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Antibacterial Prophylaxis In Prostatectomy Patients
Vol. 111, June
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1974 by The Williams & Wilkins Co.
ANTIBACTERIAL PROPHYLAXIS IN PROSTATECTOMY PATIENTS EDWARD J. MCGUIRE From the Department of Surgery, Section of Urology, Yale University School of Medicine, New Haven, Connecticut
Bacteriuria is often present in patients who have undergone prostatectomy and may be present preoperatively as a result of temporary catheter drainage. The significance of bacteriuria in these patients is difficult to assess. The response to bacteriuria may differ in the same patient and appears to be related to the operative procedure. Thus, preoperative bacteriuria is more often clinically significant than bacteriuria present 3 weeks following the procedure. Bacteriuria in the intraoperative and immediate postoperative periods may lead to septicemia. Estimates of the frequency of bacteremia during transurethral prostatic resection in bacteriuric patients have ranged from 12 to 54 per cent.'· 2 However, this is not necessarily associated either with the development of true septicemia or subsequent clinical problems with infection. The factors which determine whether a patient will experience only transient bacteremia or have clinical septicemia are not clearly established. 3 Antibacterial agents have been administered to patients undergoing prostatectomy to treat existent bacteriuria and to prevent the development of urologic sepsis. Numerous clinical studies have been done with a variety of antimicrobial agents in an attempt to demonstrate the efficacy of these agents for treatment and prophylaxis but the results are conflicting. Creevy and Feeney found that intraoperative administration of a tetracycline decreased the number of positive blood cultures at the time of operation. 2 The importance of transient intraoperative bacteremia is unknown 3 • • and many blood cultures yielded organisms which were not found on urine culture. Moreover, treated patients were not free of bacteremia and often had resistant strains of Proteus and Pseudomonas on blood culture in contrast to untreated patients who more often had Escherichia coli. Lacy and associates reported a beneficial effect from the routine prophylactic use of a cephalosporin derivative in patients undergoing prostatectomy. 5 The patients studied were infected
and uninfected at the time of prostatectomy. The infected patients received a cephalosporin without regard to culture and sensitivity data and had fewer problems with infection during their clinical course than those who were infected but received appropriate antimicrobial therapy as selected by culture and sensitivity data. Miller and associates found that antimicrobial treatment of patients with bacteriuria was effective in decreasing the number of serious febrile reactions postoperatively but prophylaxis in abacteriuric patients was considered unnecessary. 6 However, Plorde and associates found that prophylactic treatment with an aminoglycoside antimicrobial (kanamycin) is indicated in abacteriuric patients but patients with bacteriuria did not benefit from treatment unless they had a febrile response to their urinary tract infection.7 Appleton and Waisbren, 8 and Genster and Madsen• were unable to demonstrate any beneficial effect when prophylactic antimicrobials were used in patients undergoing transurethral resection. A major difficulty with the application of prophylactic treatment is the emergence of resistant organisms in hospital populations. There is some evidence that the mortality from gram-negative septicemia in urologic patients is related to the causative organism. Hewitt and associates found the highest mortality rate in patients infected with Pseudomonas species and the lowest rate with E. coli infections. ' 0 It would seem that continued selection of resistant organisms by antimicrobial treatment leads to infections which are more difficult to treat successfully. The incidence of bacteriuria in patients undergoing prostatectomy has been estimated to be between 30 and 75 per cent. The over-all mortality of 1 to 2.5 per cent for prostatectomy, even if all deaths could be attributed to infection, does not • Miller, A. L., Jr., Scott, F. B. and Scott, R., Jr.: An evaluation of antibiotics prior to prostatectomy. J. Urol., 92: 711, 1964.
Accepted for publication November 30, 1973. 1 Biorn, C. L., Browning, W. H. and Thompson, L.: Transient bacteremia immediately following transurethral prostatic resection. J. Urol., 63: 155, 1950. 2 Creevy, C. D. and Feeney, M. J.: Routine use of antibiotics in transurethral prostatic resection: a clinical investigation. J. Urol., 71: 615, 1954. 3 Bulkley, G. J., O'Conor, V. J. and Sokol, J. K.: A clinical study of bacteremia and overhydration following transurethral resection. J. Urol., 72: 1205, 1954. 4 Steyn, J. H. and Logie, N. J.: Bacteraemia following prostatectomy. Brit. J. Urol., 34: 459, 1962. 5 Lacy, S.S., Drach, G. W. and Cox, C. E.: Incidence of infection after prostatectomy and efficacy of cephaloridine prophylaxis. J. Urol., 105: 836, 1971.
7 Plorde, J. T., Kennedy, R. P., Bourne, H. H., Ansell, J. S. and Petersdorf, R. G.: Course and prognosis of prostatectomy: with a note on the incidence of bacteremia and effectiveness of chemoprophylaxis. New Engl. J. Med., 272: 269, 1965. 8 Appleton, D. M. and Waisbren, B. A.: The prophylactic use of chloramphenicol in transurethral resections of the prostate gland. J. Urol., 75: 304, 1956. 'Genster, H. G. and Madsen, P. 0.: Urinary tract infections following transurethral prostatectomy: with special reference to the use of antimicrobials. J. Urol.,
104: 163, 1970. 10 Hewitt, C. B., Overholt, E. L., Finder, R. J. and Patton, J. F.: Gram-negative septicemia in urology. J. Urol., 93: 299, 1965.
794
795
ANTIMICROBIALS IN PROSTATECTOMY
appear to reflect a high rate of sepsis among the large group of patients known to be bacteriuric. Wilson and associates noted that the rate of development of true sepsis appeared to be lower in patients with indwelling catheters related to prostatectomy than in patients who were catheterized for other conditions. 11 While antimicrobials play a role in the present low mortality rate after prostatectomy, other factors may be equally important and the precise role of antimicrobial therapy remains to be clearly established. The effects of specific antimicrobial therapy in bacteriuric patients and prophylactic therapy in abacteriuric patients were studied. On admission to the hospital for prostatectomy 114 patients were alternately assigned to a treatment or non-treatment group. Antimicrobials in the treated group were selected on the basis of culture and sensitivity data if bacteriuria was present or by the preference of the surgeon in abacteriuric patients. The untreated group received antimicrobials only in response to a febrile episode related to a urinary tract infection. Urine cultures were obtained on admission to the hospital, 24 hours preoperatively and 1 day, 1 week, 6 weeks and 10 weeks postoperatively. The clinical course of each group was compared with respect to the occurrence of fever, development of sepsis which was defined as a significant febrile response (temperature of 102F or more), urinary tract infection, and acquisition and persistence of bacteriuria during the study period. RESllLTS
Patients ranged in age from 53 to 84 years old. There were 57 patients in the treated group and 57 in the untreated group. On admission to the hospital 82 patients were abacteriuric and 32 were bacteriuric. Forty-five patients underwent open prostatectomy and 69 underwent transurethral resection. There was no significant difference in the number of patients who had a fever or a positive blood culture, nor was there a difference in the rate of clearing of bacteriuria in the postoperative period between the treated and untreated patients. Treatment of patients with infected urine preoperatively, based on culture and sensitivity of the organisms, did not appear to offer any significant advantage when compared to no treatment. Similarly, patients in the treated group who received prophylactic treatment with antimicrobials had approximately the same number of infectious complications as those who received no treatment (table 1). The antimicrobials used at various times during the study are shown in table 2. The majority of treated patients received ampicillin or a cephalosporin derivative initially. There were 15 patients in the treated group who required another antimi11 Wilson, F. M., Shumaker, E. ,J., Fentress, V. and Lerner, A. M.: Epidemiologic aspects of postoperative sepsis in a urologic practice (with a note concerning antibacierial prophylaxis). J. Urol., 105: 295, 1971.
TABLE
Treated
Not Treated --,----------
Total Number ofpatients Fever ICl!F Urologic sepsis Positive blood culture Infected at 10 weeks
Inf.' Uninf.1"
Total
Inf.' llt1inLI
57
19
:,8
57
1:l
24 1:3 2
11
1:1
rn
5 Cl
8
11
:1 :1
2
4
0
16
10
6
14
6
1:; fl
8
* Infected at the time of hospitalization. t Uninfected at tbe time of hospitalization. TABLE
2. Antimicrobials Treated
Primarv Antimicr~bial Ampicillin Cephalosporin N itrofurantoin
Tetracycline Gantrisin Gentamicin Kanamycin Totals Inappropriate antimicrobial use
2:1 2:1
!'-Jot Treated
Required Additional
Required lnstitulinn
2 :J
1 5
2 :1 57
2 7
lG
1(',l
2
crobial agent in response to a febrile and. 16 in the non-treated group who required the imtitL; tion of an antimicrobial agent in response to a febrile episode. Three patients in the treated group and 5 in the untreated group received antimicrobials inappropriately as determined by culture or for a reason other than a urinary tract infection. The incidence of bacteriuria in patients whc were infected preoperatively is shown in 1 transient decrease in the incidence of bacteriuria occurred in the treated group in the immediate postoperative period but was short-lived. The est number of febrile episodes resulting from urinary infection occurred during the first postoperative week when an approximately equal number of patients in both groups was infected. The tion and persistence of bacteriuria in patients with sterile urine cultures are shown in figure 2. Antimicrobial treatment did not appear to occurrence of bacteriuria nor did it effect the of clearing in the postoperative period. The ity of febrile episodes occurred 3 and 4 day~ postoperatively. However, the number of patients manifesting bacteriuria was highest during the second and third postoperative weeks. curred only twice during this period larger number of patients who were bacteriuric and was related to urinary retention in both cases. There was a rapid decline in the number of febrile responses to urinary tract infection following establishment of adequate voiding as shown in figure 3. The over-all incidence of sepsis was 21 per cent.
796
MCGUIRE
100 e NOT TREATED
O TREATED
80
% of Patients
60
with bocteriuria
·------- .
40
20
ADM PRE 3d
3wk
twk
10wk
6wk
OP FIG. 1. Bacteriuria in patients at intervals during study period who were infected on hospitalization 100
o e
80
TREATED NOT TREATED
60
o/o of Patients with bacteriuria
40
20
ADM
PRE 3d
OP
1wk
3wk
6wk
10wk
FIG. 2. Acquisition and persistence of bacteriuria in patients with sterile urine cultures on hospitalization
Those in whom bacteriuria was present for 30 days or more prior to hospitalization had a low rate of sepsis since only 1 in 29 had a significant febrile response as a result of a urinary tract infection. Sixty-four patients had short-term infections of less than 30 days and sepsis developed in 23, an incidence of 34 per cent. Of the 43 patients who were hospitalized in retention, 38 per cent had urologic sepsis. Of the patients who had retention and short-term urinary tract infection a febrile response to an infection occurred in 50 per cent. Patients who had a systemic febrile response to infection experienced an average delay between hospitalization and operation of 9.8 days, those who did not have sepsis had an average delay of 4.6
days and those who had retention and sepsis experienced an average delay of 14 days. Of the 59 abacteriuric patients who were hospitalized for elective operation, which was performed within 3 days of admission, 5 (9 per cent) had a febrile response to a urinary tract infection. DISCUSSION
This study indicates that patients undergoing prostatectomy do not all face the same risk from infection. Patients who were chronically bacteriuric for a prolonged period of time preoperatively, particularly those who had been on chronic catheter drainage because of severe urinary tract decom-
797
ANTIMICROBIALS IN PROSTATECTOMY
WO 0 TREATED ., NOT TREATED
80
0
SEPSIS TREATED
~ SEPSIS UNTREATED
50
of Patients with bacteriuri a
0/ 0
40
20 8
2,:,.. .~DM
i
/1 PRE
OP
3d
lwll
3wk
6w~
iOwl<
FIG. :3. Percentage of patients with bacteriuria and number of febrile episodes related to urinary infection
pensation, rarely had a significant febrile response postoperatively. However, they did have persistent bacteriuria for a longer period after prostatectomy. The duration of the postoperative bacteriuria seemed more a reflection of the degree of urinary tract damage resultant from obstruction than the type and amount of antimicrobial therapy used. Patients hospitalized without bacteriuria for elective transurethral resection had the highest rate of sterile urine cultures throughout the period of study and antimicrobial treatment seemed to offer no advantage for postoperative sepsis or morbidity since the treated patients in this group had the same clinical course as the untreated patients. Patients with recently acquired bacteriuria or those hospitalized in urinary retention who required preoperative catheterization had an increased risk of developing sepsis since 35 to 50 per cent of them had clinical evidence of systemic infection. There appeared to be a definite relationship between the incidence of sepsis and the delay between hospitalization and subsequent operation. Although antimicrobials were useful in the treatment of acute systemic infection when it occurred, they did not seem to prevent the development of sepsis in these patients when given prophylactically. It could be argued that the routine use of an aminoglycoside antimicrobial prophylactically in these patients might be effective since superinfection with resistant bacterial strains is unusual when these agents are used. Aminoglycosides were not used extensively in this study. A previous study by Plorde and associates did suggest that the use of aminoglycosides in abacteriuric patients was effective in the prevention of postoperative morbidity caused by infection. However, the differences reported by these investigators compared a
febrile response in :3 of 18 patients who received an aminoglycoside with 5 of 15 patients who received no treatment. In a sample size of :3:3, a difference oi 2 patients does not seem highly significant. Considerably more postoperative bleeding and catheter complications occurred in the untreated group and freedom from these complications in the treated group was ascribed to the antimicrobial agent used. It seems more likely that those s who experienced surgical complications, such at: bleeding requiring frequent irrigations, would un fairly weight the study in favor of the treated group with a lower incidence of these problems. Whether aminoglycosides would prevent the development of sepsis in high risk patients such as those ized in retention who experienced a delay between admission and operation has not been studied. This is a relatively small group of patients but it seems possible that they could benefit from treatment initiated not longer than a few days preoperatively to obviate problems of superinfection. In contrast are patients hospitalized without retention but with sterile urine cultures who underwen l operation without delay, of whom only 9 per cent had a serious febrile response to a urinary infection. It does not seem worthwhile to administer an aminoglycoside to this group prophylactically in view of their relatively low risk. The time at which patients undergoing prostatectomy are most at risk from the complications of infection is ;3 and 4 days postoperatively, when 29 per cent of the patients in this study had bacteri uria. However, 1 to 3 weeks postoperatively, when 60 per cent of the total number of patients had bacteriuria, there were only 2 episodes of which were related to late urinary obstruction. Bacteriuria which persisted after the establish-
798
MCGUIRE
ment of adequate voiding was asymptomatic and is probably of little clinical significance. It is evident from these findings that the generally used criteria for the evaluation of the efficacy of antimicrobial treatment in patients undergoing prostatectomy may not only reflect antibacterial activity of the agent used but also the preoperative condition of the patient. The factors of particular importance were the duration of infection, the incidence of urinary retention and the delay between hospitalization and operation. The conflicting reports in the literature on the efficacy of antimicrobials may be partially explained by differences in the preoperative status of the patients studied. It is also apparent that while the presence of bacteriuria may be transiently influenced by the antimicrobials used in this study they are of doubtful clinical value in the prevention of serious systemic infections. Finally, the duration of postoperative bacteriuria does not seem to be affected by antimicrobial treatment in that the rate of disappearance of organisms from the urine was the
same in the treated and untreated groups. Patients hospitalized with uninfected urine who acquired bacteriuria which failed to clear at 10 weeks amounted to 15 per cent of the treated group and 16 per cent of the non-treated group. In patients hospitalized with infected urine, 50 per cent failed to clear their infection in both groups. Clinical symptoms as a result of bacteriuria during the late postoperative period are an indication of urinary tract dysfunction or late obstruction rather than the virulence of the infecting organism. SUMMARY
A review is made of 114 patients who were hospitalized for prostatectomy and alternately treated with and without prophylactic antimicrobial drugs. The clinical course, incidence of infectious complications and bacteriuria did not appear to be different in the 2 groups. Host factors are probably primarily responsible for the prognosis of urinary infections in these patients.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1974 by The Williams & Wilkins Co.
ANTIBACTERIAL PROPHYLAXIS IN PROSTATECTOMY PATIENTS EDWARD J. MCGUIRE From the Department of Surgery, Section of Urology, Yale University School of Medicine, New Haven, Connecticut
Bacteriuria is often present in patients who have undergone prostatectomy and may be present preoperatively as a result of temporary catheter drainage. The significance of bacteriuria in these patients is difficult to assess. The response to bacteriuria may differ in the same patient and appears to be related to the operative procedure. Thus, preoperative bacteriuria is more often clinically significant than bacteriuria present 3 weeks following the procedure. Bacteriuria in the intraoperative and immediate postoperative periods may lead to septicemia. Estimates of the frequency of bacteremia during transurethral prostatic resection in bacteriuric patients have ranged from 12 to 54 per cent.'· 2 However, this is not necessarily associated either with the development of true septicemia or subsequent clinical problems with infection. The factors which determine whether a patient will experience only transient bacteremia or have clinical septicemia are not clearly established. 3 Antibacterial agents have been administered to patients undergoing prostatectomy to treat existent bacteriuria and to prevent the development of urologic sepsis. Numerous clinical studies have been done with a variety of antimicrobial agents in an attempt to demonstrate the efficacy of these agents for treatment and prophylaxis but the results are conflicting. Creevy and Feeney found that intraoperative administration of a tetracycline decreased the number of positive blood cultures at the time of operation. 2 The importance of transient intraoperative bacteremia is unknown 3 • • and many blood cultures yielded organisms which were not found on urine culture. Moreover, treated patients were not free of bacteremia and often had resistant strains of Proteus and Pseudomonas on blood culture in contrast to untreated patients who more often had Escherichia coli. Lacy and associates reported a beneficial effect from the routine prophylactic use of a cephalosporin derivative in patients undergoing prostatectomy. 5 The patients studied were infected
and uninfected at the time of prostatectomy. The infected patients received a cephalosporin without regard to culture and sensitivity data and had fewer problems with infection during their clinical course than those who were infected but received appropriate antimicrobial therapy as selected by culture and sensitivity data. Miller and associates found that antimicrobial treatment of patients with bacteriuria was effective in decreasing the number of serious febrile reactions postoperatively but prophylaxis in abacteriuric patients was considered unnecessary. 6 However, Plorde and associates found that prophylactic treatment with an aminoglycoside antimicrobial (kanamycin) is indicated in abacteriuric patients but patients with bacteriuria did not benefit from treatment unless they had a febrile response to their urinary tract infection.7 Appleton and Waisbren, 8 and Genster and Madsen• were unable to demonstrate any beneficial effect when prophylactic antimicrobials were used in patients undergoing transurethral resection. A major difficulty with the application of prophylactic treatment is the emergence of resistant organisms in hospital populations. There is some evidence that the mortality from gram-negative septicemia in urologic patients is related to the causative organism. Hewitt and associates found the highest mortality rate in patients infected with Pseudomonas species and the lowest rate with E. coli infections. ' 0 It would seem that continued selection of resistant organisms by antimicrobial treatment leads to infections which are more difficult to treat successfully. The incidence of bacteriuria in patients undergoing prostatectomy has been estimated to be between 30 and 75 per cent. The over-all mortality of 1 to 2.5 per cent for prostatectomy, even if all deaths could be attributed to infection, does not • Miller, A. L., Jr., Scott, F. B. and Scott, R., Jr.: An evaluation of antibiotics prior to prostatectomy. J. Urol., 92: 711, 1964.
Accepted for publication November 30, 1973. 1 Biorn, C. L., Browning, W. H. and Thompson, L.: Transient bacteremia immediately following transurethral prostatic resection. J. Urol., 63: 155, 1950. 2 Creevy, C. D. and Feeney, M. J.: Routine use of antibiotics in transurethral prostatic resection: a clinical investigation. J. Urol., 71: 615, 1954. 3 Bulkley, G. J., O'Conor, V. J. and Sokol, J. K.: A clinical study of bacteremia and overhydration following transurethral resection. J. Urol., 72: 1205, 1954. 4 Steyn, J. H. and Logie, N. J.: Bacteraemia following prostatectomy. Brit. J. Urol., 34: 459, 1962. 5 Lacy, S.S., Drach, G. W. and Cox, C. E.: Incidence of infection after prostatectomy and efficacy of cephaloridine prophylaxis. J. Urol., 105: 836, 1971.
7 Plorde, J. T., Kennedy, R. P., Bourne, H. H., Ansell, J. S. and Petersdorf, R. G.: Course and prognosis of prostatectomy: with a note on the incidence of bacteremia and effectiveness of chemoprophylaxis. New Engl. J. Med., 272: 269, 1965. 8 Appleton, D. M. and Waisbren, B. A.: The prophylactic use of chloramphenicol in transurethral resections of the prostate gland. J. Urol., 75: 304, 1956. 'Genster, H. G. and Madsen, P. 0.: Urinary tract infections following transurethral prostatectomy: with special reference to the use of antimicrobials. J. Urol.,
104: 163, 1970. 10 Hewitt, C. B., Overholt, E. L., Finder, R. J. and Patton, J. F.: Gram-negative septicemia in urology. J. Urol., 93: 299, 1965.
794
795
ANTIMICROBIALS IN PROSTATECTOMY
appear to reflect a high rate of sepsis among the large group of patients known to be bacteriuric. Wilson and associates noted that the rate of development of true sepsis appeared to be lower in patients with indwelling catheters related to prostatectomy than in patients who were catheterized for other conditions. 11 While antimicrobials play a role in the present low mortality rate after prostatectomy, other factors may be equally important and the precise role of antimicrobial therapy remains to be clearly established. The effects of specific antimicrobial therapy in bacteriuric patients and prophylactic therapy in abacteriuric patients were studied. On admission to the hospital for prostatectomy 114 patients were alternately assigned to a treatment or non-treatment group. Antimicrobials in the treated group were selected on the basis of culture and sensitivity data if bacteriuria was present or by the preference of the surgeon in abacteriuric patients. The untreated group received antimicrobials only in response to a febrile episode related to a urinary tract infection. Urine cultures were obtained on admission to the hospital, 24 hours preoperatively and 1 day, 1 week, 6 weeks and 10 weeks postoperatively. The clinical course of each group was compared with respect to the occurrence of fever, development of sepsis which was defined as a significant febrile response (temperature of 102F or more), urinary tract infection, and acquisition and persistence of bacteriuria during the study period. RESllLTS
Patients ranged in age from 53 to 84 years old. There were 57 patients in the treated group and 57 in the untreated group. On admission to the hospital 82 patients were abacteriuric and 32 were bacteriuric. Forty-five patients underwent open prostatectomy and 69 underwent transurethral resection. There was no significant difference in the number of patients who had a fever or a positive blood culture, nor was there a difference in the rate of clearing of bacteriuria in the postoperative period between the treated and untreated patients. Treatment of patients with infected urine preoperatively, based on culture and sensitivity of the organisms, did not appear to offer any significant advantage when compared to no treatment. Similarly, patients in the treated group who received prophylactic treatment with antimicrobials had approximately the same number of infectious complications as those who received no treatment (table 1). The antimicrobials used at various times during the study are shown in table 2. The majority of treated patients received ampicillin or a cephalosporin derivative initially. There were 15 patients in the treated group who required another antimi11 Wilson, F. M., Shumaker, E. ,J., Fentress, V. and Lerner, A. M.: Epidemiologic aspects of postoperative sepsis in a urologic practice (with a note concerning antibacierial prophylaxis). J. Urol., 105: 295, 1971.
TABLE
Treated
Not Treated --,----------
Total Number ofpatients Fever ICl!F Urologic sepsis Positive blood culture Infected at 10 weeks
Inf.' Uninf.1"
Total
Inf.' llt1inLI
57
19
:,8
57
1:l
24 1:3 2
11
1:1
rn
5 Cl
8
11
:1 :1
2
4
0
16
10
6
14
6
1:; fl
8
* Infected at the time of hospitalization. t Uninfected at tbe time of hospitalization. TABLE
2. Antimicrobials Treated
Primarv Antimicr~bial Ampicillin Cephalosporin N itrofurantoin
Tetracycline Gantrisin Gentamicin Kanamycin Totals Inappropriate antimicrobial use
2:1 2:1
!'-Jot Treated
Required Additional
Required lnstitulinn
2 :J
1 5
2 :1 57
2 7
lG
1(',l
2
crobial agent in response to a febrile and. 16 in the non-treated group who required the imtitL; tion of an antimicrobial agent in response to a febrile episode. Three patients in the treated group and 5 in the untreated group received antimicrobials inappropriately as determined by culture or for a reason other than a urinary tract infection. The incidence of bacteriuria in patients whc were infected preoperatively is shown in 1 transient decrease in the incidence of bacteriuria occurred in the treated group in the immediate postoperative period but was short-lived. The est number of febrile episodes resulting from urinary infection occurred during the first postoperative week when an approximately equal number of patients in both groups was infected. The tion and persistence of bacteriuria in patients with sterile urine cultures are shown in figure 2. Antimicrobial treatment did not appear to occurrence of bacteriuria nor did it effect the of clearing in the postoperative period. The ity of febrile episodes occurred 3 and 4 day~ postoperatively. However, the number of patients manifesting bacteriuria was highest during the second and third postoperative weeks. curred only twice during this period larger number of patients who were bacteriuric and was related to urinary retention in both cases. There was a rapid decline in the number of febrile responses to urinary tract infection following establishment of adequate voiding as shown in figure 3. The over-all incidence of sepsis was 21 per cent.
796
MCGUIRE
100 e NOT TREATED
O TREATED
80
% of Patients
60
with bocteriuria
·------- .
40
20
ADM PRE 3d
3wk
twk
10wk
6wk
OP FIG. 1. Bacteriuria in patients at intervals during study period who were infected on hospitalization 100
o e
80
TREATED NOT TREATED
60
o/o of Patients with bacteriuria
40
20
ADM
PRE 3d
OP
1wk
3wk
6wk
10wk
FIG. 2. Acquisition and persistence of bacteriuria in patients with sterile urine cultures on hospitalization
Those in whom bacteriuria was present for 30 days or more prior to hospitalization had a low rate of sepsis since only 1 in 29 had a significant febrile response as a result of a urinary tract infection. Sixty-four patients had short-term infections of less than 30 days and sepsis developed in 23, an incidence of 34 per cent. Of the 43 patients who were hospitalized in retention, 38 per cent had urologic sepsis. Of the patients who had retention and short-term urinary tract infection a febrile response to an infection occurred in 50 per cent. Patients who had a systemic febrile response to infection experienced an average delay between hospitalization and operation of 9.8 days, those who did not have sepsis had an average delay of 4.6
days and those who had retention and sepsis experienced an average delay of 14 days. Of the 59 abacteriuric patients who were hospitalized for elective operation, which was performed within 3 days of admission, 5 (9 per cent) had a febrile response to a urinary tract infection. DISCUSSION
This study indicates that patients undergoing prostatectomy do not all face the same risk from infection. Patients who were chronically bacteriuric for a prolonged period of time preoperatively, particularly those who had been on chronic catheter drainage because of severe urinary tract decom-
797
ANTIMICROBIALS IN PROSTATECTOMY
WO 0 TREATED ., NOT TREATED
80
0
SEPSIS TREATED
~ SEPSIS UNTREATED
50
of Patients with bacteriuri a
0/ 0
40
20 8
2,:,.. .~DM
i
/1 PRE
OP
3d
lwll
3wk
6w~
iOwl<
FIG. :3. Percentage of patients with bacteriuria and number of febrile episodes related to urinary infection
pensation, rarely had a significant febrile response postoperatively. However, they did have persistent bacteriuria for a longer period after prostatectomy. The duration of the postoperative bacteriuria seemed more a reflection of the degree of urinary tract damage resultant from obstruction than the type and amount of antimicrobial therapy used. Patients hospitalized without bacteriuria for elective transurethral resection had the highest rate of sterile urine cultures throughout the period of study and antimicrobial treatment seemed to offer no advantage for postoperative sepsis or morbidity since the treated patients in this group had the same clinical course as the untreated patients. Patients with recently acquired bacteriuria or those hospitalized in urinary retention who required preoperative catheterization had an increased risk of developing sepsis since 35 to 50 per cent of them had clinical evidence of systemic infection. There appeared to be a definite relationship between the incidence of sepsis and the delay between hospitalization and subsequent operation. Although antimicrobials were useful in the treatment of acute systemic infection when it occurred, they did not seem to prevent the development of sepsis in these patients when given prophylactically. It could be argued that the routine use of an aminoglycoside antimicrobial prophylactically in these patients might be effective since superinfection with resistant bacterial strains is unusual when these agents are used. Aminoglycosides were not used extensively in this study. A previous study by Plorde and associates did suggest that the use of aminoglycosides in abacteriuric patients was effective in the prevention of postoperative morbidity caused by infection. However, the differences reported by these investigators compared a
febrile response in :3 of 18 patients who received an aminoglycoside with 5 of 15 patients who received no treatment. In a sample size of :3:3, a difference oi 2 patients does not seem highly significant. Considerably more postoperative bleeding and catheter complications occurred in the untreated group and freedom from these complications in the treated group was ascribed to the antimicrobial agent used. It seems more likely that those s who experienced surgical complications, such at: bleeding requiring frequent irrigations, would un fairly weight the study in favor of the treated group with a lower incidence of these problems. Whether aminoglycosides would prevent the development of sepsis in high risk patients such as those ized in retention who experienced a delay between admission and operation has not been studied. This is a relatively small group of patients but it seems possible that they could benefit from treatment initiated not longer than a few days preoperatively to obviate problems of superinfection. In contrast are patients hospitalized without retention but with sterile urine cultures who underwen l operation without delay, of whom only 9 per cent had a serious febrile response to a urinary infection. It does not seem worthwhile to administer an aminoglycoside to this group prophylactically in view of their relatively low risk. The time at which patients undergoing prostatectomy are most at risk from the complications of infection is ;3 and 4 days postoperatively, when 29 per cent of the patients in this study had bacteri uria. However, 1 to 3 weeks postoperatively, when 60 per cent of the total number of patients had bacteriuria, there were only 2 episodes of which were related to late urinary obstruction. Bacteriuria which persisted after the establish-
798
MCGUIRE
ment of adequate voiding was asymptomatic and is probably of little clinical significance. It is evident from these findings that the generally used criteria for the evaluation of the efficacy of antimicrobial treatment in patients undergoing prostatectomy may not only reflect antibacterial activity of the agent used but also the preoperative condition of the patient. The factors of particular importance were the duration of infection, the incidence of urinary retention and the delay between hospitalization and operation. The conflicting reports in the literature on the efficacy of antimicrobials may be partially explained by differences in the preoperative status of the patients studied. It is also apparent that while the presence of bacteriuria may be transiently influenced by the antimicrobials used in this study they are of doubtful clinical value in the prevention of serious systemic infections. Finally, the duration of postoperative bacteriuria does not seem to be affected by antimicrobial treatment in that the rate of disappearance of organisms from the urine was the
same in the treated and untreated groups. Patients hospitalized with uninfected urine who acquired bacteriuria which failed to clear at 10 weeks amounted to 15 per cent of the treated group and 16 per cent of the non-treated group. In patients hospitalized with infected urine, 50 per cent failed to clear their infection in both groups. Clinical symptoms as a result of bacteriuria during the late postoperative period are an indication of urinary tract dysfunction or late obstruction rather than the virulence of the infecting organism. SUMMARY
A review is made of 114 patients who were hospitalized for prostatectomy and alternately treated with and without prophylactic antimicrobial drugs. The clinical course, incidence of infectious complications and bacteriuria did not appear to be different in the 2 groups. Host factors are probably primarily responsible for the prognosis of urinary infections in these patients.