JAC Advance Access originally published online on June 16, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):349-358; doi:10.1093/jac/dkl250
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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
1 Microbiology Department, School of Medicine, Universidad Complutense Avda. Complutense s/n, 28040 Madrid, Spain 2 Microbiology Department, Hospital Donostia, Paseo Dr Beguiristáin s/n 20014 Donostia, San Sebastián, Spain
Received 1 March 2006; returned 11 May 2006; revised 24 May 2006; accepted 24 May 2006
*Corresponding author. Tel: +34-91-3941508; Fax: +34-91-3941511; E-mail: jprieto{at}med.ucm.es
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 
108 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 (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.
Keywords: moxifloxacin , levofloxacin , azithromycin , pharmacodynamics