Antibiotic Prophylaxis at Urinary Catheter Removal Prevents Urinary Tract Infection After Kidney Transplantation H.H. Woltersa,*, D. Palmesa, E. Lordugina, R. Bahdea, N. Senningera, J.-P. Hölzenb, and L. Kebschulla a Department of General and Visceral Surgery, University Clinic Muenster, Muenster, Germany; and bDepartment of General Surgery, Herz-Jesu-Krankenhaus-Münster-Hiltrup, Muenster, Germany
ABSTRACT Background. Urinary tract infections (UTI) are common nosocomial infections in kidney transplant recipients, with limited evidence to guide antibiotic prophylaxis at urinary catheter removal. The aim of our study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation. Methods. Twenty kidney transplant recipients received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urinary catheter and were compared with 20 kidney transplant recipients without prophylaxis. UTI was diagnosed by use of urine culture and clinical signs. Results. All patients were comparable in sex, age, etiology of end-stage renal failure, immunosuppression, donor type, and initial function. After catheter removal at the 6th postoperative day, a rapid rise of UTI in kidney transplant recipients without prophylaxis (n ¼ 12, 60%) was observed, whereas in patients with antibiotic prophylaxis the rate of UTI could be significantly reduced to 20%. Escherichia coli was the most isolated pathogen in the patients with UTI and was detected at the catheter tip in more than 50% of cases. In 2 patients (10%) after antibiotic prophylaxis, a ciprofloxacin-resistant E coli strain was detected. Conclusions. The use of antibiotic prophylaxis during urinary catheter removal is recommended to prevent UTI in kidney transplant recipients.
P
OSTOPERATIVE urinary tract infection (UTI) after kidney transplantation is a common cause of patient morbidity and represents a potential risk factor for poorer graft and recipient outcome [1]. In kidney transplant recipients, besides the immunodeficiency resulting from immunosuppression, the presence of ureteral stents and postoperative vesicoureteral reflux plays an important role for UTI. Thus, the prevalence of UTI in kidney transplant recipients is up to 30% [2,3]. There are 2 critical times for the development of UTI after kidney transplantation: the perioperative period and the time of catheter removal [4]. Although antibiotic prophylaxis during the perioperative period is widely accepted as a standard after kidney transplantation, it remains a matter of debate whether a prolonged perioperative antibiotic prophylaxis can reduce UTI [5]. Therefore, the aim of the present study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation. We hypothesized that the addition of ciprofloxacin at urinary
catheter removal would lower the incidence of UTI after kidney transplantation. METHODS We performed a prospective, observational study in patients undergoing kidney transplantation. At admission, they were randomly assigned into 2 groups. Written informed consent was obtained from all patients before undergoing their operation. This study was approved by an independent ethics committee. Kidney transplant recipients were compared with similar demographic features, considering the etiology of end-stage renal disease, age, sex, donor type, and number of kidney transplantations (Table 1). A double-J ureteral stent was used in all patients. *Address correspondence to Heiner H. Wolters, University Clinic Muenster, Department of General and Visceral Surgery, AlbertSchweitzer Campus 1, Gebäude W1, 48149 Münster, Germany. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.04.019
Transplantation Proceedings, 46, 3463e3465 (2014)
3463
3464
WOLTERS, PALMES, LORDUGIN ET AL Table 1. Demographic and Clinical Features
Age (years) Sex (female/male) ESRD etiology Diabetes Hypertension GN PCKD Other Donor type Postmortal Living donor Kidney transplantation First Second Initial function Good DGF
Group 1 (Without Prophylaxis)
Group 2 (Prophylaxis)
48.3 18.1 10:10
52.7 14.6 10:10
8 4 3 3 2
7 4 2 2 5
11 9
13 7
19 1
18 2
18 2
18 2
Abbreviations: ESRD, end-stage renal disease; GN, glomerulonephritis; PCKD, polycystic kidney disease; DGF, delayed graft function.
Postoperative immunosuppression consisted of tacrolimus, glucocorticosteroids, and mycophenolate motefil and induction therapy with basiliximab. In all patients, a urinary catheter was inserted perioperatively and was removed at day 6 after transplantation, whereas the double-J ureteral stent was removed at 6 weeks. All patients received cefuroxime 750 to 1500 mg intravenously as a single-shot prophylaxis 30 minutes before kidney transplantation. In the prophylaxis group, all patients additionally received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urethral catheter. Because the double-J catheters have no contact with the outer urinary tract, we did not give any antibiotic prophylaxis when removing the double-J. catheters. UTI was diagnosed in patients with positive urine culture (105 microorganisms per cm3) and at least 1 of the following signs or symptoms: fever (>38 C), urgency, frequency, dysuria, or suprapubic tenderness. Statistical analysis was performed with the use of SPSS software. Continuous data are expressed as mean SD. Comparisons of categorical and continuous variables were performed with the use of the Fisher exact test and Student t test, respectively. A value of P < .05 was considered statistically significant.
RESULTS
Demographic data, clinical data, and urine cultures were analyzed in 40 patients after kidney transplantation, including 20 women and 20 men with overall mean age of 48.3 18.1 years (group 1) and 52.7 14.6 years (group 2), respectively. The etiologies of end-stage renal failure were diabetic nephropathy (n ¼ 15, 37.5%), hypertensive nephropathy (n ¼ 8, 20%), glomerulonephritis (n ¼ 5, 12.5%), autosomal-dominant polycystic kidney disease (n ¼ 5, 12.5%), and other causes (n ¼ 7, 17.5%). All patients underwent first kidney transplantation; 24 patients (60%) received grafts from postmortal donors and 16 recipients (40%) from living donors. Eighteen patients (90%) had good initial function, whereas 4 patients (10%) had delayed graft function.
During the postoperative observation period, we performed urine cultures (Fig 1) on 4 occasions. Before catheter removal in 8 patients, a UTI occurred; 5 patients showed symptoms, for example, dysuria or suprapubic tenderness. After catheter removal at the 6th postoperative day, a rapid rise of UTI in group 1 without prophylaxis (n ¼ 12, 60%) was observed, whereas in group 2 (with antibiotic prophylaxis), the rate of UTI was significantly reduced to 20% (P < .05, Fig 1). Even 7 and 10 days after kidney transplantation, a UTI could be still detected in half of the patients without antibiotic prophylaxis, and 6 patients had symptoms of UTI. In contrast, UTI was reduced to 15% at day 10 in group 2 with antibiotic prophylaxis. Escherichia coli, Enterococcus faecalis, Enterococcus faecium, and Staphylococcus epidermidis were the most isolated pathogens in the patients with UTI (Table 2). It is worth noting that in particular E coli was detected at the catheter tip in more than 50% of all patients. In 2 patients (10%) after antibiotic prophylaxis (group 2), a ciprofloxacin-resistant E coli strain could be detected. These patients showed persistent UTI at the 7th and 10th postoperative days. DISCUSSION
UTI occur with an incidence up to 50% and remain a major problem in kidney transplant recipients, resulting in increased morbidity and mortality rates, prolonged hospital stay, and possibly reduced long-term graft survival [6,7]. The general risk factors for UTI in kidney transplant recipients were female sex, age, reflux disease, deceased donor, and immunosuppression by azathioprine [8]. In the present study, we showed that the tip of the urinary catheter represents the main source of UTI in the shortterm follow-up after kidney transplantation and that the removal of the urinary catheter is associated with a significant release of bacteria from the catheter tip. Therefore, we used the approach of an antibiotic prophylaxis consisting of a brief course of antibiotics administered before and during the removal of the urinary catheter to minimize bacteriuria. We chose ciprofloxacin for antibiotic prophylaxis in our study because of its widespread use, its effectiveness, and its low cost [9]. Ciprofloxacin is highly effective in the
Fig 1. Urinary cultures and urinary tract infections.
ANTIBIOTIC PROPHYLAXIS AT URINARY CATHETER REMOVAL
3465
Table 2. Bacteria Isolated in Patients With Significant Bacteriuria (Multiple Species in 1 Sample Possible) Without Prophylaxis
Escherichia coli Enterococcus faecalis Enterococcus faecium Enterobacter cloacae Staphylococcus epidermidis Pseudomonas aeruginosa Staphylococcus haemolyticus Staphylococcus agalactiae
With Prophylaxis
Catheter Tip
Before Catheter Removal
After Catheter Removal
Catheter Tip
Before Catheter Removal
After Catheter Removal
12 3 2 2 4 2 2 1
1 1 0 0 1 1 0 0
5 2 2 1 2 1 0 0
11 3 4 2 4 0 3 2
2 1 0 0 1 0 0 0
2* 0 0 0 0 0 0 0
*With resistance.
treatment of complicated UTI, for example, in kidney transplant recipients, and is currently recommended as first-line treatment in our setting [9]. Although in this study the antibiotic prophylaxis with ciprofloxacin was successful against both Gram-negative and Gram-positive bacteria, we observed 2 patients with resistant strains of E coli. Therefore, ciprofloxacin might need to be replaced by other antibiotics in the future. Whereas in our protocol an antibiotic prophylaxis at urinary catheter removal prevents UTI effectively, this may be different when urinary catheters are removed earlier or later after kidney transplantation. To what extent double-J catheters, which are used routinely in our department, affect UTI could not be clarified with this study. Although this observational study is limited because of the number of patients, all patients had the same immunosuppression and comparable risk factors for the development of UTI, that is, female sex and presence of diabetes. The follow-up was limited to the 10th day after kidney transplantation because most UTI manifested 3 days after catheter removal [4]. However, it is possible that further UTI after discharge were missed, for example, occurring after removal of the double-J ureteral stent. Of the basis of the findings of our observational study, we recommend the use of antibiotic prophylaxis during urinary catheter removal to prevent UTI in kidney transplant recipients.
REFERENCES [1] Gołe˛biewska J, De˛bska-Slizie n A, Komarnicka J, et al. Urinary tract infections in renal transplant recipients. Transplant Proc 2011;43:2985e90. [2] Memikoglu KO, Keven K, Sengül S, et al. Urinary tract infections following renal transplantation: a single-center experience. Transplant Proc 2007;39:3131e4. [3] Sorto R, Irizar SS, Delgadillo G, et al. Risk factors for urinary tract infections during the first year after kidney transplantation. Transplant Proc 2010;42:280e1. [4] Pfefferkorn U, Lea S, Moldenhauer J, et al. Antibiotic prophylaxis at urinary catheter removal prevents urinary tract infections: a prospective randomized trial. Ann Surg 2009;249: 573e5. [5] Wojciechowski D, Chandran S. Effect of ciprofloxacin combined with sulfamethoxazole-trimethoprim prophylaxis on the incidence of urinary tract infections after kidney transplantation. Transplantation 2013;96:400e5. [6] Ariza-Heredia EJ, Beam EN, Lesnick TG, et al. Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis. Ann Transplant 2013;18:195e204. [7] Veroux M, Giuffrida G, Corona D, et al. Infective complications in renal allograft recipients: epidemiology and outcome. Transplant Proc 2008;40:1873e6. [8] Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clin Transplant 2005;19:230e5. [9] Hörl WH. Urinary tract infections. Internist (Berl) 2011;52: 1026e31.
ABSTRACT Background. Urinary tract infections (UTI) are common nosocomial infections in kidney transplant recipients, with limited evidence to guide antibiotic prophylaxis at urinary catheter removal. The aim of our study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation. Methods. Twenty kidney transplant recipients received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urinary catheter and were compared with 20 kidney transplant recipients without prophylaxis. UTI was diagnosed by use of urine culture and clinical signs. Results. All patients were comparable in sex, age, etiology of end-stage renal failure, immunosuppression, donor type, and initial function. After catheter removal at the 6th postoperative day, a rapid rise of UTI in kidney transplant recipients without prophylaxis (n ¼ 12, 60%) was observed, whereas in patients with antibiotic prophylaxis the rate of UTI could be significantly reduced to 20%. Escherichia coli was the most isolated pathogen in the patients with UTI and was detected at the catheter tip in more than 50% of cases. In 2 patients (10%) after antibiotic prophylaxis, a ciprofloxacin-resistant E coli strain was detected. Conclusions. The use of antibiotic prophylaxis during urinary catheter removal is recommended to prevent UTI in kidney transplant recipients.
P
OSTOPERATIVE urinary tract infection (UTI) after kidney transplantation is a common cause of patient morbidity and represents a potential risk factor for poorer graft and recipient outcome [1]. In kidney transplant recipients, besides the immunodeficiency resulting from immunosuppression, the presence of ureteral stents and postoperative vesicoureteral reflux plays an important role for UTI. Thus, the prevalence of UTI in kidney transplant recipients is up to 30% [2,3]. There are 2 critical times for the development of UTI after kidney transplantation: the perioperative period and the time of catheter removal [4]. Although antibiotic prophylaxis during the perioperative period is widely accepted as a standard after kidney transplantation, it remains a matter of debate whether a prolonged perioperative antibiotic prophylaxis can reduce UTI [5]. Therefore, the aim of the present study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation. We hypothesized that the addition of ciprofloxacin at urinary
catheter removal would lower the incidence of UTI after kidney transplantation. METHODS We performed a prospective, observational study in patients undergoing kidney transplantation. At admission, they were randomly assigned into 2 groups. Written informed consent was obtained from all patients before undergoing their operation. This study was approved by an independent ethics committee. Kidney transplant recipients were compared with similar demographic features, considering the etiology of end-stage renal disease, age, sex, donor type, and number of kidney transplantations (Table 1). A double-J ureteral stent was used in all patients. *Address correspondence to Heiner H. Wolters, University Clinic Muenster, Department of General and Visceral Surgery, AlbertSchweitzer Campus 1, Gebäude W1, 48149 Münster, Germany. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.04.019
Transplantation Proceedings, 46, 3463e3465 (2014)
3463
3464
WOLTERS, PALMES, LORDUGIN ET AL Table 1. Demographic and Clinical Features
Age (years) Sex (female/male) ESRD etiology Diabetes Hypertension GN PCKD Other Donor type Postmortal Living donor Kidney transplantation First Second Initial function Good DGF
Group 1 (Without Prophylaxis)
Group 2 (Prophylaxis)
48.3 18.1 10:10
52.7 14.6 10:10
8 4 3 3 2
7 4 2 2 5
11 9
13 7
19 1
18 2
18 2
18 2
Abbreviations: ESRD, end-stage renal disease; GN, glomerulonephritis; PCKD, polycystic kidney disease; DGF, delayed graft function.
Postoperative immunosuppression consisted of tacrolimus, glucocorticosteroids, and mycophenolate motefil and induction therapy with basiliximab. In all patients, a urinary catheter was inserted perioperatively and was removed at day 6 after transplantation, whereas the double-J ureteral stent was removed at 6 weeks. All patients received cefuroxime 750 to 1500 mg intravenously as a single-shot prophylaxis 30 minutes before kidney transplantation. In the prophylaxis group, all patients additionally received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urethral catheter. Because the double-J catheters have no contact with the outer urinary tract, we did not give any antibiotic prophylaxis when removing the double-J. catheters. UTI was diagnosed in patients with positive urine culture (105 microorganisms per cm3) and at least 1 of the following signs or symptoms: fever (>38 C), urgency, frequency, dysuria, or suprapubic tenderness. Statistical analysis was performed with the use of SPSS software. Continuous data are expressed as mean SD. Comparisons of categorical and continuous variables were performed with the use of the Fisher exact test and Student t test, respectively. A value of P < .05 was considered statistically significant.
RESULTS
Demographic data, clinical data, and urine cultures were analyzed in 40 patients after kidney transplantation, including 20 women and 20 men with overall mean age of 48.3 18.1 years (group 1) and 52.7 14.6 years (group 2), respectively. The etiologies of end-stage renal failure were diabetic nephropathy (n ¼ 15, 37.5%), hypertensive nephropathy (n ¼ 8, 20%), glomerulonephritis (n ¼ 5, 12.5%), autosomal-dominant polycystic kidney disease (n ¼ 5, 12.5%), and other causes (n ¼ 7, 17.5%). All patients underwent first kidney transplantation; 24 patients (60%) received grafts from postmortal donors and 16 recipients (40%) from living donors. Eighteen patients (90%) had good initial function, whereas 4 patients (10%) had delayed graft function.
During the postoperative observation period, we performed urine cultures (Fig 1) on 4 occasions. Before catheter removal in 8 patients, a UTI occurred; 5 patients showed symptoms, for example, dysuria or suprapubic tenderness. After catheter removal at the 6th postoperative day, a rapid rise of UTI in group 1 without prophylaxis (n ¼ 12, 60%) was observed, whereas in group 2 (with antibiotic prophylaxis), the rate of UTI was significantly reduced to 20% (P < .05, Fig 1). Even 7 and 10 days after kidney transplantation, a UTI could be still detected in half of the patients without antibiotic prophylaxis, and 6 patients had symptoms of UTI. In contrast, UTI was reduced to 15% at day 10 in group 2 with antibiotic prophylaxis. Escherichia coli, Enterococcus faecalis, Enterococcus faecium, and Staphylococcus epidermidis were the most isolated pathogens in the patients with UTI (Table 2). It is worth noting that in particular E coli was detected at the catheter tip in more than 50% of all patients. In 2 patients (10%) after antibiotic prophylaxis (group 2), a ciprofloxacin-resistant E coli strain could be detected. These patients showed persistent UTI at the 7th and 10th postoperative days. DISCUSSION
UTI occur with an incidence up to 50% and remain a major problem in kidney transplant recipients, resulting in increased morbidity and mortality rates, prolonged hospital stay, and possibly reduced long-term graft survival [6,7]. The general risk factors for UTI in kidney transplant recipients were female sex, age, reflux disease, deceased donor, and immunosuppression by azathioprine [8]. In the present study, we showed that the tip of the urinary catheter represents the main source of UTI in the shortterm follow-up after kidney transplantation and that the removal of the urinary catheter is associated with a significant release of bacteria from the catheter tip. Therefore, we used the approach of an antibiotic prophylaxis consisting of a brief course of antibiotics administered before and during the removal of the urinary catheter to minimize bacteriuria. We chose ciprofloxacin for antibiotic prophylaxis in our study because of its widespread use, its effectiveness, and its low cost [9]. Ciprofloxacin is highly effective in the
Fig 1. Urinary cultures and urinary tract infections.
ANTIBIOTIC PROPHYLAXIS AT URINARY CATHETER REMOVAL
3465
Table 2. Bacteria Isolated in Patients With Significant Bacteriuria (Multiple Species in 1 Sample Possible) Without Prophylaxis
Escherichia coli Enterococcus faecalis Enterococcus faecium Enterobacter cloacae Staphylococcus epidermidis Pseudomonas aeruginosa Staphylococcus haemolyticus Staphylococcus agalactiae
With Prophylaxis
Catheter Tip
Before Catheter Removal
After Catheter Removal
Catheter Tip
Before Catheter Removal
After Catheter Removal
12 3 2 2 4 2 2 1
1 1 0 0 1 1 0 0
5 2 2 1 2 1 0 0
11 3 4 2 4 0 3 2
2 1 0 0 1 0 0 0
2* 0 0 0 0 0 0 0
*With resistance.
treatment of complicated UTI, for example, in kidney transplant recipients, and is currently recommended as first-line treatment in our setting [9]. Although in this study the antibiotic prophylaxis with ciprofloxacin was successful against both Gram-negative and Gram-positive bacteria, we observed 2 patients with resistant strains of E coli. Therefore, ciprofloxacin might need to be replaced by other antibiotics in the future. Whereas in our protocol an antibiotic prophylaxis at urinary catheter removal prevents UTI effectively, this may be different when urinary catheters are removed earlier or later after kidney transplantation. To what extent double-J catheters, which are used routinely in our department, affect UTI could not be clarified with this study. Although this observational study is limited because of the number of patients, all patients had the same immunosuppression and comparable risk factors for the development of UTI, that is, female sex and presence of diabetes. The follow-up was limited to the 10th day after kidney transplantation because most UTI manifested 3 days after catheter removal [4]. However, it is possible that further UTI after discharge were missed, for example, occurring after removal of the double-J ureteral stent. Of the basis of the findings of our observational study, we recommend the use of antibiotic prophylaxis during urinary catheter removal to prevent UTI in kidney transplant recipients.
REFERENCES [1] Gołe˛biewska J, De˛bska-Slizie n A, Komarnicka J, et al. Urinary tract infections in renal transplant recipients. Transplant Proc 2011;43:2985e90. [2] Memikoglu KO, Keven K, Sengül S, et al. Urinary tract infections following renal transplantation: a single-center experience. Transplant Proc 2007;39:3131e4. [3] Sorto R, Irizar SS, Delgadillo G, et al. Risk factors for urinary tract infections during the first year after kidney transplantation. Transplant Proc 2010;42:280e1. [4] Pfefferkorn U, Lea S, Moldenhauer J, et al. Antibiotic prophylaxis at urinary catheter removal prevents urinary tract infections: a prospective randomized trial. Ann Surg 2009;249: 573e5. [5] Wojciechowski D, Chandran S. Effect of ciprofloxacin combined with sulfamethoxazole-trimethoprim prophylaxis on the incidence of urinary tract infections after kidney transplantation. Transplantation 2013;96:400e5. [6] Ariza-Heredia EJ, Beam EN, Lesnick TG, et al. Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis. Ann Transplant 2013;18:195e204. [7] Veroux M, Giuffrida G, Corona D, et al. Infective complications in renal allograft recipients: epidemiology and outcome. Transplant Proc 2008;40:1873e6. [8] Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clin Transplant 2005;19:230e5. [9] Hörl WH. Urinary tract infections. Internist (Berl) 2011;52: 1026e31.
