
hospital stay, frequency of subhepatic drains, and
histopathological characteristics were not Of 130 bile culture results, 83 were negative
significantly differed between groups (table 1). (table 3). E coli, Klebsiella and Staphylococcus
Bile infection, rupture of gallbladder, spillage of aureus were the most common cultured bacteria.
gallstone or bile, the need for sub hepatic drainage Nevertheless, differences in culture results were
and surgical site infection were the most frequent not statistically significant between patients
complications (table 2). Mean surgical time and receiving AB and the placebo group, regardless of
hospital stay were longer in OC group, however the the surgical approach.
difference did not reach a statistically significant Totally, 3 patients in the treatment and two in
level. placebo group developed surgical site infection,

Iranian Journal of Clinical Infectious Disease 2010;5(1):3-8

6 Antibiotic therapy in cholecystectomy

however only one had positive culture result (table years (4). In this study 130 patients were randomly
4). The incidence of SSI were not statistically assigned in two groups, received antibiotic
significant between the two groups (p>0.05), thus, prophylaxis or placebo, and underwent either OC
prophylactic antibiotics had no protective effect or LC. Patients were alike for background
against bile infection or complications of surgery. variables.
This was also true in all four subgroups suggesting In our study, the result of bile culture was
that this conclusion is valid regardless of the positive in 36.2% of patients, while the main
surgical approach. cultured bacteria were: E. coli, Klebsiella and
Staphylococcus aureus. These results were in
Table 3. Results of bile culture in patients undergoing agreement with other studies. In a study in
open/laparoscopic cholecystectomy with/without Honolulu, among 501 cases of cholecystectomy,
prophylactic antibiotic
OC(n=63) LC(n=67) 46.7% of patients had positive bile culture with
AB Placebo AB Placebo dominancy of E. coli, Klebsiella, Enterobacter,
Culture result * (n=32) (n=31) (n=34) (n=33)
No growth 20 20 22 20
Enterococcus, Clostridium perfringens and
E coli 4 3 4 3 staphylococci. Wound infection was mostly seen in
Klebsiella pneumoniae 3 2 3 2
Pseudomonas aeroginosa 1 0 1 1 men and 65% of cases had the same organism in
Enterobacter 0 1 0 1 both bile and infected wound (24). In Ahmadian et
Proteus mirabillis 0 1 0 1
Staphylococcus aureus 2 2 2 2 al study, 57.5% of cultures were positive for
Streptococcus 0 1 1 1 pathogenic bacteria, and in 14% more than one
Enterococcus 1 0 1 1
Clostridium 0 1 0 1
bacterium was isolated. E. coli and staphylococci
* No statistically significant difference was noted between groups. were the most common aerobic bacteria and
OC: open cholecystectomy; LC: laparoscopic cholecystectomy;
AB: antibiotic. Clostridium species and streptococci were the most
common anaerobic isolated bacteria (25).
Table 4. Demographic and disease characteristics of In another study Sattar et al evaluated the
patients with SSI in open/laparoscopic cholecystectomy frequency of infection in cholelithiasis. Thirty six
group with/without prophylactic antibiotic
No Bile SSI Clinical Age Sex Surgical Spillage percent (36%) of patients had positive bile culture.
culture class manifestation (yr) technique of bile/ E. coli (17 patients) followed by Klebsiella (9),
results gallstone
1 Neg. II AC 38 F LC(- AB) Neg. Pseudomonas (6), Staphylococcus aureus (2),
2 Pos. III empyema 50 F LC(+AB) Neg. Salmonella (1), and Bacteroids fragalis (1) were
3 Neg. II AC 41 M LC(+AB) Neg.
4 Neg. II AC 52 M OC(+AB) Neg. the most frequent isolated bacteria. Most of the
5 Neg. III AC 50 F OC(-AB) Neg. organisms were highly sensitive to the second
OC: open cholecystectomy; LC: laparoscopic cholecystectomy; Neg.:
negative; Pos.: positive; (-AB): without antibiotic (placebo group);
generation cephalosporins and quinolones. They
(+AB): with antibiotic; SSI: surgical site infection; AC: acute concluded that both endogenous and exogenous
cholecystitis; F: female; M: male.
contamination were the causes of wound sepsis.
Nevertheless, the infection of bile did not increase
DISCUSSION the risk of postoperative wound infection when
Cholelithiasis is a common gastrointestinal prophylactic perioperative antibiotics were used
disease worldwide. The prevalence and incidence (26). In our study, 5 patients had infection of
increases with age and 20% of adults over 40 years surgical incision site with primary manifestation of
old suffer from billiary calculi. The age-adjusted acute cholecystitis (n=4) and empyema (n=1),
female-to-male ratio for gallstone disease is 2.9 however only one had positive bile results and
between the ages of 30 and 39 years, but it there was no correlation between bacteribilia and
decreases to 1.2 between the ages of 50 and 59 SSIs, a finding that was described in other studies

Iranian Journal of Clinical Infectious Disease 2010;5(1):3-8

 Mozafar M. et al 7

as well (27,28). In our setting, spillage of bile or REFERENCES

gall bladder stones occurred in 21.2% and 20.3% of 1. Kommera S. Spectroscopic characterization of biliary
patients in the treatment and placebo group, tract tissues in-vivo to assist laparoscopic
respectively, however spillage did not contribute to cholecystectomy. Available from: http://www.proquest.
com/Publication Number: AAT 1440442.
a higher SSI rate. All five patients with SSIs did
not have rupture of gallbladder, so infectious 2. Vollmer CM, Callery MP. Biliary injury following
laparoscopic cholecystectomy: why still a problem?
complications were not predictable. Many reports Gastroenterology 2007;133:1039.
have also indicated that wound infections are not
3. Afdhal NH, Vollmer CM. Complications of
related to bile culture, rupture of gallbladder, or laparoscopic cholecystectomy. In: Up to date 16.3;
spillage of gallbladder stones or bile (27,28). September 2008.
Therefore, the cause of SSIs in these five patients 4. Afdhal NH. Diseases of the gallbladder and bile ducts.
could be in part explained by inadequate skin In: Anderolli T, Cooper JA, Pappas PG, eds. Cecil
essential's of Medicine. 23rd edition. New York;
preparation, aseptic manipulation, and incomplete Saunders Co., 2007.
homeostasis.
5. Schirmer BD, Winters KL, Edlich RF. Cholelithiasis
The role of prophylactic AB in prevention of and cholecystitis. J Long Term Eff Med Implants.
infection is controversial. Although many studies 2005;15(3):329-38.
show that prophylactic AB is not necessary in 6. Ghany M. Diseases of the gallbladder and bile ducts.
elective, non complicated LC, others believe that it In: Kasper DL, Braunwald E, Fauci AS, Hauser SL,
Longo DL, Jameson JL, editors. Harrison’s principles of
can be useful in reduction of SSI after
internal medicine. 17th edition. New York: McGraw-
cholecystectomy in high risk populations (29). Our Hill; 2008.
data also showed that it is not necessary to 7. Hariharan S. Surgical fluorescence imager for
prescribe antibiotics before wound closure in order visualizing anteriorly placed biliary structures, in-vivo
to decrease the incidence of SSIs in elective during human cholecystectomy. Available from:
http://www.proquest.com/Publication Number: AAT
cholecystectomy. In elective cases, additional 1456575.
doses are generally recommended only when
8. Suarez J. Risk factors for developing complications
surgery lasts longer than 2 to 3 hours (30). On the while awaiting cholecystectomy. Available from:
other hand, prolonged use of prophylactic http://www.proquest.com/Publication Number: AAT
antibiotics may induce bacterial resistance, change 1445121.
normal bile flora, cost more, and increase further 9. Szilágyi E, Böröcz K, Gastmeier P, Kurcz A,
opportunistic nosocomial infections and SSIs (27). Horváth-Puhó E. The national nosocomial surveillance
network in Hungary: results of two years of surgical site
In conclusion, prophylactic AB did not have infection surveillance. J Hosp Infect. 2009;71(1):74-80.
any preventive effect on wound infection. This fact 10. Minchella A, Alonso S, Cazaban M, Lemoine MC,
was demonstrated regardless of surgical approach. Sotto A. Surveillance of surgical site infections after
Therefore, routine antibiotic prophylaxis as digestive surgery. Med Mal Infect. 2008 Sep;38(9):489-
94.
recommended for biliary surgery (open or
laparoscopic cholecystectomy) in general is now 11. Biscione FM, Couto RC, Pedrosa TM, Neto MC.
Comparison of the risk of surgical site infection after
questionable. laparoscopic cholecystectomy and open
cholecystectomy. Infect Control Hosp Epidemiol. 2007;
28:1103-7.
ACKNOWLEDGEMENT 12. Brill A, Ghosh K, Gunnarsson C, Rizzo J, Fullum
We wish to thank all the staff of Shohada-e- T, Maxey C, et al. The effects of laparoscopic
Tajrish hospital and also patients without their cholecystectomy, hysterectomy, and appendectomy on
nosocomial infection risks. Surg Endosc.
patience this study would not be completed. 2008;22(4):1112-8.

Iranian Journal of Clinical Infectious Disease 2010;5(1):3-8

8 Antibiotic therapy in cholecystectomy

13. Mufti TS, Ahmad S, Naveed D, Akbar M, Zafar A. 26. Sattar I, Aziz A, Rasul S, Mehmood Z, Khan A.
Laparoscopic cholecystectomy: an early experience at Frequency of infection in cholelithiasis. J Coll
Ayub Teaching Hospital Abbottabad. J Ayub Med Coll Physicians Surg Pak. 2007;17:48-50.
Abbottabad. 2007;19(4):42-4.
27. Koc M, Zulfikaroglu B, Kece C. A prospective
14. Hussain A, Mahmood HK, Dulku K. Laparoscopic randomized study of prophylactic antibiotics in elective
cholecystectomy can be safely performed in a resource- laparoscopy cholecystectomy. Surg Endosc.
limited setting: the first 49 laparoscopic 2003;17:1716-8.
cholecystectomies in Yemen. JSLS. 2008;12(1):71-6.
28. Gold Deutch R, Mashiach R, Boldure I. How dose
15. Purtak JK, Kostewicz WJ, Mularczyk T. Ten years infected bile affected the postoperative course of
of experience with laparoscopic cholecystectomy. Wiad patients undergoing laparoscopic cholecystectomy? Am
Lek. 2007;60(5-6):231-4. J Surg. 1996;172:272-4.
16. Romy S, Eisenring MC, Bettschart V, Petignat C, 29. Grande M. Wound infection after cholecystectomy-
Francioli P, Troillet N. Laparoscope use and surgical correlation between bacteria in bile and wound infection
site infections in digestive surgery. Ann Surg. after operation on the gallbladder for acute and chronic
2008;247(4):627-32. gallstone disease. Eur J Surg. 1992;158(2):109-12.
17. Strasberg SM, Hertl M, Soper NJ. An analysis of 30. Nichols RL. Preventing surgical site infection: a
the problem of biliary injury during laparoscopic surgeon's perspective. Emerg Infect Dis. 2001;7:220-4.
cholecystectomy. J Am Coll Surg. 1995;180:101-6.
18. Atadzhanov SK. The ways for reduction of
complication rate after laparoscopic cholecystectomy at
acute cholecystitis. Khirurgiia (Mosk). 2007;(12):26-9.
19. Brekalo Z, Innocenti P, Duzel G, Liddo G, Ballone
E, Simunović VJ. Ten years of laparoscopic
cholecystectomy: a comparison between a developed
and a less developed country. Wien Klin Wochenschr.
2007;119(23-24):722-8.
20. Moore MJ, Bennett CL. The learning curve for
laparoscopic cholecystectomy. The Southern Surgeons
Club. Am J Surg. 1995;170:55-9.
21. Minchella A, Alonso S, Cazaban M, Lemoine MC,
Sotto A. Surveillance of surgical site infections after
digestive surgery. Med Mal Infect. 2008;38(9):489-94.
22. Boni L, Benevento A, Rovera F, Dionigi G, Di
Giuseppe M, Bertoglio C, et al. Infective complications
in laparoscopic surgery. Surg Infect (Larchmt). 2006;7
Suppl 2:S109-11.
23. Donovan JM. Physical and metabolic factors in
gallstone pathogenesis. Gastroenterol Clin North
Am. 1999;28:75-97.
24. Mirsharifi SR, Emami Razavi SH, Jafari S, Bateni
H. The effect of antibiotic irrigation of surgical incisions
in prevention of surgery site infection. Journal of Tehran
University of Medical Sciences. 2008;11(65):71-5. (In
Persian)
25. Ahmadian A, Pour Zand A. A study of the presence
of bacteria in gall bladder diseases. Medical Journal of
Tabriz University of Medical Sciences & Health
Services. 1996;28(29):12-3. (In Persian)

Iranian Journal of Clinical Infectious Disease 2010;5(1):3-8