Impact of nutritional factors on in vitro PK/PD modelling of polymyxin B against various strains of Acinetobacter baumannii.
Int J Antimicrob Agents
; 64(1): 107189, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38697578
ABSTRACT
The main objective of this study was to assess the effect of rich artificial cation-adjusted Mueller-Hinton broth (CAMHB) on the growth of three strains of Acinetobacter baumannii (ATCC 19606 and two clinical strains), either susceptible or resistant to polymyxin B (PMB), and on PMB bactericidal activity. A pharmacokinetic (PK)/pharmacodynamic (PD) modelling approach was used to characterize the effect of PMB in various conditions. Time-kill experiments were performed using undiluted CAMHB or CAMHB diluted to 50%, 25% and 10%, with or without Ca2+ and Mg2+ compensation (known to affect PMB activity), and with PMB concentrations ranging from 0.25 to 256 mg/L based on the strain's MIC. For each strain, time-kill replicates were modelled using NONMEM. Unexpectedly, dilution of CAMHB by up to 10-fold did not affect the growth rate of any of the three strains in the absence of PMB. However, the bactericidal activity of PMB increased with medium dilution, resulting in a reduction in the apparent bacterial regrowth of the various strains observed after a few hours. Data for each strain were well characterized by a PK/PD model, with two bacterial subpopulations with different susceptibility to PMB (more susceptible and less susceptible). The impact of medium dilution and cation compensation showed relatively high, unexplained between-strain variability. Further studies are needed to characterize the mechanism underlying the medium dilution effect.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymyxin B
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Microbial Sensitivity Tests
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Culture Media
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Acinetobacter baumannii
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Anti-Bacterial Agents
Limits:
Humans
Language:
En
Journal:
Int J Antimicrob Agents
/
Int. j. antimicrob. agents
/
International journal of antimicrobial agents
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: