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

2020 ◽  
pp. 089686082095092
Author(s):  
Kathleen Hennessy ◽  
Edmund V Capparelli ◽  
Gale Romanowski ◽  
Lawrence Alejandro ◽  
William Murray ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Adverse Effects ◽  
Body Surface ◽  
First Generation ◽  
Pediatric Patients ◽  
Generation Cephalosporin ◽  
Loading Dose ◽  
Population Pk ◽  
Dosing Strategies ◽  
Dialysate Volume

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Peritonitis in Children on Chronic Peritoneal Dialysis: The Experience of a Large National Pediatric Cohort

2017 ◽  
Vol 45 (1-3) ◽  
pp. 118-125 ◽  
Author(s):  
Daniela Ponce ◽  
Thyago Proença de Moraes ◽  
Roberto Pecoits-Filho ◽  
Ana Elizabeth Figueiredo ◽  
Pasqual Barretti
Keyword(s):  
Peritoneal Dialysis ◽  
First Generation ◽  
Negative Impact ◽  
Generation Cephalosporin ◽  
Study Results ◽  
Incidence Risk ◽  
Study Methodology ◽  
Initial Choice ◽  
Technique Failure ◽  
Culture Negative

Background: We performed this study to evaluate the incidence, risk factors, microbiology, treatment, and outcome of peritonitis in pediatric Peritoneal dialysis (PD) patients at a nationwide prospective study. Methodology: Patients younger than 18 years recruited in the BRAZPD II study from 2004 to 2011, who presented their first peritonitis episode, were included in the study. Results: We found 125 first episodes of peritonitis in 491 children PD patients (0.43 episodes/patient-year). Patients free of peritonitis episode constituted 75.6% in 1 year. Culture-negative episodes were very high (59.2%) and gram-positive (GP) bacteria were the most commonly found organisms (58.8%). First-generation cephalosporin was the initial choice to cover GP (40.5%) and aminoglycosides was the most prescribed antibiotics used for gram-negative agents (27.5%). Treatment failure was 26.4%. Technique failure (TF) occurred in 12.1% and peritonitis was the main cause (65.1%). Pseudomonas (p = 0.04) and negative cultures (p < 0.001) were identified as predictors of TF. Conclusion: Peritonitis remains a common complication of PD in children and negative cultures and pseudomonas had a negative impact on TF.

Effective Treatment of Peritoneal Dialysis-Associated Peritonitis with Cefazolin and Ceftazidime in Children

2001 ◽  
Vol 21 (4) ◽  
pp. 386-389 ◽  
Author(s):  
Esther Rusthoven ◽  
Leo A.H. Monnens ◽  
Cornelis H. Schröder
Keyword(s):  
Peritoneal Dialysis ◽  
Medical Records ◽  
Pediatric Patients ◽  
Medical Center ◽  
Initial Therapy ◽  
Loading Dose ◽  
Dialysis Fluid ◽  
Causative Microorganism ◽  
The University ◽  
Antibiotic Combination

Objective To evaluate the use of the combination of cefazolin and ceftazidime for initial treatment of peritoneal dialysis (PD)-related peritonitis in pediatric patients. Design Retrospective nonrandomized study. Setting Pediatric dialysis units of the University Medical Center of Utrecht and Nijmegen, The Netherlands. Patients 40 children (median age 5.4 years) who were treated with PD during the study period of 4.5 years. Interventions All 50 episodes of peritonitis that occurred during the study period were evaluated by review of medical records. Patients were given intraperitoneal ceftazidime 500 mg/L dialysis fluid, and cefazolin 500 mg/L as a loading dose, followed by a maintenance dose of ceftazidime 125 mg/L and cefazolin 100 mg/L, intraperitoneally, 4 times daily. Antibiotics were continued for 14 days. Results After identification of the causative microorganism, one of the antibiotics was discontinued in 34 cases, and the antibiotic schedule was adapted in 2 cases. All cases were initially cured within 3 days. In 5 cases (10%), there was a peritonitis with the same organism recurring within 2 weeks after completion of treatment. There were 4 cases of PD-related peritonitis caused by pseudomonas, all of which were cured. Conclusions The antibiotic combination of cefazolin and ceftazidime is effective for the initial therapy of PD-related peritonitis in children. The toxic complications of aminoglycosides are avoided with this combination.

scholarly journals Streptococcus Bovis Peritonitis Complicating Peritoneal Dialysis—A Review of 10 Years’ Experience

2012 ◽  
Vol 32 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Desmond Y.H. Yap ◽  
Kelvin K.W. To ◽  
Terence P.S. Yip ◽  
Sing Leung Lui ◽  
Tak Mao Chan ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
First Generation ◽  
Generation Cephalosporin ◽  
Primary Response ◽  
Secondary Response ◽  
Penicillin G ◽  
Streptococcus Bovis ◽  
Subsequent Work ◽  
History Of ◽  
Moderately Resistant

ObjectiveAn association of Streptococcus bovis bacteremia with carcinoma of colon has been reported, but data regarding peritoneal dialysis (PD) peritonitis caused by S. bovis is scarce. In this study, we examined the clinical characteristics, associations, and outcomes of this disease entity.MethodsThe case records of patients with S. bovis PD peritonitis presenting to 2 renal centers between January 2000 and September 2010 were reviewed. Clinical features and outcomes were identified and analyzed.ResultsOf cultures from 23 episodes of S. bovis peritonitis in 20 patients (1.28% of all peritonitis episodes at our center), 19 (82.6%) showed S. bovis alone, and 4 (17.4%) showed mixed growth. In 7 episodes, the S. bovis was moderately resistant to penicillin G. Rates of resistance to clindamycin and erythromycin were 43.5% and 47.8% respectively. In 18 episodes (78.3%), a primary response was achieved with a first-generation cephalosporin and an aminoglycoside. In 4 episodes, a secondary response was achieved after a switch from cephalosporin to vancomycin, and in 1 episode with mixed growth, the Tenckhoff catheter had to be removed. Repeat peritonitis occurred in 3 patients at a mean of 50.0 months (range: 24.2 – 83.1 months). Of the 20 patients of S. bovis peritonitis, 10 (50%) underwent either a barium enema or a colonoscopy. One patient had history of colonic carcinoma 2 years before the peritonitis, and a subsequent work-up revealed no recurrence. Three patients had diverticulosis, and one had a concomitant sigmoid polyp. Findings in the other 6 patients were normal. No colorectal malignancy had developed in the remaining 10 patients after a mean follow-up of 76.6 months (range: 0.8 – 125.1 months).ConclusionsOutcomes in S. bovis PD peritonitis were favorable, and an association with colorectal cancer was not found in our patients. Routine colonoscopy in these patients remains controversial and should be individualized.

scholarly journals Optimizing Ceftobiprole Dosage in Pediatric Patients: A Model-Based Approach

2021 ◽  
Author(s):  
Christopher M. Rubino ◽  
Anthony P. Cammarata ◽  
Anne Smits ◽  
Sebastian Schröpf ◽  
Mark Polak ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Compartment Model ◽  
Generation Cephalosporin ◽  
Population Pharmacokinetic ◽  
Model Based ◽  
Final Population ◽  
Pediatric Study ◽  
Population Pk ◽  
Neonates And Infants

Ceftobiprole is an advanced-generation cephalosporin for intravenous administration with activity against Gram-positive and Gram-negative organisms. A population pharmacokinetic (PK) model characterizing the disposition of ceftobiprole in plasma using data from patients in three pediatric studies was developed. Model-based simulations were subsequently performed to assist in dose optimization for the treatment of pediatric patients with hospital-acquired or community-acquired pneumonia. The population PK dataset comprised 518 ceftobiprole plasma concentrations from 107 patients aged 0 (birth) to 17 years. Ceftobiprole PK was well described by a three-compartment model with linear elimination. Ceftobiprole clearance was modeled as a function of glomerular filtration rate; other PK parameters were scaled to body weight. The final population PK model provided a robust and reliable description of the PK of ceftobiprole in the pediatric study population. Model-based simulations using the final model suggested that a ceftobiprole dose of 15 mg/kg infused over 2 hours and administered every 12 hours in neonates and infants <3 months or every 8 hours in older pediatric patients would result in a ceftobiprole exposure consistent with that in adults and good pharmacokinetic-pharmacodynamic target attainment. The dose should be reduced to 10 mg/kg every 12 hours in neonates and infants <3 months who weigh <4 kg to avoid high exposures. Extended intervals and reduced doses may be required for pediatric patients older than 3 months of age with renal impairment.

Prevention and Treatment of Peritoneal Dialysis-Associated Peritonitis in Pediatric Patients

2005 ◽  
Vol 25 (3_suppl) ◽  
pp. 117-119 ◽  
Author(s):  
Günter Klaus
Keyword(s):  
Peritoneal Dialysis ◽  
First Generation ◽  
Treatment Guidelines ◽  
Generation Cephalosporin ◽  
Infectious Complications ◽  
Relative Increase ◽  
Coagulase Negative Staphylococci ◽  
Frequent Use ◽  
Empiric Antibiotic ◽  
Empiric Antibiotic Treatment

Peritoneal dialysis (PD) is the preferred dialysis modality in children and adolescents aged less than 15 years. Peritoneal dialysis-associated peritonitis remains a major cause of morbidity and reason for dropout from the PD program, although the incidence of peritonitis seems to have decreased during the past few years. Improved patient care, more frequent use of automated peritoneal dialysis (APD), use of PD catheters with downward facing exit sites, and Staphylococcus aureus prophylaxis account for this decline in infectious complications. With respect to the isolated micro-organism in PD-associated peritonitis, a predominance of gram-positive germs is found in children. Recent registry data suggest a decrease in coagulase-negative staphylococci, with a relative increase in gram-negative peritonitis episodes. The empiric antibiotic treatment regimen using a first-generation cephalosporin or a glycopeptide in combination with a third-generation cephalosporin in a risk-stratified manner was suggested in the pediatric peritonitis treatment guidelines. This regimen is currently being evaluated in the International Pediatric Peritonitis Registry.

scholarly journals Relationship between body size, fill volume, and mass transfer area coefficient in peritoneal dialysis.

1994 ◽  
Vol 4 (10) ◽  
pp. 1820-1826 ◽  
Author(s):  
P Keshaviah ◽  
P F Emerson ◽  
E F Vonesh ◽  
J C Brandes
Keyword(s):  
Mass Transfer ◽  
Peritoneal Dialysis ◽  
Body Size ◽  
Body Surface ◽  
Time Profiles ◽  
Surface Areas ◽  
Concentration Time ◽  
Fill Volume ◽  
Dialysate Volume ◽  
Tidal Peritoneal Dialysis

A peritoneal dialysate fill volume of 2 L has become the standard of clinical practice, but the relationships between body size, fill volume, and mass transfer area coefficient (KoA) have not been well established. These relationships were studied in 10 stable peritoneal dialysis patients who underwent six peritoneal equilibration studies (2 h each) at fill volumes of 0.5, 1, 1.5, 2, 2.5, and 3 L. The concentration-time profiles for urea, creatinine, and glucose were measured at each fill volume, and residual volumes were calculated from the preceding dwell period. A modified Henderson equation was used to calculate the KoA for the three solutes as a function of fill volume. By normalizing the KoA for each solute to the value at 2 L, the data for all three solutes collapsed onto the same trend line when plotting the normalized KoA versus dialysate volume. Between 0.5- and 2-L fill volumes, the average normalized KoA increases in an almost linear fashion, its value almost doubling over this range. Between 2- and 3-L fill volumes, there is less than a 10% change in the normalized KoA. However, fill volumes for peak urea KoA were found to increase with increasing body surface area (R = 0.76), being around 2.5 L for an average-sized patient and increasing to between 3 and 3.5 L for body surface areas > 2 m2. To maximize solute transport, these relationships between body size, volume, and KoA should be considered when choosing fill volumes for continuous ambulatory peritoneal dialysis and automated peritoneal dialysis and when deciding reserve and tidal volumes for tidal peritoneal dialysis.

The Effect of Changes in Dialysate Volume on Glucose and Urea Equilibration

1994 ◽  
Vol 14 (3) ◽  
pp. 236-239 ◽  
Author(s):  
Edward C. Kohaut ◽  
F. Bryson Waldo ◽  
Mark R. Benfield
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Prospective Study ◽  
Body Surface ◽  
Patient Population ◽  
Different Ages ◽  
Student’S T ◽  
A Prospective Study ◽  
Dialysate Volume ◽  
Student’S T Test

Objectives To determine the effect of changing dialysate volume on urea and glucoseequilibration curves and to determine, if dialysate volume is prescribed on the basis of body surface area, whether equilibration curves will be consistent in patients of different sizes and ages. Design A prospective study wherein children with acute or chronic renal failure had peritoneal equilibration studies done with dwell volumes of 30 mL/kg, 40 mL/kg, and 1200 mL/m2. Patient Population Twenty-two children: 7 under 3 years of age; 8 between 3 and 10 years of age; 7 older than 10 years of age. Statistics Student's t-test. Results Urea and glucose equilibrated rapidly at dwell volumes of 30 mL/kg, slower at dwell volumes of 40 mL/kg, and slowest at dwell volumes of 1200 mL/m2. Equilibration curves were similar in children of different ages when dialysate volumes of 1200 mL/m2 were infused. Conclusion Dialysate volumes of 1200 mL/m2 should be used when equilibration studies are being done to compare individuals of different ages and sizes.

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