Use of in Vitro Critical Inhibitory Concentration, a Novel Approach to Predict in Vivo Synergistic Bactericidal Effect of Combined Amikacin and Piperacillin Against Pseudomonas aeruginosa in a Systemic Rat Infection Model

Chan, Eli; Zhou, Shu‐Feng; Sahasranaman, Srikumar; Duan, Wei

doi:10.1007/s11095-006-9783-x

Cited by 12 publications

(15 citation statements)

References 30 publications

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“…aeruginosa showed an inoculum effect in all cases, regardless of the antibiotic (Table 2). In the case of piperacillin, a subclass of β-lactam antibiotics, previous studies also indicated that it showed an inoculum effect against P. aeruginosa [28,29]. When pathogens are present in a large number, they are more likely to survive because of the resistant mutants that develop via selection.…”

Section: Discussionmentioning

confidence: 99%

Microscopic Analysis of Bacterial Inoculum Effect Using Micropatterned Biochip

2021

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Antimicrobial resistance has become a major problem in public health and clinical environments. Against this background, antibiotic susceptibility testing (AST) has become necessary to cure diseases in an appropriate and timely manner as it indicates the necessary concentration of antibiotics. Recently, microfluidic based rapid AST methods using microscopic analysis have been shown to reduce the time needed for the determination of the proper antibiotics. However, owing to the inoculum effect, the accurate measurement of the minimal inhibitory concentration (MIC) is difficult. We tested four standard bacteria: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, against five different antibiotics: piperacillin, cefotaxime, amikacin, levofloxacin, and ampicillin. The results showed that overall, the microfluidic system has a similar inoculum effect compared to the conventional AST method. However, due to the different testing conditions and determination protocols of the growth of the microfluidic based rapid AST, a few results are not identical to the conventional methods using optical density. This result suggests that microfluidic based rapid AST methods require further research on the inoculum effect for practical use in hospitals and can then be used for effective antibiotic prescriptions.

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Section: Discussionmentioning

confidence: 99%

Microscopic Analysis of Bacterial Inoculum Effect Using Micropatterned Biochip

2021

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Section: Discussionmentioning

confidence: 99%

“…It is interesting to note that, based on these results, no obvious drop in antibacterial activity is to be expected while the respective concentrations of each antibiotic switch over time. Previous authors have mentioned the influence of both the concentration ratio and the dosing ratio on synergy and killing rate exhibited by antibiotic combinations (Chan et al 2006). Bacterial killing has been reported to be dependent on the concentration of the antibiotics used in the combination (Pea et al 2005), but this was not the case for the cefalexin : kanamycin combination.…”

Section: Discussionmentioning

confidence: 99%

“…The ability to predict in vivo efficacies of antibiotics through microbiological and PK data has always been one of the main objectives in antimicrobial chemotherapy (Frimodt-Møller 2002;Jacobs 2003). Several surrogate relationships have been proposed to study the correlation between the PK and PD effects of antimicrobial agents used alone, but no combined PK-PD model has ever been established for combinations of one or more antibiotics (Chan et al 2006). In the specific case of bovine mastitis, there is to our knowledge no intramammary infection model available which would be suitable to accurately assess the PD effects of a drug.…”

Section: Discussionmentioning

confidence: 99%

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Kill rate of mastitis pathogens by a combination of cefalexin and kanamycin

Maneke

Pridmore

Goby

et al. 2010

Journal of Applied Microbiology

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Aim: To assess the bacterial killing rate produced by a combination of cefalexin and kanamycin at two different concentration ratios. Methods and Results: Time–kill kinetics of cefalexin and kanamycin, individually and in combination, were determined against one strain each of Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae and Streptococcus uberis. The combination was tested using two fixed ratios (cefalexin : kanamycin ratios of 1·25 : 1 and 1 : 2·3) and two concentrations of each ratio. Time–kill curves produced with either ratio were quite similar. Against most bacterial species, higher concentrations produced faster kill. In all cases, the combination of cefalexin and kanamycin showed faster and greater kill at lower antibiotic concentrations than those observed with either drug alone. Conclusions: The combination of cefalexin and kanamycin results in a fast initial killing of major mastitis pathogens at both concentration ratios. Significance and Impact of the Study: The combination of cefalexin and kanamycin achieved rapid bacterial kill at concentrations and ratios that can be achieved in vivo following intramammary infusion of a mastitis treatment.

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“…(a) β-Lactams with aminoglycosides (Peterson et al 1984 ;Rusnak et al 1984 ;Bayer et al 1985a ;Mordenti et al 1985 ;Johnson 1985 ;Chin et al 1986 ;Chadwick et al 1986 ;Moody et al 1987 ;Gordin et al 1987 ;Gerber et al 1989 ;Ulrich et al 1989 ;Pefanis et al 1993 ;Mimoz et al 1999 ;Robaux et al 2001 ;Placensia et al 2007 ;Chan et al 2006 ;Maiques et al 2007 ;Yuan et al 2010 ); although there are exceptions (Ulrich et al 1989 ; Pefanis et al 1993 ;Robaux et al 2001 ;Johnson et al 1987 ;Chusid et al 1983 ;Kemmerich et al 1986 ;Thauvin et al 1989 ;Johnson and Thompson 1986 ;Navas et al 2004 ), many of which were strain dependent and/or were seen in endocarditis models. (b) β-Lactams with fl uoroquinolones (Ulrich et al 1989 ;Johnson et al 1987 ;Placensia et al 2007 ), with some exceptions (Ulrich et al 1989 ;Thauvin et al 1989 ).…”

Section: In Vitro Pharmacodynamic Modelsmentioning

confidence: 99%

Drug–Drug Combinations

Turnidge

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Antimicrobial combination therapy has a long history. The potential for synergy between two antimicrobial agents has been sought using in vitro techniques such as disk approximation, checkerboard titration, in vitro killing experiments with fi xed drug concentrations, through the use of in vitro pharmacodynamic models, through animal models, and through retrospective and prospective clinical studies. The most widely examined combinations are those that include aminoglycosides, especially for the treatment of serious Pseudomonas aeruginosa infections, and for the management of enterococcal and staphylococcal endocarditis. The in vitro and animal studies of P. aeruginosa support the concept that combinations of aminoglycosides with β-lactams improve effi cacy and outcomes. Some models suggest that the mechanism of improved effi cacy relates less to synergy and more the prevention of the selection of aminoglycoside-resistant mutants. However, human clinical studies to date have failed to demonstrate convincingly that there are better outcomes with combination therapy in terms of effi cacy or the prevention of resistance emergence. For endocarditis, there has been strong evidence accumulated for combination therapy enterococcal endocarditis using in vitro and animal models, although there are no randomised clinical data to confi rm these. Data supporting the use of combination in staphylococcal therapy has been less robust, and Panton-valentine leukocidin producing S. aureusCell-wall active agent + clindamycin or linezolid the role of combination treatment for this indication is now in question. Ultimately, an in vitro or animal model of the pharmacodynamic interaction of drug classes that can be shown to predict clinical outcomes is still required. Such a model does not currently exist.

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Use of in Vitro Critical Inhibitory Concentration, a Novel Approach to Predict in Vivo Synergistic Bactericidal Effect of Combined Amikacin and Piperacillin Against Pseudomonas aeruginosa in a Systemic Rat Infection Model

Abstract: The combination of amikacin and piperacillin exhibited synergistic killing effect on P. aeruginosa that could be modeled using CIC as a surrogate marker relating the PK parameters to in vivo bactericidal effect.

Cited by 12 publications

References 30 publications

Microscopic Analysis of Bacterial Inoculum Effect Using Micropatterned Biochip

Microscopic Analysis of Bacterial Inoculum Effect Using Micropatterned Biochip

Kill rate of mastitis pathogens by a combination of cefalexin and kanamycin

Drug–Drug Combinations

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