Penicillin G concentrations required for prophylaxis against Group A Streptococcus infection evaluated using a hollow fibre model and mathematical modelling.
J Antimicrob Chemother
; 77(7): 1923-1930, 2022 06 29.
Article
em En
| MEDLINE
| ID: mdl-35470370
ABSTRACT
BACKGROUND:
Acute rheumatic fever (ARF), an autoimmune reaction to Group A Streptococcus (Streptococcus pyogenes; Strep A) infection, can cause rheumatic heart disease (RHD). New formulations of long-acting penicillins are being developed for secondary prophylaxis of ARF and RHD.OBJECTIVES:
To evaluate the penicillin G concentrations required to suppress growth of Strep A.METHODS:
Broth microdilution MIC and MBC for Strep A strains M75611024, M1T15448 and M18MGAS8232 were determined. All strains were studied in a hollow fibre model (initial inoculum 4â log10 cfu/mL). Constant penicillin G concentrations of 0.008, 0.016 and 0.05â mg/L were examined against all strains, plus 0.012â mg/L against M18MGAS8232. Viable counts were determined over 144â h. Subsequently, all penicillin G-treated cartridges were emptied, reinoculated with 5â log10 cfu/mL and counts determined over a further 144â h. Mathematical modelling was performed.RESULTS:
MIC and MBC were 0.008â mg/L for all strains; small subpopulations of M75611024 and M1T15448, but not M18MGAS8232, grew at 1× MIC. Following the first inoculation, 0.008â mg/L achieved limited killing and/or stasis against M75611024 and M1T15448, with subsequent growth to â¼6â log10 cfu/mL. Following both inocula, concentrations ≥0.016â mg/L suppressed M75611024 and M1T15448 to <1â log10 cfu/mL from 6â h onwards with eradication. Concentrations ≥0.008â mg/L suppressed M18MGAS8232 to <1â log10 cfu/mL from 24â h onwards with eradication after both inoculations. Mathematical modelling well described all strains using a single set of parameter estimates, except for different maximum bacterial concentrations and proportions of bacteria growing at 1× MIC.CONCLUSIONS:
In the absence of validated animal and human challenge models, the study provides guidance on penicillin G target concentrations for development of new penicillin formulations.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Penicilina G
/
Infecções Estreptocócicas
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article