scholarly journals Net Effect of Inoculum Size on Antimicrobial Action of Ampicillin-Sulbactam: Studies Using an In Vitro Dynamic Model

2006 ◽  
Vol 50 (9) ◽  
pp. 3230-3230
Author(s):  
Alexander A. Firsov ◽  
Matthew Ruble ◽  
Deborah Gilbert ◽  
Daniele Saverino ◽  
Brenda Manzano ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Inoculum Size ◽  
Antimicrobial Action

scholarly journals Net effect of inoculum size on antimicrobial action of ampicillin-sulbactam: studies using an in vitro dynamic model.

1997 ◽  
Vol 41 (1) ◽  
pp. 7-12 ◽  
Author(s):  
A A Firsov ◽  
M Ruble ◽  
D Gilbert ◽  
D Saverino ◽  
D Savarino ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Approximate Equation ◽  
Bacterial Count ◽  
Inoculum Size ◽  
Antimicrobial Action ◽  
Time Curve ◽  
Bacterial Counts ◽  
The Difference ◽  
Different Strains

To examine the predictable effect of inoculum size on the kinetics of the antimicrobial action of ampicillin-sulbactam, five TEM-1 beta-lactamase-producing Escherichia coli strains were studied in an in vitro dynamic model at two different initial inocula (N0S). All bacteria were exposed to ampicillin-sulbactam in a simulated system reflecting the pharmacokinetic profiles in human tissue after the administration of a single intravenous dose of ampicillin (2 g) plus sulbactam (1 g). Each strain was studied at low (4.0 to 5.2 log CFU/ml) and high (5.0 to 7.1 log CFU/ml) N0S. Despite pronounced differences in susceptibilities, the patterns of the killing curves observed with a given strain at different N0S were similar. As expected, viable bacterial counts increased with inoculum size. Striking visual contrasts in the respective curves for each organism were reflected by the area under the bacterial count-time curve (AUBC) but not by the difference between the N0 and the lowest bacterial counts (Nmin) at the nadir of the killing curve: the N0-associated changes in the AUBC on average were 75%, versus 2.5% for log N0--logNmin. To examine qualitative differences in antimicrobial effects at different N0S (i.e., the net effect of the inoculum), the difference in the high and low N0S was subtracted from each point on the killing curve obtained at the higher N0 for each strain. These adjusted curves were virtually superimposable on the observed killing curves obtained at the lower N0. Moreover, by using adjusted data, the AUBC values were similar at the two inocula, although slight (average, 11%) but systematic increases in the AUBC occurred at high N0S. Thus, there was only a weak net effect of inoculum size on the antibacterial effect of ampicillin-sulbactam. Due to similar slopes of the AUBC-log N0 plots, the antibacterial action at different N0S may be easily predicted by an approximate equation; the predicted AUBCs were unbiased and well correlated with the observed AUBCs (r = 0.997). Compiled data obtained with normalized AUBCs for different strains at different N0S yielded a positive correlation (r = 0.963) between the N0-normalized AUBC and the MIC of ampicillin-sulbactam. The adjustment and normalization procedure described might be a useful tool for revealing the net effect of the inoculum and to predict the inoculum effect if there are no qualitative differences in antimicrobial action at different inocula.

A dynamic model for in-vitro evaluation of antimicrobial action by simulation of the pharmacokinetic profiles of antibiotics

1989 ◽  
Vol 23 (3) ◽  
pp. 389-399 ◽  
Author(s):  
S. M. Navashin ◽  
I. P. Fomina ◽  
A. A. Firsov ◽  
V. M. Chernykh ◽  
S. Kuznetsova
Keyword(s):  
Dynamic Model ◽  
Antimicrobial Action ◽  
In Vitro Evaluation ◽  
Pharmacokinetic Profiles

Prediction of the Effects of Inoculum Size on the Antimicrobial Action of Trovafloxacin and Ciprofloxacin againstStaphylococcus aureus and Escherichia coli in an In Vitro Dynamic Model

1999 ◽  
Vol 43 (3) ◽  
pp. 498-502 ◽  
Author(s):  
Alexander A. Firsov ◽  
Sergey N. Vostrov ◽  
Olga V. Kononenko ◽  
Stephen H. Zinner ◽  
Yury A. Portnoy
Keyword(s):  
Escherichia Coli ◽  
Dynamic Models ◽  
Antimicrobial Effect ◽  
Inoculum Size ◽  
Antimicrobial Action ◽  
Time Curve ◽  
Mean Values ◽  
E Coli ◽  
Inoculum Effect

ABSTRACT The effect of inoculum size (N 0) on antimicrobial action has not been extensively studied in in vitro dynamic models. To investigate this effect and its predictability, killing and regrowth kinetics of Staphylococcus aureus andEscherichia coli exposed to monoexponentially decreasing concentrations of trovafloxacin (as a single dose) and ciprofloxacin (two doses at a 12-h interval) were compared atN 0 = 106 and 109 CFU/ml (S. aureus) and at N 0 = 106, 107, and 109 CFU/ml (E. coli). A series of pharmacokinetic profiles of trovafloxacin and ciprofloxacin with respective half-lives of 9.2 and 4 h were simulated at different ratios of area under the concentration-time curve (AUC) to MIC (in [micrograms × hours/milliliter]/[micrograms/milliliter]): 58 to 466 with trovafloxacin and 116 to 932 with ciprofloxacin for S. aureus and 58 to 233 and 116 to 466 for E. coli, respectively. Although the effect of N 0 was more pronounced for E. coli than for S. aureus, only a minor increase in minimum numbers of surviving bacteria and an almost negligible delay in their regrowth were associated with an increase of the N 0 for both organisms. TheN 0-induced reductions of the intensity of the antimicrobial effect (IE , area between control growth and the killing-regrowth curves) were also relatively small. However, the N 0 effect could not be eliminated either by simple shifting of the time-kill curves obtained at higherN 0s by the difference between the higher and lowest N 0 or by operating withIE s determined within theN 0-adopted upper limits of bacterial numbers (IE ′s). By using multivariate correlation and regression analyses, linear relationships betweenIE and log AUC/MIC and logN 0 related to the respective mean values [(log AUC/MIC)average and (logN 0)average] were established for both trovafloxacin and ciprofloxacin against each of the strains (r 2 = 0.97 to 0.99). The antimicrobial effect may be accurately predicted at a given AUC/MIC of trovafloxacin or ciprofloxacin and at a given N 0 based on the relationship IE = a + b [(log AUC/MIC)/(log AUC/MIC)average] − c [(logN 0)/(logN 0)average]. Moreover, the relative impacts of AUC/MIC and N 0 onIE may be evaluated. Since the c/bratios for trovafloxacin and ciprofloxacin against E. coliwere much lower (0.3 to 0.4) than that for ampicillin-sulbactam as examined previously (1.9), the inoculum effect with the quinolones may be much less pronounced than with the β-lactams. The described approach to the analysis of the inoculum effect in in vitro dynamic models might be useful in studies with other antibiotic classes.

scholarly journals AZD-3043

2012 ◽  
Vol 116 (6) ◽  
pp. 1267-1277 ◽  
Author(s):  
Talmage D. Egan ◽  
Shinju Obara ◽  
Thomas E. Jenkins ◽  
Sarah S. Jaw-Tsai ◽  
Shanti Amagasu ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Metabolic Pathway ◽  
Liver Microsomes ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Duration Of Action ◽  
Chloride Currents ◽  
Gaba A ◽  
Hypnotic Agent

Background Propofol can be associated with delayed awakening after prolonged infusion. The aim of this study was to characterize the preclinical pharmacology of AZD-3043, a positive allosteric modulator of the γ-aminobutyric acid type A (GABA(A)) receptor containing a metabolically labile ester moiety. The authors postulated that its metabolic pathway would result in a short-acting clinical profile. Methods The effects of AZD-3043, propofol, and propanidid were studied on GABA(A) receptor-mediated chloride currents in embryonic rat cortical neurons. Radioligand binding studies were also performed. The in vitro stability of AZD-3043 in whole blood and liver microsomes was evaluated. The duration of the loss of righting reflex and effects on the electroencephalograph evoked by bolus or infusion intravenous administration were assessed in rats. A mixed-effects kinetic-dynamic model using minipigs permitted exploration of the clinical pharmacology of AZD-3043. Results AZD-3043 potentiated GABA(A) receptor-mediated chloride currents and inhibited [(35)S]tert-butylbicyclophosphorothionate binding to GABA(A) receptors. AZD-3043 was rapidly hydrolyzed in liver microsomes from humans and animals. AZD-3043 produced hypnosis and electroencephalograph depression in rats. Compared with propofol, AZD-3043 was shorter acting in rats and pigs. Computer simulation using the porcine kinetic-dynamic model demonstrated that AZD-3043 has very short 50 and 80% decrement times independent of infusion duration. Conclusions AZD-3043 is a positive allosteric modulator of the GABA(A) receptor in vitro and a sedative-hypnotic agent in vivo. The esterase dependent metabolic pathway results in rapid clearance and short duration of action even for long infusions. AZD-3043 may have clinical potential as a sedative-hypnotic agent with rapid and predictable recovery.

Bactericidal activity of two different dosage regimens of imipenem in an in-vitro dynamic model

1993 ◽  
Vol 32 (2) ◽  
pp. 295-300 ◽  
Author(s):  
Franco Maggiolo ◽  
Alberto Taras ◽  
Stefano Frontespezi ◽  
Francesco Bottari ◽  
Maria Cristina Legnani ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Bactericidal Activity ◽  
Dosage Regimens

scholarly journals Gastric digestion of milk protein ingredients: Study using an in vitro dynamic model

2018 ◽  
Vol 101 (8) ◽  
pp. 6842-6852 ◽  
Author(s):  
Xin Wang ◽  
Aiqian Ye ◽  
Quanquan Lin ◽  
Jianzhong Han ◽  
Harjinder Singh
Keyword(s):  
Dynamic Model ◽  
Milk Protein ◽  
Gastric Digestion

scholarly journals Pharmacodynamics of once- or twice-daily levofloxacin versus vancomycin, with or without rifampin, against Staphylococcus aureus in an in vitro model with infected platelet-fibrin clots.

1996 ◽  
Vol 40 (3) ◽  
pp. 701-705 ◽  
Author(s):  
S M Palmer ◽  
M J Rybak
Keyword(s):  
In Vitro Model ◽  
Area Under The Curve ◽  
Human Platelets ◽  
Inoculum Size ◽  
Human Pharmacokinetics ◽  
Development Of Resistance ◽  
Vitro Model ◽  
Better Than ◽  
Fibrin Clots

We compared the pharmacodynamic activities of levofloxacin versus vancomycin, with or without rifampin, in an in vitro model with infected platelet-fibrin clots simulating vegetations. Infected platelet-fibrin clots were prepared with human cryoprecipitate, human platelets, calcium, thrombin, and approximately 10(9) CFU of organisms (MSSA 1199 and MRSA 494) per g and then were suspended via monofilament line into the in vitro model containing Mueller-Hinton growth medium. Antibiotics were administered by bolus injection into the model to simulate human pharmacokinetics; the regimens simulated included levofloxacin at dosages of 800 mg every 24 h (q24h) and 400 mg q12h, vancomycin at 1 g q12h, and rifampin at 600 mg q24h. Each model was run in duplicate over a 72-h period. Infected platelet-fibrin clots were removed in duplicate from each model, weighed, homogenized, serially diluted with sterile 0.9% saline, and plated on tryptic soy agar plates and plates containing antibiotics at 3, 6, and 12 times the MIC to evaluate the emergence of resistance. Time-kill curves were constructed by plotting the inoculum size versus time. Residual inoculum at 72 h was used to compare regimens. All levofloxacin regimens were significantly better than vancomycin monotherapy against both isolates (P < 0.002). Against MSSA 1199, levofloxacin q24h was significantly better than all other regimens, including levofloxacin q12h (P < 0.002); however, no difference between the levofloxacin monotherapy and combination therapy (with rifampin) regimens against MRSA 494 was seen. Killing activity for levofloxacin appeared to correlate better with the peak/MIC ratio than with the area under the curve/MIC ratio. The addition of rifampin significantly enhanced the activity of vancomycin but had little effect upon the activity of levofloxacin. For MRSA 494, vancomycin plus rifampin resulted in the greatest killing (P < 0.05). Development of resistance was not detected with any regimen. Levofloxacin may be a useful therapeutic alternative in the treatment of staphylococcal endocarditis, and further study with animal models of endocarditis or clinical trials are warranted.

scholarly journals Biofilm formation on dental implant surfaces ‐ in vitro dynamic model

2019 ◽  
Vol 30 (S19) ◽  
pp. 8-8
Author(s):  
Honorato Ribeiro‐Vidal ◽  
Maria Del Carmen Sanchez ◽  
Elena Figuero ◽  
David Herrera ◽  
Mariano Sanz
Keyword(s):  
Dynamic Model ◽  
Dental Implant ◽  
Biofilm Formation
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