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Aminoglycoside pharmacokinetics

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https://www.readbyqxmd.com/read/29311078/in-vitro-drug-susceptibility-of-mycobacterium-tuberculosis-for-amikacin-kanamycin-and-capreomycin
#1
J A Dijkstra, T van der Laan, O W Akkerman, M S Bolhuis, W C M de Lange, J G W Kosterink, T S van der Werf, J W C Alffenaar, D van Soolingen
Amikacin, kanamycin and capreomycin are listed among the most important 2nd line drugs for multidrug resistant tuberculosis. Although amikacin and kanamycin are administered in the same dose and show the same pharmacokinetics, they have different WHO breakpoints suggesting that the two drugs have a different minimal inhibitory concentrations (MIC). The aim of this paper was to investigate possible differences in MIC between the aminoglycosides and capreomycin.Using the direct concentration method, a concentration range of amikacin, kanamycin and capreomycin (0...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29309652/proline-rich-antimicrobial-peptides-show-a-long-lasting-post-antibiotic-effect-on-enterobacteriaceae-and-pseudomonas-aeruginosa
#2
Luzia Holfeld, Daniel Knappe, Ralf Hoffmann
Background: Proline-rich antimicrobial peptides (PrAMPs) represent a promising class of potential therapeutics to treat multiresistant infections. They inhibit bacterial protein translation at the 70S ribosome by either blocking the peptide-exit tunnel (oncocin type) or trapping release factors (apidaecin type). Objectives: Besides direct concentration-dependent antibacterial effects, the post-antibiotic effect (PAE) is the second most important criterion of antimicrobial pharmacodynamics to be determined in vitro...
December 21, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29290237/antibiotic-pharmacokinetic-and-pharmacodynamic-parameters-in-pediatric-clinical-practice
#3
R Cohen, E Grimprel
Progress in the knowledge of antibiotic mechanisms of action allows to determine the pharmacodynamics/pharmacokinetic (PK/PD) parameters predictive of antibiotic efficacy in bacterial infections. According to the antibiotic compound, the bacterial species implicated, the location of the infection, and the severity of the disease, these parameters may vary. The PK/PD parameters described in this paper, focus only on blood compartments. These PK/PD parameters best predict efficacy in the most frequent infections (e...
December 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29273613/implementation-of-a-prioritized-scoring-tool-to-improve-time-to-pharmacist-intervention
#4
Andre Harvin, John J J Mellett, Daren Knoell, Jay Mirtallo, Ryan W Naseman, Nicole Brown, Crystal R Tubbs
PURPOSE: The implementation of a prioritized scoring tool to improve time to pharmacist intervention is described. SUMMARY: At the Ohio State University Wexner Medical Center, pharmacists are accepted providers of therapeutic drug monitoring of vancomycin and aminoglycosides. At the onset of this initiative and despite the implementation of an integrated electronic medical record (EMR), management of pharmacokinetically monitored medications was conducted using a paper monitoring form...
January 1, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29180163/a-needs-assessment-of-pharmacokinetic-skills-performed-on-advanced-pharmacy-practice-experiences-by-student-pharmacists
#5
Emily K Dornblaser
INTRODUCTION: Pharmacokinetic (PK) calculations are an important competency for pharmacy students, however, there is little to guide which medications should be included in pharmacy curricula. Additionally, many new medications require therapeutic drug monitoring (TDM)-but not PK calculations-to ensure safe use. The objectives of this study were to quantify which medications are most frequently encountered by pharmacy students during advanced pharmacy practice experiences (APPE's) and to what extent PK calculations or TDM were completed by students while on APPE's at the University of New England...
January 2017: Currents in Pharmacy Teaching & Learning
https://www.readbyqxmd.com/read/29119059/the-bacteriological-profile-of-the-burned-patients-in-the-center-of-burns-in-chu-mohamed-vi-marrakech-about-123-cases
#6
Yassine Benchamkha, Ouafaa Dhaidah, Adil Dahazze, Quaboul Meriem, Moulay Driss Elamrani, Salwa Ettalbi
The bacterial nosocomial infection is one of the leading causes of morbidity and mortality for burned patient; we conducted a retrospective study of 123 patients hospitalized in the burns center CHUMED VI of Marrakechover a period of 3 years, from January 1(st), 2013 to December 31(st), 2016. The criteria for nosocomial infection were those of the Center for Disease Control in Atlanta in 1988. Incidence rates were calculated. The bacterial ecology of the department was described as also antibiotype. The predominancy of the population was male...
2017: International Journal of Burns and Trauma
https://www.readbyqxmd.com/read/29063877/optimisation-of-antimicrobial-dosing-based-on-pharmacokinetic-and-pharmacodynamic-principles
#7
REVIEW
Grace Si Ru Hoo, Yi Xin Liew, Andrea Lay-Hoon Kwa
While suboptimal dosing of antimicrobials has been attributed to poorer clinical outcomes, clinical cure and mortality advantages have been demonstrated when target pharmacokinetic (PK) and pharmacodynamic (PD) indices for various classes of antimicrobials were achieved to maximise antibiotic activity. Dosing optimisation requires a good knowledge of PK/PD principles. This review serves to provide a foundation in PK/PD principles for the commonly prescribed antibiotics (β-lactams, vancomycin, fluoroquinolones and aminoglycosides), as well as dosing considerations in special populations (critically ill and obese patients)...
July 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28993332/amikacin-pharmacokinetics-to-optimize-dosing-in-neonates-with-perinatal-asphyxia-treated-with-hypothermia
#8
Sinziana Cristea, Anne Smits, Aida Kulo, Catherijne A J Knibbe, Mirjam van Weissenbruch, Elke H J Krekels, Karel Allegaert
Aminoglycosides pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed to treat neonates with (suspected) septicemia, however, none provide adjustments in the case of PATH. Therefore, we aimed to quantify the differences in amikacin PK between neonates with and without PATH to propose suitable dosing recommendations.Based on amikacin therapeutic drug monitoring data collected retrospectively from neonates with PATH, combined with a published dataset, we assessed the impact of PATH on amikacin PK using population modelling...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28992413/phenotypic-optimization-of-urea-thiophene-carboxamides-to-yield-potent-well-tolerated-and-orally-active-protective-agents-against-aminoglycoside-induced-hearing-loss
#9
Sarwat Chowdhury, Kelly N Owens, R Jason Herr, Qin Jiang, Xinchao Chen, Graham Johnson, Vincent E Groppi, David W Raible, Edwin W Rubel, Julian A Simon
Hearing loss is a major public health concern with no pharmaceutical intervention for hearing protection or restoration. Using zebrafish neuromast hair cells, a robust model for mammalian auditory and vestibular hair cells, we identified a urea-thiophene carboxamide, 1 (ORC-001), as protective against aminoglycoside antibiotic (AGA)-induced hair cell death. The 50% protection (HC50) concentration conferred by 1 is 3.2 μM with protection against 200 μM neomycin approaching 100%. Compound 1 was sufficiently safe and drug-like to validate otoprotection in an in vivo rat hearing loss model...
October 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28881316/development-and-validation-of-a-sensitive-lc-ms-ms-method-without-derivatization-ion-pairing-agents-for-etimicin-quantification-in-rat-plasma-internal-ear-and-kidney
#10
Lan Yao, Fang Zhou, Mingmin Cai, Ying Peng, Jianguo Sun, Qianying Chen, Xiaoliang Jin, Guangji Wang, Jingwei Zhang
Etimicin (ETM), which belongs to the newest generation of aminoglycosides (AGs), has been proven to not only maintain but also strengthen the advantages of former AGs with relatively less toxicity. Now, it is widely applied for the treatment of bacterial infections in the clinic. Nevertheless, nephrotoxicity and ototoxicity are unavoidable issues for AGs, and while ETM is no exception, the seriousness of these issues is different. To explore the reason why ETM exhibits less toxicity and to better direct the optimization and development of new AGs, it is of great necessity and importance to monitor the pharmacokinetic behaviors of ETM in its potential toxicity target organs, the kidney and internal ear, as well as in plasma...
August 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28750947/polymyxins-for-cns-infections-pharmacology-and-neurotoxicity
#11
REVIEW
Tony Velkov, Chongshan Dai, Giuseppe D Ciccotosto, Roberto Cappai, Daniel Hoyer, Jian Li
Central nervous system (CNS) infections caused by multi-drug resistant (MDR) Gram-negative bacteria present a major health and economic burden worldwide. Due to the nearly empty antibiotic discovery pipeline, polymyxins (i.e. polymyxin B and colistin) are used as the last-line therapy against Gram-negative 'superbugs' when all other treatment modalities have failed. The treatment of CNS infections due to multi-drug resistant Gram-negative bacteria is problematic and associated with high mortality rates. Colistin shows significant efficacy for the treatment of CNS infections caused by MDR Gram-negative bacteria that are resistant to all other antibiotics...
July 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28749392/evaluation-of-evidence-for-pharmacokinetics-pharmacodynamics-based-dose-optimization-of-antimicrobials-for-treating-gram-negative-infections-in-neonates
#12
REVIEW
Nusrat Shafiq, Samir Malhotra, Vikas Gautam, Harpreet Kaur, Pravin Kumar, Sourabh Dutta, Pallab Ray, Nilima A Kshirsagar
BACKGROUND & OBJECTIVES: Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in neonates, and inpatient treatment along with critical care is needed for the management of these infections. Dosing recommendations are often extrapolated from evidence generated in older patient populations. This systematic review was done to identify the knowledge gaps in the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for parenteral antimicrobials for Gram-negative neonatal infections...
March 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28696058/early-postnatal-gentamicin-and-ceftazidime-treatment-in-normal-and-food-restricted-neonatal-wistar-rats-implications-for-kidney-development
#13
Ruud R G Bueters, Annelies Jeronimus-Klaasen, Roger J M Brüggemann, Lambertus P van den Heuvel, Michiel F Schreuder
BACKGROUND: Up to two-thirds of premature born neonates are treated for infections with aminoglycosides such as gentamicin. Although acute toxicities are well described, there is uncertainty on developmental changes after treatment of premature born neonates. We studied the effect of gentamicin and ceftazidime on kidney development in the rat. Additionally, we evaluated the modulating effect of extrauterine growth restriction. METHODS: On postnatal day (PND) 2, Wistar rats were cross-fostered into normal sized litters (12 pups) or large litters (20 pups) to create normal food (NF) or food restricted (FR) litters to simulate growth restriction and dosed daily intraperitoneally with placebo, 4 mg/kg of gentamicin or 50 mg/kg ceftazidime until PND 8...
July 11, 2017: Birth Defects Research
https://www.readbyqxmd.com/read/28647460/a-prospective-study-evaluating-tobramycin-pharmacokinetics-and-optimal-once-daily-dosing-in-burn-patients
#14
Colin Lee, Sandra A N Walker, Scott E Walker, Winnie Seto, Andrew Simor, Marc Jeschke
BACKGROUND: Once-daily aminoglycoside dosing (ODA) is used in most patient populations to optimize antibacterial activity and reduce toxicity. Unfortunately, burn patients are excluded from ODA due to concerns over altered pharmacokinetics resulting in a shortened half-life and low peak aminoglycoside concentrations. Retrospective studies suggest that ODA may be appropriate if higher milligram/kilogram doses are used. However, no prospective clinical trials in burn patients exist to confirm these findings...
June 21, 2017: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/28639230/intracellular-pharmacokinetics-of-antibacterials-and-their-clinical-implications
#15
REVIEW
Federico Pea
The intracellular pharmacokinetics of the different classes of antimicrobials into surrogate markers of tissue accumulation (alveolar macrophages and/or total alveolar cells collected by means of bronchoalveolar lavage or peripheral white blood cells) was reviewed. The aim of this review was to discuss the clinical implications of the intracellular pharmacokinetics of antibacterials, either from the therapeutic or toxicological perspective. The different pharmacokinetic behaviour of antimicrobials within cells is mainly related to their physicochemical properties (hydrophilicity and lipophilicity), and may have several clinical implications...
June 21, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28375030/aminoglycosides-against-carbapenem-resistant-enterobacteriaceae-in-the-critically-ill-the-pitfalls-of-aminoglycoside-susceptibility
#16
Alexandre P Zavascki, Brandon O Klee, Jürgen B Bulitta
The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has brought aminoglycosides to the frontline since an aminoglycoside may be the only antimicrobial to which CRE isolates show in vitro susceptibility. The appropriateness of aminoglycoside-based therapies for severe infections by CRE is discussed considering the current breakpoints and recent pharmacokinetic (PK) studies in critically ill patients. Areas covered: Many aminoglycoside-susceptible CRE isolates present minimal inhibitory concentrations (MICs) at or slightly below the breakpoint of amikacin or gentamicin...
June 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28184305/once-daily-aerosolised-tobramycin-in-adult-patients-with-cystic-fibrosis-in-the-management-of-pseudomonas-aeruginosa-chronic-infection
#17
Marco Mantero, Andrea Gramegna, Giovanna Pizzamiglio, Alice D'Adda, Paolo Tarsia, Francesco Blasi
It is estimated that about 60-70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection, with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic to be used against P. aeruginosa; inhalatory tobramycin frequency of administration is twice daily and inhalation time is estimated to be 15 to 20 min...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28096164/pharmacodynamics-of-ceftaroline-plus-ampicillin-against-enterococcus-faecalis-in-an-in-vitro-pharmacokinetic-pharmacodynamic-model-of-simulated-endocardial-vegetations
#18
Brian J Werth, Laura M Shireman
The combination of ampicillin plus ceftaroline has been suggested to be more reliably synergistic against Enterococcus faecalis than ampicillin plus ceftriaxone using time-kill methods. The purpose of this study was to determine if this trend persists in a two-compartment model of simulated endocardial vegetations (SEV) using clinically relevant pharmacokinetic exposures of these antimicrobials. Three clinically derived E. faecalis strains were included in the study. The MICs of study antimicrobials were determined by broth microdilution...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28095918/anti-staphylococcal-activity-resulting-from-epithelial-lining-fluid-elf-concentrations-of-amikacin-inhale-administered-via-the-pulmonary-drug-delivery-system
#19
Islam M Ghazi, Mordechai Grupper, David P Nicolau
BACKGROUND: Amikacin inhale (BAY41-6551), a unique drug-device combination of a specially formulated drug solution and a pulmonary drug delivery system device (AMK-I) is currently under phase III study as an adjunctive therapy to IV antibiotics for the treatment of Gram-negative pneumonia in mechanically ventilated patients. While the epidemiology of nosocomial pneumonia is predominated by Gram-negative pathogens such as Pseudomonas aeruginosa and the Enterobacteriaceae, Staphylococcus aureus is increasingly recognized as a pathogen of concern for these pulmonary based infections...
January 17, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28069654/reduced-chance-of-hearing-loss-associated-with-therapeutic-drug-monitoring-of-aminoglycosides-in-the-treatment-of-multidrug-resistant-tuberculosis
#20
R van Altena, J A Dijkstra, M E van der Meer, J F Borjas Howard, J G W Kosterink, D van Soolingen, T S van der Werf, J W C Alffenaar
Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study...
March 2017: Antimicrobial Agents and Chemotherapy
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