Journal
of Hospital
Znfection (1991)
17, 303-306
SHORT
A randomized ceftizoxime prophylaxis
prospective study to compare with cephradine as single dose in elective cholecystectomy
D. Skipper, University
Surgical
REPORT
A. P. Corder
and S. J. Karran
Unit, Southampton General Hospital, Southampton SO9 4X Y
Accepted for publication 21 January
Tremona Road,
1991
Summary:
This study compares the efficacy of ceftizoxime with that of cephradine as single agent prophylaxis in elective cholecystectomy. The incidence of purulent wound infection was low in both groups (ceftizoxime l/99; cephradine 2/92). No adverse reactions to the trial antibiotics occurred in either group. Ceftizoxime is a safe, effective, convenient and well-tolerated antibiotic for use as single agent prophylaxis in elective cholecystectomy. However, because it has no demonstrable advantage over cephradine and is three times as expensive, its routine use is not justified.
Keywords: antibiotic
Ceftizoxime; prophylaxis.
cephradine;
elective
cholecystectomy;
single
dose
Introduction
The principle of single dose antibiotic prophylaxis in elective cholecystectomy is now well established, and cephalosporins are widely used for this purpose. Choice of antibiotic should be based on efficacy, Wellcome) is a third generation safety and cost.’ Ceftizoxime (‘Cefizox’; cephalosporin with a wide spectrum of activity against Gram-negative organisms.2 The aims of this study were to evaluate the safety and efficacy of ceftizoxime as a single agent prophylactic antibiotic in elective cholecystectomy, and compare it to cephradine, whose efficacy is proven.3 Materials
and
method
All patients undergoing elective cholecystectomy, with or without exploration of the common bile duct, in two centres, were considered for inclusion in the study. Patients were excluded if there was an allergy to Correspondence Road, London 0,95-6701/91/040303
to: Mr D. Skipper, SW17 OQT. f04
Department
of Vascular
Surgery,
St. George’s
Hospital,
C 1991 The Hospital
SO3.0010 303
Blackshaw
Infection
Socrety
D. Skipper
304
et al.
p-lactam antibiotics, if they had received antibiotics in the 7 days prior to surgery, if there was hepatic or renal impairment, or if they were pregnant. Patient consent and Ethical Committee approval were obtained. Patients were randomized in equal numbers to receive either ceftizoxime 2 g or cephradine 2 g intravenously at induction of anaesthesia. Data were collected prospectively for each patient by one investigator in each centre, laboratory investigations and detailing age, sex, history, examination, operative details. At operation, swabs were taken of the opened gall-bladder, of common duct bile (if this could be obtained without needling the common bile duct), and of the wound fat before closure. The wounds were inspected postoperatively by the investigator and were graded ‘0’ = no wound infection; ‘1’ = erythema; ‘2’ = purulent or bacteriologically positive discharge; or ‘3’ = severe wound infection with or without dehiscence. Swabs were taken of infected wounds. For the purposes of this study bacterial isolates were not assessedfor sensitivity to ceftizoxime and cephradine. The occurrence of other infective and non-infective complications was noted. Patients were seen 1 month post discharge, and complications, particularly those relating to the wound, were recorded. Results
Two hundred and ten patients were recruited (106 randomized to receive ceftizoxime and 104 to receive cephradine). Subsequent withdrawal left 99 remaining in the ceftizoxime group and 92 in the cephradine group. Both groups were well matched for age and sex. Males comprised 25% of each group and tended to be older than the females. The incidence of wound infection was low and there was no significant difference between the two treatment groups (Table I). In both groups grade ‘1’ (ceftizoxime 4/99; cephradine 4/92) and grade ‘2’ (ceftizoxime l/99; cephradine 2/92) infections occurred. No wounds were classified as severe infection (grade ‘3’). Wound infections tended to occur early in the postoperative course, with a median onset around the fifth postoperative day. Staphylococcus
Table Wound
infection
1.
Incidence and grade of wound infections
grade*
by treatment group
Treatment
group
Ceftizoxime
Cephradine
Total
3
94 (95%) 4( 4%) l( 1%) 0
86 (93.5%) 4 ( 4.5%) 2 ( 2%) 0
180 (94%) 8 ( 4.5%) 3 ( 1.5%) 0
Total
99
0 :
t x*=0.190;
1d.f.;
not a significant
difference.
b
92 * See text for explanation.
it
191
Cholecystectomy Table
II.
Summary
of infective
complications
prophylaxis other
than
wound Treatment
Ceftizoxime Chest infection Urinary tract infection Fever of unknown origin Sub-hepatic collection Infected bile leak Septicaemia
(N=99)
305 infections
by treatment
group
group Cephradine
(N=92)
7 ; : 1 :
i 1 1
aureus was an important cause of wound infection in this study, occurring in all purulent (grade ‘2’) infections (in one case mixed coliforms were also isolated). Bacteria grew from peroperative swabs in the ceftizoxime group (wound 10%; bile duct 13%; gall-bladder 12%) and in the cephradine group (wound 14%; bile duct 18%; gall-bladder 19%), but most of these patients had no subsequent wound infection. In only one case was the wound infection isolate the same as the peroperative wound isolate (S. aureus). Wound infections did not occur more commonly if the bile duct was explored. The incidence of other infective complications was low (Table II) with no significant difference between the two treatment groups. Non-infective complications included: pulmonary embolism 4; bile leak 2; haematemesis 1; prolonged ileus 4 and urinary retention 8. All recovered without sequelae. No adverse reaction to the antibiotics occurred in either treatment group. Nineteen patients were withdrawn from the study for the following reasons: extra antibiotics given at the discretion of the surgeon (14 patients); carcinoma of the pancreas first diagnosed at laparotomy (2 patients); bile duct injury requiring duct re-anastomosis (2 patients); subsequently found to be on long-term low-dose tetracycline (1 patient). One death occurred of a 71 -year-old female receiving cephradine. She had a carcinoma of the head of the pancreas, was withdrawn from the study, and died 2 months postoperatively. Discussion
Wound infection rates were low in this study (overall infection rate ceftizoxime 5 %, cephradine 6.5 %; purulent wound infections ceftizoxime l%, cephradine 2%). These results compare favourably with those from other studies using single dose cephalosporin prophylaxis in elective cholecystectomy.3 In all three cases of purulent wound infection, the infecting organism was S. aureus, combined with Escherichia coli on one occasion. This finding supports other studies which have shown S. aureus to
306
D. Skipper
et al.
be an important cause of wound infection after biliary surgery in those patients who received antibiotic prophylaxis.4 However, S. aureus was grown from peroperative swabs in only one of the three patients who subsequently developed wound infection with this organism, confirming the observation of previous workers that the peroperative contaminating organism does not predict the organism which is responsible for subsequent wound infection.5 Other infective complications were few in number and were not significantly more common in one treatment group. No adverse reaction to either of the trial antibiotics occurred, and the one death in the study period was not related to failure of antibiotic therapy. Cephradine is well recognized as an effective antibiotic for single dose prophylaxis in biliary surgery. Ceftizoxime is a third generation cephalosporin with greater activity against Gram-negative organisms than cephradine, although at the expense of activity against S. UZLWUS.~ From the results of this study it is clear that ceftizoxime is a safe, effective, convenient and well-tolerated antibiotic when used for single dose prophylaxis in elective biliary surgery. Its efficacy is comparable to that of cephradine. However, as it has no demonstrable clinical superiority over cephradine and is almost three times as expensive [cephradine (iv) E3.90 per 2 g; ceftizoxime (iv) E11.00 per 2 g]* it cannot therefore be recommended for routine use. We are grateful to the Surgeons of Basingstoke District Infirmary for allowing us to study their patients, and Laboratory Staff of these hospitals for their help.
Hospital to the
and Salisbury Medical and
General Technical
References 1. Burnakis
TG.
Surgical
antimicrobial
prophylaxis:
Pharmacotherapy 1984; 4: 248-27 1. 2. British National Formulary 1989; 16: 208-209. 3. Karran SJ, Lewington V, Allen, S, Cooper A. Prospective
4. 5.
principles
and
guidelines.
double blind evaluation of single dose intravenous prophylaxis using three cephalosporins in biliary surgery. Proceedings of the XV Congress of the European Society for Surgical Research 1981, Garmisch-Partenkirchen. Masterton RG. Antimicrobial prophylaxis in low risk biliary surgery. 3 Antimicrob Chemother 1986; 18: 4-6. Garibaldi RA, Maglio S, Lyons R et al. Postcholecystectomy wound infection. Ann Surg
1986: 20: 65G654.
of Hospital
Znfection (1991)
17, 303-306
SHORT
A randomized ceftizoxime prophylaxis
prospective study to compare with cephradine as single dose in elective cholecystectomy
D. Skipper, University
Surgical
REPORT
A. P. Corder
and S. J. Karran
Unit, Southampton General Hospital, Southampton SO9 4X Y
Accepted for publication 21 January
Tremona Road,
1991
Summary:
This study compares the efficacy of ceftizoxime with that of cephradine as single agent prophylaxis in elective cholecystectomy. The incidence of purulent wound infection was low in both groups (ceftizoxime l/99; cephradine 2/92). No adverse reactions to the trial antibiotics occurred in either group. Ceftizoxime is a safe, effective, convenient and well-tolerated antibiotic for use as single agent prophylaxis in elective cholecystectomy. However, because it has no demonstrable advantage over cephradine and is three times as expensive, its routine use is not justified.
Keywords: antibiotic
Ceftizoxime; prophylaxis.
cephradine;
elective
cholecystectomy;
single
dose
Introduction
The principle of single dose antibiotic prophylaxis in elective cholecystectomy is now well established, and cephalosporins are widely used for this purpose. Choice of antibiotic should be based on efficacy, Wellcome) is a third generation safety and cost.’ Ceftizoxime (‘Cefizox’; cephalosporin with a wide spectrum of activity against Gram-negative organisms.2 The aims of this study were to evaluate the safety and efficacy of ceftizoxime as a single agent prophylactic antibiotic in elective cholecystectomy, and compare it to cephradine, whose efficacy is proven.3 Materials
and
method
All patients undergoing elective cholecystectomy, with or without exploration of the common bile duct, in two centres, were considered for inclusion in the study. Patients were excluded if there was an allergy to Correspondence Road, London 0,95-6701/91/040303
to: Mr D. Skipper, SW17 OQT. f04
Department
of Vascular
Surgery,
St. George’s
Hospital,
C 1991 The Hospital
SO3.0010 303
Blackshaw
Infection
Socrety
D. Skipper
304
et al.
p-lactam antibiotics, if they had received antibiotics in the 7 days prior to surgery, if there was hepatic or renal impairment, or if they were pregnant. Patient consent and Ethical Committee approval were obtained. Patients were randomized in equal numbers to receive either ceftizoxime 2 g or cephradine 2 g intravenously at induction of anaesthesia. Data were collected prospectively for each patient by one investigator in each centre, laboratory investigations and detailing age, sex, history, examination, operative details. At operation, swabs were taken of the opened gall-bladder, of common duct bile (if this could be obtained without needling the common bile duct), and of the wound fat before closure. The wounds were inspected postoperatively by the investigator and were graded ‘0’ = no wound infection; ‘1’ = erythema; ‘2’ = purulent or bacteriologically positive discharge; or ‘3’ = severe wound infection with or without dehiscence. Swabs were taken of infected wounds. For the purposes of this study bacterial isolates were not assessedfor sensitivity to ceftizoxime and cephradine. The occurrence of other infective and non-infective complications was noted. Patients were seen 1 month post discharge, and complications, particularly those relating to the wound, were recorded. Results
Two hundred and ten patients were recruited (106 randomized to receive ceftizoxime and 104 to receive cephradine). Subsequent withdrawal left 99 remaining in the ceftizoxime group and 92 in the cephradine group. Both groups were well matched for age and sex. Males comprised 25% of each group and tended to be older than the females. The incidence of wound infection was low and there was no significant difference between the two treatment groups (Table I). In both groups grade ‘1’ (ceftizoxime 4/99; cephradine 4/92) and grade ‘2’ (ceftizoxime l/99; cephradine 2/92) infections occurred. No wounds were classified as severe infection (grade ‘3’). Wound infections tended to occur early in the postoperative course, with a median onset around the fifth postoperative day. Staphylococcus
Table Wound
infection
1.
Incidence and grade of wound infections
grade*
by treatment group
Treatment
group
Ceftizoxime
Cephradine
Total
3
94 (95%) 4( 4%) l( 1%) 0
86 (93.5%) 4 ( 4.5%) 2 ( 2%) 0
180 (94%) 8 ( 4.5%) 3 ( 1.5%) 0
Total
99
0 :
t x*=0.190;
1d.f.;
not a significant
difference.
b
92 * See text for explanation.
it
191
Cholecystectomy Table
II.
Summary
of infective
complications
prophylaxis other
than
wound Treatment
Ceftizoxime Chest infection Urinary tract infection Fever of unknown origin Sub-hepatic collection Infected bile leak Septicaemia
(N=99)
305 infections
by treatment
group
group Cephradine
(N=92)
7 ; : 1 :
i 1 1
aureus was an important cause of wound infection in this study, occurring in all purulent (grade ‘2’) infections (in one case mixed coliforms were also isolated). Bacteria grew from peroperative swabs in the ceftizoxime group (wound 10%; bile duct 13%; gall-bladder 12%) and in the cephradine group (wound 14%; bile duct 18%; gall-bladder 19%), but most of these patients had no subsequent wound infection. In only one case was the wound infection isolate the same as the peroperative wound isolate (S. aureus). Wound infections did not occur more commonly if the bile duct was explored. The incidence of other infective complications was low (Table II) with no significant difference between the two treatment groups. Non-infective complications included: pulmonary embolism 4; bile leak 2; haematemesis 1; prolonged ileus 4 and urinary retention 8. All recovered without sequelae. No adverse reaction to the antibiotics occurred in either treatment group. Nineteen patients were withdrawn from the study for the following reasons: extra antibiotics given at the discretion of the surgeon (14 patients); carcinoma of the pancreas first diagnosed at laparotomy (2 patients); bile duct injury requiring duct re-anastomosis (2 patients); subsequently found to be on long-term low-dose tetracycline (1 patient). One death occurred of a 71 -year-old female receiving cephradine. She had a carcinoma of the head of the pancreas, was withdrawn from the study, and died 2 months postoperatively. Discussion
Wound infection rates were low in this study (overall infection rate ceftizoxime 5 %, cephradine 6.5 %; purulent wound infections ceftizoxime l%, cephradine 2%). These results compare favourably with those from other studies using single dose cephalosporin prophylaxis in elective cholecystectomy.3 In all three cases of purulent wound infection, the infecting organism was S. aureus, combined with Escherichia coli on one occasion. This finding supports other studies which have shown S. aureus to
306
D. Skipper
et al.
be an important cause of wound infection after biliary surgery in those patients who received antibiotic prophylaxis.4 However, S. aureus was grown from peroperative swabs in only one of the three patients who subsequently developed wound infection with this organism, confirming the observation of previous workers that the peroperative contaminating organism does not predict the organism which is responsible for subsequent wound infection.5 Other infective complications were few in number and were not significantly more common in one treatment group. No adverse reaction to either of the trial antibiotics occurred, and the one death in the study period was not related to failure of antibiotic therapy. Cephradine is well recognized as an effective antibiotic for single dose prophylaxis in biliary surgery. Ceftizoxime is a third generation cephalosporin with greater activity against Gram-negative organisms than cephradine, although at the expense of activity against S. UZLWUS.~ From the results of this study it is clear that ceftizoxime is a safe, effective, convenient and well-tolerated antibiotic when used for single dose prophylaxis in elective biliary surgery. Its efficacy is comparable to that of cephradine. However, as it has no demonstrable clinical superiority over cephradine and is almost three times as expensive [cephradine (iv) E3.90 per 2 g; ceftizoxime (iv) E11.00 per 2 g]* it cannot therefore be recommended for routine use. We are grateful to the Surgeons of Basingstoke District Infirmary for allowing us to study their patients, and Laboratory Staff of these hospitals for their help.
Hospital to the
and Salisbury Medical and
General Technical
References 1. Burnakis
TG.
Surgical
antimicrobial
prophylaxis:
Pharmacotherapy 1984; 4: 248-27 1. 2. British National Formulary 1989; 16: 208-209. 3. Karran SJ, Lewington V, Allen, S, Cooper A. Prospective
4. 5.
principles
and
guidelines.
double blind evaluation of single dose intravenous prophylaxis using three cephalosporins in biliary surgery. Proceedings of the XV Congress of the European Society for Surgical Research 1981, Garmisch-Partenkirchen. Masterton RG. Antimicrobial prophylaxis in low risk biliary surgery. 3 Antimicrob Chemother 1986; 18: 4-6. Garibaldi RA, Maglio S, Lyons R et al. Postcholecystectomy wound infection. Ann Surg
1986: 20: 65G654.
