Vol.60 No.3 May 2012

In vitro antibactericidal activity of tosufloxacin against non-typeable Haemophilus influenzae forming biofilm

Yoko Sugiura, Masahiro Takahata, Yoshiko Fukuda and Nobuhiko Nomura

Research Laboratories, Toyama Chemical Co., Ltd. , 2-4-1 Shimookui, Toyama, Japan

Abstract

The minimum inhibitory concentration(MIC) of tosufloxacin(TFLX) against non-typeable Haemophilus influenzae(NTHi) isolated from pediatric otitis media was determined, and was compared to those of amoxicillin(AMPC), clavulanic acid/amoxicillin(CVA/AMPC, 1 : 14), cefditoren(CDTR), cefcapene(CFPN) and tebipenem(TBPM). The in vitro antibactericidal activity of TFLX against β-lactamase-negative, ampicillin(ABPC)-susceptible H. influenzae(BLNAS) and β-lactamase-negative, ABPC-resistant H. influenzae(BLNAR) forming biofilm was also compared to those of CVA/AMPC, CDTR and TBPM. The results are summarized as follows:
1. The MIC₉₀s of TFLX against 51 strains of BLNAS and 58 strains of BLNAR were 0.0078 and 0.0156 μg/mL, respectively, and were 1/8 to 1/512 of those of reference agents. MICs of TFLX against all 5 strains of β-lactamase-positive, ABPC-resistant H. influenzae were 0.0039 μg/mL, and were 1/2 to<1/16,384 of those of reference agents. TFLX has potent antibacterial activities against NTHi including β-lactam-resistant strains isolated from pediatric otitis media.
2. In BLNAS I-2716 and BLNAR I-2580 forming biofilm, TFLX reduced 3.03- >6.46 Log₁₀ CFU/mL in viable cell counts from the initial inoculum, after exposure to 100 times the MIC, which is equivalent to the free-drug AUC_0-24(fAUC_0-24) at a clinical dosage in pediatric patients for 24 hours or 10 times the MIC (1/10 of fAUC_0-24). Scanning electron microscopy demonstrated a reduction of bacterial layer forming biofilm after exposure to TFLX. In contrast, β-lactam antibacterial agents showed little bactericidal activity and almost no alteration of the shape of bacterial layer.
In conclusion, TFLX can be expected to be a valuable agent in the treatment of persistent otitis media in pediatrics caused by NTHi forming biofilm.

Key word

tosufloxacin, biofilm, non-typeable H. influenzae, in vitro bactericidal activity

Received

August 31, 2011

Accepted

February 21, 2012

Jpn. J. Chemother. 60 (3): 327-334, 2012