Antibiotic prophylaxis in abdominal hysterectomy, with special reference to the duration of the prophylaxis F.W. Eckenhausen and P.L. Jonker Introduction Several papers have been published on the prophylactic use of antibiotics in gynaecological surgery [1-4]. In general, the opinions tend to be favourable, although for abdominal hysterectomy there was until recently no conclusive evidence t h a t antimicrobial prophylaxis is beneficial to the patient. 9Recently, a meta-analysis was performed to address this issue [5 6]. This analysis showed a c l e a r advantage for antimicrobial prophylaxis as compared to a placebo. The optimal duration of the prophylactic regimen is still debatable. The use of indwelling urinary catheters presents an increased risk for the development of u r i n a r y tract infections. One could argue t h a t antimicrobial prophylaxis during the catheterization period might reduce the incidence of u r i n a r y tract infections. The principal aim of our study was to compare the efficacy, with regard to the incidence of postoperative u r i n a r y tract infections and wound infections, of a single per-operative dose versus a 24-h peri-operative regimen, of the combination of cefuroxime and metronidazole. Methods

Patients The eligibility criteria were as follows. Women undergoing abdominal hysterectomy, with the exception of the following groups: - p a t i e n t s who received any antibiotic treatment within 48 h prior to the hysterectomy; - patients with a history of an allergic reaction to a cephalosporin or an anaphylactic reaction to penicillin; - patients suffering from a carcinoma of the cervix.

All patients had an indwelling u r i n a r y catheter during the first 24 h after surgery. Procedure Two consecutive studies were performed from 1982 to 1984, containing two groups of patients of approximately the same size. There were no differences between the two studies with regard to factors known to influence the incidence of post-operative infection. In order to minimize the ~effects of different operation techniques on the results, all patients were operated by the same surgeon. Both studies were conducted in accordance to the Declaration of Helsinki (with the Tokyo revisions) of the World MediCal Association. Patients were only included after giving informed consent and the protocol was approved by the local ethical committee. 9 In the first study prophylactic antibiotics were administered peri-operativety a i m i n g at a 24-h coverage; whereas the second restricted therapy to a single pre-operative dose. In both studies the pre-operative dose was administered by short infusion, 30 min preoperatively, containing 1,500 mg of cefuroxime and 500 mg of metronidaZole. In the first study, this was followed by 750 mg of cefuroxime and 500 mg of metronidazole, intravenously, at 8 and 16 h after the first dose. This patient group is referred to as '24-h (prophylaxis) group.' Definitions The following definitions were adhered to. Urinary tract infection: a persistently positive bacteriological culture of catheter- or mid stream-urine with concomitant clinical signs and symptoms of an infection i, e. frequency and other

Keywords Antibiotics Cefuroxime Clinical trials Hysterectomy Metronidazole Preoperative care Dr. F.W. Eckenhausen (correspondence): Department of Obstetrics and Gynaecelogy, Refaja Hospital, Boerhaavestraat 1, 9501 HE Stadskanaal, the Netherlands. Present address: Louis Pasteurstraat 4, 9501 HJ Stadskanaa], the Netherlands. P.L. Jonker: Medical Department, Glaxo BV, Wattbaan 51, 3439 ML Nieuwegein, the Netherlands.

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Eckenhausen FW, Jonker PL. Antibiotic prophylaxis in abdominal hysterectomy, with special reference to the duration of the prophylaxis. Pharm Weekbl [Sci] 1990;12(6A):289-91. Abstract Two consecutive open studies were performed of the efficacy of a prophylactic cefuroxime/metronidazole combination in abdominal hysterectomy. The first group received a 24-h regimen, the second group a single pre-operative dose. The incidence of post-operative wound infections and urinary tract infections were similar in both groups [wound infections in 1/75 versus 2/84 patients (NS), urinary tract infections 4/75 versus 3/84 patients (NS), respectively, in the 24-h group and single-dose group]. No significant differences in other parameters, such as pyrexia and duration of post-operative hospitalization , could be detected.

Accepted 25 September 1990.

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Table

1

Patient characteristics

N u m b e r of patients Mean age (+ SD) (years) Mean weight (+ SD) (kg) Mean duration of surgery (min)

24-h Regimen

Single-dose regimen

75 43+11 66_+10 66

84 44__9 67_+9 60

signs of dysuria, fever ( _ 38.0~ , tenderness and pain along the urinary tract. Pyrexia: deviations in post-operative temperatures of __ 38.0~ measured rectally, on two or more successive days, with the exception of the first two post-operative days. Wound infection: clinical signs and symptoms of wound inflammation with or without dehyscention of the wound and/or positive culture of the secreta. Prolonged hospitalization: a post-operative stay in hospital exceeding 10 days. Morbidity: presence of any of the conditions mentioned above.

Statistical analysis The following methods of statistical analysis were used. Chi squared (x2) test: for morbidity, prolonged hospital stay; Fisher's exact test: infection rates and pyrexia; Wilcoxon's test: for average duration of operation; Student's t-test: for age- and weight averages. Results

In the group receiving 24-h coverage, 77 patients were entered, while 89 patients were admitted to the single-dose study. In the singledose group, 4 patients received concomitant antibiotics other t h a n the study medication and i patient appeared to suffer from an adenocarcinoma and was thus referred to the oncological centre. Thus, 84 patients were evaluable. In the 24-h group 2 patients were excluded because of

Table

2

Number of patients with post-operative morbidity, showing 95% confidence intervals of differences (24-h minus single-dose results) 24-h Regimen Single-dose 95% Confidence number (%) number (%) intervals of observed differences (%)

Pyrexia Urinary tract infections Wound infection Prolonged hospital stay

290

27 (36.0)

33 (39.3)

concurrent use of other antibiotics, resulting 75 evaluable patients. There were no differences between the two groups in age, weight or duration of the operation (Table 1). Post-operative wound infections were scored in 3 patients, i in the 24-h group and 3 in the single-dose group (NS). U r i n a r y tract infections in the post-operative hospitalization period developed in 4 patients in the 24-h group versus 3 patients in the single-dose group (NS). One urinary tract infection in the 24-h group was associated with the presence of urethral stones. Other parameters, including prolonged postoperative stay and pyrexia, also showed similar scores in both groups. Table 2 summarizes the results, including the 95% confidence intervals of observed differences. Discussion

No major difference was found between the single-dose and the 24-h regimen. Although the size of this study is limited, resulting in wide ranges for the 95% confidence intervals of the observed differences, our data are in accordance with the findings published in the review of Hirsch [4]. Incidences of both wound infections and urinary tract infections correspond well with the meta-analysis by Wttewaall-Evelaar et al. [5 6]. Brouwer et al. observed only i wound infection and no urinary tract infections in 26 patients after abdominal hysterectomy [7]. Their antibiotic regimen consisted of three infusions of cefuroxime (1,500 rag) and metronidazole (500 mg) administered at induction, 6 and 12 h later. Gonen et al. [8] compared 3 versus 6 doses of cefazolin (t.d.s. dosage) in elective abdominal hysterectomy and found significantly better results for the 6-dose regimen (11/90 or 12.2% versus 15/63 or 23.8% morbidity, P < 0.005). Our results do suggest that a single pre-operative dose of an appropriate antibiotic or combination is as good as multiple doses. This is confirmed by other studies. Jandial et al. [9], observed a 5.8% (7/120) incidence of post-operative urinary tract infections in patients undergoing abdominal surgery (90 hysterectomies and 30 other gynaecological operations), following a single pre-operative dose of 1,500 mg cefuroxime. This was significantly better t h a n the untreated control group (19/120 or 15.8%, P < 0.05). Boodt et al. [10] also showed that a single prophylactic dose results in a low incidence of post-operative infectionsl which is similar to a 24-h cover [Boodt PJ, Snijders WP, personal communication]. We conclude t h a t single-dose prophylaxis appears to be effective in abdominal hysterectomy.

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Acknowledgements

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The studies were supported financially by Glaxo BV.

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References

1 Shapiro N, Munoz A, Tager IB, et al. Risk factors for infection at the operative site after abdominal or vaginal hysterectomy. N Engl J Med 1982;307:1661-6. 2 Cartwright PS, Pittaway DE, Jones III HW, et al. The use of prophylactic antibiotics in obstetrics and gynae-

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cology. A review. Obstet Gynecol Surv 1984;39:537-53. 3 Shapiro N, Schoenbaum SC, Tager IB, et al. Benefitcost analysis of antimicrobial prophylaxis in abdominal and vaginal hysterectomy.JAMA 1983;249:1290-4. 4 Hirsch HA. Prophylactic antibiotics in obstetrics and gynecology. Am J Med 1985;78(Suppl B):170-6. 5 Wttewaall-Evelaar EW, Kroeks MV, Verbrugh HA. The value of prophylaxis in abdominal hysterectomy, a meta- analysis. Abstracts of the twenty-ninth interscience conference on antimicrobial agents and chemotherapy Washington: American Society for Microbiology, 1989:abstract 399. 6 Wttewaall-Evelaar EW. Meta-analysis of randomized controlled trials of antibiotic prophylaxis in abdominal hysterectomy. Pharm Weekbl [Sci] 1990;12:296-9.

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7 Brouwer WK, Kuiper KM, Langbroek W. The efficacy of prophylaxis with cefuroxime and metronidazol in gynecological surgery. Res Clin Forums 1984;6:25-31. 8 Gonen R, Hakim M, Somberg I, et al. Short-term prophylaxis for elective abdominal hysterectomy: how short? Eur J Obstet Gynecol Reprod Biol 1985;20: 229-34. 9 Jandial L, Reid TM, Jandial V, et al. Prophylactic use of cefuroxime in major gynecological surgery. Proc R Soc Med 1981;38:41-9. 10 Boodt PJ, Snijders WP, Janknegt R. Single-dose prophylaxis in hysterectomies. An interim analysis. Pharm Weekbl [Sci] 1990;12:280-3.

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Antibiotic prophylaxis in abdominal hysterectomy, with special reference to the duration of the prophylaxis.

Two consecutive open studies were performed of the efficacy of a prophylactic cefuroxime/metronidazole combination in abdominal hysterectomy. The firs...
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