International Journal of Current Research and Review
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IJCRR - 4(23), December, 2012

Pages: 124-130

Date of Publication: 15-Dec-2012


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RANDOMIZED CLINICAL TRIAL OF SINGLE VERSUS THREE DOSES OF CEFAZOLIN AS PROPHYLAXIS FOR NONPERFORATED ACUTE APPENDICITIS

Author: Sheik Abdullah, Rajan Vaithianathan, Kannan Rajendiran, Ramachandran Santhanam

Category: Healthcare

Abstract:Background: The most common and significant cause for morbidity following emergency appendicectomy is surgical wound infection. There are conflicting reports regarding the optimal duration of antibiotic prophylaxis in nonperforated appendicitis. The efficacy of prolonged prophylactic antibiotic treatment in preventing wound infection for nonperforated appendicitis is poorly defined. Objective: A prospective randomized study was carried out to compare the efficacy of single dose cefazolin with three doses of cefazolin in reducing the incidence of postoperative wound infection for patients with nonperforated acute appendicitis. Methods: One hundred patients with a clinical diagnosis of appendicitis were randomized into two groups. Group 1 received single intravenous dose of 1gm cefazolin at induction of anaesthesia and group 2 received two further doses of cefazolin following surgery. Postoperative wound infection was the primary endpoint. Results: The two groups were similar with regard to demographic data, pathologic condition of the appendix and duration of hospital stay. The postoperative wound infection rate was not significantly different among the two groups, 11% in group 1 and 9% group 2 (p =0.986). Conclusions: Single-dose cefazolin is equally effective to multiple-dose cefazolin in preventing postoperative wound infection in patients undergoing open appendicectomy for nonperforated acute appendicitis. However, because of the greater convenience and economic implications, single pre-operative dose of cefazolin is the choice of prophylaxis for nonperforated appendicitis.

Keywords: acute appendicitis, antibiotic, single dose, nonperforated

Full Text:

INTRODUCTION
Appendicectomy is one of the most common emergency surgical procedures with a postoperative wound infection rate of 1-10%1-4 . Wound infection following open appendicectomy is a major cause for post-operative morbidity, prolonged hospitalization and increased costs. The pathologic state of the appendix is the most important determinant of postoperative wound infection following appendicectomy5, 6. The incidence of wound infection in patients with complicated appendicitis (perforated or gangrenous appendix) is nearly four to five times greater than that of nonperforated cases. The efficacy of antibiotic prophylaxis in reducing wound infection in patients undergoing open appendicectomy is well established. Many randomized and observational studies have shown that appropriate use of antibiotics reduces the risk of infection by 40–60%4, 7-10 . Based on prospective clinical studies, guidelines have been established regarding the choice of prophylactic antibiotics, it’s timing and route of administration for emergency appendicetomy11. However, the duration of antibiotic usage remains a contentious issue and there is no definite consensus among the surgical community12, 13 . Single dose antibiotic prophylaxis has been recommended for majority of elective general surgical procedures14. In reality, this practice is not universally accepted and multiple dose regimens are still in use at many centres. In the emergency setting, though postoperative antibiotics are universally used for perforated appendicitis, no consensus exists regarding the efficacy of postoperative antibiotics in preventing surgical site infections in nonperforated cases. The main purpose of our study was to compare the efficacy of single dose of cefazolin with multiple doses of cefazolin in reducing the rate of wound infection in nonperforated appendicitis.

RESEARCH METHODOLOGY
A randomized prospective study of 100 patients with a clinical diagnosis of acute appendicitis presenting to the Emergency Department of Mahatma Gandhi Medical College was carried out over a period of two years. Before performing an emergency open appendicectomy, the patients were randomized into two groups by opening a sealed envelope containing details of the prophylactic antibiotic regimen to be used. Group 1 received single dose of cefazolin 1gm i.v. at time of induction of anaesthesia. In group 2, two further doses of cefazolin were given intravenously at 8 hours and 16 hours from the time of index surgery. Appendicectomy was carried out in all the patients by the standard protocol of open surgical technique. The surgical wound was closed in layers.

Exclusion criteria:
1.Gangrenous or perforated appendix

2. Abscess found at time of surgery

3. Allergic to cephalosporins

4. Prior antibiotic treatment

During the post-operative period, the progress of the surgical wound was monitored on a daily basis for all the patients included in the study. Wound infection was graded using the Southampton scoring system15.

Wound healing was taken as normal for grades 0, 1 and 2. Infection of the wound was categorised as minimal for grade 3 and as major for grades 4 and 5. Patients who developed major infection were treated appropriately with daily wound irrigation and antibiotics based on culture reports. Informed consent was obtained from all the patients and the study was carried out with prior clearance from the ethical committee.

Study parameters:

  • Demographic data –age and sex
  • Final histopathological report of the appendix
  • Grade of wound infection
  • Length of hospital stay

Statistical Method - Comparison of proportions by ‘CHI Square’ test.

RESULTS
In our study, 100 patients were included with a diagnosis of acute appendicitis and randomized to two groups, with fifty patients in each group. The age group varied from 15 to 55 years in both groups, with a mean age of 28.2 years in group 1 and 29.1 years in group 2 (p=0.147) , as shown in table 1 and fig 1. The male to female ratio was 1.63 and 1.94 in group 1 and group 2 respectively (p=0.676) as shown in table 2 and fig 2. The histopathological examination of the removed appendix revealed features of acute inflammation in 44(88%) patients in group 1 and 45(90%) in group 2. Six patients in group 1 and 5 from group 2 were excluded from the study in view of the presence of perforation, gangrenous or normal appendix (table 3 and fig 3). In the postoperative period, the surgical wounds were examined and graded using the Southampton scoring system. Normal wound healing was observed in 34(77%) patients in group 1 and 37(82%) in the other group. Minimal wound infection which resolved spontaneously was present in 5 out of 44 patients (11%) in group 1 and 4 of 45 (9%) patients belonging to group 2. Discharge of pus (grade 4) was observed in 5(11%) patients in group 1 and 4(9%) in group 2. No patients in either group developed grade 5 wound infection. Using Chi square test for analysis, the incidence pattern and the grade of wound infections in both the study groups were found statistically not significant(p=0.986), table 4 and fig 4. The mean hospital stays of the single-dose and three-dose groups were 4.6 days and 5.2 days. The median duration of stay was 5 days in both groups. There was no significant difference in length of hospital stay between the two groups.

DISCUSSION
Usage of appropriate antibiotics is well known to control wound infection rates following open appendicectomy for uncomplicated acute appendicitis. While antibiotic prophylaxis is common in surgical procedures16, inappropriate use of antibiotics occurs in 25–50% of general elective surgeries17-21. A Cochrane systematic review found that antibiotic use in patients having uncomplicated appendicitis was superior to placebo in reducing the rates of postoperative complications but concluded that no recommendations can be made regarding the duration of antibiotic use. At the same time, in patients with severe form of appendicitis, it has advised to continue a comprehensive antibiotic regime, as the risk of infective complications is quite high in this group1 . The choice of antibiotic for prophylaxis varies widely in different centres and even among the different surgical units attached to the same Institute. The American Society of Health System Pharmacists (ASHP) recommends cephalosporins as drug of choice for prophylaxis for nonperforated appendicitis and gentamicin with metronidazole only in cases of penicillin allergy22, 23. The major controversy lies in the optimum duration of prophylaxis in cases of acute nonperforated appendicitis. Many studies have shown that single preoperative dose of antibiotic is as effective as multiple postoperative doses in preventing wound complications following appendicectomy24-26 . A randomized control study by Mui et al have shown that single dose of preoperative antibiotic is adequate for prevention of infective complications of the wound in patients undergoing surgery for uncomplicated appendicitis. Their conclusion was that the prolonged antibiotic administration was cost-ineffective and led to unnecessary complications27 . In our study, we have used a more objective method to assess the progress of the surgical wounds by correlating with the Southampton scoring system. There was no significant difference (p=0.986) between wound infection rates of the single-dose group (11%) and the threedose group (9%). These findings are in full agreement to the similar studies in the literature24- 27 . Moreover, comparing the incidence of wound infection across all the grades in both the groups by using the Chi-square test has shown no significant difference between the two groups(p=0.986). Cefazolin was chosen in our study as it was readily available, cheaper and has very good antibacterial spectrum for pathogens causing post appendicectomy sepsis. This choice of antibiotic is in line with the recommendations given by the ASHP22. We also found from our study that there was no significant difference in the length of the hospital stay between the two groups. The median duration of stay in both groups was 5 days. Many studies have highlighted and repeatedly emphasised the effects of improper choice and inappropriately prolonged duration of prophylactic antibiotics on the rising emergence of antimicrobial resistance among the common pathogens28-33. Coakley et al, in a recent study, have consistently proven that postoperative antibiotic treatment for nonperforated appendicitis did not reduce infectious complications. In fact, their study showed significantly increased rate of adverse effects like Clostridium difficile infection, diarrhea, longer length of hospital stay and higher treatment cost. Patients receiving postoperative antibiotics were also more frequently readmitted and reoperated34 . A possible benefit that can be derived from our study is that by using a single preoperative dose, the surgeon can be certain of having given an effective prophylaxis at induction of anaesthesia without the need to monitor further postoperative doses. Moreover, avoiding further intravenous doses of antibiotics may lead to savings in terms of nursing effort, time and the cost of treatment.

CONCLUSION
It is evident that prophylactic postoperative doses of cefazolin confer no additional benefit over a single preoperative dose of cefazolin. With additional benefits of the greater ease of administration and decreased cost, single-dose cefazolin is the prophylaxis of choice for appendicectomy in patients with nonperforated appendicitis. It is essential for surgeons and surgical departments to update their routine practice of antibiotic prophylaxis to comply with updated guidelines and evidence base.

ACKNOWLEDGEMENT
Authors acknowledge the immense help received from the scholars whose articles are citied and included in references of this manuscript. The authors are also grateful to authors/ editors/publishers of all those articles, journals and books from where the literature for this article has been review and discussed. The authors also thank all the residents and staff in the Department of Surgery, Dean and Vice Chancellor of Mahatma Gandhi Medical College and Research Institute for their support throughout the study period, without which this study would not have been possible.

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A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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