Efficacy of Quinupristin-Dalfopristin against Methicillin-Resistant <i>Staphylococcus aureus</i> and Vancomycin-Insensitive <i>S. aureus</i> in a Model of Hematogenous Pulmonary Infection

Abstract

Background: Quinupristin-dalfopristin (Q-D) is a mixture of quinupristin and dalfopristin, which are semisynthetic antibiotics of streptogramin groups B and A, respectively. Methods: We compared the effect of Q-D to that of vancomycin (VCM) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA). Results: Treatment with Q-D resulted in a significant decrease in the number of viable bacteria in the lungs of mice in an MRSA infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean ± SEM): 2.99 ± 0.44, 6.38 ± 0.32, 5.75 ± 0.43 and 8.40 ± 0.14 log₁₀ CFU/lung, respectively]. Compared with VCM, high-dose Q-D significantly reduced the number of bacteria detected in the VISA hematogenous infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean ± SEM): 5.17 ± 0.52, 7.03 ± 0.11, 7.10 ± 0.49 and 7.18 ± 0.36 log₁₀ CFU/lung, respectively]. Histopathological examination confirmed the effect of Q-D. Conclusion: Our results suggest that Q-D is potent and effective in the treatment of MRSA and VISA hematogenous pulmonary infections.

Potency of SMP-601, a Novel Carbapenem, in Hematogenous Murine Bronchopneumonia Caused by Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus

“…In the VISA study, while vancomycin had little effect on bacteriological analysis and survival rate, SMP-601 protected mice against fatal pneumonia and resulted in a significant reduction in mortality. We previously showed that linezolid, the first oxazolidinone agent, DQ-113 and DX-619, novel quinolone agents, and quinupristin-dalfopristin, a complex of streptogramin A and B, are also effective against MRSA and VISA in this model, while vancomycin repeatedly shows little effect (6,(12)(13)(14).…”

“…The method of inoculation was described previously (6,8,(12)(13)(14). Briefly, for the MRSA study, NUMR101 was cultured overnight on MuellerHinton II agar plates at 37°C.…”

“…In order to evaluate the efficacy of antibacterial agents and the pathogenesis of blood-borne staphylococcal pneumonia, we previously established a murine model of pulmonary infection with S. aureus by intravenous injection of bacteria enmeshed in agar beads (6,8,(12)(13)(14). The aim of the present study was to evaluate the activity of SMP-601 against pulmonary infection caused by MRSA and VISA, in comparison with vancomycin, using the above model.…”

Surface properties of new virginiamycin M1 derivatives

“…However with the growing problem of antibiotic resistance, interest in this antibiotic has been renewed and new derivatives of virginiamycin have been developed, such as dalfopristine. Synercid, a 70/30 combination of dalfopristin/quinupristin has been used against Staphylococcus aureus and Staphylococcus epidermidis resistant to methycillin and Enterococcus faecium resistant to vancomycin, which are Gram positive bacteria particularly important in nosocomial infections [3][4][5][6].…”

Potency of DX-619, a novel des-F(6)-quinolone, in haematogenous murine bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate Staphylococcus aureus

“…To evaluate the efficacy of antibacterial agents and the pathogenesis of blood-borne staphylococcal pneumonia, we previously established a new murine model of pulmonary infection with S. aureus by intravenous injection of bacteria enmeshed in agar beads [5][6][7][8]. The aim of the present study was to evaluate the activity of DX-619 against pulmonary infection caused by MRSA and VISA compared with vancomycin (VCM) using the above model.…”