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Quinupristin/dalfopristin: therapeutic potential for vancomycin-resistant enterococcal infections
1Department of Medicine, Beth Israël Deaconess Medical Center, Boston, MA 02215, USA.
Abstract:
Vancomycin-resistant Enterococcus faecium (VREF) is an opportunistic pathogen, which causes infections among severely ill, hospitalized patients, in whom it is likely to increase the risk of progressive local or systemic disease and to worsen the prognosis. Because these organisms are often highly resistant to penicillin, ampicillin and many other antimicrobials including the glycopeptides, there are few proven therapeutic alternatives for the treatment of infection caused by VREF. Quinupristin/dalfopristin is highly active against VREF in vitro. A prolonged post-antibiotic effect, good polymorphonuclear leucocyte/macrophage penetration and slow release, and active metabolites allow this agent to be used with an 8 or 12 h dosing interval. The combined results from a Phase III non-comparative study and an emergency-use study of quinupristin/dalfopristin for the treatment of VREF infection produced a clinical response rate (cure or improvement) in 142 (73.6%) of 193 clinically evaluable patients. The baseline pathogen was eradicated or presumed eradicated from 110 of 156 (70.5%) bacteriologically evaluable patients. Fifty-two per cent of the severely ill patients in these two studies died, but no death was attributed to quinupristin/dalfopristin therapy. The most common adverse event was arthralgia (9.1%). Quinupristin/dalfopristin has demonstrated efficacy for the treatment of serious VREF infections, including those that have failed conventional therapy.
Insights
Vancomycin-resistant Enterococcus faecium (VREF) infections are difficult to treat due to antimicrobial resistance. Quinupristin/dalfopristin shows efficacy in treating serious VREF infections, offering a viable therapeutic option.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Vancomycin-resistant Enterococcus faecium (VREF) is a significant opportunistic pathogen in hospitalized patients.
- VREF infections pose a challenge due to high resistance to conventional antibiotics, including glycopeptides.
- Limited therapeutic alternatives exist for treating VREF infections.
Purpose of the Study:
- To evaluate the efficacy and safety of quinupristin/dalfopristin for treating VREF infections.
- To assess quinupristin/dalfopristin as a treatment option for patients with serious VREF infections, including those with prior treatment failures.
Main Methods:
- Combined analysis of a Phase III non-comparative study and an emergency-use study.
- Evaluation of clinical response (cure or improvement) and microbiological eradication rates.
- Assessment of adverse events associated with quinupristin/dalfopristin therapy.
Main Results:
- A clinical response rate of 73.6% (142/193) was observed in clinically evaluable patients.
- Microbiological eradication was achieved in 70.5% (110/156) of bacteriologically evaluable patients.
- The most common adverse event was arthralgia (9.1%); no deaths were attributed to the therapy.
Conclusions:
- Quinupristin/dalfopristin demonstrated significant efficacy in treating serious VREF infections.
- The drug is a valuable therapeutic option for VREF infections, particularly when conventional therapies have failed.
- Quinupristin/dalfopristin offers a favorable safety profile for managing VREF infections in severely ill patients.