scholarly journals Pharmacodynamics of Trovafloxacin, Ofloxacin, and Ciprofloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model

1999 ◽  
Vol 43 (5) ◽  
pp. 1118-1123 ◽  
Author(s):  
Philip D. Lister ◽  
Christine C. Sanders
Keyword(s):  
Antibacterial Activity ◽  
Streptococcus Pneumoniae ◽  
Human Serum ◽  
Clinical Data ◽  
Pharmacokinetic Model ◽  
The Other ◽  
Logarithmic Phase ◽  
Bacterial Counts ◽  
Oral Doses

ABSTRACT An in vitro pharmacokinetic model was used to simulate the pharmacokinetics of trovafloxacin, ofloxacin, and ciprofloxacin in human serum and to compare their pharmacodynamics against eightStreptococcus pneumoniae strains. The MICs of ofloxacin and ciprofloxacin ranged from 1 to 2 μg/ml. Trovafloxacin was 8- to 32-fold more potent, with MICs of 0.06 to 0.12 μg/ml. Logarithmic-phase cultures were exposed to peak concentrations of trovafloxacin, ofloxacin, or ciprofloxacin achieved in human serum after 200-, 400-, and 750-mg oral doses, respectively. Trovafloxacin was dosed at 0 and 24 h, and ofloxacin and ciprofloxacin were dosed at 0, 12, and 24 h. Human elimination pharmacokinetics were simulated, and viable bacterial counts were measured at 0, 2, 4, 6, 8, 12, 24, and 36 h. Trovafloxacin was rapidly and significantly bactericidal against all eight strains evaluated, with viable bacterial counts decreasing at least 5 logs to undetectable levels. Times to 99.9% killing were only 1 to 3 h. Although the rate of killing with ofloxacin was substantially slower than that with trovafloxacin, ofloxacin was also able to eradicate all eight strains from the model, despite a simulated area under the inhibitory curve/MIC ratio (AUC/MIC) of only 49. In contrast, ciprofloxacin eradicated only five strains (AUC/MIC = 44) from the model. Against the other three strains (AUC/MIC = 22), the antibacterial activity of ciprofloxacin was substantially diminished. These data corroborate clinical data and suggest that trovafloxacin has a pharmacodynamic advantage over ciprofloxacin and ofloxacin against S. pneumoniae in relation to its enhanced antipneumococcal activity.

scholarly journals Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model: Impact of Area under the Curve/MIC Ratios on Eradication

2002 ◽  
Vol 46 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Philip D. Lister
Keyword(s):  
Streptococcus Pneumoniae ◽  
Peak Concentration ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Logarithmic Phase ◽  
Pharmacokinetic Models ◽  
Elimination Half ◽  
The Impact ◽  
Similar Peak

ABSTRACT Previous studies have demonstrated that fluoroquinolone area under the curve (AUC)/MIC ratios of 30 to 50 are sufficient to eradicate pneumococci from in vitro pharmacokinetic models (IVPMs). However, more systematic studies of the impact of AUC/MIC ratios on the antipneumococcal activities of fluoroquinolones are needed. In the present study, a two-compartment IVPM was used to evaluate the impact of AUC/MIC ratios on the pharmacodynamics of gatifloxacin against four strains of Streptococcus pneumoniae. Gatifloxacin MICs were 0.4 to 1 μg/ml, whereas levofloxacin MICs were 1.8 to 3.2 μg/ml. Since both peak concentration/MIC (peak/MIC) and AUC/MIC ratios affect fluoroquinolone pharmacodynamics, logarithmic-phase cultures (5 × 107 CFU/ml) were exposed to gatifloxacin at constant peak/MIC ratios of 2:1 to 3:1 at 0 and 24 h, elimination half-lives were varied to provide a range of AUC/MIC ratios, and changes in viable counts were measured over 30 h. As a comparison, levofloxacin was evaluated at similar peak/MIC ratios and at AUC/MIC ratios of 30 to 38. For each strain, killing rates through 4 to 8 h were similar since peak/MIC ratios were kept constant. However, continued killing and eradication were observed only when gatifloxacin AUC/MIC ratios were 27 to 48. Levofloxacin also provided eradication. In contrast, substantial regrowth was observed in most experiments when gatifloxacin AUC/MIC ratios were 9 to 24. These data provide further support that fluoroquinolone AUC/MIC ratios of approximately 30 or higher can be sufficient for eradication of pneumococci from IVPMs. Furthermore, the overall impact of the AUC/MIC ratio was not influenced by the strain evaluated or its susceptibility to gatifloxacin. Further studies with other fluoroquinolones and pneumococci that exhibit wider ranges of susceptibilities are warranted. In addition, similar studies with higher peak/MIC ratios are needed to better define the impact of AUC/MIC ratios and peak/MIC ratios on the antipneumococcal pharmacodynamics of fluoroquinolones.

scholarly journals Cefepime-Aztreonam: a Unique Double β-Lactam Combination for Pseudomonas aeruginosa

1998 ◽  
Vol 42 (7) ◽  
pp. 1610-1619 ◽  
Author(s):  
Philip D. Lister ◽  
W. Eugene Sanders ◽  
Christine C. Sanders
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Pharmacokinetic Model ◽  
Logarithmic Phase ◽  
Positive Interaction ◽  
Before And After ◽  
Dosing Intervals ◽  
Extracellular Environment ◽  
Hydrolysis Activity

ABSTRACT An in vitro pharmacokinetic model was used to determine if aztreonam could enhance the pharmacodynamics of cefepime or ceftazidime against an isogenic panel of Pseudomonas aeruginosa 164, including wild-type (WT), partially derepressed (PD), and fully derepressed (FD) phenotypes. Logarithmic-phase cultures were exposed to peak concentrations achieved in serum with 1- or 2-g intravenous doses, elimination pharmacokinetics were simulated, and viable bacterial counts were measured over three 8-h dosing intervals. In studies with cefepime and cefepime-aztreonam against the PD strain, samples were also filter sterilized, assayed for active cefepime, and assayed for nitrocefin hydrolysis activity before and after overnight dialysis. Against WT strains, the cefepime-aztreonam combination was the most active regimen, but viable counts at 24 h were only 1 log below those in cefepime-treated cultures. Against PD and FD strains, the antibacterial activity of cefepime-aztreonam was significantly enhanced over that of each drug alone, with 3.5 logs of killing by 24 h. Hydrolysis and bioassay studies demonstrated that aztreonam was inhibiting the extracellular cephalosporinase that had accumulated and was thus protecting cefepime in the extracellular environment. In contrast to cefepime-aztreonam, the pharmacodynamics of ceftazidime-aztreonam were not enhanced over those of aztreonam alone. Further pharmacodynamic studies with five other P. aeruginosa strains producing increased levels of cephalosporinase demonstrated that the enhanced pharmacodynamics of cefepime-aztreonam were not unique to the isogenic panel. The results of these studies demonstrate that aztreonam can enhance the antibacterial activity of cefepime against derepressed mutants of P. aeruginosaproducing increased levels of cephalosporinase. This positive interaction appears to be due in part to the ability of aztreonam to protect cefepime from extracellular cephalosporinase inactivation. Clinical evaluation of this combination is warranted.

scholarly journals Importance of beta-lactamase inhibitor pharmacokinetics in the pharmacodynamics of inhibitor-drug combinations: studies with piperacillin-tazobactam and piperacillin-sulbactam.

1997 ◽  
Vol 41 (4) ◽  
pp. 721-727 ◽  
Author(s):  
P D Lister ◽  
A M Prevan ◽  
C C Sanders
Keyword(s):  
Antibacterial Activity ◽  
Critical Concentration ◽  
Specific Inhibitor ◽  
Logarithmic Phase ◽  
Critical Ratio ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Dosing Regimens ◽  
Lactamase Inhibitor

An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases. Logarithmic-phase cultures were exposed to peak antibiotic concentrations observed in human serum after the administration of intravenous doses of 3 g of piperacillin and 0.375 g of tazobactam or 0.5 g of sulbactam. Piperacillin and inhibitor were either dosed simultaneously or piperacillin was dosed sequentially 0.5 h after dosing with the inhibitor. In studies with all four test strains, the pharmacodynamics observed after simultaneous dosing were similar to those observed with the sequential regimen. Since the ratio between piperacillin and tazobactam was in constant fluctuation after sequential dosing, these data suggest that the pharmacodynamics of the piperacillin-inhibitor combinations were not dependent upon maintenance of a critical ratio between the components. Furthermore, when regrowth was observed, the time at which bacterial counts began to increase was similar between the simultaneous and sequential dosing regimens. Since the pharmacokinetics of the inhibitors were the same for all regimens, these data suggest that the length of time that the antibacterial activity was maintained over the dosing interval with these combinations was dictated by the pharmacokinetics of the beta-lactamase inhibitor in the combination. The antibacterial activity of the combination appeared to be lost when the amount of inhibitor available fell below some critical concentration. This critical concentration varied depending upon the type and amount of enzyme produced, as well as the specific inhibitor used. These results indicate that the antibacterial activity of drug-inhibitor combinations, when dosed at their currently recommended ratios, is more dependent on the pharmacokinetics of the inhibitor than on those of the beta-lactam drug.

scholarly journals Evaluation of Antibacterial Activity of Cymbopogon citratus Ethanolic Leaf Crude Extract against Streptococcus pneumoniae isolated from Kampala International University Teaching Hospital Western Campus, Uganda

2019 ◽  
Vol 7 (1) ◽  
pp. 31-38
Author(s):  
Ibrahim Ntulume ◽  
Ninsiima Victoria ◽  
Abubakar Sunusi Adam ◽  
Adamu Almustapha Aliero
Keyword(s):  
Antibacterial Activity ◽  
Streptococcus Pneumoniae ◽  
Crude Extract ◽  
Clinical Isolates ◽  
University Teaching ◽  
Zone Of Inhibition ◽  
Cymbopogon Citratus ◽  
Alternative Intervention ◽  
Adults And Children

Streptococcus pneumoniae is the common cause of pneumonia, meningitis, bacteremia and Septicemia among adults and children worldwide. Resistance to antimicrobials agents has been reported among S. pneumoniae which necessitate the need for alternative intervention such as ethno-medicinal plants. Cymbopogon citratus is an ethno-medicinal plant which is known to have pharmacological activities including antibacterial activity. This study aimed at determining the in vitro antibacterial activity of C. citratus ethanolic leaves crude extract against clinical isolates of S.  pneumoniae. A fresh leaves of C. citratus were collected early in the morning; shed dried, pulverized and extracted using ethanol (96%) using standard extraction method. The antibacterial activity, Minimum Inhibitory and Minimum Bactericidal Concentrations of C. citratus ethanolic leaves crude extract were determined against clinical isolates of S. pneumoniae. C. citratus ethanolic leaves extract crude showed antibacterial activity against S. pneumoniae at 500mg/ml concentration with mean and standard deviation zone of inhibition (26.33 ± 1.53 mm) in comparison with that of 250mg/ml concentration which gave 20.33 ± 2.08 mm mean and standard zone of inhibition. The minimum inhibitory concentration of the plant crude extract against S. pneumoniae was 15.63 mg/ml while the minimum bactericidal concentration was 125mg/ml. The study found that C. citratus leaves ethanolic crude extract was active against S. pneumoniae. It is recommended that studies should be done focusing on isolation of specific phytochemicals of the C. citratus leaves crude extract and then determines their antibacterial activity against clinical isolates of S. pneumoniae. Int. J. Appl. Sci. Biotechnol. Vol 7(1): 31-38

scholarly journals Antibacterial and Hemolytic Activity of Crotalus triseriatus and Crotalus ravus Venom

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 281
Author(s):  
Adrian Zaragoza-Bastida ◽  
Saudy Consepcion Flores-Aguilar ◽  
Liliana Mireya Aguilar-Castro ◽  
Ana Lizet Morales-Ubaldo ◽  
Benjamín Valladares-Carranza ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Minimum Inhibitory Concentration ◽  
Hemolytic Activity ◽  
Inhibitory Concentration ◽  
Minimum Bactericidal Concentration ◽  
The Other ◽  
Medical Treatments ◽  
First Time

Rattlesnakes have venoms with a complex toxin mixture comprised of polypeptides and proteins. Previous studies have shown that some of these polypeptides are of high value for the development of new medical treatments. The aim of the present study is to evaluate, in vitro, the antibacterial and hemolytic activity of Crotalus triseriatus and Crotalus ravus venoms. A direct field search was conducted to obtain Crotalus triseriatus and Crotalus ravus venom samples. These were evaluated to determine their antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa through the techniques of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Hemolytic activity was also determined. Antibacterial activity was determined for treatments (Crotalus triseriatus 2) CT2 and (Crotalus ravus 3) CR3, obtaining a Minimum Inhibitory Concentration of 50 µg/mL and a Minimum Bactericidal Concentration of 100 µg/mL against Pseudomonas aeruginosa. CT1 (Crotalus triseriatus 1), CT2, and CR3 presented hemolytic activity; on the other hand, Crotalus ravus 4 (CR4) did not show hemolytic activity. The results of the present study indicate for the first time that Crotalus triseriatus and Crotalus ravus venoms contain some bioactive compounds with bactericidal activity against Pseudomonas aeruginosa which could be used as alternative treatment in diseases caused by this pathogenic bacterium.

Antibacterial activity and in vitro cytotoxicity evaluation of alginate-AgNP fibers

2016 ◽  
Vol 87 (11) ◽  
pp. 1377-1386 ◽  
Author(s):  
Xihui Zhao ◽  
Qun Li ◽  
Xiaowen Li ◽  
Yanzhi Xia ◽  
Bing Wang ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Treatment Time ◽  
Biological Activities ◽  
In Vitro Cytotoxicity ◽  
Cell Counting ◽  
Logarithmic Phase ◽  
E Coli ◽  
Alginate Fibers ◽  
And Staphylococcus Aureus

Biopolymer nanocomposites containing metal nanoparticles have attracted much attention due to their excellent properties and broad applications. In this work, alginate fibers embedded with silver nanoparticles (AgNPs) were prepared. The as-obtained alginate-AgNP fibers exhibited antibacterial activity against both Gram microorganisms of model microbes Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). A growth kinetic study with S. aureus and E. coli displayed the inhibition of bacterial growth at the logarithmic phase. The cytotoxic effect of the fibers in human cervical cancer (HeLa) cells was assessed by cell counting kit-8 (CCK-8) assay and flow cytometry. The as-prepared alginate-AgNP fibers, particularly with high amount and long treatment time, showed high cell-killing efficiency. These findings emphasize that such alginate-AgNP fibers with multifaceted biological activities are a promising material for applications in the textile or biomedical fields.

scholarly journals Comparative In Vitro Activities of Daptomycin and Vancomycin against Resistant Gram-Positive Pathogens

2000 ◽  
Vol 44 (12) ◽  
pp. 3447-3450 ◽  
Author(s):  
D. R. Snydman ◽  
N. V. Jacobus ◽  
L. A. McDermott ◽  
J. R. Lonks ◽  
J. M. Boyce
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Streptococcus Pneumoniae ◽  
Calcium Concentration ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Vancomycin Resistant ◽  
Gram Positive Cocci

ABSTRACT The in vitro activity of daptomycin against 224 current gram-positive clinical isolates including vancomycin-resistantEnterococcus faecium (VREF), methicillin-resistantStaphylococcus aureus (MRSA), methicillin-resistantStaphylococcus spp. (MRSS), and penicillin-resistantStreptococcus pneumoniae (PRSP) was evaluated. The MICs at which 90% of isolates are inhibited for daptomycin and vancomycin, respectively, were as follows: MRSA, 1 and 2 μg/ml; MRSS, 1 and 4 μg/ml; PRSP, 1 and 0.5 μg/ml; and VREF, 2 and >64 μg/ml. Daptomycin was bactericidal against 82% of 17 VREF isolates. The antibacterial activity of daptomycin was strongly dependent on the calcium concentration of the medium. Daptomycin was active against all gram-positive cocci tested.

scholarly journals Evaluation of antimicrobial and antibiofilm activities of stingless bee Trigona honey (Malaysia) against Streptococcus pneumoniae

10.3823/856 ◽  
2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Mohammad A. Alkafaween ◽  
Hamid A. Nagi Al-Jamal ◽  
Abu Bakar Mohmd Hilmi
Keyword(s):  
Antibacterial Activity ◽  
Streptococcus Pneumoniae ◽  
Biofilm Formation ◽  
Stingless Bee ◽  
Expression Of Genes ◽  
Zones Of Inhibition

Background: The study aims to evaluate the antibacterial activity of Trigona honey against S. pneumonia. Methods: The effect of Trigona honey on S. pneumonia investigated using agar well diffusion, MIC, MBC, biofilm formation and RT-qPCR. Results: Trigona honey samples showed the larger zones of inhibition against S. pneumonia, 22.2±0.4 at 100% concentration. Trigona honey possessed the lowest MIC, MBC, MIC50 and MIC90 against S. pneumoniae, 25%, 30%, 12.5% and 25% (w/v) respectively. Trigona honey permeated established biofilms of S. pneumonia, resulting in significant decreased the cells from the biofilm. RT-qPCR revealed that the expression of genes amiF, ftsY, mvaS, pnpA, argG, mvd1, purN, miaA and pbp2a were upregulated, glcK, marR, prmA and ccpA­­­ were downregulated after exposure to honey. Conclusion: Trigona honey demonstrated the highest antibacterial activity against S. pneumoniae. By limiting study in vitro on Trigona honey, we infer that Trigona honey impacts on S. pneumoniae.

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