- Email: [email protected]
A randomized prospective study of cefoxitin versus piperacillin in appendicectomy
Journal
of Hospital
Infection
(1994)
26, 133~-136
SHORT
REPORT
A randomized prospective study of cefoxitin piperacillin in appendicectomy I. M. A. Salam, K. H, Abu Galala, Chandran, N. N. Asham
versus
Y. I. El Ashaal, V. P. Prem and A. J. W. Sim
Department of Surgery, Al Ain Hospital and Faculty of Medicine and Health Sciences, United Arab Emirates Accepted for publication 20 October 1993 Summary: A randomized prospective study of antibiotic prophylaxis using a single dose of either cefoxitin or piperacillin is presented. The trial was carried out in Al Ain Hospital in the period 1989-l 992 on 250 adult patients with non-perforated appendicitis. One group (124 patients) received 2 g cefoxitin, the other group (126 patients) 2g piperacillin. Antibiotics were administered intravenously in the operating theatre immediately before surgery. Wound infection occurred in three patients, 2.4% of the cefoxitin group and in five patients (4%) of the second group (with no significant difference). The commonest infecting organisms were Escherichia coli (5 out of 8). Mean hospital stay for patients with wound infection was 15 days (range 12-21) compared with 6 days, (range C-8) for non-infected cases. Prophylactic cefoxitin or piperacillin were each therefore similarly effective in minimizing the rate of vvound infections in patients with non-perforated appendicitis. Keywords:
.L\ppendicectomy;
single
dose
antibiotic
prophylaxis
Introduction Appendicectomy is the commonest abdominal emergency operation and wound infection is the main cause of postoperative morbidity. There is still a continuing interest in the use of prophylactic antibiotics in appendicectomy, although the choice of antibiotic used and its dosage depend largely on the operating surgeon. Without the use of prophylactic antibiotics, wound infection rates can be as high as 10% even when the appendix is histologically normal.’ We have conducted a prospective trial to compare cefoxitin (‘Mefoxin’, MSD) with piperacillin (‘Pipril’, Lederle) for prevention of postoperative wound infection in patients with acute non-perforated appendicitis. Correspondence 0195%6701,‘94:020133+04
to: Isam 41. A. Salam, $08
Consultant
Surgeon,
OO#O
133
P.O.
Box 1006, X1 Xin,
U.4.E
134
I. M. A. Salam
et al.
Patients and methods All patients admitted to a single surgical unit in Al Ain Hospital, with the diagnosis of acute appendicitis, were considered for this trial which started in October 1989 and ended in October 1992. Patients with the diagnosis of localized or generalized peritonitis were excluded from the trial and were treated with gentamicin and metronidazole for 5 days. Prior to entry in the trial, patients were tested by intradermal injection, in the ward, for drug hypersensitivity to cefoxitin and piperacillin. Those who were allergic to either drug were withdrawn from the trial. Randomization was carried out in the operating theatre by a nurse, who picked one of two envelopes enclosing a paper printed with either the letter C (cefoxitin) or P (piperacillin). Patients received a single dose (2 g) of either cefoxitin or piperacillin. The antibiotic was diluted in 20 ml of water for injection and then administered intravenously (iv) prior to skin incision. Appendicectomy was standard and performed by an experienced surgeon. When the appendix was gangrenous, perforated, or a mass was found, the patient was withdrawn from the trial; these patients were treated with 80 mg of gentamicin and 500 mg metronidazole 8-hourly for 5 days. Peritoneal fluid and the appendix stump were swabbed and cultured. Abdominal or wound drains were not used and no topical antibiotics were employed. Wounds were closed in layers and a light dressing applied. Incisions were not inspected routinely. Stitches were usually removed on the seventh postoperative day. Earlier removal was performed in exceptional cases of wound infection. Patients were reviewed in the ‘out-patients’ department on the 14th postoperative day and 6 weeks later. Wound infection was defined as discharge of pus or positive bacteriological culture from a wound discharge. A stitch abscess, remote from the incision, or erythema that did not progress to suppuration were excluded.* The statistical method employed was a test of two proportions using 2 distribution, to test the hypothesis that the two drugs may be equal or unequal in efficacy;3 specification of the significance level was 9.5%.
Results Out of 330 patients, 30 were diagnosed preoperatively as having perforated or gangrenous appendicitis and therefore were not randomized. Five patients had drug allergy, (three cefoxitin, two piperacillin) and were excluded. Of the 29.5 patients randomized, 42 were diagnosed during surgery as having perforated or gangrenous appendicitis and were excluded after randomization. Three patients were subsequently excluded because they received further doses of antibiotics postoperatively. Of the 250 patients remaining in the study, 124 received cefoxitin and 126 piperacillin. There were 200 males and 50 females aged from 13-60 years (mean 27). The groups were well matched for age (mean 27 years, range 13-60; mean 27
Antibiotic
prophylaxis
135
in appendicectomy
years, range 14-58) and gender (M 98 F 26; M 102 F24). Wound infection occurred in three patients (2.4%) in the cefoxitin group and in five patients (4%) in the piperacillin group. This difference was not significant (P= 0.50). The infecting organisms were Escherichia coli (S), Staphylococcus aweus (l), Enterococcusfaecalis (1) and Klebsiella sp. (1). Four of the wound infections appeared 4 weeks after discharge home and these patients were readmitted for dressing. Hospital stay for patients with wound infections was 12-21 days (mean 15) and for the others 48 days (mean 6). Discussion
Both cefoxitin and piperacillin are bactericidal antibiotics with broad spectrum coverage of Gram-positive and Gram-negative microorganisms.“a5 They are active against anaerobic organisms including Bacteriodes fragilis, clostridia, peptococci and peptostreptococci. W’ithout antibiotic prophylaxis, wound infection rates following appendicectomy are reported to be 10% when the appendix is normal, increasing to 30% when the appendix is gangrenous or perforated.’ In our study we eliminated factors known to influence the incidence of wound infection, such as inclusion of patients with gangrenous or perforated appendicitis. We did not apply topical antibiotics and furthermore we did not use peritoneal or wound drains. As appendicectomy is a relatively short operation (30-45 min) we felt that a single dose (2 g) of either antibiotic was sufficient cover for the period of potential contamination. We followed up our patients for 6 weeks after the operation and were able to pick up delayed wound infections. All patients who had a wound infection had positive cultures from peritoneal fluid and/or the appendix stump. ‘I’his agrees with other studies that reported incidences of 90%-93% of contamination in infected patients.“,7 Mean hospital stay was more than double in infected patients (15 days) as compared with those without infection (6 days). Avoiding wound infection after appendicectomy should be the aim of all surgeons. One of the ways to achieve this is by single dose antibiotic prophylaxis. 8.9Although the incidence in wound infection in the two groups was not significantly different, we cannot exclude a type 2 error. However a study of 1891 patients in each arm of the study would be required in order to demonstrate the significance of a difference and exclude a type 2 error. Overall the wound infection rates observed in our study were low, indicating that either antibiotic would be a suitable choice for prophylaxis. We are grateful to Mr. typing the manuscript.
I. 0.
Klafalla
for
his
help
with
statistics
and
to lXlr.
Khurshid
for
References 1. Krukowski Surg 1988;
ZH, Irwin ST, 75: 1023-1033.
Denholm
S et al. Wound
infection
after
appendicectomy.
BrJ
I. M. A. Salam
136 2. Ljungguist 3. Terre1 D.
V. A Statistics, 5th 4. Corder AP, appendicitis-a intravenously. 5. Winslow LE,
et al.
Wound sepsis after clean operations. Lancet 1965; I: 1095-1097. test for the difference between two population proportions. In: Business edn. Boston: Houghton Muffin 1989; 343, 1344. ISBN o-395-36905-3. Prior JE, Bates TE et al. Metronidazole versus cefoxitin in severe trial to compare a single intraoperative dose of two antibiotics given Postgrad Med J 1983; 59: 720-723. Dean RE, Harley JW, et al. Acute nonperforating appendicitis. Arch Surg
1983; 118: 651-665.
6. Holmes B, Richard DM, Brogden RN, et al. Piperacillin: A review of its antibacterial activity, pharmacokinetics properties and therapeutic use. Drugs 1984; 28: 375-425. 7. Donovan IA, Ellis D, Gatehouse D, et al. One dose antibiotic prophylaxis against wound infection after appendicectomy: a randomized trial of clindamycin, cephazolin sodium and a placebo. BY J Suyg 1979; 66: 1930. 8. Gledhill T, Odurni A, Weaver PC et al. A controlled trial of single dosage cephamandole in the prophylaxis of wound infections in appendicectomy. Surg Gynecol Obstet 1983;
156: 29-36. 9. Gaffney
PR.
74: 791-794.
Wound
infection
in appendicitis:
effective
prophylaxis.
World J Surg 1984;
of Hospital
Infection
(1994)
26, 133~-136
SHORT
REPORT
A randomized prospective study of cefoxitin piperacillin in appendicectomy I. M. A. Salam, K. H, Abu Galala, Chandran, N. N. Asham
versus
Y. I. El Ashaal, V. P. Prem and A. J. W. Sim
Department of Surgery, Al Ain Hospital and Faculty of Medicine and Health Sciences, United Arab Emirates Accepted for publication 20 October 1993 Summary: A randomized prospective study of antibiotic prophylaxis using a single dose of either cefoxitin or piperacillin is presented. The trial was carried out in Al Ain Hospital in the period 1989-l 992 on 250 adult patients with non-perforated appendicitis. One group (124 patients) received 2 g cefoxitin, the other group (126 patients) 2g piperacillin. Antibiotics were administered intravenously in the operating theatre immediately before surgery. Wound infection occurred in three patients, 2.4% of the cefoxitin group and in five patients (4%) of the second group (with no significant difference). The commonest infecting organisms were Escherichia coli (5 out of 8). Mean hospital stay for patients with wound infection was 15 days (range 12-21) compared with 6 days, (range C-8) for non-infected cases. Prophylactic cefoxitin or piperacillin were each therefore similarly effective in minimizing the rate of vvound infections in patients with non-perforated appendicitis. Keywords:
.L\ppendicectomy;
single
dose
antibiotic
prophylaxis
Introduction Appendicectomy is the commonest abdominal emergency operation and wound infection is the main cause of postoperative morbidity. There is still a continuing interest in the use of prophylactic antibiotics in appendicectomy, although the choice of antibiotic used and its dosage depend largely on the operating surgeon. Without the use of prophylactic antibiotics, wound infection rates can be as high as 10% even when the appendix is histologically normal.’ We have conducted a prospective trial to compare cefoxitin (‘Mefoxin’, MSD) with piperacillin (‘Pipril’, Lederle) for prevention of postoperative wound infection in patients with acute non-perforated appendicitis. Correspondence 0195%6701,‘94:020133+04
to: Isam 41. A. Salam, $08
Consultant
Surgeon,
OO#O
133
P.O.
Box 1006, X1 Xin,
U.4.E
134
I. M. A. Salam
et al.
Patients and methods All patients admitted to a single surgical unit in Al Ain Hospital, with the diagnosis of acute appendicitis, were considered for this trial which started in October 1989 and ended in October 1992. Patients with the diagnosis of localized or generalized peritonitis were excluded from the trial and were treated with gentamicin and metronidazole for 5 days. Prior to entry in the trial, patients were tested by intradermal injection, in the ward, for drug hypersensitivity to cefoxitin and piperacillin. Those who were allergic to either drug were withdrawn from the trial. Randomization was carried out in the operating theatre by a nurse, who picked one of two envelopes enclosing a paper printed with either the letter C (cefoxitin) or P (piperacillin). Patients received a single dose (2 g) of either cefoxitin or piperacillin. The antibiotic was diluted in 20 ml of water for injection and then administered intravenously (iv) prior to skin incision. Appendicectomy was standard and performed by an experienced surgeon. When the appendix was gangrenous, perforated, or a mass was found, the patient was withdrawn from the trial; these patients were treated with 80 mg of gentamicin and 500 mg metronidazole 8-hourly for 5 days. Peritoneal fluid and the appendix stump were swabbed and cultured. Abdominal or wound drains were not used and no topical antibiotics were employed. Wounds were closed in layers and a light dressing applied. Incisions were not inspected routinely. Stitches were usually removed on the seventh postoperative day. Earlier removal was performed in exceptional cases of wound infection. Patients were reviewed in the ‘out-patients’ department on the 14th postoperative day and 6 weeks later. Wound infection was defined as discharge of pus or positive bacteriological culture from a wound discharge. A stitch abscess, remote from the incision, or erythema that did not progress to suppuration were excluded.* The statistical method employed was a test of two proportions using 2 distribution, to test the hypothesis that the two drugs may be equal or unequal in efficacy;3 specification of the significance level was 9.5%.
Results Out of 330 patients, 30 were diagnosed preoperatively as having perforated or gangrenous appendicitis and therefore were not randomized. Five patients had drug allergy, (three cefoxitin, two piperacillin) and were excluded. Of the 29.5 patients randomized, 42 were diagnosed during surgery as having perforated or gangrenous appendicitis and were excluded after randomization. Three patients were subsequently excluded because they received further doses of antibiotics postoperatively. Of the 250 patients remaining in the study, 124 received cefoxitin and 126 piperacillin. There were 200 males and 50 females aged from 13-60 years (mean 27). The groups were well matched for age (mean 27 years, range 13-60; mean 27
Antibiotic
prophylaxis
135
in appendicectomy
years, range 14-58) and gender (M 98 F 26; M 102 F24). Wound infection occurred in three patients (2.4%) in the cefoxitin group and in five patients (4%) in the piperacillin group. This difference was not significant (P= 0.50). The infecting organisms were Escherichia coli (S), Staphylococcus aweus (l), Enterococcusfaecalis (1) and Klebsiella sp. (1). Four of the wound infections appeared 4 weeks after discharge home and these patients were readmitted for dressing. Hospital stay for patients with wound infections was 12-21 days (mean 15) and for the others 48 days (mean 6). Discussion
Both cefoxitin and piperacillin are bactericidal antibiotics with broad spectrum coverage of Gram-positive and Gram-negative microorganisms.“a5 They are active against anaerobic organisms including Bacteriodes fragilis, clostridia, peptococci and peptostreptococci. W’ithout antibiotic prophylaxis, wound infection rates following appendicectomy are reported to be 10% when the appendix is normal, increasing to 30% when the appendix is gangrenous or perforated.’ In our study we eliminated factors known to influence the incidence of wound infection, such as inclusion of patients with gangrenous or perforated appendicitis. We did not apply topical antibiotics and furthermore we did not use peritoneal or wound drains. As appendicectomy is a relatively short operation (30-45 min) we felt that a single dose (2 g) of either antibiotic was sufficient cover for the period of potential contamination. We followed up our patients for 6 weeks after the operation and were able to pick up delayed wound infections. All patients who had a wound infection had positive cultures from peritoneal fluid and/or the appendix stump. ‘I’his agrees with other studies that reported incidences of 90%-93% of contamination in infected patients.“,7 Mean hospital stay was more than double in infected patients (15 days) as compared with those without infection (6 days). Avoiding wound infection after appendicectomy should be the aim of all surgeons. One of the ways to achieve this is by single dose antibiotic prophylaxis. 8.9Although the incidence in wound infection in the two groups was not significantly different, we cannot exclude a type 2 error. However a study of 1891 patients in each arm of the study would be required in order to demonstrate the significance of a difference and exclude a type 2 error. Overall the wound infection rates observed in our study were low, indicating that either antibiotic would be a suitable choice for prophylaxis. We are grateful to Mr. typing the manuscript.
I. 0.
Klafalla
for
his
help
with
statistics
and
to lXlr.
Khurshid
for
References 1. Krukowski Surg 1988;
ZH, Irwin ST, 75: 1023-1033.
Denholm
S et al. Wound
infection
after
appendicectomy.
BrJ
I. M. A. Salam
136 2. Ljungguist 3. Terre1 D.
V. A Statistics, 5th 4. Corder AP, appendicitis-a intravenously. 5. Winslow LE,
et al.
Wound sepsis after clean operations. Lancet 1965; I: 1095-1097. test for the difference between two population proportions. In: Business edn. Boston: Houghton Muffin 1989; 343, 1344. ISBN o-395-36905-3. Prior JE, Bates TE et al. Metronidazole versus cefoxitin in severe trial to compare a single intraoperative dose of two antibiotics given Postgrad Med J 1983; 59: 720-723. Dean RE, Harley JW, et al. Acute nonperforating appendicitis. Arch Surg
1983; 118: 651-665.
6. Holmes B, Richard DM, Brogden RN, et al. Piperacillin: A review of its antibacterial activity, pharmacokinetics properties and therapeutic use. Drugs 1984; 28: 375-425. 7. Donovan IA, Ellis D, Gatehouse D, et al. One dose antibiotic prophylaxis against wound infection after appendicectomy: a randomized trial of clindamycin, cephazolin sodium and a placebo. BY J Suyg 1979; 66: 1930. 8. Gledhill T, Odurni A, Weaver PC et al. A controlled trial of single dosage cephamandole in the prophylaxis of wound infections in appendicectomy. Surg Gynecol Obstet 1983;
156: 29-36. 9. Gaffney
PR.
74: 791-794.
Wound
infection
in appendicitis:
effective
prophylaxis.
World J Surg 1984;