Kathryn J. Wiggins

Randomized, Controlled Trial of Topical Exit-Site Application of Honey (Medihoney) versus Mupirocin for the Prevention of Catheter-Associated Infections in Hemodialysis Patients

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Encapsulating peritoneal sclerosis: incidence, predictors, and outcomes.

Encapsulating peritoneal sclerosis is a complication of peritoneal dialysis characterized by persistent, intermittent, or recurrent adhesive bowel obstruction. Here we examined the incidence, predictors, and outcomes of encapsulating peritoneal sclerosis (peritoneal fibrosis) by multivariate logistic regression in incident peritoneal dialysis patients in Australia and New Zealand. Matched case-control analysis compared the survival of patients with controls equivalent for age, gender, diabetes, and time on peritoneal dialysis. Of 7618 patients measured over a 13-year period, encapsulating peritoneal sclerosis was diagnosed in 33, giving an incidence rate of 1.8/1000 patient-years. The respective cumulative incidences of peritoneal sclerosis at 3, 5, and 8 years were 0.3, 0.8, and 3.9%. This condition was independently predicted by younger age and the duration of peritoneal dialysis, but not the rate of peritonitis. Twenty-six patients were diagnosed while still on peritoneal dialysis. Median survival following diagnosis was 4 years and not statistically different from that of 132 matched controls. Of the 18 patients who died, only 7 were attributed directly to peritoneal sclerosis. Our study shows that encapsulating peritoneal sclerosis is a rare condition, predicted by younger age and the duration of peritoneal dialysis. The risk of death is relatively low and not appreciably different from that of competing risks for mortality in matched dialysis control patients.

Predictors and outcomes of fungal peritonitis in peritoneal dialysis patients

Fungal peritonitis is a serious complication of peritoneal dialysis but previous reports on this have been limited to small, single-center studies. Using all Australian peritoneal dialysis patients, we measured predictors, treatments, and outcomes of this condition by logistic regression and multilevel, multivariate Poisson regression. This encompassed 66 centers over a 4-year period that included 162 episodes of fungal peritonitis (4.5% of all peritonitis episodes) that occurred in 158 individuals. Candida albicans (25%) and other Candida species (44%) were the most common fungi isolated. Fungal peritonitis was independently predicted by indigenous race and prior treatment of bacterial peritonitis. Peritonitis episodes occurring after 7 and 60 days of treatment for previous bacterial peritonitis decreases in the probability of fungal peritonitis 23 and 6%, respectively. Compared with other organisms, fungal peritonitis was associated with significantly higher rates of hospitalization, catheter removal, transfer to permanent hemodialysis, and death. The risks of repeat fungal peritonitis and death were lowest with catheter removal combined with antifungal therapy when compared to either intervention alone. Our study shows that fungal peritonitis is a serious complication of peritoneal dialysis and should be strongly suspected in the context of recent antibiotic treatment for bacterial peritonitis.

Associations of Dialysis Modality and Infectious Mortality in Incident Dialysis Patients in Australia and New Zealand

BACKGROUND The aim of the present investigation is to compare rates, types, causes, and timing of infectious death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients in Australia and New Zealand. STUDY DESIGN Observational cohort study using the Australian and New Zealand Dialysis and Transplant Registry data. SETTING & PARTICIPANTS The study included all patients starting dialysis therapy between April 1, 1995, and December 31, 2005. PREDICTOR Dialysis modality. OUTCOMES & MEASUREMENTS Rates of and time to infectious death were compared by using Poisson regression, Kaplan-Meier, and competing risks multivariate Cox proportional hazards model analyses. RESULTS 21,935 patients started dialysis therapy (first treatment PD, n = 6,020; HD, n = 15,915) during the study period, and 1,163 patients (5.1%) died of infectious causes (PD, 529 patients; 7.6% versus HD, 634 patients; 4.2%). Incidence rates of infectious mortality in PD and HD patients were 2.8 and 1.7/100 patient-years, respectively (incidence rate ratio PD versus HD, 1.66; 95% confidence interval [CI], 1.47 to 1.86). After performing competing risks multivariate Cox analyses allowing for an interaction between time on study and modality because of identified nonproportionality of hazards, PD consistently was associated with increased hazard of death from infection compared with HD after 6 months of treatment (<6 months hazard ratio [HR], 1.08; 95% CI, 0.76 to 1.54; 6 months to 2 years HR, 1.31; 95% CI, 1.09 to 1.59; 2 to 6 years HR, 1.51; 95% CI, 1.26 to 1.80; >6 years HR, 2.76; 95% CI, 1.76 to 4.33). This increased risk of infectious death in PD patients was largely accounted for by an increased risk of death caused by bacterial or fungal peritonitis. LIMITATIONS Patients were not randomly assigned to their initial dialysis modality. Residual confounding and coding bias could not be excluded. CONCLUSIONS Dialysis modality selection significantly influences risks, types, causes, and timing of fatal infections experienced by patients with end-stage kidney disease in Australia and New Zealand.

KHA-CARI Guideline: Early chronic kidney disease: Detection, prevention and management

Early detection of CKD may therefore have value,although criteria for a screening programme to detect thedisease must be met to balance the aggregate benefits withthe risks and costs of the screening tests. General practition-ers, in particular, play a crucial role in CKD early detectionand management. All people attending their general practi-tioner should be assessed for CKD risk factors as part ofroutine primary health encounters.A number of studies

Microbiology and outcomes of peritonitis in Australian peritoneal dialysis patients

We analyzed data from the Australia and New Zealand Dialysis and Transplant Registry for 1 October 2003 to 31 December 2008 with the aim of describing the nature of peritonitis, therapies, and outcomes in patients on peritoneal dialysis (PD) in Australia. At least 1 episode of PD was observed in 6639 patients. The overall peritonitis rate was 0.60 episodes per patient–year (95% confidence interval: 0.59 to 0.62 episodes), with 6229 peritonitis episodes occurring in 3136 patients. Of those episodes, 13% were culture-negative, and 11% were polymicrobial. Gram-positive organisms were isolated in 53.4% of single-organism peritonitis episodes, and gram-negative organisms, in 23.6%. Mycobacterial and fungal peritonitis episodes were rare. Initial antibiotic therapy for most peritonitis episodes used 2 agents (most commonly vancomycin and an aminoglycoside); in 77.2% of episodes, therapy was subsequently changed to a single agent. Tenckhoff catheter removal was required in 20.4% of cases at a median of 6 days, and catheter removal was more common in fungal, mycobacterial, and anaerobic infections, with a median time to removal of 4 – 5 days. Peritonitis was the cause of death in 2.6% of patients. Transfer to hemodialysis and hospitalization were frequent outcomes of peritonitis. There was no relationship between center size and peritonitis rate. The peritonitis rate in Australia between 2003 and 2008 was higher than that reported in many other countries, with a particularly higher rate of gram-negative peritonitis.

Recent Peritonitis Associates with Mortality among Patients Treated with Peritoneal Dialysis

Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥ 2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4-8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days.

Pseudomonas Peritonitis in Australia: Predictors, Treatment, and Outcomes in 191 Cases

BACKGROUND AND OBJECTIVES Pseudomonas peritonitis is a serious complication of peritoneal dialysis. To date, there as been no comprehensive, multicenter study of this condition. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The predictors, treatment, and clinical outcomes of Pseudomonas peritonitis were examined by binary logistic regression and multilevel, multivariate Poisson regression in all Australian PD patients in 66 centers between 2003 and 2006. RESULTS A total of 191 episodes of Pseudomonas peritonitis (5.3% of all peritonitis episodes) occurred in 171 individuals. Its occurrence was independently predicted by Maori/Pacific Islander race, Aboriginal/Torres Strait Islander race, and absence of baseline peritoneal equilibration test data. Compared with other organisms, Pseudomonas peritonitis was associated with greater frequencies of hospitalization (96 versus 79%; P = 0.006), catheter removal (44 versus 20%; P < 0.001), and permanent hemodialysis transfer (35 versus 17%; P < 0.001) but comparable death rates (3 versus 2%; P = 0.4). Initial empiric antibiotic choice did not influence outcomes, but subsequent use of dual anti-pseudomonal therapy was associated with a lower risk for permanent hemodialysis transfer (10 versus 38%, respectively; P = 0.03). Catheter removal was associated with a lower risk for death than treatment with antibiotics alone (0 versus 6%; P < 0.05). CONCLUSIONS Pseudomonas peritonitis is associated with high rates of catheter removal and permanent hemodialysis transfer. Prompt catheter removal and use of two anti-pseudomonal antibiotics are associated with better outcomes.

Intradermal versus intramuscular hepatitis B vaccination in hemodialysis patients: a prospective open-label randomized controlled trial in nonresponders to primary vaccination.

BACKGROUND Primary hepatitis B virus (HBV) vaccination through the intramuscular (IM) route is less efficacious in dialysis patients than in the general population. Previous studies suggest improved seroconversion with intradermal (ID) vaccination. STUDY DESIGN Prospective open-label randomized controlled trial. SETTING & PARTICIPANTS Hemodialysis patients nonresponsive to primary HBV vaccination. INTERVENTION Revaccination with either ID (10 microg of vaccine every week for 8 weeks) [DOSAGE ERROR CORRECTED] or IM (40 microg of vaccine at weeks 1 and 8) HBV vaccine . OUTCOMES PRIMARY OUTCOME proportion of patients achieving HBV surface antibody (anti-HBs) titer of 10 IU/L or greater within 2 months of vaccination course. SECONDARY OUTCOMES time to seroconversion, predictors of seroconversion, peak antibody titer, duration of seroprotection, and safety and tolerability of vaccine. MEASUREMENTS Anti-HBs titer to 24 months. RESULTS 59 patients were analyzed. Seroconversion rates were 79% ID versus 40% IM (P = 0.002). The unadjusted odds ratio for seroconversion for ID versus IM was 5.5 (95% confidence interval [CI], 1.6 to 18.4) and increased with adjustment for baseline differences. The only factor predictive of seroconversion was the ID vaccination route. The geometric mean peak antibody titer was significantly greater in the ID versus IM group: 239 IU/L (95% CI, 131 to 434) versus 78 IU/L (95% CI, 36 to 168; P < 0.001). There was a trend toward longer duration of seroprotection with ID vaccination. ID vaccine was safe and well tolerated. LIMITATIONS Inability to distinguish whether the mechanism of the greater efficacy of ID vaccination was the cumulative effect of multiple injections or route of administration; use of anti-HBs as a surrogate marker of protection; lack of evidence of long-term protection. CONCLUSIONS Significantly greater seroconversion rates and peak antibody titers can be achieved with ID compared with IM vaccination in hemodialysis patients nonresponsive to primary vaccination. ID vaccination should become the standard of care in this setting.

Culture-negative peritonitis in peritoneal dialysis patients in Australia: Predictors, treatment, and outcomes in 435 cases

BACKGROUND Reports of culture-negative peritoneal dialysis (PD)-associated peritonitis have been sparse, conflicting, and limited to small single-center studies. The aim of this investigation is to examine the frequency, predictors, treatment, and outcomes of culture-negative PD-associated peritonitis. STUDY DESIGN Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. SETTING & PARTICIPANTS All Australian PD patients between October 1, 2003, and December 31, 2006. PREDICTORS Demographic, clinical, and facility variables. OUTCOMES & MEASUREMENTS Culture-negative PD-associated peritonitis occurrence, relapse, hospitalization, catheter removal, hemodialysis transfer, and death. RESULTS Of 4,675 patients who received PD in Australia during the study period, 435 episodes of culture-negative peritonitis occurred in 361 individuals. Culture-negative peritonitis was not associated with demographic or clinical variables. A history of previous antibiotic treatment for peritonitis was more common with culture-negative than culture-positive peritonitis (42% vs 35%; P = 0.01). Compared with culture-positive peritonitis, culture-negative peritonitis was significantly more likely to be cured using antibiotics alone (77% vs 66%; P < 0.001) and less likely to be complicated by hospitalization (60% vs 71%; P < 0.001), catheter removal (12% vs 23%; P < 0.001), permanent hemodialysis therapy transfer (10% vs 19%; P < 0.001), or death (1% vs 2.5%; P = 0.04). Relapse rates were similar between the 2 groups. Patients with relapsed culture-negative peritonitis were more likely to have their catheters removed (29% vs 10% [P < 0.001]; OR, 3.83; 95% CI, 2.00-7.32). Administration of vancomycin or cephalosporin in the initial empiric antibiotic regimen and the timing of catheter removal were not significantly associated with clinical outcomes. LIMITATIONS Limited covariate adjustment. Residual confounding and coding bias could not be excluded. CONCLUSIONS Culture-negative peritonitis is a common complication with a relatively benign outcome. A history of previous antibiotic treatment is a significant risk factor for this condition.