scholarly journals Comparative Pharmacodynamics of Three Newer Fluoroquinolones versus Six Strains of Staphylococci in an In Vitro Model under Aerobic and Anaerobic Conditions

2002 ◽  
Vol 46 (5) ◽  
pp. 1561-1563 ◽  
Author(s):  
David H. Wright ◽  
Brent W. Gunderson ◽  
Laurie B. Hovde ◽  
Gigi H. Ross ◽  
Khalid H. Ibrahim ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Pharmacodynamic Model ◽  
Clinical Isolates ◽  
Anaerobic Conditions ◽  
Vitro Model ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

ABSTRACT Six strains of staphylococci were exposed to levofloxacin, moxifloxacin, or trovafloxacin in an in vitro pharmacodynamic model under both aerobic and anaerobic conditions. Each agent demonstrated a rapid 3-log10 kill versus susceptible isolates regardless of condition. Against clinical isolates with reduced susceptibility, regrowth occurred by 24 h and was frequently associated with further increases in MICs.

Metabolite utilization by isolated embryonic rat hearts in vitro

Development ◽  
1972 ◽  
Vol 28 (2) ◽  
pp. 235-245
Author(s):  
Steven J. Cox ◽  
David L. Gunberg
Keyword(s):  
Metabolic Pathways ◽  
Maximum Rate ◽  
Contractile Activity ◽  
Cardiac Contraction ◽  
Anaerobic Conditions ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

Isolated hearts from 11-, 12- and 13-day rat embryos were incubated in a simple defined salt solution to which was added a variety of single substrates. Utilization of the added substrate was determined by comparing the contractile rates of the hearts in the presence and absence of the compound being tested. Of all the compounds tested only those involved in the Embden-Meyerhof glycolytic pathway were capable of maintaining cardiac contraction at a maximum rate in the 11-day heart. This was accomplished under both aerobic and anaerobic conditions. Although glycolysis remained important, the 12- and 13-day hearts exhibited a shift in dependence towards other metabolic pathways. This conclusion was based on the observations that anaerobic glycolysis could no longer maintain maximum heart rates and that a variety of non-glycolytic compounds could be utilized for contractile activity by the 12- and 13-day organs.

Organic Acids and Anaerobic Microorganisms in the Contents of the Cholesteatoma SAC

1983 ◽  
Vol 92 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Yukiko Iino ◽  
Tomonori Takasaka ◽  
Etsuro Hoshino ◽  
Yutaka Kaneko ◽  
Sachiko Tomioka ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Organic Acids ◽  
Volatile Fatty Acids ◽  
Chromatographic Technique ◽  
Anaerobic Conditions ◽  
Clostridium Species ◽  
Anaerobic Microorganisms ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

Organic acids in the contents of the cholesteatoma sac from 28 cases were studied by gas chromatographic technique. Five volatile fatty acids (acetate, propionate, isobutyrate, butyrate and isovalerate) and lactate were detected in large amounts, which may lower the pH of the cholesteatoma content. These acids were considered to be derived from products of anaerobic microorganisms. Therefore, the contents from 12 cases were cultured anaerobically in a glove box. Obligate microorganisms were identified in 92% of the cases and Peptococcus, Bacteroides, and Clostridium species were frequently isolated. In vitro, such obligate anaerobes produced various organic acids from the cholesteatoma content. Facultatives such as Staphylococcus aureus and Proteus mirabilis produced acetate in the content under aerobic and anaerobic conditions, whereas no organic acid was produced by Pseudomonas aeruginosa. Organic acids in the cholesteatoma content could be fermentative products made by the microorganisms, anaerobes and facultatives, which use the content as a substrate for acid production.

scholarly journals Activity of Telavancin against Staphylococcus aureus Strains with Various Vancomycin Susceptibilities in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations

2009 ◽  
Vol 53 (7) ◽  
pp. 2928-2933 ◽  
Author(s):  
Steven N. Leonard ◽  
Céline Vidaillac ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
In Vitro Model ◽  
Therapeutic Potential ◽  
Population Analysis ◽  
Pharmacodynamic Model ◽  
Bacterial Killing ◽  
Vitro Model

ABSTRACT We investigated the activity of telavancin, a novel lipoglycopeptide, alone and combined with gentamicin or rifampin (rifampicin) against strains of Staphylococcus aureus with various vancomycin susceptibilities. Strains tested included methicillin (meticillin)-resistant S. aureus (MRSA) 494, methicillin-sensitive S. aureus (MSSA) 1199, heteroresistant glycopeptide-intermediate S. aureus (hGISA) 1629, which was confirmed by a population analysis profile, and glycopeptide-intermediate S. aureus (GISA) NJ 992. Regimens of 10 mg/kg telavancin daily and 1 g vancomycin every 12 h were investigated alone and combined with 5 mg/kg gentamicin daily or 300 mg rifampin every 8 h in an in vitro model with simulated endocardial vegetations over 96 h. Telavancin demonstrated significantly greater killing than did vancomycin (P < 0.01) for all isolates except MRSA 494 (P = 0.07). Telavancin absolute reductions, in log10 CFU/g, at 96 h were 2.8 ± 0.5 for MRSA 494, 2.8 ± 0.3 for MSSA 1199, 4.2 ± 0.2 for hGISA 1629, and 4.1 ± 0.3 for GISA NJ 992. Combinations of telavancin with gentamicin significantly enhanced killing compared to telavancin alone against all isolates (P < 0.001) except MRSA 494 (P = 0.176). This enhancement was most evident against hGISA 1629, where killing to the level of detection (2 log10 CFU/g) was achieved at 48 h (P < 0.001). The addition of rifampin to telavancin resulted in significant (P < 0.001) enhancement of killing against only MSSA 1199. No changes in telavancin susceptibilities were observed. These results suggest that telavancin may have therapeutic potential, especially against strains with reduced susceptibility to vancomycin. Combination therapy, particularly with gentamicin, may improve bacterial killing against certain strains.

The energy metabolism of adult Haemonchus contortus, in vitro

Parasitology ◽  
1978 ◽  
Vol 77 (3) ◽  
pp. 255-271 ◽  
Author(s):  
P. F. V. Ward ◽  
N. S. Huskisson
Keyword(s):  
Energy Metabolism ◽  
Haemonchus Contortus ◽  
Aerobic Incubation ◽  
Anaerobic Conditions ◽  
Physically Active ◽  
Aerobic Conditions ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

SummaryA comparison was made of the major excretory products when adult Haemonchus contortus worms were incubated with D-[U-14C]glucose under aerobic and anaerobic conditions. Catabolites measured were propan-1-ol, acetate, n-propionate and CO2 and the only major difference was that nearly twice as much CO2 both in terms of quantity and radioactivity was excreted under aerobic than anaerobic conditions. The worms were also much more physically active under aerobic conditions. When worms were incubated under aerobic conditions with increasing amounts of fluoroacetate their CO2 production was progressively reduced to the anaerobic level. Their movement and their ability to clump together was also progressively reduced. After aerobic incubation with fluoroacetate and D-[U-14C]g1ucose the quantity and radioactivity of citrate within worms increased greatly. When worms were similarly incubated anaerobically no increase in citrate occurred, no radioactivity was associated with the citrate and the worms appeared physically unaffected. When worms were incubated aerobically with fluoro[1-14C]acetate they produced radioactive fluorocitrate.

scholarly journals Kinetic Analysis of the Oxidative Conversion of the [4Fe-4S]2+ Cluster of FNR to a [2Fe-2S]2+ Cluster

2004 ◽  
Vol 186 (23) ◽  
pp. 8018-8025 ◽  
Author(s):  
Victoria R. Sutton ◽  
Erin L. Mettert ◽  
Helmut Beinert ◽  
Patricia J. Kiley
Keyword(s):  
Oxidative Conversion ◽  
Anaerobic Conditions ◽  
Protein Levels ◽  
Detectable Difference ◽  
Fnr Protein ◽  
Sense And Respond ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

ABSTRACT The ability of FNR to sense and respond to cellular O2 levels depends on its [4Fe-4S]2+ cluster. In the presence of O2, the [4Fe-4S]2+ cluster is converted to a [2Fe-2S]2+ cluster, which inactivates FNR as a transcriptional regulator. In this study, we demonstrate that ∼2 Fe2+ ions are released from the reaction of O2 with the [4Fe-4S]2+ cluster. Fe2+ release was then used as an assay of reaction progress to investigate the rate of [4Fe-4S]2+ to [2Fe-2S]2+ cluster conversion in vitro. We also found that there was no detectable difference in the rate of O2-induced cluster conversion for FNR free in solution compared to its DNA-bound form. In addition, the rate of FNR inactivation was monitored in vivo by measuring the rate at which transcriptional regulation by FNR is lost upon the exposure of cells to O2; a comparison of the in vitro and in vivo rates of conversion suggests that O2-induced cluster conversion is sufficient to explain FNR inactivation in cells. FNR protein levels were also compared for cells grown under aerobic and anaerobic conditions.

scholarly journals Antistaphylococcal Effect Related to the Area under the Curve/MIC Ratio in an In Vitro Dynamic Model: Predicted Breakpoints versus Clinically Achievable Values for Seven Fluoroquinolones

2005 ◽  
Vol 49 (7) ◽  
pp. 2642-2647 ◽  
Author(s):  
Alexander A. Firsov ◽  
Irene Y. Lubenko ◽  
Sergey N. Vostrov ◽  
Yury A. Portnoy ◽  
Stephen H. Zinner
Keyword(s):  
In Vitro Model ◽  
Therapeutic Potential ◽  
Area Under The Curve ◽  
Antimicrobial Effect ◽  
Clinical Isolates ◽  
Clinical Settings ◽  
Time Curve ◽  
Concentration Time ◽  
Vitro Model

ABSTRACT Prediction of the relative efficacies of different fluoroquinolones is often based on the ratios of the clinically achievable area under the concentration-time curve (AUC) to the MIC, usually with incorporation of the MIC50 or the MIC90 and with the assumption of antibiotic-independent patterns of the AUC/MIC-response relationships. To ascertain whether this assumption is correct, the pharmacodynamics of seven pharmacokinetically different quinolones against two clinical isolates of Staphylococcus aureus were studied by using an in vitro model. Two differentially susceptible clinical isolates of S. aureus were exposed to two 12-h doses of ciprofloxacin (CIP) and one dose of gatifloxacin (GAT), gemifloxacin (GEM), grepafloxacin (GRX), levofloxacin (LVX), moxifloxacin (MXF), and trovafloxacin (TVA) over similar AUC/MIC ranges from 58 to 932 h. A specific bacterial strain-independent AUC/MIC relationship with the antimicrobial effect (IE ) was associated with each quinolone. Based on the IE -log AUC/MIC relationships, breakpoints (BPs) that are equivalent to a CIP AUC/MIC ratio of 125 h were predicted for GRX, MXF, and TVA (75 to 78 h), GAT and GEM (95 to 103 h) and LVX (115 h). With GRX and LVX, the predicted BPs were close to those established in clinical settings (no clinical data on other quinolones are available in the literature). To determine if the predicted AUC/MIC BPs are achievable at clinical doses, i.e., at the therapeutic AUCs (AUCthers), the AUCther/MIC50 ratios were studied. These ratios exceeded the BPs for GAT, GEM, GRX, MXF, TVA, and LVX (750 mg) but not for CIP and LVX (500 mg). AUC/MIC ratios above the BPs can be considered of therapeutic potential for the quinolones. The highest ratios of AUCther/MIC50 to BP were achieved with TVA, MXF, and GEM (2.5 to 3.0); intermediate ratios (1.5 to 1.6) were achieved with GAT and GRX; and minimal ratios (0.3 to 1.2) were achieved with CIP and LVX.

scholarly journals Determination of Antibiotic Effect in an In Vitro Pharmacodynamic Model: Comparison with an Established Animal Model of Infection

2002 ◽  
Vol 46 (11) ◽  
pp. 3574-3579 ◽  
Author(s):  
Charles R. Bonapace ◽  
Lawrence V. Friedrich ◽  
John A. Bosso ◽  
Roger L. White
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
In Vitro Model ◽  
Pharmacodynamic Model ◽  
Maximum Effect ◽  
Infection Model ◽  
Regression Equations ◽  
Antibiotic Effect ◽  
Vitro Model

ABSTRACT Animal infection models have historically been used to study pharmacodynamic relationships. Similar results could theoretically be produced by using an in vitro pharmacodynamic model as an alternative to animal models. We compared the antibiotic effects of ticarcillin administered in various doses and dosing regimens against Pseudomonas aeruginosa ATCC 27853 under conditions analogous to those previously employed in a neutropenic-mouse thigh infection model (B. Vogelman et al., J. Infect. Dis. 158:831-847, 1988). Ticarcillin dosages of either 96, 192, or 384 mg/day were administered at 1-, 2-, 3-, 4-, 8-, 12-, or 24-h intervals into a two-compartment model in order to duplicate the concentration-time profiles of the animal model. Colony counts were enumerated at 0 and 24 h. Linear regression and sigmoidal maximum-effect (Emax) model fitting were used to assess the relationship between the percentage of time that the concentration remained above the MIC (%T>MIC) or above four times the MIC (%T>4×MIC) and the change in the log10 CFU per milliliter (Δlog10 CFU/ml) in the central and peripheral compartments. Statistical analysis of the Δlog10 CFU/ml values was performed for matched regimens of the in vitro and animal models based on the %T>MICs. The slopes of the regression equations of %T>MICs relative to Δlog10 CFU/ml values were similar for the in vitro and animal models, but the y intercept was greater with the in vitro model. The Δlog10 CFU/ml values of the 0- to 24-h colony counts at equivalent %T>MICs in the two models were not statistically different (P = 0.087). Overall, the peripheral compartment of the in vitro model was a better predictor of effect than the central compartment. This study, which compares pharmacodynamic principles between an in vitro and an animal model, demonstrated similar relationships between %T>MICs and effects.

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