Safe use of imipenem/cilastatin in a neonatal intensive care unit

Infection and Drug Resistance, 2015

Imipenem/cilastatin is an antibacterial agent of the carbapenem class of β-lactams that is known to have an extremely wide spectrum of activity against Gram-positive, Gram-negative, aerobic, anaerobic, and even multidrug-resistant strains. The objective of this study was to evaluate the appropriate use of imipenem/cilastatin in a local tertiary care hospital. The study assessed the indication both empirically and after the culture results were available, the dose and dose adjustment in renal failure, as well as the incidence of seizure in hospitalized patients receiving imipenem/cilastatin. This observational study was conducted in a tertiary care hospital over a 3-month period. The treatment of 100 patients with imipenem/cilastatin was evaluated both empirically and after culture results were available. Analysis of the appropriateness of imipenem/cilastatin indication, dose, and monitoring of seizure frequency was based on the package insert, updated published guidelines, and clinical judgment. Patients from internal medicine and intensive care units comprised approximately 50% of the population in the study. The patients received imipenem/cilastatin mainly for urinary tract infections (27%) or for sepsis of an unknown focus (22%). The use of imipenem/cilastatin empirically was appropriate in 97.2% (n=69/71) of the cases, and its use postculture in 86% of the cases. There were 29% of the patients who were not started on imipenem/cilastatin empirically. Four patients out of the 29 patients (13.8%) who were not started on imipenem/cilastatin empirically inappropriately received imipenem/cilastatin post-culture results. Thirty-three patients (33%) were not dosed appropriately, 30 of whom had renal impairment and creatinine clearance fluctuations. Only one patient developed a seizure while on imipenem/cilastatin. The prescription of imipenem/cilastatin at our setting was mostly appropriate to what is recommended in the guidelines and the literature, although a few cases could have been managed better. Dosage adjustment, however, was not as appropriate, mainly in patients who did not have a stable creatinine clearance.

Current Drug Safety, 2024

Background: Imipenem-cilastatin, a carbapenem antibiotic, is commonly used for severe bacterial infections. While generally well-tolerated, it can rarely cause central nervous system toxicity, including seizures. We have, herein, reported a case of imipenem-cilastatin-induced seizure in a 20-year-old patient. Case Presentation: A 20-year-old male was admitted to the intensive care unit for febrile status epilepticus and acute respiratory distress syndrome. Initial evaluations ruled out underlying causes and anti-epileptic treatment has been initiated. Despite having an effective anti-epileptic treatment for three months of hospitalization, seizure recurrence occurred, leading to antibiotic regimen adjustment as the imputability of imipenem-cilastatin was suspected. After discontinuation of the involved drug, the patient remained neurologically stable. Previous literature has reported cases of imipenem-cilastatin-induced seizures, particularly in elderly patients or at higher dosages. The causality assessment was conducted using the updated French method, which rated the chronological criterion as C2 and the semiological criterion as S2. The intrinsic imputability score was I3, indicating plausible causality, and the extrinsic bibliographic score was B3. Conclusion: Our case has highlighted the importance of promptly recognizing imipenem-cilastatin-induced epileptic seizures in order to treat them more effectively and thus optimize the patient's care. Therefore, we emphasize that clinicians be vigilant about the side effects of its use, particularly in patients with neurological susceptibilities. We also advocate a personalized choice of antibiotics, taking into account both antimicrobial efficacy and potential adverse effects, for better outcomes with fewer risks.

Antimicrobial Agents and Chemotherapy, 1985

The single-dose pharmacokinetics of imipenem (N-formimidoyl thienamycin), a I8-lactam antibiotic, used in combination with cilastatin, a renal dehydropeptidase I inhibitor, were evaluated in 10 neonates 1 to 8 days of age. The imipenem-cilastatin combination was given intravenously over a 15-min period at a dose of 15 or 25 mg/kg. Drug concentrations in serum, urine, and cerebrospinal fluid (when available) were determined by high-pressure liquid chromotography, and plasma disposition of the drugs was described by a two-compartment open model. The mean peak plasma levels of imipenem 30 min postinfusion were 55.4 and 27.2 ,ug1ml, and the mean t1i20 values were 2.1 and 1.8 h at doses of 25 and 15 mg/kg, respectively. The calculated volume of distribution was 0.41 liters/kg. In two patients from whom cerebrospinal fluid was obtained 1.5 h postinfusion, imipenem levels were 5.6 and 1.1 ,ug/ml at doses of 25 and 15 mg/kg, respectively, representing 10 and 4% of the 1-h serum levels. No side effects attributable to a single dose of imipenem-cilastatin were noted.

Clinical Pharmacology and Therapeutics, 1985

The safety and tolerability of 1 gm imipenem and cilastatin given together every 6 hours for 10 days was evaluated in a randomized, double-blind, placebo-controlled trial in normal subjects. Nausea was more common in the drug-treated group (five of six subjects) than in the control group (two of six subjects). No consistent changes in hepatic function indices were noted. Although P,-microglobulin excretion showed a significant trend of rising over time in the drug group, there were no differences between groups with regard to 24-hour urinary excretion of either N-acetyl-P-glucosaminidase or P,-microglobulin. Urinalysis did not reveal any casts and serial creatinine clearance determinations showed no change in renal function in either the drug-or placebo-treated groups. Pure tone audiograms were performed before and after dosing in 11 of 12 subjects; no changes were noted. We conclude that the combination of imipenem and cilastatin was well tolerated and safe. (CLIN PHARMACOL WR 37539443, 1985.

Antimicrobial Agents and Chemotherapy, 2006

Plasma imipenem concentrations were measured in 19 critically ill children (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual variations (2 to 4؋ at peak and >10؋ at trough concentrations) resulted in unpredictable plasma levels in several children. To avoid subtherapeutic drug levels, we recommend treatment with at least 100 mg/kg of body weight/day of imipenem-cilastatin for critically ill children requiring such therapy.

Journal of Antimicrobial Chemotherapy, 2009

Arquivos De Neuro-psiquiatria, 2010

El Six Sigma es un término definido por el ingeniero Bill Smith, durante los años ochenta, creando en Motorola una propuesta de reducción de defectos en los productos mediante la resolución de problemas. Incluye como mejoras la cuantificación del objetivo de la prestación de un proceso y se utilizó satisfactoriamente también en General Electric. La carta griega sigma es un término matemático que simplemente representa una medida de variación, como la extensión alrededor del promedio de cualquier proceso. El valor de sigma, o la desviación estándar, indican cómo cualquier proceso funciona. Mientras más alto el valor, menos serán los defectos por millón de oportunidades. Seis Sigma también es el uso disciplinado de las herramientas estadísticas de resolución de problemas que indican gastos derrochadores y dirige pasos exactos para la mejora. Es un método basado en datos que examina los procesos repetitivos de las empresas y su objetivo es llevar la calidad a niveles altos y se propone una cifra de 3,4 errores por un millón de oportunidades. Además, se corrigen los problemas antes de que se presenten. Six Sigma constituye un modelo de gestión de calidad que también se conoce como DMAIC, siglas de las palabras en inglés: define, measure, analyze, improve y control. En español: definir, medir, analizar, mejorar y controlar. Los cuales aplican una metodología de medida para lograr entender el funcionamiento y las variables que afectan la calidad de productos y servicios. Es importante conocer la forma de aplicación, sus principales características y si implica o no una inversión o un gasto la aplicación del six sigma para la administración de un negocio esto, con el fin de mejorar la calidad, tomando en cuenta que ciertas empresas que ofrecen un servicio o un producto no pueden tener margen de error y su calidad debe ser alta para satisfacer al cliente y para lograrlo es necesario definir y comprender algunos conceptos básicos importantes para lograr el éxito mediante esta implementación ya sea, en una organización con procesos simples o una con procesos más complejos.

АРХЕОЛОГІЯ & ФОРТИФІКАЦІЯ, 2024

Статтю присвячено огляду експериментів, проведених авторами впродовж 2018–2022 рр. із метою вивчення технологічних стратегій і соціо-поведінкових шаблонів гомінін нижньопалеолітичних стоянок Меджибожа. Відповідно до контексту пам’яток, а також техніко-типологічних особливостей їхніх індустрій, було реалізовано кілька експериментальних моделей, спрямованих на виявлення артефакт-діагностичних характеристик продуктів каменеобробки, дослідження техніко-морфологічних індикаторів застосування конкретної техніки первинної чи вторинної обробки, з’ясування умов виникнення нарізок на кістках різної морфології.

Epigraphers have long appreciated that one of the distinguishing features of the developed linear alphabetic scripts of the first millennium Levant (e.g., Phoenician, Old Hebrew, Aramaic) is unidirectional writing from right to left in horizontal lines. Frank Moore Cross had determined that the shift to this new meta-script profile was complete by ca. 1050 BCE. 1 More recent epigraphic finds, such as the inscribed bowl fragment from Tell eṣ-Ṣ afi, 2 the ostracon from Khirbet Qeiyafa, 3 and the Meggido jug sherd, 4 require lowering this date by as much as a century or more, to 1000/950 BCE and possibly later. 5 The phase of alphabetic writing that leads up to this point witnesses the loss of iconicity in the shapes of individual letters as they become more cursive or schematized (linear) and an increased incidence of unidirectional, horizontal writing, though multidirectional writing still appears. 6 What