Systematic Review on Treatment and Outcomes of Tuberculous Peritonitis in Patients on Peritoneal Dialysis.

Introduction: Peritoneal dialysis (PD)-associated peritonitis due to tuberculosis (TB) is associated with poor outcomes and optimal treatment strategies for this condition remain unknown. Our study aimed to: (i) systematically review the published literature on peritonitis caused by Mycobacterium tuberculosis in patients on PD and (ii) review cases of peritonitis due to M tuberculosis in patients on PD reported in Australia and New Zealand to determine the epidemiology, management strategies, and outcomes of this condition. Methods: A literature search of Medline, Scopus, Embase, ClinicalTrials.gov, Cochrane CENTRAL Register of Controlled Trials and Google Scholar for articles published from inception date to June 2022 was conducted. To be eligible, articles had to describe patient characteristics, initial anti-TB therapy, and treatment outcomes in all patients on PD with peritonitis caused by M tuberculosis. Data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry of patients on PD who developed peritonitis due to M tuberculosis between September 2001 and December 2020 were included and analyzed. Results: The systematic literature review identified 70 case studies (151 patients) and 8 cohort studies (97 patients), whereas the ANZDATA Registry identified 17 cases of peritonitis due to M tuberculosis. Overall, in patients diagnosed with peritonitis due to M tuberculosis, the rates of PD catheter removal and permanent transfer to hemodialysis (HD) were numerically higher in the ANZDATA Registry cases (82%) than in the case studies (23%) and cohort studies (20%). Observed all-cause mortality rates were also higher as observed in the case studies (33%) and cohort studies (26%) than in the ANZDATA Registry cases (6%). Conclusion: Tuberculous peritonitis is uncommon in patients on PD and is associated with poor outcomes. Prospective studies are warranted to study the effect of retaining PD catheters after M tuberculosis infection on patient outcomes.

Predictors and patterns of empirical antibiotic therapy and associated outcomes in COVID-19 patients: a retrospective study in a tertiary care facility in South India.

BACKGROUND: The coronavirus disease (COVID-19) led to a global health crisis. Inappropriate use of antibiotics in COVID-19 patients has been a concern, leading to antimicrobial resistance. This study evaluated the patterns and predictors of empirical antibiotic therapy in COVID-19 patients and associated outcomes. METHODS: A hospital-based retrospective study was conducted with 525 patients admitted to Kasturba Hospital, Manipal, India, with moderate and severe COVID-19 from 1 March to 1 August 2021. They were divided based on empirical therapy, and predictors of antibiotic usage were assessed by logistic regression. RESULTS: Four hundred and eighty (91.4%) COVID-19 patients received at least one course of antibiotics, with 440 (83.8%) initiating empirical therapy. Patients with severe COVID-19 manifestations were more likely to be prescribed empirical antibiotics. Multivariable analysis showed that patients initiated on empirical antibiotics had significantly elevated levels of procalcitonin [OR: 3.91 (95% CI: 1.66-9.16) (p = 0.001)], invasive ventilation [OR: 3.93 (95% CI: 1.70-9.09) (p = 0.001)], shortness of breath [OR: 2.25 (95% CI: 1.30-3.89) (p = 0.003)] and higher CRP levels [OR: 1.01 (95% CI: 1.00-1.01) (p = 0.005)]. Most antibiotics (65.9%) were prescribed from the 'Watch' group, the highest being ceftriaxone. Only 23.8% of the patients had microbiologically confirmed infections. CONCLUSION: The study identified predictors for initiating empirical antibacterial therapy in our setting.

Impact of a pharmacy-led screening and intervention in people at risk of or living with chronic kidney disease in a primary care setting: a cluster randomised trial protocol.

INTRODUCTION: Chronic kidney disease (CKD) is increasingly recognised as a growing global public health problem. Early detection and management can significantly reduce the loss of kidney function. The proposed trial aims to evaluate the impact of a community pharmacy-led intervention combining CKD screening and medication review on CKD detection and quality use of medicines (QUM) for patients with CKD. We hypothesise that the proposed intervention will enhance detection of newly diagnosed CKD cases and reduce potentially inappropriate medications use by people at risk of or living with CKD. METHODS AND ANALYSIS: This study is a multicentre, pragmatic, two-level cluster randomised controlled trial which will be conducted across different regions in Australia. Clusters of community pharmacies from geographical groups of co-located postcodes will be randomised. The project will be conducted in 122 community pharmacies distributed across metropolitan and rural areas. The trial consists of two arms: (1) Control Group: a risk assessment using the QKidney CKD risk assessment tool, and (2) Intervention Group: a risk assessment using the QKidney CKD plus Point-of-Care Testing for kidney function markers (serum creatinine and estimated glomerular filtration rate), followed by a QUM service. The primary outcomes of the study are the proportion of patients newly diagnosed with CKD at the end of the study period (12 months); and rates of changes in the number of medications considered problematic in kidney disease (number of medications prescribed at inappropriate doses based on kidney function and/or number of nephrotoxic medications) over the same period. Secondary outcomes include proportion of people on potentially inappropriate medications, types of recommendations provided by the pharmacist (and acceptance rate by general practitioners), proportion of people who were screened, referred, and took up the referral to visit their general practitioners, and economic and other patient-centred outcomes. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Human Research Ethics Committee at the University of Sydney (2022/044) and the findings of the study will be presented at scientific conferences and published in peer-reviewed journal(s). TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12622000329763).

Hospitalisation Due to Community-Acquired Acute Kidney Injury and the Role of Medications: A Retrospective Audit.

The aim of this study is to assess the use of high-risk medications in patients with community-acquired acute kidney injury (CA-AKI) and the differences in the characteristics and outcomes of CA-AKI based on the use of these medications. This is a retrospective audit of adults (≥35 years) with CA-AKI admitted to a large tertiary care hospital over a two-year period. We investigated the prevalence of SADMANS (sulfonylureas; angiotensin converting enzyme inhibitors; diuretics; metformin; angiotensin receptor blockers; nonsteroidal anti-inflammatory drugs; and sodium glucose co-transporter 2 inhibitors) medications use in people with CA-AKI prior to hospitalisation. Outcomes including CA-AKI severity, kidney function recovery and in-hospital mortality were examined and stratified by use of SADMANS medications. The study included 329 patients, with a mean (SD) age of 75 (12) years and a 52% proportion of females, who were hospitalised with CA-AKI. Most patients (77.5%) were taking at least one regular SADMANS medication upon admission. Overall, 40% of patients (n = 132) and 41% of those on SADMANS (n = 104) had hypovolaemia or associated symptoms such as vomiting and diarrhoea during admission. Over two-thirds (68.1%) had mild AKI on admission and patients who were taking SADMANS medications were more likely to have mild AKI. Patients on SADMANS had more comorbidities and a higher medication burden, but there were no differences in AKI severity on admission or outcomes such as length of hospitalisation, ICU admission, need for dialysis, recovery rates and mortality between the two groups. However, the high prevalence of SADMANS medications use among patients with CA-AKI indicates a potential for preventability of CA-AKI-led hospitalisations. Future studies are needed to gain better insights into the role of withholding this group of medications, especially during an acute illness.

Practices, beliefs, and attitudes of clinicians in prescribing direct oral anticoagulants for obese adults with atrial fibrillation: a qualitative study.

BACKGROUND: Atrial fibrillation (AF) and obesity affect over 60 and 650 million people, respectively. AIM: This study aimed to explore clinician practices, beliefs, and attitudes towards the use of direct oral anticoagulants (DOACs) in obese adults (BMI ≥ 30 kg/m2) with AF. METHOD: Semi-structured interviews via video conference were conducted with multidisciplinary clinicians from across Australia, with expertise in DOAC use in adults with AF. Clinicians were invited to participate using purposive and snowball sampling techniques. Data were analysed in NVIVO using thematic analysis. RESULTS: Fifteen clinicians including cardiologists (n = 5), hospital and academic pharmacists (n = 5), general practitioners (n = 2), a haematologist, a neurologist and a clinical pharmacologist participated. Interviews were on average 31 ± 9 min. Key themes identified were: Health system factors in decision-making Disparities between rural and metropolitan geographic areas, availability of health services, and time limitations for in-patient decision-making, were described; Condition-related factors in decision-making Clinicians questioned the significance of obesity as part of decision-making due to the practical limitations of dose modification, and the rarity of the extremely obese cohort; Decision-making in the context of uncertainty Clinicians reported limited availability, reliability and awareness of primary evidence including limited guidance from clinical guidelines for DOAC use in obesity. CONCLUSION: This study highlights the complexity of decision-making for clinicians, due to the limited availability, reliability and awareness of evidence, the intrinsic complexity of the obese cohort and limited guidance from clinical guidelines. This highlights the urgent need for contemporary research to improve the quality of evidence to guide informed shared decision-making.

Hospital-acquired peritonitis in patients on peritoneal dialysis: A call to action.

Peritonitis remains a significant complication of peritoneal dialysis (PD), and severe episodes of peritonitis lead to structural and functional alterations of the peritoneal membrane, which can result in a permanent transfer to hemodialysis. Although PD is designed primarily to be delivered in the community setting, patients on PD get hospitalized for a number of reasons. In this commentary, we highlight the enormous risks each hospitalization has on the occurrence of peritonitis in patients on PD and the need to understand factors that predispose patients to hospital-acquired peritonitis. Furthermore, we suggest directions on several strategies that could not only reduce the risks of developing peritonitis but also improve outcomes of patients on PD who get hospitalized for an unrelated illness.

Clinical characteristics and outcomes of community acquired-acute kidney injury.

PURPOSE: Published works have reported the impact of a nephrologist intervention on outcomes for patients with hospital-acquired acute kidney injury (HA-AKI), however little is known about the clinical characteristics of patients with community-acquired acute kidney injury (CA-AKI) and the impact of nephrology interventions on outcomes in these patients. METHODS: A retrospective study on all adult patients admitted to a large tertiary care hospital in 2019 who were identified to have CA-AKI were followed from hospital admission to discharge. Clinical characteristics and outcomes of these patients were analysed by receipt of nephrology consultation. Statistical analysis included descriptive, simple Chi-squared/Fischer Exact test, independent samples t-test/Mann-Whitney U test and logistic regression. RESULTS: 182 patients fulfilled the study inclusion criteria. Mean age was 75 ± 14 years, 41% were female, 64% had stage 1 AKI on admission, 35% received nephrology input and 52% had achieved recovery of kidney function by discharge. Higher admission and discharge serum creatinine (SCr) (290.5 vs 159 and 173 vs 109 µmol/L respectively, p = < 0.001), and younger age (68 vs 79, p = < 0.001) were associated with nephrology consultations, whilst length of hospitalisation, mortality and rehospitalisation rates were not significantly different between the two groups. At least 65% were recorded to be on at least one nephrotoxic medication. CONCLUSION: Our findings provide a snapshot of current practice where close to two-thirds of hospitalised patients with CA-AKI had a mild form of AKI that was associated with good clinical outcomes. While higher SCr on admission and younger age were predictors of receiving a nephrology consultation, nephrology consultations did not have any impact on outcomes.

Treatment and outcomes of peritonitis due to Rothia species in patients on peritoneal dialysis: A systematic review and multicentre registry analysis.

Peritoneal dialysis (PD)-associated peritonitis remains a severe complication of PD. Although peritonitis due to Rothia spp. is rare, the treatment recommendations and outcomes are uncertain. Our study aims to review (1) published literature on peritonitis caused by Rothia spp. and (2) reported cases of peritonitis due to Rothia spp. in patients on PD in Australia and New Zealand. A literature search of PubMed, Scopus, Embase and Google Scholar for articles published between January 1949 and February 2022 was conducted. To be eligible, articles had to describe antibiotic therapy and treatment outcomes in all PD patients for peritonitis caused by Rothia or Stomatococcus spp. Data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry of PD patients who developed peritonitis due to Rothia spp. between July 2011 and May 2020 were also reviewed. A total of 12 articles and 28 episodes were identified from the literature search and ANZDATA registry analysis, respectively. Over 60% of the peritonitis cases due to Rothia spp. were from the Rothia mucilaginosa species (8/12 and 17/28, respectively), while Rothia dentocariosa was the second most commonly identified species in both the literature search and the ANZDATA registry analysis (4/12 and 5/28, respectively). A majority 8 (66.7%) of the articles in the literature search employed a combination antibiotic regimen, while the remaining 4 (33.3%) used a single antibiotic regimen. In contrast, most of the episodes, 22 (78.6%) described in the ANZDATA registry analysis, employed a single antibiotic regimen, and only 6 (21.4%) episodes were treated with a combination antibiotic regimen. The duration of antibiotic therapy ranged from 2 to 3 weeks in the literature search, and 1 to 3 weeks in the ANZDATA registry. While no deaths within 30 days of developing peritonitis were reported, catheter removal was reported in three (25%) and two (7.1%) episodes in both the literature search and the ANZDATA registry analysis, respectively, of which the majority occurred in patients treated for ≤2 weeks. PD-associated peritonitis due to Rothia spp. is uncommon and associated with relatively good outcomes. Antibiotic treatment for 3 weeks is associated with better outcomes.

Sick day management in people with chronic kidney disease: a scoping review.

BACKGROUND: Use of certain medications during an acute illness may put patients at an increased risk of acute kidney injury (AKI). Patients with chronic kidney disease (CKD) are at higher risk of developing superimposed AKI. The aim of this scoping review is to collate and characterise existing evidence on sick day management considerations and practices during acute illness in people with CKD. METHODS: We searched Embase, CINAHL, MEDLINE, International Pharmaceutical Abstract, Scopus, Google Scholar and grey literature sources. We followed the methodological framework for scoping reviews, while information was extracted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Findings are presented thematically. RESULTS: Ten studies and seven guidelines met the inclusion criteria. Studies were targeted at patients, general practitioners, pharmacists, and nurses. The major themes identified included development and feasibility testing of a sick day management protocol, current practice of temporary medication discontinuation, and outcomes. Most guidelines provided recommendations for sick day management largely based on expert consensus. A digital intervention was deemed highly acceptable and easy to use, whereas patient handouts were more effective when provided along with dialogue with a health professional. While there is little evidence on the impact of sick day protocols on outcomes, a single randomised trial reported no significant association between sick day protocols and change in kidney function, AKI incidents or risk of hospitalisation. CONCLUSION: The nascent literature on sick day management in patients with CKD revealed the limited available evidence to provide guidance on implementation and on outcomes. Future research needs to clarify sick day recommendations and assess their impact on clinical outcomes including prevention of superimposed AKI or hospitalisations, as well as to address barriers to implementation.

Hospital-Acquired Acute Kidney Injury in Noncritical Care Setting: Clinical Characteristics and Outcomes.

Background: There is limited Australian data on the incidence and outcomes of hospital-acquired acute kidney injury (HA-AKI) in noncritically ill patients. Aims: This study aimed to characterise HA-AKI and assess the impact of nephrology consultations on outcomes. Methods: A retrospective cohort of all noncritically ill patients with HA-AKI admitted to a large tertiary hospital in 2018 were followed up from hospital admission to discharge. HA-AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The primary outcome of this study was the clinical characteristics of patients who developed HA-AKI and the difference in these characteristics by nephrology consultation. Results: A total of 222 noncritically ill patients were included in the study. The mean age of included patients was 74.8 ± 15.8 years and 57.2% were females. While most patients (92%)were characterised to have KDIGO stage 1, 14% received a nephrology consultation, and 80% had complete or partial recovery of kidney function at discharge. Lower recovery rates (65% versus 83%, P = 0.022), longer hospitalisations (10 versus 5 days, P = 0.001), and higher serum creatinine values on discharge (152 versus 101 µmol/L, P < 0.001) were associated with receipt of nephrology consultation. There was no difference in mortality rates (13% versus 11%, P = 0.754) between those with and without nephrology consultation. Conclusions: Our findings indicate that signficant proportion of noncritically ill patients experience mild form of AKI and have good recovery of kidney function during hospitalisation. Although severity of AKI and length of hospitalisation were associated with nephrology interventions, large scale study is required to understand the impact of such interventions on clinical outcomes, such as hospital readmission and mortality.

Practice variations in antibiotic administration for the management of peritonitis in patients on automated peritoneal dialysis in Australia and New Zealand.

In the absence of guidelines on the management of peritoneal dialysis (PD)-associated peritonitis in patients on automated peritoneal dialysis (APD), variations in clinical practice potentially exist between PD units that could affect clinical outcomes. This study aimed to document the current practices of treating PD-associated peritonitis in patients on APD across Australia and New Zealand and the reasons for practice variations using a cross-sectional online survey. Of the 62 PD units, 34 medical leads (55%) responded to the survey. When treating APD-associated peritonitis, 21 units (62%) continued patients on APD and administered intraperitoneal (IP) antibiotics in manual daytime exchanges; of these, 17 (81%) considered allowing at least 6 h dwell time for adequate absorption of the IP antibiotics as an important reason for adding manual daytime exchange. Nine units (26%) temporarily switched patients from APD to continuous ambulatory peritoneal dialysis (CAPD); of these, five (55%) reported a lack of pharmacokinetic (PK) data for IP antibiotics in APD, four (44%) reported a shortage of APD-trained nursing staff to perform APD exchanges during hospitalisation and three (33%) reported inadequate time for absorption of IP antibiotics on APD as important reasons for their practice. Four units (12%) continued patients on APD and administered IP antibiotics during APD exchanges; of these, three (75%) believed that PK data available in CAPD could be extrapolated to APD. This study demonstrates wide variations in the management of APD-associated peritonitis in Australia and New Zealand; it points towards the lack of PK on antibiotics used to treat peritonitis as an important reason underpinning practice variations.

Effectiveness of Direct Oral Anticoagulants in Obese Adults With Atrial Fibrillation: A Systematic Review of Systematic Reviews and Meta-Analysis.

Background: Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia. Obesity is an independent risk factor for AF. Anticoagulants have been strongly recommended by all international guidelines to prevent stroke. However, altered pathophysiology in obese adults may influence anticoagulant pharmacology. Direct oral anticoagulants (DOACs) in the context of obesity and AF have been examined in recent systematic reviews. Despite the similarities in included studies, their results and conclusions do not agree. Methods and Results: The protocol for this review was registered with PROSPERO (CRD42020181510). Seven key electronic databases were searched using search terms such as "atrial fibrillation," "obese,*" "overweight," "novel oral anticoagulant," "direct oral anticoagulant," "DOAC," "NOAC," "apixaban," dabigatran," "rivaroxaban," and "edoxaban" to locate published and unpublished studies. Only systematic reviews with meta-analyses that examined the effect of DOACs in overweight or obese adults with AF, published in the English language, were included. A total of 9,547 articles were initially retrieved. After removing the duplicates, title and abstract review and full-text review, five articles were included in the systematic review. From these only RCTs were included in the meta-analyses. There was disagreement within the published systematic reviews on DOACs in obesity. The results from our meta-analysis did not show any significant difference between all body mass index (BMI) groups for all outcomes at both 12 months and for the entire trial duration. Non-significant differences were seen among the different types of DOACs. Conclusion: There was no difference between the BMI classes in any of the outcomes assessed. This may be due to the limited number of people in the trial that were in the obese class, especially obese class III. There is a need for large prospective trials to confirm which DOACs are safe and efficacious in the obese class III adults and at which dose.

Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review.

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.

Quality use of medicines in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) affects drug elimination and patients with CKD require appropriate adjustment of renally cleared medications to ensure safe and effective pharmacotherapy. The main objective of this study was to determine the extent of potentially inappropriate prescribing (PIP; defined as the use of a contraindicated medication or inappropriately high dose according to the kidney function) of renally-cleared medications commonly prescribed in Australian primary care, based on two measures of kidney function. A secondary aim was to assess agreement between the two measures. METHODS: Retrospective analysis of routinely collected de-identified Australian general practice patient data (NPS MedicineWise MedicineInsight from January 1, 2013, to June 1, 2016; collected from 329 general practices). All adults (aged ≥18 years) with CKD presenting to general practices across Australia were included in the analysis. Patients were considered to have CKD if they had two or more estimated glomerular filtration rate (eGFR) recorded values < 60 mL/min/1.73m2, and/or two urinary albumin/creatinine ratios ≥3.5 mg/mmol in females (≥2.5 mg/mmol in males) at least 90 days apart. PIP was assessed for 49 commonly prescribed medications using the Cockcroft-Gault (CG) equation/eGFR as per the instructions in the Australian Medicines Handbook. RESULTS: A total of 48,731 patients met the Kidney Health Australia (KHA) definition for CKD and had prescriptions recorded within 90 days of measuring serum creatinine (SCr)/estimated glomerular filtration rate (eGFR). Overall, 28,729 patients were prescribed one or more of the 49 medications of interest. Approximately 35% (n = 9926) of these patients had at least one PIP based on either the Cockcroft-Gault (CG) equation or eGFR (CKD-EPI; CKD-Epidemiology Collaboration Equation). There was good agreement between CG and eGFR while determining the appropriateness of medications, with approximately 97% of the medications classified as appropriate by eGFR also being considered appropriate by the CG equation. CONCLUSION: This study highlights that PIP commonly occurs in primary care patients with CKD and the need for further research to understand why and how this can be minimised. The findings also show that the eGFR provides clinicians a potential alternative to the CG formula when estimating kidney function to guide drug appropriateness and dosing.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Medication Adherence, Burden and Health-Related Quality of Life in Adults with Predialysis Chronic Kidney Disease: A Prospective Cohort Study.

This study examines the associations between medication adherence and burden, and health-related quality of life (HRQOL) in predialysis chronic kidney disease (CKD). A prospective study targeting adults with advanced CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2) and not receiving renal replacement therapy was conducted in Tasmania, Australia. The actual medication burden was assessed using the 65-item Medication Regimen Complexity Index, whereas perceived burden was self-reported using a brief validated questionnaire. Medication adherence was assessed using a four-item Morisky-Green-Levine Scale (MGLS) and the Tool for Adherence Behaviour Screening (TABS). The Kidney Disease and Quality of Life Short-Form was used to assess HRQOL. Of 464 eligible adults, 101 participated in the baseline interview and 63 completed a follow-up interview at around 14 months. Participants were predominantly men (67%), with a mean age of 72 (SD 11) years and eGFR of 21 (SD 6) mL/min/1.73 m2. Overall, 43% and 60% of participants reported medication nonadherence based on MGLS and TABS, respectively. Higher perceived medication burden and desire for decision-making were associated with nonadherent behaviour. Poorer HRQOL was associated with higher regimen complexity, whereas nonadherence was associated with a decline in physical HRQOL over time. Medication nonadherence, driven by perceived medication burden, was prevalent in this cohort, and was associated with a decline in physical HRQOL over time.

High Pyridine Generation in Ceftazidime-Icodextrin Admixtures Used to Treat Peritoneal Dialysis-associated Peritonitis.

PURPOSE: To investigate the amount of pyridine generated from degradation of ceftazidime in icodextrin peritoneal dialysis (PD) solutions. METHODS: PD solutions that contained 1 and 1.5 g of ceftazidime were stored at 25 °C for 12 hours and then at 37 °C for 14 hours. An aliquot was withdrawn at predefined time points and analyzed for the concentrations of ceftazidime and pyridine. FINDINGS: The amount of pyridine generated was >225% and 400% of its maximum recommended daily exposure in the 1- and 1.5-g ceftazidime-PD admixtures, respectively. IMPLICATIONS: Until these results are confirmed with appropriate in vivo studies, intermittent intraperitoneal dosing of ceftazidime admixed with icodextrin should be used with caution and appropriate clinical monitoring or a suitable alternative antibiotic should be used.