Session VII
R. A. Janknegt
Prophylaxis in Urological Surgery Summary: Prophylaxis in urological surgery is usually taken to mean antibacterial agents. However, in this study, other factors such as the environment, patient risk and surgical risk factors are also taken into account. Because patients have a wide variety of possible risk factors, individual variations must be possible. In standard transurethral resection in non-risk patients, single-dose preoperative prophylaxis may be sufficient. In open surgery prophylactic measures should be varied according to the extent of the procedure. Zusammenfassung: Prophylaxe bei urologischen Operationen. Prophytaxe bei urologischen Operationen bedeutet gew6hnlich die Anwendung von Antibiotika. In dieser Arbeit werden jedoch auch andere Faktoren, wie diejenigen, die in der Umgebung vorkommen, sowie Risikofaktoren des Patienten und des chirurgischen Eingriffes berticksichtigt. Da die Patienten einer grof3en Anzahl von Risikofaktoren unterworfen sind, mfissen individuelle Anpassungen m6glich sein. Bei der transurethralen Standardresektion sollte die Prophylaxe bei Patienten ohne zus/itzliches Risiko mit einer pr/ioperativen Dosis ausreichend sein. Bei offenen Operationen sotlten die Prophylaxemal3nahmen dem Ausmal3 des Eingriffes angepal3t werden.
Introduction
Urinary tract infections (15I'1) are still an important factor in daily urological practice and remain so in spite of the development of new techniques and new antimicrobial agents. Many articles on prophylaxis have been published, mainly on transurethral surgery. However, it is difficult to draw definite conclusions from. them because many criteria are used, such as different inclusion criteria (risk factors) as well as different pre- and postoperative procedures, open and closed drainage systems and - most of all - different antibiotics (different sensitivity, different half-life, etc.) [1-3]. The recent introduction of fluoroquinolones has brought the advantage of oral administration and a broad spectrum of activity that includes Pseudomonas. Patients with Preoperative Bacteriuria
Prophylaxis is given to uninfected patients. Those who already have preoperative bacteriuria should have preoperative treatment, which cannot be considered prophylactic. In these patients a large variety of risk
factors such as indwelling catheters, which cannot always be removed after the operation, must be considered. Prevention of bacteraemia is the primary goal in these patients. Treatment must necessarily be extended and the choice of antimicrobial agent depends on the sensitivity of the bacteria in the urine [4,5]. Definition of Bacteriuria and Bacteraemia
In bacteriuria the arbitrary level of > 105 cfu/ml in urine is mostly used to define significant bacteriuria. However, some publications suggest that even lower cell counts may lead to urinary tract infection [1,6]. Although the role of asymptomatic bacteriuria is questionable, looking at prophylaxis in previously non-infected patients it should be stressed that if postoperative bacteria of any cell count are found they should be classified as "infected". However, in three recent studies this is not defined, and comparison of the various prophylactic measures is therefore difficult [7-9]. Bacteraemia is usually an index of renal parenchymatous infection. These infections generally lead to fever. However, other conditions such as transient tissue necrosis immediately after the operation may lead to temporary fever, so fever alone is not a good parameter. The combination of fever and bacteraemia may lead to dangerous sepsis, such as systemic infection leading to hypotension, and is the most dangerous hazard following operations on the urinary tract. Prophylaxis should be aimed at preventing sepsis, which is seen in 0-4% of all operated patients. Bacteraemia progresses to sepsis in less than 25% of cases. Acute pyelonephritis may lead to sclerosis of the kidneys and in 83% of these patients bacteraemia and fever are found. Prophylaxis should therefore aim at a high concentration of the antimicrobial agent in all parenchymatous organs such as the kidneys, prostate and testes. Justification for Prophylaxis
When discussing prophylactic measures an exact definition of the criteria is necessary: 1. Do we want to prevent bacteraemia (sepsis)? 2. Do we want to prevent (asymptomatic) bacteriuria? Although it is tempting to give a single line of advice on prophylaxis in either open surgery or catheter management, there are many factors requiring a change of schedule from patient to patient. We must differentiate between non-risk patients and patients with risk factors
R. A. Janknegt, M. D., Ph. D., Dept. of Urology, University Hospital Maastricht, P. O. Box 5800, NL-6202AZ Maastricht, The Netherlands.
Infection 20 (1992) Suppl. 3 © MMV Medizin Verlag GmbH Miinchen, Mtinchen 1992
S 213
R. A. Janknegt: Prophylaxis in Urological Surgery (Table 1 ). There are two groups of risk factors that place patients at greater risk of infection: Primary risk factors [1,10,11] - h i s t o r y of recurrent urinary tract infections or prostatitis - sex (female) - age (elderly) - serious underlying disease (poorly controlled diabetes, immunosuppression, obesity, malnutrition, haematological disorders, remote infection and cancer). Secondary risk factors [12-14] indwelling catheter prolonged preoperative hospitalisation preoperative shaving During surgery: - inexperienced operator prolonged operation time contaminated equipment - increased blood loss improper drainage - excessive cautery necrotic debris Postoperative: bacteriuria - leucocyturia Most investigators report transient bacteriuria in 20-40% of the patients during the first month after transurethral resection (TUR). However, some investigators failed to differentiate between leucocyturia and bacteriuria in their studies. Leucocyturia may simply be the result of the granulation process in the resected prostatic area. However, in studies reporting a bacterial count of 103 to 105 cfu/ml, more patients had postoperative symptoms for a longer period than those who had sterile urine. In many studies it was stated of preoperatively sterile patients who had no prophylaxis, 6-70% had postoperative bacteriuria, with a mean value of 25%. In open surgery, wound infections and bacteriuria have been reported to range from 2.3 - 9.2% [11]. Because the percentage of infection either for open surgery or TUR is unacceptably high in non-protected patients and because so many have additional risk factors, prophylaxis, in my view, is justified and necessary. Choice
of
Antimicrobial
Agent
and
Duration
of
Treatment
As is well known, urinary tract infections are due mainly to gram-negative bacilli. Escherichia coli accounts for approximately 30% of the bacteriurias followed by Proteus, Pseudomonas, Klebsietla, Enterobacter and Serratia (Table 2) [6]. Usually 75% of patients who have not been hospitalized before have gram-negative bacilli as the causative organism. The source of bacteria is mostly either the distal urethra or the urine. However, patients with a longer hospital stay usually have nosocomial infections with organisms such as Pseudomonas, Klebsiella and Serratia. In S 214
Table 1 : Factors influencing the choice of prophylaxis.
BACTERIAL FACTORS ~x
ENVIRONMENT (ASEPTIC CONDITIONS)
~ PROPHYLAXIS PATIENT RISK FACI'ORS
SURGICALFACTORS
Table 2: Cultures from urine samples of patients from the outpatient department and of patients staying longer than two days at the department of urology of the University Hospital Maastricht in 1990. , .
, , ,
,
.
.
.
.
Escherichia coli
Pseudomonas spp. Enterococcus Proteus spp. Klebsietla spp. Enterobacter spp.
.
.
.
:
.
,
..
39.6 16.2 13.6 10.5 9.6 4.4
.
.
.
.
.
.
.
.
....
.. . . . . . . . . .
Enterococcus
Escherichiacoil Pseudomonasspp. Klebsiellaspp. Proteusspp. Enterobacterspp.
: - . . ,
............
,
27.7 26.5 18.1 6.0 4.8 3.7
such patients there is a tendency towards increasing resistance to the more commonly used antimicrobial agents, particularly sulphonamides, nitrufurantoin, ampicillin and tetracyclin, and such patients may need treatment with modern cephalosporins, aminoglycosides or quinolones. When choosing an antibiotic we should give preference to those with: - broad spectrum high renal parenchymatous concentration long half-life - low toxicity oral administration - low cost. The newer cephalosporins and quinolones fulfil most of these criteria except for low cost. Therefore the antibiotic should belong to one of these two categories. Concerning the time and duration of prophylaxis, most authors agree that antibacterial prophylaxis is most important at the moment of operation. The introduction of bacteria into the bloodstream or urine depends on the type of operation. The scientific rationale for giving antibiotics just before a surgical procedure was provided in animal experiments by Burke [2]. He infected incision wounds with Staphylococcus aureus and treated them with four different antibiotics. The results of his experiments have been applied to human surgery involving virtually all organ systems. Short courses of antibiotics have the advantage of low costs and fewer side effects. Therefore, proper prophylaxis should aim at very short courses that include the moment of introduction of the bacteria at either open surgery or T U R . Nielsen and Madsen could not confirm these facts in animal experiments when they gave antibiotics 11/zh before or 6 h after surgery. The infection rate was the
Infection20 (1992) Suppl. 3 © MMV MedizinVerlag GmbHMiinchen,Mfinchen1992
1L A~Janknegt: Prophylaxis in Urological Surgery same [15]. Thus, antibiotics should be given within the 6 h postoperative period. Antibiotics given later are useless as prophylaxis and are only used as treatment. Single-dose antibiotics with a long half-life can prevent the introduction of bacteria during the procedure and should be given 1 h prior to or at the start of the operation [3]. Auxiliary Factors
Auxiliary factors may play a role in the incidence of sepsis. I have compared prophylactic measures and auxiliary measures between 1986 and 1990 (Table 3). Table 3 shows that not only aseptic conditions but also the experience of the operator may play a role. One concludes that the antibiotic is not the only factor in prophylaxis (Table 2). In many studies antibiotic prophylaxis is given for different periods, such as: - always for ten days - until catheter removal (three days) - until two days after catheter removal (four days) - single dose perioperative - no antibiotics, unless indicated (fever, bacteraemia, or risk factors) Strategy in O p e n Surgery
The chance of wound infection was studied by Cruse and Foord [11]. They compared "clean" and "dirty" operations (with contaminated organs). In "clean" operations the wound infection rate was 1.5% and in "dirty" operations 40%. Considering prophylaxis in open surgery, one should take into account the following factors: - is the patient at risk? - are there any secondary risk factors? - were any catheters left in situ? - were intestinal parts used during the operation (bladder replacement, etc.)? In patients who are not at risk and in whom there are no secondary risk factors, prophylaxis may not be needed. However, bacteriuria and wound infection can still be reduced by giving a single broad-spectrum antibiotic at the start of the procedure. Patients at risk or with secondary risk factors may require prophylaxis up to three days. If intestinal parts are involved, then gram-positive and anaerobic bacteria may cause contamination. In such cases, newer cephalosporins or quinolones should be used in combination with metronidazole. Although aminoglycosides such as gentamicin and tobramycin have a broad spectrum that includes Pseudomonas, they are not effective against some gram-positive organisms (e.g. streptococci) and have the drawback of nephro- and ototoxicity. The newer cephalosporins and the quinolones come close to having the ideal spectrum of activity, although limited enterococcal activity is still a disadvantage. Also, they have an excellent safety record. Most of them, for example
Table 3: Various factors in one hospital which have affected infection prevention over the years. Some are environmental, others surgical or bacteriological.
Few aseptic measures No aseptic room 30% catheters preoperative Drainage by open system Experienced operator Always 10 day prophylaxis (ampicillin) Hospital stay: at least 7 days Result: Bacteraemia3%
Aseptic measures Aseptic room
R. A. Janknegt
Prophylaxis in Urological Surgery Summary: Prophylaxis in urological surgery is usually taken to mean antibacterial agents. However, in this study, other factors such as the environment, patient risk and surgical risk factors are also taken into account. Because patients have a wide variety of possible risk factors, individual variations must be possible. In standard transurethral resection in non-risk patients, single-dose preoperative prophylaxis may be sufficient. In open surgery prophylactic measures should be varied according to the extent of the procedure. Zusammenfassung: Prophylaxe bei urologischen Operationen. Prophytaxe bei urologischen Operationen bedeutet gew6hnlich die Anwendung von Antibiotika. In dieser Arbeit werden jedoch auch andere Faktoren, wie diejenigen, die in der Umgebung vorkommen, sowie Risikofaktoren des Patienten und des chirurgischen Eingriffes berticksichtigt. Da die Patienten einer grof3en Anzahl von Risikofaktoren unterworfen sind, mfissen individuelle Anpassungen m6glich sein. Bei der transurethralen Standardresektion sollte die Prophylaxe bei Patienten ohne zus/itzliches Risiko mit einer pr/ioperativen Dosis ausreichend sein. Bei offenen Operationen sotlten die Prophylaxemal3nahmen dem Ausmal3 des Eingriffes angepal3t werden.
Introduction
Urinary tract infections (15I'1) are still an important factor in daily urological practice and remain so in spite of the development of new techniques and new antimicrobial agents. Many articles on prophylaxis have been published, mainly on transurethral surgery. However, it is difficult to draw definite conclusions from. them because many criteria are used, such as different inclusion criteria (risk factors) as well as different pre- and postoperative procedures, open and closed drainage systems and - most of all - different antibiotics (different sensitivity, different half-life, etc.) [1-3]. The recent introduction of fluoroquinolones has brought the advantage of oral administration and a broad spectrum of activity that includes Pseudomonas. Patients with Preoperative Bacteriuria
Prophylaxis is given to uninfected patients. Those who already have preoperative bacteriuria should have preoperative treatment, which cannot be considered prophylactic. In these patients a large variety of risk
factors such as indwelling catheters, which cannot always be removed after the operation, must be considered. Prevention of bacteraemia is the primary goal in these patients. Treatment must necessarily be extended and the choice of antimicrobial agent depends on the sensitivity of the bacteria in the urine [4,5]. Definition of Bacteriuria and Bacteraemia
In bacteriuria the arbitrary level of > 105 cfu/ml in urine is mostly used to define significant bacteriuria. However, some publications suggest that even lower cell counts may lead to urinary tract infection [1,6]. Although the role of asymptomatic bacteriuria is questionable, looking at prophylaxis in previously non-infected patients it should be stressed that if postoperative bacteria of any cell count are found they should be classified as "infected". However, in three recent studies this is not defined, and comparison of the various prophylactic measures is therefore difficult [7-9]. Bacteraemia is usually an index of renal parenchymatous infection. These infections generally lead to fever. However, other conditions such as transient tissue necrosis immediately after the operation may lead to temporary fever, so fever alone is not a good parameter. The combination of fever and bacteraemia may lead to dangerous sepsis, such as systemic infection leading to hypotension, and is the most dangerous hazard following operations on the urinary tract. Prophylaxis should be aimed at preventing sepsis, which is seen in 0-4% of all operated patients. Bacteraemia progresses to sepsis in less than 25% of cases. Acute pyelonephritis may lead to sclerosis of the kidneys and in 83% of these patients bacteraemia and fever are found. Prophylaxis should therefore aim at a high concentration of the antimicrobial agent in all parenchymatous organs such as the kidneys, prostate and testes. Justification for Prophylaxis
When discussing prophylactic measures an exact definition of the criteria is necessary: 1. Do we want to prevent bacteraemia (sepsis)? 2. Do we want to prevent (asymptomatic) bacteriuria? Although it is tempting to give a single line of advice on prophylaxis in either open surgery or catheter management, there are many factors requiring a change of schedule from patient to patient. We must differentiate between non-risk patients and patients with risk factors
R. A. Janknegt, M. D., Ph. D., Dept. of Urology, University Hospital Maastricht, P. O. Box 5800, NL-6202AZ Maastricht, The Netherlands.
Infection 20 (1992) Suppl. 3 © MMV Medizin Verlag GmbH Miinchen, Mtinchen 1992
S 213
R. A. Janknegt: Prophylaxis in Urological Surgery (Table 1 ). There are two groups of risk factors that place patients at greater risk of infection: Primary risk factors [1,10,11] - h i s t o r y of recurrent urinary tract infections or prostatitis - sex (female) - age (elderly) - serious underlying disease (poorly controlled diabetes, immunosuppression, obesity, malnutrition, haematological disorders, remote infection and cancer). Secondary risk factors [12-14] indwelling catheter prolonged preoperative hospitalisation preoperative shaving During surgery: - inexperienced operator prolonged operation time contaminated equipment - increased blood loss improper drainage - excessive cautery necrotic debris Postoperative: bacteriuria - leucocyturia Most investigators report transient bacteriuria in 20-40% of the patients during the first month after transurethral resection (TUR). However, some investigators failed to differentiate between leucocyturia and bacteriuria in their studies. Leucocyturia may simply be the result of the granulation process in the resected prostatic area. However, in studies reporting a bacterial count of 103 to 105 cfu/ml, more patients had postoperative symptoms for a longer period than those who had sterile urine. In many studies it was stated of preoperatively sterile patients who had no prophylaxis, 6-70% had postoperative bacteriuria, with a mean value of 25%. In open surgery, wound infections and bacteriuria have been reported to range from 2.3 - 9.2% [11]. Because the percentage of infection either for open surgery or TUR is unacceptably high in non-protected patients and because so many have additional risk factors, prophylaxis, in my view, is justified and necessary. Choice
of
Antimicrobial
Agent
and
Duration
of
Treatment
As is well known, urinary tract infections are due mainly to gram-negative bacilli. Escherichia coli accounts for approximately 30% of the bacteriurias followed by Proteus, Pseudomonas, Klebsietla, Enterobacter and Serratia (Table 2) [6]. Usually 75% of patients who have not been hospitalized before have gram-negative bacilli as the causative organism. The source of bacteria is mostly either the distal urethra or the urine. However, patients with a longer hospital stay usually have nosocomial infections with organisms such as Pseudomonas, Klebsiella and Serratia. In S 214
Table 1 : Factors influencing the choice of prophylaxis.
BACTERIAL FACTORS ~x
ENVIRONMENT (ASEPTIC CONDITIONS)
~ PROPHYLAXIS PATIENT RISK FACI'ORS
SURGICALFACTORS
Table 2: Cultures from urine samples of patients from the outpatient department and of patients staying longer than two days at the department of urology of the University Hospital Maastricht in 1990. , .
, , ,
,
.
.
.
.
Escherichia coli
Pseudomonas spp. Enterococcus Proteus spp. Klebsietla spp. Enterobacter spp.
.
.
.
:
.
,
..
39.6 16.2 13.6 10.5 9.6 4.4
.
.
.
.
.
.
.
.
....
.. . . . . . . . . .
Enterococcus
Escherichiacoil Pseudomonasspp. Klebsiellaspp. Proteusspp. Enterobacterspp.
: - . . ,
............
,
27.7 26.5 18.1 6.0 4.8 3.7
such patients there is a tendency towards increasing resistance to the more commonly used antimicrobial agents, particularly sulphonamides, nitrufurantoin, ampicillin and tetracyclin, and such patients may need treatment with modern cephalosporins, aminoglycosides or quinolones. When choosing an antibiotic we should give preference to those with: - broad spectrum high renal parenchymatous concentration long half-life - low toxicity oral administration - low cost. The newer cephalosporins and quinolones fulfil most of these criteria except for low cost. Therefore the antibiotic should belong to one of these two categories. Concerning the time and duration of prophylaxis, most authors agree that antibacterial prophylaxis is most important at the moment of operation. The introduction of bacteria into the bloodstream or urine depends on the type of operation. The scientific rationale for giving antibiotics just before a surgical procedure was provided in animal experiments by Burke [2]. He infected incision wounds with Staphylococcus aureus and treated them with four different antibiotics. The results of his experiments have been applied to human surgery involving virtually all organ systems. Short courses of antibiotics have the advantage of low costs and fewer side effects. Therefore, proper prophylaxis should aim at very short courses that include the moment of introduction of the bacteria at either open surgery or T U R . Nielsen and Madsen could not confirm these facts in animal experiments when they gave antibiotics 11/zh before or 6 h after surgery. The infection rate was the
Infection20 (1992) Suppl. 3 © MMV MedizinVerlag GmbHMiinchen,Mfinchen1992
1L A~Janknegt: Prophylaxis in Urological Surgery same [15]. Thus, antibiotics should be given within the 6 h postoperative period. Antibiotics given later are useless as prophylaxis and are only used as treatment. Single-dose antibiotics with a long half-life can prevent the introduction of bacteria during the procedure and should be given 1 h prior to or at the start of the operation [3]. Auxiliary Factors
Auxiliary factors may play a role in the incidence of sepsis. I have compared prophylactic measures and auxiliary measures between 1986 and 1990 (Table 3). Table 3 shows that not only aseptic conditions but also the experience of the operator may play a role. One concludes that the antibiotic is not the only factor in prophylaxis (Table 2). In many studies antibiotic prophylaxis is given for different periods, such as: - always for ten days - until catheter removal (three days) - until two days after catheter removal (four days) - single dose perioperative - no antibiotics, unless indicated (fever, bacteraemia, or risk factors) Strategy in O p e n Surgery
The chance of wound infection was studied by Cruse and Foord [11]. They compared "clean" and "dirty" operations (with contaminated organs). In "clean" operations the wound infection rate was 1.5% and in "dirty" operations 40%. Considering prophylaxis in open surgery, one should take into account the following factors: - is the patient at risk? - are there any secondary risk factors? - were any catheters left in situ? - were intestinal parts used during the operation (bladder replacement, etc.)? In patients who are not at risk and in whom there are no secondary risk factors, prophylaxis may not be needed. However, bacteriuria and wound infection can still be reduced by giving a single broad-spectrum antibiotic at the start of the procedure. Patients at risk or with secondary risk factors may require prophylaxis up to three days. If intestinal parts are involved, then gram-positive and anaerobic bacteria may cause contamination. In such cases, newer cephalosporins or quinolones should be used in combination with metronidazole. Although aminoglycosides such as gentamicin and tobramycin have a broad spectrum that includes Pseudomonas, they are not effective against some gram-positive organisms (e.g. streptococci) and have the drawback of nephro- and ototoxicity. The newer cephalosporins and the quinolones come close to having the ideal spectrum of activity, although limited enterococcal activity is still a disadvantage. Also, they have an excellent safety record. Most of them, for example
Table 3: Various factors in one hospital which have affected infection prevention over the years. Some are environmental, others surgical or bacteriological.
Few aseptic measures No aseptic room 30% catheters preoperative Drainage by open system Experienced operator Always 10 day prophylaxis (ampicillin) Hospital stay: at least 7 days Result: Bacteraemia3%
Aseptic measures Aseptic room
