Low-cost and versatile analytical tool with purpose-made capillary electrophoresis coupled to contactless conductivity detection: Application to antibiotics quality control in Vietnam.

In this study, the development of our purpose-made capacitively coupled contactless conductivity detection (C4 D) for CE is reported. These systems have been employed as a simple, versatile, and cost-effective analytical tool. CE-C4 D devices, whose principle is based on the control of the ion movements under an electrical field, can be constructed even with a modest financial budget and limited infrastructure. A featured application was developed for quality control of antimicrobial drugs using CE-C4 D, with most recent work on determination of aminoglycoside and glycopeptide antibiotics being communicated. For aminoglycosides, the development of CE-C4 D methods was adapted to two categories. The first one includes drugs (liquid or powder form) for intravenous injection, containing either amikacin, streptomycin, kanamycin A, or kanamycin B. The second one covers drugs for eye drops (liquid or ointment form), containing either neomycin, tobramycin, or polymyxin. The CE-C4 D method development was also made for determination of some popular glycopeptide antibiotics in Vietnam, including vancomycin and teicoplanin. The best detection limit achieved using the developed CE-C4 D methods was 0.5 mg/L. Good agreement between results from CE-C4 D and the confirmation method (HPLC- Photometric Diode Array ) was achieved, with their result deviations less than 8% and 13% for aminoglycoside and glycopeptide antibiotics, respectively.

Aminoglycosides for infective endocarditis: time to say goodbye?

BACKGROUND: Based on experimental studies showing synergism with ß-lactams and glycopeptides, aminoglycosides have long been considered essential in the treatment of infective endocarditis (IE). However, their use is associated with a high risk of renal failure, especially in elderly patients. AIMS: The aim of this narrative review was to summarize the evidence to support reducing or even avoiding the use of aminoglycosides for the treatment of IE. We also analysed data supporting the use of aminoglycosides in specific subgroup of IE patients. SOURCES: PubMed database was searched up to July 2019 to identify relevant studies. CONTENTS: Recent European Guidelines reduced the use of aminoglycosides in IE, no longer recommended in Staphylococcus aureus native-valve IE, and shortened to 2 weeks for IE related to Enterococcus faecalis and streptococci with penicillin MIC >0.125 µg/mL. In addition, an alternative regimen without aminoglycosides (ampicillin or amoxicillin plus ceftriaxone) is proposed for E. faecalis. Observational studies suggested that gentamicin would not be necessary in the case of staphylococcal prosthetic valve IE as long as rifampicin is maintained. Recent clinical studies showed that for streptococcal IE, gentamicin could be restricted to isolates with penicillin MIC >0.5 µg/mL. For the empirical and definitive treatment of E. faecalis IE, amoxicillin or ampicillin plus ceftriaxone may be considered, irrespective of high-level of aminoglycoside resistance. IMPLICATIONS: In a scenario of progressive increase in the age and frailty of IE patients, the use of aminoglycosides can be reduced or avoided in ~90% cases. This should result in reduced incidence of renal failure, an important prognostic factor in IE.

Antibióticos y trastornos de la marcha / Antibiotics and gait disorders

Resumen. La toxicidad neurológica de muchos antibióticos se ha documentado en numerosos artículos y notas clínicas. En esta revisión se clasifican los antibióticos en función del mecanismo fisiopatogénico por el que pueden provocar un trastorno de la marcha, teniendo en cuenta tanto datos clínicos como experimentales. Se ha realizado una búsqueda exhaustiva en Google Scholar y PubMed con el objetivo de encontrar revisiones, artículos y casos clínicos acerca de trastornos de la marcha secundarios a distintos antibióticos. Se han separado los diferentes antibióticos en función del mecanismo fisiopatogénico por el cual podrían producir una alteración de la marcha. Se han clasificado en antibióticos capaces de producir ataxia cerebelosa, ataxia vestibular, ataxia sensitiva o un trastorno de la marcha extrapiramidal. El principal objetivo era agrupar todos los fármacos que pueden provocar un trastorno de la marcha, para facilitar la sospecha clínica y, en consecuencia, el tratamiento de los pacientes (AU)

Summary. The neurological toxicity of many antibiotics has been reported in a number of articles and clinical notes. In this review antibiotics are classified according to the physiopathogenic mechanism that can give rise to a gait disorder, taking both clinical and experimental data into account. An exhaustive search was conducted in Google Scholar and PubMed with the aim of finding reviews, articles and clinical cases dealing with gait disorders secondary to different antibiotics. The different antibiotics were separated according to the physiopathogenic mechanism that could cause them to trigger a gait disorder. They were classified into antibiotics capable of producing cerebellar ataxia, vestibular ataxia, sensitive ataxia or an extrapyramidal gait disorder. The main aim was to group all the drugs that can give rise to a gait disorder, in order to facilitate the clinical suspicion and, consequently, the management of patients (AU)

Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity.

The new Australian Therapeutic Guidelines: Antibiotic, version 14 have revised the recommendations for the use and monitoring of aminoglycosides. The guidelines have clear distinctions between empirical and directed therapy as well as revised recommendations about the monitoring of aminoglycosides. This has led many clinicians to review their current practice with regard to the use of aminoglycosides. This review summarizes why aminoglycosides are still a valid treatment option and discusses the rationale for current dosing regimens in Gram-negative infections. In particular it focuses on the various methods for monitoring aminoglycosides that are currently being used. The aminoglycoside monitoring methods can be categorized into three groups: linear regression analysis (one compartment model), population methods and Bayesian estimation procedures. Although the population methods are easy to use and require minimal resources they can recommend clinically inappropriate doses as they have constant pharmacokinetic parameters and are not valid in special population groups, that is, renal impairment. The linear regression and Bayesian methods recommend more accurate dosage regimens; however, they require additional resources, such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offer additional advantages, such as calculation of doses based on a single serum concentration and optimization of the patient's previous pharmacokinetic data, in order to determine subsequent dosage regimens. We recommend the Bayesian estimation procedures be used, wherever feasible. However, they require the expertise of healthcare practitioners with a good understanding of pharmacokinetic principles, such as clinical pharmacists/clinical pharmacologists, in order to make appropriate recommendations.

Pharmacist-driven aminoglycoside quality improvement program.

Our objective was to determine the impact of a pharmacist-driven aminoglycoside quality improvement program on the dosing methods of aminoglycosides at our institution. We assessed our current quality through retrospective review of all patients receiving aminoglycosides during a 5-month period. we then developed and implemented a pharmacist-driven aminoglycoside dosing program and prospectively assessed patients during a matched 5-month period. two hundred and sixteen patients were evaluated, 87 pre-program and 129 post-program. Prior to standardized pharmacist intervention, 44% of patients achieved optimal therapy. Oost implementation, patients achieving optimal therapy increased to 80% (p < 0.001). Patients in the pre-program group had a higher rate of acute changes in renal function compared to the post-program group (14.9% versus 6.2% [p <0.05]). This pharmacist-driven aminoglycoside dosing quality improvement program increased the frequency of optimal dosing of aminoglycosides and reduced the incidence of nephrotoxicity at our institution.

[Control of the quality of antibiotics in the European Pharmacopoeia: recent development in the case of aminoglycosides]. / Contrôle de qualité des antibiotiques dans la Pharmacopée Européenne: évolution récente dans le cas des aminosides.

Aminoglycosides constitute a particular class of antibiotics presenting aminoglycoside moieties linked to a central aminocyclitol ring. Several aminoglycosides are described by a monograph in the European Pharmacopoeia. The related substances test is used to check for impurities. For this purpose, thin layer chromatography is now being replaced by high performance liquid chromatography. In the case of aminoglycosides the main challenge is the detection of these compounds since they do not possess a chromophore in their structure. Different possibilities are proposed in the monographs. Amikacine is detected at 340 nm after pre-column derivatization. In more recent monographs, pulsed amperometry detection is proposed. However, this mode of detection requires skillful manipulations. Evaporative light scattering detection could be a valuable alternative. The advantages and drawbacks of each approach will be discussed.