Bactericidal activity of cefadroxil, cephalexin, and cephradine in an in vitro pharmacokinetic model.

Leitner, F.; Goodhines, Richard A.; Buck, R. E.; Price, K. E.

doi:10.7164/antibiotics.32.718

Cited by 16 publications

(5 citation statements)

References 5 publications

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“…Several in vitro pharmacokinetic models to simulate human pharmacokinetics have been described, based on either dilution (3,4,16,17,20,23, 26,28,32) or diffusion (1,5,12,34,39). We developed an in vitro pharmacodynamic model based on a dialyzer unit, which is described here.…”

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confidence: 99%

Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model

Mouton

Hollander

1994

Antimicrob Agents Chemother

260

197

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An in vitro pharmacokinetic model mimicking human serum drug concentrations, based on a dialyzer unit, was developed to study the efficacies of continuous infusion and intermittent administration of ceftazidime over a period of 36 h. The daily dose of ceftazidime was 300 mg/liter/24 h given either as a continuous infusion or as three bolus doses. The intermittent dosing regimen yielded peak and trough concentrations after the fourth dose of 92.3 (standard deviation, 8.0) and 1.4 (standard deviation, 0.9) mg/liter, respectively. Continuous administration yielded concentrations of approximately 20 mg/liter. To study efficacy, three Pseudomonas aeruginosa strains, ATCC 27853, CF4, and CF16, were used. The MICs of ceftazidime for these strains were 1, 4, and 16 mg/liter, respectively. Strain CF16 was killed initially during both regimens and then started to regrow. At the end of the fourth dosing interval, i.e., after 32 h, viable counts showed no difference between the regimens. Strains ATCC 27853 and CF4 were killed initially during both dosing schedules, and after the first dosing interval viable counts were similar. However, after the fourth interval, there was a marked difference between bacterial counts during continuous and intermittent infusion, being 2.2 and 2.8 loglo, respectively, demonstrating a greater efficacy during continuous infusion. The results indicate that, in the absence of other factors, a sustained level of ceftazidime around or slightly above the MIC is not high enough to maintain efficacy over more than one (8-h) dosing interval. When sustained concentrations higher than four times the MIC are employed, continuous administration in this model is more efficacious than intermittent dosing.Time-kill curves for beta-lactam antibiotics against Pseudomonas aeruginosa show time-dependent killing which is maximal at relatively low concentrations (35). Concentrations much higher than the MIC contribute no extra effect. From these experiments, it can be deduced that continuous serum drug concentrations above the MIC of the antibiotic used to combat the microorganism in question should be more efficacious than declining concentrations, as observed after intermittent dosing (8, 10). During the latter regimen, concentrations fall below the MIC during part of the dosing interval. It has been shown in several animal models that continuous infusion is indeed more efficacious than intermittent dosing (14,21, 27). However, the half-life of most drugs is severely shortened in the animals studied, and conclusions regarding the pharmacodynamics in humans are difficult to make (15). For, if the shortened half-life is taken into account, the time during which the concentration is below the MIC applies for almost the entire dosing interval, which is contrary to the situation as observed in humans. This problem has, however, been partly overcome by fractional dosing to mimic human pharmacokinetics (13).In vitro simulation of human pharmacokinetics may thus give additional information with respect to kinetics of kil...

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confidence: 99%

Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model

Mouton

Hollander

1994

Antimicrob Agents Chemother

260

197

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“…Also, the tendency to use integral estimates of microbial growth curves in the presence of an antibiotic can be distinctly traced in the recent literature. Attempts have been made to characterize these curves by the number of CFU at the end of the drug dosage interval (at the moment of the next drug injection) or by the ratio of this number to that at the moment of antibiotic administration (5,12,13,16,17,(22)(23)(24). In other words, the vertical section of kinetic curves (by time) is usually considered.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of antimicrobial effect kinetics in an in vitro dynamic model

Firsov

Chernykh

Navashin

1990

Antimicrob Agents Chemother

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Variants of the available methods for estimating antimicrobial effect kinetics in an in vitro dynamic model were analyzed. Two integral parameters characterizing antimicrobial effect duration (TE) and intensity (IE) are suggested to define and analyze the concentration-effect relationships in these models, irrespective of the method of recording. TE is defined by the time from the moment of antibiotic administration to the moment when the bacterial count again reaches its initial level. IE is defined by the area between the microbial growth curves in the presence and absence of an antibiotic. TE and IE were used to quantify the antimicrobial effects of sisomicin on Pseudomonas aeruginosa 58, Escherichia coli 93, and Klebsiella pneumoniae 5056, simulating the pharmacokinetic profiles of the drugs observed following intramuscular administration in therapeutic doses, including the variability of aminoglycoside concentrations in human blood.The development of dynamic models that allow the simulation of antibiotic pharmacokinetic profiles for the study of the kinetics of antimicrobial effect (AME) has provided a means for evaluating the role of the pharmacokinetic factor in the development of AME (5,8,10) and has stimulated the in vitro assessment of the relative effectiveness of various antibiotics and dosage regimens. However, despite strictly controlled conditions for experiments with dynamic models, conclusions about the preference of one drug or dosage regimen over another are essentially qualitative and not always unequivocal. This results to a considerable degree from deficiencies in the available methods for quantifying AME.The analysis of AME kinetics or, strictly speaking, the kinetics of microbial growth in the presence of an antibiotic traditionally employs models that describe the initial phase of cell growth inhibition under the action of the drug and compare microbial growth rates in the presence and absence of the antibiotic.It has been proposed that four parameters be evaluated to characterize more completely the quantitative change in microbial counts in the presence of an antibiotic. These include the time required for microbial count to be reduced by 99% (Tgg), the time required to reach the minimum count (Tmin), the minimum bacterial cell concentration (Bmin), and the time required for a subsequent 10-fold (1-log) increase in bacterial count (tulg) (19). Unfortunately, the last three parameters can be estimated only by counting CFU after samples are grown on solid nutrient media or with the microcalorimetric technique for Tgg (4). Since the high sensitivity of colony counts is "compensated" for by its insufficient accuracy, the estimates for the parameters Tgg, tjug, and especially Tmin may be only approximate. Moreover, the use of multiple parameters often does not allow the definitive assessment of AME, because of conflicting values of Tg, Bmin, and tjg. A comprehensive analysis of these and other AME parameters is presented elsewhere (8).In view of the above-mentioned considerations, we hav...

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“…This group typically has activity against most S pneumoniae strains, but their activity against H influenzae and M catarrhalis is unreliable (i.e., higher MICs) as the extended-spectrum cephalosporins. [63][64][65] The oral extended-spectrum cephalosporins include cefaclor, loracarbef, cefuroxime axetil, cefixime, cefprozil, cefpodoxime proxetil, ceftibuten, and cefdinir. These medications are dosed less frequently than their first generation counterparts, and their activity against H influenzae and M catarrhalis is also more reliable.…”

Section: A N T I M I C R O B I a L T H E R A P Ymentioning

confidence: 99%

“…These medications are dosed less frequently than their first generation counterparts, and their activity against H influenzae and M catarrhalis is also more reliable. [63][64][65][66] The extended-spectrum group has variable activity against S pneumoniae depending on the strain's susceptibility to penicillin. Cefpodoxime, cefuroxime, and cefprozil seem to have better activity against the penicillin-intermediately susceptible strains than the other other oral cephalosporins, but this can vary from location to location.…”

Section: A N T I M I C R O B I a L T H E R A P Ymentioning

confidence: 99%

An update on community-acquired pneumonia in adults

Gotfried

Freeman

2000

Compr Ther

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Bactericidal activity of cefadroxil, cephalexin, and cephradine in an in vitro pharmacokinetic model.

Cited by 16 publications

References 5 publications

Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model

Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model

Quantitative analysis of antimicrobial effect kinetics in an in vitro dynamic model

An update on community-acquired pneumonia in adults

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