Filitsa H. Bender

Randomized, Double-Blind Trial of Antibiotic Exit Site Cream for Prevention of Exit Site Infection in Peritoneal Dialysis Patients

Infection is the Achilles heel of peritoneal dialysis. Exit site mupirocin prevents Staphylococcus aureus peritoneal dialysis (PD) infections but does not reduce Pseudomonas aeruginosa or other Gram-negative infections, which are associated with considerable morbidity and sometimes death. Patients from three centers (53% incident to PD and 47% prevalent) were randomized in a double-blinded manner to daily mupirocin or gentamicin cream to the catheter exit site. Infections were tracked prospectively by organism and expressed as episodes per dialysis-year at risk. A total of 133 patients were randomized, 67 to gentamicin and 66 to mupirocin cream. Catheter infection rates were 0.23/yr with gentamicin cream versus 0.54/yr with mupirocin (P = 0.005). Time to first catheter infection was longer using gentamicin (P = 0.03). There were no P. aeruginosa catheter infections using gentamicin compared with 0.11/yr using mupirocin (P < 0.003). S. aureus exit site infections were infrequent in both groups (0.06 and 0.08/yr; P = 0.44). Peritonitis rates were 0.34/yr versus 0.52/yr (P = 0.03), with a striking decrease in Gram-negative peritonitis (0.02/yr versus 0.15/yr; P = 0.003) using gentamicin compared with mupirocin cream, respectively. Gentamicin use was a significant predictor of lower peritonitis rates (relative risk, 0.52; 95% confidence interval, 0.29 to 0.93; P < 0.03), controlling for center and incident versus prevalent patients. Gentamicin cream applied daily to the peritoneal catheter exit site reduced P. aeruginosa and other Gram-negative catheter infections and reduced peritonitis by 35%, particularly Gram-negative organisms. Gentamicin cream was as effective as mupirocin in preventing S. aureus infections. Daily gentamicin cream at the exit site should be the prophylaxis of choice for PD patients.

Calcium Mass Transfer With Dialysate Containing 1.25 and 1.75 mmol/L Calcium in Peritoneal Dialysis Patients

Studies with 1.75 mmol/L calcium dialysate have shown that patients gain calcium from dialysate. Thus, hypercalcemia, especially when calcium compounds are used for phosphate control, is a commonly seen complication. Dialysate with 1.25 mmol/L calcium has been available since 1989. Little is known about calcium mass transfer (CMT) with dialysate of this calcium concentration. CMT was measured in 20 stable adult peritoneal dialysis patients. Each CMT study consisted of a 2-L continuous ambulatory peritoneal dialysis (CAPD) exchange with a dwell time of 4 hours. CMT studies were performed using 1.25 and 1.75 mmol/L calcium dialysate with 1.5, 2.5, and 4.25 g/dL dextrose concentrations. CMT with 1.25 mmol/L calcium dialysate was compared to that with 1.75 mmol/L for each dextrose concentration. With a dextrose concentration of 1.5 g/dL, the mean CMT for 1.25 mmol/L calcium dialysate was -0.1 +/- 0.3 mmol versus 0.6 +/- 0.3 mmol for 1.75 mmol/L calcium dialysate (P < 0.0001). A dextrose concentration of 2.5 g/dL resulted in a mean CMT of -0.4 +/- 0.2 mmol for 1.25 mmol/L calcium versus 0.45 +/- 0.25 mmol for 1.75 mmol/L calcium (P < 0.0001). Using a dextrose concentration of 4.25 g/dL, the mean CMT was -0.7 +/- 0.25 mmol for 1.25 mmol/L calcium versus -0.05 +/- 0.35 mmol for 1.75 mmol/L calcium (P < 0.0001). Mean serum ionized calcium (SiCa) was between 1.15 and 1.20 mmol/L for all study groups. CMT inversely correlated with SiCa for each type of dialysate used. CMT was dependent on the concentrations of calcium and dextrose in the dialysate and the SiCa level at the time of the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of Different Hepatitis B Vaccination Strategies in Patients Receiving Hemodialysis

Patients with end-stage renal disease have an impaired immune response to vaccination against Hepatitis B. The efficacy of different vaccines and vaccine schedules was studied in a group of patients receiving long-term hemodialysis. All patients received an initial 6 month course of intramuscular vaccine with either three doses of Recombivax (48 patients) or four doses of Engerix B (50 patients). This was successful in 71% and 74% of patients, respectively. In 10 patients unresponsive to 4 doses of Engerix B, a second course (2-4 doses) was successful in 5, thus increasing the overall success rate to 84%. Repetitive doses of vaccine intradermally were used as an alternative approach in eight patients who were unresponsive to intramuscular vaccination resulting in seroconversion in six. Finally, booster doses of intramuscular Engerix B have been used in 26 patients who lost their antibodies after successful vaccination.

The United States' Perspectives on Home Dialysis

Home dialysis in the United States, both home hemodialysis and peritoneal dialysis, peaked in the early 1990s. Since then, there has been a striking increase in the numbers and proportion of patients on in-center home hemodialysis (HD). As of 2008, there were approximately 27,000 patients on peritoneal dialysis (PD) and 2,455 on home HD with over 300,000 on in-center HD. There are multiple barriers to home dialysis in the United States, including lack of adequate patient education on modalities prior to starting dialysis, physician competence with home dialysis, lack of infrastructure in many programs for home dialysis, and a misinterpretation of literature and research with selection bias that suggests higher mortality on PD versus in-center HD. These barriers to home dialysis can be overcome.

Why is the evidence favoring hemodialysis over peritoneal dialysis misleading

‘‘To PD or not to PD’’—that is the question. One could debate whether this question should be asked each time a patient presents with advanced chronic kidney disease and the need to initiate renal replacement therapy. It seems to me however, that this question often is not asked, or if it is, it is answered in more of a philosophical than medical evidence way. Let me ask the question again—‘‘To PD or not to PD?’’ When I do so, am I asking: (A) should a dialysis facility honestly and enthusiastically offer PD to all their patients with ESRD based on clinical appropriateness? or (B) am I asking—Is this patient who presents with ESRD a candidate for PD? or finally (C) am I implying we should do both? Obviously if the answer to question A above is no, one cannot either consider answering question B or C. This may be the case in the United States. Consider that according to the United States Renal Data Systems (USRDS) 2006 report, in 2004 only 7.7% of prevalent patients in the United States are on PDwhile the prevalence varies from as high as 70% in Mexico to 3.6% in Japan (1). Let us review contemporary reports to see if the point prevalence data are justified based on medical outcome data. A prospective randomized trial comparing similar patients with similar doses of dialysis and care on either PD or HD would be the best study to address this question. It turns out there are none and, very likely, never will be any such study. It is important to note that organizing such a PD versus HD trial has been attempted. Baxter Healthcare tried to conduct a multi-center prospective randomized trial of PD versus HD, but because of very poor enrollment, the trial was discontinued and no outcome data are available (2). In a second trial conducted in theNetherlands (3), 735 eligible patients were identified for potential randomization; however, after informed consent, only 38 patients agreed to randomization. This is an important point—in contrast to some other studies, the data on the recruitment process and the inclusion ⁄exclusion data for the study were included in the manuscript. After an informed consent process (implies that in this study the answer to question A above was yes), 95%of patients did not want to be randomized; they wanted to make a choice (52% of time for HD, 48% of time for PD). To me, these data are the most important results of the study. Although the power was quite small, the primary outcome (survival results) for those who agreed to be randomized showed a survival advantage to starting on PD. Does this help you answer the question ‘‘to PD or not to PD’’ above? One problem with any retrospective analysis of epidemiologic observations is that although one can adjust for known variables you cannot easily adjust for differences in the severity of co-morbidity, overall health of the patient, and patient choice. One study attempted to circumvent this issue. In this study the authors assumed that patients on the transplant waiting list are equally healthy and do not have severe co-morbidities. They evaluated the 2 year survival for transplant wait listed patients on PD andHD. This showed that modality was not predictive of 2-year survival (unadjusted 2-year mortality 6.6% on PD, 6.9% on HD (4). Does this help you answer the question above? If not, consider the next level of evidence—epidemiologic data. However when doing so, consider the acknowledged limitations of these studies: no randomization; inherent flaws from data collection; no ability to adjust for selection bias (which could mean presentation bias, infrastructure bias, availability bias, answering question A above in the negative); and others. In other words, results from these studies are only hypothesisgenerating observations. Now for a new question, question D: Should epidemiologic observational studies determine or drive our clinical practices? (Be careful how you answer at this point and remember the Woman’s Health Initiative studies.) Given these caveats, there are contemporary observational publications we should consider, perhaps foremost those from the USRDS and other similar national registries. Consider figure 6.3 from the 2005 USRDS report (5) which suggests that the probability of surviving 5 years on dialysis for nondiabetics starting dialysis between 1994 and 1998 was 41.1% for PD and 39.0% for HD. Given that over 50% of new ESRD patients do not have diabetes mellitus (1) this would certainly suggest that more than 7.7% of prevalent patients would do Address correspondence to: John Burkart, MD, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157-1053, or e-mail: jburkart@wfubmc.edu. Seminars in Dialysis—Vol 20, No 3 (May–June) 2007 pp. 200–202 DOI: 10.1111/j.1525-139X.2007.00274.x

LONG-TERM EXIT-SITE GENTAMICIN PROPHYLAXIS AND GENTAMICIN RESISTANCE IN A PERITONEAL DIALYSIS PROGRAM

♦ Background: Daily gentamicin cream exit-site prophylaxis reduces peritoneal dialysis (PD)-related gram-negative infections. However, there is a concern about the potential for increasing gentamicin resistance with the long-term use of prophylactic gentamicin. This study evaluated the incidence of gentamicin-resistant PD-related infections over more than 2 decades. ♦ Methods: Study data on prevalent PD patients were retrieved from a prospectively maintained institutional review board (IRB)-approved PD registry at a single center from January 1, 1991, to December 31, 2000, and January 1, 2004, to December 31, 2013. The rates of gram-negative infections, fungal infections and those infections with organisms resistant to gentamicin were examined for the 2 periods. Period 1 from 1991 to 2000 when S. aureus prophylaxis consisted initially of oral rifampin to treat nasal carriage with S. aureus, and was then daily exit-site mupirocin ointment for all PD patients, was compared to the period from 2004 to 2013 when daily exit-site gentamicin cream was prescribed as prophylaxis (Period 2). ♦ Results: The study included a total of 444 PD patients (265 and 179 in Period 1 and Period 2, respectively). No significant difference was noted in demographics between the 2 periods except race. The gram-negative exit-site infection rates for Period 1 and Period 2 were 0.109 versus 0.027 (p < 0.0001). Gram-negative peritonitis rates were similar. There were 3 episodes of gentamicin-resistant infections in each period. Fungal infections remained consistently low. ♦ Conclusion: Despite a decade of exit-site gentamicin prophylaxis, gentamicin-resistant PD-related infections and fungal infections remained very low and similar to the prior period.

Health literacy in patients on maintenance peritoneal dialysis: prevalence and outcomes.

6. Schaefer F, Borzych-Duzalka D, Azocar M, Munarriz RL, Sever L, Aksu N, et al. Impact of global economic disparities on practices and outcomes of chronic peritoneal dialysis in children: insights from the International Pediatric Peritoneal Dialysis Network Registry. Perit Dial Int 2012; 32:399–409. 7. Furth SL, Donaldson LA, Sullivan EK, Watkins SL. Peritoneal dialysis catheter infections and peritonitis in children: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 2000; 15:179–82. 8. Abu-Aisha H, Elhassan EA, Khamis AH, Fedail H, Kaballo B, Abdelraheem MB, et al. Rates and causes of peritonitis in a National Multicenter Continuous Ambulatory Peritoneal Dialysis program in Sudan: first-year experience. Saudi J Kidney Dis Transpl 2007; 18:565–70. 9. Holloway M, Mujais S, Kandert M, Warady BA. Pediatric peritoneal dialysis training: characteristics and impact on peritonitis rates. Perit Dial Int 2001; 21:401–4. doi: 10.3747/pdi.2013.00342

How should peritoneal-dialysis-associated peritonitis be treated?

In this Practice Point commentary, we discuss Wiggins et al.s systematic review of the treatment of peritonitis, a serious problem in peritoneal dialysis patients. Wiggins and co-workers reported that most antibiotic classes were similarly effective for the treatment of peritonitis. Despite the limited data available, the investigators found that the intraperitoneal route was more effective than the intravenous route in preventing treatment failure, that intermittent dosing of various antibiotics was as effective as continuous administration of these drugs, and that glycopeptide-based regimens were more likely than first-generation cephalosporins to achieve a complete cure. Here, we discuss the importance of treating peritonitis and the lack of and limitations of existing data, and emphasize the urgent need for well-designed, large randomized trials in this area.

Avoiding Harm in Peritoneal Dialysis Patients

This review is focused on minimizing complications and avoiding harm in peritoneal dialysis (PD) patients. Issues related to planning for PD are covered first, with emphasis on PD versus hemodialysis outcomes. Catheter types and insertion techniques are described next, including relevant recommendations by the International Society for Peritoneal Dialysis. A brief review of both noninfectious and infectious complications follows, with emphasis on cardiovascular and metabolic complications. Finally, recommendations for preventing PD-related infections are provided. In conclusion, with proper catheter insertion technique, good training, and attention to detail during the tenure in PD, excellent outcomes can be obtained in a well-informed motivated patient.

Outcomes of PD Patients at 6 Months.

The peritoneal dialysis (PD) patient population has grown rapidly in the past few years with concern over poor early outcomes. We report 6-month outcomes of incident PD patients in an experienced program with a strong focus on quality care. We analyzed data from an Institutional Review Board (IRB)- approved registry of all incident PD patients from January 1, 1991, to December 31, 2013, with follow-up to June 30, 2014. Time at risk began on the first day of training. Age, gender, race, diabetes mellitus (DM), Charlson comorbidity index (CCI), and albumin were collected at PD start. Exit-site infection (ESI), peritonitis, hospitalizations, and reasons for stopping PD were recorded. Multivariate analysis was done to examine outcomes.