RT Journal Article
T1 A pharmacodynamic approach to antimicrobial activity in serum and epithelial lining fluid against in vivo-selected Streptococcus pneumoniae mutants and association with clinical failure in pneumonia
A1 Alou Cervera, Luis
A1 Giménez, María José
A1 Sevillano Fernández, David
A1 Aguilar, Lorenzo
A1 Cafini, Fabio
A1 Echeverría, Olatz
A1 Pérez Trallero, Emilio
A1 Prieto Prieto, José
AB Objectives: Emergence of resistance may be prevented by killing both the parental infecting strain and subsequent less susceptible step-mutants. The present study analyses eradication and resistance selection in Streptococcus pneumoniae with moxifloxacin, levofloxacin and azithromycin, using a parental serotype 3 clinical strain (strain A) and its correspondent step-mutant derivatives resistant to these antibiotics (B, C, D), which were selected in vivo in a patient with pneumonia.Methods: Moxifloxacin, levofloxacin and azithromycin MICs were 1, 2 and 0.5 mg/L for the parental strain; 4, 16 and 4 mg/L for isolate B; and 4, 16 and >128 mg/L for isolates C and D, respectively. A pharmacokinetic computerized device was used to simulate serum and epithelial lining fluid (ELF) concentrations. Initial inoculum was approximately 10(8) cfu/mL. Population analysis profiles were performed using plates with increasing antimicrobial concentrations.Results: In ELF simulations, moxifloxacin showed a bactericidal pattern against all isolates with a minority (approximately 100 cfu/mL) of the surviving population (isolates B, C and D) growing on plates with moxifloxacin concentrations just above those in ELF. Levofloxacin and azithromycin showed a bactericidal pattern only against isolate A, with the whole population of isolates B, C and D growing on plates with levofloxacin concentrations higher (16-64 mg/L) than those in ELF and in plates with azithromycin concentrations as high as 2048 mg/L (for isolates C and D).Conclusions: Antimicrobial activity in pulmonary tissue against possible emerging resistant mutants during pneumonia treatment may prevent failures more than the solely activity against the S. pneumoniae parental infecting strain.
PB Oxford University Press
SN 0305-7453
YR 2006
FD 2006-05-30
LK https://hdl.handle.net/20.500.14352/107175
UL https://hdl.handle.net/20.500.14352/107175
LA eng
NO Alou L, Giménez MJ, Sevillano D, Aguilar L, Cafini F, Echeverría O, Pérez-Trallero E, Prieto J. A pharmacodynamic approach to antimicrobial activity in serum and epithelial lining fluid against in vivo-selected Streptococcus pneumoniae mutants and association with clinical failure in pneumonia. J Antimicrob Chemother. 2006 Aug;58(2):349-58.
DS Docta Complutense
RD 9 abr 2025