- Email: [email protected]
Prophylactic antimicrobial agents in urologic laparoscopic surgery: 1-day versus 3-day treatment
J Infect Chemother (2004) 10:168–171 DOI 10.1007/s10156-004-0317-3
© Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2004
ORIGINAL ARTICLE Koh Takeyama · Toshiaki Shimizu · Masatoshi Mutoh Naotaka Nishiyama · Yasuharu Kunishima Masanori Matsukawa · Satoshi Takahashi · Hiroshi Hotta Naoki Itoh · Taiji Tsukamoto
Prophylactic antimicrobial agents in urologic laparoscopic surgery: 1-day versus 3-day treatments
Received: February 12, 2004 / Accepted: April 28, 2004
Abstract Although the incidence of surgical site infection (SSI) is generally low in laparoscopic urologic surgery, the standard protocol for prophylactic use of antimicrobial agents remains to be established. We retrospectively compared the incidence and severity of SSI after laparoscopic surgery between two different protocols for prophylactic use of antimicrobial agents. This study included 114 patients who underwent urologic laparoscopic surgery categorized as “clean” or “clean-contaminated” in Sapporo Medical University School Hospital between January 1996 and October 2002. As a prophylactic antimicrobial agent, one of the cephalosporins or penicillins was administered intravenously to all patients. For 46 consecutive patients between January 1996 and July 2000, an antimicrobial agent was given 30 min before operation and thereafter every 12 h on the same day and the next 2 days after operation (the 3-day group). For 68 consecutive patients from August 2000 to October 2002, an antimicrobial agent was given once 30 min before operation and was additionally given only in the evening or night of the day of operation (the 1-day group). The incidence of SSI was retrospectively investigated. There were two patients who developed SSI in each group (4.3% in the 3-day group and 2.9% in the 1-day group). The incidence of SSI was not significantly different between the two groups. The 1-day protocol has efficacy equal to that of the 3-day protocol in prophylaxis of SSI. The 1-day use of a prophylactic antimicrobial agent may be recommended for the clean or clean-contaminated urologic laparoscopic surgery described above.
Introduction Recently, laparoscopic surgery has become widely available. One of the advantages of this type of surgery is its low invasiveness.1,2 Laparoscopic colorectal surgery and appendectomy have lower incidences of surgical site infection (SSI) than open surgery.3,4 However, the incidence of SSI in urologic laparoscopic surgery remains to be determined. In addition, the standard protocol for prophylactic use of antimicrobial agents has not been established for prevention of SSI in urologic laparoscopic surgery. Thus, it is necessary to clarify the incidence of SSI in such surgery and to establish appropriate use of prophylactic antimicrobial agents. When we started this type of surgery in 1996, we traditionally treated patients with prophylactic use of an antimicrobial agent under the 3-day protocol described below. After we became familiar with the surgery in terms of intra- and postoperative care of patients, we thought that the duration of prophylactic antimicrobial agent administration might be shortened without compromising the postoperative course of the patient. Thus, we changed our protocol to a 1-day protocol in 2000. The details are presented in the Patients and methods section. In this context, we retrospectively compared the clinical efficacy of the 1-day protocol of prophylactic antimicrobial agents with the 3-day protocol in urologic laparoscopic surgery. Thereby, we determined whether the 1-day protocol was as effective as the 3-day protocol for postoperative management of patients who received laparoscopic surgery.
Key words Prophylaxis · Antimicrobial agents · Urologic laparoscopic surgery · Surgical site infection
Patients and methods K. Takeyama · T. Shimizu · M. Mutoh · N. Nishiyama · Y. Kunishima · M. Matsukawa · S. Takahashi · H. Hotta · N. Itoh · T. Tsukamoto (*) Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan Tel. ⫹81-11-611-2111 (ext. 3480); Fax ⫹81-11-612-2709 e-mail [email protected]
Patients and protocol for prophylactic use of antimicrobial agents This study included 114 patients who received laparoscopic surgery for treatment of adrenal tumors, renal cell carcinoma, urothelial cancer of the upper urinary tract, and ure-
169 Table 1. Patient demographics Parameter
3-day group (46 patients)
1-day group (68 patients)
Mean age (SD) Number of patients: Male/femalea Mean body mass index (SD) Surgical procedures Adrenalectomy Radical nephrectomy Radical nephroureterectomy Pyeloplasty Pelvic lymph node dissection Prophylactic antimicrobial agentsb Aspoxicillin Piperacillin Cefazolin Cefotiam Ceftazidime Cefepime Cefoselis Cefmetazole Ampicillin sodium Sulbactam sodium
56.1 (14.3)
57.6 (15.1)
19/27 23.02 (4.6)
41/27 24.2 (3.6)
25 (54.3%) 11 (23.9%) 3 (6.5%) 0 7 (15.3%)
26 (38.2%) 22 (32.4%) 7 (10.3%) 4 (5.9%) 9 (13.2%)
8 (17.4%) 14 (30.4%) 0 15 (32.6%) 0 0 1 (2.2%) 7 (15.2%)
3 (4.4%) 13 (19.1%) 18 (26.4%) 13 (19.1%) 1 (1.4%) 1 (1.4%) 0 18 (26.4%)
1 (2.2%)
1 (1.4%)
a b
P ⫽ 0.046 by the χ test P ⫽ 0.016 by the χ2 test 2
teropelvic junction obstruction, and for the diagnostic purpose of checking for pelvic lymph node metastasis of prostate cancer during the period from January 1996 to October 2002 in Sapporo Medical University Hospital (Table 1). No patients were found to have severe diseases that were uncontrolled by medical treatments or conditions that strongly affected the postoperative development of SSI. Patients were classified into the following two groups. The 3-day group consisted of 46 patients operated on between January 1996 and July 2000 and the 1-day group included 68 patients operated on between August 2000 and October 2002. All patients were intravenously given a prophylactic antimicrobial agent 30 min before the operation and an additional administration during the operation if it lasted for more than 3 h. After the operation, patients in the 3-day group were intravenously given the same agent every 12 h on the day of the operation and until postoperative day (POD) 2. In the 1-day group, patients were additionally given an intravenous antimicrobial agent only once, i.e., in the evening or the night of the day of the operation, depending on the time that the operation was completed. For prophylactic use, one of the penicillins or the first- or second-generation cephalosporins was given to the patient according to the physician’s preference. The dose of administration at one time was within the range of usual usage, according to the manual. The operations The operations in this study consisted of adrenalectomy, radical nephrectomy, radical nephroureterectomy, pelvic lymph node dissection, and pyeloplasty. These operations required four or five ports with skin incisions for an endo-
scope and instruments. For adrenalectomy, pelvic lymphadenectomy, and pyeloplasty, the skin incisions were up to 20 mm long. For radical nephrectomy and radical nephroureterectomy, a hand-assisted laparoscopic technique was used and a skin incision 6–8 cm in length was made near the umbilicus for hand insertion. In radical nephroureterectomy, the distal end of the ureter or bladder cuff was managed with the open ureterectomy or pluck technique.5 Adrenalectomy, radical nephrectomy, and pelvic lymph node dissection were categorized as “clean” operations and radical nephroureterectomy and pyeloplasty as “clean– contaminated” operations, according to the possibility of urine contamination in the surgical field.6 Preoperative preparation and postoperative care All operations were done in the standard aseptic manner. The surgical site was wiped with 10% povidone iodine solution before the operation. After the surgical wound was closed, it was gently wiped with 10% povidone iodine solution or normal saline. Then the site was covered with sterile gauze or an OpSite dressing (Smith and Nephew, Tokyo, Japan) that was kept in place until removal of sutures. Sutures were removed on POD 7. End points In this study we used SSI as the end point because prophylactic antimicrobial agents are basically given for the purpose of prevention of SSI.7 Any SSI within 30 days after the operation was analyzed according to the guideline authorized by the Centers for Disease Control and Prevention (CDC).6 If there were any infectious symptoms or signs, blood cell count, blood chemistry, urine, X-ray, and bacteriological examinations were done, depending on the severity of the symptoms or signs. The χ2 test and unpaired t test were used in statistical analysis of results.
Results Although the 1-day group had a predominant number of male patients, the age and body mass index did not differ between the two groups (Table 1). Adrenalectomy was most frequently done in this study, followed by radical nephrectomy, pelvic lymph node dissection, and radical nephroureterectomy. Pyeloplasty was included only in the 1-day group. No significant differences in surgical procedures was found between the groups (P ⫽ 0.24 by the chisquare test). Preoperative asymptomatic bacteriuria with 10 000 CFU/ml or greater was found in two patients in the 3-day group and four in the 1-day group. Because these patients underwent clean operations such as hand-assisted radical nephrectomy, adrenalectomy, or pelvic lymphadenectomy, we did not eradicate bacteria in the urine with antimicrobial agents before surgery.
170
There was a distinct difference in the use of antimicrobial agents between the two groups (P ⫽ 0.016 by the χ2 test). In the 3-day group, the proportions of penicillins and second-generation cephalosporins were almost equal. However, first-generation cephalosporins were more frequently used in the 1-day group. Prophylactic use of third- and fourth-generation drugs was exceptional. We analyzed biases such as operation time and frequency of intraoperative additional administration that might have affected the occurrence of SSI (Table 2). Operation times for adrenalectomy, radical nephroureterectomy, and pelvic lymph node dissection were significantly shorter in the 1-day group. Additional antimicrobial administration for operations lasting more than 3 h was intraoperatively done for 12 patients of the 1-day group (25.0%) and 19 of the 3-day group (27.9%). For adrenalectomy, the frequency of additional administration was significantly different between the two groups (P ⫽ 0.03 by the chi-squared test). The antimicrobial agent was administered beyond the period of each protocol for 7 patients in the 3-day group (15.2%) and 7 in the 1-day group (10.3%), who postoperatively seemed to have findings potentially indicating infectious disease. However, the retrospective analysis revealed
Table 2. Operation times and the numbers of patients who received additional administration of prophylactic antimicrobial agents Parameter Operation time (min, SD) Adrenalectomya Radical nephrectomyb Radical nephroureterectomyc Pelvic lymph node dissectiond Pyeloplasty Number of patients receiving intraoperative additional administration Adrenalectomye Radical nephrectomyb Radical nephroureterectomyb Pelvic lymph node dissection Pyeloplasty
3-day group
1-day group
189 (68) 234 (53) 343 (18) 146 (14) Not done
141 (45) 204 (69) 288 (36) 117 (30) 323 (44)
6/25 (24)f 4/11 (36) 2/3 (67) 0/7 (0) Not done
1/26 (4) 8/22 (36) 6/7 (86) 0/9 (0) 4/4 (100)
P ⫽ 0.004 by the unpaired t test not significant P ⫽ 0.04 by the unpaired t test d P ⫽ 0.03 by the unpaired t test e P ⫽ 0.03 by the chi-squared test f Number of patients who received additional antimicrobial agents/ Total number of patients (%) a
b c
that the findings were transient in nature and that no patients had concrete evidence of infections disease. The incidences of such events did not differ between the groups (P ⫽ 0.56 by χ2 test). SSIs were found in four patients. These SSIs occurred in clean operations. All infections were diagnosed no later than 9 days after the operation. They were all superficial incisional infections that healed without any specific treatment (Table 3). The incidence of SSIs did not differ between the groups (4.3% in the 3-day group versus 2.9% in the 1-day group, P ⫽ 0.69 by the χ2 test). Pseudomonas aeruginosa was isolated from the wound pus of two patients and Staphylococcus epidermidis from that of one patient. No patients who preoperatively had significant bacteriuria developed SSI. Life-threatening infectious complications such as sepsis were not found in the study.
Discussion The current retrospective study revealed that the overall rate of SSI in urologic laparoscopic surgery was 4.3% in the 3-day group and 2.9% in the 1-day group. In addition, all of the SSIs were clinically manageable with nonspecific treatment. Thus, we confirmed that the 1-day protocol of prophylactic antimicrobial treatment was adequate to prevent SSI in laparoscopic surgery. The rates of SSI after laparoscopic adrenalectomy have been reported to be from 1.3% to 8%, depending on its definition.8–10 With respect to hand-assisted laparoscopic radical nephrectomy, the rates are reported to be from 1.1% to 9%.11,12 In hand-assisted procedures, a 6- to 9-cm incision is required for hand insertion; thus, the surgical wound is much larger than that in a purely laparoscopic procedure. The SSI rates for laparoscopic adrenalectomy and hand-assisted laparoscopic radical nephrectomy in our study were similar to those of previous reports. However, direct comparison of the rates may not appropriate because the rates in previous studies were not necessarily determined by the definitions of the CDC guidelines.6 The duration of the use of prophylactic antimicrobial agents should be kept as short as possible, not only to avoid the induction of bacterial resistance, but also so as not to waste medical resources. Indeed, some studies have already raised the question of whether prophylactic antimicrobial agents are really needed at all in laparoscopic surgery.13,14 In
Table 3. Surgical site infection in patients who underwent urologic laparoscopic surgery Age (sex)
Group
Operation
Diagnosis at POD
Bacteria isolated (specimens)
58 (F) 67 (M) 58 (M) 46 (F)
3-day 3-day 1-day 1-day
Radical nephrectomy Adrenalectomy Adrenalectomy Adrenalectomy
8 3 5 8
P. aeruginosa (wound pus) negative (wound pus) P. aeruginosa (wound pus) S. epidermidis (wound pus)
POD, postoperative day
171 15
laparoscopic cholecystectomy, Tocchi et al. reported that the infectious complication rate was not significantly different between patients who received a prophylactic antimicrobial agent and those who did not. Dobay et al.14 also emphasized that prophylactic use of antimicrobial agents was not needed to prevent SSI, except for high-risk patients such as those who were elderly, required a longer time for the operation, or had significant comorbidity. Thus, the prophylactic use of an antimicrobial agent may not be necessary in selected patients who have no risk factors for development of postoperative infectious complications and receive a clean urological operation such as laparoscopic adrenalectomy. This issue will be our next study project. In urological surgery having the possibility of urine contamination in the operative field, preoperative urinary tract infection and significant bacteriuria are critical issues for management of postoperative care.16 In particular, preoperative bacteriuria with methicillin-resistant Staphylococcus aureus (MRSA) may be a high risk factor for postoperative SSI.17 Fortunately, in this study there were no patients with MRSA bacteriuria preoperatively and this fact may explain why no patients developed severe SSI. Even in laparoscopic surgery it may be necessary to properly manage obvious infections preoperatively for prevention of SSI when there may be a possibility of urine contamination in the field of operation. Antimicrobial therapy for laparoscopic surgery should be individually designed considering potential causative organisms (e.g., urinary bacteria) as well as the site of the surgical wound.18 This study has several limitations. First is the effect of the learning curve on the occurrence of SSI. In general, as operation time becomes longer the risk of postoperative complications increases. In our analysis, the operation times of several operations of the 3-day group were significantly longer than for the 1-day group. This issue is related to additional intraoperative administration of antimicrobial agents. Indeed, in adrenalectomy, additional administration was more frequent in the 3-day group than in the 1-day group. Second, the number of subjects should be taken into consideration. In particular, the number of clean– contaminated operations might be too small to support the rationale for our protocol. It will be necessary to analyze a larger number of cases in the future. Finally, there were distinct differences in the kinds of prophylactic antimicrobial agents between the two groups. These biases might have affected the occurrence of SSI. In conclusion, the 1-day use of prophylactic antimicrobial agents had an effect equivalent to 3-day use for prevention of SSI in patients with clean or clean–contaminated urologic operations such as laparoscopic adrenalectomy, nephrectomy, nephroureterectomy, pyeloplasty, and pelvic lymph node dissection, especially when the patient has no preoperative urinary tract infection or significant bacteriuria.
Conclusion Clean or clean–contaminated urologic laparoscopic operations such as adrenalectomy, nephrectomy, nephroureterectomy, pyeloplasty, and pelvic lymph node dissection require only the 1-day use of antimicrobial agents for prophylaxis of SSI.
References 1. Lennerling A, Blohme I, Ostraat O, Lonroth H, Olausson M, Nyberg G. Laparoscopic or open surgery for living donor nephrectomy. Nephrol Dial Transplant 2001;16:383–86. 2. Klinger A, Henle KP, Beller S, Rechner J, Zerz A, Wetscher GJ. Laparoscopic adrenalectomy does not change the incidence of postoperative infectious complications. Am J Surg 1998;175:232– 35. 3. Braga M, Vignali A, Gianotti L, Zuliani W, Radaelli G, Gruarin P, et al. Laparoscopic versus open colorectal surgery: A randomized trial on short-term outcome. Ann Surg 2002;236:759–67. 4. Meynaud-Kraemer L, Colin C, Vergnon P, Barth X. Wound infection in open versus laparoscopic appendectomy. Int J Technol Assess Health Care 1999;15:380–91. 5. Arango O, Bielsa O, Carles J, Gelabert-Mas A. Massive tumor implantation in the endoscopic resected area in modified nephrouretectomy. J Urol 1997;157:1839. 6. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection. Infect Control Hosp Epideminol 1999;20:247–78. 7. Sumiyama Y. Guidelines for perioperative antibiotic use in digestive tract surgery. J Jpn Surg Soc 2001;102:856–59. 8. Soulie M, Salomon L, Seguin P, Mervant C, Mouly P, Hoznek A, et al. Multi-institutional study of complications in 1085 laparoscopic urologic procedures. Urology 2001;58:899–903. 9. Terachi T. Laparoscopic surgery adrenalectomy. Geka Chiryo 1999;80:441–5. 10. Yokoi S, Takahashi Y, Deguchi T, Takeuchi T, Maeda S, Kanimoto Y, et al. Comparison of laparoscopic versus open surgery for adrenal tumor. Acta Urol Jpn 2002;48:203–6. 11. Kawauchi A, Fujito A, Miki K. Hand-assisted retroperitoneoscopic radical nephrectomy. Jpn J Endourol ESWL 2003;16:24–9. 12. Nelson CP, Wolf JS. Comparison of hand assisted versus standard laparoscopic radical nephrectomy for suspected renal cell carcinoma. J Urol 2002;167:1989–94. 13. Higgins A, London J, Charland S, Ratzer E, Clark J, Haun W, et al. Prophylactic antibiotics for elective laparoscopic cholecystectomy: are they necessary? Arch Surg 1999;134:611–3. 14. Dobay KJ, Freier DT, Albear P. The absent role of prophylactic antibiotics in low-risk patients undergoing laparoscopic cholecystectomy. Am Surg 1999;65:226–8. 15. Tocchi A, Lepre L, Costa G, Liotta G, Mazzoni G, Maggiolini F. The need for antibiotic prophylaxis in elective laparoscopic cholecystectomy: a prospective randomized study. Arch Surg 2000; 135:67–70. 16. Drach GW, Cox CE. Bladder bacteriuria: Common but unique cause for sepsis. Postoperative endotoxin responses. J Urol 1971;106:67–71. 17. Matsukawa M, Kunishima Y, Takahashi S, Takeyama K, Tsukamoto T. Staphylococcus aureus bacteriuria and surgical site infections by methicillin-resistant Staphylococcus aureus. Int J Antimicrob Agents 2001;17:327–30. 18. Weiser AC, Schaeffer AJ. The use and misuse of antimicrobial agents in urology. AUA Update Series 2002;21:289–96.
© Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2004
ORIGINAL ARTICLE Koh Takeyama · Toshiaki Shimizu · Masatoshi Mutoh Naotaka Nishiyama · Yasuharu Kunishima Masanori Matsukawa · Satoshi Takahashi · Hiroshi Hotta Naoki Itoh · Taiji Tsukamoto
Prophylactic antimicrobial agents in urologic laparoscopic surgery: 1-day versus 3-day treatments
Received: February 12, 2004 / Accepted: April 28, 2004
Abstract Although the incidence of surgical site infection (SSI) is generally low in laparoscopic urologic surgery, the standard protocol for prophylactic use of antimicrobial agents remains to be established. We retrospectively compared the incidence and severity of SSI after laparoscopic surgery between two different protocols for prophylactic use of antimicrobial agents. This study included 114 patients who underwent urologic laparoscopic surgery categorized as “clean” or “clean-contaminated” in Sapporo Medical University School Hospital between January 1996 and October 2002. As a prophylactic antimicrobial agent, one of the cephalosporins or penicillins was administered intravenously to all patients. For 46 consecutive patients between January 1996 and July 2000, an antimicrobial agent was given 30 min before operation and thereafter every 12 h on the same day and the next 2 days after operation (the 3-day group). For 68 consecutive patients from August 2000 to October 2002, an antimicrobial agent was given once 30 min before operation and was additionally given only in the evening or night of the day of operation (the 1-day group). The incidence of SSI was retrospectively investigated. There were two patients who developed SSI in each group (4.3% in the 3-day group and 2.9% in the 1-day group). The incidence of SSI was not significantly different between the two groups. The 1-day protocol has efficacy equal to that of the 3-day protocol in prophylaxis of SSI. The 1-day use of a prophylactic antimicrobial agent may be recommended for the clean or clean-contaminated urologic laparoscopic surgery described above.
Introduction Recently, laparoscopic surgery has become widely available. One of the advantages of this type of surgery is its low invasiveness.1,2 Laparoscopic colorectal surgery and appendectomy have lower incidences of surgical site infection (SSI) than open surgery.3,4 However, the incidence of SSI in urologic laparoscopic surgery remains to be determined. In addition, the standard protocol for prophylactic use of antimicrobial agents has not been established for prevention of SSI in urologic laparoscopic surgery. Thus, it is necessary to clarify the incidence of SSI in such surgery and to establish appropriate use of prophylactic antimicrobial agents. When we started this type of surgery in 1996, we traditionally treated patients with prophylactic use of an antimicrobial agent under the 3-day protocol described below. After we became familiar with the surgery in terms of intra- and postoperative care of patients, we thought that the duration of prophylactic antimicrobial agent administration might be shortened without compromising the postoperative course of the patient. Thus, we changed our protocol to a 1-day protocol in 2000. The details are presented in the Patients and methods section. In this context, we retrospectively compared the clinical efficacy of the 1-day protocol of prophylactic antimicrobial agents with the 3-day protocol in urologic laparoscopic surgery. Thereby, we determined whether the 1-day protocol was as effective as the 3-day protocol for postoperative management of patients who received laparoscopic surgery.
Key words Prophylaxis · Antimicrobial agents · Urologic laparoscopic surgery · Surgical site infection
Patients and methods K. Takeyama · T. Shimizu · M. Mutoh · N. Nishiyama · Y. Kunishima · M. Matsukawa · S. Takahashi · H. Hotta · N. Itoh · T. Tsukamoto (*) Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan Tel. ⫹81-11-611-2111 (ext. 3480); Fax ⫹81-11-612-2709 e-mail [email protected]
Patients and protocol for prophylactic use of antimicrobial agents This study included 114 patients who received laparoscopic surgery for treatment of adrenal tumors, renal cell carcinoma, urothelial cancer of the upper urinary tract, and ure-
169 Table 1. Patient demographics Parameter
3-day group (46 patients)
1-day group (68 patients)
Mean age (SD) Number of patients: Male/femalea Mean body mass index (SD) Surgical procedures Adrenalectomy Radical nephrectomy Radical nephroureterectomy Pyeloplasty Pelvic lymph node dissection Prophylactic antimicrobial agentsb Aspoxicillin Piperacillin Cefazolin Cefotiam Ceftazidime Cefepime Cefoselis Cefmetazole Ampicillin sodium Sulbactam sodium
56.1 (14.3)
57.6 (15.1)
19/27 23.02 (4.6)
41/27 24.2 (3.6)
25 (54.3%) 11 (23.9%) 3 (6.5%) 0 7 (15.3%)
26 (38.2%) 22 (32.4%) 7 (10.3%) 4 (5.9%) 9 (13.2%)
8 (17.4%) 14 (30.4%) 0 15 (32.6%) 0 0 1 (2.2%) 7 (15.2%)
3 (4.4%) 13 (19.1%) 18 (26.4%) 13 (19.1%) 1 (1.4%) 1 (1.4%) 0 18 (26.4%)
1 (2.2%)
1 (1.4%)
a b
P ⫽ 0.046 by the χ test P ⫽ 0.016 by the χ2 test 2
teropelvic junction obstruction, and for the diagnostic purpose of checking for pelvic lymph node metastasis of prostate cancer during the period from January 1996 to October 2002 in Sapporo Medical University Hospital (Table 1). No patients were found to have severe diseases that were uncontrolled by medical treatments or conditions that strongly affected the postoperative development of SSI. Patients were classified into the following two groups. The 3-day group consisted of 46 patients operated on between January 1996 and July 2000 and the 1-day group included 68 patients operated on between August 2000 and October 2002. All patients were intravenously given a prophylactic antimicrobial agent 30 min before the operation and an additional administration during the operation if it lasted for more than 3 h. After the operation, patients in the 3-day group were intravenously given the same agent every 12 h on the day of the operation and until postoperative day (POD) 2. In the 1-day group, patients were additionally given an intravenous antimicrobial agent only once, i.e., in the evening or the night of the day of the operation, depending on the time that the operation was completed. For prophylactic use, one of the penicillins or the first- or second-generation cephalosporins was given to the patient according to the physician’s preference. The dose of administration at one time was within the range of usual usage, according to the manual. The operations The operations in this study consisted of adrenalectomy, radical nephrectomy, radical nephroureterectomy, pelvic lymph node dissection, and pyeloplasty. These operations required four or five ports with skin incisions for an endo-
scope and instruments. For adrenalectomy, pelvic lymphadenectomy, and pyeloplasty, the skin incisions were up to 20 mm long. For radical nephrectomy and radical nephroureterectomy, a hand-assisted laparoscopic technique was used and a skin incision 6–8 cm in length was made near the umbilicus for hand insertion. In radical nephroureterectomy, the distal end of the ureter or bladder cuff was managed with the open ureterectomy or pluck technique.5 Adrenalectomy, radical nephrectomy, and pelvic lymph node dissection were categorized as “clean” operations and radical nephroureterectomy and pyeloplasty as “clean– contaminated” operations, according to the possibility of urine contamination in the surgical field.6 Preoperative preparation and postoperative care All operations were done in the standard aseptic manner. The surgical site was wiped with 10% povidone iodine solution before the operation. After the surgical wound was closed, it was gently wiped with 10% povidone iodine solution or normal saline. Then the site was covered with sterile gauze or an OpSite dressing (Smith and Nephew, Tokyo, Japan) that was kept in place until removal of sutures. Sutures were removed on POD 7. End points In this study we used SSI as the end point because prophylactic antimicrobial agents are basically given for the purpose of prevention of SSI.7 Any SSI within 30 days after the operation was analyzed according to the guideline authorized by the Centers for Disease Control and Prevention (CDC).6 If there were any infectious symptoms or signs, blood cell count, blood chemistry, urine, X-ray, and bacteriological examinations were done, depending on the severity of the symptoms or signs. The χ2 test and unpaired t test were used in statistical analysis of results.
Results Although the 1-day group had a predominant number of male patients, the age and body mass index did not differ between the two groups (Table 1). Adrenalectomy was most frequently done in this study, followed by radical nephrectomy, pelvic lymph node dissection, and radical nephroureterectomy. Pyeloplasty was included only in the 1-day group. No significant differences in surgical procedures was found between the groups (P ⫽ 0.24 by the chisquare test). Preoperative asymptomatic bacteriuria with 10 000 CFU/ml or greater was found in two patients in the 3-day group and four in the 1-day group. Because these patients underwent clean operations such as hand-assisted radical nephrectomy, adrenalectomy, or pelvic lymphadenectomy, we did not eradicate bacteria in the urine with antimicrobial agents before surgery.
170
There was a distinct difference in the use of antimicrobial agents between the two groups (P ⫽ 0.016 by the χ2 test). In the 3-day group, the proportions of penicillins and second-generation cephalosporins were almost equal. However, first-generation cephalosporins were more frequently used in the 1-day group. Prophylactic use of third- and fourth-generation drugs was exceptional. We analyzed biases such as operation time and frequency of intraoperative additional administration that might have affected the occurrence of SSI (Table 2). Operation times for adrenalectomy, radical nephroureterectomy, and pelvic lymph node dissection were significantly shorter in the 1-day group. Additional antimicrobial administration for operations lasting more than 3 h was intraoperatively done for 12 patients of the 1-day group (25.0%) and 19 of the 3-day group (27.9%). For adrenalectomy, the frequency of additional administration was significantly different between the two groups (P ⫽ 0.03 by the chi-squared test). The antimicrobial agent was administered beyond the period of each protocol for 7 patients in the 3-day group (15.2%) and 7 in the 1-day group (10.3%), who postoperatively seemed to have findings potentially indicating infectious disease. However, the retrospective analysis revealed
Table 2. Operation times and the numbers of patients who received additional administration of prophylactic antimicrobial agents Parameter Operation time (min, SD) Adrenalectomya Radical nephrectomyb Radical nephroureterectomyc Pelvic lymph node dissectiond Pyeloplasty Number of patients receiving intraoperative additional administration Adrenalectomye Radical nephrectomyb Radical nephroureterectomyb Pelvic lymph node dissection Pyeloplasty
3-day group
1-day group
189 (68) 234 (53) 343 (18) 146 (14) Not done
141 (45) 204 (69) 288 (36) 117 (30) 323 (44)
6/25 (24)f 4/11 (36) 2/3 (67) 0/7 (0) Not done
1/26 (4) 8/22 (36) 6/7 (86) 0/9 (0) 4/4 (100)
P ⫽ 0.004 by the unpaired t test not significant P ⫽ 0.04 by the unpaired t test d P ⫽ 0.03 by the unpaired t test e P ⫽ 0.03 by the chi-squared test f Number of patients who received additional antimicrobial agents/ Total number of patients (%) a
b c
that the findings were transient in nature and that no patients had concrete evidence of infections disease. The incidences of such events did not differ between the groups (P ⫽ 0.56 by χ2 test). SSIs were found in four patients. These SSIs occurred in clean operations. All infections were diagnosed no later than 9 days after the operation. They were all superficial incisional infections that healed without any specific treatment (Table 3). The incidence of SSIs did not differ between the groups (4.3% in the 3-day group versus 2.9% in the 1-day group, P ⫽ 0.69 by the χ2 test). Pseudomonas aeruginosa was isolated from the wound pus of two patients and Staphylococcus epidermidis from that of one patient. No patients who preoperatively had significant bacteriuria developed SSI. Life-threatening infectious complications such as sepsis were not found in the study.
Discussion The current retrospective study revealed that the overall rate of SSI in urologic laparoscopic surgery was 4.3% in the 3-day group and 2.9% in the 1-day group. In addition, all of the SSIs were clinically manageable with nonspecific treatment. Thus, we confirmed that the 1-day protocol of prophylactic antimicrobial treatment was adequate to prevent SSI in laparoscopic surgery. The rates of SSI after laparoscopic adrenalectomy have been reported to be from 1.3% to 8%, depending on its definition.8–10 With respect to hand-assisted laparoscopic radical nephrectomy, the rates are reported to be from 1.1% to 9%.11,12 In hand-assisted procedures, a 6- to 9-cm incision is required for hand insertion; thus, the surgical wound is much larger than that in a purely laparoscopic procedure. The SSI rates for laparoscopic adrenalectomy and hand-assisted laparoscopic radical nephrectomy in our study were similar to those of previous reports. However, direct comparison of the rates may not appropriate because the rates in previous studies were not necessarily determined by the definitions of the CDC guidelines.6 The duration of the use of prophylactic antimicrobial agents should be kept as short as possible, not only to avoid the induction of bacterial resistance, but also so as not to waste medical resources. Indeed, some studies have already raised the question of whether prophylactic antimicrobial agents are really needed at all in laparoscopic surgery.13,14 In
Table 3. Surgical site infection in patients who underwent urologic laparoscopic surgery Age (sex)
Group
Operation
Diagnosis at POD
Bacteria isolated (specimens)
58 (F) 67 (M) 58 (M) 46 (F)
3-day 3-day 1-day 1-day
Radical nephrectomy Adrenalectomy Adrenalectomy Adrenalectomy
8 3 5 8
P. aeruginosa (wound pus) negative (wound pus) P. aeruginosa (wound pus) S. epidermidis (wound pus)
POD, postoperative day
171 15
laparoscopic cholecystectomy, Tocchi et al. reported that the infectious complication rate was not significantly different between patients who received a prophylactic antimicrobial agent and those who did not. Dobay et al.14 also emphasized that prophylactic use of antimicrobial agents was not needed to prevent SSI, except for high-risk patients such as those who were elderly, required a longer time for the operation, or had significant comorbidity. Thus, the prophylactic use of an antimicrobial agent may not be necessary in selected patients who have no risk factors for development of postoperative infectious complications and receive a clean urological operation such as laparoscopic adrenalectomy. This issue will be our next study project. In urological surgery having the possibility of urine contamination in the operative field, preoperative urinary tract infection and significant bacteriuria are critical issues for management of postoperative care.16 In particular, preoperative bacteriuria with methicillin-resistant Staphylococcus aureus (MRSA) may be a high risk factor for postoperative SSI.17 Fortunately, in this study there were no patients with MRSA bacteriuria preoperatively and this fact may explain why no patients developed severe SSI. Even in laparoscopic surgery it may be necessary to properly manage obvious infections preoperatively for prevention of SSI when there may be a possibility of urine contamination in the field of operation. Antimicrobial therapy for laparoscopic surgery should be individually designed considering potential causative organisms (e.g., urinary bacteria) as well as the site of the surgical wound.18 This study has several limitations. First is the effect of the learning curve on the occurrence of SSI. In general, as operation time becomes longer the risk of postoperative complications increases. In our analysis, the operation times of several operations of the 3-day group were significantly longer than for the 1-day group. This issue is related to additional intraoperative administration of antimicrobial agents. Indeed, in adrenalectomy, additional administration was more frequent in the 3-day group than in the 1-day group. Second, the number of subjects should be taken into consideration. In particular, the number of clean– contaminated operations might be too small to support the rationale for our protocol. It will be necessary to analyze a larger number of cases in the future. Finally, there were distinct differences in the kinds of prophylactic antimicrobial agents between the two groups. These biases might have affected the occurrence of SSI. In conclusion, the 1-day use of prophylactic antimicrobial agents had an effect equivalent to 3-day use for prevention of SSI in patients with clean or clean–contaminated urologic operations such as laparoscopic adrenalectomy, nephrectomy, nephroureterectomy, pyeloplasty, and pelvic lymph node dissection, especially when the patient has no preoperative urinary tract infection or significant bacteriuria.
Conclusion Clean or clean–contaminated urologic laparoscopic operations such as adrenalectomy, nephrectomy, nephroureterectomy, pyeloplasty, and pelvic lymph node dissection require only the 1-day use of antimicrobial agents for prophylaxis of SSI.
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