A different PET test: The relationship between pet ownership and peritonitis risk in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

Pet ownership is common around the world, with pet ownership increasing in many countries. Current guidelines are not supportive of pet ownership for peritoneal dialysis (PD) patients. We examined the association between ownership of cats and dogs and the incidence of peritonitis among PD patients participating in the prospective, observational Peritoneal Dialysis Outcomes and Practice Patterns Study. A total of 3655 PD patients from eight different countries was included, with a median follow-up of 14 months and a total exposure time of 55,475 patient-months. There were 1347 peritonitis episodes with an overall peritonitis rate of 0.29 episodes per patient year. There was no significant increased risk of peritonitis with any type of pet ownership, adjusted hazard ratio (HR) of 1.09 (95% confidence interval (95% CI): 0.96-1.25). However, patients who owned both cats and dogs had an increased risk of peritonitis compared to patients without pets, HR = 1.45 (95% CI: 1.14-1.86). These results suggest that there is no increased risk of peritonitis with pet ownership except for those with both cats and dogs. This information should not prevent PD patients from owning pets but may be helpful for PD patients and their care team to direct training to minimise the risk of peritonitis.

Peritoneal Dialysis-Associated Peritonitis Trends Using Medicare Claims Data, 2013-2017.

RATIONALE & OBJECTIVE: The occurrence and consequences of peritoneal dialysis (PD)-associated peritonitis limit its use in populations with kidney failure. Studies of large clinical populations may enhance our understanding of peritonitis. To facilitate these studies we developed an approach to measuring peritonitis rates using Medicare claims data to characterize peritonitis trends and identify its clinical risk factors. STUDY DESIGN: Retrospective cohort study of PD-associated peritonitis. SETTING & PARTICIPANTS: US Renal Data System standard analysis files were used for claims, eligibility, modality, and demographic information. The sample consisted of patients receiving PD treated at some time between 2013 and 2017 who were covered by Medicare fee-for-service (FFS) insurance with paid claims for dialysis or hospital services. EXPOSURES/PREDICTORS: Peritonitis risk was characterized by year, age, sex, race, ethnicity, vintage of kidney replacement therapy, cause of kidney failure, and prior peritonitis episodes. OUTCOME: The major outcome was peritonitis, identified using ICD-9 and ICD-10 diagnosis codes. Closely spaced peritonitis claims (30 days) were aggregated into 1 peritonitis episode. ANALYTICAL APPROACH: Patient-level risk factors for peritonitis were modeled using Poisson regression. RESULTS: We identified 70,271 peritonitis episodes from 396,289 peritonitis claims. Although various codes were used to record an episode of peritonitis, none was used predominantly. Peritonitis episodes were often identified by multiple aggregated claims, with the mean and median claims per episode being 5.6 and 2, respectively. We found 40% of episodes were exclusively outpatient, 9% exclusively inpatient, and 16% were exclusively based on codes that do not clearly distinguish peritonitis from catheter infections/inflammation ("catheter codes"). The overall peritonitis rate was 0.54 episodes per patient-year (EPPY). The rate was 0.45 EPPY after excluding catheter codes and 0.35 EPPY when limited to episodes that only included claims from nephrologists or dialysis providers. The peritonitis rate declined by 5%/year and varied by patient factors including age (lower rates at higher ages), race (Black > White>Asian), and prior peritonitis episodes (higher rate with each prior episode). LIMITATIONS: Coding heterogeneity indicates a lack of standardization. Episodes based exclusively on catheter codes could represent false positives. Peritonitis episodes were not validated against symptoms or microbiologic data. CONCLUSIONS: PD-associated peritonitis rates decline over time and were lower among older patients. A claims-based approach offers a promising framework for the study of PD-associated peritonitis.

Establishing a Core Outcome Measure for Peritoneal Dialysis-related Peritonitis: A Standardized Outcomes in Nephrology-Peritoneal Dialysis Consensus Workshop Report.

Introduction: Peritoneal dialysis (PD)-related peritonitis is one of the leading causes of discontinuation of PD and is considered a critically important outcome for patients on PD. However, there is no universally accepted method of measuring this outcome in clinical trials. Methods: We convened an online consensus workshop to establish a core outcome measure for PD-related peritonitis in clinical trials. Results: A total of 53 participants, including 18 patients and caregivers, from 12 countries engaged in breakout discussions in this workshop. Transcripts were analyzed thematically. We identified the following 3 themes: (i) feasibility and applicability across diverse settings, which reflected the difficulty with implementing laboratory-based measures in resource-limited environments; (ii) ensuring validity, which included minimizing false positives and considering the specificity of symptoms; and (iii) being meaningful and tangible to patients, which meant that the measure should be easy to interpret, reflect the impact that symptoms have on patients, and promote transparency by standardizing the reporting of peritonitis among dialysis units. Conclusion: A core outcome measure for PD-related peritonitis should include both symptom-based and laboratory-based criteria. Thus, the International Society for Peritoneal Dialysis (ISPD) definition of peritonitis is acceptable. However, there should be consideration of reporting suspected peritonitis in cases where laboratory confirmation is not possible. The measure should include all infections from the time of catheter insertion and capture both the rate of infection and the number of patients who remain peritonitis free. A core outcome measure with these features would increase the impact of clinical trials on the care and decision-making of patients receiving PD.

ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment.

Peritoneal dialysis (PD)-associated peritonitis is a serious complication of PD and prevention and treatment of such is important in reducing patient morbidity and mortality. The ISPD 2022 updated recommendations have revised and clarified definitions for refractory peritonitis, relapsing peritonitis, peritonitis-associated catheter removal, PD-associated haemodialysis transfer, peritonitis-associated death and peritonitis-associated hospitalisation. New peritonitis categories and outcomes including pre-PD peritonitis, enteric peritonitis, catheter-related peritonitis and medical cure are defined. The new targets recommended for overall peritonitis rate should be no more than 0.40 episodes per year at risk and the percentage of patients free of peritonitis per unit time should be targeted at >80% per year. Revised recommendations regarding management of contamination of PD systems, antibiotic prophylaxis for invasive procedures and PD training and reassessment are included. New recommendations regarding management of modifiable peritonitis risk factors like domestic pets, hypokalaemia and histamine-2 receptor antagonists are highlighted. Updated recommendations regarding empirical antibiotic selection and dosage of antibiotics and also treatment of peritonitis due to specific microorganisms are made with new recommendation regarding adjunctive oral N-acetylcysteine therapy for mitigating aminoglycoside ototoxicity. Areas for future research in prevention and treatment of PD-related peritonitis are suggested.

International peritoneal dialysis training practices and the risk of peritonitis.

BACKGROUND: The effects of training practices on outcomes of patients receiving peritoneal dialysis (PD) are poorly understood and there is a lack of evidence informing best training practices. This prospective cohort study aims to describe and compare international PD training practices and their association with peritonitis. METHODS: Adult patients on PD <3 months participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) were included. Training characteristics (including duration, location, nurse affiliation, modality, training of family members, use of individual/group training and use of written/oral competency assessments) were reported at patient and facility levels. The hazard ratio (HR) for time to first peritonitis was estimated using Cox models, adjusted for selected patient and facility case-mix variables. RESULTS: A total of 1376 PD patients from 120 facilities across seven countries were included. Training was most commonly performed at the facility (81%) by facility-affiliated nurses (87%) in a 1:1 setting (79%). In the UK, being trained by both facility and third-party nurses was associated with a reduced peritonitis risk [adjusted HR 0.31 (95% confidence interval 0.15-0.62) versus facility nurses only]. However, this training practice was utilized in only 5 of 14 UK facilities. No other training characteristics were convincingly associated with peritonitis risk. CONCLUSIONS: There was no evidence to support that peritonitis risk was associated with when, where, how or how long PD patients are trained.

Variation in Peritoneal Dialysis-Related Peritonitis Outcomes in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

RATIONALE & OBJECTIVE: Peritoneal dialysis (PD)-associated peritonitis is a significant PD-related complication. We describe the likelihood of cure after a peritonitis episode, exploring its association with various patient, peritonitis, and treatment characteristics. STUDY DESIGN: Observational prospective cohort study. SETTING & PARTICIPANTS: 1,631 peritonitis episodes (1,190 patients, 126 facilities) in Australia, New Zealand, Canada, Japan, Thailand, the United Kingdom, and the United States. EXPOSURE: Patient characteristics (demographics, patient history, laboratory values), peritonitis characteristics (organism category, concomitant exit-site infection), dialysis center characteristics (use of icodextrin and low glucose degradation product solutions, policies regarding antibiotic self-administration), and peritonitis treatment characteristics (antibiotic used). OUTCOME: Cure, defined as absence of death, transfer to hemodialysis (HD), PD catheter removal, relapse, or recurrent peritonitis within 50 days of a peritonitis episode. ANALYTICAL APPROACH: Mixed-effects logistic models. RESULTS: Overall, 65% of episodes resulted in a cure. Adjusted odds ratios (AOR) for cure were similar across countries (range, 54%-68%), by age, sex, dialysis vintage, and diabetes status. Compared with Gram-positive peritonitis, the odds of cure were lower for Gram-negative (AOR, 0.41 [95% CI, 0.30-0.57]), polymicrobial (AOR, 0.30 [95% CI, 0.20-0.47]), and fungal (AOR, 0.01 [95% CI, 0.00-0.07]) peritonitis. Odds of cure were higher with automated PD versus continuous ambulatory PD (AOR, 1.36 [95% CI, 1.02-1.82]), facility icodextrin use (AOR per 10% greater icodextrin use, 1.06 [95% CI, 1.01-1.12]), empirical aminoglycoside use (AOR, 3.95 [95% CI, 1.23-12.68]), and ciprofloxacin use versus ceftazidime use for Gram-negative peritonitis (AOR, 5.73 [95% CI, 1.07-30.61]). Prior peritonitis episodes (AOR, 0.85 [95% CI, 0.74-0.99]) and concomitant exit-site infection (AOR, 0.41 [95% CI, 0.26-0.64]) were associated with a lower odds of cure. LIMITATIONS: Sample selection may be biased and generalizability may be limited. Residual confounding and confounding by indication limit inferences. Use of facility-level treatment variables may not capture patient-level treatments. CONCLUSIONS: Outcomes after peritonitis vary by patient characteristics, peritonitis characteristics, and modifiable peritonitis treatment practices. Differences in the odds of cure across infecting organisms and antibiotic regimens suggest that organism-specific treatment considerations warrant further investigation.

Intraperitoneal pharmacokinetics of vancomycin in patients on automated peritoneal dialysis.

It is unclear if the pharmacokinetics of vancomycin are the same during automated peritoneal dialysis (APD), where cycler exchanges may affect the systemic, peritoneal, and urinary disposition of drug. We conducted a prospective pharmacokinetic study evaluating the pharmacokinetics of vancomycin in plasma, dialysis fluid, and urine in peritonitis-negative patients on APD. Patients underwent four drug-free exchanges with 1.5% or 2.5% dextrose following the initial dwell period. Plasma, dialysis fluid, and urine was collected over the course of 7 days for pharmacokinetic analysis. Four patients completed the study with no adverse events. Following a median (range) dwell of 14.6 (14.2-17.6 h), the mean (±SD) observed maximum plasma concentration was 28.7 ± 4.9 mg/L with a mean bioavailability of 98.5 ± 1.4% prior to starting the cycler. The overall mean total plasma clearance estimated from study start to completion was 7.6 ± 1.2 ml/min. Mean total clearance during the dialytic exchange was 13.6 ± 4.9 ml/min. In patients with residual renal function, the mean vancomycin renal clearance was 3.1 ± 1.5 ml/min, representing 21.4%-58.9% of the overall total plasma clearance during the study period. Despite the small sample size, this pilot study suggests that the dwell time has important implications for systemic vancomycin exposure, time to therapeutic plasma concentration, and dosing. Dose is driven by dwell time, whereas the cycler determines the dosing interval. Rapid exchanges from APD will determine the frequency of dosing rather than the adequacy of absorption when vancomycin is given in the peritoneum.

Optimizing Peritoneal Dialysis-Associated Peritonitis Prevention in the United States: From Standardized Peritoneal Dialysis-Associated Peritonitis Reporting and Beyond.

Peritoneal dialysis (PD)-associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.

Peritoneal dialysis-associated peritonitis outcomes reported in trials and observational studies: A systematic review.

BACKGROUND: Peritoneal dialysis (PD)-associated peritonitis carries significant morbidity, mortality, and is a leading cause of PD technique failure. This study aimed to assess the scope and variability of PD-associated peritonitis reported in randomized trials and observational studies. METHODS: Cochrane Controlled Register of Trials, MEDLINE, and Embase were searched from 2007 to June 2018 for randomized trials and observational studies in adult and pediatric patients on PD that reported PD-associated peritonitis as a primary outcome or as a part of composite primary outcome. We assessed the peritonitis definitions used, characteristics of peritonitis, and outcome reporting and analysis. RESULTS: Seventy-seven studies were included, three were randomized trials. Thirty-eight (49%) of the included studies were registry-based observational studies. Twenty-nine percent (n = 22) of the studies did not specify how PD-associated peritonitis was defined. Among those providing a definition of peritonitis, three components were reported: effluent cell count (n = 42, 54%), clinical features consistent with peritonitis (e.g. abdominal pain and/or cloudy dialysis effluent) (n = 35, 45%), and positive effluent culture (n = 19, 25%). Of those components, 1 was required to make the diagnosis in 6 studies (8%), 2 out of 2 were required in 22 studies (29%), 2 out of 3 in 11 studies (14%), and 3 out of 3 in 4 studies (5%). Peritonitis characteristics and outcomes reported across studies included culture-negative peritonitis (n = 47, 61%), refractory peritonitis (n = 42, 55%), repeat peritonitis (n = 9, 12%), relapsing peritonitis (n = 5, 7%), concomitant exit site (n = 16, 21%), and tunnel infections (n = 8, 10%). Peritonitis-related hospitalization was reported in 38% of the studies (n = 29), and peritonitis-related mortality was variably defined and reported in 55% of the studies (n = 42). Peritonitis rate was most frequently reported as episodes per patient year (n = 40, 52%). CONCLUSION: Large variability exists in the definitions, methods of reporting, and analysis of PD-associated peritonitis across trials and observational studies. Standardizing definitions for reporting of peritonitis and associated outcomes will better enable assessment of the comparative effect of interventions on peritonitis. This will facilitate continuous quality improvement measures through reliable benchmarking of this patient-important outcome across centers and countries.

Vancomycin in peritoneal dialysis: Clinical pharmacology considerations in therapy.

Intraperitoneal vancomycin is the first-line therapy in the management of peritoneal dialysis (PD)-related peritonitis. However, due to the paucity of data, vancomycin dosing for peritonitis in patients on automated peritoneal dialysis (APD) is empiric and based on clinical experience rather than evidence. Studies in continuous ambulatory peritoneal dialysis (CAPD) patients have been used to provide guidelines for dosing and are often extrapolated for APD use, but it is unclear whether this is appropriate. This review summarizes the available pharmacokinetic data used to inform optimal dosing in patients on CAPD or APD. The determinants of vancomycin disposition and pharmacodynamic effects are critically summarized, knowledge gaps explored, and a vancomycin dosing algorithm in PD patients is proposed.

Peritoneal Dialysis-Related Infection Rates and Outcomes: Results From the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

RATIONALE & OBJECTIVE: Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). STUDY DESIGN: Observational prospective cohort study. SETTING & PARTICIPANTS: 7,051 adult PD patients in 209 facilities across 7 countries (Australia, New Zealand, Canada, Japan, Thailand, United Kingdom, United States). EXPOSURES: Facility characteristics (census count, facility age, nurse to patient ratio) and selected facility practices (use of automated PD, use of icodextrin or biocompatible PD solutions, antibiotic prophylaxis strategies, duration of PD training). OUTCOMES: Peritonitis rate (by country, overall and variation across facilities), microbiology patterns. ANALYTICAL APPROACH: Poisson rate estimation, proportional rate models adjusted for selected patient case-mix variables. RESULTS: 2,272 peritonitis episodes were identified in 7,051 patients (crude rate, 0.28 episodes/patient-year). Facility peritonitis rates were variable within each country and exceeded 0.50/patient-year in 10% of facilities. Overall peritonitis rates, in episodes per patient-year, were 0.40 (95% CI, 0.36-0.46) in Thailand, 0.38 (95% CI, 0.32-0.46) in the United Kingdom, 0.35 (95% CI, 0.30-0.40) in Australia/New Zealand, 0.29 (95% CI, 0.26-0.32) in Canada, 0.27 (95% CI, 0.25-0.30) in Japan, and 0.26 (95% CI, 0.24-0.27) in the United States. The microbiology of peritonitis was similar across countries, except in Thailand, where Gram-negative infections and culture-negative peritonitis were more common. Facility size was positively associated with risk for peritonitis in Japan (rate ratio [RR] per 10 patients, 1.07; 95% CI, 1.04-1.09). Lower peritonitis risk was observed in facilities that had higher automated PD use (RR per 10 percentage points greater, 0.95; 95% CI, 0.91-1.00), facilities that used antibiotics at catheter insertion (RR, 0.83; 95% CI, 0.69-0.99), and facilities with PD training duration of 6 or more (vs <6) days (RR, 0.81; 95% CI, 0.68-0.96). Lower peritonitis risk was seen in facilities that used topical exit-site mupirocin or aminoglycoside ointment, but this association did not achieve conventional levels of statistical significance (RR, 0.79; 95% CI, 0.62-1.01). LIMITATIONS: Sampling variation, selection bias (rate estimates), and residual confounding (associations). CONCLUSIONS: Important international differences exist in the risk for peritonitis that may result from varied and potentially modifiable treatment practices. These findings may inform future guidelines in potentially setting lower maximally acceptable peritonitis rates.

Review of Antibiotic Dosing with Peritonitis in APD.

Peritonitis is the leading cause of transfer from peritoneal dialysis (PD) to hemodialysis (HD). It is also the leading cause of hospitalization of PD patients. The usual treatment of peritonitis for automated PD (APD) patients consists of antibiotics given once daily in the long dwell. However, the once-daily antibiotic dosing recommendations are based primarily on studies with continuous ambulatory PD (CAPD) regimens. Published studies on antibiotic dosing in APD are very limited. We will review the scant literature on this topic. It is possible that extrapolating once-daily dosing from CAPD to APD may lead to underdosing. There is a need for further pharmacokinetic studies of antibiotic dosing in APD.

Regional variation in the treatment and prevention of peritoneal dialysis-related infections in the Peritoneal Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Peritoneal dialysis (PD)-related infections lead to significant morbidity. The International Society for Peritoneal Dialysis (ISPD) guidelines for the prevention and treatment of PD-related infections are based on variable evidence. We describe practice patterns across facilities participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). METHODS: PDOPPS, a prospective cohort study, enrolled nationally representative samples of PD patients in Australia/New Zealand (ANZ), Canada, Thailand, Japan, the UK and the USA. Data on PD-related infection prevention and treatment practices across facilities were obtained from a survey of medical directors'. RESULTS: A total of 170 centers, caring for >11 000 patients, were included. The proportion of facilities reporting antibiotic administration at the time of PD catheter insertion was lowest in the USA (63%) and highest in Canada and the UK (100%). Exit-site antimicrobial prophylaxis was variably used across countries, with Japan (4%) and Thailand (28%) having the lowest proportions. Exit-site mupirocin was the predominant exit-site prophylactic strategy in ANZ (56%), Canada (50%) and the UK (47%), while exit-site aminoglycosides were more common in the USA (72%). Empiric Gram-positive peritonitis treatment with vancomycin was most common in the UK (88%) and USA (83%) compared with 10-45% elsewhere. Empiric Gram-negative peritonitis treatment with aminoglycoside therapy was highest in ANZ (72%) and the UK (77%) compared with 10-45% elsewhere. CONCLUSIONS: Variation in PD-related infection prevention and treatment strategies exist across countries with limited uptake of ISPD guideline recommendations. Further work will aim to understand the impact these differences have on the wide variation in infection risk between facilities and other clinically relevant PD outcomes.

The mystery of the nonfunctioning catheter: An unusual complication of peritoneal dialysis outflow failure.

Noninfectious complications of peritoneal dialysis (PD) remain an important impediment to successful implementation of PD. Rare noninfectious complications of the PD catheter are sparsely reported. We report an unusual complication of outflow failure due to a peritoneal catheter that separated into two distinct intra-abdominal segments, due to an unusual method of placement in which two catheters were connected to make a long intra-abdominal portion to permit a high exit site on the abdominal wall. The application of this unusual rather a unique technique led to separation of the two catheter portions and the outflow failure shortly after the patient started continuous ambulatory PD. We reviewed other unusual causes of PD catheter failure, and these included luminal stones blocking the PD catheter, pneumomediastinum related to inappropriate technique, catheter deformation and leak due to the use of antibiotic ointment at the exit site of polyurethane catheters, vesicoperitoneal fistula and perforation of the bladder from the placement of PD catheters, rare site migrations of the catheter, and subcutaneous titanium connector infection in a presternal catheter. Knowledge of these unusual complications may allow prevention and/or early recognition.