Antibiotic prophylaxis in vaginal hysterectomy Three doses of cefuroxime plus metronidazole versus one dose of ciprofloxacin W.K. Brouwer, J.A.A. Hoogkamp-Korstanje and K.M. Kuiper Introduction
Vaginal hysterectomies are being performed in c o n t a m i n a t e d e n v i r o n m e n t s and, despite thorough pre-operative disinfection, complete sterility of the operation field cannot be attained [1]. In a pilot study on the use of antimicrobial prophylaxis in vaginal hysterectomy, post-operative febrile morbidity was observed in h a l f of the patients: 29 of 54 undergoing vaginal hysterectomy had post-operative febrile morbidity and 6 of 29 patients had vaginal cuff infiltrates. It did not m a t t e r w h e t h e r the hysterectomy was combined with a prolapse repair or not. The purpose of the f i r s t s t u d y (I) was to demonstrate the efficacy of antibiotic prophylaxis in vaginal hysterectomy. For this study, we used a combination of three intravenous doses cefuroxime 1,500 m g plus metronidazole 500 mg. In study II, the prophylactic efficacy of this combination was compared with one 200 mg intravenous dose of ciprofloxacin. Ciprofloxacin has activity against most aerobic microflora of t h e v a g i n a and also some anaerobic activity. Yet, this is less t h a n t h a t of the cefuroxime plus metronidazole combination. The impact of drugs on the cervical flora and the post-operative u r i n a r y tract infections have been described earlier [2]. Methods
Patients Study I was a prospective, randomized, doubleblind and placebo-controlled trial. Cefuroxime 1,500 mg plus metronidazole 500 mg were administered intravenously at the s t a r t of each operation, and after 6 and 12 h. The placebo was isotonic saline. To blind the trial, riboflavine was added to all solutions to produce a common yellow colour. S t u d y II was a non-blinded prospective compar-
ative study of one 200 m g dose of ciprofloxacin intravenously (generously provided by Bayer AG, Leverkusen, FRG) at the s t a r t of the operation, versus the cefuroxime plus metronidazole scheme of study I. The end-point of the study was when at least 50 patients had been enrolled in each group. After entry, the patients were alternately allocated to one of the two groups. All patients in study I and II were judged by the first author. The eligibility criteria for entry were: - all patients referred to our practice for vaginal hysterectomy with or without a prolapse repair; - no use of any antibiotic in the preceding 48 h; - no u r i n a r y tract infection; - normal liver and kidney function; - informed written consent. All patients received an indwelling u r i n a r y catheter which was removed after one day (without repair) or after seven days (with repair). In study I, we used u r e t h r a catheters, in study II, patients with a repair received a suprapubic catheter. The patients were operated by 2 gynaecologists and senior registrars. The surgeons were equally divided a m o n g the two groups, the registrars only operated in the second study. Rectal t e m p e r a t u r e was recorded twice daily. The time of discharge was determined by the patients' condition (normal t e m p e r a t u r e and feeling well). The criteria for post-operative infection were: - f e b r i l e morbidity: a t e m p e r a t u r e of > 3 8 ~ during two consecutive days or more excluding the first and second post-operative day; - u r i n a r y tract infection: > 1000 micro-organisms per ml in catheter urine with > 10 leukocytes per microscopic field (400 x); - v a g i n a l cuff infiltrate: palpable a b n o r m a l i t y with fever and p u r u l e n t discharge.
Keywords
Cefuroxime Ciprofloxacin Drug therapy Hysterectomy Metronidazole Pre-operative care Dr. W.K. Brouwer (correspondence) and Dr. K.M. Kuiper: Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD Leeuwarden, the Netherlands. Dr. J.A.A. Hoogkamp-Korstanje: Laboratory for Public Health, Jelsumerstraat 6, 8917 EN Leeuwarden, the Netherlands.
292
Brouwer WK, Hoogkamp-Korstanje JAA, Kuiper KM. Antibiotic prophylaxe in vaginal hysterectomy. Three doses of cefuroxime plus metronidazole versus one dose of ciprofloxacin. Pharm Weekbl [Sci] 1990;12(6A):292-5. Abstract The prophylactic efficacy of three intravenous doses of cefuroxime 1,500 mg plus metronidazole 500 mg in vaginal hysterectomy was compared with placebo in a prospective double-blind randomized study. Febrile morbidity occurred in 13 of 26 patients in the placebo group and 0 of 27 patients in the study group. In a second prospective randomized study, the efficacy of intravenous ciprofloxacin (200 mg single dose) was compared with the cefuroxime plus metronidazole regimen. Febrile morbidity was found in 3 of 54 patients in the ciprofloxacin group, but in none of the 58 patients in the cefuroxime plus metronidazole group. Accepted 26 November 1990.
P h a r m a c e u t i s c h Weekblad Scientific edition
12(6A) 1990
Table
1
Patient and operation details in study I
Patients Mean age (years) Mean weight (kg)
Operation indications - cervical carcinoma in situ - cervical micro-invasive carcinoma - bleeding complaint - pain - prolapse Operation details - without prolapse repair: (urethra catheter removed after 2 days) - with prolapse repair: (urethra catheter removed after 7 days) - mean operation duration (rain)
Cefuroxime plus metronidazole
Placebo
n = 27 47.2 (range 28-80) 67.6 (range 51-110)
n = 26 53.2 (range 31-79) 68.9 (range 56-88)
4 2 4 3 14
0 6 4 15
13
11
14
15
59.8 (range 30-90)
59.2 (range 30-120)
Results
2
Occurrence and nature of post-operative infections in study I Cefuroxime plus metronidazole (n = 27) Febrile morbidity Vagina top infiltrate U r i n a r y tract infection Duration of hospitalization after operation (days)
12(6A) 1990
Urinary tract infections 22 Patients developed an urinary tract infec/ tion: 16 in study I and 6 in study II. These infections were all but one associated with the presence of a 7-day urinary c a t h e t e r , inserted in patients with vaginal repair. Escherichia coli was the most prominent p a t h o g e n . Conclusion
Study I 27 Patients received cefuroxime plus metronidazole, and 26 received the placebo. Table 1 shows the patient characteristics and operation details. There were no differences between the two groups regarding age, weight, clinical indication, surgery with or without repair and duration of the operation. The occurrence and nature of the post-operative infections are given in Table 2. Febrile morbidity was observed in 13 (2 with a cuff infiltrate) of 26 patients given placebo and in none of 27 receiving cefuroxime plus metronidazole (Fisher's exact test: P
Vaginal hysterectomies are being performed in c o n t a m i n a t e d e n v i r o n m e n t s and, despite thorough pre-operative disinfection, complete sterility of the operation field cannot be attained [1]. In a pilot study on the use of antimicrobial prophylaxis in vaginal hysterectomy, post-operative febrile morbidity was observed in h a l f of the patients: 29 of 54 undergoing vaginal hysterectomy had post-operative febrile morbidity and 6 of 29 patients had vaginal cuff infiltrates. It did not m a t t e r w h e t h e r the hysterectomy was combined with a prolapse repair or not. The purpose of the f i r s t s t u d y (I) was to demonstrate the efficacy of antibiotic prophylaxis in vaginal hysterectomy. For this study, we used a combination of three intravenous doses cefuroxime 1,500 m g plus metronidazole 500 mg. In study II, the prophylactic efficacy of this combination was compared with one 200 mg intravenous dose of ciprofloxacin. Ciprofloxacin has activity against most aerobic microflora of t h e v a g i n a and also some anaerobic activity. Yet, this is less t h a n t h a t of the cefuroxime plus metronidazole combination. The impact of drugs on the cervical flora and the post-operative u r i n a r y tract infections have been described earlier [2]. Methods
Patients Study I was a prospective, randomized, doubleblind and placebo-controlled trial. Cefuroxime 1,500 mg plus metronidazole 500 mg were administered intravenously at the s t a r t of each operation, and after 6 and 12 h. The placebo was isotonic saline. To blind the trial, riboflavine was added to all solutions to produce a common yellow colour. S t u d y II was a non-blinded prospective compar-
ative study of one 200 m g dose of ciprofloxacin intravenously (generously provided by Bayer AG, Leverkusen, FRG) at the s t a r t of the operation, versus the cefuroxime plus metronidazole scheme of study I. The end-point of the study was when at least 50 patients had been enrolled in each group. After entry, the patients were alternately allocated to one of the two groups. All patients in study I and II were judged by the first author. The eligibility criteria for entry were: - all patients referred to our practice for vaginal hysterectomy with or without a prolapse repair; - no use of any antibiotic in the preceding 48 h; - no u r i n a r y tract infection; - normal liver and kidney function; - informed written consent. All patients received an indwelling u r i n a r y catheter which was removed after one day (without repair) or after seven days (with repair). In study I, we used u r e t h r a catheters, in study II, patients with a repair received a suprapubic catheter. The patients were operated by 2 gynaecologists and senior registrars. The surgeons were equally divided a m o n g the two groups, the registrars only operated in the second study. Rectal t e m p e r a t u r e was recorded twice daily. The time of discharge was determined by the patients' condition (normal t e m p e r a t u r e and feeling well). The criteria for post-operative infection were: - f e b r i l e morbidity: a t e m p e r a t u r e of > 3 8 ~ during two consecutive days or more excluding the first and second post-operative day; - u r i n a r y tract infection: > 1000 micro-organisms per ml in catheter urine with > 10 leukocytes per microscopic field (400 x); - v a g i n a l cuff infiltrate: palpable a b n o r m a l i t y with fever and p u r u l e n t discharge.
Keywords
Cefuroxime Ciprofloxacin Drug therapy Hysterectomy Metronidazole Pre-operative care Dr. W.K. Brouwer (correspondence) and Dr. K.M. Kuiper: Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD Leeuwarden, the Netherlands. Dr. J.A.A. Hoogkamp-Korstanje: Laboratory for Public Health, Jelsumerstraat 6, 8917 EN Leeuwarden, the Netherlands.
292
Brouwer WK, Hoogkamp-Korstanje JAA, Kuiper KM. Antibiotic prophylaxe in vaginal hysterectomy. Three doses of cefuroxime plus metronidazole versus one dose of ciprofloxacin. Pharm Weekbl [Sci] 1990;12(6A):292-5. Abstract The prophylactic efficacy of three intravenous doses of cefuroxime 1,500 mg plus metronidazole 500 mg in vaginal hysterectomy was compared with placebo in a prospective double-blind randomized study. Febrile morbidity occurred in 13 of 26 patients in the placebo group and 0 of 27 patients in the study group. In a second prospective randomized study, the efficacy of intravenous ciprofloxacin (200 mg single dose) was compared with the cefuroxime plus metronidazole regimen. Febrile morbidity was found in 3 of 54 patients in the ciprofloxacin group, but in none of the 58 patients in the cefuroxime plus metronidazole group. Accepted 26 November 1990.
P h a r m a c e u t i s c h Weekblad Scientific edition
12(6A) 1990
Table
1
Patient and operation details in study I
Patients Mean age (years) Mean weight (kg)
Operation indications - cervical carcinoma in situ - cervical micro-invasive carcinoma - bleeding complaint - pain - prolapse Operation details - without prolapse repair: (urethra catheter removed after 2 days) - with prolapse repair: (urethra catheter removed after 7 days) - mean operation duration (rain)
Cefuroxime plus metronidazole
Placebo
n = 27 47.2 (range 28-80) 67.6 (range 51-110)
n = 26 53.2 (range 31-79) 68.9 (range 56-88)
4 2 4 3 14
0 6 4 15
13
11
14
15
59.8 (range 30-90)
59.2 (range 30-120)
Results
2
Occurrence and nature of post-operative infections in study I Cefuroxime plus metronidazole (n = 27) Febrile morbidity Vagina top infiltrate U r i n a r y tract infection Duration of hospitalization after operation (days)
12(6A) 1990
Urinary tract infections 22 Patients developed an urinary tract infec/ tion: 16 in study I and 6 in study II. These infections were all but one associated with the presence of a 7-day urinary c a t h e t e r , inserted in patients with vaginal repair. Escherichia coli was the most prominent p a t h o g e n . Conclusion
Study I 27 Patients received cefuroxime plus metronidazole, and 26 received the placebo. Table 1 shows the patient characteristics and operation details. There were no differences between the two groups regarding age, weight, clinical indication, surgery with or without repair and duration of the operation. The occurrence and nature of the post-operative infections are given in Table 2. Febrile morbidity was observed in 13 (2 with a cuff infiltrate) of 26 patients given placebo and in none of 27 receiving cefuroxime plus metronidazole (Fisher's exact test: P
