British Journalof Urology (1990), 66,509-514
0007-1331/90/0066-0509/$10.00
01990 British Journal of Urology
Antibiotic Compared with Antiseptic Prophylaxis for Prostatic Surgery S. PRESCOlT, M. A. HADI. R. A. ELTON,A. W. S. RITCHIE, G. C. FOUBISTER, J. C. GOULD and T. B. HARGREAVE Department of Surgery1Urology and Central Microbiological Laiboratories, Western General Hospital; Medical Statistics Unit, University Medical School, Edinburgh
Summary-Two different regimens of cephalosporin antibiotic prophylaxis were compared with antiseptic lubricating jelly to try to prevent infection and complications in 196 men after prostatic surgery. Pre-operative urine was cultured and prostatic chips (170 cases) were also cultured to define the source of any infection. The use of antibiotics was associated with a reduced risk of postoperative bacteriuria. No serious complications occurred, although 1 patient in the antiseptic treated group developed rigors; 79 of 170 patients (46%) had positive prostatic chip cultures, of whom 74 had sterile pre-operative urine. There was no association lbetween the result of chip culture and the presence of a pre-operative catheter. Culture positive patients had an increased risk of postoperative urine infection, although the same organism was found in the prostate and urine in only 36% of cases of post-operative bacteriuria and in 43 (54%) the organism cultured from the prostate was Staphylococcus albus. This study provides further evidence of the benefit of true prophylactic antibiotic therapy for transurethral prostatic surgery and the prostatic chip data suggest that some of the risk is due to pre-operative contamination of the prostate in the absence of per-operative urinary infection or catheterisation.
Transurethral resection of the prostate is the commonest operation performed on men over the age of 65 years and has a low morbidity and perioperative mortality rate of less than 1% (Murphy et al., 1983). Whilst the majority of deaths that do occur are due to unavoidable cardiovascular complications, there are a number of men who die from avoidable septicaemic shock. The incidence of septicaeniia is 0 to 4%, although 10 to 32% will have a transient bacteraemia (Grabe, 1987). There is little debate about the need for antibiotic prophylaxis in patients who are known to have a pre-operative bacteriuria. However, only 10% of urologists in the United Kingdom routinely give antibiotics to all patients undergoing T U R P (Wilson and Lewi, 1985). The most commonly cited reasons for not giving prophylaxis are the generally low level of infective complications, lack of proof of efficacy, cost and the possibility of selecting Accepted for publication 15 February 1990
antibiotic resistant strains of bacteria. We have shown in a randomised control trial involving a group of patients without known pre-operative urinary infection undergoing TURP, that 48 hours of peri-operative parenteral cefotaxime resulted in a signiificant reduction in morbidity and mortality, including shorter hospitalisation when compared with no treatment (Hargreave et al., 1982). Moreover, ithis regime was significantly more effective than a single pre-operative dose (Hargreave et al., 1984), which is in agreement with other series (Grabe, 1987). In addition, the use of broad spectrum cephalosporins during a continuous 5year period did not result in the emergence of any new bacterial resistance patterns (Bentsi et al., 1987). Between 6 and 70%of patients with pre-operative sterile urine will develop significant bacteriuria post-oiperatively (Grabe, 1987). Unless the organism is Staphylococcus albus, urinary bacterial counts of 1O3 organisms/ml progress to significant
509
510 infection within 4 days (Gordon et al., 1983). The sources of post-operative bacteraemia in patients with previously uninfected urine may be several. Skin or urethral bacteria may be introduced into the circulation directly from the urethra by instrumental or catheter trauma or indirectly following colonisation of the urine. This may occur at the time of surgery or afterwards, particularly via the catheter lumen if accidental breaks of the closed drainage system occur or the catheter needs to be unblocked. Finally, it has been shown that quantitatively the most important factor associated with bacteraemia is positive culture from resected prostatic tissue, frequently in the presence of negative urinary culture (Robinson et al., 1982). The aims of the present randomised study were 3-fold 1. To compare the use of prophylactic antibiotic treated groups with pre-operative lubrication of the urethra and all instruments with antiseptic jelly containing chlorhexidine. 2. To assess further the prognostic value of culture of prostatic chippings from patients with negative urine culture at the time of surgery. 3. To compare the effectiveness of 48 hours’ treatment with parenteral cefotaxime with a similar course of another third generation broad spectrum cephalosporin, ceftizoxime.
Patients and Methods All patients undergoing transurethral prostatic surgery were eligible for entry to the trial with the following exclusions; those with known pre-operative bacteriuria, those already receiving antibiotic therapy and those who had a history of allergy to penicillins or cephalosporins. We also excluded patients with severe renal or hepatic failure. Some patients had bacteriuria prior to surgery but this was not known until afterwards. We have included these patients in our analysis. All patients gave informed consent before participating in the study. The patients were divided into 2 groups: those with and those without a urinary catheter preoperatively. Each group was randomised separately to receive 1 of the following regimes : Intravenous cefotaxime 1 g pre-operatively, followed by 3 further intramuscular doses at 12hourIy intervals. Intravenous ceftizoxime 1 g pre-operatively, followed by 3 further intramuscular doses at 12hourly intervals. Lubrication of the urethra with sterile petroleum
BRITISH JOURNAL OF UROLOGY
jelly containing 0.5% chlorhexidine 5 min prior to instrumentation, with lubrication of all instruments, including the catheter, with the same jelly. The patients in the first 2 groups received KY jelly as lubricant for all instruments but in all other respects all 3 groups were treated similarly. The operative technique was standardised as far as possible, although the operations were performed by different surgeons. If urethral dilatation was required the Otis was used and this fact recorded. During the procedure a glycine solution was used to irrigate the bladder. After completion of resection a 3-way Foley catheter was inserted and continuous irrigation with saline used until haemostasis was adequate. Details of the operation and daily clinical progress were recorded on special pro-formas. At the time the clinical recordings were made the doctor making the recordings was unaware to which treatment regimen the patient was allocated. Recatheterisation was necessary when a patient was not able to void either after removal of the catheter or when a catheter had become blocked by blood clots. Continence problems refer to temporary incontinence lasting for more than 24 h after removal of the catheter; dysuria was recorded only if symptoms persisted for more than 24 h after removal of the catheter. Fresh urine samples in the form of mid-stream samples or aspirates from the catheter tubing were sent prior to surgery and daily afterwards until the day of discharge or tenth postoperative day. These samples were specially identified and handled separately by the bacteriology department. They were examined microscopically and cultured using a quantitative technique. Isolates were identified and sensitivity tests to a range of commonly used antibacterial agents in addition to cefotaxime and ceftizoxime were carried out. Prostatic chips were collected aseptically at operation and transferred to dry sterile containers for immediate despatch to the laboratory. The chips were shaken vigorously in broth for 30 min and aliquots of the broth plated for culture. The remaining chips were then incubated in the broth overnight. Colony counts were made on the incubated plates and the organisms identified and tested for their antibiotic sensitivity as above. Blood samples for haemoglobin and white cell count and urea and electrolytes were taken both pre- and post-operatively. Blood cultures were taken when appropriate. A 2-stage analysis of the results was performed,
51 1
ANTIBIOTIC COMPARED WITH ANTISEPTIC PROPHYLAXIS FOR PROSTATIC SURGERY
firstly comparing cefotaxime with ceftizoxime and then antibiotics against antiseptic jelly. Statistical analysis was carried out by x2 tests or Wilcoxon rank sum tests as appropriate.
Results The study group included 196 patients. Of these, 64 patients received cefotaxime, 67 received ceftizoxime and 65 received topical antiseptic jelly. The groups were well balanced for age, indication for surgery, the presence of a pre-operative catheter or unknown pre-operative bacteriuria and also for routine haematological and biochemical parameters (Table 1). There were also no differences in the operative details between the groups (Table 2) or in the ratesof immediate complications in the recovery room such as hypotension, clot retention and bladder washout.
Table 3 shows comparative post-operative progress and complications for the 3 groups. There was no significant difference either for the overall incidence of post-operative complications or for any of these taken individually. The antiseptic treated patients required significantly more additional antibiotic therapy than the other groups during their admission (P< 0.05). Ceftizoxime treated patients had a significantly lower morning temperature than either cefotaxime (P
0007-1331/90/0066-0509/$10.00
01990 British Journal of Urology
Antibiotic Compared with Antiseptic Prophylaxis for Prostatic Surgery S. PRESCOlT, M. A. HADI. R. A. ELTON,A. W. S. RITCHIE, G. C. FOUBISTER, J. C. GOULD and T. B. HARGREAVE Department of Surgery1Urology and Central Microbiological Laiboratories, Western General Hospital; Medical Statistics Unit, University Medical School, Edinburgh
Summary-Two different regimens of cephalosporin antibiotic prophylaxis were compared with antiseptic lubricating jelly to try to prevent infection and complications in 196 men after prostatic surgery. Pre-operative urine was cultured and prostatic chips (170 cases) were also cultured to define the source of any infection. The use of antibiotics was associated with a reduced risk of postoperative bacteriuria. No serious complications occurred, although 1 patient in the antiseptic treated group developed rigors; 79 of 170 patients (46%) had positive prostatic chip cultures, of whom 74 had sterile pre-operative urine. There was no association lbetween the result of chip culture and the presence of a pre-operative catheter. Culture positive patients had an increased risk of postoperative urine infection, although the same organism was found in the prostate and urine in only 36% of cases of post-operative bacteriuria and in 43 (54%) the organism cultured from the prostate was Staphylococcus albus. This study provides further evidence of the benefit of true prophylactic antibiotic therapy for transurethral prostatic surgery and the prostatic chip data suggest that some of the risk is due to pre-operative contamination of the prostate in the absence of per-operative urinary infection or catheterisation.
Transurethral resection of the prostate is the commonest operation performed on men over the age of 65 years and has a low morbidity and perioperative mortality rate of less than 1% (Murphy et al., 1983). Whilst the majority of deaths that do occur are due to unavoidable cardiovascular complications, there are a number of men who die from avoidable septicaemic shock. The incidence of septicaeniia is 0 to 4%, although 10 to 32% will have a transient bacteraemia (Grabe, 1987). There is little debate about the need for antibiotic prophylaxis in patients who are known to have a pre-operative bacteriuria. However, only 10% of urologists in the United Kingdom routinely give antibiotics to all patients undergoing T U R P (Wilson and Lewi, 1985). The most commonly cited reasons for not giving prophylaxis are the generally low level of infective complications, lack of proof of efficacy, cost and the possibility of selecting Accepted for publication 15 February 1990
antibiotic resistant strains of bacteria. We have shown in a randomised control trial involving a group of patients without known pre-operative urinary infection undergoing TURP, that 48 hours of peri-operative parenteral cefotaxime resulted in a signiificant reduction in morbidity and mortality, including shorter hospitalisation when compared with no treatment (Hargreave et al., 1982). Moreover, ithis regime was significantly more effective than a single pre-operative dose (Hargreave et al., 1984), which is in agreement with other series (Grabe, 1987). In addition, the use of broad spectrum cephalosporins during a continuous 5year period did not result in the emergence of any new bacterial resistance patterns (Bentsi et al., 1987). Between 6 and 70%of patients with pre-operative sterile urine will develop significant bacteriuria post-oiperatively (Grabe, 1987). Unless the organism is Staphylococcus albus, urinary bacterial counts of 1O3 organisms/ml progress to significant
509
510 infection within 4 days (Gordon et al., 1983). The sources of post-operative bacteraemia in patients with previously uninfected urine may be several. Skin or urethral bacteria may be introduced into the circulation directly from the urethra by instrumental or catheter trauma or indirectly following colonisation of the urine. This may occur at the time of surgery or afterwards, particularly via the catheter lumen if accidental breaks of the closed drainage system occur or the catheter needs to be unblocked. Finally, it has been shown that quantitatively the most important factor associated with bacteraemia is positive culture from resected prostatic tissue, frequently in the presence of negative urinary culture (Robinson et al., 1982). The aims of the present randomised study were 3-fold 1. To compare the use of prophylactic antibiotic treated groups with pre-operative lubrication of the urethra and all instruments with antiseptic jelly containing chlorhexidine. 2. To assess further the prognostic value of culture of prostatic chippings from patients with negative urine culture at the time of surgery. 3. To compare the effectiveness of 48 hours’ treatment with parenteral cefotaxime with a similar course of another third generation broad spectrum cephalosporin, ceftizoxime.
Patients and Methods All patients undergoing transurethral prostatic surgery were eligible for entry to the trial with the following exclusions; those with known pre-operative bacteriuria, those already receiving antibiotic therapy and those who had a history of allergy to penicillins or cephalosporins. We also excluded patients with severe renal or hepatic failure. Some patients had bacteriuria prior to surgery but this was not known until afterwards. We have included these patients in our analysis. All patients gave informed consent before participating in the study. The patients were divided into 2 groups: those with and those without a urinary catheter preoperatively. Each group was randomised separately to receive 1 of the following regimes : Intravenous cefotaxime 1 g pre-operatively, followed by 3 further intramuscular doses at 12hourIy intervals. Intravenous ceftizoxime 1 g pre-operatively, followed by 3 further intramuscular doses at 12hourly intervals. Lubrication of the urethra with sterile petroleum
BRITISH JOURNAL OF UROLOGY
jelly containing 0.5% chlorhexidine 5 min prior to instrumentation, with lubrication of all instruments, including the catheter, with the same jelly. The patients in the first 2 groups received KY jelly as lubricant for all instruments but in all other respects all 3 groups were treated similarly. The operative technique was standardised as far as possible, although the operations were performed by different surgeons. If urethral dilatation was required the Otis was used and this fact recorded. During the procedure a glycine solution was used to irrigate the bladder. After completion of resection a 3-way Foley catheter was inserted and continuous irrigation with saline used until haemostasis was adequate. Details of the operation and daily clinical progress were recorded on special pro-formas. At the time the clinical recordings were made the doctor making the recordings was unaware to which treatment regimen the patient was allocated. Recatheterisation was necessary when a patient was not able to void either after removal of the catheter or when a catheter had become blocked by blood clots. Continence problems refer to temporary incontinence lasting for more than 24 h after removal of the catheter; dysuria was recorded only if symptoms persisted for more than 24 h after removal of the catheter. Fresh urine samples in the form of mid-stream samples or aspirates from the catheter tubing were sent prior to surgery and daily afterwards until the day of discharge or tenth postoperative day. These samples were specially identified and handled separately by the bacteriology department. They were examined microscopically and cultured using a quantitative technique. Isolates were identified and sensitivity tests to a range of commonly used antibacterial agents in addition to cefotaxime and ceftizoxime were carried out. Prostatic chips were collected aseptically at operation and transferred to dry sterile containers for immediate despatch to the laboratory. The chips were shaken vigorously in broth for 30 min and aliquots of the broth plated for culture. The remaining chips were then incubated in the broth overnight. Colony counts were made on the incubated plates and the organisms identified and tested for their antibiotic sensitivity as above. Blood samples for haemoglobin and white cell count and urea and electrolytes were taken both pre- and post-operatively. Blood cultures were taken when appropriate. A 2-stage analysis of the results was performed,
51 1
ANTIBIOTIC COMPARED WITH ANTISEPTIC PROPHYLAXIS FOR PROSTATIC SURGERY
firstly comparing cefotaxime with ceftizoxime and then antibiotics against antiseptic jelly. Statistical analysis was carried out by x2 tests or Wilcoxon rank sum tests as appropriate.
Results The study group included 196 patients. Of these, 64 patients received cefotaxime, 67 received ceftizoxime and 65 received topical antiseptic jelly. The groups were well balanced for age, indication for surgery, the presence of a pre-operative catheter or unknown pre-operative bacteriuria and also for routine haematological and biochemical parameters (Table 1). There were also no differences in the operative details between the groups (Table 2) or in the ratesof immediate complications in the recovery room such as hypotension, clot retention and bladder washout.
Table 3 shows comparative post-operative progress and complications for the 3 groups. There was no significant difference either for the overall incidence of post-operative complications or for any of these taken individually. The antiseptic treated patients required significantly more additional antibiotic therapy than the other groups during their admission (P< 0.05). Ceftizoxime treated patients had a significantly lower morning temperature than either cefotaxime (P
