Pharmacokinetics of intraperitoneal and intravenous fosfomycin in automated peritoneal dialysis patients without peritonitis.
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ABSTRACT:
SUBMITTER: Tobudic S
PROVIDER: S-EPMC3393440 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
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Pharmacokinetics of intraperitoneal and intravenous fosfomycin in automated peritoneal dialysis patients without peritonitis.
Tobudic Selma S Matzneller Peter P Stoiser Brigitte B Wenisch Judith Maria JM Zeitlinger Markus M Vychytil Andreas A Jaeger Walter W Boehmdorfer Michaela M Reznicek Gottfried G Burgmann Heinz H
Antimicrobial agents and chemotherapy 20120507 7
Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure aft ...[more]
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Project description: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.
| S-EPMC8932706 | biostudies-literature
Project description:Unlabelled?BackgroundThe standard treatment of peritoneal dialysis (PD)-associated peritonitis (PD-peritonitis) is intraperitoneal (IP) administration of antibiotics. Only limited data on the pharmacokinetics and appropriateness of contemporary dose recommendations of IP cefalothin and cefazolin exist. The aim of this study was to describe the pharmacokinetics of IP cefalothin and cefazolin in patients treated for PD-peritonitis. ?MethodsAs per international guidelines, IP cefalothin or cefazolin 15 mg/kg once daily was dosed with gentamicin in a 6-hour dwell to patients with PD-peritonitis during routine care. Serial plasma and PD effluent samples were collected over the first 24 hours of therapy. Antibiotic concentrations were quantified using a validated chromatographic method with pharmacokinetic analysis performed using a non-compartmental approach. ?ResultsNineteen patients were included (cefalothin n = 8, cefazolin n = 11). The median bioavailability for both antibiotics exceeded 92%, but other pharmacokinetic parameters varied markedly between antibiotics. Both antibiotics achieved high PD effluent concentrations throughout the antibiotic dwell. Cefazolin had a smaller volume of distribution compared with cefalothin (14 vs 40 L, p = 0.003). The median trough total plasma antibiotic concentration for cefazolin and cefalothin during the dwell differed (plasma 56 vs 13 mg/L, p < 0.0001) despite a similar concentration in PD effluent (37 vs 38 mg/L, p = 0.58). Lower antibiotic concentrations were noted during PD dwells not containing antibiotic, particularly cefalothin, which was frequently undetectable in plasma and PD effluent. The median duration that the unbound antibiotic concentration was above the minimum inhibitory concentration (MIC) was approximately 13% (plasma) and 25% (IP) for cefalothin, and 100% (plasma and IP) for cefazolin, of the dosing interval. ?ConclusionsWhen IP cefalothin or cefazolin is allowed to dwell for 6 hours, sufficient PD effluent concentrations are present for common pathogens during this time. However, with once-daily IP dosing, in contrast to cefazolin, there is a risk of subtherapeutic plasma and PD effluent cefalothin concentrations, so more frequent dosing may be required.
| S-EPMC4934436 | biostudies-literature
Project description:Rationale & objectiveConventional culture can be insensitive for the detection of rare infections and for the detection of common infections in the setting of recent antibiotic usage. Patients receiving peritoneal dialysis (PD) with suspected peritonitis have a significant proportion of negative conventional cultures. This study examines the utility of metagenomic sequencing of peritoneal effluent cell-free DNA (cfDNA) for evaluating the peritoneal effluent in PD patients with and without peritonitis.Study designProspective cohort study.Setting & participantsWe prospectively characterized cfDNA in 68 peritoneal effluent samples obtained from 33 patients receiving PD at a single center from September 2016 to July 2018.OutcomesPeritoneal effluent, microbial, and human cfDNA characteristics were evaluated in culture-confirmed peritonitis and culture-negative peritonitis.Analytical approachDescriptive statistics were analyzed and microbial cfDNA was detected in culture-confirmed peritonitis and culture-negative peritonitis.ResultsMetagenomic sequencing of cfDNA was able to detect and identify bacterial, viral, and eukaryotic pathogens in the peritoneal effluent from PD patients with culture-confirmed peritonitis, as well as patients with recent antibiotic usage and in cases of culture-negative peritonitis.LimitationsParallel cultures were not obtained in all the peritoneal effluent specimens.ConclusionsMetagenomic cfDNA sequencing of the peritoneal effluent can identify pathogens in PD patients with peritonitis, including culture-negative peritonitis.
| S-EPMC8767090 | biostudies-literature
Project description:BackgroundResults concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up.MethodsThis retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality.ResultsA total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21-48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46-2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28-2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47-9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years.ConclusionsPeritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.
| S-EPMC5460447 | biostudies-literature
Project description:INTRODUCTION: Continuous ambulatory peritoneal dialysis (CAPD) peritonitis may develop after endoscopic procedures, and the benefit of prophylactic antibiotics is unclear. In the present study, we investigated whether prophylactic antibiotics reduce the incidence of peritonitis in these patients. PATIENTS AND METHODS: We retrospectively reviewed all endoscopic procedures, including esophagogastroduodenoscopy (EGD), colonoscopy, sigmoidoscopy, cystoscopy, hysteroscopy, and hysteroscopy-assisted intrauterine device (IUD) implantation/removal, performed in CAPD patients at Chang Gung Memorial Hospital, Taiwan, between February 2001 and February 2012. RESULTS: Four hundred and thirty-three patients were enrolled, and 125 endoscopies were performed in 45 patients. Eight (6.4%) peritonitis episodes developed after the examination. Antibiotics were used in 26 procedures, and none of the patients had peritonitis (0% vs. 8.1% without antibiotic use; p=0.20). The peritonitis rate was significantly higher in the non-EGD group than in the EGD group (15.9% [7/44] vs. 1.2% [1/81]; p<0.005). Antibiotic use prior to non-EGD examinations significantly reduced the endoscopy-associated peritonitis rate compared to that without antibiotic use (0% [0/16] vs. 25% [7/28]; p<0.05). Peritonitis only occurred if invasive procedures were performed, such as biopsy, polypectomy, or IUD implantation, (noninvasive procedures, 0% [0/20] vs. invasive procedures, 30.4% [7/23]; p<0.05). No peritonitis was noted if antibiotics were used prior to examination with invasive procedures (0% [0/10] vs. 53.8% [7/13] without antibiotic use; p<0.05). Although not statistically significant, antibiotics may play a role in preventing gynecologic procedure-related peritonitis (antibiotics, 0% [0/4] vs. no antibiotics, 55.6% [5/9]; p=0.10). CONCLUSION: Antibiotic prophylaxis significantly reduced endoscopy-associated PD peritonitis in the non-EGD group. Endoscopically assisted invasive procedures, such as biopsy, polypectomy, IUD implantation/removal, and dilatation and curettage (D&C), pose a high risk for peritonitis. Prophylactic antibiotics for peritonitis prevention may be required in colonoscopic procedures and gynecologic procedures.
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Project description:ABSTRACT Background Increased intraperitoneal pressure (IPP) is associated with abdominal wall complications and technical failure in peritoneal dialysis (PD). Since the standard measurement of IPP is limited due to its cumbersome procedures, we aimed to develop and validate equations for estimating IPP. Methods We performed a cross-sectional study with a total of 200 prevalent PD patients who were divided into development and validation datasets after random sampling matched by body mass index. The IPPs were measured using the Durand method, with whole-body and abdominal anthropometry indices collected. Equations with 2.0-L and 1.5-L fill volumes were generated by stepwise linear regression modelling. The bias, accuracy and precision of the estimated IPP (eIPP) with 2-L and 1.5-L fill volumes were compared with actual IPPs by the Durand method. The eIPP for the 2-L fill volume was also compared with other existing equations. Results Two new equations incorporating waist circumference and height from the decubitus plane to mid-axillary line were generated. The eIPPs exhibited small biases in relation to the Durand method , with median differences of −0.24 cmH2O and −0.10 cmH2O for 2 L and 1.5 L, respectively. The precisions evaluated by the standard deviation of the absolute value of the differences were 2.59 cmH2O and 2.50 cmH2O, respectively. The accuracies evaluated by the value of the percentage of estimates that differed by >20% for the eIPP were 26% for 2.0 L and 27% for 1.5 L. Better bias, precision and accuracy were observed for the eIPP equation compared with other existing equations for the 2.0-L fill volume. Conclusions We provided two new equations developed from abdominal anthropometry indices to accurately estimate the IPP in the PD population. Graphical Abstract Graphical Abstract
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Project description:In peritoneal dialysis (PD) patients, fungi and Pseudomonas aeruginosa are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and Pseudomonas aeruginosa peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and Pseudomonas aeruginosa-peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and Pseudomonas aeruginosa-peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and Pseudomonas aeruginosa-peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.
| S-EPMC10252763 | biostudies-literature
Project description:Background and objectivesThere is conflicting evidence comparing peritonitis rates among patients treated with continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). This study aims to clarify the relationship between peritoneal dialysis (PD) modality (APD versus CAPD) and the risk of developing PD-associated peritonitis.Design, setting, participants, & measurementsThis study examined the association between PD modality (APD versus CAPD) and the risks, microbiology, and clinical outcomes of PD-associated peritonitis in 6959 incident Australian PD patients between October 1, 2003, and December 31, 2011, using data from the Australia and New Zealand Dialysis and Transplant Registry. Median follow-up time was 1.9 years.ResultsPatients receiving APD were younger (60 versus 64 years) and had fewer comorbidities. There was no association between PD modality and time to first peritonitis episode (adjusted hazard ratio [HR] for APD versus CAPD, 0.98; 95% confidence interval [95% CI], 0.91 to 1.07; P=0.71). However, there was a lower hazard of developing Gram-positive peritonitis with APD than CAPD, which reached borderline significance (HR, 0.90; 95% CI, 0.80 to 1.00; P=0.05). No statistically significant difference was found in the risk of hospitalizations (odds ratio, 1.12; 95% CI, 0.93 to 1.35; P=0.22), but there was a nonsignificant higher likelihood of 30-day mortality (odds ratio, 1.33; 95% CI, 0.93 to 1.88; P=0.11) at the time of the first episode of peritonitis for patients receiving APD. For all peritonitis episodes (including subsequent episodes of peritonitis), APD was associated with lower rates of culture-negative peritonitis (incidence rate ratio [IRR], 0.81; 95% CI, 0.69 to 0.94; P=0.002) and higher rates of gram-negative peritonitis (IRR, 1.28; 95% CI, 1.13 to 1.46; P=0.01).ConclusionsPD modality was not associated with a higher likelihood of developing peritonitis. However, APD was associated with a borderline reduction in the likelihood of a first episode of Gram-positive peritonitis compared with CAPD, and with lower rates of culture-negative peritonitis and higher rates of Gram-negative peritonitis. Peritonitis outcomes were comparable between both modalities.
| S-EPMC4046732 | biostudies-literature
Project description:Dermabacter hominis was the cause of a peritoneal dialysis-associated peritonitis. D. hominis was identified by phenotypic criteria and by sequencing the 16S rRNA gene. Clinical cure was achieved with cefuroxime treatment despite the isolate's reduced susceptibility to this drug (MIC, 12 mg/liter) on in vitro testing. The successful treatment was probably due to the high concentrations attained by intraperitoneal administration of the drug.
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