- Email: [email protected]
Incidence of Urinary Tract Infections Caused by Germs Resistant to Antibiotics Commonly Used After Renal Transplantation
Incidence of Urinary Tract Infections Caused by Germs Resistant to Antibiotics Commonly Used After Renal Transplantation P. Di Cocco, G. Orlando, C. Mazzotta, V. Rizza, M. D’Angelo, K. Clemente, S. Greco, A. Famulari, and F. Pisani ABSTRACT Background. The inadequate utilization of antibiotics is responsible for the development of urinary tract infections (UTI) after renal transplantation (RT), through the induction of resistance to the antibiotics themselves. The purpose of this study was to evaluate the incidence of resistance to cefotaxime (CEF) and trimethoprim/sulfamethoxazole (TMP-SMX), routinely used for surgical perioperative prophylaxis and prevention of Pneumocystis carinii, respectively. Materials and Methods. We enrolled all adult patients having received an RT from 2001 to 2006 and having a minimum follow-up of 6 months. Urine cultures (UC) were routinely performed at every outpatient clinic control and whenever required by the onset of significant clinical signs/symptoms. UTI was diagnosed by the presence of a positive UC. The endpoint of the study was the emergence of bacterial strains resistant to either CEF or TMP/SMX. Results. We recorded 169 UTI in 76 patients (38 men/38 women, 33%) over a mean follow-up of 779.9 ⫾ 523.3 days. Thirty-nine patients (51%) developed more than 1 UTI episode. When gram-negative bacteria were considered, 102/144 (70.8%) tests showed resistance to TMP/SMX, while data were available in about only 7 gram-positive infections (5/7, 71%). CEF was tested less frequently with 21/43 (49%) germs resistant to this molecule. Conclusions. The onset of bacterial resistance to either TMP/SMX or CEF is frequent after RT. A wiser stricter utilization of antibiotics is mandatory. Standard antibiotic protocols should be revised.
I
NFECTIONS CURRENTLY REPRESENT the main cause of morbidity, mortality, and hospitalization after renal transplantation (RT),1 due to the more aggressive immunosuppression which has permitted effective prevention and control of acute rejection episodes. Prophylactic antibacterial, antifungal, and antiviral molecules have therefore become part of the standard care worldwide. Urinary tract infections (UTI) remain the most frequent complication after RT with a reported incidence up to 63%.2– 4 Recognized risk factors for UTI are RT itself, the reduction of immunosurveillance induced by antirejection treatment, exposure to nosocomial pathogens, and the necessity for devices such as urinary catheters and intravascular lines in the first postoperative days.5 We believe that the inadequate utilization of antibiotics (ie, not driven by the antibiogram) is an important though often neglected
and/or underestimated variable responsible for the development of UTI and infections in general after transplantation through the induction of resistance to the antibiotics themselves. In this retrospective study, we evaluated the incidence of UTI caused by germs resistant to cefotaxime (CEF) and trimethoprim/sulfamethoxazole (TMP-SMX), which were routinely administered for perioperative antibiotic and antiPneumocystis carinii prophylaxis. Our findings corroborated From the Transplant and Renal Failure Unit, Department of Surgery, University of L’Aquila, and San Salvatore Hospital, L’Aquila, Italy. Address reprint requests to Giuseppe Orlando, MD, PhD, Marie Curie Fellow, Wake Forest Institute for Regenerative Medicine, Medical Center Blvd, NC 27157. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.014
Transplantation Proceedings, 40, 1881–1884 (2008)
1881
1882
DI COCCO, ORLANDO, MAZZOTTA ET AL
the need for a more effective, safer utilization of this class of molecules. MATERIALS AND METHODS Among 218 adult patients (149 men/69 women) of overall mean age of 46.1 ⫾ 10.2 years who received an RT between January 2001 and December 2006, we retrospectively investigated the incidence of UTI and the frequency of bacterial strains resistant to TMPSMX and/or CEF. All patients received basiliximab (Simulect, Novartis) as induction immunotherapy and were maintained on sodium mycophenolate mofetil (Myfortic, Novartis), prednisone, and cyclosporine (n ⫽ 75); mycophenolate mofetil (CellCept, Roche), prednisone, and cyclosporine (n ⫽ 8); mycophenolate mofetil, prednisone, and tacrolimus (n ⫽ 78); sodium mycophenolate mofetil, prednisone, and tacrolimus (n ⫽ 30); cyclosporine, prednisone, and sirolimus (Rapamune, Wyeth) (n ⫽ 14); or cyclosporine, everolimus (Certican, Novartis), and prednisone (n ⫽ 13). In addition, either sirolimus or everolimus was given to 24 patients suffering from chronic toxicity due to a calcineurin inhibitor. The operation was performed according to the standard technique.6 The urinary tract was reconstructed by reimplanting the donor ureter extravesically (Lich-Gregoir technique). A double-J ureteral stent, placed during the transplantation procedure, was removed at 4 weeks posttransplantation. The urethral catheter placed in each patient was removed within 4 to 6 postoperative days. Postoperative care consisted of antibiotic prophylaxis with CEF (2 g twice a day, given intravenously from days 0 –3), antiPneumocystis carinii prophylaxis with oral TMP-SMX (80/400 mg/d), and antifungal prophylaxis with nystatin rinse, both given from resumption of food intake to the end of the sixth postoperative month. The central line was normally removed on day 4 after the last dose of basiliximab, as well as the urinary catheter. The one surgical drain routinely placed in the iliac fossa omolateral to the graft was removed as soon as the output was ⬍50 mL/d. The policy adopted at our center was to perform urine culture (UC) routinely at every control during follow-up and whenever required by the onset of significant clinical signs/symptoms: dysuria,
fever, suprapubic or penis pain, hematuria, increased blood creatinine and/or white blood cell count above 12,000 cells/mL. UTI was diagnosed by a positive UC (⬎100,000 colony forming units [CFU]), because the presence of bacteriuria fulfills the criteria for UTI in RT patients.7 The term was comprehensive of both asymptomatic and symptomatic bacteriuria. Treatment was antibiogram-driven and restricted to only symptomatic cases of UTI. The endpoint of the study was the sensitivity of isolated pathogens to either CEF or TMP-SMX.
RESULTS
We recorded 169 UTI in 76 patients (38 men/38 women, 33%) over a mean follow-up of 779.9 ⫾ 523.3 days. Thirty-nine patients (51%) developed more than 1 UTI episode. The average number of episodes per patient was 2.2 (range, 1– 8 episodes); UTI most frequently occurred within the first postoperative month. Interestingly, bacteriuria was asymptomatic in 79.5% of cases (140/176). Antibiogramdriven therapy was given only in cases of symptomatic bacteriuria. Table 1 reports the various bacterial strains isolated and their in vitro responses to CEF or TMP/SMX, when available. When gram-negative bacteria are considered, 102/144 (70.8%) tests showed resistance to TMP/SMX, while data were only available for 7 cases of gram-positive infections (5/7, 71%). CEF was tested less frequently: 21/43 (49%) germs were resistant to this molecule. Noteworthy, the 2 molecules were not always tested in the antibiogram. DISCUSSION
We demonstrated that the onset of bacterial resistance to either TMP/SMX or CEF, ie, the antibiotics used perioperatively to minimize the incidence of surgery-related infections, was frequent after RT. In addition, resistance to TMP/SMX occurred more frequently than to CEF, due to the fact that the compound was administered for a much longer period than CEF. It should be emphasized that the
Table 1. Incidence of Resistance to the Study Molecules, According to the Isolated Bacterium Pathogen
Gram-negative bacteria Escherichia coli Pseudomonas aeruginosa Klebsiella sp. Citrobacter koseri Enterobacter sp. Proteus mirabilis Stenotrophomonas maltophilia Providencia rettgeri Gram-positive bacteria Enterococcus faecalis Staphylococcus epidermidis Staphylococcus aureus Staphylococcus haemoliticus Streptococcus agalactiae NA, not available.
Episodes of Infection
Sensitivity to TMP/SMX
Resistance to TMP/SMX
Sensitivity to CEF
Resistance to CEF
144 112 7 13 3 3 3 1 2 25 17 5 1 1 1
40 31 1 3 2 2 1 NA NA 2 NA 2 NA NA NA
102 81 6 8 1 1 2 1 2 5
43 34 NA 5 NA NA 1 1 2 NA NA NA NA NA NA
21 18 1 1 1 NA NA NA NA NA NA NA NA NA NA
3 1 1 NA
UTI AND RESISTANCE TO ANTIBIOTICS AFTER RT
development of resistance to antibiotics does not necessarily require long-term administration, but only few repeated doses. In fact, despite the fact that at our institution CEF was given only during the first 3 days after RT, almost half of the isolated germs were resistant to it. The World Health Organization (WHO) has declared that the increase in resistance to antibiotics is a “major public health problem in both developed and developing countries throughout the world.”8,9 The incidence of such phenomena has increased at an alarming pace in recent years. It is expected to increase at a similar or even greater rate in the future, as antimicrobial agents continue to lose their effectiveness. In addition to being a serious threat to human health, resistance to antimicrobial agents is a significant economic threat as well. For this reason the WHO strongly recommends global programs to reduce the inappropriate use of antibiotics in human medicine. In such a dramatic setting, stricter and wiser utilization of antibiotics is clearly mandatory. Therefore, are anti-Pneumocystis carinii and perioperative antibiotic prophylaxes necessary after RT? The answer to the first part of the question is yes: TMP/SMX is still necessary. In fact, the literature shows that anti-Pneumocystis carinii prophylaxis reduces to about 0 the incidence of the infection after RT, even when the drug is given at the dose of 400 mg thrice a week to reduce side effects.10,11 When the second part of the question is considered, the one-shot protocol (1 single dose of antibiotic administered when anesthesia is induced) is extremely effective in preventing surgery-related infections.12 Despite that the literature on the topic is poor and few data are available, a recent Scandinavian survey reported not only that a one-shot regimen was as effective as a multidose regimen, but—more interestingly—that 11% of responding centers in 11 countries do not routinely use antibiotic prophylaxis.13 Finally, it should be emphasized that the guidelines regarding the perioperative antibiotic prophylaxis after RT are unclear (http://www.pnlg.it/LG/009/ 009.pdf) and usually based on the single center physician personal experience and resources, rather than on prospective randomized multicenter trials. The one-shot protocol has largely been used in noncontaminated major surgery for more than a decade. Our findings were consistent with previous reports describing a peak of bacteriuria during the first month postsurgery.14 Asymptomatic bacteriuria, the most frequent infection after RT, was normally benign, unless there were urological or surgical complications, or major impairment of immunosurveillance. Whether treatment is indicated remains a matter of debate. The administration of antibiotics in cases of asymptomatic bacteriuria did not improve the outcomes of RT patients.15 Despite effective sterilization of the urine, it did not decrease the number of symptomatic episodes on hospitalizations thereafter.16 These data were consistent with similar findings in diabetic patients presenting asymptomatic bacteriuria.17 Finally, in agreement with data from the general population, we observed that UTIs were more frequent among female
1883
patients,1–3,18 as 38/69 (55%) women vs 38/149 (25%) men developed UTIs. Speculation on the underlying mechanisms is not within the purposes of the present manuscript. In conclusion, our experience demonstrated that the incidence of resistance to antibiotics was high in the RT population. Resistance developed even after the administration of only a few doses. As a corollary, respecting strict hygiene and sterility guidelines is of paramount importance especially in the care of transplant patients to prevent infections. The use of antibiotics should be optimized to reduce the onset of resistant strains and the guidelines for nosocomial hygiene strictly respected. There is a need for revision of guidelines regarding surgical antibiotic prophylaxis. Sterility should be emphasized in the operating room and on the ward, and external tools such as urinary catheters, central lines, and surgical drains should be removed as soon as possible.
REFERENCES 1. Dharnidharka VR, Stablein DM, Harmon WE: Post-transplant infections now exceed acute rejection as cause for hospitalization: a report of the NAPRTCS. Am J Transplant 4:384, 2004 2. Alangaden GJ, Thyagarajan R, Gruber SA, et al: Infectious complications after kidney transplantation: current epidemiology and associated risk factors. Clin Transpl 20:401, 2006 3. Chuang P, Parikh CR, Langone A: Urinary tract infections after renal transplantation: a retrospective review at two US transplant centres. Clin Transpl 19:230, 2005 4. Martinez-Marcos F, Cisneros J, Gentil M, et al: Prospective study of renal transplant infections in 50 consecutive patients. Eur J Clin Microbiol Infect Dis 13:1023, 1994 5. Fishman JA, Rubin RH: Infection in organ-transplant recipients. N Engl J Med 338:1741, 1998 6. Singer J, Gritsch HA, Rosenthal JT: The transplant operation and its surgical complications. In Danovitch GM (ed): Handbook of Kidney Transplantation. Philadelphia: Lippincott Williams & Wilkins; 2005, p 193 7. Rubin RH, Shapiro ED, Andriole VT, et al: Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Clin Infect Dis 15:216, 1992 8. World Health Organization: WHO Scientific Working Group on Monitoring and Management of Bacterial Resistance to Antimicrobial Agents. Geneva: WHO; 1994 9. Gupta K, Hooton TM, Stamm WE: Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann Intern Med 135:41, 2001 10. Kovacs JA, Gill VJ, Meshnick S, et al: New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 286:2450, 2001 11. Fishman JA: Prevention of infection caused by Pneumocystis carinii in transplant recipients. CID 33:1397, 2001 12. Tilney NL, Strom TB, Vineyard GC, et al: Factors contributing to the declining mortality rate in renal transplantation. N Engl J Med 24:1321, 1978 13. Midtvedt K, Hartmann A, Midtvedt T, et al: Routine perioperative antibiotic prophylaxis in renal transplantation. Nephrol Dial Transplant 13:1637, 1998
1884 14. Sharifian M, Rees L, Trompeter RS: High incidence of bacteriuria following renal transplantation in children. Nephrol Dial Transplant 13:432, 1998 15. Moradi M, Abbasi M, Moradi A, et al: Effect of antibiotic therapy on asymptomatic bacteriuria in kidney transplant recipients. Urol J 2:32, 2005 16. Belitsky P, Lannon SG, MacDonald AS, et al: Urinary tract infections (UTI) after kidney transplantation. Transpl Proc 14:696, 1982
DI COCCO, ORLANDO, MAZZOTTA ET AL 17. Harding KM, Zhanel GG, Nicolle LE, et al, for the Manitoba Diabetes Urinary Tract Infection Study Group: Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med 347:1576, 2002 18. Maraha B, Bonten H, van Hooff H, et al: Infectious complications and antibiotic use in renal transplant recipients during a 1-year follow-up. Clin Microbiol Infect 7:619, 2001
I
NFECTIONS CURRENTLY REPRESENT the main cause of morbidity, mortality, and hospitalization after renal transplantation (RT),1 due to the more aggressive immunosuppression which has permitted effective prevention and control of acute rejection episodes. Prophylactic antibacterial, antifungal, and antiviral molecules have therefore become part of the standard care worldwide. Urinary tract infections (UTI) remain the most frequent complication after RT with a reported incidence up to 63%.2– 4 Recognized risk factors for UTI are RT itself, the reduction of immunosurveillance induced by antirejection treatment, exposure to nosocomial pathogens, and the necessity for devices such as urinary catheters and intravascular lines in the first postoperative days.5 We believe that the inadequate utilization of antibiotics (ie, not driven by the antibiogram) is an important though often neglected
and/or underestimated variable responsible for the development of UTI and infections in general after transplantation through the induction of resistance to the antibiotics themselves. In this retrospective study, we evaluated the incidence of UTI caused by germs resistant to cefotaxime (CEF) and trimethoprim/sulfamethoxazole (TMP-SMX), which were routinely administered for perioperative antibiotic and antiPneumocystis carinii prophylaxis. Our findings corroborated From the Transplant and Renal Failure Unit, Department of Surgery, University of L’Aquila, and San Salvatore Hospital, L’Aquila, Italy. Address reprint requests to Giuseppe Orlando, MD, PhD, Marie Curie Fellow, Wake Forest Institute for Regenerative Medicine, Medical Center Blvd, NC 27157. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.014
Transplantation Proceedings, 40, 1881–1884 (2008)
1881
1882
DI COCCO, ORLANDO, MAZZOTTA ET AL
the need for a more effective, safer utilization of this class of molecules. MATERIALS AND METHODS Among 218 adult patients (149 men/69 women) of overall mean age of 46.1 ⫾ 10.2 years who received an RT between January 2001 and December 2006, we retrospectively investigated the incidence of UTI and the frequency of bacterial strains resistant to TMPSMX and/or CEF. All patients received basiliximab (Simulect, Novartis) as induction immunotherapy and were maintained on sodium mycophenolate mofetil (Myfortic, Novartis), prednisone, and cyclosporine (n ⫽ 75); mycophenolate mofetil (CellCept, Roche), prednisone, and cyclosporine (n ⫽ 8); mycophenolate mofetil, prednisone, and tacrolimus (n ⫽ 78); sodium mycophenolate mofetil, prednisone, and tacrolimus (n ⫽ 30); cyclosporine, prednisone, and sirolimus (Rapamune, Wyeth) (n ⫽ 14); or cyclosporine, everolimus (Certican, Novartis), and prednisone (n ⫽ 13). In addition, either sirolimus or everolimus was given to 24 patients suffering from chronic toxicity due to a calcineurin inhibitor. The operation was performed according to the standard technique.6 The urinary tract was reconstructed by reimplanting the donor ureter extravesically (Lich-Gregoir technique). A double-J ureteral stent, placed during the transplantation procedure, was removed at 4 weeks posttransplantation. The urethral catheter placed in each patient was removed within 4 to 6 postoperative days. Postoperative care consisted of antibiotic prophylaxis with CEF (2 g twice a day, given intravenously from days 0 –3), antiPneumocystis carinii prophylaxis with oral TMP-SMX (80/400 mg/d), and antifungal prophylaxis with nystatin rinse, both given from resumption of food intake to the end of the sixth postoperative month. The central line was normally removed on day 4 after the last dose of basiliximab, as well as the urinary catheter. The one surgical drain routinely placed in the iliac fossa omolateral to the graft was removed as soon as the output was ⬍50 mL/d. The policy adopted at our center was to perform urine culture (UC) routinely at every control during follow-up and whenever required by the onset of significant clinical signs/symptoms: dysuria,
fever, suprapubic or penis pain, hematuria, increased blood creatinine and/or white blood cell count above 12,000 cells/mL. UTI was diagnosed by a positive UC (⬎100,000 colony forming units [CFU]), because the presence of bacteriuria fulfills the criteria for UTI in RT patients.7 The term was comprehensive of both asymptomatic and symptomatic bacteriuria. Treatment was antibiogram-driven and restricted to only symptomatic cases of UTI. The endpoint of the study was the sensitivity of isolated pathogens to either CEF or TMP-SMX.
RESULTS
We recorded 169 UTI in 76 patients (38 men/38 women, 33%) over a mean follow-up of 779.9 ⫾ 523.3 days. Thirty-nine patients (51%) developed more than 1 UTI episode. The average number of episodes per patient was 2.2 (range, 1– 8 episodes); UTI most frequently occurred within the first postoperative month. Interestingly, bacteriuria was asymptomatic in 79.5% of cases (140/176). Antibiogramdriven therapy was given only in cases of symptomatic bacteriuria. Table 1 reports the various bacterial strains isolated and their in vitro responses to CEF or TMP/SMX, when available. When gram-negative bacteria are considered, 102/144 (70.8%) tests showed resistance to TMP/SMX, while data were only available for 7 cases of gram-positive infections (5/7, 71%). CEF was tested less frequently: 21/43 (49%) germs were resistant to this molecule. Noteworthy, the 2 molecules were not always tested in the antibiogram. DISCUSSION
We demonstrated that the onset of bacterial resistance to either TMP/SMX or CEF, ie, the antibiotics used perioperatively to minimize the incidence of surgery-related infections, was frequent after RT. In addition, resistance to TMP/SMX occurred more frequently than to CEF, due to the fact that the compound was administered for a much longer period than CEF. It should be emphasized that the
Table 1. Incidence of Resistance to the Study Molecules, According to the Isolated Bacterium Pathogen
Gram-negative bacteria Escherichia coli Pseudomonas aeruginosa Klebsiella sp. Citrobacter koseri Enterobacter sp. Proteus mirabilis Stenotrophomonas maltophilia Providencia rettgeri Gram-positive bacteria Enterococcus faecalis Staphylococcus epidermidis Staphylococcus aureus Staphylococcus haemoliticus Streptococcus agalactiae NA, not available.
Episodes of Infection
Sensitivity to TMP/SMX
Resistance to TMP/SMX
Sensitivity to CEF
Resistance to CEF
144 112 7 13 3 3 3 1 2 25 17 5 1 1 1
40 31 1 3 2 2 1 NA NA 2 NA 2 NA NA NA
102 81 6 8 1 1 2 1 2 5
43 34 NA 5 NA NA 1 1 2 NA NA NA NA NA NA
21 18 1 1 1 NA NA NA NA NA NA NA NA NA NA
3 1 1 NA
UTI AND RESISTANCE TO ANTIBIOTICS AFTER RT
development of resistance to antibiotics does not necessarily require long-term administration, but only few repeated doses. In fact, despite the fact that at our institution CEF was given only during the first 3 days after RT, almost half of the isolated germs were resistant to it. The World Health Organization (WHO) has declared that the increase in resistance to antibiotics is a “major public health problem in both developed and developing countries throughout the world.”8,9 The incidence of such phenomena has increased at an alarming pace in recent years. It is expected to increase at a similar or even greater rate in the future, as antimicrobial agents continue to lose their effectiveness. In addition to being a serious threat to human health, resistance to antimicrobial agents is a significant economic threat as well. For this reason the WHO strongly recommends global programs to reduce the inappropriate use of antibiotics in human medicine. In such a dramatic setting, stricter and wiser utilization of antibiotics is clearly mandatory. Therefore, are anti-Pneumocystis carinii and perioperative antibiotic prophylaxes necessary after RT? The answer to the first part of the question is yes: TMP/SMX is still necessary. In fact, the literature shows that anti-Pneumocystis carinii prophylaxis reduces to about 0 the incidence of the infection after RT, even when the drug is given at the dose of 400 mg thrice a week to reduce side effects.10,11 When the second part of the question is considered, the one-shot protocol (1 single dose of antibiotic administered when anesthesia is induced) is extremely effective in preventing surgery-related infections.12 Despite that the literature on the topic is poor and few data are available, a recent Scandinavian survey reported not only that a one-shot regimen was as effective as a multidose regimen, but—more interestingly—that 11% of responding centers in 11 countries do not routinely use antibiotic prophylaxis.13 Finally, it should be emphasized that the guidelines regarding the perioperative antibiotic prophylaxis after RT are unclear (http://www.pnlg.it/LG/009/ 009.pdf) and usually based on the single center physician personal experience and resources, rather than on prospective randomized multicenter trials. The one-shot protocol has largely been used in noncontaminated major surgery for more than a decade. Our findings were consistent with previous reports describing a peak of bacteriuria during the first month postsurgery.14 Asymptomatic bacteriuria, the most frequent infection after RT, was normally benign, unless there were urological or surgical complications, or major impairment of immunosurveillance. Whether treatment is indicated remains a matter of debate. The administration of antibiotics in cases of asymptomatic bacteriuria did not improve the outcomes of RT patients.15 Despite effective sterilization of the urine, it did not decrease the number of symptomatic episodes on hospitalizations thereafter.16 These data were consistent with similar findings in diabetic patients presenting asymptomatic bacteriuria.17 Finally, in agreement with data from the general population, we observed that UTIs were more frequent among female
1883
patients,1–3,18 as 38/69 (55%) women vs 38/149 (25%) men developed UTIs. Speculation on the underlying mechanisms is not within the purposes of the present manuscript. In conclusion, our experience demonstrated that the incidence of resistance to antibiotics was high in the RT population. Resistance developed even after the administration of only a few doses. As a corollary, respecting strict hygiene and sterility guidelines is of paramount importance especially in the care of transplant patients to prevent infections. The use of antibiotics should be optimized to reduce the onset of resistant strains and the guidelines for nosocomial hygiene strictly respected. There is a need for revision of guidelines regarding surgical antibiotic prophylaxis. Sterility should be emphasized in the operating room and on the ward, and external tools such as urinary catheters, central lines, and surgical drains should be removed as soon as possible.
REFERENCES 1. Dharnidharka VR, Stablein DM, Harmon WE: Post-transplant infections now exceed acute rejection as cause for hospitalization: a report of the NAPRTCS. Am J Transplant 4:384, 2004 2. Alangaden GJ, Thyagarajan R, Gruber SA, et al: Infectious complications after kidney transplantation: current epidemiology and associated risk factors. Clin Transpl 20:401, 2006 3. Chuang P, Parikh CR, Langone A: Urinary tract infections after renal transplantation: a retrospective review at two US transplant centres. Clin Transpl 19:230, 2005 4. Martinez-Marcos F, Cisneros J, Gentil M, et al: Prospective study of renal transplant infections in 50 consecutive patients. Eur J Clin Microbiol Infect Dis 13:1023, 1994 5. Fishman JA, Rubin RH: Infection in organ-transplant recipients. N Engl J Med 338:1741, 1998 6. Singer J, Gritsch HA, Rosenthal JT: The transplant operation and its surgical complications. In Danovitch GM (ed): Handbook of Kidney Transplantation. Philadelphia: Lippincott Williams & Wilkins; 2005, p 193 7. Rubin RH, Shapiro ED, Andriole VT, et al: Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Clin Infect Dis 15:216, 1992 8. World Health Organization: WHO Scientific Working Group on Monitoring and Management of Bacterial Resistance to Antimicrobial Agents. Geneva: WHO; 1994 9. Gupta K, Hooton TM, Stamm WE: Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann Intern Med 135:41, 2001 10. Kovacs JA, Gill VJ, Meshnick S, et al: New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 286:2450, 2001 11. Fishman JA: Prevention of infection caused by Pneumocystis carinii in transplant recipients. CID 33:1397, 2001 12. Tilney NL, Strom TB, Vineyard GC, et al: Factors contributing to the declining mortality rate in renal transplantation. N Engl J Med 24:1321, 1978 13. Midtvedt K, Hartmann A, Midtvedt T, et al: Routine perioperative antibiotic prophylaxis in renal transplantation. Nephrol Dial Transplant 13:1637, 1998
1884 14. Sharifian M, Rees L, Trompeter RS: High incidence of bacteriuria following renal transplantation in children. Nephrol Dial Transplant 13:432, 1998 15. Moradi M, Abbasi M, Moradi A, et al: Effect of antibiotic therapy on asymptomatic bacteriuria in kidney transplant recipients. Urol J 2:32, 2005 16. Belitsky P, Lannon SG, MacDonald AS, et al: Urinary tract infections (UTI) after kidney transplantation. Transpl Proc 14:696, 1982
DI COCCO, ORLANDO, MAZZOTTA ET AL 17. Harding KM, Zhanel GG, Nicolle LE, et al, for the Manitoba Diabetes Urinary Tract Infection Study Group: Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med 347:1576, 2002 18. Maraha B, Bonten H, van Hooff H, et al: Infectious complications and antibiotic use in renal transplant recipients during a 1-year follow-up. Clin Microbiol Infect 7:619, 2001