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ABDOMINAL SURGERY

Official Journal of the American Society of Abdominal Surgeons, Inc.

This article originally appeared in the Winter 20011 / Spring 2012 issue of the Journal.

Intraoperative Peritoneal Swabs and Antibiotic Therapy in Appendicitis: Review of our Results and Results of Literature

Stanko Cavar1
Tomislav Luetic1
Dinko Bagatin1
Zlatko Hrgovic2

1. Department of Surgery, University Hospital Center
Zagreb „Rebro“,Zagreb, Croatia

2. Kaiserstrasse 15, 60311 Frankfurt, Germany

Address for correspondence:
Prof. Zlatko Hrgovic, MD, PhD.
E-mail: info@hrgovic.de


ABSTRACT

There are necessity of taking intraperioneal swabs in patients with appendicitis, sensitivity and resistency on antibiotics of most often isolated bacterias and results of empiric antibiotic therapy on development of postoperative infections.

MATERIALS AND METHODS

Retrospective study was performed on appendectomy patients through 2005. on Surgery Department of University Hospital Center Zagreb. Number of patients was 256. This trial included 104 patients with acute appendicitis verified on patohystologic analysis in which were taken intraoperativly peritoneal swabs in the area around appendix for aerobe and anaerobe bacterias. From trial were excluded 152 patients in who peritoneal samples were not taken or acute appendicitis was not comfirmed with patohystologic analysis. Patients were divided in two groups according to pathohystology results: complicated group with 46 patients with gangrenous and perforated appendicitis and uncomplicated group with 58 patients who had phlegmonous appendicitis.

RESULTS AND DISCUSSION

Most common isolated were Eschericia coli and Bacteroides spp. In 19% of patients in uncomplicated group and in 37% of patients in complicated group isolated microorganisams were sensitive to gentamicin, cefazolin and cefuroxim. Resistency in both groups was on antibiotics in group of penicillins: natual penicillins, amoxicillin, ampicillin in 43,5% in complicated group and in 19% in uncomplicated group. Most common ordinated empiric antibiotic therapy in both groups was combination of gentamicin and metronidasol. Wound infections were most common complication in both groups. Results and conclusion of this study show that most common bacterias were E. Coli and Bacteroides spp. and routine use of peritoneal samples were not necessary. In almost 50% patients who were isolated bacterias from culture swabs had sensitivity on all three antimicrobe drugs: gentamicin, cefazolin, cefuroxim, and that some of this drugs can be used in prevention of infective complications. There is also high level of resistency on antibiotics from group of penicillins and these should be taken with caution.

INTRODUCTION

Retrospective studies show that therapeutic procedures for acute appendicitis were different among Surgical Centers and even between surgeons in same departments (III. Level of proof).1-3 The number of infective complicatons in appendicitis are significantly less now with use of antibiotic therapy.1,3 Antibiotic therapy is used after isolated bacterias, mostly for E. Coli and Bacteroides fragilis what is based on intraperitoneal swabs. We did not advise routine use of peritoneal swabs because excellent results are obtained with empiric antibiotic therapy. Gram(–) bacterias were most common isolated bacterial population which had a good response on empiric antibiotic therapy, and used antibiotics are not changed on results of intraperitoneal swabs.3

Table 1
Intraoperative peritoneal swabs

click to enlarge

Duration of antibiotic therapy were not precisely determined. 1-3 Increasing antibiotic resistancy is another problem. Recent data about isolated peritoneal cultures in gangenous and perforated appendicitis did mention some bacterias which were not isolated until now. (Bennion RS, Thompson JE, Baron EJ, Finegold SM. Gangrenous and perforated appendicitis with peritonitis: Treatment and bacteriology. Clinical Therapeutics 1990; 12: 31-44.)

Aim of this study is taking of peritoneal swabs in patients in surgery for appendicitis, sensitivity and resistency on antibiotics most commonly isolated bacterias and results of empiric antibiotic therapy on development of postoperative infections.

MATERIALS AND METHODS

Retrospective study was conducted on 256 appendectomied patients with positive findings during 2005 at the Department of Surgery, University Hospital Centar Zagreb. Intraoperative peritoneal swabs of ileococeal region on both aerobic and anaerobic bacteria were taken in 104 patients. Peritoneal swabss were not obtained for 152 patients with positive appendicitis. Patients were divided in two groups based on pathohistologic analysis: complicated group with 46 patients who had gangenous or perforated appendicitis and uncomplicated group with 58 patients who had catarrhal or phlegmonous appendicitis. Average age of patients was 29 ± 20, 17 years, and 37 were females (35,57%) and 66 were males (63,46%). Intraperitonel swabs were analysed for the presence of aerobic and anaerobic bacteria with standard labarotory techniques.5 Vermiform appendix was fixed in 10% formalin and then in parafin. Cuts wide 4 μm were stained with hematoxylin and eosin.

Operative techique Appendectomies were made through McBurney’s incision with ligation of appendiceal stump and inversion with purse string suture at the base of coecum and than „Z“ suture. Every wound opened postoperatively was considered infected independent despite of purulent secretion and positive culture for microorganisams from the wound swab. Every suspected intraabdominal infection was confirmed with ultrasonography or MSCT scan.

Statistical data analysis Descriptive statistical data analysis were made, diference between two groups was tested with Hi quadrat test and Fischer Exact test. Distribution of data was tested with Kolmogorov-Smirnovs test. Difference between investigated groups at p< 0,05 has been taken as statisticaly important. Statistical analysis was made with SPSS statistical softver (SPSS for Windows 10,0, SPSS, Chicago, IL, U.S.A.).

RESULTS

The most of isolates were gram negative bacterias in both groups showed in Table 1.

In uncomplicated group in 19 (32,8%) patients were isolated one bacterial species and in 9 (15,5%) patients were isolated two or more bacterial species from culture swabs. In complicated group in 9 (19,6%) patients were isolated one bacteria and in 23 (50,0%) are islated two or more bacterial species from culture swabs.

Table 2
Empiric antibiotic therapy

click to enlarge

Isolated bacterias in both groups were sensitive on following antimicrobe drugs: gentamicin 12,2%, cefazolin 11,4%, cefuroxim 10,8%, amoxicillin clavulanate 9,7%, ciproflaxicin 9,5%, piperacillin tazobactam 7,5%, metronidazol 6,5%, klindamycin 6,5% and other drugs with sensitivity less than 6%. In complicated group N 32 (69,6%) patients showed sensitivity of isolated bacterias on antimicrobe drugs from which 17 (37%) showed sensitivity on all three antibiotics: gentamicin, cefazolin and cefuroxim. In uncomplicated group N 28 (48,3%) patients showed sensitivity of isolated bacterias on antimicrobe drugs from who 11 (19%)showed sensitivity on all three antimicrobe drugs: gentamicin, cefazolin and cefuroxim. Isolated bacterias were resistant on following antimicrobe drugs: natural penicillins (G or V) 28,0%, amoxicillin 21,3%,ampicillin 18,7%, klindamycin 8,0%, azithromycin 5,3% and other drugs with less than 4% resistency.In complicated group N 20 (43,5%)and in N 4 patients were resistent on klindamycin, in N 3 patients on ciprofloxacin, in N 2 on azitromycin and meropenem, in N 1 on metron- idazol, gentamicin, piperacillin and chloramfenicol. In uncomplicated group N 11 (19%) of patients were resistent on antimicrobe drugs. Also all patients in uncomplicated group who were resistent on some of antimicrobe drugs were resistent on antibiotics in group of penicillins N 11 (19%), and in N 2 on klindamycin and azitromycin, and in N 1 on metronidazol and cefuroxim.

Mostly ordinated empiric antibiotic therapy were combination of gentamicin and metronidazol in both groups what is showed in table 2.

In just one case empiric therapy was changed and antibiotics were ordinated based on antibiogram and that was after development of complication: abdominal abscess after perforated appendicitis.

Average duration of ordinated therapy in complicated group was 3,5 +-2,16 days and in uncomplicated group 3,33 +- 3,0 days without statistcly important difference (p=0,75).

Wound infections were more often present in group of patients with complicated appendicitis what is shown in table 3.

DISCUSSION

This study is byitself limited because it is retrospective and for many surgeons with different experience did surgical procedures. Despite this we can make some conclusions from our data. Making same clinical algoritams for more successful treatment of acute appendicitis is not finished and it is based on retrospective studys.2 In both groups most common isolated microorganisams are gram (-) bacterias E. coli and Bacteroides fragilis. E. coli is more often isolated (in complicated group 17,3%, in uncomlicated group 13,7%) than Bacteroides Fragilis (in complicated group 10,8% and in uncomplicaed group 3,4%) in both groups with large number of sterile samples (in complicated group 30,4% and in uncomplicated group 51,7%) what is also showed in other studies.6,7,8,9 There is statisticly important difference in bacterial contamination of peritoneum between two analysed groups found also in previous studies.7 Anderson and Parry showed that gangrenous and perforated appendicitis can not be divided as separate entities because in both conditions appendiceal wall is necrotic without protection against bacterial translocation.10 Knowledge of bacterial flora helps clinitians to choose empiric antibiotics for elimination of infective complications.2,7,11,12

Our result were that the most common isolated bacterias from peritoneal swabs were same as in other studies and for that there was no need for routine peritoneal swabs.2,3,13,14

Table 3
Complications in appendicitis

click to enlarge

Results were that most common bacterial isolates were sensitive to gentamicin, cefazolin and cefuroxim from 12% to 11% of all isolated bacterias. Sensitivity of isolated bacterias on gentamicin, cefazolin and cefuroxim were in complicated group in 37% of patients and in uncomplicated group in 19% of patients what was around 50% of patients in both groups in which peritoneal samples were positive and for that some of this drugs can be used for therapy in acute appendicitis. There are many protocols for use of antibiotic therapy and profilactic therapy in acute appendicitis which are dfferent in group of antibiotics and in one or more antibotics as are ampicillin, gentamicin and metronidazol or klindamycin, cefuroxim and klindamycin in therapy purpose or cefofetan or cefuroxime in profilactic purpose.1,2,3,15 For infections caused by E. Coli there are differen data from those who propose as first choice ampicillin with aminoglycozide, cephalosporine first generation to those who claim that resistency to ampicillin and first generation of cephalosporins is rapidly grown so it cant be considered as a therapy of first choice.15,16 It is known that gentamicin is not efficient for anaerobes. Monotherapy with second generation of cefalosporins is less expencive, safe and as efficient as antibiotic therapy in combination with amynoglicosides which should be reserved for resistant bacterias and nosocomial infections in complicated appendicitis.17 Generally, if one efficient, untoxic drug is used to prevent nfection with specific microorganisms or for eradication of infection imidiatly or soon after it begun, then is chemoprofilaxis mostly efficient.15 Usual profilaxisis antibacterial treatment in goal of making less expences, toxicity and risk of development bacterial resistency, it is desirable to have quick and most efficient profilaxis for postoperative complications. Antibiotic chemprofilaxis is efficient in prevention of postoperative complications in appendectomy patients without consideration on nature of removed appendix and it should be used in consideration as a rutine in emergency appendectomy.18,19 Profilactic chemotherapy should be efficient against anaerobes, E. Coli and bacteroides fragilis and it should contained one drug which is untoxic and cheep.11 In our results were shown difference about 1% in sensitivity between gentamicin on one side and cefazolin and cefuroxim on other with taking in consideration large number of isolated anaerobes on which gentamicin doesnt work, need for measuring therapeutic concentracion of gentamicin in blood and possible need for preserving gentamicin as one of antibiotics for resistent bacterias we could decide on use of cefazolin or cefuroxm in profilactic purposes with caution on posibility of resistecy E. Coli on I. generation cephalosporins which is mentoned in literature and we didnt find in our results. In antimicrobe therapy in complicated appendicitis we should take in consideration one of this three drugs: gentamicin, cefazolin and cefuroxim in combination with other drugs depending on clinical expirience, and sensitivity and resistency of bacterias in some facilities. Atibiotic profilaxis is one of many measures which shuld be taken in consideration in goal of reduction postoperative morbidity primarly wound infection.18

Our results demonstrated resistent isolated bacterias, among others on some of earlier mentioned antibiotics from group of penicillins: natural penicillins, amoxicillin, ampicillin in 43,5% of patients in complicated group and in 19% of patients in uncomplicaed group. Isolated bacterias which were resistant on antimicrobe drugs in all patients in both groups also were resistent on some antibiotics from group of penicillins and for that when these three penicilin antibotics are used in group of complicaed appendicitis we should be caution. More then 95% Bacteroides fragilis species were resistent to penicillin and ampicillin with exception of ceftizoxim, resistency were on penicillins of broad spectar and there were even higher resistency on klindamycin.20 Our results about resistency isolated bacterias on mentioned drugs from group of penicillins are same with other published results.16,20

The mostly ordinated therapy in both groups were: combination of gentamicin and metronidazol. Triple antibiotic therapy gentamicin, metronidazol and cefazolin are significatly more given to group of patients with complicated appendicitis what is expected on local apearence. Neither one patient in complicated group was without antibiotic therapy while there were nine patients in uncomplicated group. There are no same protocols about need for antibiotic therapy in uncomplicated appendcitis.2,3,11,18,19 An antibiotic profilaxis and therapy in appendicitis is different between facilities and between surgeons in same facility and it is based more on tradition than on evidence based data.1,2, 3,18,21,22 In conclusion: In University Hospital Center Zagreb we dont have same protocol for use of profilactic and antibotic therapy in acute appendicitis. We changed antibiotic therapy in just one patient with intraabdominal abscess after appendectomy and antibiotic is used after antibiogram for patient was febrile despite used empiric therapy. It is known that patients in who is changed antibiotic therapy after antibiogram have worse outcome than those who were treated empiricly. Often there is a difference between first intraoperative swab form those were taken afterward from intraabdominal abscess and therapy should be changed after antibiogram only if empiric therapy is not efficient.3,9,13 Final results of many studies showed that antibiotic therapy is more efficient than placebo in prevention of wound infections and intraabdominal abscesses without clear difference in nature of operated appendix.18 Use of agressive antibiotic therapy for number of complicatons: wound infections and intraabdominal abscesses are significatly lower from 63% to 0% depending on what type of appendicitis was there (complicated or uncomplicated) with standard range from 3 to 7% for wound infections and 2 to 7% for intraabdominal infections.1,3,7,11,14,18,19,21-23

Despite that earlier results support triple antibiotic therapy in cutting down infective complication many new reports show that same results can be accomplished with one antibiotic of broad spectar activity. Historicaly many protocols used for therapy in acute appendicitis were developted from large studies in children hospitals.2,3,22

The number of complications are statisticly significant and different between two groups (p=0,04). Number of wound infections is significantly higher in complicated group what was expected and number of intraabdominal infections is around the same. In table 2. are data of statisticly significant difference in use of antibiotic therapy betwen two analysed groups with almost the same duration of using antibiotics 3,5 days without statisticly signifiant difference. In complicated group is used more agressive antibiotic treatment and complications: wound infections are despite that higher in same group. It is a fact that this more agressive treatment in complicated group cut down infective complications in compare with other studies with similar population which gather together adults and children with usual age around 20 years or that our complications are lower.7,18,22Wound infectons and intraabdominal infecions are most often postoperative complications and stage of appendicitis and/or qulity of surgical procedure made our results as they are with used antibiotic therapy.7,18 Usualy used antibiotic therapy is different between different facilities from those which dont use antibiotics for uncomplicated appendicitis to those who use therapy for more than two days and for complicated appendicitis used therapy is from 3 to 10 days and duration of therapy is based or not based on clinical parameters.1-3,11,14,19,21,22 Usualy used antibiotic therapy in both analysed grups were 3,5 days without statisticly important difference. Duration of antibiotic therapy for 3,5 days in complicated group is accepted while in uncomplicated group antibiotic therapy for 3,3 days is not accepted even it makes postoperative complications lower. To make this conclusion for sure helps that in our Center we dont have uniqe protocol for use of antibiotic therapy for patients with acute appendicitis. When we compare our results with other similar studies antibiotic therapy in duration of 3,5 days can be enough for cutting down infective complications after appendectomies in patients with complicated appendicitis. Nevertheless our study is retrospective and it didnt analysed what minimal duration of antibiotic therapy should be and what also depend on selection of antimicrobe drugs. Based on data from 28 studies it seems that number of infecive complications is higher with duration of antibiotic therapy for three days when it is compered with therapy that last longer for therapy in complicated appendicitis in children.14

CONCLUSION

Mostly isolated bacterias from peritoneal swabs in our patients with acute appendicitis are gram (-) negative bacterias E. Coli and Bacteroides what is same with present studies and from that we can conclude that routinly taking of peritoneal swabs are not necessary. We found in around 50% of patients who had isolated bacterias from swabs sensitivity on every of three mentioned antimicrobe drugs: gentamicin, cefazolin and cefuroxim and we could use some of this drugs for prevention of infective complications. Resistency of isolated microorganisams were in 43,5% of patients in complicated group, and in 19% of patents in uncomplicated group and all of those had resistency on some of mentioned antibiotics from group of penicillins: penicillins, amoxicilin and ampicillin so we recomend caution with use of this antibiotics.

ACKNOWLEDGEMENTS

The authors declare that they have no conflicts of interest. This work was supported by institutional and departmental funds only.

REFERENCES

1. Meier D E, Guzzetta P C, Barber R G, Hynan L S, Seetharamaiah R. Perforated appendicitis in children: is there a best treatment? J Pediatr Surg 2003; 38: 1520-1524

2. Muehlstedt S G, Pham T Q, Schmeling D J. The management of pediatric appendicitis: a survey of north american pediatric surgeons. J Pediatr Surg 2004; 39:875-879

3. Emil S, Laberge J M, Mikhail P et al. Appendicitis in children: a ten-year update of therapeutic recommendations. J Pediatr Surg 2003; 38:236-242

4. Bennion RS, Thompson JE, Baron EJ, Finegold SM. Gangrenous and perforated appendicitis with peritonitis: Treatment and bacteriology. Clinical Therapeutics 1990; 12:31-44.

5. Clinical Microbiology Procedures Handbook. Henry D. Isenberg. Second Edition. 2004. ASM Press.

6. Gilmore O J A, Martin T D M. Aetiology and prevention of wound infection in appendicectomy. Brit J Surg 1974; 61:281-287

7. Leigh D A, Simmons K, Norman E. Bacterial flora of the appendix fossa in appendcitis and postoperative wound infection. J clin Path 1974; 27:997-1000.

8. Mosdell D M, Morris D M, Fray D E. Peritoneal cultures and antibiotic therapy in pediatric perforated appendicitis. American Journal of surgery 1994;167:313-316

9. Soffer D, Zait S, Klausner J, Kluger Y. Peritoneal culutres and antibiotic treatment with perforated appendicitis. Europen Journal of Surgery 2001;167:214-216

10. Anderson K D, Parry R L. Appendicitis, in O’Neill J A, Rowe M I, Grosfeld J L, et al.: Pediatric Surgery, St Louis, M O. Mosby, 1998.1369-1379

11. Górecki W J, Grochowski J A. Are antibiotics necessary in nonperforated appendicitis in children? A double blind randomized controlled trial. Med Sci Monit 2001; 7:289-292

12. Page CP, Bohnen J M A, Fletcher J R et al. Antimicrobial Prophylaxis for Surgical Wounds. Guidelines for Clinical Care. Arch Surg 1993; 128:79-88

13. Kokoska E R, Silen M L, Tracy T F, et al. The impact of intraoperative culture on treatment and outcome in children with perforated appendicitis. J Pediatr Surg 1999; 34:749-753

14. Snelling C M H, Poenaru D, Drover J W. Minimum postoperative antibiotic duration in advanced appendicitis in children: a review. Pediatr Surg Int 2004; 20:838-845

15. Goodman & Gilman’s the pharmacological basis of therapeutics. Hardman J G, Limbird L E, Molinoff P B, Ruddon R W, Goodman Gilman A. Ninth Edition. 1996. The McGraw-Hill Companies.

16. Medical Microbiology. Baron S et al. Fourth Edition. 1996. The Universitiy of Texas Medical Branch at Galveston

17. Hopkins J A, Wilson S E, Bobey D G. Adjunctive antimicrobial therapy for complicated appendicitis: bacterial overkill by combination therapy. World J Surg 1994; 18:933-938

18. Andersen B R, Kallehave F L, Andersen H K. Antibiotics versus placebo for prevention of postoperative infection after appendectomy. Cochrane Database of Systematic Reviews. 2005; 3.

19. Mui L M, Ng Calvin S H, Wong Simon K H et al. Optimum duration of prophylactic antibiotics in acute non-perforated appendicitis. ANZ J. Surg. 2005:75: 425-428.

20. Manual of Clinical Microbiology. Murray P R, Baron E J, Pfaller M A, Tenover F C, Yolken R H. 7th Edition. 1999. American Society for Microbiology.

21. Pearl R H, Hale D A, Molloy M, Schutt D C, Jaques D P. Pediatric appendectomy. Journal of Pediatric Surgery 1995; 30:173-181

22. Taylor E, Dev V, Shah D, Festekjian J, Gaw F. Complicated Appendicitis: Is there a minimum intravenous antibiotic requirement? A prospective randomized trial. American College of Surgeons 2000; 66:887-90.

23. Almqvist P, Leandoer L, Törnqvist A. Timing of antibiotic treatment in non-perforated gangrenous appendicitis. Eur J Surg 1995; 161:431- 3.

24. Meller J L, Reyes H M, Loeff D S, Federer L, Hall J R. One-drug versus two-drug anthibiotic therapy in pediatric perforated appendicitis: A prospective randomized study. Surgery 1991; 110:764-8.



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The American Society of Abdominal Surgeons, Inc.
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Louis F. Alfano, Jr., M.D., Editor-in-Chief
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Director of Continuing Medical Education


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Table I:

Intraoperative peritoneal swabs

Table 2:

Empiric antibiotic therapy

Table 3:

Complications in appendicitis