meropenem and Kidney-Failure--Chronic

Meropenem is frequently used to treat severe infections in critically ill children. However, pharmacokinetic data on meropenem in children with end-stage renal disease (ESRD) undergoing prolonged intermittent renal replacement therapy (PIRRT) is limited. Our objectives were to evaluate meropenem clearance in a child with ESRD with and without PIRRT, compare the results to previous continuous renal replacement therapy studies in children, toddlers and neonates, and assess whether the currently used dose of meropenem is sufficient.. A 5-year-old girl with an estimated glomerular filtration rate of 12.8 mL/min/1.73 m 2 was diagnosed with pulmonary infection and treated with 300 mg meropenem once a day. PIRRT was performed for 8 hours every 2 days. We used WinNonlin to evaluate meropenem clearance with and without PIRRT.. Our case showed that PIRRT increased the clearance of meropenem from 1.39 (1.3) to 2.42 L/h (2.3 mL/kg/min) and caught up 42.6% of the total clearance. This result is in accordance with previous studies in children but slightly less than seen in toddlers and neonates under continuous renal replacement therapy. The current dose of 300 mg once a day is not sufficient to reach the therapeutic target.. Predicting meropenem clearance in children with ESRD undergoing PIRRT is difficult as clearance will be affected by renal function, PIRRT settings and other factors. Further studies are needed to explore the individual variability of meropenem clearance and optimize the dosing regimen.

Topics: Anti-Bacterial Agents; Child, Preschool; Continuous Renal Replacement Therapy; Critical Illness; Drug Elimination Routes; Female; Humans; Intermittent Renal Replacement Therapy; Kidney Failure, Chronic; Meropenem

To investigate the clinical course and outcome of peritoneal dialysis-associated peritonitis secondary to Gordonia species.. We reviewed all Gordonia peritonitis episodes occurring in a single dialysis unit from 1994 to 2013.. During the study period, four episodes of Gordonia peritonitis were recorded. All were male patients. One patient responded to vancomycin therapy. One patient had refractory peritonitis despite vancomycin, but responded to imipenem and amikacin combination therapy. One patient had relapsing peritonitis and required catheter removal. The fourth patient had an elective Tenckhoff catheter exchange. No patient died of peritonitis. Causative organism was not fully identified until 7 to 18 days of peritonitis.. Gordonia species is increasingly recognized to cause serious infections. In patients undergoing peritoneal dialysis, Gordonia peritonitis should be considered in case of refractory Gram-positive bacilli peritonitis, especially when the exact organism could not be identified one week after the onset of peritonitis. A close liaison with a microbiologist is needed for a timely diagnosis.

Topics: Actinomycetales Infections; Aged; Anti-Bacterial Agents; Device Removal; Disease Management; Gordonia Bacterium; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Male; Meropenem; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prosthesis-Related Infections; Recurrence; Thienamycins; Treatment Outcome; Vancomycin

The safety profile of meropenem in the elderly (aged > 65 years, n=843) and/or renally impaired (creatinine clearance < 51 ml/min, n=436) was assessed by evaluating data from 26 phase III studies which compared the use of meropenem (0.5 or 1.0 g, i.v. every 8 h) with other antimicrobial agents in patients with bacterial infections. The overall pattern and frequency of adverse events following meropenem therapy in the elderly and/or renally impaired were similar to those in younger and/or non-renally impaired cohorts and to imipenem/cilastatin and injectable third generation cephalosporins. Both dosages of meropenem (0.5 and 1.0 g, i.v. every 8 h) were generally well tolerated. There was no clinically significant mean change in indicators of renal flux between baseline and the end of treatment in any patient sub-group. Importantly, meropenem-related seizures were rare (0.1%), even in patients with renal impairment. In summary, meropenem has an excellent safety profile and is therefore suitable for use in elderly and/or renally impaired patients.

Topics: Aged; Bacterial Infections; Humans; Kidney Failure, Chronic; Meropenem; Seizures; Thienamycins

To evaluate the effect of direct hemoperfusion with polymyxin B immobilized cartridge (DHP-PMX) on meropenem pharmacokinetics in critically ill patients with sepsis requiring continuous venovenous hemofiltration (CVVH).. After intravenous infusion of 1 g meropenem over 3 h repeated every 8 h for at least 3 doses, 2 serial blood and ultrafiltration fluid samples were collected: one over a dose interval of meropenem with DHP-PMX therapy; and the other on the following day over a dose interval of meropenem with no DHP-PMX therapy. Meropenem concentrations were measured by high performance liquid chromatography. Pharmacokinetic parameters of meropenem and extraction ratio of DHP-PMX were calculated.. No significant effect of DHP-PMX on meropenem pharmacokinetics was observed among severe sepsis/septic shock patients during CVVH treatment.. Clinical Trial Registry detail: NCT registry: 02413541 (First registered March 3, 2015, last update October 16, 2017).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Female; Hemoperfusion; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Meropenem; Middle Aged; Polymyxin B; Prospective Studies; Shock, Septic; Treatment Outcome

We analysed the pharmacokinetics of meropenem and piperacillin-tazobactam in patients undergoing a standardised session of sustained low efficiency haemodiafiltration (SLED-HDF) to inform the dosing of these drugs in an acute setting.. Six stable patients with end-stage kidney disease.. An open-label pilot pharmacokinetic study of meropenem and piperacillin-tazobactam. SLED-HDF was undertaken for 4 h. Plasma drug concentrations were measured pre- and post-filter and in the effluent at multiple time points. The pharmacokinetic data was analysed using non-compartmental methods. The fraction of time that individual plasma concentration profiles were predicted to remain above the MIC break-points for commonly isolated gram-negative pathogens during a prolonged SLED-HDF session was assessed using two targets; fT > MIC (fraction of time above the MIC) and the more aggressive fT > 4 × MIC (fraction of time above 4 × MIC).. Meropenem total and SLED-HDF clearance ranged from 141 to 180 mL/min and 126-205 mL/min, respectively. Piperacillin total and SLED-HDF clearance values ranged from 131 to 252 mL/min and 135-162 mL/min, respectively. Our results suggest that prolonged SLED-HDF (12 h) will only maintain a sufficient meropenem and piperacillin-tazobactam plasma concentration to achieve a target of fT > MIC for gram-negative pathogens (MIC 2 mg/L-meropenem, 8 mg/L-piperacillin-tazobactam) for less than 40% of the time. Plasma concentrations would be inadequate to achieve the more aggressive target of 100 % fT > 4xMIC target recommended for critically unwell patients.. The pharmacokinetic data obtained from this pilot study demonstrate significant quantities of meropenem and piperacillin are removed during a SLED-HDF session. This may lead to subtherapeutic concentrations of piperacillin and meropenem over the duration of HDF session.. Australasian Clinical Trials Registry Network (ACTRN12616000078459).

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Hemodiafiltration; Humans; Kidney Failure, Chronic; Male; Meropenem; Middle Aged; Pilot Projects; Piperacillin, Tazobactam Drug Combination

The objectives of this study were to evaluate the effect of hemodialysis (HD) on the pharmacokinetics (PK) of meropenem/vaborbactam, an approved beta-lactam/beta-lactamase inhibitor combination, and provide the rationale for the recommended timing of meropenem/vaborbactam administration relative to HD in end-stage renal disease (ESRD) patients. Population PK models were developed separately for meropenem and vaborbactam in subjects with normal renal function and different degrees of renal impairment, including those receiving HD. Simulations were performed to evaluate the exposure of meropenem and vaborbactam in ESRD patients who received a fixed dose of 0.5 g/0.5 g meropenem/vaborbactam every 12 hours as a 3-hour intravenous infusion under various drug administration schedules relative to HD. The probability of target attainment (PTA) analyses were conducted with pharmacokinetic/pharmacodynamic (PK/PD) targets of meropenem and vaborbactam. Simulations showed that HD reduces the accumulation of vaborbactam, but the exposure of vaborbactam is still above the PK/PD target regardless of whether meropenem/vaborbactam is administered predialysis or postdialysis. For meropenem, drug infusion completed right prior to initiation of HD may substantially reduce exposure leading to poor PTA results. In contrast, drug infusion completed at least 2 hours prior to initiation of HD is not predicted to result in efficacy loss based on PTA analysis. The results of simulation indicate that meropenem/vaborbactam infusion completed at least 2 hours prior to initiation of HD or administered immediately after the end of HD can avoid potential efficacy loss in ESRD patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Boronic Acids; Clinical Trials as Topic; Computer Simulation; Creatinine; Drug Administration Schedule; Drug Combinations; Glomerular Filtration Rate; Heterocyclic Compounds, 1-Ring; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Meropenem; Middle Aged; Models, Biological; Renal Dialysis; Young Adult

A 57-year-old woman with Hurley Stage 3 hidradenitis suppurativa (HS) and multiple co-morbidities is presented. She had failed multiple antibiotic therapies and etanercept. She had end stage renal disease and was on dialysis. Her HS was put into remission with one month of daily IV treatment with 1.2 grams linezolid and 1 gram of meropenem, administered daily through her dialysis shunt. Unfortunately, her disease flared again two weeks after the cessation of the IV treatment. Nevertheless, more conventional therapy was then able to maintain her disease at a level that was significantly improved over baseline prior to the IV treatment. This case highlights above all a primary etiology of HS is stimulus of immune system's over-reaction in HS to the bacterial microbiome. If antibiotics are administered to a patient with stage 3 HS powerful enough to wipe out the bacterial biome, the immune system having no target retreats, permanent scarring in its wake and retreats to a certain but hardly permanent normalcy.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Female; Hidradenitis Suppurativa; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Linezolid; Meropenem; Middle Aged; Obesity, Morbid; Polycystic Kidney Diseases; Remission Induction; Thienamycins

Topics: Adult; Allografts; Anastomosis, Surgical; Aneurysm, Infected; Gout; Humans; Hyperuricemia; Iliac Artery; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Meropenem; Postoperative Complications; Renal Artery; Teicoplanin; Thienamycins; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Ceftazidime; Coronary Sinus; Diagnosis, Differential; Endocarditis; Female; Follow-Up Studies; Gentamicins; Humans; Hypertension; Kidney Failure, Chronic; Meropenem; Renal Dialysis; Thienamycins; Treatment Outcome; Ultrasonography; Young Adult

Topics: Aged; beta-Lactamases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Renal Dialysis; Republic of Korea

The purpose of this study was to examine the removal of meropenem during an 8-h sustained low-efficiency dialysis (SLED) session. Using a minimum inhibitory concentration (MIC) = 2 microg/mL as our reference point, we also evaluated the therapeutic adequacy of dosing meropenem as 1 g every 12 h during SLED.. This was a prospective, open-label study involving 10 intensive care unit patients with renal failure needing SLED. Meropenem was dosed as 1 g every 12 h. To ensure a steady state, the patients received at least two doses prior to the study. SLED was initiated at least 2 h after the last meropenem dose, and each session was at least 8 h. Blood samples were collected during SLED at 0, 2, 4 and 8 h. The 8-h sample approximated the trough level. After centrifuging the samples, the supernatants were analysed by high-performance liquid chromatography.. Most patients were male with a mean age of 63.7 years and a mean weight of 88.9 kg. The SLED prescription was based on each patient's needs, and the blood flow, dialysate flow and ultrafiltration rates varied by up to 150 mL/min. The mean reduction of plasma meropenem concentration was 79.1 +/- 7.3%, and the mean half-life was 3.6 +/- 0.8 h during the 8-h SLED. Significantly more meropenem was removed in the first 4 h of SLED compared with the rest of the sessions. The mean plasma trough concentration was 4 +/- 1.6 microg/mL.. Meropenem was significantly removed from the blood compartment during SLED. Dosing 1 g of meropenem every 12 h during a typical 8-h SLED session maintains adequate plasma concentrations.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Critical Illness; Dose-Response Relationship, Drug; Female; Humans; Intensive Care Units; Kidney Failure, Chronic; Male; Meropenem; Middle Aged; Prospective Studies; Regional Blood Flow; Renal Dialysis; Thienamycins; Time Factors; Ultrafiltration

Acinetobacter baumannii are emerging as the causal agents of healthcare-associated infections. We describe arenal transplant recipient who developed bacteremia caused by multiresistant A. baumannii, which received a combination of tigecycline, colistin, and meropenem in continuous infusion. The clinical outcome was favorable. In this article we made a molecular study of this multiresistant strain. Our analysis reveals the presence of abla-OXA-72 gene,a class D of oxacillinase belonging to bla-OXA-40-like group,which constitutes the most disseminated familiy of carbapenemases in Spain. Thus, we found different susceptibility patterns of A. baumannii when we used different Mueller-Hinton agars with different manganese concentrations. Lastly, we explain the combination of these three antibiotics administered to increase microbiologic and pharmacodynamic yield.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Meropenem; Microbial Sensitivity Tests; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins; Tigecycline

Calciphylaxis is a rare complication that occurs in 1% of patients with end-stage renal disease (ESRD) each year. Extensive microvascular calcification and occlusion/thrombosis lead to violaceous skin lesions, which progress to nonhealing ulcers with secondary infection, often leading to sepsis and death. The lower extremities are predominantly involved (roughly 90% of patients). Although most calciphylaxis patients have abnormalities of the calcium-phosphate axis or elevated levels of parathyroid hormone, these abnormalities do not appear to be fundamental to the pathophysiology of the disorder. We report on a case of histologically proven calciphylaxis in a 54-year-old woman with normal renal function and normal calcium-parathyroid homeostasis. She had a history of alcoholic cardiomyopathy, and was treated with warfarin anticoagulation. She has been successfully treated with antibiotics, i.v. biophosphonates and intensive local wound care. We recorded a complete wound healing in contrast to what is reported in other series.

Topics: Alcoholism; Anti-Bacterial Agents; Anticoagulants; Calciphylaxis; Clindamycin; Diphosphonates; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Meropenem; Middle Aged; Risk Factors; Thienamycins; Vancomycin; Warfarin

Topics: Adult; Anti-Bacterial Agents; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Neutrophils; Phagocytosis; Thienamycins

Chryseobacterium meningosepticum is a lactose-nonfermenting gram-negative bacilli ubiquitously found in the natural and hospital environment. Clinical infection caused by C. meningosepticum is very rare among healthy adults. We present the case of a patient with end-stage renal disease who developed purulent pericarditis with C. meningosepticum infection, which rapidly evolved into cardiac tamponade and death. To our knowledge, this is the first case in which C. meningosepticum caused fatal purulent pericarditis in a hemodialysis patient.

Topics: Aged; Anti-Bacterial Agents; Cardiac Tamponade; Chryseobacterium; Ciprofloxacin; Fatal Outcome; Flavobacteriaceae Infections; Humans; Kidney Failure, Chronic; Male; Meropenem; Pericarditis; Renal Dialysis; Thienamycins; Vancomycin

Topics: Anti-Bacterial Agents; Ascitic Fluid; Child, Preschool; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Imipenem; Infusions, Parenteral; Kidney Failure, Chronic; Male; Medication Errors; Meropenem; Myoclonus; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Thienamycins; Tobramycin

The emergence of multi-drug-resistant bacteria is of great concern to the care of pediatric end-stage renal disease (ESRD) patients who receive either hemodialysis or peritoneal dialysis via a catheter. Infections with gram-negative organisms, especially Pseudomonas aeruginosa, are difficult to eradicate and often necessitate catheter removal. Meropenem, a broad-spectrum antibiotic of the carbapenem class of beta-lactams, is effective against most gram-positive and gram-negative bacteria and has enhanced activity against P. aeruginosa. We studied the pharmacokinetics of meropenem during and between hemodialysis treatments in seven pediatric patients. Meropenem was given as a single dose of 20 mg/kg (maximum 500 mg) before and after two separate hemodialysis treatments. Meropenem administration was tolerated without any adverse effects. Hemodialysis effectively cleared meropenem in a manner that correlated with percent urea reduction. Median drug half-life was 7.3 h off dialysis (range 4.9-11.7 h). The dose of 20 mg/kg was not sufficient to produce an acceptable interdialytic pharmacodynamic profile of 70% duration with a meropenem concentration >4 microg/ml, the MIC90 of meropenem for P. aeruginosa. Dosing simulations revealed that a daily dose of 25 mg/kg or an alternate day dose of 40 mg/kg would result in an acceptable pharmacodynamic profile. Both simulated doses achieved acceptable peak concentrations.

Topics: Adolescent; Child; Child, Preschool; Computer Simulation; Dose-Response Relationship, Drug; Female; Humans; Infant; Kidney Failure, Chronic; Male; Meropenem; Models, Theoretical; Renal Dialysis; Thienamycins

The safety profile of meropenem in the elderly (aged > 65 years, n = 843) and/or renally impaired (creatinine clearance < 51 ml/min, n = 436) was assessed by evaluating data from 26 phase III studies which compared the use of meropenem (0.5 or 1.0 g, i.v. every 8 h) with other antimicrobial agents in patients with bacterial infections. The overall pattern and frequency of adverse events following meropenem therapy in the elderly and/or renally impaired were similar to those in younger and/or non-renally impaired cohorts and to imipenem/cilastatin and injectable third generation cephalosporins. Both dosages of meropenem (0.5 and 1.0 g, i.v. every 8 h) were generally well tolerated. There was no clinically significant mean change in indicators of renal flux between baseline and the end of treatment in any patient sub-group. Importantly, meropenem-related seizures were rare (0.1%), even in patients with renal impairment. In summary, meropenem has an excellent safety profile and is therefore suitable for use in elderly and/or renally impaired patients.

Topics: Aged; Bacterial Infections; Humans; Kidney Failure, Chronic; Meropenem; Seizures; Thienamycins

The pharmacokinetics of meropenem were studied after intravenous infusion in 13 patients grouped according to the impairment of their renal function. Creatinine clearance (CLCR) was greater than 50, 50 to 30, and less than 30 ml/min in groups I, II, and III, respectively. Two other groups, groups IV and V, each comprising four patients with end-stage renal disease (CLCR, < 5 ml/min), were also studied, the former on days off of hemodialysis and the latter on days of hemodialysis. The elimination half-lives of meropenem were 1.54 +/- 0.70 h in group I patients, 3.36 +/- 1.02 h in group II patients, and 5.00 +/- 1.05 h in group III patients. Cumulative urinary excretion accounted for 48.5% of the dose in group I patients and decreased progressively with a decline in renal function. Hemodialysis shortened the elimination half-life of meropenem from 7.0 h to 2.9 h. H-4295, the main metabolite of meropenem, had a peak level in plasma of 0.5 to 1.0 h in patients with renal failure. The level of H-4295 decreased with hemodialysis. The dosing interval of meropenem should be prolonged in a regular proportion to the decline in CLCR (12 h in group II patients and 24 h in group III patients). In patients receiving hemodialysis, dosing after each hemodialysis session is recommended.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Infusions, Intravenous; Kidney Diseases; Kidney Failure, Chronic; Male; Meropenem; Middle Aged; Models, Biological; Pyrroles; Renal Dialysis; Thienamycins

The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 micrograms.ml-1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.

Topics: Adult; Glomerular Filtration Rate; Humans; Injections, Intravenous; Kidney Failure, Chronic; Meropenem; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Thienamycins; Time Factors; Uremia