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Stephen I. Vas MD PhD FRCPc

Professor of Medicine, Laboratory Medicine and Pathobiology University of Toronto.
University Health Network Toronto Western Hospital
Toronto, Ontario. Canada


Dialysis is a rapidly growing treatment of end stage renal failure (ESRD). Since transplantation is the only way out of ESRD and the number of organ donors is woefully small, this treatment modality will grow in the coming years. It is estimated that presently more than one million patients are on some form of dialysis worldwide, and that 80-85 % of these are in Europe, USA, and Japan. In these countries there will also be rapid increase of dialysis. Below is an estimate for Canada [1 ]

19942005Increase annually %
 No pts/106 No pts /106No pts/ 106
Hemodialysis5840207.7 12075379.66.85.6
Peritoneal dialysis3318118.0 6555206.16.45.2
Transplant5904210.0 12874404.77.36.1
Total15062535.8 31505990.46.95.7

The economic changes occurring in the developing countries will result in a rapid increase of dialysis patients in these areas where health care will not be adequate, hygienic conditions low, and cost considerations important.

Infections being the most common complication of dialysis, it is important to have a proper approach to the management of infections. In the last few years three clinical guidelines dealt with the problem [2-4]. They describe the management of infections as to the present.

In this article the changes expected or already under way in dialysis methodology and their expected impact on infections will be discussed.


Biofilm, an almost ubiquitous slimy layer formed by almost all microorganisms on surfaces, is a puzzling phenomenon [5,6] . While certain microorganisms show increased ability to form it (Coagulase-negative staphylococci, Pseudomonas ) the pathogenic role of these biofilms are still argued; they are a potential source of infections, particularly of the chronic or recurrent type. The slimy layer gives protection to the microorganisms against antibiotics.

Research on prevention of biofilm formation is centered on (1) material resistant to biofilm - not very successful. (2) Antibacterial coating [8] it is - effective in the short run. (3) Therapeutic antibiotics to kill biofilms [7] - difficult to achieve.


Access site [9]

An AV fistula (Cimino) shows the lowest rates of infections. This is therefore the recommended access method [10]. Polytetrafluoroethylene (PTFE) grafts have a higher infection rate and are more resistant to antibiotic therapy. Surgical graft revision is often required. Central vascular catheters are used more often, not only for acute hemodialysis, but also for more permanent access [11}. They present special problems [12]. Meticulous exit site care is necessary for longterm use. Their advantage is that often they can be changed over a guidewire [13]. Prophylaxis of infections is being attempted by using antibiotic locks. Infections manifest themselves in bacteremias, which, in case of S aureus the most common causative organism, may lead to secondary abscesses, endocarditis, etc.

The search for novel access sites resulted in subcutaneous injecton chambers [14, 15]. Initial clinical studies are in progress.

New approaches to hemodialysis.

Doqi guidelines [10] placed strong emphasis on adequacy of dialysis which leads to better patient survival. This can be achieved by longer hours on hemodialysis. The increase in hours is inconvenient to patients, therefore the frequency of dialysis was investigated [16, 17]. Preliminary results are very encouraging. Since this method doubles the penetration of access sites, the frequency of infectious episodes is watched carefully.

Prevention of hemodialysis infections

Increasing hygienic conditions in hemodialysis units shows reduction of infectious episodes [2, 4]. Special care has to be taken of the regular treatment of the exit site of central line catheters [18]. The role of S aureus nasal carriers has been well documented and approaches to reduce risk have been established [19].

Peritoneal dialysis

15-30 % of the dialysis population is on peritoneal dialysis. The question of equivalence of HD versus PD has been settled [20] .They are equally efficacious, each having advantages and disadvantages.

While initially peritoneal dialysis (PD) had high rates of peritonitis (1/3 peritonitis episodes/ patient month) it is not unusual to find units with a rate of 1/36 – 1/48 patient months. .

Peritoneal access.

There are many types of new catheters. It appears that catheters with a double cuff have slight advantage over single cuff catheters as far as infections are concerned. On the other hand double cuff catheters require surgical implantation while single cuff catheters can be implanted by laparascopic methods [21]. As far as the shape of the catheter is concerned, there are no convincing differences in infection rates.

Methods of peritoneal dialysis

The initial "spike" method was slowly replaced by the Y tube or double bag method ("flush before fill") resulting in significant reduction of infections [22]. More recently automated peritoneal dialysis (APD) started to gain ground [23]. In some countries ~30 % of PD patients are on APD. As a consequence of trying to achieve more efficient dialysis continuous flow peritoneal dialysis (CFPD) was introduced [24, 25]. The jury is out on this method.

Connection systems

There is still competition to devise a better connection. The standard Luer lock system has been modified to include more secure connections, disinfectant (providone) locked in the connection site etc.

New dialysis fluids

New fluids have been introduced [26, 27]. For malnourished patients a dialysis fluid is available containing an amino acid mixture which provides an easy source for protein synthesis. While it is relatively expensive, and can be used only once a day, it is effective. There is a polyglucose (icodextrin) containing solution instead of glucose as the osmotic agent. It is useful to manage water transport where normal solutions are failing.

New solutions are under development, where the fluid’s acidity and osmolality are managed more physiologically. It is expected that these solutions are going to provide a more natural environment, leading to longer preservation of the transport capacity of the peritoneum. Also, it is hoped, that this better milieu will help in the defense functions of the peritoneum.

Infection rates

With the introduction of APD it was expected that peritonitis rates would increase since the system is connected overnight and the patient may require disconnection and reconnection. It is a closed system, with the necessary safe connections. It does not appear to have a higher peritonitis rate and the distribution of organisms is the same as for the double bag system [28].

Diagnosis and treatment

The formerly established diagnostic criteria: cell count in the peritoneal fluid of > 100 cells / mm3 with > 50 % neutrophils and/or abdominal pain and rebound tenderness and/or bacteria on culture (two out of three criteria present) proved to be reliable and practical. Cultural procedures have been discussed previously [3]. One difficulty in patients on APD is that there is no bag with sufficient dwell time to use for the above diagnostic criteria, which were established for standard 4-6 hour dwell times. Shorter times may give misleadingly low cell counts and false negative cultures.

It is therefore necessary for appropriate diagnosis to provide a dwell time of 4-6 hours either by prolonging the last (night) dwell and collecting the last drain or by having the patient carry a 4-6 hour extra day-dwell. Laboratory diagnosis in the usual manner should be performed on such drainage fluids.

Antibiotic therapy shifted in recent years to single intraperitoneal daily doses [29, 30].

Decreasing residual renal function is an independent predictor of dialysis outcome. Therefore preserving residual function is a necessity. Aminoglycoside use is the most common reason for decrease of residual renal function. The Committee on treatment of peritonitis in CAPD patients recommended treatment [3] briefly outlined below.

Intermittent (1x day) therapy is preferred.

Patients with < 100 ml 24h urine should be started on 0.6 mg/kg (50 mg for BW > 60 kg, 40 mg for BW < 60 kg) aminoglycoside and 15 mg/kg cefazolin once daily with a dwell time of at least 3-4 hours.

Patients with > 100 ml 24h urine should start on 1500 mg ceftazidime and 20 mg/kg (1.5 gr) cefazolin once daily with a dwell time of at least 3-4 hours.

Vancomycin is still recommended only for methicillin resistant organisms.

Antibiotics adjusted when sensitivities available.

For patients on automated peritoneal dialysis the antibiotics should be placed in an extra day dwell of appropriate volume for 4-6 hours to assure appropriate antibiotic transfer.

Prevention of peritonitis

The importance of the reduction of S aureus exit site infection as a cause of peritonitis has been stressed previously [18]. Recent clinical reports of the use of mupirocin ointment at the exit site [31-33] further strengthened the recommendation to follow this practice.


1. Schaubel DE, Morrison HI, Desmeules M, Parsons D, Fenton SS End-stage renal disease projections for Canada to 2005 using Poisson and Markov models. Int J Epidemiol. 1998 Apr;27(2):274-81.

2. Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady N, Harris JS, Craven DE. Guidelines for the management of intravascular catheter-related infections. Infect Control Hosp Epidemiol. 2001 Apr;22(4):222-42.

3. Keane WF, Bailie GR, Boeschoten E, Gokal R, Golper TA, Holmes CJ, Kawaguchi Y, Piraino B, Riella M, Vas S. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int. 2000 Jul-Aug;20(4):396-411.

4.Tokars JI, Arduino MJ, Alter MJ.Infection control in hemodialysis units. Infect Dis Clin North Am. 2001 Sep;15(3):797-812, viii

5. Donlan (2001) Biofilms. Clin Infect Dis 33:1387-1392

6. Darouiche RO Device associated infections: A macroproblem that starts with microadherence Clin Inf Dis 2001. 33:

7. Donlan RM Role of biofilms in antimicrobial resistance. ASAIO Journal 2000; 46:547-552

8. Pai MP, Pendland SL, Danziger LH Antimicrobial-coated/bonded and -impregnated intravascular catheters. Ann Pharmacother. 2001 Oct;35(10):1255-63.

9. Lew SQ, Kaveh K. Dialysis access related infections. ASIO Journal 2000; 46:S6-S12.

10. http://www.kidney.org/professionals/doqi

11. Jean G, Charra B, Chazot C, Vanel T, Terrat JC, Hurot JM. Long-term outcome of permanent hemodialysis catheters: a controlled study. Blood Purif. 2001;19(4):401-7.

12. Farr BM Prevention of CatheterRelated Infections. 2001; Clin Infect Dis 33:1733-1738

13. Carlisle EJ, Blake P, McCarthy F, Vas S, Uldall R. Septicemia in long-term jugular hemodialysis catheters; eradicating infection by changing the catheter over a guidewire. Int J Artif Organs. 1991 Mar;14(3):150-3.

14. Beathard GA, Posen GA. Initial clinical results with the LifeSite Hemodialysis Access System. Kidney Int. 2000 Nov;58(5):2221-7.

15. Canaud B, My H, Morena M, Lamy-Lacavalerie B, Leray-Moragues H, Bosc JY, Flavier JL, Chomel PY, Polaschegg HD, Prosl FR, Megerman J. Dialock: a new vascular access device for extracorporeal renal replacement therapy. Preliminary clinical results. Nephrol Dial Transplant. 1999 Mar;14(3):692-8.

16. Nissenson AR. Daily hemodialysis: Challenges and opportunities in the delivery and financing of end-stage renal disease patient care.Adv Ren Replace Ther. 2001 Oct;8(4):286-90.

17. Lockridge RS Jr, Spencer M, Craft V, Pipkin M, Campbell D, McPhatter L, Albert J, Anderson H, Jennings F, Barger T.Nocturnal home hemodialysis in North America. Adv Ren Replace Ther. 2001 Oct;8(4):250-6.

18. Piraino B Staphylococcus aureus infections in dialysis patients: focus on prevention. ASAIO J. 2000 Nov-Dec;46(6):S13-7. Review.

19. Humar A, Ostromecki A, Direnfeld J, Marshall JC, Lazar N, Houston PC, Boiteau P, Conly JM.Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection. Clin Infect Dis. 2000 Oct;31(4):1001-7.

20. Schaubel DE, Morrison HI, Fenton SS Comparing mortality rates on CAPD/CCPD and hemodialysis. The Canadian experience: fact or fiction? Perit Dial Int. 1998 Sep-Oct;18(5):478-84.

21. Gokal R. Alexander S. Ash S. Chen TW. Danielson A. Holmes C. Joffe P. Moncrief J. Nichols K. Piraino B. Prowant B. Slingeneyer A. Stegmayr B. Twardowski Z. Vas S. Peritoneal catheters and exit-site practices toward optimum peritoneal access: 1998 update. Perit Dial Intern. 18(1):11-33

22. Daly CD, Campbell MK, MacLeod AM, Cody DJ, Vale LD, Grant AM, Donaldson C, Wallace SA, Lawrence PD, Khan IH. Do the Y-set and double-bag systems reduce the incidence of CAPD peritonitis? A systematic review of randomized controlled trials. Nephrol Dial Transplant. 2001 Feb;16(2):341-7.

23. Ronco C, Diaz-Buxo JA.Automated peritoneal dialysis. Revisitation of the past or beginning of a new PD era? Nephron. 2001 Jan;87(1):1-7.

24. Diaz-Buxo JA. Evolution of continuous flow peritoneal dialysis and the current state of the art Semin Dial. 2001 Sep-Oct;14(5):373-7.

25. Ronco C .Continuous Flow Peritoneal Dialysis: Is There a Need for it?. Semin Dial. 2001 Sep-Oct;14(5):395-400.

26. Alflaiw A, Vas S. QreopoulosDG. Peritonitis in APD Patients: Diagnosis and Treatment. In: Contributions to Nephrology. Automated Peritoneal dialisis Ed. Ronco C, Amici G, Feriani M, Virga G. Karger AG Basel. 1999. pp 213-228

27. Johnson DW, Arndt M, O'Shea A, Watt R, Hamilton J, Vincent K.Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload. BMC Nephrol. 2001;2(1):2.

28. Jorres A.Innovative approaches to the preservation of the peritoneal membrane: From bench to bedside. Adv Ren Replace Ther. 2001 Jul;8(3):164-72.

29. Vas SI. Single daily dose of aminoglycosides in the treatment of continuous ambulatory peritoneal dialysis peritonitis. Perit Dial Intern. 13 Suppl 2:S355-356, 1993.

30. Vas S, Bargman J, Oreopoulos DG. Treatment in PD patients of peritonitis caused by gram-positive organisms with single daily dose of antibiotics. Perit Dial Int. 1997; 17:91-94.

31.Bernardini J, Piraino B, Holley J, Johnston JR, Lutes R.A randomized trial of Staphylococcus aureus prophylaxis in peritoneal dialysis patients: mupirocin calcium ointment 2% applied to the exit site versus cyclic oral rifampin. Am J Kidney Dis. 1996 May;27(5):695-700.

32. Thodis E, Bhaskaran S, Pasadakis P, Bargman JM, Vas SI, Oreopoulos DG Decrease in Staphylococcus aureus exit-site infections and peritonitis in CAPD patients by local application of mupirocin ointment at the catheter exit site. Perit Dial Int. 1998 May-Jun;18(3):261-70.

33. Thodis E, Passadakis P, Panagoutsos S, Bacharaki D, Euthimiadou A, Vargemezis V.The effectiveness of mupirocin preventing Staphylococcus aureus in catheter-related infections in peritoneal dialysis. Adv Perit Dial. 2000;16:257-61.