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Background: Intraperitoneal (IP) aminoglycosides (AGs) continue to be the cornerstone of empiric management of peritonitis. AG dosing during automated peritoneal dialysis (APD), however, has not been well studied in patients with peritonitis. We sought to identify differences in AG exposure in the peritoneum and plasma for two different dosing regimens with little supporting evidence in patients on APD with peritonitis., Methods: A retrospective design that utilised the peritoneal and plasma concentration-time data from a prior study of 18 continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis to generate an in silico peritoneal and plasma PK model. This model was then used to compare via simulation using Phoenix© WinNonlin Software with IP AG dosing for a loading-dose regimen (1.5 mg/kg first dose) versus a fixed-dose regimen (0.6 mg/kg/d) in patients on APD with peritonitis., Results: Outcome measures were (1) percentage of time where peritoneal peak concentrations/minimal inhibitory concentration (MIC) ratio >10, (2) AUC/MIC > 74 and (3) plasma Cmin concentrations. Both regimens resulted in > 90% optimal peak/MIC ratio and AUC/MIC ratios on days 1 and 5 of the dose protocol. The loading-dose regimen resulted in IP exposures that were 2.5 times greater in the peritoneal compartment on day 1. By day 5, both protocols resulted in similar accumulation of AG plasma Cmin concentrations of 2.5-3.4 mg/L versus 2.4-3.3 mg/L, respectively, for the loading-dose regimen versus fixed-dose regimen., Conclusions: The current international guidelines for the treatment of peritoneal dialysis-associated peritonitis can continue to recommend the fixed-dose regimen for those on APD with the addition of plasma Cmin monitoring after 3 days to assess for drug accumulation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Program: The ongoing shortage of organs for transplant combined with the highest prevalence of end-stage kidney disease (ESKD) in Canada has resulted in long wait times for a deceased donor transplant in Manitoba. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes an age-targeted program intended to increase the use of transplants with a kidney donor profile index (KDPI) >85 by allocating them to suitable pre-consented recipients age ≥65 with low wait times. The goal is to improve survival and quality of life for older recipients by maximizing a previously under-utilized donor pool., Sources of Information: Scoping literature review; Transplant Manitoba deceased donor audit; and key stakeholder engagement with patient partners, inter-disciplinary health care providers, and health system leaders., Methods: The alternative donor pool criteria include deceased donor kidneys with KDPI 86-100 or another concern for graft longevity but are otherwise suitable for transplantation. Patients with no living donor, age ≥65, low wait times and otherwise eligible for transplant listing will be educated, and if suitable, pre-consented for the age-targeted program. All patients remain eligible for a standard criteria donor according to the local allocation criteria. The age-targeted program waitlist follows the same provincial allocation rules using wait time, panel reactive antibody (PRA), and human leukocyte antigen (HLA) match points for determining rank order. If an age-targeted recipient experiences early graft loss from a KDPI 86-100 kidney within 12 months from transplant, their cumulative wait time, including time with the transplant, will be reinstated upon relisting., Key Findings: Transplant Manitoba's provincial allocation rules do not permit bypassing top of the list recipients for kidney offers; therefore, transplant providers were previously reluctant to utilize KDPI 86-100 donor kidneys to top of the list recipients eligible for higher quality kidneys. This age-targeted program facilitates allocation of KDPI 86-100 kidneys to suitable older pre-consented recipients with low wait times, who may obtain a survival and quality of life benefit from these transplants. This approach expands the utilized deceased donor pool to benefit all Manitobans awaiting a deceased donor kidney transplant., Limitations: This program was launched in January 2023, and there are no data reported on outcomes given the small numbers and abbreviated follow-up., Implications: The goal of this quality improvement project is to improve access to deceased donor kidney transplantation for Manitobans with ESKD. This program was developed with patient and provider feedback, including multimedia patient education materials which may be helpful for other programs. We anticipate this program is a safe and effective way to expand access to deceased donor kidney transplantation using a previously under-utilized donor pool., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Given the morbidity and mortality associated with bloodstream infections in hemodialysis patients, understanding the microbiology is essential to optimizing treatment in this high-risk population., Objectives: To conduct a retrospective surveillance study of clinical blood isolates from adult hemodialysis patients, and to predict the microbiological coverage of empiric therapies for bloodstream infections in this population., Methods: Clinical blood isolate data were collected from the 4 main outpatient hemodialysis units in Winnipeg, Manitoba, from 2007 to 2014. The distribution of organisms and antimicrobial susceptibilities were characterized. When appropriate, changes over time were tested using time series analysis. Study data were used to predict and compare the microbiological coverage of various empiric therapies for bloodstream infections in hemodialysis patients., Results: The estimated annual number of patients receiving chronic hemodialysis increased steadily over the study period ( p < 0.001), whereas the number of blood isolates increased initially, then decreased significantly, from 180 in 2011 to 93 in 2014 ( p = 0.04). Gram-positive bacteria represented 72.6% (743/1024) of isolates, including Staphylococcus aureus (36.9%, 378/1024) and coagulase-negative staphylococci (23.1%, 237/1024). Only 26.1% (267/1024) of the isolates were gram-negative bacteria, the majority Enterobacteriaceae. The overall rate of methicillin resistance in S. aureus was 17.5%, and although annual rates were variable, there was a significant increase over time ( p = 0.04). Antibiotic resistance in gram-negative bacteria was relatively low, except in Escherichia coli , where 13.5% and 16.2% of isolates were resistant to ceftriaxone and ciprofloxacin, respectively. Empiric therapy with vancomycin plus an agent for gram-negative coverage was predicted to cover 98.8% to 99.7% of blood isolates from hemodialysis patients, whereas cefazolin plus an agent for gram-negative coverage would cover only 67.5% to 68.4%., Conclusions: In an era of increasing antimicrobial resistance, data such as these and ongoing surveillance are essential components of antimicrobial stewardship in the hemodialysis population., Competing Interests: Competing interests: Wolters Kluwer-Lexicomp has asked J Christine Davis to be a consultant (compensated) for drug dosing in kidney disease (outside the submitted work). No other competing interests declared., (2020 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

♦ BACKGROUND: Information related to the microbiology of peritonitis is critical to the optimal management of patients receiving peritoneal dialysis (PD). The goal was to characterize the microbiological etiology and antimicrobial susceptibilities of PD-related peritonitis (PDRP) from 2005 to 2014, inclusive. ♦ METHODS: The distribution of organisms in culture-positive PDRP was described for new episodes and relapse infections, and further detailed for monomicrobial and polymicrobial peritonitis. Annual and overall rates of PDRP were also characterized. Antimicrobial susceptibility rates were calculated for the most common and significant organisms. ♦ RESULTS: We identified 539 episodes of PDRP including 501 new and 38 relapse infections. New episodes of peritonitis were associated with a single organism in 85% of cases, and 44% of those involved staphylococci. Polymicrobial PDRP was more likely to involve gram-negative organisms, observed in 58% versus 24% of monomicrobial infections. Antimicrobial resistance was relatively stable from 2005 to 2014. Methicillin resistance was present in 57% of Staphylococcus epidermidis and 20% of other coagulase-negative staphylococci. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for only 11% of S. aureus peritonitis compared with 2% in our previous study of PDRP from 1991 to 1998. Ciprofloxacin resistance in Escherichia coli increased from 3% in our previous study to 24% in 2005 - 2014. ♦ CONCLUSIONS: This study characterizes important differences in the distribution of organisms in new episodes of PDRP and relapse infections, as well as monomicrobial versus polymicrobial peritonitis. It also shows relatively stable rates of antimicrobial resistance from 2005 to 2014, but some increases compared with our previous study., (Copyright © 2017 International Society for Peritoneal Dialysis.)

Background: Cocaine is a risk factor for acute kidney injury and chronic kidney disease with progression to end-stage renal disease. Levamisole is an adulterant that is added to cocaine to enhance its euphoric effects. Levamisole-adulterated cocaine (LAC) is associated with the distinct clinical syndromes of agranulocytosis, leukocytoclastic vasculitis, cocaine-induced midline destructive lesions (CIMDL), and ANCA-associated vasculitis (AAV) with pauci-immune necrotizing glomerulonephritis., Methods: We reviewed all cases of AAV secondary to LAC at our institution., Results: We report 3 cases of AAV secondary to LAC and associated membranous nephropathy (MN). The first and second cases are concurrent AAV secondary to LAC and associated MN while the third case involves the development of MN after AAV secondary to LAC., Conclusions: Clinicians should be aware of this novel association of LAC with MN., (© 2017 S. Karger AG, Basel.)

Background: Peritoneal dialysis (PD) for long-term management of diuretic resistant volume overload in heart failure (HF) may provide potential benefit with few adverse consequences. We examined the impact of PD on clinical status hospitalizations, and complications of therapy in severe end-stage HF., Methods: A consecutive case series of 10 transplant ineligible patients receiving PD solely for HF volume management between 2007 and 2011 was evaluated with clinical data reviewed pre- and post-PD initiation., Results: The mean ejection fraction (EF) pre-PD was 24.5 ± 6.0% with the majority of patients having NYHA class IIIB symptoms and moderate-severe right ventricular dysfunction. 9/10 patients were Stage 3 chronic kidney disease (CKD) or worse. After PD initiation, average weight loss was almost 7 kg (p = 0.016) with improvement in diuretic response, peripheral edema, and functional class. There was a significant decrease in re-hospitalization from an average of 3.2 ± 2.5 to 0.1 ± 0.3 admissions per patient (p = 0.007) and reduced average length of stay from 37 ± 36.7 to 0.78 ± 2.3 days (p = 0.019)., Summary: Objective criteriabased institution of PD for the treatment of diuretic refractory severe-end-stage HF was well tolerated and demonstrated favorable outcomes; these included improved clinical status, reduced hospitalizations and length of stay, with very few and easily treatable PDrelated complications. PD appears to be a viable option in refractory, end-stage congestive heart failure (CHF).

Background and Objectives: First Nations (FN) patients on peritoneal dialysis experience poor outcomes. Whether discrepancies exist regarding the microbiology, rate of infections, and outcomes between FN and non-FN peoples remains unknown. Design, setting, participants, & measures: All adult peritoneal dialysis patients (n = 727) from 1997 to 2007 residing in Manitoba, Canada, were included. Parametric and nonparametric tests were used as necessary. Negative binomial regression was used to determine the relationship of rates of exit site infections (ESIs) and peritonitis between FN and non-FN peoples., Results: A total of 161 FN and 566 non-FN subjects were included in the analyses. The unadjusted relative rates of peritonitis and ESIs in FN subjects were 132.7 and 86.0/100 patient-years compared with 87.8 and 78.2/100 patient-years in non-FN populations, respectively. FN subjects were more likely to have culture-negative peritonitis (36.5 versus 20.8%, P < 0.0001) and Staphylococcus ESIs (54.1 versus 32.9%, P < 0.0001). The crude and adjusted rates of peritonitis were higher in FN subjects for total episodes and culture-negative and gram-negative peritonitis. Catheter removal because of peritonitis was similar in both groups (42.9 versus 38.1% for FN and non-FN subjects, respectively; P = 0.261)., Conclusions: FN patients experience higher rates of peritonitis and similar rates of ESIs compared with non-FN patients. Interventions to improve outcomes and prevent infections should specifically be targeted to the FN population.

Background: The Aboriginal population in Canada experiences high rates of end-stage renal disease and need for dialytic therapies. Our objective was to examine rates of mortality, technique failure and peritonitis among adult aboriginal patients receiving peritoneal dialysis in the province of Manitoba. We also aimed to explore whether differences in these rates may be accounted for by location of residence (i.e., urban versus rural)., Methods: We included all adult patients residing in the province of Manitoba who received peritoneal dialysis during the period from 1997-2007 (n = 727). We extracted data from a local administrative database and from the Canadian Organ Replacement Registry and the Peritonitis Organism Exit-sites/Tunnel infections (POET) database. We used Cox and logistic regression models to determine the relationship between outcomes and Aboriginal ethnicity. We performed Kaplan-Meier analyses to examine the relationship between outcomes and urban (i.e., 50 km or less from the primary dialysis centre in Winnipeg) versus rural (i.e., more than 50 km from the centre) residency among patients who were aboriginal., Results: One hundred sixty-one Aboriginal and 566 non-Aboriginal patients were included in the analyses. Adjusted hazard ratios for mortality (HR 1.476, CI 1.073-2.030) and adjusted time to peritonitis (HR 1.785, CI 1.352-2.357) were significantly higher among Aboriginal patients than among non-Aboriginal patients. We found no significant differences in mortality, technique failure or peritonitis between urban- or rural-residing Aboriginal patients., Interpretation: Compared with non-Aboriginal patients receiving peritoneal dialysis, Aboriginal patients receiving peritoneal dialysis had higher mortality and faster time to peritonitis independent of comorbidities and demographic characteristics. This effect was not influenced by place of residence, whether rural or urban.