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Infectious Diseases Now Nov 2023Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations... (Review)
Review
Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations published by the Groupe de Pathologie Infectieuse de Pédiatrique (GPIP-SFP). Except in rare situations (newborns, neutropenia, sepsis), a positive urine dipstick for leukocytes and/or nitrites should precede a urine culture examination and any antibiotic therapy. After rising steadily between 2000 and 2012, the proportion of Escherichia coli strains resistant to extended-spectrum ß-lactamases (E-ESBL) has remained stable over the last ten years (between 7% and 10% in pediatrics). However, in many cases no oral antibiotic is active on E-ESBL leading either to prolonged parenteral treatment, or to use of a non-orthodox combination such as cefixime + clavulanate. With the aim of avoiding penem antibiotics and encouraging outpatient management, this guide favors initial treatment of febrile urinary tract infections (suspected or actual E-ESBL infection), with amikacin. Amikacin remains active against the majority of E-ESBL strains. It could be prescribed as monotherapy for patients in pediatric emergency departments or otherwise hospitalized patients.
Topics: Humans; Child; Infant, Newborn; Amikacin; Urinary Tract Infections; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Escherichia coli
PubMed: 37730164
DOI: 10.1016/j.idnow.2023.104786 -
International Journal of Environmental... Feb 2022Children show a very wide range of physical development processes. These changes impact pharmacokinetic (PK) variability in pediatric patients. Most PK studies have been... (Review)
Review
Children show a very wide range of physical development processes. These changes impact pharmacokinetic (PK) variability in pediatric patients. Most PK studies have been conducted on the Caucasian population. Therefore, whether current evidence of how developmental change affects PK and exposure-response relationships applies to Japanese pediatric patients remains unclear. This narrative review focuses on amikacin therapy in Japanese pediatric patients and shows the relationship between amikacin concentrations and efficacy/toxicity. Ten relevant articles were identified. Of these, nine articles were published in the 1980s. All studies reported a maximum concentration (Cmax) and minimum concentration (Cmin) of amikacin. Overall, articles reporting PK/pharmacodynamic (PD) indices and minimum inhibitory concentration (MIC) of isolated bacteria in Japanese pediatric patients is lacking, whereas all patients recovered from an infection state and showed negative cultures. Five of the included studies reported the association between Cmin and toxicity. The Cmin in three of four patients who developed toxicity was above 10 mg/L. This narrative review shows that further PK study of amikacin in Japanese pediatric patients is necessary. In particular, the pursuit of knowledge of Cmax/MIC ratio is vital. On the other hand, this review demonstrates that the optimal Cmin for Japanese pediatric patients is below 10 mg/L as a candidate concentration. However, it is noted that the number of patients who developed toxicity is very small.
Topics: Amikacin; Anti-Bacterial Agents; Bacteria; Child; Humans; Japan; Microbial Sensitivity Tests
PubMed: 35206156
DOI: 10.3390/ijerph19041972 -
Chest Sep 2021
Topics: Amikacin; Anti-Bacterial Agents; Humans; Liposomes
PubMed: 34488977
DOI: 10.1016/j.chest.2021.05.050 -
Nature Communications Aug 2023Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of...
Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of kanamycin, is commonly used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries the 4-amino-2-hydroxy butyrate (AHB) moiety at the N amino group of the central 2-deoxystreptamine (2-DOS) ring, which may confer amikacin a unique ribosome inhibition profile. Here we use in vitro fast kinetics combined with X-ray crystallography and cryo-EM to dissect the mechanisms of ribosome inhibition by amikacin and the parent compound, kanamycin. Amikacin interferes with tRNA translocation, release factor-mediated peptidyl-tRNA hydrolysis, and ribosome recycling, traits attributed to the additional interactions amikacin makes with the decoding center. The binding site in the large ribosomal subunit proximal to the 3'-end of tRNA in the peptidyl (P) site lays the groundwork for rational design of amikacin derivatives with improved antibacterial properties.
Topics: Amikacin; Anti-Bacterial Agents; Models, Molecular; Ribosomes; Kanamycin; RNA, Transfer
PubMed: 37537169
DOI: 10.1038/s41467-023-40416-5 -
Current Opinion in Pulmonary Medicine May 2023The incidence of bacterial respiratory tract infections is growing. In a context of increasing antibiotic resistance and lack of new classes of antibiotics, inhaled... (Review)
Review
PURPOSE OF REVIEW
The incidence of bacterial respiratory tract infections is growing. In a context of increasing antibiotic resistance and lack of new classes of antibiotics, inhaled antibiotics emerge as a promising therapeutic strategy. Although they are generally used for cystic fibrosis, their use in other conditions is becoming more frequent, including no-cystic fibrosis bronchiectasis, pneumonia and mycobacterial infections.
RECENT FINDINGS
Inhaled antibiotics exert beneficial microbiological effects in bronchiectasis and chronic bronchial infection. In nosocomial and ventilator-associated pneumonia, aerosolized antibiotics improve cure rates and bacterial eradication. In refractory Mycobacterium avium complex infections, amikacin liposome inhalation suspension is more effective in achieving long-lasting sputum conversion. In relation to biological inhaled antibiotics (antimicrobial peptides, interfering RNA and bacteriophages), currently in development, there is no still enough evidence that support their use in clinical practice.
SUMMARY
The effective antimicrobiological activity of inhaled antibiotics, added to their potential to overcoming resistances to systemic antibiotics, make inhaled antibiotics a plausible alternative.
Topics: Humans; Anti-Bacterial Agents; Administration, Inhalation; Respiratory Tract Infections; Amikacin; Bronchiectasis
PubMed: 36866728
DOI: 10.1097/MCP.0000000000000952 -
Clinical Microbiology and Infection :... Oct 2023Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due...
OBJECTIVES
Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option. Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole-genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCCs), the likelihood of patient-to-patient transmission and the presence of prophages.
METHODS
Antibiotic susceptibility testing was performed using CLSI breakpoints (n = 95), and plaque assays were used for phage susceptibility testing (subset of n = 88, 35 rough and 53 smooth morphology). WGS was completed using the Illumina platform and analysed using Snippy/snp-dists and Discovery and Extraction of Phages Tool (DEPhT).
RESULTS
Amikacin and Tigecycline were the most active drugs (with 2 strains resistant to amikacin, and one strain with Tigecycline MIC of 4 μg/mL). Most strains were resistant to all other drugs tested, with Linezolid and Imipenem showing the least resistance, at 38% (36/95) and 55% (52/95), respectively. Rough colony morphotype strains were more phage-susceptible than smooth strains (77%-27/35 versus 48%-25/53 in the plaque assays, but smooth strains are not killed efficiently by those phages in liquid infection assay). We have also identified 100 resident prophages, some of which were propagated lytically. DCC1 (20%-18/90) and DCC4 (22%-20/90) were observed to be the major clones and WGS identified 6 events of possible patient-to-patient transmission.
DISCUSSION
Many strains of M. abscessus complex are intrinsically resistant to available antibiotics and bacteriophages represent an alternative therapeutic option, but only for strains with rough morphology. Further studies are needed to elucidate the role of hospital-borne M. abscessus transmission.
Topics: Humans; Mycobacterium abscessus; Amikacin; Tigecycline; Bacteriophages; Phylogeny; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Drug Resistance, Multiple; Delivery of Health Care; Microbial Sensitivity Tests
PubMed: 37364635
DOI: 10.1016/j.cmi.2023.06.026 -
European Journal of Pharmaceutical... Aug 2022The aim of this study was to characterize the population pharmacokinetics of amikacin in elderly patients by means of nonlinear mixed effects modelling and to propose...
OBJECTIVE
The aim of this study was to characterize the population pharmacokinetics of amikacin in elderly patients by means of nonlinear mixed effects modelling and to propose initial dosing schemes to optimize therapy based on PK/PD targets.
METHOD
A total of 137 elderly patients from 65 to 94 years receiving intravenous amikacin and routine therapeutic drug monitoring at Hospital Universitario Severo Ochoa were included. Concentration-time data and clinical information were retrospectively collected; initial doses of amikacin ranged from 5.7 to 22.5 mg/kg/day and each patient provided between 1 and 10 samples.
RESULTS
Amikacin pharmacokinetics were best described by a two-compartment open model; creatinine clearance (CrCL) was related to drug clearance (2.75 L/h/80 mL/min) and it was augmented 28% when non-steroidal anti-inflammatory drugs were concomitantly administered. Body mass index (BMI) influenced the central volume of distribution (17.4 L/25 kg/m). Relative absolute prediction error was reduced from 33.2% (base model) to 17.9% (final model) when predictive performance was evaluated with a different group of elderly patients. A nomogram for initial amikacin dosage was developed and evaluated based on stochastic simulations considering final model to achieve PK/PD targets (Cmax/MIC>10 and AUC/MIC>75) and to avoid toxic threshold (Cmin<2.5 mg/L).
CONCLUSION
Initial dosing approach for amikacin was designed for elderly patients based on nonlinear mixed effects modeling to maximize the probability to attain efficacy and safety targets considering individual BMI and CrCL.
Topics: Administration, Intravenous; Aged; Amikacin; Anti-Bacterial Agents; Humans; Metabolic Clearance Rate; Retrospective Studies
PubMed: 35618200
DOI: 10.1016/j.ejps.2022.106219 -
Veterinary Clinical Pathology Mar 2022Physiologically, feline platelets are more reactive and prone to aggregation, which interferes with platelet counts using automated counters and manual methods. The use...
INTRODUCTION
Physiologically, feline platelets are more reactive and prone to aggregation, which interferes with platelet counts using automated counters and manual methods. The use of aminoglycoside amikacin in association with EDTA has proven to be efficient in preventing platelet aggregates in cases of pseudo thrombocytopenia (PTP) in people.
OBJECTIVES
This study evaluated the efficacy of amikacin in preventing platelet aggregation in EDTA-containing feline blood samples and investigated the possible effects on hematologic measurands.
MATERIALS AND METHODS
Blood samples (1.0 mL) collected from 100 healthy cats were stored in two EDTA tubes: 0.5 mL in a microtube containing 10 μL of 250 mg/mL amikacin (EDTA-AMK group) and 0.5 mL in a microtube containing only K2 EDTA 10% (EDTA group). A CBC was executed with an automated impedance blood analyzer, and a microscopic examination of the blood smears was performed.
RESULTS
Platelet clumps were observed in 56% of samples from the EDTA group and 5% of samples from the EDTA-AMK group. Platelet counts (PLT), plateletcrit (PCT), and WBC counts were significantly higher (P < .001) in the EDTA-AMK group compared withi the EDTA group.
CONCLUSIONS
Amikacin prevents platelet aggregation in feline venous blood samples and does not cause clinically relevant changes in other hematologic measurands. To our knowledge, this is the first report showing the use of amikacin in preventing platelet aggregation in feline blood samples. Based on this study, amikacin could be added to EDTA collection tubes for complete blood counts in cats.
Topics: Amikacin; Animals; Cat Diseases; Cats; Edetic Acid; Humans; Platelet Aggregation; Platelet Count; Thrombocytopenia
PubMed: 35141933
DOI: 10.1111/vcp.13074 -
Veterinary Clinical Pathology Jun 2023Pseudothrombocytopenia may lead to the erroneous diagnosis of thrombocytopenia, resulting in unnecessary testing and treatment. The addition of exogenous substances to...
BACKGROUND
Pseudothrombocytopenia may lead to the erroneous diagnosis of thrombocytopenia, resulting in unnecessary testing and treatment. The addition of exogenous substances to blood samples prior to collection has been shown to mitigate platelet (PLT) clumps in blood samples. Postcollection additives aiming to disaggregate PLT clumps have been largely unexplored.
OBJECTIVES
We aimed to determine if the addition of amikacin to blood samples postcollection aids in the disaggregation of PLT clumps in cats and dogs.
METHODS
For this prospective study, EDTA-collected blood samples from 28 cats and 17 dogs were obtained from a hospital population at UC Davis Veterinary Medical Teaching Hospital. Samples had PLT clumps detected on blood smears and thrombocytopenia per analyzer count. Amikacin was added to samples postcollection, and an additional CBC was performed. Flow cytometry was performed to assess PLT-fibrinogen binding in amikacin-treated aliquots.
RESULTS
PLT-clumped samples treated with amikacin significantly increased PLT numbers by 134% and decreased mean platelet volume (MPV) values by 14% (P ≤ 0.0001) in cats, and increased PLT numbers by 32% (P = 0.04) and increased MPV values by 9% (P = 0.02) in dogs. Mean cell volume (MCV) slightly increased (<4%) for both species. No other CBC parameters were substantially affected by the addition of amikacin. Flow cytometry showed decreased PLT-fibrinogen binding in the majority of cats but was not significant (P > 0.05).
CONCLUSIONS
Adding amikacin to PLT-clumped blood samples postcollection may be a convenient solution for pseudothrombocytopenia in cats and dogs. Future studies are needed to elucidate the mechanism of amikacin and its effectiveness under different storage conditions. This is the first reported use of amikacin postcollection to disaggregate PLT clumps in blood samples from animals.
Topics: Cats; Dogs; Animals; Platelet Count; Amikacin; Edetic Acid; Prospective Studies; Thrombocytopenia; Fibrinogen; Cat Diseases; Dog Diseases
PubMed: 36849708
DOI: 10.1111/vcp.13203 -
Clinical Pharmacokinetics Feb 2017Amikacin is an aminoglycoside commonly used in intensive care units for the treatment of patients with life-threatening Gram-negative infections. Although... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amikacin is an aminoglycoside commonly used in intensive care units for the treatment of patients with life-threatening Gram-negative infections. Although aminoglycosides are extensively used, the accurate determination of their optimal dosage is complicated by marked intra- and interindividual variability in intensive care unit patients. Amikacin pharmacokinetics have been described in numerous studies over the past 25 years.
OBJECTIVE
This review presents a synthesis of the population pharmacokinetic models for amikacin described in critically ill patients. The objective was to determine whether there was a consensus on a structural model and which covariates had been identified.
METHODS
A literature search was conducted from the PubMed database, from its inception up until December 2015, using the following terms: 'amikacin', 'pharmacokinetic(s)', 'population', 'model(ling)' and 'nonlinear mixed effect'. Articles were excluded if they were not pertinent. The reference lists of all selected articles were also evaluated.
RESULTS
Ten articles were included in this review: pharmacokinetics of amikacin were described by a one-compartment or a two-compartment model. Various covariates were tested, but only two (creatinine clearance and total body weight) were included in almost all of the described models. After inclusion of these covariates, the interindividual variability (range) in clearance and the volume of distribution were 44.4 % (28.2-69.4 %) and 31.3 % (8.1-44.7 %), respectively. The residual variability (range) was around 21.0 % (9.0-31.0 %), using a proportional model, and for a combined model (proportional/additive), the median (range) values were 0.615 mg/L (0.2-1.03 mg/L) and 29.2 % (26.8-31.6 %).
CONCLUSION
This review highlights the different population pharmacokinetic models for amikacin developed in critically ill patients over the past decades and proposes relevant information for clinicians and researchers. To optimize amikacin dosage, this review points out the relevant covariates according to the target population. In a population of critically ill patients, dose optimization mainly depends on creatinine clearance and total body weight. New pharmacokinetic population studies could be considered, with new covariates of interest to be tested in model building and to further explain variability. Another future perspective could be external evaluation of previously published models.
Topics: Amikacin; Anti-Bacterial Agents; Clinical Trials as Topic; Critical Illness; Female; Humans; Male
PubMed: 27324191
DOI: 10.1007/s40262-016-0428-x