Vol. 3, No. 3 Printed in U.SA.
JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 1976, p. 246-250 Copyright © 1976 American Society for Microbiology
Polymicrobic Bacteriuria: Significant Association with Bacteremia PETER A. GROSS,'* MARGARET FLOWER, AND GERTRUDE BARDEN Veterans Administration Hospital, West Haven, Connecticut 06516, and Yale University School ofMedicine and Department of Medicine, New Haven, Connecticut 06510 Received for publication 3 December 1975
Current clinical practice states that a urine culture yielding three or more isolates must be considered a contaminated specimen and discarded. The validity of this practice was tested by reviewing all patients at the West Haven Veterans Administration Hospital with positive blood cultures for 1 year to determine how many were associated with polymicrobic bacteriuria (two or more urine isolates each present at >105 colonies/ml). During 1973 there were 18 patients who had bacteremia associated with a urinary tract infection in which the same organism with the identical antibiogram was found in both the blood and the urine. Of these 18 patients with monomicrobic bacteremia, 11 (61%) had polymicrobic bacteriuria, with a mean of an additional 1.75 urinary pathogens present in significant quantities. In these patients with polymicrobic bacteriuria, an indwelling bladder catheter was present for a mean period of 4.4 months before the episode of bacteremia. Only 5 of the 11 patients with polymicrobic bacteriuria had temporally associated urinary tract manipulation. Monomicrobic bacteriuria occurred in seven patients (39%). The mean indwelling bladder catheter time was 0.9 days, and urinary tract manipulation near the time of bacteremia occurred in all seven patients. Prospectively, nine other patients with polymicrobic bacteriuria were recultured by one of us to be certain that appropriate collection and transportation methods were used; the presence of polymicrobic bacteriuria was repeatedly demonstrated in 7 (78%). This study illustrates the clinical importance of polymicrobic bacteriuria. A few decades ago, when quantitative counts of bacteria in the urine were not done routinely to rule out contamination, it was not uncommon to observe multiple different bacterial isolates from the same specimen in patients with urinary tract instrumentation (2, 7). Polymicrobic bacteriuria was also observed with open Foley catheter drainage (8). However, since closed systems for Foley catheter drainage have become common practice and quantitative urine bacteriology has been instituted, polymicrobic bacteriuria with significant numbers equal to or greater than 105 colonies/ml for each isolate has become distinctly unusual and when encountered is usually ignored. Current clinical practice now states that a urine culture yielding three or more isolates must be considered a contaminated specimen and discarded (1, 6). The recommendation ignores the fact that many patients may have multiple bacterial isolates in significant quantities in their urine on repeated occasions. This phenomenon occurs primarily in patients with I
Infectious Disease Division, Hackensack Hospital,
Hackensack, N.J. 07601.
246
long-term indwelling Foley or suprapubic catheters. At the present time most clinicians continue to ignore such culture reports and do not treat patients with polymicrobic bacteriuria. The validity ofthis current clinical practice was tested by looking at bacteremia, the most severe complication of bacteriuria and polymicrobic bacteriuria. MATERIALS AND METHODS During 1973 at the West Haven Veterans Administration Hospital, the records of all patients with bacteremia were reviewed. All patients with a urine culture 1 week before the appearance of bacteremia or within 1 day after the appearance of bacteremia were evaluated for a possible association between the bacteremia and the urinary tract infection. Bacteriuria was considered significant when the organism was present in quantities equal to or greater than 105 colonies/ml. Polymicrobic bacteriuria was defined as the presence of two or more isolates, each in significant quantities. Monomicrobic bacteriuria was defined as the presence of one bacterial isolate in significant quantities. All indwelling bladder catheters used in our hospital were connected to a closed system for drainage.
VOL. 3, 1976
POLYMICROBIC BACTERIURIA
RESULTS During 1973 there were 93 patients with significant blood culture isolates at the West Haven Veterans Administration Hospital. All cultures positive for Staphylococcus epidermidis, Bacillus sp., and Propionibacterium were excluded from this group if they were found in one set of blood cultures only and if the clinical condition was not compatible with sepsis either transient or continuous. Of the 93 patients with significant blood culture isolates, there were 72 patients in which a urine culture had been obtained within the defined period of time surrounding the episode of bacteremia. Of these 72 patients, 18 (25%) had a urinary tract infection with the same bacterial species found in the blood. The antibiograms of the organisms in each case were identical. Of these 18 patients with associated urinary tract infection and bacteremia, 11 (61%) had associated polymicrobic bacteriuria and 7 (39%) had monomicrobic bacteriuria. The clinical details of the patients with polymicrobic bacteriuria are shown in Table 1. There were 12 episodes of bacteremia in 11
247
patients. The mean age was 68 years. Two of the patients died near the time of sepsis. There was a mean of 1.75 other organisms found in significant quantities per urine culture in this group of patients. The most common organism isolated from the urine was Escherichia coli. Each time it was found in the urine it was the cause of sepsis, and in no instance was it present in the urine and not related to sepsis. Proteus mirabilis and Pseudomonas aeruginosa were found in the urine as often as E. coli. However, the former two organisms did not always give rise to bacteremia. Serratia, Enterococci, Proteus morganii, and other organisms were found in the urine in significant quantities but did not result in bacteremia. Urine cultures were done in most patients on the same day that the bacteremia was detected. In three instances the cultures were obtained 2 to 5 days before the blood became positive, and in one instance the urine culture was done the day after bacteremia was documented. In three patients two urine cultures were done before the bacteremia episode, and in all instances the same organisms were demonstrated in both urine cultures.
TABLE 1. Clinical presentation of patients with polymicrobic bacteriuria Patient
L. F.
A
ge
83
Organism in blood and urine'
Escherichia coli
Day urine culture was done before blood culture
Other urinary organisms
Predisposing factors for sepsis
0
Proteus vulgaris En-
Indwelling suprapubic tube Indwelling suprapubic tube Foley changed
terococcus
L.F.
83
E. coli
0
Serratia
C.L.
59
Pseudomonas aeruginosa
0
G.R.
53
Providencia
0
M.V. T.K.
56 76
Proteus mirabilis E. coli
0 0
C. diversusb a-streptococcus Veillonella Anaerobic GPCc Pseudomonas aeruginosa Enterococcus Proteus mirabilisd
J.W.
80
P. mirabilis
4
F.C.
67
E. coli
5
D.G.
60
E. coli
2
E.V.
73
E. coli
0
H.R.
77
P. mirabilis
le
Enterococcusb
Serratia Proteus morganii Serratiad PseuEnterococcus domonas aeruginosa P. aeruginosa P. aeruginosad Enterococcus Proteus morganii Serratia
0 Proteus mirabilisb Klebsiella pneumoniae a Urine and blood isolates had some antibiogram. b Same organisms present in previous urine. c GPC, Gram-positive coccus. d Different antibiograms. e Urine obtained 1 day after blood culture.
E.S.
68
Indwelling suprapubic tube Difficult Foley insertion Indwelling suprapubic tube Foley changed
Foley indwelling
Foley changed Foley indwelling Transurethral resection and Foley inserted
Foley indwelling
248
J. CLIN. MICROBIOL.
GROSS, FLOWER, AND BARDEN
There were two major predisposing factors that were characteristic for the patients in this group. First, the presence of an indwelling bladder catheter was documented in most cases for a long period of time before the episode of bacteremia and clinical sepsis. This time interval varied from 1 day to 19 months, with a mean of 4.4 months for the group. Ten of the 11 patients had a catheter in their bladder for more than 5 days before the episode of sepsis, and six patients had some type of bladder catheter indwelling for more than 1 month before the episode of sepsis. The second characteristic was that some type of urinary tract manipulation was not always recorded near the time of sepsis. A characteristic factor usually associated with bacteremia in patients with urinary tract infections is the documentation of urinary tract manipulation near the time of sepsis. In this group of patients manipulation could be documented for less than half of the episodes of bacteremia. Five of the eight patients with Foley catheters had some type of manipulation of the catheter around the time of sepsis, and in one of these patients the manipulation was a transurethral resection at the time of sepsis. Of the 12 episodes of bacteremia, 5 were associated with urinary tract manipulation. The other seven episodes were not precipitated by obvious urinary tract manipulation. All of the patients with a suprapubic tube had bacteremia without any prior urinary tract manipulation. The clinical presentations of the patients with monomicrobic bacteriuria and simultaneous bacteremia are shown in Table 2. There were seven episodes of bacteremia in seven patients. The mean age in this group was 64 years, not significantly different from that of the patients with polymicrobic bacteriuria. None of the patients in this group died at or near the time of sepsis. The most common isolates were E. coli and Pseudomonas aerugi-
The indwelling time for the catheters in these patients ranged between 0 and 4 days, with a mean indwelling time of 0.9 days. This time was significantly different from the mean of 4.4 months in the polymicrobic bacteriuria group (P < 0.001). There were no indwelling suprapubic tubes in any of the patients in this group. The urinary tract was thought to be the source of bacteremia in five patients, and in all of these patients some type of urinary tract manipulation occurred near the time of sepsis. In the other two patients the source of bacteremia was thought to be Pseudomonas pneumonia in one and Staphylococcus epidermidis endocarditis in the other. In the five patients with monomicrobic bacteriuria in which the urinary tract was the primary source of bacteremia, urinary tract manipulation was documented in all instances. In contrast, in the 11 patients with polymicrobic bacteriuria, where the urinary tract was thought to be the source of sepsis in all instances, urinary tract manipulation could be documented in only 5 of 11 patients. The frequency of polymicrobic bacteriuria was then reviewed prospectively in our laboratory. During a 2-month interval, 954 urine cultures were submitted to the laboratory. Twenty-four percent or 233 were shown to have at least 105 colonies of at least one organism per ml. Of these 233 positive cultures, 93 (40%) had more than one organism in significant quantities, whereas 140 (60%) had only one organism. During this interval oftime there were approximately 1.5 urine cultures submitted per patient. When the number of patients rather than organisms was used as the denominator, 41% of the patients with significant bacteriuria had polymicrobic bacteriuria. Finally, the chance of error in collection of the urine cultures was tested prospectively. Nine patients were studied whose urine speci-
nosa.
TABLE 2. Clinical presentation ofpatients with monomicrobic bacteriuria Day urine cultient
Age
Organism in blood and urinea
ture was done culture
J.H. J. C. E.F. R. P. R.M. F.V.
75 59 50 59 49 81
Escherichia coli Serratia Enterococci Pseudomonas aeruginosa P. aeruginosa E. coli
0 0 0 0 1 0
W.S.
76
Staphylococcus
o
a b
epidermidis
Urine and blood isolates had some antibiogram. Same organism present in previous urine.
Predisposing factors for sepsis
Urinary tract instrumentation Transurethral resection prostate Foley inserted Foley inserted Pseudomonas pneumonia Difficult cystoscopy Foley inserted Endocarditis secondary to intravenous catheter
VOL. 3, 1976
mens contained significant polymicrobic growth (defined as two or more organisms each present at 105/ml or greater). Repeat urine specimens were properly collected and brought to the bacteriology laboratory immediately by one of us. In seven of nine patients (78%), the repeated, properly collected urine specimens again grew out multiple organisms each in significant quantities. In five of these seven patients, all urine isolates had been fully identified as to species on the first specimen. Seventeen isolates (each >105 organisms/ml) were found in these five patients on the initial specimen, and 15 of the 17 were found in the second specimen, which was properly collected and transported. Repeat specimens from two of the nine patients (22%) failed to yield significant numbers (104 or less). Similar reproducibility has been noted by others (Lawrence A. Miller, personal communication). In addition, polymicrobic bacteriuria with two or more organisms present at greater than 105 organisms per ml has been observed in suprapubic bladder aspirations of urine (F. L. Sapico, P. A. Wideman, and S. M. Finegold, Abstr. Am. Soc. Microbiol. 1975, p. 37). In this small, prospectively studied group, the presence of a Foley catheter again was directly related to the presence of polymicrobic bacteriuria. Six of the seven patients with repeatedly demonstrated polymicrobic bacteriuria had had Foley catheters in place for long periods. The two cases in which the repeat urine culture failed to demonstrate polymicrobic bacteriuria involved patients who did not have Foley catheters. DISCUSSION It appears from this study that the presence of polymicrobic bacteriuria is not an insignificant observation since it can on occasion result in bacteremia. In our hospital patients, bacteremia was more often associated with polymicrobic bacteriuria than with monomicrobic bacteriuria. Patients with polymicrobic bacteriuria characteristically had an indwelling Foley or suprapubic catheter in place for more than 4 months before the onset of bacteremia. In addition, these patients did not necessarily have urinary tract instrumentation or manipulation near the time of bacteremia. In contrast, the patients with monomicrobic bacteriuria and bacteremia characteristically had a Foley catheter in for not more than a day, and urinary tract manipulation occurred in all instances. Suprapubic tubes were not present in this latter group. There were no marked differences in the types of organisms that caused bacteremia or
POLYMICROBIC BACTERIURIA
249
bacteriuria in either group. In the group with polymicrobic bacteriuria there were multiple common urinary tract pathogens present, and it would have been impossible to predict which one of these organisms was going to give rise to bacteremia. In general, however, if E. coli was present in the urine it was likely that it would result in bacteremia. In contrast, P. aeruginosa and P. mirabilis were found as often as E. coli in the urine, but they rarely gave rise to bacteremia. The numbers here, however, are small, and it would be difficult to generalize from this group as to which organisms in a mixture would be more likely to result in blood-borne infection. Despite the presence of polymicrobic bacteriuria, no instance of polymicrobic bacteremia was observed. In a series of patients with polymicrobic bacteremia the urinary tract was thought to be the source of infection in only a few patients (5). It was not stated in that article whether or not the polymicrobic bacteremia in patients with urinary tract disease was associated with polymicrobic bacteriuria. The patients described often had urinary tract obstruction or surgery before the development of polymicrobic bacteremia. Perhaps lack of obstruction in our patients with polymicrobic bacteriuria prevented most of the isolates from becoming blood-borne. The extent of the problem of polymicrobic bacteriuria can better be appreciated given information regarding the characteristics of the patient population for our hospital. The West Haven Veterans Administration Hospital has approximately equal numbers of beds for chronic- and acute-care patients. Since most patients with polymicrobic bacteriuria have long indwelling times for the bladder catheters used, it is expected that there would be a significant percentage of patients with polymicrobic bacteriuria. Indeed, in a 2-month period 40% of the positive urine cultures were polymicrobic. If polymicrobic bacteriuria gives rise to significant bacteremia, which it does as demonstrated by our study, it is not surprising that we would have a significant number of cases of bacteremia related to polymicrobic bacteriuria. In fact, 61% of our patients with bacteremia associated with significant bacteriuria had polymicrobic bacteriuria, whereas among all the patients with positive urine cultures only 41% were
polymicrobic. Thus, in our particular hospital setting, polymicrobic bacteriuria was more likely to result in bacteremia than was monomicrobic bacteriuria. What should be done about this problem? First, the phenomenon of polymicrobic bacteriuria should be taken more seriously. When or-
250
GROSS, FLOWER, AND BARDEN
dering a urine culture from a patient with an indwelling Foley catheter or suprapubic tube, the latter information should be communicated to the microbiology laboratory so that all organisms isolated in significant numbers will be identified and antibiograms obtained. Once polymicrobic bacteriuria has been found, a second urine culture should be done to confirm its presence. The patient might then be put on a urinary tract antiseptic such as a methenamine salt, nitrofurantoin, nalidixic acid, or a sulfonamide to act as a chronic urinary tract suppressant (3). The use of a constant bladder irrigation system with neomycin and polymyxin (8) in patients with long-term bladder catheterization will not eliminate preexisting bacteriuria and will not decrease the likelihood of acquiring new organisms in the urine when compared with a simple closed system of drainage (10). Finally, since bacteremia regularly occurs in bacteriuric patients after urinary tract instrumentation (9), patients with repeatedly documented polymicrobic bacteriuria should be treated prophylactically with an appropriate broad-spectrum antibiotic when urinary tract manipulation is to be conducted. Although these recommendations appear reasonable, it would be appropriate to conduct prospective controlled studies to determine their value in patients with polymicrobic bacteriuria. In particular, studies on the chronic use of urinary tract suppressants in patients with long-term indwelling bladder catheters would be helpful. Acceptance of the significance of polymicrobic bacteriuria and attempts to document its presence by a second confirmatory specimen
J. CLIN. MICROBIOL.
will put an added burden on the time and expense of the clinical microbiology laboratory. Perhaps this added effort can be compensated for by the elimination of cultures of Foley catheter tips (4) and other clinically irrelevant specimens. LITERATURE CITED 1. Bartlett, R. C. 1974. Medical microbiology: quality, cost, and clinical relevance, p. 252. J. Wiley & Sons, New York. 2. Coleman, P. N., and S. Taylor. 1949. Coliform infection of the urinary tract. J. Clin. Pathol. 2:134-137. 3. Freeman, R. B., L. Bromer, F. Brancato, et al. 1968. Prevention of recurrent bacteriuria with continuous chemotherapy: U.S. Public Health Service Cooperative Study. Ann. Inn. Intern. Med. 69:655-672. 4. Gross, P. A., L. M. Harkavy, G. E. Barden, and M. Kerstein. 1974. Positive Foley catheter tip: fact or fancy? J. Am. Med. Assoc. 228:72-73. 5. Hermans, P. E., and J. A. Washington II. 1970. Polymicrobial bacteremia. Ann. Intern. Med. 73:387-391. 6. Isenberg, H. D., J. A. Washington II, A. Balows, and A. C. Sonnenwirth. 1974. Collection, handling, and processing of specimens, p. 59-88. In E. H. Lennette, E. H. Spaulding, and J. P. Truant (ed.), Manual of clinical microbiology, 2nd ed. American Society for
Microbiology, Washington, D.C. 7. Kass, E. H. 1955. Chemotherapeutic and antibiotic drugs in the management of infections of the urinary tract. Am. J. Med. 18:764-781. 8. Martin, C. M., and E. N. Bookrajian. 1962. Bacteriuria prevention after indwelling urinary catheterization: a controlled study. Arch. Intern. Med. 110:209-217. 9. Sullivan, N. M., V. L. Sutter, W. T. Carter, H. R. Attebery, and S. M. Finegold. 1972. Bacteremia after genitourinary tract manipulation: bacteriological aspects and evaluation of various blood culture systems. Appl. Microbiol. 23:1101-1106. 10. Thornton, G. F., B. Lytton, and V. T. Andriole. 1966. Bacteriuria during indwelling catheter drainage: effect of constant bladder rinse. J. Am. Med. Assoc. 195:117-121.
JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 1976, p. 246-250 Copyright © 1976 American Society for Microbiology
Polymicrobic Bacteriuria: Significant Association with Bacteremia PETER A. GROSS,'* MARGARET FLOWER, AND GERTRUDE BARDEN Veterans Administration Hospital, West Haven, Connecticut 06516, and Yale University School ofMedicine and Department of Medicine, New Haven, Connecticut 06510 Received for publication 3 December 1975
Current clinical practice states that a urine culture yielding three or more isolates must be considered a contaminated specimen and discarded. The validity of this practice was tested by reviewing all patients at the West Haven Veterans Administration Hospital with positive blood cultures for 1 year to determine how many were associated with polymicrobic bacteriuria (two or more urine isolates each present at >105 colonies/ml). During 1973 there were 18 patients who had bacteremia associated with a urinary tract infection in which the same organism with the identical antibiogram was found in both the blood and the urine. Of these 18 patients with monomicrobic bacteremia, 11 (61%) had polymicrobic bacteriuria, with a mean of an additional 1.75 urinary pathogens present in significant quantities. In these patients with polymicrobic bacteriuria, an indwelling bladder catheter was present for a mean period of 4.4 months before the episode of bacteremia. Only 5 of the 11 patients with polymicrobic bacteriuria had temporally associated urinary tract manipulation. Monomicrobic bacteriuria occurred in seven patients (39%). The mean indwelling bladder catheter time was 0.9 days, and urinary tract manipulation near the time of bacteremia occurred in all seven patients. Prospectively, nine other patients with polymicrobic bacteriuria were recultured by one of us to be certain that appropriate collection and transportation methods were used; the presence of polymicrobic bacteriuria was repeatedly demonstrated in 7 (78%). This study illustrates the clinical importance of polymicrobic bacteriuria. A few decades ago, when quantitative counts of bacteria in the urine were not done routinely to rule out contamination, it was not uncommon to observe multiple different bacterial isolates from the same specimen in patients with urinary tract instrumentation (2, 7). Polymicrobic bacteriuria was also observed with open Foley catheter drainage (8). However, since closed systems for Foley catheter drainage have become common practice and quantitative urine bacteriology has been instituted, polymicrobic bacteriuria with significant numbers equal to or greater than 105 colonies/ml for each isolate has become distinctly unusual and when encountered is usually ignored. Current clinical practice now states that a urine culture yielding three or more isolates must be considered a contaminated specimen and discarded (1, 6). The recommendation ignores the fact that many patients may have multiple bacterial isolates in significant quantities in their urine on repeated occasions. This phenomenon occurs primarily in patients with I
Infectious Disease Division, Hackensack Hospital,
Hackensack, N.J. 07601.
246
long-term indwelling Foley or suprapubic catheters. At the present time most clinicians continue to ignore such culture reports and do not treat patients with polymicrobic bacteriuria. The validity ofthis current clinical practice was tested by looking at bacteremia, the most severe complication of bacteriuria and polymicrobic bacteriuria. MATERIALS AND METHODS During 1973 at the West Haven Veterans Administration Hospital, the records of all patients with bacteremia were reviewed. All patients with a urine culture 1 week before the appearance of bacteremia or within 1 day after the appearance of bacteremia were evaluated for a possible association between the bacteremia and the urinary tract infection. Bacteriuria was considered significant when the organism was present in quantities equal to or greater than 105 colonies/ml. Polymicrobic bacteriuria was defined as the presence of two or more isolates, each in significant quantities. Monomicrobic bacteriuria was defined as the presence of one bacterial isolate in significant quantities. All indwelling bladder catheters used in our hospital were connected to a closed system for drainage.
VOL. 3, 1976
POLYMICROBIC BACTERIURIA
RESULTS During 1973 there were 93 patients with significant blood culture isolates at the West Haven Veterans Administration Hospital. All cultures positive for Staphylococcus epidermidis, Bacillus sp., and Propionibacterium were excluded from this group if they were found in one set of blood cultures only and if the clinical condition was not compatible with sepsis either transient or continuous. Of the 93 patients with significant blood culture isolates, there were 72 patients in which a urine culture had been obtained within the defined period of time surrounding the episode of bacteremia. Of these 72 patients, 18 (25%) had a urinary tract infection with the same bacterial species found in the blood. The antibiograms of the organisms in each case were identical. Of these 18 patients with associated urinary tract infection and bacteremia, 11 (61%) had associated polymicrobic bacteriuria and 7 (39%) had monomicrobic bacteriuria. The clinical details of the patients with polymicrobic bacteriuria are shown in Table 1. There were 12 episodes of bacteremia in 11
247
patients. The mean age was 68 years. Two of the patients died near the time of sepsis. There was a mean of 1.75 other organisms found in significant quantities per urine culture in this group of patients. The most common organism isolated from the urine was Escherichia coli. Each time it was found in the urine it was the cause of sepsis, and in no instance was it present in the urine and not related to sepsis. Proteus mirabilis and Pseudomonas aeruginosa were found in the urine as often as E. coli. However, the former two organisms did not always give rise to bacteremia. Serratia, Enterococci, Proteus morganii, and other organisms were found in the urine in significant quantities but did not result in bacteremia. Urine cultures were done in most patients on the same day that the bacteremia was detected. In three instances the cultures were obtained 2 to 5 days before the blood became positive, and in one instance the urine culture was done the day after bacteremia was documented. In three patients two urine cultures were done before the bacteremia episode, and in all instances the same organisms were demonstrated in both urine cultures.
TABLE 1. Clinical presentation of patients with polymicrobic bacteriuria Patient
L. F.
A
ge
83
Organism in blood and urine'
Escherichia coli
Day urine culture was done before blood culture
Other urinary organisms
Predisposing factors for sepsis
0
Proteus vulgaris En-
Indwelling suprapubic tube Indwelling suprapubic tube Foley changed
terococcus
L.F.
83
E. coli
0
Serratia
C.L.
59
Pseudomonas aeruginosa
0
G.R.
53
Providencia
0
M.V. T.K.
56 76
Proteus mirabilis E. coli
0 0
C. diversusb a-streptococcus Veillonella Anaerobic GPCc Pseudomonas aeruginosa Enterococcus Proteus mirabilisd
J.W.
80
P. mirabilis
4
F.C.
67
E. coli
5
D.G.
60
E. coli
2
E.V.
73
E. coli
0
H.R.
77
P. mirabilis
le
Enterococcusb
Serratia Proteus morganii Serratiad PseuEnterococcus domonas aeruginosa P. aeruginosa P. aeruginosad Enterococcus Proteus morganii Serratia
0 Proteus mirabilisb Klebsiella pneumoniae a Urine and blood isolates had some antibiogram. b Same organisms present in previous urine. c GPC, Gram-positive coccus. d Different antibiograms. e Urine obtained 1 day after blood culture.
E.S.
68
Indwelling suprapubic tube Difficult Foley insertion Indwelling suprapubic tube Foley changed
Foley indwelling
Foley changed Foley indwelling Transurethral resection and Foley inserted
Foley indwelling
248
J. CLIN. MICROBIOL.
GROSS, FLOWER, AND BARDEN
There were two major predisposing factors that were characteristic for the patients in this group. First, the presence of an indwelling bladder catheter was documented in most cases for a long period of time before the episode of bacteremia and clinical sepsis. This time interval varied from 1 day to 19 months, with a mean of 4.4 months for the group. Ten of the 11 patients had a catheter in their bladder for more than 5 days before the episode of sepsis, and six patients had some type of bladder catheter indwelling for more than 1 month before the episode of sepsis. The second characteristic was that some type of urinary tract manipulation was not always recorded near the time of sepsis. A characteristic factor usually associated with bacteremia in patients with urinary tract infections is the documentation of urinary tract manipulation near the time of sepsis. In this group of patients manipulation could be documented for less than half of the episodes of bacteremia. Five of the eight patients with Foley catheters had some type of manipulation of the catheter around the time of sepsis, and in one of these patients the manipulation was a transurethral resection at the time of sepsis. Of the 12 episodes of bacteremia, 5 were associated with urinary tract manipulation. The other seven episodes were not precipitated by obvious urinary tract manipulation. All of the patients with a suprapubic tube had bacteremia without any prior urinary tract manipulation. The clinical presentations of the patients with monomicrobic bacteriuria and simultaneous bacteremia are shown in Table 2. There were seven episodes of bacteremia in seven patients. The mean age in this group was 64 years, not significantly different from that of the patients with polymicrobic bacteriuria. None of the patients in this group died at or near the time of sepsis. The most common isolates were E. coli and Pseudomonas aerugi-
The indwelling time for the catheters in these patients ranged between 0 and 4 days, with a mean indwelling time of 0.9 days. This time was significantly different from the mean of 4.4 months in the polymicrobic bacteriuria group (P < 0.001). There were no indwelling suprapubic tubes in any of the patients in this group. The urinary tract was thought to be the source of bacteremia in five patients, and in all of these patients some type of urinary tract manipulation occurred near the time of sepsis. In the other two patients the source of bacteremia was thought to be Pseudomonas pneumonia in one and Staphylococcus epidermidis endocarditis in the other. In the five patients with monomicrobic bacteriuria in which the urinary tract was the primary source of bacteremia, urinary tract manipulation was documented in all instances. In contrast, in the 11 patients with polymicrobic bacteriuria, where the urinary tract was thought to be the source of sepsis in all instances, urinary tract manipulation could be documented in only 5 of 11 patients. The frequency of polymicrobic bacteriuria was then reviewed prospectively in our laboratory. During a 2-month interval, 954 urine cultures were submitted to the laboratory. Twenty-four percent or 233 were shown to have at least 105 colonies of at least one organism per ml. Of these 233 positive cultures, 93 (40%) had more than one organism in significant quantities, whereas 140 (60%) had only one organism. During this interval oftime there were approximately 1.5 urine cultures submitted per patient. When the number of patients rather than organisms was used as the denominator, 41% of the patients with significant bacteriuria had polymicrobic bacteriuria. Finally, the chance of error in collection of the urine cultures was tested prospectively. Nine patients were studied whose urine speci-
nosa.
TABLE 2. Clinical presentation ofpatients with monomicrobic bacteriuria Day urine cultient
Age
Organism in blood and urinea
ture was done culture
J.H. J. C. E.F. R. P. R.M. F.V.
75 59 50 59 49 81
Escherichia coli Serratia Enterococci Pseudomonas aeruginosa P. aeruginosa E. coli
0 0 0 0 1 0
W.S.
76
Staphylococcus
o
a b
epidermidis
Urine and blood isolates had some antibiogram. Same organism present in previous urine.
Predisposing factors for sepsis
Urinary tract instrumentation Transurethral resection prostate Foley inserted Foley inserted Pseudomonas pneumonia Difficult cystoscopy Foley inserted Endocarditis secondary to intravenous catheter
VOL. 3, 1976
mens contained significant polymicrobic growth (defined as two or more organisms each present at 105/ml or greater). Repeat urine specimens were properly collected and brought to the bacteriology laboratory immediately by one of us. In seven of nine patients (78%), the repeated, properly collected urine specimens again grew out multiple organisms each in significant quantities. In five of these seven patients, all urine isolates had been fully identified as to species on the first specimen. Seventeen isolates (each >105 organisms/ml) were found in these five patients on the initial specimen, and 15 of the 17 were found in the second specimen, which was properly collected and transported. Repeat specimens from two of the nine patients (22%) failed to yield significant numbers (104 or less). Similar reproducibility has been noted by others (Lawrence A. Miller, personal communication). In addition, polymicrobic bacteriuria with two or more organisms present at greater than 105 organisms per ml has been observed in suprapubic bladder aspirations of urine (F. L. Sapico, P. A. Wideman, and S. M. Finegold, Abstr. Am. Soc. Microbiol. 1975, p. 37). In this small, prospectively studied group, the presence of a Foley catheter again was directly related to the presence of polymicrobic bacteriuria. Six of the seven patients with repeatedly demonstrated polymicrobic bacteriuria had had Foley catheters in place for long periods. The two cases in which the repeat urine culture failed to demonstrate polymicrobic bacteriuria involved patients who did not have Foley catheters. DISCUSSION It appears from this study that the presence of polymicrobic bacteriuria is not an insignificant observation since it can on occasion result in bacteremia. In our hospital patients, bacteremia was more often associated with polymicrobic bacteriuria than with monomicrobic bacteriuria. Patients with polymicrobic bacteriuria characteristically had an indwelling Foley or suprapubic catheter in place for more than 4 months before the onset of bacteremia. In addition, these patients did not necessarily have urinary tract instrumentation or manipulation near the time of bacteremia. In contrast, the patients with monomicrobic bacteriuria and bacteremia characteristically had a Foley catheter in for not more than a day, and urinary tract manipulation occurred in all instances. Suprapubic tubes were not present in this latter group. There were no marked differences in the types of organisms that caused bacteremia or
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bacteriuria in either group. In the group with polymicrobic bacteriuria there were multiple common urinary tract pathogens present, and it would have been impossible to predict which one of these organisms was going to give rise to bacteremia. In general, however, if E. coli was present in the urine it was likely that it would result in bacteremia. In contrast, P. aeruginosa and P. mirabilis were found as often as E. coli in the urine, but they rarely gave rise to bacteremia. The numbers here, however, are small, and it would be difficult to generalize from this group as to which organisms in a mixture would be more likely to result in blood-borne infection. Despite the presence of polymicrobic bacteriuria, no instance of polymicrobic bacteremia was observed. In a series of patients with polymicrobic bacteremia the urinary tract was thought to be the source of infection in only a few patients (5). It was not stated in that article whether or not the polymicrobic bacteremia in patients with urinary tract disease was associated with polymicrobic bacteriuria. The patients described often had urinary tract obstruction or surgery before the development of polymicrobic bacteremia. Perhaps lack of obstruction in our patients with polymicrobic bacteriuria prevented most of the isolates from becoming blood-borne. The extent of the problem of polymicrobic bacteriuria can better be appreciated given information regarding the characteristics of the patient population for our hospital. The West Haven Veterans Administration Hospital has approximately equal numbers of beds for chronic- and acute-care patients. Since most patients with polymicrobic bacteriuria have long indwelling times for the bladder catheters used, it is expected that there would be a significant percentage of patients with polymicrobic bacteriuria. Indeed, in a 2-month period 40% of the positive urine cultures were polymicrobic. If polymicrobic bacteriuria gives rise to significant bacteremia, which it does as demonstrated by our study, it is not surprising that we would have a significant number of cases of bacteremia related to polymicrobic bacteriuria. In fact, 61% of our patients with bacteremia associated with significant bacteriuria had polymicrobic bacteriuria, whereas among all the patients with positive urine cultures only 41% were
polymicrobic. Thus, in our particular hospital setting, polymicrobic bacteriuria was more likely to result in bacteremia than was monomicrobic bacteriuria. What should be done about this problem? First, the phenomenon of polymicrobic bacteriuria should be taken more seriously. When or-
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dering a urine culture from a patient with an indwelling Foley catheter or suprapubic tube, the latter information should be communicated to the microbiology laboratory so that all organisms isolated in significant numbers will be identified and antibiograms obtained. Once polymicrobic bacteriuria has been found, a second urine culture should be done to confirm its presence. The patient might then be put on a urinary tract antiseptic such as a methenamine salt, nitrofurantoin, nalidixic acid, or a sulfonamide to act as a chronic urinary tract suppressant (3). The use of a constant bladder irrigation system with neomycin and polymyxin (8) in patients with long-term bladder catheterization will not eliminate preexisting bacteriuria and will not decrease the likelihood of acquiring new organisms in the urine when compared with a simple closed system of drainage (10). Finally, since bacteremia regularly occurs in bacteriuric patients after urinary tract instrumentation (9), patients with repeatedly documented polymicrobic bacteriuria should be treated prophylactically with an appropriate broad-spectrum antibiotic when urinary tract manipulation is to be conducted. Although these recommendations appear reasonable, it would be appropriate to conduct prospective controlled studies to determine their value in patients with polymicrobic bacteriuria. In particular, studies on the chronic use of urinary tract suppressants in patients with long-term indwelling bladder catheters would be helpful. Acceptance of the significance of polymicrobic bacteriuria and attempts to document its presence by a second confirmatory specimen
J. CLIN. MICROBIOL.
will put an added burden on the time and expense of the clinical microbiology laboratory. Perhaps this added effort can be compensated for by the elimination of cultures of Foley catheter tips (4) and other clinically irrelevant specimens. LITERATURE CITED 1. Bartlett, R. C. 1974. Medical microbiology: quality, cost, and clinical relevance, p. 252. J. Wiley & Sons, New York. 2. Coleman, P. N., and S. Taylor. 1949. Coliform infection of the urinary tract. J. Clin. Pathol. 2:134-137. 3. Freeman, R. B., L. Bromer, F. Brancato, et al. 1968. Prevention of recurrent bacteriuria with continuous chemotherapy: U.S. Public Health Service Cooperative Study. Ann. Inn. Intern. Med. 69:655-672. 4. Gross, P. A., L. M. Harkavy, G. E. Barden, and M. Kerstein. 1974. Positive Foley catheter tip: fact or fancy? J. Am. Med. Assoc. 228:72-73. 5. Hermans, P. E., and J. A. Washington II. 1970. Polymicrobial bacteremia. Ann. Intern. Med. 73:387-391. 6. Isenberg, H. D., J. A. Washington II, A. Balows, and A. C. Sonnenwirth. 1974. Collection, handling, and processing of specimens, p. 59-88. In E. H. Lennette, E. H. Spaulding, and J. P. Truant (ed.), Manual of clinical microbiology, 2nd ed. American Society for
Microbiology, Washington, D.C. 7. Kass, E. H. 1955. Chemotherapeutic and antibiotic drugs in the management of infections of the urinary tract. Am. J. Med. 18:764-781. 8. Martin, C. M., and E. N. Bookrajian. 1962. Bacteriuria prevention after indwelling urinary catheterization: a controlled study. Arch. Intern. Med. 110:209-217. 9. Sullivan, N. M., V. L. Sutter, W. T. Carter, H. R. Attebery, and S. M. Finegold. 1972. Bacteremia after genitourinary tract manipulation: bacteriological aspects and evaluation of various blood culture systems. Appl. Microbiol. 23:1101-1106. 10. Thornton, G. F., B. Lytton, and V. T. Andriole. 1966. Bacteriuria during indwelling catheter drainage: effect of constant bladder rinse. J. Am. Med. Assoc. 195:117-121.
