quinupristin

Action and Spectrum

Actions and Spectrum: 

Actions: 

Quinupristin exerts its actions primarily by interfering with bacterial protein synthesis through its binding to a specific site on the 50S subunit of the bacterial ribosome. This binding disrupts the elongation phase of the developing peptide chain during the process of protein synthesis, ultimately leading to the inhibition of bacterial growth. Furthermore, when quinupristin is employed in conjunction with dalfopristin, which targets a different site on the 50S subunit of the bacterial ribosome, a synergistic effect is achieved. This dual mechanism of action enhances the overall efficacy of the quinupristin/dalfopristin combination, making it particularly effective against certain Gram-positive bacteria, even those resistant to other antibiotics. 

Spectrum: 

Quinupristin, commonly administered in conjunction with dalfopristin as quinupristin/dalfopristin, displays a range of activity primarily targeting Gram-positive bacteria. This encompasses strains such as Staphylococcus aureus (including resistant forms like MRSA), Streptococcus pneumoniae, Streptococcus pyogenes, and Enterococcus faecium (inclusive of strains resistant to vancomycin, such as VREF). It is crucial to emphasize that quinupristin might not be as effective against Gram-negative bacterial strains. The combination of quinupristin and dalfopristin holds particular significance for its efficacy in addressing infections induced by multidrug-resistant Gram-positive bacteria, catering to a specific therapeutic domain where the effectiveness of other antibiotics may be diminished. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10 % 

Local edema (17-18 %) 

Local pain (40-44 %) 

Hyperbilirubinemia (3-35 %) 

Infusion site reaction (12-13 %) 

Inflammation at injection site (38-42 %) 

1-10 % 

Nausea (3-5 %) 

Arthralgia (<1-8 %) 

Vomiting (3-4 %) 

Rash (3 %) 

Pain (2 – 3 %) 

Diarrhea (3 %) 

Myalgia (<1- 5 %) 

LDH elevated levels (3 %) 

Anemia (3 %) 

Headache (2 %) 

Increased GGT (2 %) 

Thrombophlebitis (2 %) 

Pruritis (2 %) 

Hyperglycemia (1 %) 

Increased CPK (2 %) 

Black Box Warning

Follow the indicated IV infusion rate and refrain from going above the upper limit. Rapid IV infusion of quinupristin/dalfopristin produced higher levels of toxicity in animal trials than did a slower IV infusion technique.

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions 

• Renal impairment 
• Hepatic impairment 
• Drug interactions 
• Pregnancy  
• Breastfeeding 
• Not infected with E. faecalis 
• Extended usage could lead to bacterial or fungal superinfection 
• Phlebitis, hyperbilirubinemia, and myalgias/arthralgias may result 
• When used in conjunction with cisapride, it may extend QTc 
• CYP3A4-metabolized medicines’ metabolism is inhibited 
• If a medication is prescribed without a preventive indication, a confirmed or highly suspected bacterial illness, or both, the patient is unlikely to benefit and the likelihood of drug-resistant bacteria developing increases 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy category: B 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: B 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

Quinupristin prevents the bacterial ribosome from undergoing its last stage of protein synthesis. By binding to the 23S region of the ribosomal subunit 50S and altering its shape, dalapristin increases quinupristin’s binding by a factor of roughly 100. Moreover, it prevents peptidyl transferase from working. Quinupristin causes defective strands to be released and stops the polypeptide from elongating by binding to a neighboring location on the ribosomal subunit 50S. 

Pharmacodynamics: 

Pristinamycin I is the source of quinupristin, a streptogramin antibiotic. Protein synthesis is hampered when bacterial ribosomal subunits are suppressed, which ultimately results in stasis or bacterial cell death. 

Pharmacokinetics: 

Absorption 

The time to achieve peak effect is 6 hours 

Distribution 

Protein-bound is 11% 

The volume of distribution is 0.45 L/kg 

Metabolism 

Quinupristin is transformed into two conjugated main active metabolites—one with cysteine and the other with glutathione. 

Elimination and Excretion 

The half-life is 3.1 hours 

The drug is excreted 15% in urine.

Adminstartion

Quinupristin is commonly introduced into the body through intravenous (IV) administration, utilizing a vein as the entry point. The exact dosage and infusion rate vary, contingent on factors such as the patient’s weight, the medical condition being treated, and other pertinent considerations. Adherence to prescribing guidelines is crucial for healthcare professionals, ensuring the proper administration of quinupristin in alignment with the prescribed protocol. 

In most scenarios, quinupristin is employed in combination with dalfopristin, forming a dual therapy known as quinupristin/dalfopristin. This combined treatment is administered via IV infusion, and the infusion rate is adjusted based on the specific infection being targeted. Additionally, quinupristin/dalfopristin is commonly delivered as a single infusion through a dedicated line. Alternatively, it may be administered separately if mixed with other intravenous solutions that are compatible with the treatment. Careful consideration of these variables ensures the effective and safe administration of quinupristin in clinical settings.

Patient Information Leaflet

Patient information leaflet 

Generic Name: quinupristin 

Pronounced: kwih-nyoo-PRIS-tin 

Why do we use quinupristin? 

Quinupristin, often administered in conjunction with dalfopristin as quinupristin/dalfopristin, functions as an antibiotic with significant applications in treating specific bacterial infections. Its usage is driven by various key considerations: 

Effectiveness Against Gram-Positive Infections: Quinupristin demonstrates significant effectiveness against Gram-positive bacteria, even those strains that show resistance to other antibiotics. It is commonly utilized for treating infections caused by organisms like Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Enterococcus faecium. 

Management of Multidrug-Resistant Bacteria: The combined therapy of quinupristin/dalfopristin is particularly advantageous in addressing infections arising from multidrug-resistant Gram-positive bacteria. This encompasses strains resistant to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF). 

Treatment of Specific Infections: Quinupristin/dalfopristin is employed for the precise treatment of distinct bacterial infections, including skin and soft tissue infections, especially when caused by susceptible Gram-positive bacteria. 

Enhanced Therapeutic Efficacy: The synergistic collaboration of quinupristin and dalfopristin amplifies the overall effectiveness of the therapy against specific bacterial strains. This attribute proves particularly advantageous in scenarios where the efficacy of other antibiotics may be compromised due to resistance.