Use of an in-vitro kinetic model to study antibiotic combinations

Zinner, Stephen H.; Blaser, Jürg; Stone, Benjamin B.; Groner, M C

doi:10.1093/jac/15.suppl_a.221

Cited by 18 publications

(10 citation statements)

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“…The model can be used for simulation of both continuous and intermittent drug administration (13). Simultaneous first order elimination kinetics of two drugs with different half-lives were simulated to study antibacterial effects of drug combinations (120,119,14).…”

Section: Models With Variable Antibiotic Concentrationsmentioning

confidence: 99%

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Kill Curves versus MIC

Mueller

Peña

Derendorf

2004

Antimicrob Agents Chemother

269

233

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Section: Models With Variable Antibiotic Concentrationsmentioning

confidence: 99%

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Kill Curves versus MIC

Mueller

Peña

Derendorf

2004

Antimicrob Agents Chemother

269

233

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“…Linezolid (16 g/ml) was used to simulate clinically achievable peak serum concentrations in patients administered 600 mg every 12 h (q12h) (10). Additionally, a previously described one-compartment in vitro pharmacodynamic model (IVPM) provided continuous exposure of bacteria to changing concentrations of antibiotics (3,29). All model simulations were conducted over 48 h and were performed at minimum in triplicate.…”

mentioning

confidence: 99%

Evaluating Aztreonam and Ceftazidime Pharmacodynamics with Escherichia coli in Combination with Daptomycin, Linezolid, or Vancomycin in an In Vitro Pharmacodynamic Model

LaPlante

Sakoulas

2009

Antimicrob Agents Chemother

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In an in vitro pharmacodynamic model, linezolid attenuated the activity of aztreonam and ceftazidime against Escherichia coli. Conversely, synergy was detected at 24 and 48 h when daptomycin or vancomycin was added to aztreonam and ceftazidime. We conclude that significant yet underappreciated interactions may occur between gram-positive-spectrum and gram-negative-spectrum antibacterials. Chicago, IL, 2007). Linezolid demonstrates minimal activity against gram-negative bacteria, so an explanation for worse outcomes in patients receiving linezolid is not obvious (22). However, there are cases of documented antagonism between beta-lactam agents and chloramphenicol, a drug similar to linezolid, by mechanisms of action (binding to domain V of the 50S subunit of rRNA) and resistance mechanisms (1,12,17,19,27,28). Therefore, it is practical to hypothesize that beta-lactam agents may be antagonized in the presence of linezolid or other protein synthesis inhibitors. The aim of this study was to evaluate the in vitro activities of aztreonam and ceftazidime in the presence or absence of linezolid, daptomycin, and vancomycin against two Escherichia coli strains.( Drug concentrations for time kill analyses were equal to one (0.19 mg/ml for aztreonam and 0.19 mg/ml for ceftazidime) and two (0.38 mg/ml for aztreonam and 0.38 mg/ml for ceftazidime) times the MIC of each drug. Linezolid (16 g/ml) was used to simulate clinically achievable peak serum concentrations in patients administered 600 mg every 12 h (q12h) (10). Additionally, a previously described one-compartment in vitro pharmacodynamic model (IVPM) provided continuous exposure of bacteria to changing concentrations of antibiotics (3, 29). All model simulations were conducted over 48 h and were performed at minimum in triplicate. Calculated free-drug concentrations were simulated from the following total pharmacokinetic concentrations: for aztreonam, 1 g q8h (half-life [t 1/2 ], 2 h; maximum concentration of drug in serum [C max ], 75 g/ml; protein binding, 55%; free maximum concentration (fC max ), 34 g/ml) (25); for ceftazidime, 1 g q8h (t 1/2 , 2.3 h; C max , 60 g/ml; protein binding, 10%; fC max , 54 g/ml) (4); for daptomycin, 6 mg/kg of body weight q24h (t 1/2 , 8 h; C max , 98.6 g/ml; protein binding, 92%; fC max , 7.9 g/ml) (8); for linezolid, 600 mg q12h; (t 1/2 , 6 h; C max , 18 g/ml; protein binding, 31%; fC max , 12.4 g/ml) (23); and for vancomycin, 1.25 g q12h (t 1/2 , 6 h; C max , 45 g/ml; minimum concentration of drug in serum, 15 to 20 g/ml; protein binding, 55%; fC max , 20.3 g/ml) (18). A peristaltic pump (Masterflex; Cole-Parmer Instrument Company, Chicago, IL) was used to continually replace antibiotic-containing medium with fresh Mueller-Hinton broth supplemented with 25 g/ml calcium and 12.5 g/ml

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“…In an in vitro pharmacokinetic model, Zinner et al [1985] concluded that the am inoglycoside had an immediate effect and reduced the concentration of viable bacte ria by three decades in 2 h. However, bac terial regrowth started after 6 h and subse quent aminoglycoside doses had no effect. With a P-lactam combination regimen, rapid bacterial killing was not followed by bacterial regrowth [Zinner and Dudley, 1986].…”

Section: Discussionmentioning

confidence: 99%

One Shot of High-Dose Amikacin: A Working Hypothesis

Yourassowsky

Linden

Crokaert³

1990

Chemotherapy

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Recent information suggests that single, large daily dosages of amikacin are less nephrotoxic. The killing rate of amikacin for Escherichia coli and Pseudomonas aeruginosa also suggests to put emphasis on a high peak value. A decrease of 3 logio CFU/ml was observed for E. coli and P. aeruginosa at 64 and 128 (ig/ml in 20 min. In comparison, the killing rate of piperacillin was dose-independent and about 6 h were required for a reduction of 10³ CFU/ml of P. aeruginosa. In theory, the way to proceed in the future would possibly be the one-shot administration of amikacin, followed by a long course of a β-lactam antibiotic.

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Use of an in-vitro kinetic model to study antibiotic combinations

Cited by 18 publications

References 0 publications

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Kill Curves versus MIC

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Kill Curves versus MIC

Evaluating Aztreonam and Ceftazidime Pharmacodynamics with Escherichia coli in Combination with Daptomycin, Linezolid, or Vancomycin in an In Vitro Pharmacodynamic Model

One Shot of High-Dose Amikacin: A Working Hypothesis

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