The method of inoculation was described previously ( 8). In the present study, we used the model to evaluate the antibacterial and histopathological effects of DQ-113 against MRSA and VISA by comparing these effects with those of VCM and TEIC.
aureus by intravenous injection of bacteria enmeshed in agar beads was previously established ( 8) to evaluate the efficacies of antibiotics and the pathogenesis of blood-borne staphylococcal pneumonia. It is expected that DQ-113 will be effective against severe staphylococcal infections, such as pneumonia, septicemia, and pulmonary abscesses.Ī murine model of pulmonary infection with S. ( 10) reported that DQ-113, a new quinolone-type antibacterial agent, showed potent in vitro activities against various bacteria, including multiple-resistant strains, such as MRSA, VISA, and penicillin-resistant Streptococcus pneumoniae. Thus, some new agents with activities against MRSA and VISA, such as linezolid, daptomycin, and quinupristin-dalfopristin, have been developed ( 6).
aureus ) strains from the United States, France, Korea, South Africa, and Brazil confirmed that the emergence of VCM resistance in S. Subsequent isolation of several VCM-resistant S. However, the first report of a Japanese patient harboring an MRSA strain resistant to VCM appeared in 1996 ( 3). Glycopeptides, such as vancomycin (VCM) and teicoplanin (TEIC), are the most reliable therapeutic agents against infections caused by MRSA. MRSA infection develops mainly in inpatients with risk factors related to health care ( 5), although it has also recently been described in the general population ( 1). Methicillin-resistant Staphylococcus aureus (MRSA) was first identified in the 1960s and was reported to colonize the upper respiratory tract and to cause severe infections, such as pneumonia, pulmonary abscesses, and septicemia. Our results suggest that DQ-113 is potent and effective for the treatment of hematogenous pulmonary infections caused by MRSA and VISA strains. Of the antibiotics analyzed, the parameters of area under the concentration-time from 0 to 6 h (AUC 0-6)/MIC and the time that the AUC 0-6 exceeded the MIC were the highest for DQ-113. Histopathological examination revealed milder inflammatory changes in DQ-113-treated mice than in the mice in the other groups. DQ-113 also significantly ( P < 0.05) reduced the number of viable bacteria in the lungs compared with those in the lungs of the other three groups (counts in mice treated with DQ-113, VCM, and TEIC and control mice, 5.76 ± 0.39, 7.33 ± 0.07, 6.90 ± 0.21, and 7.44 ± 0.17 log 10 CFU/lung, respectively).
At the end of this period, 90% of the DQ-113-treated mice were still alive, whereas only 45 to 55% of the mice in the other three groups were still alive ( P < 0.05 for the group treated with DQ-113 compared with the group treated with VCM or TEIC or the untreated group]). Mice infected with VISA were pretreated with cyclophosphamide, and the survival rate was recorded daily for 10 days. Treatment with DQ-113 resulted in a significant decrease in the number of viable bacteria in the lungs of the mice used in the MRSA infection model (counts in mice treated with DQ-113, VCM, and TEIC and control mice, 6.33 ± 0.22, 7.99 ± 0.14, 7.36 ± 0.20, and 8.47 ± 0.22 log 10 CFU/lung, respectively ). The MICs of DQ-113, VCM, and TEIC for MRSA were 0.125, 1.0, and 0.5 μg/ml, respectively and those for VISA were 0.25, 8.0, and 8.0 μg/ml, respectively. We compared the effects of DQ-113, a new quinolone, to those of vancomycin (VCM) and teicoplanin (TEIC) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S.