Urinary Tract Infections in Kidney Transplant Recipients Don E.
Ramsey, MD;
W.
Tyree Finch, MD;
Alan G.
Birtch, MD
\s=b\ In 65
kidney transplant recipients who were followed up for a period of 14.7 months, the incidence of urinary tract infection (UTI), and how the incidence was affected by length of graft survival, age, HLA-A and HLA-B matches, complications, duration of Foley catheter use, and other aspects, were examined. The total incidence of infection included an unexpectedly high rate of late infections. The incidence was found to be statistically increased with nephrectomy, splenectomy, recatheterization, and age older than 40 years. There was no correlation noted with graft source, antigen match, graft loss, or previous history of UTI. A group of patients with persistent UTI was noted and an inability to suppress UTI with long-term therapy with antibiotics was found. The asymptomatic nature of most of the UTIs confirmed the need for frequent periodic cultures of urine in the immunosuppressed patient. (Arch Surg 114:1022-1025, 1979) mean
taken for urinalysis and culture at each visit. The surgical technique, as previously reported,'" was the same for the entire group of patients. All patients received prophylactic antibiotics for three days posttransplant. Cephalothin sodium and methicillin were used in all patients without an allergy to these drugs. At the time of surgery, a Foley catheter was placed after a careful preparation with providone-iodine (Betadine) by the surgeon and the bladder was irrigated with 5 dL of 0.5% neomycin solution. The bladder was then filled with 1 dL of 0.5% neomycin sulfate solution, which was left in place until just prior to the time the bladder was opened. A ureteroneocystostomy was used, as previously described,"1 in all of these cases as the method of establishing urinary drainage. The urethral meatus was cleansed with providone-iodine every six hours while the catheter was in
place.
A UTI was defined as having two consecutive cultures that grew than 100,000 colonies. A persistent UTI was defined as one that continued (but was not necessarily continuous) throughout a three-month period. more
(UTIs) occurring Urinary receiving kidney transplants perplexing problem.'" Urinary tract infections
in patients have continued to be a tract infections are the most common infection in this group of immunosuppressed patients,7 are reportedly associated with severe morbidity in terms of sepsis,5·8 and have been implicated as a possible cause in transplant rejection." Because of these problems, the present study was undertaken to analyze the incidence and morbidity of UTI in our immunosuppressed kidney-
transplant recipients.
SUBJECTS AND METHODS consecutive patients who received 68 kidney trans¬ from July 2, 1973, to Nov 1, 1977, were retrospectively reviewed. No patient received a transplant with a UTI present or suspected and the results of all immediate pretransplant cultures were negative. Fifty-two patients received transplants of cadaver kidneys and 16 received a graft from a living relative. The mean follow-up period of these patients was 14.7 months. Of all the transplanted kidneys, 68% were functioning at the end of the
Sixty-five
plants
study period. Immunosuppression consisted of the administration of oral prednisone, 1.5 mg/kg/day, tapered off to 0.2 mg/kg/day, and azathioprine, 2.0 to 2.5 mg/kg/day. Rejection episodes were treated with intravenous (IV) methylprednisolone sodium succinate, the usual dosage being 1.5 to 3.0 g given over a five-day period. All patients had a specimen taken for culture at the time the Foley catheter was removed, once a week while hospitalized; and when followed up as an outpatient, all had a urine specimen
Accepted for publication May 7, 1979. From the Department of General Surgery, Division of Transplantation, Southern Illinois University School of Medicine, Springfield. Reprint requests to Department of General Surgery, Division of Transplantation, Southern Illinois University School of Medicine, PO Box 3926, Springfield, IL 62705 (Dr Birtch).
RESULTS
Of the 65 patients in this study, 30 remained free of UTI. In 35 patients (54%), one or more infections developed, and in 11 (17%), persistent infections developed. Three patients received two transplants in this series; therefore, 68 trans¬ plant courses were examined and included 31 without infection and 37 with infection. Of 37 patients in whom infection developed, five were not treated. Four untreated patients had cultures that grew multiple organisms and were thought to have contaminated specimens; and, although one fulfilled the criteria for persistent infection, all subsequently had ster¬ ile cultures of urine. Although counted as infections, these four were probably instances of false-positive culture results. One patient with recurrent infection with a single organism died from an unrelated cause prior to treatment. No complications related to urosepsis were seen in these five patients. Of the 32 patients treated, 15 (42%) had a single episode of infection and maintained sterile urines for the remain¬ der of the study. Seven patients had two or more separate UTIs and ten patients had either a continuous infection or a recurrent infection. The majority of the UTIs (91%) were asymptomatic. Only six of 65 infections had associated dysuria or fever, and two of these infections had both dysuria and fever. Pyuria, defined as more than 50 WBCs per high power field, was present in only 27 (42%) of 65 infections. None of the infections led to bacteremia or other signs of systemic infection (Fig 1). The patient's WBC count at the time of UTI was
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/22/2015
Table
No Pyuria
ry-a
Dysuria
27
'//////////////
1—Organism Causing Urinary
Tract Infection
Episodes of 38
Nonpersistent
Persistent
Causing Renal Failure Urinary Tract Infection
and Associated
Predominant Organism Escherichia coli Streptococcus faecalis Other Streptococcus Proteus Enterobacter
^2
Fever
Infection
Staphylococcus epidermi¬ Fever and
No
Dysuria
Symptoms
2
dis S aureus Serraba Aeromonas Pseudomonas
2
y//////////////^77777A ^ O
IO
20
~~
30
40
50
60
70 Table 2—Disease
Episodes of Infection Fig
1.—Incidence of signs, symptoms, and tract infection.
pyuria
in 65
cases
of Disease
urinary
examined and no correlation was found. Only five of 65 infections were found to have a WBC count of less than 3,000 (7.8%), whereas a WBC count of greater than 12,000 was found with only two infections (3%). The predominant organism from each infection was tabulated and, whereas in many cases more than one organism was grown, only the one dominant organism from each infection was listed. The most common organism was Escherichia coli (26). There were 23 cultures of Streptococcus, including 13 of S faecalis and ten of a streptococci. There were a number of infections caused by other Gram-negative organisms and a few by staphylococci (Table 1). Persistent infections where results of multiple urine cultures were positive for the same organism were counted only once. The renal disease that precipitated these patients' renal failure is noted in Table 2. As in most series, the majority of patients had a diagnosis of chronic glomerulonephritis. There were no statistically significant differences in the incidence of UTI among these various renal diseases. However, there was a 100% incidence in nephrectomized patients with chronic pyelonephritis and polycystic kidney disease. In 20 of the 37 patients (54%), UTI developed in the first four weeks after transplantation (Fig 2). The appearance of a primary infection one year after transplantation was unusual, but recurrent infections occurred throughout. As shown in Fig 3, there were great differences in the occurrence of UTI in patients who underwent splenectomy, infections developing in ten of 12 patients (83%). In nephrectomized patients, infections developed in ten of 12 patients (83%). These differences were significant
(P
=
.02).
Female patients had a higher incidence of infection than did male patients: 16 of 23 patients (71%), as opposed to 19 of 42 patients (44%). This difference, however, was not
significant.
Of all the patients, 46% had their urinary bladder catheters removed on or before the second postoperative day. If these patients did not require recatheterization, they had an infection rate of 5.6% (2/36) within the next
Chronic glomerulonephritis Arteriolar nephrosclerosis
Congenital hypoplasia Chronic proliferative glomerulonephritis Chronic pyelonephritis Polycystic kidneys Other
No. of Patients 28 10 6 5 4
3 9
% Infected 43 80 33
60 100 100 44
weeks; whereas, patients who did not have their catheters removed until the third postoperative day or later, and did not require recatheterization, had an infec¬ tion rate of 17.2% (5/29) within the next two weeks. Eleven of the 14 patients who were recatheterized at some time in the posttransplant period had UTI at a rate (79%) that was very different from that of patients who did not require recatheterization (46%). Whereas seven of ten (70%) of all diabetic patients or patients with steroid-induced diabetes had infections, this was not extremely different from the rate for those who were nondiabetic. In patients who had a history of UTI preoperatively, 13 of 18 (72%) became reinfected, but this also was not very different from the incidence in patients who did not have preoperative UTI. Patients with two or more rejections, and thus receiving higher dosages of steroids, had a much higher incidence of persistent infection, eight of 31 patients, than did those with no or with one rejection, three of 38 patients. Howev¬ er, there was no correlation with the number of rejections and the overall infection rate (Table 3). Age played a role, as in 17 of 41 patients (41.5%) who were younger than 40 years, infections developed, whereas in 18 of 24 patients older than 40 years (75%), infection developed (P < .01). Interestingly, the mean age of those patients who remained free from infection was 33.6 years, those in whom a nonpersistent infection developed had a mean age of 35 years, but those who had a persistent infection had a mean age of 45.4 years. There were no great differences in the incidence of infection by graft source (cadaver graft 56% vs livingrelation graft 50%), nor did the number of antigens that were matched in the cadaver grafts affect the incidence of two
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/22/2015
20
'
First Infections
Z23 Recurrent Infection
18
I I
P-C.02
Splenectomy
0 EU
16 14
No Infection Infected Persistent Infection
P-C.02
Nephrectomy
12 10
Female 1
6 J
•S
Not
Significant
Male
4 2
Catheterized More Than Once
-I ooo tn
id
oo w H
'í
w
o m
P
Ramsey, MD;
W.
Tyree Finch, MD;
Alan G.
Birtch, MD
\s=b\ In 65
kidney transplant recipients who were followed up for a period of 14.7 months, the incidence of urinary tract infection (UTI), and how the incidence was affected by length of graft survival, age, HLA-A and HLA-B matches, complications, duration of Foley catheter use, and other aspects, were examined. The total incidence of infection included an unexpectedly high rate of late infections. The incidence was found to be statistically increased with nephrectomy, splenectomy, recatheterization, and age older than 40 years. There was no correlation noted with graft source, antigen match, graft loss, or previous history of UTI. A group of patients with persistent UTI was noted and an inability to suppress UTI with long-term therapy with antibiotics was found. The asymptomatic nature of most of the UTIs confirmed the need for frequent periodic cultures of urine in the immunosuppressed patient. (Arch Surg 114:1022-1025, 1979) mean
taken for urinalysis and culture at each visit. The surgical technique, as previously reported,'" was the same for the entire group of patients. All patients received prophylactic antibiotics for three days posttransplant. Cephalothin sodium and methicillin were used in all patients without an allergy to these drugs. At the time of surgery, a Foley catheter was placed after a careful preparation with providone-iodine (Betadine) by the surgeon and the bladder was irrigated with 5 dL of 0.5% neomycin solution. The bladder was then filled with 1 dL of 0.5% neomycin sulfate solution, which was left in place until just prior to the time the bladder was opened. A ureteroneocystostomy was used, as previously described,"1 in all of these cases as the method of establishing urinary drainage. The urethral meatus was cleansed with providone-iodine every six hours while the catheter was in
place.
A UTI was defined as having two consecutive cultures that grew than 100,000 colonies. A persistent UTI was defined as one that continued (but was not necessarily continuous) throughout a three-month period. more
(UTIs) occurring Urinary receiving kidney transplants perplexing problem.'" Urinary tract infections
in patients have continued to be a tract infections are the most common infection in this group of immunosuppressed patients,7 are reportedly associated with severe morbidity in terms of sepsis,5·8 and have been implicated as a possible cause in transplant rejection." Because of these problems, the present study was undertaken to analyze the incidence and morbidity of UTI in our immunosuppressed kidney-
transplant recipients.
SUBJECTS AND METHODS consecutive patients who received 68 kidney trans¬ from July 2, 1973, to Nov 1, 1977, were retrospectively reviewed. No patient received a transplant with a UTI present or suspected and the results of all immediate pretransplant cultures were negative. Fifty-two patients received transplants of cadaver kidneys and 16 received a graft from a living relative. The mean follow-up period of these patients was 14.7 months. Of all the transplanted kidneys, 68% were functioning at the end of the
Sixty-five
plants
study period. Immunosuppression consisted of the administration of oral prednisone, 1.5 mg/kg/day, tapered off to 0.2 mg/kg/day, and azathioprine, 2.0 to 2.5 mg/kg/day. Rejection episodes were treated with intravenous (IV) methylprednisolone sodium succinate, the usual dosage being 1.5 to 3.0 g given over a five-day period. All patients had a specimen taken for culture at the time the Foley catheter was removed, once a week while hospitalized; and when followed up as an outpatient, all had a urine specimen
Accepted for publication May 7, 1979. From the Department of General Surgery, Division of Transplantation, Southern Illinois University School of Medicine, Springfield. Reprint requests to Department of General Surgery, Division of Transplantation, Southern Illinois University School of Medicine, PO Box 3926, Springfield, IL 62705 (Dr Birtch).
RESULTS
Of the 65 patients in this study, 30 remained free of UTI. In 35 patients (54%), one or more infections developed, and in 11 (17%), persistent infections developed. Three patients received two transplants in this series; therefore, 68 trans¬ plant courses were examined and included 31 without infection and 37 with infection. Of 37 patients in whom infection developed, five were not treated. Four untreated patients had cultures that grew multiple organisms and were thought to have contaminated specimens; and, although one fulfilled the criteria for persistent infection, all subsequently had ster¬ ile cultures of urine. Although counted as infections, these four were probably instances of false-positive culture results. One patient with recurrent infection with a single organism died from an unrelated cause prior to treatment. No complications related to urosepsis were seen in these five patients. Of the 32 patients treated, 15 (42%) had a single episode of infection and maintained sterile urines for the remain¬ der of the study. Seven patients had two or more separate UTIs and ten patients had either a continuous infection or a recurrent infection. The majority of the UTIs (91%) were asymptomatic. Only six of 65 infections had associated dysuria or fever, and two of these infections had both dysuria and fever. Pyuria, defined as more than 50 WBCs per high power field, was present in only 27 (42%) of 65 infections. None of the infections led to bacteremia or other signs of systemic infection (Fig 1). The patient's WBC count at the time of UTI was
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/22/2015
Table
No Pyuria
ry-a
Dysuria
27
'//////////////
1—Organism Causing Urinary
Tract Infection
Episodes of 38
Nonpersistent
Persistent
Causing Renal Failure Urinary Tract Infection
and Associated
Predominant Organism Escherichia coli Streptococcus faecalis Other Streptococcus Proteus Enterobacter
^2
Fever
Infection
Staphylococcus epidermi¬ Fever and
No
Dysuria
Symptoms
2
dis S aureus Serraba Aeromonas Pseudomonas
2
y//////////////^77777A ^ O
IO
20
~~
30
40
50
60
70 Table 2—Disease
Episodes of Infection Fig
1.—Incidence of signs, symptoms, and tract infection.
pyuria
in 65
cases
of Disease
urinary
examined and no correlation was found. Only five of 65 infections were found to have a WBC count of less than 3,000 (7.8%), whereas a WBC count of greater than 12,000 was found with only two infections (3%). The predominant organism from each infection was tabulated and, whereas in many cases more than one organism was grown, only the one dominant organism from each infection was listed. The most common organism was Escherichia coli (26). There were 23 cultures of Streptococcus, including 13 of S faecalis and ten of a streptococci. There were a number of infections caused by other Gram-negative organisms and a few by staphylococci (Table 1). Persistent infections where results of multiple urine cultures were positive for the same organism were counted only once. The renal disease that precipitated these patients' renal failure is noted in Table 2. As in most series, the majority of patients had a diagnosis of chronic glomerulonephritis. There were no statistically significant differences in the incidence of UTI among these various renal diseases. However, there was a 100% incidence in nephrectomized patients with chronic pyelonephritis and polycystic kidney disease. In 20 of the 37 patients (54%), UTI developed in the first four weeks after transplantation (Fig 2). The appearance of a primary infection one year after transplantation was unusual, but recurrent infections occurred throughout. As shown in Fig 3, there were great differences in the occurrence of UTI in patients who underwent splenectomy, infections developing in ten of 12 patients (83%). In nephrectomized patients, infections developed in ten of 12 patients (83%). These differences were significant
(P
=
.02).
Female patients had a higher incidence of infection than did male patients: 16 of 23 patients (71%), as opposed to 19 of 42 patients (44%). This difference, however, was not
significant.
Of all the patients, 46% had their urinary bladder catheters removed on or before the second postoperative day. If these patients did not require recatheterization, they had an infection rate of 5.6% (2/36) within the next
Chronic glomerulonephritis Arteriolar nephrosclerosis
Congenital hypoplasia Chronic proliferative glomerulonephritis Chronic pyelonephritis Polycystic kidneys Other
No. of Patients 28 10 6 5 4
3 9
% Infected 43 80 33
60 100 100 44
weeks; whereas, patients who did not have their catheters removed until the third postoperative day or later, and did not require recatheterization, had an infec¬ tion rate of 17.2% (5/29) within the next two weeks. Eleven of the 14 patients who were recatheterized at some time in the posttransplant period had UTI at a rate (79%) that was very different from that of patients who did not require recatheterization (46%). Whereas seven of ten (70%) of all diabetic patients or patients with steroid-induced diabetes had infections, this was not extremely different from the rate for those who were nondiabetic. In patients who had a history of UTI preoperatively, 13 of 18 (72%) became reinfected, but this also was not very different from the incidence in patients who did not have preoperative UTI. Patients with two or more rejections, and thus receiving higher dosages of steroids, had a much higher incidence of persistent infection, eight of 31 patients, than did those with no or with one rejection, three of 38 patients. Howev¬ er, there was no correlation with the number of rejections and the overall infection rate (Table 3). Age played a role, as in 17 of 41 patients (41.5%) who were younger than 40 years, infections developed, whereas in 18 of 24 patients older than 40 years (75%), infection developed (P < .01). Interestingly, the mean age of those patients who remained free from infection was 33.6 years, those in whom a nonpersistent infection developed had a mean age of 35 years, but those who had a persistent infection had a mean age of 45.4 years. There were no great differences in the incidence of infection by graft source (cadaver graft 56% vs livingrelation graft 50%), nor did the number of antigens that were matched in the cadaver grafts affect the incidence of two
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/22/2015
20
'
First Infections
Z23 Recurrent Infection
18
I I
P-C.02
Splenectomy
0 EU
16 14
No Infection Infected Persistent Infection
P-C.02
Nephrectomy
12 10
Female 1
6 J
•S
Not
Significant
Male
4 2
Catheterized More Than Once
-I ooo tn
id
oo w H
'í
w
o m
P
