Vol.74 No.1 January 2026

Investigation of the mutant selection window of lascufloxacin against Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae based on the PK/PD theory

Masamitsu Kono¹⁾, Hiroshi Matsumoto²⁾, Shigeki Hatakeyama²⁾, Yasuyuki Ishikawa²⁾ and Muneki Hotomi¹⁾

¹⁾Department of Otorhinolaryngology-Head and Neck Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Japan
²⁾Medical affairs, Clinical Development Center, Kyorin Pharmaceutical Co., Ltd.

Abstract

Antimicrobial-resistant strains of Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, the major causative pathogens responsible for upper respiratory tract infections, have been designated as targets on the Bacterial Priority Pathogens List, highlighting the need for urgent countermeasures. In Japan, emergence of strains exhibiting resistance or reduced susceptibility to the respiratory quinolones has also been reported. Antimicrobial stewardship based on the pharmacokinetic/pharmacodynamic (PK/PD) theory is strongly advocated as a strategy to reduce antimicrobial resistance (AMR). In this study, we investigated the minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of lascufloxacin (LSFX) against S. pyogenes, S. pneumoniae, and H. influenzae using 30 clinical isolates of each species. The isolates were obtained from patients with acute pharyngotonsillitis, acute rhinosinusitis, and acute otitis media. Based on these data, we determined the mutant selection window (MSW) for each bacterial species. We further compared these values with the previously reported concentrations of LSFX in upper respiratory tract tissues.
The MIC₉₀ and MPC₉₀ of LSFX against S. pyogenes were 0.06 μg/mL and 0.12 μg/mL, respectively. For S. pneumoniae, the MIC₉₀ was 0.12 μg/mL and the MPC₉₀ was 0.25 μg/mL for both clinical isolates obtained from patients with acute rhinosinusitis and patients with acute otitis media. For H. influenzae, both MIC₉₀ and MPC₉₀ values were 0.06 μg/mL, regardless of the clinical source of the isolate. Reported tissue concentrations of LSFX following standard clinical dosing are 1.30 μg/g in the palatine tonsils, 1.32 μg/g in the paranasal sinus mucosa, and 0.87 μg/g in the middle ear mucosa. These tissue concentrations exceeded the MPC₉₀ values for all the studied pathogens by more than threefold. These findings suggest that sufficient concentrations of LSFX were achieved in upper respiratory tract tissues to allow the drug concentrations to remain above the MSW, thereby minimizing the likelihood of selection of resistant strains during antimicrobial treatment of upper respiratory tract infections.

Key word

lascufloxacin, mutant selection window, pharmacokinetics/pharmacodynamics, antibiotic resistance, upper respiratory tract infection

Received

July 30, 2025

Accepted

November 6, 2025

Jpn. J. Chemother. 74 (1): 9-15, 2026