Pharmacokinetics of intravenous piperacillin/tazobactam among patients with peritoneal dialysis-associated peritonitis.

Currently, pharmacokinetic information on intravenous (IV) piperacillin/tazobactam in patients with peritoneal dialysis-associated peritonitis (PD peritonitis) is limited. This study employed a prospective single-dose pharmacokinetic design to assess the pharmacokinetics of IV piperacillin/tazobactam in these patients. Four patients with PD peritonitis who received an IV loading dose of 4000 mg/500 mg piperacillin/tazobactam were enrolled in this study. The concentrations of piperacillin and tazobactam in plasma, peritoneal dialysis fluid (PDF) and urine were determined by high-performance liquid chromatography. Non-compartmental methods were used for pharmacokinetic analysis. During a 6-h dwell time for chronic ambulatory peritoneal dialysis (CAPD), 9.23 ± 4.01% of the piperacillin was recovered in the PDF. This result is greater than that observed in patients without peritonitis in prior research. Piperacillin's PD clearance (CLPD), steady-state volume of distribution (Vss) and terminal half-life (t 1/2) were 5.79 ± 2.55 mL/min, 24.35 ± 11.26 L and 5.74 ± 1.53 h, respectively. These values are also higher than those of patients without peritonitis in a prior study. Eight hours following the loading dosage, the plasma and PDF piperacillin concentrations of all patients (98.25 ± 26.03 and 52.70 ± 22.99 mg/L, respectively) surpassed the Pseudomonas aeruginosa and Enterobacterales Clinical and Laboratory Standards Institute susceptible breakpoints. In summary, the CLPD, Vss and t 1/2 for piperacillin were found to be greater in patients with PD peritonitis than in CAPD patients without peritonitis when compared with the results of a previous study. The IV loading dose of 4000 mg/500 mg piperacillin/tazobactam is sufficient to treat peritonitis caused by susceptible P. aeruginosa and Enterobacterales. The multiple-dose pharmacokinetics of IV piperacillin and tazobactam in this specific patient group should be further investigated.

Serum Galactomannan: A Predictor of Poor Outcomes in Peritoneal Dialysis Patients With Fungal Peritonitis.

Introduction: The potential value of serum galactomannan index (GMI) in monitoring treatment response in patients with fungal peritonitis who are receiving peritoneal dialysis (PD) was assessed in the present study. Methods: The study included all Thailand fungal PD-related infectious complications surveillance (MycoPDICS) DATA study participants who had timely PD catheter removal and availability of both baseline and ≥2 subsequent serum GMI measurements after starting antifungal therapy (if available). Serum GMI was assessed by direct double-sandwich enzyme-linked immunosorbent assay with reference to positive and negative control samples. Comparisons of categorical variables among groups were analyzed by Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous variables. Mortality outcomes were analyzed by survival analyses using Kaplan-Meier curves with Log-rank test. Results: Seventy-six (46%) of 166 participants from 21 PD centers between 2018 and 2022 were included. The median age was 58 (50-65) years, and a half of the patients (50%) had type II diabetes. Nineteen (25%) and 57 (75%) episodes were caused by yeast and mold, respectively. Death occurred in 11 (14%) patients at 3 months, and no differences were observed in demographics, laboratories, treatment characteristics, or in baseline serum GMI between those who died and those who survived. Serum GMI progressively declined over the follow-up period after the completion of treatment. Patients who died had significantly higher posttreatment serum GMI levels and were more likely to have positive GMI after treatment. Conclusion: Serum GMI is an excellent biomarker for risk stratification and treatment response monitoring in patients on PD with fungal peritonitis.

Peritoneal dialysis-associated peritonitis from pauci-septated mold: Life-threatening but curable.

Two cases of PD-associated peritonitis due to Cunninghamella (C. bertholletiae and C. guizhouensis) were reported here with favorable outcomes, albeit presenting with septicemia. Both patients presented with classic features of bacterial peritonitis, cloudy effluent with a neutrophil predominance, followed by fever and septicemia/septic shock. The pathogen species were confirmed and verified by molecular phylogeny using universal and specific fungal primers. All isolations were susceptible/intermediately susceptible to amphotericin B but resistant to other antifungal agents, including triazoles, caspofungin, and terbinafine. Both cases were successfully treated with timely PD catheter removal and antifungal medications for 2-4 weeks.

Constipation and clinical outcomes in peritoneal dialysis: Results from Thailand PDOPPS.

BACKGROUND: Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes. METHODS: We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis. RESULTS: Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin. CONCLUSION: Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.

Peritonitis due to Aspergillus tamarii in peritoneal dialysis patients.

Aspergillus peritonitis is uncommon, but it is associated with high mortality and morbidity in patients undergoing peritoneal dialysis (PD). We report two cases of Aspergillus tamarii peritonitis that were initially misidentified as A. flavus by the conventional culture method. Nucleotide sequences of internal transcribed spacer regions of the ribosomal DNA gene as A. tamarii correctly identified the isolate. Despite early catheter removal and an appropriate antifunal agent, both patients had dismal outcomes. Nucleic acid sequencing offers an additional tool for better diagnosing the species within the genus of pathogenic microbes.

Predictors and outcomes of peritoneal dialysis-related infections due to filamentous molds (MycoPDICS).

INTRODUCTION: We sought to evaluate the predictors and outcomes of mold peritonitis in patients with peritoneal dialysis (PD). METHODS: This cohort study included PD patients from the MycoPDICS database who had fungal peritonitis between July 2015-June 2020. Patient outcomes were analyzed by Kaplan Meier curves and the Log-rank test. Multivariable Cox proportional hazards model regression was used to estimating associations between fungal types and patients' outcomes. RESULTS: The study included 304 fungal peritonitis episodes (yeasts n = 129, hyaline molds n = 122, non-hyaline molds n = 44, and mixed fungi n = 9) in 303 patients. Fungal infections were common during the wet season (p <0.001). Mold peritonitis was significantly more frequent in patients with higher hemoglobin levels, presentations with catheter problems, and positive galactomannan (a fungal cell wall component) tests. Patient survival rates were lowest for non-hyaline mold peritonitis. A higher hazard of death was significantly associated with leaving the catheter in-situ (adjusted hazard ratio [HR] = 6.15, 95%confidence interval [CI]: 2.86-13.23) or delaying catheter removal after the diagnosis of fungal peritonitis (HR = 1.56, 95%CI: 1.00-2.44), as well as not receiving antifungal treatment (HR = 2.23, 95%CI: 1.25-4.01) or receiving it for less than 2 weeks (HR = 2.13, 95%CI: 1.33-3.43). Each additional day of antifungal therapy beyond the minimum 14-day duration was associated with a 2% lower risk of death (HR = 0.98, 95%CI: 0.95-0.999). CONCLUSION: Non-hyaline-mold peritonitis had worse survival. Longer duration and higher daily dosage of antifungal treatment were associated with better survival. Deviations from the 2016 ISPD Peritonitis Guideline recommendations concerning treatment duration and catheter removal timing were independently associated with higher mortality.

Implementation of PDOPPS in a middle-income country: Early lessons from Thailand.

BACKGROUND: Despite the implementation of a 'Peritoneal Dialysis (PD) First' policy in Thailand since 2008, nationwide PD practices and patients' outcomes have rarely been reported. METHODS: As part of the multinational PD Outcomes and Practice Patterns Study (PDOPPS), PD patients from 22 PD centres from different geographic regions, sizes and affiliations, representing Thailand PD facilities, have been enrolled starting in May 2016. Demographic, clinical and laboratory data and patients' outcomes were prospectively collected and analysed. RESULTS: The pilot and implementation phases demonstrated excellent concordance between study data and validation data collected at enrolment. In the implementation phase, 848 PD patients (including 262 (31%) incident PD patients) were randomly sampled from 5090 patients in participating centres. Almost all participants (95%) performed continuous ambulatory PD (CAPD), and a high proportion had hypoalbuminemia (67%, serum albumin < 3.5 g/dL), anaemia (42%, haemoglobin <10 g/dL) and hypokalaemia (37%, serum potassium < 3.5 mmol/L). The peritonitis rate was 0.40 episodes/year, but the culture-negative rate was high (0.13 episodes/year, 28% of total episodes). The patients from PD clinics located in Bangkok metropolitan region had higher socio-economic status, more optimal nutritional markers, blood chemistries, haemoglobin level and lower peritonitis rates compared to the provincial regions, emphasizing the centre effect on key success factors in PD. CONCLUSIONS: Participation in the PDOPPS helps unveil the critical barriers to improving outcomes of PD patients in Thailand, including a high prevalence of hypokalaemia, anaemia, poor nutritional status and culture-negative peritonitis. These factors should be acted upon to formulate solutions and implement quality improvement on a national level.

Association of Local Unit Sampling and Microbiology Laboratory Culture Practices With the Ability to Identify Causative Pathogens in Peritoneal Dialysis-Associated Peritonitis in Thailand.

INTRODUCTION: This describes variations in facility peritoneal dialysis (PD) effluent (PDE) culture techniques and local microbiology laboratory practices, competencies, and quality assurance associated with peritonitis, with a specific emphasis on factors associated with culture-negative peritonitis (CNP). METHODS: Peritonitis data were prospectively collected from 22 Thai PD centers between May 2016 and October 2017 as part of the Peritoneal Dialysis Outcomes and Practice Patterns Study. The first cloudy PD bags from PD participants with suspected peritonitis were sent to local and central laboratories for comparison of pathogen identification. The associations between these characteristics and CNP were evaluated. RESULTS: CNP was significantly more frequent in local laboratories (38%) compared with paired PDE samples sent to the central laboratory (12%, P < 0.05). Marked variations were observed in PD center practices, particularly with respect to specimen collection and processing, which often deviated from International Society for Peritoneal Dialysis Guideline recommendations, and laboratory capacities, capabilities, and certification. Lower rates of CNP were associated with PD nurse specimen collection, centrifugation of PDE, immediate transfer of samples to the laboratory, larger hospital size, larger PD unit size, availability of an on-site nephrologist, higher laboratory capacity, and laboratory ability to perform aerobic cultures, undertake standard operating procedures in antimicrobial susceptibilities, and obtain local accreditation. CONCLUSION: There were large variations in PD center and laboratory capacities, capabilities, and practices, which in turn were associated with the likelihood of culturing and correctly identifying organisms responsible for causing PD-associated peritonitis. Deviations in practice from International Society for Peritoneal Dialysis guideline recommendations were associated with higher CNP rates.

Effect of fish oil on oxidative stress, lipid profile and renal function in IgA nephropathy.

The omega-3 polyunsaturated fatty acids in fish oil have been shown to produce beneficial effects, such as a reduction in blood pressure, proteinuria, lipid levels and inflammation. Aggregated immunoglobulin A obtained from IgA nephropathy patients induced greater oxygen free radicals in polymorphonuclear leukocytes than other glomerulopathy. All of which may affect the course of IgA nephropathy. Twenty-three adult patients with biopsy proven IgA nephropathy, with proteinuria more than 1 g/day, serum creatinine less than 3 mg/dl and blood pressure control less than 130/80 mmHg were given omega-3 polyunsaturated fatty acids (PUFA) in the form of an Omacor capsule 4 g/day equivalent to eicosapentaenoic acid (EPA) 1.88 g and docosahexaenoic acid (DHA) 1.48 g for 6 months. A 3 to 6 month follow-up was planned, with monthly evaluations of the patients. By six months, the serum triglyceride was significantly reduced (143.45 +/- 62.65 vs 91 +/- 42.89 mg/dl, p = 0.002), serum cholesterol was also reduced but not statistically significant (234.16 +/- 56.29 vs 219.76 +/- 51.25 mg/dl, p = 0.07). There was a trend of increased serum high density lipoprotein (HDL)-cholesterol (39.26 +/- 10.56 vs 42.72 +/- 8.37 mg/dl, p = 0.056). Urine beta-2-microglobulin was elevated in IgA patients and decreased statistically significant after 3 months (453 +/- 580 vs 308 +/- 274 microg/24 h, p < 0.001) and 6 months of fish oil therapy (453 +/- 580 vs 142 +/- 182, p < 0.03) while urine N-acetyl-glucosaminidase (NAG) was of no significant difference both before and after fish oil administration (21 +/- 10 vs 22 +/- 10 and 21 +/- 9 U/24 h, p = 0.08). Plasma malondialdehyde (MDA), the end product of oxidative stress was statistically, significantly decreased (1.09 +/- 0.51 vs 0.89 +/- 0.49 nmol/L, p = 0.003). The study did not show any change in blood pressure, proteinuria, or serum creatinine. The authors conclude from the results of this study that patients with idiopathic IgA nephropathy with proteinuria and mildly reduced GFR did not benefit from short-term treatment with 4 g per day of omega-3 PUFA regarding the total protein excretion and glomerular filtration rate (GFR), but the advantage was the improvement in tubular dysfunction, lipid profiles, and oxidative stress.