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Aminoglycoside pharmacokinetics

Anouk E Muller, Benedikt Huttner, Angela Huttner
Antibiotics are among the medications most frequently administered to the critically ill, a population with high levels of intra- and inter-individual pharmacokinetic variability. Our knowledge of the relationships among antibiotic dosing, exposure and clinical effect in this population has increased in recent decades. Therapeutic drug monitoring (TDM) of serum antibiotic concentrations is the most practical means of assessing adequate antibiotic exposure, though until recently, it has been underutilised for this end...
February 23, 2018: Drugs
Farhad Najmeddin, Bita Shahrami, Sayna Azadbakht, Mehrnoush Dianatkhah, Mohammad Reza Rouini, Atabak Najafi, Arezoo Ahmadi, Hamidreza Sharifnia, Mojtaba Mojtahedzadeh
INTRODUCTION: Classically, aminoglycosides are known to have low penetration into the lung tissue. So far, no study has been conducted on human adult patients to evaluate amikacin concentration in epithelial lining fluid (ELF) of the alveoli. Therefore, convincing data are not available from the perspective of pharmacokinetics to support the fact that a dosage of 20 mg/kg of amikacin is sufficient to treat patients with ventilator-associated pneumonia (VAP). METHOD: This was a pilot study of amikacin concentration measurement in the alveolar site of action in critically ill adult patients with VAP who required aminoglycoside therapy...
January 1, 2018: Journal of Intensive Care Medicine
R Cohen, M Tauzin, S Béchet, L Caeymaex
Pharmacokinetic and pharmacodynamics (PK/PD) data on antimicrobial agents enable physicians to optimize their use in clinical practice. Neonates exhibit a large inter-individual variability in antibiotic levels due to immaturity and maturational changes in the first weeks of life. This variability explains the large therapeutic margins needed to ensure an optimal efficacy of antibiotics. These pharmacokinetic characteristics have to be taken into account when treating neonatal sepsis, along with pharmacodynamics targets for each antibiotic and notably minimal inhibitory concentration for usual causes of neonatal bacterial infections (group B streptococcus and Escherichia coli)...
December 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Ni Wentao, Li Guobao, Zhao Jin, Cui Junchang, Wang Rui, Gao Zhancheng, Liu Youning
This study assessed the in vitro antibacterial activity of minocycline-aminoglycoside combination against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Seventy non-duplicate clinical isolates of KPC-producing K. pneumoniae were collected from patients with bloodstream infections. The synergistic activity of minocycline-aminoglycoside combination was studied by the checkerboard method and time-kill assays in strains with different susceptibilities, and the mutant prevention concentration (MPC) and mutant selection window (MSW) of drugs alone and in combination were determined...
February 7, 2018: Journal of Antibiotics
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
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
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
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
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
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
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
Sinziana Cristea, Anne Smits, Aida Kulo, Catherijne A J Knibbe, Mirjam van Weissenbruch, Elke H J Krekels, Karel Allegaert
Aminoglycoside pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed for treating neonates with (suspected) septicemia; however, none provide adjustments for cases 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 data set, we assessed the impact of PATH on amikacin PK by using population modeling...
December 2017: Antimicrobial Agents and Chemotherapy
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...
January 11, 2018: Journal of Medicinal Chemistry
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
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...
January 2018: Pharmacology & Therapeutics
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
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
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...
December 2017: Burns: Journal of the International Society for Burn Injuries
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
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
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