meropenem and Kidney-Diseases

Essential for drug dose adjustment is the glomerular filtration rate (GFR) not the serum creatinine level. In acute disease, a loading dose must be given that usually corresponds to the normal dose. The eliminated half-life is used to estimate the administration interval. For anti-infective drugs with a concentration-dependent effect, the target is the high peak such as for daptomycin, linezolide, and colistin. For anti-infective drugs with a time-dependent effect, the target is the high trough such as for piperacillin, meropenem and vancomycin. Such drugs with a time-dependent action should best be administered by infusion not by bolus dosing. With continuous renal replacement therapy (CRRT), the total filtration rate corresponds to a GFR of 30-50 ml/min and many antibiotics will not need a dose reduction on CRRT. After intermittent hemodialysis, a new loading dose should be given to ascertain sufficiently high concentrations in the interval until the next dose or next dialysis.

Topics: Anti-Bacterial Agents; Critical Illness; Glomerular Filtration Rate; Humans; Kidney Diseases; Meropenem; Pharmacokinetics; Piperacillin; Vancomycin

Meropenem is a recently developed carbapenem antibiotic, similar to imipenem, with a wide spectrum of activity against Gram-positive and Gram-negative bacteria. In comparison with imipenem, meropenem is relatively stable to hydrolysis by the enzyme dehydropeptidase I (DHP-I), thus precluding the need for coadministration with an inhibitor of DHP-I, such as cilastatin. Furthermore, meropenem may be less nephrotoxic and neurotoxic than imipenem. Plasma meropenem concentrations reach a peak (Cmax) of approximately 30 mg/L after administration of a standard dose of 1 g intravenously. The elimination half-life (t1/2) is approximately 1 hour, and the area under the plasma concentration-time curve increases linearly in a dose-related manner. The volume of distribution is 21L, indicating predominantly extracellular distribution. Meropenem distributes partly into cerebrospinal fluid. The drug is eliminated both by metabolism and excretion. In normal volunteers, up to 70% is recovered in urine, and the remainder is accounted for by a beta-lactam ring-opened form of the compound, ICI 213689. The t1/2 of meropenem is prolonged in patients with renal insufficiency and correlates well with creatinine clearance. Dosage adjustments in people with decreased creatinine clearance can, thus, be made on the basis of creatinine clearance.

Topics: Aged; Child; Humans; Kidney Diseases; Meropenem; Postoperative Care; Thienamycins

Meropenem is a new carbapenem antibiotic which differs chemically from imipenem/cilastatin by having a 1-beta-methyl substitution, providing it with excellent intrinsic stability to human renal dehydropeptidase-I. In addition, an altered 2' side chain enhances its anti-pseudomonal activity. The drug has one identified metabolite, a beta-lactam ring-opened form which is devoid of microbiological activity, as would be expected. The parent compound displays linear pharmacokinetics over a dose range of 250 mg to 2 g. The terminal half-life is approximately 1 hour and the plasma clearance is approximately 15.5 L/h/70 kg. The plasma concentrations after a 1 g dose show a trough concentration (8 hours) of slightly greater than 0.25 mg/L. The renal route is the major clearance pathway for this drug and its metabolite, with renal clearance accounting for approximately 70% of the plasma clearance and there being approximately 70% of an administered dose recovered in the urine as intact parent compound over 12 hours. When combined with metabolite, over 90% of administered radiolabel is recovered in the urine over this 12 hour period. As expected, renal functional impairment alters the clearance of meropenem, but the alteration is predictable. Hepatic functional impairment does not alter drug disposition and no dosing alterations are required here. In summary, meropenem's disposition is similar to that seen for imipenem/cilastatin, except that no renal dehydropeptidase-I inhibitor is required. When evaluated against the background of its excellent profile of in vitro activity, it is clear that this is a drug of great promise which should be extensively evaluated in clinical trials of seriously ill patients with nosocomial infections.

Topics: Animals; Biological Availability; Half-Life; Humans; Kidney; Kidney Diseases; Liver Diseases; Meropenem; Middle Aged; Thienamycins

The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 +/- 0.12) was similar to the unbound fraction (0.79 +/- 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.

Topics: Acrylic Resins; Acrylonitrile; Adult; Aged; Aged, 80 and over; Alkanesulfonates; Anti-Bacterial Agents; Female; Hemodiafiltration; Hemofiltration; Humans; Kidney Diseases; Male; Membranes, Artificial; Meropenem; Middle Aged; Permeability; Polymers; Sulfones; Thienamycins

The possible role of JC virus in determining urinary tract involvement has only recently been recognized. The case of a man with laboratory-confirmed JC virus replication in the urine after a maintenance schedule of rituximab administered for a lymphoproliferative disorder is reported herein. The patient developed severe renal and urinary tract impairment, characterized by the onset of nephropathy, bilateral ureteral strictures, and a serious reduction in vesical compliance, ultimately requiring an ileal neobladder configuration. The renal and urinary tract involvement was finally attributed to JC virus reactivation. This observation suggests that renal and urinary tract diseases related to JC virus might be associated with long-term rituximab treatment.

Topics: Antineoplastic Agents, Immunological; Humans; JC Virus; Kidney Diseases; Linezolid; Lymphoproliferative Disorders; Male; Meropenem; Middle Aged; Mirtazapine; Polyomavirus Infections; Rituximab; Tumor Virus Infections; Virus Activation; Virus Latency

Acinetobacter baumannii has emerged as an important nosocomial pathogen worldwide. In Thailand, the incidence and mortality rate of carbapenem-resistant A. baumannii (CRAB) is continuously increasing. This organism is a common pathogen that can cause HAP and VAP. CRAB tends to be susceptible to only colistin, so colistin would be the last line of treatment for CRAB. The recent data from in-vitro studies found that colistin and meropenem combination therapy could exert synergistic effects. However, some in-vivo studies have shown no significant difference in antibacterial effect between colistin monotherapy and colistin plus meropenem. Moreover, the clinical data are recently limited and not clear. Thus, the objective of this study was to compare clinical outcome, microbiological response, mortality rate and nephrotoxicity between loading dose (LD) colistin monotherapy and LD colistin-meropenem for treatment of infection caused by CRAB in Maharaj Nakorn Chiang Mai Hospital.. This study is a retrospective analytical study. The data were collected from patients who received LD colistin monotherapy or LD colistin plus meropenem combination therapy for treatment of CRAB from 1 January 2013 to 31 August 2017 at Maharaj Nakorn Chiang Mai Hospital. A total of 324 patients met the inclusion criteria. The data were analyzed by descriptive statistics and inferential statistics, and were adjusted for confounding factors by logistic regression analysis.. The adjusted OR of good clinical outcome of patients who received LD colistin plus meropenem was 1.05 times that of patients who received loading dose colistin monotherapy (95%CI 0.62-1.74, p=0.860). Patients who received LD colistin plus meropenem had 0.93 times (adjusted OR) mortality rate at the end of treatment compared to patients who received LD colistin monotherapy (95%CI=0.51-1.71, p=0.935). In addition, microbiological response was defined as eradication of pre-treatment isolated pathogens in post-treatment cultures. Patients who received LD colistin plus meropenem could eradicate pathogens 1.28 times more than LD colistin monotherapy (95% CI=0.74-2.20, p=0.371). Also there was no significant difference in nephrotoxicity (adjusted OR=0.84, 95% CI 0.52-1.36, p=0.492) between LD colistin monotherapy and LD colistin plus meropenem.. There were no significant differences in effectiveness and nephrotoxicity of LD colistin monotherapy versus LD colistin plus meropenem for treatment of CRAB infection, so colistin combination therapy was not necessary for the management of infection caused by CRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Kidney; Kidney Diseases; Male; Meropenem; Middle Aged; Retrospective Studies; Thailand

Topics: Adult; Aged; Cilastatin, Imipenem Drug Combination; Drug Therapy, Combination; Female; Humans; Kidney Diseases; Male; Meropenem; Middle Aged; Propensity Score; Retrospective Studies; Vancomycin

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

Meropenem is a restricted, broad spectrum and expensive antibiotic. The major consequences of irrational use of restricted antibiotics are increase drug resistance and drug expenditure. The use of antibiotics, specifically restricted antibiotics, must be monitored continuously to increase its adherence to the standard guidelines to avoid such problems. The objective of this study was to evaluate the appropriateness of meropenem use with respect to renal status of patients in a teaching based hospital. A retrospective study was carried out from 1st January 2013 to 30th June 2013 to determine the evaluation of meropenem use in accordance to the criteria developed through national (Infectious disease society of Pakistan) and international guidelines (Health care infection control practices advisory committee). The data was recorded on data collection form by thorough reviewing of patients' medical records. Main outcomes measured were indication, dose, interval, duration, creatinine clearance, complete blood count and culture sensitivity test. Correlation of different variable (side effects and generalized health) was also observed with reference to renal status of patients. Statistical analyses were performed using descriptive statistics. A total of 201 cases of meropenem prescription were identified during the study period. The variable, which was most consistent with the criteria was 'indication', in which 97.52% of meropenem prescription was indicated in diseases encouraged by guidelines. However, the use of meropenem as an empirical therapy was the major problem reported in this study as it adhered to in only 43% of the cases. It was also noted that prevalence of side effects increased when meropenem was prescribed in renal compromised patients, and also observed that generalized health of patients decreased with meronem use in renal unstable patients. Thrombocytopenia was the major problem associated with the meropenem use (37.81%). The study detected various areas where use of meropenem was not according to the standards. Strict policies and procedures need to be implemented to use meropenem in line with the standard guidelines.

Topics: Anti-Bacterial Agents; Bacterial Infections; Comorbidity; Drug Prescriptions; Drug Utilization Review; Guideline Adherence; Hospitals, Teaching; Humans; Kidney; Kidney Diseases; Meropenem; Patient Selection; Practice Guidelines as Topic; Practice Patterns, Physicians'; Retrospective Studies; Risk Assessment; Risk Factors; Thienamycins; Time Factors; Treatment Outcome

We describe a case of a 66-year-old immunocompetent man affected by Achromobacter denitrificans renal abscess related to renal stones. The patient was treated successfully with meropenem 1 g three times daily for 60 days. To our knowledge, this is the first ever case reported of Achromobacter denitrificans renal abscess.

Topics: Abscess; Achromobacter denitrificans; Aged; Anti-Bacterial Agents; Humans; Kidney Diseases; Male; Meropenem; Thienamycins

CW-270031 is a novel synthesized carbapenem antibiotic with a broad antimicrobial activity. Carbapenem antibiotics are well known for their nephrotoxicity. In this study, we evaluated the nephrotoxicity potential of this compound in rabbits, which are known for being more sensitive than other animals to renal insult. CW-270031 was administered to NZW male rabbits via an ear vein (200 mg/kg, single injection). Blood samples were collected on 2, 3, and 4 days after treatment. Urea nitrogen and creatinine in plasma were quantified. Four days after the treatment, all animals were autopsied and histopathological examinations were performed on their kidneys, revealing that cephaloridine and imipenem were highly nephrotoxic, and cefazolin had mild renal toxicity, whereas CW-270031 as well as meropenem and tienam had no toxicity to the kidney. The present findings suggest that CW-270031 is a potential carbapenem antibiotic with no nephrotoxicity.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Cilastatin; Imipenem; Kidney; Kidney Diseases; Male; Meropenem; Pyrrolidines; Rabbits; Thienamycins

The antibacterial activities of imipenem-cilastatin, meropenem-cilastatin, cefepime and ceftazidime against Enterobacter cloacae NOR-1, which produces the carbapenem-hydrolyzing beta-lactamase NmcA and a cephalosporinase, and against one of its in vitro-obtained ceftazidime-resistant mutant were compared by using an experimental model of pneumonia with immunocompetent rats. The MICs of the beta-lactams with an inoculum of 5 log(10) CFU/ml were as follows for E. cloacae NOR-1 and its ceftazidime-resistant mutant, respectively: imipenem, 16 and 128 microg/ml, meropenem, 4 and 32 microg/ml, cefepime, <0.03 and 1 microg/ml, and ceftazidime, 1 and 512 microg/ml. The chromosomally located cephalosporinase and carbapenem-hydrolyzing beta-lactamase NmcA were inducible by cefoxitin and meropenem in E. cloacae NOR-1, and both were stably overproduced in the ceftazidime-resistant mutant. Renal impairment was induced (uranyl nitrate, 1 mg/kg of body weight) in rats to simulate the human pharmacokinetic parameters for the beta-lactams studied. Animals were intratracheally inoculated with 8.5 log(10) CFU of E. cloacae, and therapy was initiated 3 h later. At that time, animal lungs showed bilateral pneumonia containing more than 6 log(10) CFU of E. cloacae per g of tissue. Despite the relative low MIC of meropenem for E. cloacae NOR-1, the carbapenem-treated rats had no decrease in bacterial counts in their lungs 60 h after therapy onset compared to the counts for the controls, regardless of whether E. cloacae NOR-1 or its ceftazidime-resistant mutant was inoculated. A significant decrease in bacterial titers was observed for the ceftazidime-treated rats infected with E. cloacae NOR-1 only. Cefepime was the only beta-lactam tested effective as treatment against infections due to E. cloacae NOR-1 or its ceftazidime-resistant mutant.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; beta-Lactamases; Carbapenems; Cefepime; Ceftazidime; Cephalosporins; Creatinine; Drug Resistance, Microbial; Enterobacter cloacae; Enterobacteriaceae Infections; Half-Life; Imipenem; Kidney Diseases; Male; Meropenem; Penicillinase; Pneumonia, Bacterial; Protein Binding; Rats; Rats, Wistar; Thienamycins; Uranyl Nitrate

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 meropenem (ICI 194,660) and its open-ring metabolite (ICI 213,689) were studied in 6 healthy volunteers and 16 patients with moderate to severe renal impairment after a single intravenous dose of 500 mg given as a 30-min infusion. Concentrations of unchanged meropenem in plasma and urine were measured by both microbiological and high-pressure liquid chromatographic (HPLC) assays. A good correlation was found between the two techniques. Pharmacokinetic parameters of unchanged meropenem were determined by using the HPLC data. The terminal half-life of unchanged meropenem increased in relation to the degree of renal impairment, being 1.2 h in subjects with normal renal function and 10 h in patients with end-stage renal failure. Total body clearance and renal clearance of unchanged meropenem are linearly related to creatinine clearance. The concentrations of the metabolite in plasma, which are very low in healthy subjects, significantly increased in uremic patients. The apparent half-life of ICI 213,689 increased in uremic patients and was about 35 h in patients with severe renal insufficiency. Meropenem and its metabolite are effectively removed by hemodialysis. The dialysis clearance of the unchanged drug was 81 +/- 22 ml/min. Dosage adjustments of meropenem will be necessary in patients with severe renal impairment.

Topics: Adult; Humans; Kidney Diseases; Meropenem; Middle Aged; Pyrroles; Renal Dialysis; Thienamycins; Uremia

Five healthy volunteers and 18 patients with various degrees of renal impairment received 500 mg of meropenem intravenously as a 30-min infusion. Five dialysis patients were dosed 2 h prior to hemodialysis, and four of them were also dosed between hemodialysis treatments. Plasma and urine samples were collected for up to 48 h and 12 h, respectively. Concentrations of meropenem and its open ring metabolite ICI 213,689 were determined by high-performance liquid chromatography and radioimmunoassay, respectively. The subjects were divided into four groups with glomerular filtration rates (GFR) of greater than 80, 30 to 80, 5 to 29, or less than 5 ml/min. There were linear correlations between the GFR and the rates for total plasma clearance as well as renal clearance of meropenem (group mean values for total clearance of 186, 74, 53, and 19 ml/min/1.73 m2, respectively). In subjects with normal renal function, nonrenal clearance accounted for approximately 20% of total elimination, increasing to about 50% in patients with GFR between 5 and 29 ml/min/1.73 m2. The terminal half-life of meropenem increased from 0.9 h in the healthy volunteers to 6.8 h in patients with end-stage renal disease. The half-life of ICI 213,689 was 2.31 h in the healthy volunteers and increased to 23.6 h in patients with GFR of 5 to 29 ml/min. In patients with end-stage renal disease, half-lives could not be measured, as concentrations were hardly declining during the 48-h observation period. The area under the concentration-time curve for meropenem increased more than 10-fold. Both meropenem and its open ring metabolite were readily dialyzable, with dialysis clearances of 79 and 81 ml/min/1.73 m2, respectively.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Female; Glomerular Filtration Rate; Half-Life; Humans; Infusions, Intravenous; Kidney Diseases; Male; Meropenem; Middle Aged; Renal Dialysis; Thienamycins

The effect of meropenem on animal kidneys has been assessed in rats (5 of each sex/group), rabbits (3 of each sex/group) and monkeys (3 of each sex/group) in comparative iv studies with ceftazidime, cefotaxime, cephaloridine and imipenem (without cilastatin). Diarrhoea occurred in rabbits and monkeys dosed with imipenem or meropenem. Emesis occurred only after the administration of imipenem to monkeys. After 14 days administration to rats evidence of nephrotoxicity was seen only in males dosed with cephaloridine (850 mg/kg); no changes were seen with ceftazidime, cefotaxime or meropenem (all at 1000 mg/kg). Four days after a single dose to rabbits renal tubular necrosis was seen in all animals receiving imipenem (150 mg/kg) and cephaloridine (250 mg/kg). Minimal histopathological changes to the kidneys were seen with cefotaxime, ceftazidime and meropenem (all at 400 mg/kg). After seven days' administration to cynomolgus monkeys imipenem (180 mg/kg) caused moderate to severe tubular necrosis. No tubular damage was seen with meropenem at 180 mg/kg or with cefotaxime or ceftazidime (both at 500 mg/kg). At 500 mg/kg meropenem caused mild tubular regeneration and/or fat accumulation in 3/6 animals, with mild tubular necrosis in one of these. The data from these three species indicate that meropenem has a low nephrotoxic potential in these animal models.

Topics: Animals; Anti-Bacterial Agents; Blood Chemical Analysis; Carbapenems; Cefotaxime; Ceftazidime; Cephaloridine; Female; Kidney Diseases; Macaca fascicularis; Male; Meropenem; Rabbits; Rats; Rats, Inbred Strains; Species Specificity; Thienamycins