Peritoneal Dialysis-associated Peritonitis Research Articles

A Retrospective Analysis of Peritoneal Dialysis-associated Peritonitis at a Single-care Children’s Hospital in Saudi Arabia

Peritoneal dialysis (PD) may lead to infection, which could cause dialysis failure. Estimates of infectious peritonitis rate, identification of causative microbes, and infection outcomes are scarcely reported in Saudi Arabia. We conducted this study to provide epidemiological data as a geographical reference for PD-associated peritonitis. Epidemiological, microbiological, and clinical data were retrospectively collected from pediatric patients' medical records who were on PD between 2009 and 2018. A total of 54 pediatric patients on PD were involved in the study. The median age of the patients was 3.6 years [interquartile range (IQR) 1.7-8.0]; 56% were female children. The median time spent on PD was 39.5 months (IQR 19.75-64.25), with an overall peritonitis rate of 0.52 episodes per patient-year. In terms of infection, 116 PD-associated peritonitis episodes were identified in 37 patients. There were 38 infection episodes (32.3%) due to skin microbiota, 22 (18.8%) of gut microbiota, 12 (10.2%) of environmental microbiota, three (2.6%) of polymicrobial, and 27 (23.2%) of culture negative peritonitis. There were 45 (39%) episodes of noncomplicated peritonitis and 71 (61%) complicated peritonitis episodes. The latter included 14 (19%) relapses, 45 (63%) repeated infections, and 12 (17%) catheter removals. Using multivariate analysis, the history of peritonitis [OD 7.59, 95% confidence interval (CI) 2.87-20.00] and the presence of cardiovascular disease (OD 3.24,95% CI 1.18-8.85) were independent predictors of a complicated peritonitis episode. History of infectious peritonitis and the presence of cardiovascular disease are potential predictors of complicated PD-associated peritonitis and may provide an identifier of high-risk patients.

The Prevalence of Peritonitis among Pediatric Peritoneal Dialysis Patients at Large Saudi Center.

Peritonitis is a common and serious complication of peritoneal dialysis (PD) and it is a direct or major contributing cause of death in around 16% of PD patients. Severe or prolonged peritonitis leads to structural and functional alterations of the peritoneal membrane, eventually leading to membrane failure, PD technique failure, and conversion to long-term hemodialysis (HD). This is cross-sectional record-based study in which the records of all children aged <14 years with end-stage renal disease on PD either on coiled or straight PD catheter had been reviewed at pediatric nephrology department in a tertiary care hospital, Riyadh, over the period of three years from 2017 to 2019. All information was collected using a structured data collection form. Our study had 30 patients on automated PD with 10 females (33.3%) and 20 males (66.7%) during the study period. The age ranged from 11 months to 14 years with a median 5.5 years, all of them were new to dialysis. A total of 11 out of 30 patients had multiple episodes of PD-associated peritonitis and the prevalence of peritonitis among the 30 patients was 37%. Peritoneal fluid cultures were positive in 100% episodes. Gram-positive, Gram-negative, and fungal organisms were identified in 72.7%, 18.1%, and 9.0% episodes, respectively. The analysis showed the exit-site infection (ESI) to be a risk factor to develop peritonitis, where 21 patients out of 30 had at least one ESI, 52% end by peritonitis in coiled catheter group. No mortality among our cohort of patients was noted, even removal of or changing PD catheter and transfer to HD. Our data showed that the prevalence of peritonitis secondary to ESI with Gram-positive organisms was significantly high, especially in coiled catheter group.

Acinetobacter johnsonii Peritonitis in a Patient on Peritoneal Dialysis: A Case Report and Review of the Literature

Acinetobacter species have important role in modern medicine due to their increasing presence in health-care facilities and antibiotic resistance. They are non-fermentative, aerobic, Gram-negative coccobacilli and are important bacteria causing peritonitis in patients on peritoneal dialysis. Acinetobacter johnsonii is widely found in the aquatic environment and animals. Peritonitis caused by A. johnsonii is rarely encountered and reported. Here we report a case of A. johnsonii peritonitis in a patient on peritoneal dialysis. To the best of our knowledge, this is the first case of peritoneal dialysis-associated peritonitis by A. johnsonii reported from India.

Clinical characteristics and treatment outcomes of first peritonitis in patients receiving long-term peritoneal dialysis: a multicenter study

To analyze the clinical characteristics and treatment outcomes of the first episode of peritoneal dialysis-associated peritonitis (PDAP) in patients receiving long-term peritoneal dialysis. The clinical data of patients with the first episode of PDAP in 4 general hospitals in Jilin Province from 2013 to 2019 were collected retrospectively. According to the duration of dialysis, the patients were divided into long-term (≥36 months) and short-term (< 36 months) dialysis groups for comparison of the clinical data, treatment outcomes and long-term prognostic events. A total of 625 patients with PDAP were enrolled, including 93 on long-term and 532 on short-term dialysis. Compared with those on short-term dialysis, the patients on long-term dialysis had significantly higher hemoglobin levels and lower glomerular filtration rates when the first episode of PDAP occurred (P < 0.05), were more susceptible to gram-negative bacterial infections (P < 0.05), and had significantly lower initial treatment response rate (P=0.009) and complete cure rate (P=0.018) and higher extubation rate (P=0.017). Multivariate logistic regression analysis showed that in patients on long-term dialysis, the risks of extubation and treatment failure for the first episode of PDAP were 3.05 times (OR: 3.05, 95%CI: 1.35-6.91, P=0.008) and 2.81 times (OR: 2.81, 95%CI: 1.45-5.44, P=0.002) those in patients with short-term dialysis, respectively. Fungal infection (OR: 45.40, 95%CI: 1.488-1385.5, P=0.029) and mixed bacterial infection (OR: 16.50, 95%CI: 1.106-246.123, P=0.042) were independent risk factors for treatment failure of the first episode of PDAP in patients on long-term dialysis. Maintenance peritoneal dialysis, technical failure, or all-cause mortality did not differ significantly between the two groups. Multivariate Cox regression analysis suggested that long-term dialysis was not an independent risk factor for technical failure (OR: 1.36, 95%CI: 0.84-2.19, P=0.206) or all-cause mortality (OR: 1.51, 95%CI: 0.97-2.35, P=0.068) in patients with PDAP. Compared with those on short-term dialysis, patients on long-term dialysis are prone to gram-negative bacterial infection when the first episode of PDAP occurs with worse treatment outcomes but similar long-term outcomes. Long-term dialysis is an independent risk factor of extubation and treatment failure for the first episode of PDAP, and fungal and mixed bacterial infections are independent risk factors for treatment failure of the first PDAP in patients with long-term dialysis.

Mycobacterium abscessus - an uncommon, but important cause of peritoneal dialysis-associated peritonitis \u2013 case report and literature review

BackgroundPeritoneal dialysis (PD) is a form of therapy for end-stage kidney disease (ESKD), and peritonitis is a known complication. Mycobacterium (M) species associated peritonitis in PD patients is uncommon. Our experience of managing PD associated peritonitis caused by M abscessus in a middle-aged man with ESKD due to focal segmental glomerulosclerosis is shared in this article with a review of the literature on this condition.Case presentationA 49-year old man presented to our unit with symptoms of peritonitis and cloudy PD effluent. Initial analysis of PD fluid showed Gram stain was negative, with no organism grown. Empirical PD peritonitis treatment with intra-peritoneal antibiotics did not improve his symptoms and he required intravenous antibiotics, PD catheter removal and a switch to haemodialysis. Cultures of the PD fluid later grew M abscessus, and the antibiotic regimen was changed appropriately, leading to clinical improvement.ConclusionM abscessus associated peritonitis in PD patients is rare. It needs to be borne in mind when clinical improvement is not seen with standard broad-spectrum antibiotics, especially in situations where the PD fluid is initially deemed to be culture negative. PD fluid samples should be sent for acid-fast bacillus and if detected, should be further analysed with genome-wide sequencing to confirm the species of the Mycobacterium. Prompt removal of the catheter with peritoneal washout is critical for clinical improvement.

Comparison of clinical features and outcomes in peritoneal dialysis-associated peritonitis patients with and without diabetes: A multicenter retrospective cohort study.

BACKGROUNDThe number of end-stage renal disease patients with diabetes mellitus (DM) who are undergoing peritoneal dialysis is increasing. Peritoneal dialysis-associated peritonitis (PDAP) is a serious complication of peritoneal dialysis leading to technical failure and increased mortality in patients undergoing peritoneal dialysis. The profile of clinical symptoms, distribution of pathogenic organisms, and response of PDAP to medical management in the subset of end-stage renal disease patients with DM have not been reported previously. Discrepant results have been found in long-term prognostic outcomes of PDAP in patients with DM. We inferred that DM is associated with bad outcomes in PDAP patients.AIMTo compare the clinical features and outcomes of PDAP between patients with DM and those without.METHODSIn this multicenter retrospective cohort study, we enrolled patients who had at least one episode of PDAP during the study period. The patients were followed for a median of 31.1 mo. They were divided into a DM group and a non-DM group. Clinical features, therapeutic outcomes, and long-term prognostic outcomes were compared between the two groups. Risk factors associated with therapeutic outcomes of PDAP were analyzed using multivariable logistic regression. A Cox proportional hazards model was constructed to examine the influence of DM on patient survival and incidence of technical failure.RESULTSOverall, 373 episodes occurred in the DM group (n = 214) and 692 episodes occurred in the non-DM group (n = 395). The rates of abdominal pain and fever were similar in the two groups (P > 0.05). The DM group had more infections with coagulase-negative Staphylococcus and less infections with Escherichia coli (E. coli) as compared to the non-DM group (P < 0.05). Multivariate logistic regression analysis revealed no association between the presence of diabetes and rates of complete cure, catheter removal, PDAP-related death, or relapse of PDAP (P > 0.05). Patients in the DM group were older and had a higher burden of cardiovascular disease, with lower level of serum albumin, but a higher estimated glomerular filtration rate (P < 0.05). Cox proportional hazards model confirmed that the presence of diabetes was a significant predictor of all-cause mortality (hazard ratio = 1.531, 95% confidence interval: 1.091-2.148, P < 0.05), but did not predict the occurrence of technical failure (P > 0.05).CONCLUSIONPDAP patients with diabetes have similar symptomology and are predisposed to coagulase-negative Staphylococcus but not E. coli infection compared those without. Diabetes is associated with higher all-cause mortality but not therapeutic outcomes of PDAP.

Patient-Reported Factors and Peritonitis Risk: Results from the Optimizing Prevention of Peritoneal Dialysis-Associated Peritonitis in the US Study (OPPUS)

Patient-Reported Factors and Peritonitis Risk: Results from the Optimizing Prevention of Peritoneal Dialysis-Associated Peritonitis in the US Study (OPPUS)

Continuous ambulatory peritoneal dialysis-associated Histoplasma capsulatum peritonitis: a case report and literature review

BackgroundFungal peritonitis (FP) is a rare complication of peritoneal dialysis. We herein describe the second case in Asia of Histoplasma capsulatum peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD).Case presentationAn 85-year-old woman with end-stage renal disease (ESRD) who had been on CAPD for 3 years and who had a history of 3 prior episodes of peritonitis presented with intermittent abdominal pain for 2 weeks and high-grade fever for 3 days. Elevated white blood cell (WBC) count and rare small oval budding yeasts were found in her peritoneal dialysis (PD) fluid. From this fluid, a white mold colony was observed macroscopically after 7 days of incubation, and numerous large, round with rough-walled tuberculate macroconidia along with small smooth-walled microconidia were observed microscopically upon tease slide preparation, which is consistent with H. capsulatum. The peritoneal dialysis (PD) catheter was then removed, and it also grew H. capsulatum after 20 days of incubation. The patient was switched from CAPD to hemodialysis. The patient was successfully treated with intravenous amphotericin B deoxycholate (AmBD) for 2 weeks, followed by oral itraconazole for 6 months with satisfactory result. The patient remains on hemodialysis and continues to be clinically stable.ConclusionH. capsulatum peritonitis is an extremely rare condition that is associated with high morbidity and mortality. Demonstration of small yeasts upon staining of PD fluid, and isolation of slow growing mold in the culture of clinical specimen should provide important clues for diagnosis of H. capsulatum peritonitis. Prompt removal of the PD catheter and empirical treatment with amphotericin B or itraconazole is recommended until the culture results are known.

Intraperitoneal ampicillin treatment for peritoneal dialysis- related peritonitis with Listeria monocytogenes \u2013 a case report

BackgroundPeritoneal dialysis (PD)-related peritonitis is a rare but serious complication and is associated with increased morbidity and mortality rates. It is most commonly caused by Staphylococcus aureus or Staphylococcus epidermidis, but infection with Listeria monocytogenes may also occur. Recommendations for antibiotic treatment of a Listeria infection are currently based on a small number of case reports and suggest the administration of ampicillin. But unlike vancomycin or gentamicin, for ampicillin the route of application, the dosage, and the duration of treatment have not yet been established. We report a case in which PD-associated peritonitis due to Listeria infection was treated with ampicillin administered intravenously and intraperitoneally, separately and in combination.Case presentationA 72-year-old man with chronic kidney disease stage 5 dialysis (CKDG5D) secondary to hypertension and diabetes was hospitalised in April 2020 because of PD-related peritonitis caused by a Listeria infection. In accordance with the results of resistance tests, the patient was treated with intravenous ampicillin at a dosage of 6 g twice daily. After initial treatment the leukocyte count in the PD effluent had decreased substantially, but it was permanently reduced only with the addition of intraperitoneal ampicillin (4 g daily). Efficient serum concentrations of ampicillin were determined for both routes of administration, intravenous and intraperitoneal.ConclusionThis is the first case report demonstrating that PD-related peritonitis due to Listeria monocytogenes infection can be treated with intraperitoneal ampicillin and monitored by the determination of peripheral serum concentrations of ampicillin.

Intraperitoneal vancomycin for peritoneal dialysis-associated peritonitis in children: Evaluation of loading dose guidelines.

Current pediatric International Society for Peritoneal Dialysis guidelines for initial treatment of peritoneal dialysis (PD)-associated peritonitis suggest either monotherapy with cefepime or double therapy with first-generation cephalosporin or glycopeptide and ceftazidime or aminoglycoside. When using vancomycin, the intraperitoneal (IP) recommended pediatric loading dosage is 1000 mg/L of dialysate. This is based on adult pharmacokinetic (PK) studies and roughly translates to the adult recommendation where 30 mg/kg in 2 L is approximately 1000 mg/L. However, since the dialysate volume in pediatric patients is normalized to body surface area and not weight, the current recommended dosing can result in high vancomycin exposure in children. Vancomycin can potentially cause adverse effects. We aimed to determine if the IP vancomycin dosing of 1000 mg/L was causing elevated vancomycin levels and to offer possible dosing recommendations based on PK modeling and simulation. Retrospective review of pediatric patients who had been treated with IP vancomycin for PD-associated peritonitis. Vancomycin levels obtained for clinical monitoring were analyzed using NONMEM to generate population and individual (empiric Bayesian) estimates of vancomycin PK parameters and estimated peak levels. Predicted vancomycin peaks were also simulated from virtual pediatrics patients 3-70 kg following various dosing strategies. Six episodes of peritonitis in three patients were analyzed. In the two episodes treated with 1000 mg/L, the first vancomycin levels (h post) were 95.6 ug/mL (3) and 49 (33) and following 500 mg/L were 33.2 (11), 30.2 (11), 23.6 (24), and 22.1 (11). All patients were cured of their peritonitis without the need for catheter removal. Based on our population PK model, a 1000 mg/L IP vancomycin loading dose will typically result in peak > 50 mg/L in patients weighing <35 kg and >60 mg/L in patients <15 kg. Vancomycin levels will remain above 20 mg/L for over 2 days without additional vancomycin dosing. The data suggest that a loading dose of vancomycin 1000 mg/L leads to higher than desired vancomycin levels and should be lowered. A 500 mg/L loading dosing appears more appropriate and needs further study.

Incidence and characteristics of methicillin-resistant coagulase-negative Staphylococcus aureus in peritoneal dialysis-associated peritonitis in a single center using molecular methods.

Peritonitis is a serious complication of peritoneal dialysis and coagulase-negative Staphylococcus (CNS) is the most frequent cause of peritoneal dialysis (PD)-infections in many centers. This study aimed to investigate the molecular epidemiology of CNS isolated from PD-peritonitis in a Brazilian single center, focusing on the genetic determinants conferring methicillin resistance. Bacterial strains were isolated from peritoneal fluid of patients presenting PD-peritonitis, identified by phenotypic and molecular methods, and those identified as CNS were submitted to mecA detection, SCCmec, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Over the 18-year period of this study (1995-2011), a total of 878 peritonitis episodes were diagnosed in this unit, 115 were caused by coagulase-negative staphylococci of which 72 by Staphylococcus epidermidis. mecA gene was detected in 55 CNS (47.8%), more frequently on the more recent years. SCCmec type III was the most frequent cassette, followed by SCCmec type IV and SCCmec type II. A diverstity of pulsotypes was observed among the S. epidermidis isolates, but five clusters (based on the 80% cutoff) were identified. Diversified sequence types (ST02, ST05, ST06, ST09, ST23, ST59 and ST371) were detected. Detection of SCCmec type III among coagulase-negative Staphylococcus underscores the role of hospital environments as potential source of methicillin-resistant Staphylococcus causing peritonitis in PD patients.

P1162RED BLOOD CELL DISTRIBUTION WIDTH AND PERITONEAL DIALYSIS-ASSOCIATED PERITONITIS PROGNOSIS

Abstract Background and Aims The red blood cell distribution width (RDW) is a parameter of the heterogeneity of circulating erythrocyte size. Recent researches have pointed out a link among RDW, chronic kidney disease and inflammation. We sought to investigate the prognostic value of baseline RDW in patients with peritoneal dialysis-associated peritonitis (PDAP), which remains unknown. Method Our study included 337 peritonitis episodes experienced by 202 patients who were undergoing continuous ambulatory peritoneal dialysis (CAPD) at a single center from 2013 to 2018. Episodes were categorized according to the tertiles of baseline RDW levels (T1, &amp;lt;13.2%; T2, 13.2 - 14.3%; T3, &amp;gt;14.3%). Routine logistic regression, generalized estimating equation and restricted cubic spline were used to estimate the association between RDW and treatment failure, which was defined as relapse or recurrent episodes, catheter removal, or death during peritonitis therapy. The predictive performance of multivariate models including RDW and other potential predictors were also evaluated. Results After adjusting for other potential predictors, RDW exhibited an incremental relationship with the risk of treatment failure. The baseline RDW of &amp;gt;14.3% (T3) indicated a 43% and 52% increased venture of treatment failure in logistic and GEE analyses, respectively, compared with &amp;lt; 13.2% (T1). As a continuous variable, the fitting curve based on restricted cubic spiline showed that the relationship was nolinearly but positively correlated. The multivariate model A (combined RDW with age, duration on PD, albumin and ferritin) showed an area under the curve (AUC) of 0.671 (95% CI, 0.592 to 0.749) for the prediction of treatment failure. In sensitive analyses, the predictive performances for other unfavourable outcomes were also reliable (AUC for catheter removal, 0.72, 0.62 to 0.81; for relapse or recurrence, 0.61, 0.48 to 0.74). Conclusion Higher levels of baseline RDW was significantly associated with greater rates of treatment failure among peritonitis episodes independent of other potential predictors.

Clinical Manifestations and Therapeutic Implications of Peritonitis

Clinical Manifestations and Therapeutic Implications of Peritonitis Abstract. Peritonitis is a heterogenous disease, commonly classified into three types. Primary peritonitis, defined by the absence of another directly related intraabdominal abnormality, can often be treated conservatively and is thus distinguished from secondary peritonitis, which results from an independent diagnosis like the perforation or necrosis of an intraabdominal organ and usually requires surgical therapy. The more recently defined tertiary peritonitis is a form of secondary peritonitis that relapses or persists after 48 hours of adequate therapy with no surgically removable focus. This article addresses three important clinical manifestations of peritonitis and their therapeutic implications: spontaneous bacterial peritonitis as the mayor manifestation of primary peritonitis; postoperative peritonitis as a severe subform of secondary peritonitis; and peritoneal dialysis-associated peritonitis as a distinctive clinical picture.

The prevalence and bacterial distribution of peritonitis amongst adults undergoing continuous ambulatory peritoneal dialysis at Universitas hospital.

BackgroundPeritonitis is the leading cause of morbidity and technique failure in peritoneal dialysis (PD) patients. The International Society for Peritoneal Dialysis (ISPD) recommends each centre to monitor the peritonitis rates and the causative organisms in order to guide local empiric antibiotic protocols. The aim of this study was to report on the peritonitis rates and describe the causative microorganisms and the antibiotic susceptibility in continuous ambulatory peritoneal dialysis (CAPD) adult patients at the Universitas Academic Hospital.MethodsA single-centre, retrospective descriptive survey was conducted to determine the peritonitis rates in PD patients (January–December 2016). All CAPD patients aged ≥18 years, who presented with clinical features of PD-associated peritonitis, were included. The peritonitis episodes were studied per patient, and the causative microorganisms and the antibiotic susceptibility of the organisms were described.ResultsOne hundred and twenty-eight patients underwent CAPD. The peritonitis rate was 1.45 episodes per year at risk. The prevalence of CAPD patients affected by at least one episode of CAPD-associated peritonitis during 2016 was 56.3%. The majority of episodes (76.7%) (n = 122) were mono-microbial. Gram-positive organisms accounted for 73.0% (n = 116) of the peritonitis episodes, coagulase-negative Staphylococcus being the most common. Gram-negative organisms accounted for 15.7% (n = 25) of the peritonitis episodes, and the common pathogens was Enterobacteriaceae.ConclusionThe peritonitis rate was alarmingly high, with 1.45 episodes per year at risk; this is three times more than the recommended 0.5 episodes per year according to the ISPD guidelines. The culture-negative rate of 8.8% is within ISPD-acceptable limits. There is a need to strengthen preventive measures with regard to peritonitis.

Flexibility in peritoneal dialysis prescription: Impact on technique survival.

Patient burnout is a major cause of technique failure on peritoneal dialysis (PD). Reducing the PD prescription on an individual basis, dependent upon residual kidney function (RKF), may have a role in prolonging time on PD by reducing dialysis burden. This retrospective study aimed to determine the safety and impact of flexible PD prescribing on technique and patient survival. All patients (186) from our centre starting PD from 1st January 2012 to 31st December 2016 were included. Data on dialysis prescription were collected for each patient from the time they had started PD, and dialysis adequacy measured regularly (3-6 monthly) using PD Adequest. Median age at start of dialysis was 61 years. Only 49% started on PD 7 days a week and this dropped to 27% at 3 months following the first clearance test. Over 90% achieved creatinine clearance > 50 L/week/1.73 m2 up to 2 years of follow-up, with 87% achieving this standard at 3 years. Patient and technique survival at 1, 2 and 3 years were 91%, 81%, and 72%, and 89%, 87% and 78% respectively. Factors on univariate analysis affecting technique survival included increasing age (HR 0.98, p = 0.04, 95% CI (0.96-0.999)), two or more episodes of PD-associated peritonitis (HR 4.52, p = 0.00, 95% CI (1.87-10.91)) and increasing PD intensity (HR 3.30, p = 0.02, 95% CI (1.22-8.93)). After multivariate adjustment which included baseline kidney function, low PD intensity continued to be associated with better technique survival (HR 0.17, p = 0.03, 95% CI (0.03-0.85)). Tailoring the PD prescription to RKF enables days off dialysis while still maintaining recommended levels of small solute clearance. This approach reduces dialysis burden and is associated with higher technique survival.

SAT-272 The role of plasma and dialysate vancomycin and amikacin levels in patients with peritoneal dialysis-associated peritonitis

SAT-272 The role of plasma and dialysate vancomycin and amikacin levels in patients with peritoneal dialysis-associated peritonitis

Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions.

Peritonitis is a common and serious complication of peritoneal dialysis (PD). PD-associated peritonitis (PDAP) caused by Pseudomonas is usually resistant to most antibiotics, resulting in high failure rates. Ceftolozane/tazobactam (C/T) has been shown to be effective in treating urinary tract and intra-abdominal infections caused by beta-lactam resistant Pseudomonas and other gram-negative bacteria. Given its favourable adverse effects profile, it has a potential role in the treatment of PDAP caused by Pseudomonas species resistant to other antibiotics. Intraperitoneal administration of antibiotics admixed with PD solutions for the treatment of PDAP is associated with superior outcomes. However, there is a lack of published data on the stability of C/T in PD solutions. Therefore, this study investigated the physical and chemical stability of C/T in commonly used PD solutions at different temperatures. A total of 27 PD bags (3 PD bags for each type of PD solution including Dianeal®, Extraneal®, Balance® and Physioneal® PD bags) containing C/T were prepared and stored at 25°C for 6 h, followed by 4°C for 168 h and then 37°C for 12 h. An aliquot from each PD bag was withdrawn, and the concentration of C/T before (0 h) and after predefined time points was determined using a stability-indicating high-performance liquid chromatography assay. Samples were also assessed for pH, colour change and particulate matter immediately after preparation and on each day of analysis. C/T retained more than 97% of their initial concentration when stored at 25°C for 6 h followed by storage at 4°C for 168 h and then at 37°C for 12 h. Particle formation was not detected at any time under the tested storage conditions. The pH and colour remained essentially unchanged throughout the study. These results provide a platform for clinical studies to determine the safety and therapeutic efficacy of intraperitoneal C/T for the treatment of PDAP caused by resistant Pseudomonas species.

Anti-fibrotic effect of decorin in peritoneal dialysis and PD-associated peritonitis.

BackgroundProgressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We investigated the anti-fibrotic properties of decorin secreted by peritoneal mesothelial cells.MethodsDialysate decorin level in stable PD patients and those with peritonitis was measured. In vitro experiments were conducted to investigate the effect of decorin in fibrotic response in human peritoneal mesothelial cells (HPMC).FindingsIncreasing PD duration was associated with a progressive decrease of dialysate decorin and CA125 levels. Dialysate decorin level correlated with CA125 level. Peritonitis episodes were associated with a massive drop of dialysate decorin, which persisted for over three months despite clinical recovery. Dialysate decorin level correlated with that of TGF-β1, but was inversely related to IL-1β and IL-8. TGF-β1, IL-1β, IL-6, IL-8, or TNF-α reduced decorin secretion in HPMC, but induced fibronectin expression. The effects were mediated in part through increased p38 MAPK and AKT/PI3K phosphorylation. Decorin abrogated the induction of fibronectin expression in mesothelial cells by PD fluids or pro-fibrotic cytokines, through decreased TGF-βRI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3β phosphorylation. Decorin gene-silencing resulted in increased fibronectin expression under these conditions.InterpretationOur data demonstrate anti-fibrotic actions of decorin in HPMC, when these cells are subjected to the pro-fibrotic effect of peritoneal dialysate and pro-fibrotic cytokines in PD, especially during peritonitis.

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

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. 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. 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%). 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.

Pyridine levels in ceftazidime - peritoneal dialysis admixtures stored at body temperature.

For the treatment of peritoneal dialysis-associated peritonitis (PDAP), ceftazidime is routinely admixed with peritoneal dialysis (PD) solutions before its intraperitoneal administration. One of the major degradation products of ceftazidime is pyridine, a potentially toxic compound. Depending on the type of PD solution, ceftazidime is exposed to an environment with acidic or basic pH, and depending on the type of dosing and individual unit practices related to preparation and storage, ceftazidime can be at body temperature for 4-10 h, resulting in potentially varying rates of degradation to pyridine by-product. No study has investigated whether the amount of generated pyridine exceeds the maximum daily exposure limit of 2 mg when ceftazidime-PD admixtures are kept at body temperature. Therefore, the current study aimed to determine the levels of pyridine generated in PD-ceftazidime admixtures kept at 37°C for various time points. Ceftazidime was admixed with 2 L Dianeal (1.5%, 2.5% and 4.25% dextrose) and 2 L Physioneal (1.36%, 2.27% and 3.86% glucose) PD solutions to obtain a concentration of 125 mg/L (continuous dosing model) or 500 mg/L (intermittent dosing model). A total of 36 PD admixtures (3 bags for each type of PD solution and 3 bags for each type of dosing) were prepared and stored at 37°C for 10 h. An aliquot was withdrawn at time 0 (baseline) and after 2, 6, 8 and 10 h of storage. The withdrawn samples were then analysed to determine the concentrations of ceftazidime and pyridine using high-performance liquid chromatography. With the intermittent dosing model (500 mg/L), ceftazidime was found to be stable for only 2 and 6 h when admixed with 3.86% and 2.27% glucose Physioneal PD solutions, respectively. While ceftazidime (500 mg/L) retained more than 90% of its initial concentration in the three types of Dianeal and 1.36% dextrose Physioneal solutions for 10 and 8 h, respectively, the generated amount of pyridine ranged between approximately 290% and 371% more than the daily recommended limit. With the continuous dosing model (125 mg/L), ceftazidime was found to be stable for 6 h in all three types of Physioneal PD solutions, but the total amount of generated pyridine with four daily exchanges (6 h each) was estimated to be 170-360% over the daily recommended limit. Ceftazidime (125 mg/L) was chemically stable when admixed with three types of Dianeal PD solutions and stored at 37°C for 10 h, and the levels of pyridine were estimated to be less than the maximum recommended daily limit. Until the outcomes of this in vitro study are confirmed by appropriate in vivo studies, continuous dosing of ceftzadime-Dianeal admixtures for the treatment of PDAP may be preferred over continuous dosing of ceftazidime-Physioneal admixtures, and intermittent dosing of ceftazidime-Physioneal and ceftazidime-Dianeal admixtures, as ceftazidime remains stable and the generated levels of pyridine are below the maximum recommended daily exposure.