Intracellular pharmacodynamics of antibiotics

Carryn, Stéphane; Chanteux, Hugues; Seral, Cristina; Mingeot‐Leclercq, Marie‐Paule; Bambeke, Françoise Van; Tulkens, Paul M.

doi:10.1016/s0891-5520(03)00066-7

Cited by 172 publications

(163 citation statements)

References 98 publications

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“…Consequently, when equilibrium has been reached, one might predict that the concentration in leucocytes will be reflected by the external concentration of flumequine and oxolinic acid in the surrounding fluid or organ. In general, fluoroquinolones have a fast in-and outflux of cells, which our results confirm, although a much higher intracellular accumulation, 7-and 8-fold at equilibrium, has been described for ciprofloxacin and moxifloxacin, respectively, in human macrophages (Carryn et al 2003). The differences concerning intra-versus extracellular concentrations may reflect both differences between human and Atlantic cod macrophages and pharmacokinetic differences between quinolones.…”

Section: Discussionsupporting

confidence: 84%

“…There is a consensus that fluoroquinolones are effective in treatment of various bacterial infections caused by both obligate and facultative intracellular organisms (Carryn et al 2003). However, Carryn et al (2002) also observed a decrease in intracellular bactericidal activity especially of ciprofloxacin and to a lesser extent of moxifloxacin against Listeria monocytogenes.…”

Section: Discussionmentioning

confidence: 99%

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Antibiotic uptake by cultured Atlantic cod leucocytes and effect on intracellular Francisella noatunensis subsp. noatunensis replication

Kaldestad¹,

Haugland²,

Rønneseth³

et al. 2014

Dis. Aquat. Org.

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The granuloma disease caused by Francisella noatunensis subsp. noatunensis in farmed Atlantic cod has not been successfully treated by use of antibacterials, even when antibacterial resistance testing indicates a sufficient effect. The reason for this treatment failure may be the intracellular existence of the bacteria within immune cells, mainly macrophages. To investigate the effect of antibacterials on intracellular Francisella replication, we established a protocol for the detection of drugs within Atlantic cod immune cells using high-performance liquid chromatography (HPLC). When the uptake and intracellular concentrations of oxolinic acid and flumequine were analysed in isolated adherent head kidney leucocytes (HKLs) by HPLC, we found that uptake was rapid and the intracellular concentrations reflected the extracellular exposure concentrations. To investigate the effect of the antibacterial compounds on intracellular bacterial replication, adherent HKLs experimentally infected with the bacteria were analysed using flow cytometry and intracellular labelling of bacteria by specific antibodies. We found that flumequine did not inhibit intracellular bacterial replication. Unexpectedly, the results indicated that the intracellularly effiacy of the drug was reduced. The HPLC method used proved to be highly applicable for accurate determination of intracellular drug concentrations. When combined with sensitive and specific flow cytometry analyses for identification and measurement of intracellular bacterial replication, we suggest that this approach can be very valuable for the design of antibacterial treatments of intracellular pathogens.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Antibiotic uptake by cultured Atlantic cod leucocytes and effect on intracellular Francisella noatunensis subsp. noatunensis replication

Kaldestad¹,

Haugland²,

Rønneseth³

et al. 2014

Dis. Aquat. Org.

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“…The intracellular concentration depends on 8 penetration, accumulation and disposition [20,49]. However, as discussed above, GEN, being polar, does not pass efficiently across membranes, and therefore is taken up by endocytosis, which results in an exclusively lysosomal localization helped by its lysosomotropism.…”

Section: Gentamicin Biodisponibility and Drug Delivery Systemsmentioning

confidence: 99%

Chemical and Biological Factors in the Control of Brucella and Brucellosis

Gamazo¹,

Lecaroz²,

Prior³

et al. 2006

CDD

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“…This study could provide the descriptive information on the kinetics of bacterial killing effects, whether it is concentration-dependent or time-dependent. The discrepancy in bacterial killing effects is due to the interrelationship between the pharmacokinetic and pharmacodynamic factors [1] . The time-kill curves study provides more accurate description on the pharmacodynamics of antimicrobial agents than the MIC [2,3] .…”

mentioning

confidence: 99%

“…In addition to that, the concentration-dependent pattern showed is more likely to be associated with the pharmacokineticpharmacodynamic properties of the plant extract during the antimicrobial therapy [15] . According to Carryn et al [1] the pharmacokinetics is described as the cellular uptake and disposition of antibiotics whilst pharmacodynamics is related with the intracellular activity of the antibiotics. The killing activity of an antibiotic is initiated with the binding of the drug to its target site of the bacteria.…”

mentioning

confidence: 99%

In vitro Antibacterial Activity and Cytotoxicity of Lagerstroemia speciosa Bark Extract

Lai¹,

Darah²

2016

ijps

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Lai, et al.: Antibacterial and Cytotoxicity of Lagerstroemia speciosa ExtractLagerstroemia speciosa bark extract was investigated for its pharmacokinetic and pharmacodynamic parameters against two selected pathogenic bacteria by the time-kill curves assay. The brine shrimp lethality test was carried out to determine the toxic level of the extract towards the eukaryotic cells. The extract showed a concentration-dependent killing effect for both B. spizizenii ATCC 6633 and A. anitratus. The number of bacteria was significantly reduced when they were exposed to 2MIC (minimum inhibition concentration) level. Bacteria B. spizizenii ATCC 6633 was more susceptible to the extract as compared to A. anitratus. The extract was found to be nontoxic during the short term (acute) exposure but it was toxic during the prolonged time (chronic) exposure. The LC 50 for acute test and chronic test were 3422.68 and 35.30 µg/ml, respectively. This study indicated that the methanol extract of L. speciosa is a promising candidate for the search of natural antimicrobial and anticancer drugs.

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Intracellular pharmacodynamics of antibiotics

Cited by 172 publications

References 98 publications

Antibiotic uptake by cultured Atlantic cod leucocytes and effect on intracellular Francisella noatunensis subsp. noatunensis replication

Antibiotic uptake by cultured Atlantic cod leucocytes and effect on intracellular Francisella noatunensis subsp. noatunensis replication

Chemical and Biological Factors in the Control of Brucella and Brucellosis

In vitro Antibacterial Activity and Cytotoxicity of Lagerstroemia speciosa Bark Extract

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