scholarly journals In vitro time-kill kinetics of dalbavancin against Staphylococcus spp. biofilms over prolonged exposure times

2020 ◽  
Vol 96 (2) ◽  
pp. 114901 ◽  
Author(s):  
Vincenzo Di Pilato ◽  
Federica Ceccherini ◽  
Samanta Sennati ◽  
Federico D'Agostino ◽  
Fabio Arena ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Time Kill ◽  
Staphylococcus Spp ◽  
Kinetics Of

scholarly journals Antibacterial activity and time kill kinetics of Amlodipine, Thioridazine and Promethazine against pathogenic clinical bacterial isolates

2021 ◽  
Vol 22 (3) ◽  
pp. 397-406
Author(s):  
O.J. Akinjogunla ◽  
A.N. Umo ◽  
M.F. Alozie ◽  
G.O. Oshosanya ◽  
G.I. Saturday
Keyword(s):  
Antibacterial Activities ◽  
Post Inoculation ◽  
Disc Diffusion ◽  
Bacterial Isolates ◽  
E Coli ◽  
Cell Counts ◽  
Antibiotic Drugs ◽  
Time Kill ◽  
Kinetics Of

Background: The emergence of multi-drug resistant bacterial strains worldwide has necessitated the scientific search for novel, potent, and affordable antimicrobial agents including medicinal plants and non-antibiotic drugs for therapy of infectious diseases. The objective of this study is to assess in vitro antibacterial activities and time kill kinetics of some non-antibiotic drugs against pathogenic clinical bacterial isolates.Methodology: In vitro antibacterial activities including minimum inhibitory concentration (MIC), minimum bactericidal concentration  (MBC) and time kill kinetics of Amlodipine (AML), Thioridazine (THI) and Promethazine (PRO) against Staphylococcus aureus, coagulase negative staphylococci (CoNS), Streptococcus spp, Escherichia coli, Enterobacter spp, Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates were determined using disc diffusion, broth microdilution and plate count techniques.Results: The mean growth inhibition zones by the disc diffusion assay of AML, THI and PRO against the isolates were ≤15.1±1.0 mm with MIC and MBC values ranging from 12.5 to 50μg/ml and 25 to 100μg/ml respectively. The time-kill assay revealed bactericidal effect of AML, THI and PRO on Gram positive bacteria evidenced by mean log reductions in viable bacterial cell counts ranging from 0.13 Log10 to 2.41 Log10 CFU/ml for S. aureus, 0.88 Log10 to 2.08 Log10 CFU/ml for Streptococcus spp, and 0.26 Log10 to 2.34 Log10 CFU/ml for CoNS after ≤30hrs post inoculation at 1xMIC. The range of log reduction in viable cell counts of Gram-negative bacteria exposed to AML, THI and PRO were E. coli (0.11 to 3.23 Log10 CFU/ml), P. aeruginosa (0.52 to 2.56 Log10 CFU/ml), K. pneumoniae (0.85 to 3.0 Log10 CFU/ml) and  Enterobacter spp (0.38 to 2.08 Log10 CFU/ml) after ≤30 hrs post inoculation at 1x MIC.Conclusion: These findings demonstrate in vitro antibacterial efficacies and time kill kinetics of AML, THI and PRO against pathogenic clinical bacterial isolates, which indicate that these non-antibiotic drugs may be useful therapeutic alternatives in the bid to reduce the burden of infectious diseases associated with antibiotic resistant pathogens. Keywords: Amlodipine, Thioridazine, Promethazine, Time-Kill, Kinetics, MIC, MBC, bacteria   French title: Activité antibactérienne et cinétique de destruction du temps de l'amlodipine, de la thioridazine et de la prométhazine contre les isolats bactériens cliniques pathogènes Contexte: L'émergence de souches bactériennes multirésistantes dans le monde a rendu nécessaire la recherche scientifique d'agents antimicrobiens nouveaux, puissants et abordables, notamment des plantes médicinales et des médicaments non antibiotiques pour le traitement des maladies infectieuses. L'objectif de cette étude est d'évaluer les activités antibactériennes in vitro et la cinétique de destruction temporelle de certains médicaments non antibiotiques contre les isolats bactériens cliniques pathogènes. Méthodologie: activités antibactériennes in vitro, y compris la concentration minimale inhibitrice (CMI), la concentration bactéricide minimale (MBC) et la cinétique de destruction du temps de l'amlodipine (AML), de la thioridazine (THI) et de la prométhazine (PRO) contre Staphylococcus aureus, les staphylocoques à coagulase négative (CoNS), Streptococcus spp, Escherichia coli, Enterobacter spp, Klebsiella pneumoniae et Pseudomonas aeruginosa ont été déterminés en utilisant des techniques de diffusion sur disque, de microdilution en bouillon et de numération sur plaque. Résultats: Les zones moyennes d'inhibition de la croissance par le test de diffusion de disque d'AML, THI et PRO contre les isolats étaient ≤15,1±1,0mm avec des valeurs MIC et MBC allant de 12,5 à 50μg/ml et de 25 à 100μg/ml respectivement. Le dosage temporel a révélé un effet bactéricide de la LMA, du THI et du PRO sur les bactéries Gram positives, mis en évidence par des réductions logarithmiques moyennes du nombre de cellules bactériennes viables allant de 0,13 Log10 à 2,41 Log10 CFU/ml pour S. aureus, 0,88 Log10 à 2,08 Log10 CFU/ml pour Streptococcus spp et 0,26 Log10 à 2,34 Log10 CFU/ml pour CoNS après ≤ 30 heures après l'inoculation à 1 x MIC. La plage de réduction logarithmique du nombre de cellules viables de bactéries à Gram négatif exposées à la LMA, au THI et au PRO était E. coli (0,11 à 3,23 Log10 CFU/ml), P. aeruginosa (0,52 à 2,56 Log10 CFU/ml), K. pneumoniae (0,85 à 3,0 Log10 CFU/ml) et Enterobacter spp (0,38 à 2,08 Log10 CFU/ml) après ≤ 30 heures après l'inoculation à 1 x MIC. Conclusion: Ces résultats démontrent une efficacité antibactérienne in vitro et une cinétique de destruction du temps des LMA, THI et PRO contre les isolats bactériens cliniques pathogènes, ce qui indique que ces médicaments non antibiotiques peuvent être des alternatives thérapeutiques utiles dans le but de réduire le fardeau des maladies infectieuses associées aux antibiotiques pathogènes résistants. Mots-clés: Amlodipine, Thioridazine, Prométhazine, Time-Kill, Cinétique, MIC, MBC, bactéries  

Comparative Killing Kinetics of Methicillin-Resistant Staphylococcus aureus by Bacitracin or Mupirocin

1996 ◽  
Vol 17 (3) ◽  
pp. 178-180
Author(s):  
Edward K. Chapnick ◽  
Jeremy D. Gradon ◽  
Barry Kreiswirth ◽  
Larry I. Lutwick ◽  
Benjamin C. Schaffer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Lower Cost ◽  
In Vivo Studies ◽  
Methicillin Resistant ◽  
Log Reduction ◽  
Different Strains ◽  
Time Kill ◽  
Kinetics Of

AbstractThe in vitro activities of bacitracin and mupirocin were compared for seven different strains of methicillin-resistant Staphylococcus aureus. Six of seven strains showed bacitracin minimum inhibitory concentrations (MICs) of 0.5 to 1.0 units/mL, and all seven had mupirocin MICs of 0.5 to 2 μg/mL. Time-kill studies revealed 2.6- to 4.5-log reduction in 24 hours with strains susceptible to bacitracin (4 units/mL) and 0 to 2.2 reduction with mupirocin (16 μg/mL). Bacitracin should be considered further for in vivo studies because of enhanced bacteriocidal effect and lower cost.

scholarly journals Minocycline Has No Clear Role in the Treatment of Mycobacterium abscessus Disease

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Mike M. Ruth ◽  
Jasper J. N. Sangen ◽  
Lian J. Pennings ◽  
Jodie A. Schildkraut ◽  
Wouter Hoefsloot ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Treatment Modality ◽  
Mycobacterium Abscessus ◽  
Continuation Phase ◽  
Content Type ◽  
Intravenous Treatment ◽  
Time Kill ◽  
Kinetics Of ◽  
Rapid Emergence

ABSTRACT Mycobacterium abscessus causes a difficult-to-treat pulmonary disease (MAb-PD). After initial intravenous treatment, minocycline is recommended in the oral continuation phase of treatment. We determined the MICs, synergy, and time-kill kinetics of minocycline against M. abscessus. With MICs of 8 to 512 mg/liter, rapid emergence of tolerance in time-kill assays, and no synergy with other drugs used to treat MAb-PD, minocycline appears ineffective against M. abscessus. These in vitro data question its role as a MAb-PD treatment modality.

Antifungal activity and killing kinetics of anidulafungin, caspofungin and amphotericin B against Candida auris

2019 ◽  
Vol 74 (8) ◽  
pp. 2295-2302 ◽  
Author(s):  
Catiana Dudiuk ◽  
Indira Berrio ◽  
Florencia Leonardelli ◽  
Soraya Morales-Lopez ◽  
Laura Theill ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungicidal Activity ◽  
Geometric Mean ◽  
Candida Auris ◽  
Initial Inoculum ◽  
Concentration Maximum ◽  
High Concentrations ◽  
Time Kill ◽  
Kinetics Of

AbstractBackgroundCandida auris is an emerging MDR pathogen. It shows reduced susceptibility to azole drugs and, in some strains, high amphotericin B MICs have been described. For these reasons, echinocandins were proposed as first-line treatment for C. auris infections. However, information on how echinocandins and amphotericin B act against this species is lacking.ObjectivesOur aim was to establish the killing kinetics of anidulafungin, caspofungin and amphotericin B against C. auris by time–kill methodology and to determine if these antifungals behave as fungicidal or fungistatic agents against this species.MethodsThe susceptibility of 50 C. auris strains was studied. Nine strains were selected (based on echinocandin MICs) to be further studied. Minimal fungicidal concentrations, in vitro dose–response and time–kill patterns were determined.ResultsEchinocandins showed lower MIC values than amphotericin B (geometric mean of 0.12 and 0.94 mg/L, respectively). Anidulafungin and caspofungin showed no fungicidal activity at any concentration (maximum log decreases in cfu/mL between 1.34 and 2.22). On the other hand, amphotericin B showed fungicidal activity, but at high concentrations (≥2.00 mg/L). In addition, the tested polyene was faster than echinocandins at killing 50% of the initial inoculum (0.92 versus >8.00 h, respectively).ConclusionsAmphotericin B was the only agent regarded as fungicidal against C. auris. Moreover, C. auris should be considered tolerant to caspofungin and anidulafungin considering that their MFC:MIC ratios were mostly ≥32 and that after 6 h of incubation the starting inoculum was not reduced in >90%.

scholarly journals Time-Kill Kinetics of Rezafungin (CD101) in Vagina-Simulative Medium for Fluconazole-Susceptible and Fluconazole-ResistantCandida albicansand Non-albicans CandidaSpecies

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jeffrey B. Locke ◽  
Amanda L. Almaguer ◽  
Joanna L. Donatelli ◽  
Ken F. Bartizal
Keyword(s):  
Antifungal Activity ◽  
Fungicidal Activity ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
The Novel ◽  
Testing Conditions ◽  
Fluconazole Resistant ◽  
Time Kill ◽  
Kinetics Of

Background.While echinocandins demonstrate excellent efficacy againstCandidaspecies in disseminated infections and demonstrate potent minimal inhibitory concentration (MIC) values under standard susceptibility testing conditions, investigation under conditions relevant to the vaginal environment was needed. We assessed the antifungal activity and time-kill kinetics of the novel echinocandin rezafungin (formerly CD101) under such conditions, againstCandidaspecies relevant to vulvovaginal candidiasis (VVC).Methods. Susceptibility testing of fluconazole-susceptible and fluconazole-resistantC. albicans,C. glabrata,C. tropicalis,C. parapsilosis, andC. kruseiwas performed in RPMI at pH 7.0 and in vagina-simulative medium (VSM) at pH 4.2 for topical rezafungin, terconazole, fluconazole, and amphotericin B. Time-kill kinetics were evaluated for rezafungin and terconazole at 2, 8, 32, and 128 μg/ml over 72 hours.Results.Rezafungin MIC values were the same or 2-fold higher in VSM/pH 4.2 versus RPMI/pH 7.0. SomeC. albicansterconazole MIC values were lower, but most were significantly higher in VSM than in RPMI. Rezafungin was fungicidal against 11/14 strains and near-fungicidal against the others. Terconazole (128 μg/ml) was fungicidal againstC. kruseiand near-fungicidal against susceptibleC. parapsilosisbut fungistatic versus all other strains evaluated.Conclusion.Rezafungin retained anti-Candidaactivity and fungicidal activity under in vitro conditions relevant to VVC.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

Acquired Haemophilia: Functional Study of Antibodies to Factor VIII

1981 ◽  
Vol 45 (03) ◽  
pp. 285-289 ◽  
Author(s):  
J P Allain ◽  
A Gaillandre ◽  
D Frommel
Keyword(s):  
Factor Viii ◽  
Functional Study ◽  
Factor Viii Inhibitor ◽  
Acquired Haemophilia ◽  
Viii Inhibitor ◽  
Kinetics Of ◽  
Antibody Function ◽  
Native Plasma

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.

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