Comparative Study of Single-Dose Cefotaxime and Multiple Doses of Cefoxitin and Cefazolin as Prophylaxis in Gynecologic Surgery Francisco Campillo, MD, Jos6 Manuel Rubio, MD, Madrid, Spain
In this comparative, randomized, m u h i c e n t e r trial, 2 7 3 patients scheduled for gynecologic surgery were studied: 87 received a single 1-g dose of cefotaxime 30 minutes before surgery; 81 were given a 1-g dose of cefoxitin 3 0 minutes before surgery and 1 g every 6 hours for 2 4 hours after surgery (total dose 4 g); and 105 received a 1-g dose of eefazolin 30 minutes before surgery, followed by 1 g every 8 hours for 4 8 hours (total dose 6 g). Patients who received cefotaxime had a significantly lower incidence of postoperative fever compared with those t r e a t e d with cefoxitin or cefazolin (p < 0 . 0 1 ) . The incidence of positive urinary cultures was lower in the cefotaxime and cefazolin groups when c o m p a r e d with the cefoxitin g r o u p (p < 0 . 0 1 and p < 0 . 0 5 , respectively). The results of this study confirm the efficacy of cefotaxime as prophylaxis in surgical infections and demonstrate that single-dose cefotaxime is m o r e effective than a four-dose regimen of cefoxitin.
From the Hospital Ramon y Cajal, Carretera de Colmenar, Madrid, Spain. Requests for reprints should be addressed to Francisco Campillo, MD, C/San Francisco de Sales, 28-6~B, 28003 Madrid, Spain. 12S
infection is the most frequent complication in gynecologic and obstetric surgery, particuFlarlyPostoperative in cesarean sections, myomectomies, and total vaginal and abdominal hysterectomies [1-3]. The type of wound infections are similar to those in other abdominal operations such as the involvement of skin flora. In the case of vaginal bacterial infections the most frequently observed pathogens were Bacteroides species, Peptostreptococcus, and Enterobacteriaceae (usually Escherichia coli). In our study groups, Staphylococcus aureus as well as a variety of gram-negative pathogens, such as Pseudomonas aeruginosa were encountered. Clean-contaminated wounds included surgical wounds in which the genitourinary tract was involved, but without significant bacterial contamination of the operative field. Other factors that may have influenced the postoperative infection rate were obesity, malnutrition, diabetes mellitus, and other concomitant illnesses. The perioperative utilization of antimicrobial agents has significantly reduced the number of infectious morbidities and their associated costs [4]. In recent years much research has been carried out to establish the optimal dosage regimen and the selection of the most cost-effective agents. Cefotaxime was selected for this study due to its broad spectrum of activity and the presence of an active metabolite that produces an effective, extended antibiotic coverage. Cefotaxime provides the opportunity to compare a third-generation cephalosporin with cephalosporins of the first and second generations, and provides the possibility of evaluating cefotaxime in a single-dose prophylaxis regimen. The current multicenter study was carried out in a total of ten hospitals to investigate the efficacy and tolerability of single-dose cefotaxime compared with multiple doses of cefoxitin or cefazolin. MATERIALS AND METHODS Patients: Patients eligible for entry were women about to undergo a wide range of gynecologic procedures, both abdominal and vaginal. Of the patients, 40% underwent total hysterectomies with bilateral adnexectomy; 15% underwent simple hysterectomies or hysterectomies with unilateral adnexectomies; 20% underwent adnexectomies or removal of ovarian cysts; and the remainder underwent a variety of other operations that included myomectomy, Manchester operation, vulvectomy, laparoscopy with biopsy, and tubal occlusion with curettage. Patients who had used any kind of antibiotics during the month prior to the surgery were excluded from the
THE AMERICAN JOURNAL OF SURGERY VOLUME 164 NO. 4A (SUPPL) OCTOBER 1992
CEFOTAXIME SINGLE DOSE PROPHYLAXIS
study. The following groups of patients were also not eligible for enrollment: (a) Patients undergoing minor surgery. The low incidence of infections and the short duration of hospitalization in these patients make effective follow-up difficult. (b) Patients undergoing surgery for the treatment of urinary incontinence; in these patients urine catheters are used for long periods of time, which differentiates them from the other groups studied. (c) Patients who were allergic to penicillins; possible cross-reactions with cephalosporins might also
TABLE I Mean Age of Patients Average Age (years)
Group
Typical Deviation
Age Range
Group h Cefotaxime Group I1:Cefoxitin
48
13
18--79
46
12
21--76
Group I11:Cefazolin
48
13
18---80
Variance analysis: F = 0,788 (not significant),
occur.
Prophylactic treatment: A total of 273 patients were entered into the trial; these patients were divided according to the following treatment groups: Group I (n = 87): cefotaxime (CTX)--a single 1-g dose intravenously (IV) 30 minutes before surgery; Group II (n = 81): cefoxitin (FOX)--I g IV 30 minutes before surgery and 1 g IV every 6 hours for 24 hours (total dose 4 g); Group III (n = 105): cefazolin (CZ)--I g IV 30 minutes before surgery and 1 g IV every 8 hours for 48 hours (total dose 6 g). Of the 273, 247 patients (90%) required the use of urinary catheters (78 in Group I, 74 in group II and 95 in group III). There were no differences in this respect among the three groups. No other antibiotics were administered. A s s e s s m e n t of efficacy: The following parameters were analyzed: (a) postsurgery temperature; (b) postsurgery positive urine cultures; (c) the incidence of postoperative infections in the abdominal lining and the appearance of other infections; (d) and adverse reactions. The efficacy analysis was based on the following six-point postsurgery illness evaluation scale: 0, no postsurgery infection; 1, slight alterations (such as a mild temperature rise); 2, elevated temperature; 3, positive urine cultures; 4, elevated temperature and infection; 5, additional complications. Efficacy was defined as a patient being free of postoperative infection or, at most, falling into the "slight alteration" category. The inclusion of one parameter in the efficacy definition differed from center to center because a number of surgeons used the "no postsurgery infection" parameter as the only efficacy criterion. M u l t i e e n t e r group: This study was conducted at the following hospitals in Spain: Hospital de Cfidiz; Hospital Clinico de Valladolid; Hospital de Covadonga, Oviedo; Hospital de la Esperanza, Barcelona; Hospital General de Vigo; Hospital San Milhin, Logrofio; Hospital Virgen de la Arrixaca, Murcia; Hospital Virgen del Camino, Pamplona; Hospital Virgen del Rocio, Sevilla; Hospital Ram6n y Cajal, Madrid.
TABLE II Percentage of Patients With Concomitant Illnesses and Treatments Employed
CTX (%)
FOX (%)
CZ (%)
Overall (%)
Concomitant illness* Present
20 (23)
14 (18)
22 (21)
(21)
Absent
6 7 (78)
66 (83)
8 2 (79)
(79)
18 (22)
42 (40)
(29)
63 (78)
63 (60)
(71)
Additional treatments t Administered
20 (23)
Not administered
67
(77)
*Chi-square - 0.79, degrees of freedom 2, p = 0.67, not significant. tChi-square - 9.43; degrees of freedom 2, p = 0.008; significant (p < 0.01) between c'rx and FOX with respect to CZ; no antibiotic treatment was given, C'FX = cefotaxime; FOX = cefoxitin; CZ = cefazolin.
TABLE III Type of Surgery According to Group
Abdominal
Vaginal
CTX (%)
FOX (%)
CZ (%)
Overall (%)
78 (94)
72 (92)
88 (87)
(91)
5 (6)
6 (8)
13 (13)
(9)
Chi-square = 2,85; degrees of freedom 2, p = 0.23, not significant. CTX = cefotaxime; FOX = cefoxitin; CZ = cefazolin.
RESULTS The three study groups were comparable in age (Table I), concomitant illness, and additional treatment (Table II). Among the diseases associated with the etiology that justified surgery, the most common were diabetes, peripheral vasculopathy, chronic hepatic disease, and various allergies. The most frequently used treatment was heparin or insulin. Groups were also comparable in duration of surgery, catheterization, and type of surgery (abdominal or vaginal), although slightly more patients underwent vaginal surgery in the cefazolin group (Table III). The duration of the operation was similar for all three treatment groups with an average of 65.6 minutes for group I (CTX); 64.2 for group II (FOX); and 64.9 for group III (CZ). The variance analysis was F = 0.248 (not significant). Prophylaxis was administered preoperatively in group
THE AMERICAN JOURNAL OF SURGERY VOLUME 164 NO. 4A (SUPPL) OCTOBER 1992 135
CAMPILLO AND RUBIO
TABLE IV Incidence of Postoperative Fever CTX (%)
FOX (%)
CZ (%)
p Value
5 (6) 81 (94)
12 (16) 63 (84)
24 (24) 78 (76)
p < 0.01 between CTX and FOX/CZ
Fever present Fever absent
CTX - cefotaxime; FOX = cefoxitin; CZ = cefazolin.
TABLE V Incidence of Postoperative Infections CTX (%) FOX (%) CZ (%)
p Value
Urine culture Positive
12 (14)
20 (27)
9 (9)
Negative
72 (86)
54 (73)
8 6 (91)
84 (98)
75 (95)
97 (97)
2 (2)
4 (5)
3 (3)
p
In this comparative, randomized, m u h i c e n t e r trial, 2 7 3 patients scheduled for gynecologic surgery were studied: 87 received a single 1-g dose of cefotaxime 30 minutes before surgery; 81 were given a 1-g dose of cefoxitin 3 0 minutes before surgery and 1 g every 6 hours for 2 4 hours after surgery (total dose 4 g); and 105 received a 1-g dose of eefazolin 30 minutes before surgery, followed by 1 g every 8 hours for 4 8 hours (total dose 6 g). Patients who received cefotaxime had a significantly lower incidence of postoperative fever compared with those t r e a t e d with cefoxitin or cefazolin (p < 0 . 0 1 ) . The incidence of positive urinary cultures was lower in the cefotaxime and cefazolin groups when c o m p a r e d with the cefoxitin g r o u p (p < 0 . 0 1 and p < 0 . 0 5 , respectively). The results of this study confirm the efficacy of cefotaxime as prophylaxis in surgical infections and demonstrate that single-dose cefotaxime is m o r e effective than a four-dose regimen of cefoxitin.
From the Hospital Ramon y Cajal, Carretera de Colmenar, Madrid, Spain. Requests for reprints should be addressed to Francisco Campillo, MD, C/San Francisco de Sales, 28-6~B, 28003 Madrid, Spain. 12S
infection is the most frequent complication in gynecologic and obstetric surgery, particuFlarlyPostoperative in cesarean sections, myomectomies, and total vaginal and abdominal hysterectomies [1-3]. The type of wound infections are similar to those in other abdominal operations such as the involvement of skin flora. In the case of vaginal bacterial infections the most frequently observed pathogens were Bacteroides species, Peptostreptococcus, and Enterobacteriaceae (usually Escherichia coli). In our study groups, Staphylococcus aureus as well as a variety of gram-negative pathogens, such as Pseudomonas aeruginosa were encountered. Clean-contaminated wounds included surgical wounds in which the genitourinary tract was involved, but without significant bacterial contamination of the operative field. Other factors that may have influenced the postoperative infection rate were obesity, malnutrition, diabetes mellitus, and other concomitant illnesses. The perioperative utilization of antimicrobial agents has significantly reduced the number of infectious morbidities and their associated costs [4]. In recent years much research has been carried out to establish the optimal dosage regimen and the selection of the most cost-effective agents. Cefotaxime was selected for this study due to its broad spectrum of activity and the presence of an active metabolite that produces an effective, extended antibiotic coverage. Cefotaxime provides the opportunity to compare a third-generation cephalosporin with cephalosporins of the first and second generations, and provides the possibility of evaluating cefotaxime in a single-dose prophylaxis regimen. The current multicenter study was carried out in a total of ten hospitals to investigate the efficacy and tolerability of single-dose cefotaxime compared with multiple doses of cefoxitin or cefazolin. MATERIALS AND METHODS Patients: Patients eligible for entry were women about to undergo a wide range of gynecologic procedures, both abdominal and vaginal. Of the patients, 40% underwent total hysterectomies with bilateral adnexectomy; 15% underwent simple hysterectomies or hysterectomies with unilateral adnexectomies; 20% underwent adnexectomies or removal of ovarian cysts; and the remainder underwent a variety of other operations that included myomectomy, Manchester operation, vulvectomy, laparoscopy with biopsy, and tubal occlusion with curettage. Patients who had used any kind of antibiotics during the month prior to the surgery were excluded from the
THE AMERICAN JOURNAL OF SURGERY VOLUME 164 NO. 4A (SUPPL) OCTOBER 1992
CEFOTAXIME SINGLE DOSE PROPHYLAXIS
study. The following groups of patients were also not eligible for enrollment: (a) Patients undergoing minor surgery. The low incidence of infections and the short duration of hospitalization in these patients make effective follow-up difficult. (b) Patients undergoing surgery for the treatment of urinary incontinence; in these patients urine catheters are used for long periods of time, which differentiates them from the other groups studied. (c) Patients who were allergic to penicillins; possible cross-reactions with cephalosporins might also
TABLE I Mean Age of Patients Average Age (years)
Group
Typical Deviation
Age Range
Group h Cefotaxime Group I1:Cefoxitin
48
13
18--79
46
12
21--76
Group I11:Cefazolin
48
13
18---80
Variance analysis: F = 0,788 (not significant),
occur.
Prophylactic treatment: A total of 273 patients were entered into the trial; these patients were divided according to the following treatment groups: Group I (n = 87): cefotaxime (CTX)--a single 1-g dose intravenously (IV) 30 minutes before surgery; Group II (n = 81): cefoxitin (FOX)--I g IV 30 minutes before surgery and 1 g IV every 6 hours for 24 hours (total dose 4 g); Group III (n = 105): cefazolin (CZ)--I g IV 30 minutes before surgery and 1 g IV every 8 hours for 48 hours (total dose 6 g). Of the 273, 247 patients (90%) required the use of urinary catheters (78 in Group I, 74 in group II and 95 in group III). There were no differences in this respect among the three groups. No other antibiotics were administered. A s s e s s m e n t of efficacy: The following parameters were analyzed: (a) postsurgery temperature; (b) postsurgery positive urine cultures; (c) the incidence of postoperative infections in the abdominal lining and the appearance of other infections; (d) and adverse reactions. The efficacy analysis was based on the following six-point postsurgery illness evaluation scale: 0, no postsurgery infection; 1, slight alterations (such as a mild temperature rise); 2, elevated temperature; 3, positive urine cultures; 4, elevated temperature and infection; 5, additional complications. Efficacy was defined as a patient being free of postoperative infection or, at most, falling into the "slight alteration" category. The inclusion of one parameter in the efficacy definition differed from center to center because a number of surgeons used the "no postsurgery infection" parameter as the only efficacy criterion. M u l t i e e n t e r group: This study was conducted at the following hospitals in Spain: Hospital de Cfidiz; Hospital Clinico de Valladolid; Hospital de Covadonga, Oviedo; Hospital de la Esperanza, Barcelona; Hospital General de Vigo; Hospital San Milhin, Logrofio; Hospital Virgen de la Arrixaca, Murcia; Hospital Virgen del Camino, Pamplona; Hospital Virgen del Rocio, Sevilla; Hospital Ram6n y Cajal, Madrid.
TABLE II Percentage of Patients With Concomitant Illnesses and Treatments Employed
CTX (%)
FOX (%)
CZ (%)
Overall (%)
Concomitant illness* Present
20 (23)
14 (18)
22 (21)
(21)
Absent
6 7 (78)
66 (83)
8 2 (79)
(79)
18 (22)
42 (40)
(29)
63 (78)
63 (60)
(71)
Additional treatments t Administered
20 (23)
Not administered
67
(77)
*Chi-square - 0.79, degrees of freedom 2, p = 0.67, not significant. tChi-square - 9.43; degrees of freedom 2, p = 0.008; significant (p < 0.01) between c'rx and FOX with respect to CZ; no antibiotic treatment was given, C'FX = cefotaxime; FOX = cefoxitin; CZ = cefazolin.
TABLE III Type of Surgery According to Group
Abdominal
Vaginal
CTX (%)
FOX (%)
CZ (%)
Overall (%)
78 (94)
72 (92)
88 (87)
(91)
5 (6)
6 (8)
13 (13)
(9)
Chi-square = 2,85; degrees of freedom 2, p = 0.23, not significant. CTX = cefotaxime; FOX = cefoxitin; CZ = cefazolin.
RESULTS The three study groups were comparable in age (Table I), concomitant illness, and additional treatment (Table II). Among the diseases associated with the etiology that justified surgery, the most common were diabetes, peripheral vasculopathy, chronic hepatic disease, and various allergies. The most frequently used treatment was heparin or insulin. Groups were also comparable in duration of surgery, catheterization, and type of surgery (abdominal or vaginal), although slightly more patients underwent vaginal surgery in the cefazolin group (Table III). The duration of the operation was similar for all three treatment groups with an average of 65.6 minutes for group I (CTX); 64.2 for group II (FOX); and 64.9 for group III (CZ). The variance analysis was F = 0.248 (not significant). Prophylaxis was administered preoperatively in group
THE AMERICAN JOURNAL OF SURGERY VOLUME 164 NO. 4A (SUPPL) OCTOBER 1992 135
CAMPILLO AND RUBIO
TABLE IV Incidence of Postoperative Fever CTX (%)
FOX (%)
CZ (%)
p Value
5 (6) 81 (94)
12 (16) 63 (84)
24 (24) 78 (76)
p < 0.01 between CTX and FOX/CZ
Fever present Fever absent
CTX - cefotaxime; FOX = cefoxitin; CZ = cefazolin.
TABLE V Incidence of Postoperative Infections CTX (%) FOX (%) CZ (%)
p Value
Urine culture Positive
12 (14)
20 (27)
9 (9)
Negative
72 (86)
54 (73)
8 6 (91)
84 (98)
75 (95)
97 (97)
2 (2)
4 (5)
3 (3)
p
