ABSTRACT
Previous research has determined that the required doses for treating febrile neutropenia with vancomycin are higher than the doses used conventionally. These recommendations have been made considering pharmacotherapeutic goals based on minimum concentration (Cmin) between 15-20 mg/L. This study was developed to evaluate dose recommendations based on the achievement of a target consisting of ratio of area under the curve over minimum inhibitory concentration (AUC24h/MIC) ≥400 in this population of individuals. This study was conducted in a referral hospital for cancer treatment, study participants received vancomycin doses of 1g every 12 h in 2-4-h infusions. Vancomycin was described by a two-compartment pharmacokinetic model with clearance dependent on the estimated glomerular filtration rate. Simulations were performed taking into account a reduced version of the model to establish the influence of controllable and non-controllable variables on the probability of achieving several PK-PD targets. A dose of 2.5g/day in patients with estimated glomerular filtration rate (eGFR) between 80 and 122mL/min/1.73m2 was adequate to achieve the pharmacotherapeutic target. A discrepancy was found between AUC-based and Cmin-based PK/PD indices, the former being affected by the dose and creatinine clearance while the latter highly influenced by the interval between doses.
ABSTRACT
Resistance mechanisms occur in almost all clinical bacterial isolates and represent one of the most worrisome health problems worldwide. Bacteria can form biofilms and communicate through quorum sensing (QS), which allow them to develop resistance against conventional antibiotics. Thus, new therapeutic candidates are sought. We focus on alkylglycerols (AKGs) because of their recently discovered quorum sensing inhibition (QSI) ability and antibiofilm potential. Fifteen natural enantiopure AKGs were tested to determine their effect on the biofilm formation of other clinical bacterial isolates, two reference strains and their QSI was determined using Chromobacterium violaceum ATCC 12472. The highest biofilm inhibition rates (%) and minimum QS inhibitory concentration were determined by a microtiter plate assay and ciprofloxacin was used as the standard antibiotic. At subinhibitory concentrations, each AKG reduced biofilm formation in a concentration-dependent manner against seven bacterial isolates, with values up to 97.2%. Each AKG displayed QSI at different levels of ability without affecting the growth of C. violaceum. AKG (2S)-3-O-(cis-13'-docosenyl)-1,2-propanediol was the best QS inhibitor (20 µM), while (2S)-3-O-(cis-9'-hexadecenyl)-1,2-propanediol was the least effective (795 µM). The results showed for the first time the QSI activity of this natural AKG series and suggest that AKGs could be promising candidates for further studies on preventing antimicrobial resistance.
ABSTRACT
Alkylglycerols (AKGs) are bioactive natural compounds that vary by alkyl chain length and degree of unsaturation, and their absolute configuration is 2S. Three AKGs (5l-5n) were synthesised in enantiomerically pure form, and were characterised for the first time together with 12 other known and naturally occurring AKGs (5a-5k, 5o). Their structures were established using 1H and 13C APT NMR with 2D-NMR, ESI-MS or HRESI-MS and optical rotation data, and they were tested for their antibacterial and antibiofilm activities. AKGs 5a-5m and 5o showed activity against five clinical isolates and P. aeruginosa ATCC 15442, with MIC values in the range of 15-125 µg/mL. In addition, at half of the MIC, most of the AKGs reduced S. aureus biofilm formation in the range of 23%-99% and P. aeruginosa ATCC 15442 biofilm formation in the range of 14%-64%. The antibiofilm activity of the AKGs assessed in this work had not previously been studied.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Infective Agents , Pseudomonas aeruginosa/chemistry , Staphylococcus aureus , BiofilmsABSTRACT
El principal inconveniente en la combustión de los hidrocarburos es la conversión del azufre y el nitrógeno a sus respectivos óxidos, los cuales participan en la formación de lluvia acida y deterioran el medio ambiente e infraestructuras. La remoción de azufre a partir de compuestos órgano-azufrados mediante el uso de microorganismos ha surgido como una alternativa frente al proceso catalítico de hidrodesulfurización (HDS). En el presente trabajo se evaluó la actividad desulfurizadora de veintitrés aislados nativos de Pseudomonas spp. sobre dibenzotiofeno (DBT), usando un sistema de fermentación con igual proporción de fase acuosa y orgánica (n-hexano) en presencia de oleato de etanolamina. Los aislados 02,05 y 06 conservaron su viabilidad en este medio y presentaron una remoción de azufre entre 6,0 y 9,4%, generando los metabolitos DBT-sulfona, DBT-sulfóxido, 2-hidroxibifenilo (2-HBP) y sulfato presentes en la ruta metabólica 4S. Con estos aislados se evaluó la actividad desulfurizadora sobre keroseno y se observó una remoción de azufre entre 19,9 y 62,6% y una disminución del poder calorífico entre 0,45 y 5,55%.
The main difficulty with fossil fuel combustión lies in sulphur and nitrogen becoming converted to their respective oxides, forming part of the acid rain which deteriorates the environment and infrastructure. Removing sulphur from organo-sulfur compounds by using micro-organisms has become an alternative to hydrodesulphurisation (HDS). Twenty-three Pseudomonas spp. native strains' desulphurisation activity on dibenzothiophene (DBT) was evaluated by using a fermentation system having equal proportions of aqueous and organic (n-hexane) phases in the presence of ethanolamine oléate. The 02, 05 and 06 strains maintained their viability in this médium, presenting 6,0% to 9,4% sulphur removal, producing DBT-sulphone, DBT-sulphoxide, 2-hydroxybiphenyl (2-HBP) metabolites and sulphate belonging to the 4S pathway. These native strains' desulphurisation activity was evaluated on kerosene, presenting 19,9% to 62,2% sulphur removal having 0,45% to 5,55% calorific power loss.
