What is Quinupristin?
Quinupristin is an antibiotic belonging to the streptogramin class. It is not used as a single agent but is part of a combination product with another streptogramin, dalfopristin, in a 30:70 ratio. This combination is marketed under the brand name Synercid. The two components are derived from natural streptogramin compounds produced by Streptomyces pristinaespiralis, modified to increase water solubility for intravenous administration. While each component is only bacteriostatic on its own, their combined synergistic effect makes the formulation bactericidal against many susceptible bacteria.
The Synergistic Mechanism of Action
The synergistic action of quinupristin and dalfopristin is crucial to its effectiveness. The two compounds work together to inhibit bacterial protein synthesis by binding to different sites on the 50S subunit of the bacterial ribosome.
- Dalfopristin's Role: The dalfopristin component binds to a specific site on the 50S ribosomal subunit, which causes a conformational change in the ribosome. This action blocks the initial steps of protein synthesis.
- Quinupristin's Role: Quinupristin then binds to a nearby site on the altered ribosome. This enhanced binding affinity prevents the elongation of the peptide chain and leads to the release of incomplete protein chains.
The dual attack prevents the bacteria from producing the proteins essential for their growth and survival, leading to cell death.
What is the Drug Quinupristin Used For?
The quinupristin-dalfopristin combination is reserved for severe, life-threatening infections, particularly those caused by resistant Gram-positive bacteria where other therapies have failed. The main indications include:
- Vancomycin-Resistant Enterococcus faecium (VRE) Bacteremia: One of the primary uses is for treating serious bloodstream infections caused by VRE. Notably, it is not active against Enterococcus faecalis, which is inherently resistant.
- Complicated Skin and Skin Structure Infections (cSSSI): It is used to treat skin infections caused by susceptible strains of Staphylococcus aureus (including methicillin-susceptible strains) and Streptococcus pyogenes. In some cases, it may be used for methicillin-resistant Staphylococcus aureus (MRSA), although clinical data can be limited.
Due to the availability of newer antibiotics with fewer side effects and drug interactions, the use of quinupristin-dalfopristin is less common today. It is often considered a second-line therapy or an option when resistance patterns or allergies prevent the use of first-line agents like linezolid.
Administration and Adverse Effects
The quinupristin-dalfopristin combination is administered intravenously (IV) as a one-hour infusion, typically every 8 or 12 hours depending on the infection. The infusion should be given through a central venous line, such as a PICC line, to avoid significant venous irritation and phlebitis, which is a common problem with peripheral administration. The diluted solution should be flushed with 5% Dextrose in Water (D5W) and not saline or heparin to prevent incompatibility issues.
Common side effects include:
- Infusion Site Reactions: Pain, inflammation, swelling, and redness at the injection site are frequently reported and can be severe.
- Musculoskeletal Pain: Arthralgia (joint pain) and myalgia (muscle pain) are common and can be severe enough to require discontinuation of treatment in a significant portion of patients.
- Gastrointestinal Distress: Nausea, diarrhea (including Clostridioides difficile associated diarrhea), and vomiting can occur.
- Hyperbilirubinemia: The drug may cause elevated serum bilirubin levels, though this is often mild and transient.
Significant Drug Interactions and Resistance Concerns
Quinupristin-dalfopristin is a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system. This can significantly increase the blood levels of many co-administered medications, necessitating careful monitoring or dosage adjustments. Examples of affected drugs include cyclosporine, certain statins (atorvastatin, simvastatin), and some calcium channel blockers.
The emergence of resistance to quinupristin-dalfopristin is a significant concern. Resistance can develop during therapy, and cross-resistance can be seen with other antibiotics. The use of related streptogramin antibiotics in animal feed has also contributed to the reservoir of resistant bacteria.
Comparison: Quinupristin/Dalfopristin vs. Linezolid
| Feature | Quinupristin/Dalfopristin (Synercid) | Linezolid (Zyvox) |
|---|---|---|
| Drug Class | Streptogramin combination | Oxazolidinone antibiotic |
| Activity | Bactericidal for most susceptible organisms; bacteriostatic against VRE | Bacteriostatic, inhibiting protein synthesis |
| Spectrum | Resistant Gram-positive bacteria, including VRE (E. faecium only), MSSA, and S. pyogenes | Broad against Gram-positive bacteria, including MRSA and VRE (E. faecalis and E. faecium) |
| Route of Administration | Intravenous (IV) infusion only | Oral and Intravenous (almost 100% bioavailability) |
| Administration Issues | High risk of venous irritation (requires central line) | Generally well-tolerated at infusion site |
| Common Side Effects | Myalgia, arthralgia, nausea, diarrhea, infusion site pain | Nausea, headache, diarrhea, thrombocytopenia (low platelet count) with prolonged use |
| Drug Interactions | Potent CYP3A4 inhibitor | Weak CYP inhibitor, but potential for serotonin syndrome |
| Resistance Development | More frequently observed, particularly in VRE | Very rare, especially in staphylococci |
Conclusion
In summary, what the drug quinupristin is used for is to treat serious, specific Gram-positive bacterial infections, particularly those demonstrating resistance to other therapies, such as VRE bacteremia and complicated skin infections. Administered intravenously in combination with dalfopristin under the brand name Synercid, it operates by synergistically inhibiting bacterial protein synthesis. While it offered a vital treatment option against resistant bacteria, its clinical application has become more limited over time. Concerns over frequent side effects like infusion site pain, arthralgia, myalgia, significant drug-drug interactions via CYP3A4 inhibition, and the development of resistance have made newer alternatives, like linezolid, more favorable for many indications. Nonetheless, it remains a crucial tool in the arsenal against specific, resistant infections when other options are not viable.
Note: The content provided here is for informational purposes only and is not medical advice. Patients should consult their healthcare provider for any questions regarding quinupristin or any other medication. https://www.medlineplus.gov/druginfo/meds/a603007.html
