dalfopristin

Action and Spectrum

Actions and Spectrum: 

Actions: 

Dalfopristin works by attaching to the 50S subunit of the bacterial ribosome and preventing the developing peptide chain from reaching its elongation phase during protein synthesis at a particular spot. This inhibits the synthesis of proteins by bacteria. When used with quinupristin, which targets a different location on the bacterial ribosome’s 50S subunit, the two work together to produce a synergistic effect. Due to their complementary mechanisms of action, quinupristin and daloxopristin are more effective against some Gram-positive bacteria together. 

Spectrum: 

Dalfopristin demonstrates a range of effectiveness primarily targeting Gram-positive bacteria, encompassing strains such as Staphylococcus aureus (including methicillin-resistant varieties like MRSA), Streptococcus pneumoniae, Streptococcus pyogenes, and Enterococcus faecium (including vancomycin-resistant types like VREF). It’s crucial to emphasize that while dalfopristin, frequently administered in conjunction with quinupristin as quinupristin/dalfopristin, exhibits efficacy against these Gram-positive bacteria, it may not be as effective against Gram-negative bacterial strains. This combination is especially prized for its ability to address infections caused by multidrug-resistant Gram-positive bacteria, catering to a specific therapeutic niche where other antibiotics may prove less effective. 

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: 

Pristinamycin IIA (streptogramin A) is the parent compound of dalfopristin, a semi-synthetic derivative. By attaching to the 70S subunit, it prevents the bacterial ribosome from undergoing the initial stage of protein synthesis. Intravenous administration is used. 

Pharmacodynamics: 

The pharmacodynamics of dalfopristin pertains to the drug’s impact on the body and its mode of action. Frequently employed in conjunction with quinupristin as quinupristin/dalfopristin therapy, these compounds jointly constitute an antibiotic class known as streptogramins. 

Dalfopristin hinders bacterial protein synthesis by attaching to the bacterial ribosome, specifically binding to the 50S subunit. This subunit is pivotal in the protein synthesis process, and dalfopristin’s binding disrupts the elongation of the developing peptide chain, ultimately impeding bacterial growth. 

Quinupristin, the complementary element in this combination, also targets the bacterial ribosome but binds to the 50S subunit at a distinct site from dalfopristin. This dual mechanism of action renders the quinupristin/dalfopristin combination effective against specific Gram-positive bacteria, including strains resistant to other antibiotics. 

The combined use of quinupristin and dalfopristin proves especially valuable in addressing infections caused by multidrug-resistant bacteria, such as vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant Staphylococcus aureus (MRSA). 

It’s noteworthy that understanding the pharmacodynamics of dalfopristin within the context of the quinupristin/dalfopristin combination is instrumental in enhancing its effectiveness against bacterial infections. This knowledge assists healthcare professionals in tailoring treatment plans for patients facing particular types of infections. 

Pharmacokinetics: 

Absorption 

The time to achieve peak effect is 6 hours 

Distribution 

Protein-bound is 26% 

The volume of distribution is 6.5 μg/L 

Metabolism 

N/A 

Elimination and Excretion 

The half-life is 1 hour 

The drug is excreted 19% in urine. 

Adminstartion

Administration: 

Dalfopristin is commonly administered intravenously (IV), meaning it is introduced into the body through a vein. The specific dosage and infusion rate can vary on the basis of the patient’s weight and the medical condition being addressed. Adherence to the prescribing healthcare professional’s instructions and guidelines is imperative for the proper administration of dalfopristin. 

As dalfopristin is frequently utilized in conjunction with another antibiotic called quinupristin (forming a combination therapy known as quinupristin/dalfopristin), it may be delivered as a singular infusion using a dedicated line or as a separate infusion when mixed with other compatible intravenous solutions.

Patient Information Leaflet

Patient information leaflet 

Generic Name: dalfopristin 

Pronounced: dal-fo-PRIS-tin 

Why do we use dalfopristin? 

Dalfopristin, often administered in conjunction with quinupristin, constitutes a pharmaceutical intervention referred to as quinupristin/dalfopristin. This therapeutic combination is utilized for its antibiotic attributes, specifically targeting bacterial infections, especially those instigated by Gram-positive bacteria. The application of dalfopristin serves various purposes, addressing distinct medical needs. It proves effective in combating multidrug-resistant infections, showcasing its potency against certain Gram-positive bacteria that have developed resistance to conventional antibiotics.

Furthermore, it is a valuable option for treating specific infections, notably those caused by bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF). Dalfopristin may also be prescribed to manage skin and soft tissue infections resulting from susceptible bacteria.

In certain cases, it finds utility in the care of immunocompromised patients, who, due to their compromised immune systems, may be at heightened risk of specific bacterial infections. The diverse applications of dalfopristin highlight its significance in addressing varied bacterial challenges, underscoring the importance of tailored antibiotic treatments.