INFECTIONS RELATED TO PROSTHETIC MATERIALS IN PATIENTS ON CHRONIC DIALYSIS.
Stephen I. Vas MD PhD FRCPc
Professor of Medicine, Laboratory Medicine and Pathobiology
University of Toronto.
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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  it is - effective in the short run. (3) Therapeutic antibiotics to kill biofilms  - difficult to achieve.
Access site 
An AV fistula (Cimino) shows the lowest rates of infections. This is therefore the recommended access method . 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 . Meticulous exit site care is necessary for longterm use. Their advantage is that often they can be changed over a guidewire . 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  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 . The role of S aureus nasal carriers has been well documented and approaches to reduce risk have been established .
15-30 % of the dialysis population is on peritoneal dialysis. The question of equivalence of HD versus PD has been settled  .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. .
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 . 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 . More recently automated peritoneal dialysis (APD) started to gain ground . 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.
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.
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 .
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 . 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  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 . Recent clinical reports of the use of mupirocin ointment at the exit site [31-33] further strengthened the recommendation to follow this practice.
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