Quinupristin and Dalfopristin (Synercid) is an intravenous antibiotic that belongs to the class of medications called streptogramin. It is actually a combination of two antibiotics and is used to treat complicated infections that are not responsive to the first-line antibiotics. It is also used in the treatment of vancomycin-resistant bacterial meningitis and ventriculitis. Ventriculitis is a very serious infection of the brain ventricles. It is a complication of bacterial meningitis that can cause loculated hydrocephalus in children.

Quinupristin and dalfopristin Uses:

• Complicated skin and skin structure infections:

  • Used to treat complex infections of the skin and skin structures brought on by MSSA (methicillin-susceptible Staphylococcus aureus) or Streptococcus pyogenes

• Off Label Use of Quinupristin and dalfopristin in Adults:

  • Bacteremia caused by MSSA;
  • Infective endocarditis caused by MSSA;
  • Infective endocarditis caused by multidrug resistant Enterococcus faecium;
  • Intravascular catheter-associated bloodstream infection caused by methicillin-resistant coagulase negative staphylococci or ampicillin- and vancomycin-resistant E. faecium;
  • Bacterial Meningitis and ventriculitis caused by vancomycin-resistant E. faecium

Quinupristin and Dalfopristin (Synercid) Dose in Adults

Quinupristin and Dalfopristin (Synercid) Dose for treating complicated Skin and skin structure infection:

• IV: 7.5 mg/kg twice each day for a minimum of 7 days.

Quinupristin and Dalfopristin (Synercid) Dose for treating Bacteremia caused by methicillin-resistant Staphylococcus aureus (off-label):

• IV: 7.5 mg/kg thrice a day. Note: May be considered in case of vancomycin failure and when there is reduced susceptibility to vancomycin and daptomycin.

Quinupristin and Dalfopristin (Synercid) Dose in the treatment of Infective endocarditis caused by methicillin-resistant Staphylococcus aureus (off-label):

• IV: Three times a day at 7.5 mg/kg, with or without additional antibiotics. To more clearly characterise the role of quinupristin/dalfopristin in the therapy of this illness, more information is needed.

Quinupristin and Dalfopristin (Synercid) Dose in the treatment of Infective endocarditis caused by multidrug-resistant Enterococcus faecium (off-label):

• IV: 7.5 mg/kg thrice a day with other antibiotics (eg, high-dose ampicillin or the combination of doxycycline and rifampin).

Quinupristin and Dalfopristin (Synercid) Dose in the treatment of Intravascular catheter-associated bloodstream infection (methicillin-resistant coagulase-negative staphylococci or ampicillin- and vancomycin-resistant E. faecium) (off-label):

• IV: 7.5 mg/kg thrice a day

Synercid Dose in the treatment of Bacterial Meningitis and ventriculitis (alternative adjunct to systemic therapy for vancomycin-resistant E. faecium) (off- label):

Note: A preservative-free preparation should be used:

• Intrathecal: 1 to 4 mg daily.
• Intraventricular: 2 mg daily or 2 to 5 mg daily.
• Clamp drain for 15 to 60 minutes after administration when administered via a ventricular drain(allow the solution to equilibrate in cerebrospinal fluid [CSF]).

Note:  Intraventricular administration is generally reserved for use in 2 conditions:

• In patients who fail parenteral therapy despite the removal of CSF shunt.
• When CSF shunt cannot be removed.

Quinupristin and Dalfopristin (Synercid) Dose in Childrens

Quinupristin and Dalfopristin (Synercid) General dosing in susceptible infections in children:

• Severe infection:

  • Infants, Children, and Adolescents: Data available in infants and children <12 years is limited:
    • IV: 7.5 mg per kg twice or thrice a day

Treatment of Enterococcus faecium, vancomycin resistant (VREF): Limited data available:

• Infants, Children, and Adolescents:

  • IV: 7.5 mg per kg per dose thrice a day; dosing based on an EmergencyUse Program (n=127, mean age: 7.3 years [range: 1.2 months to 17 years]) and two case series (total n=17, range: 10 months to 18 years)

Synercid Dose in the treatment of MRSA infection, vancomycin failure salvage therapy: Limited data available:

• Infants, Children, and Adolescents:

  • IV: 7.5 mg per kg per dose three times a day

Synercid Dose for treating Skin and skin structure infection:

• Infants, Children, and Adolescents: Limited data available in infants and children <12 years:

  • IV: 7.5 mg/kg/dose two times a day for a week

Synercid Dose in the treatment of VP-shunt infection and ventriculitis that is caused by multidrug-resistant bacteria: Limited data available:

• Infants, Children, and Adolescents:

  • Intraventricular/intrathecal (use a preservative-free preparation):

    • Usual dose: 1 to 2 mg/day;
    • The reported range: 1 to 5 mg; in adults, the usual range is 2 to 5 mg/day;
    • It should be used in combination with IV quinupristin/dalfopristin therapy

Pregnancy Risk Category: B

• Animal reproduction studies have not shown any adverse reactions. Considerations for Breast-Feeding

Use during breastfeeding:

• The secretion of quinupristin/dalfopristin in breast milk is not known.
• According to the manufacturer, caution be exercised when administering quinupristin/dalfopristin to a nursing woman.
• Excretion into human milk may be minimized due to the increased molecular weight of quinupristin/dalfopristin.
• Non-dosage-related effects could cause a change in the bowel flora.

Dose in Kidney Disease:

Dosage adjustment not necessary.

Dose in Liver disease:

No dosage adjustments have been provided in the manufacturer’s labeling. However,  dosage adjustment may be necessary according to pharmacokinetic data.

Common Side Effects of Quinupristin and Dalfopristin (Synercid):

• Hepatic:

  • Hyperbilirubinemia

• Local:

  • Local Pain
  • Local Inflammation
  • Localized Edema
  • Infusion Site Reaction

• Neuromuscular & Skeletal:

  • Arthralgia
  • Myalgia

Less Common Side Effects of Quinupristin and Dalfopristin (Synercid):

• Cardiovascular:

  • Thrombophlebitis

• Central Nervous System:

  • Pain
  • Headache

• Dermatologic:

  • Skin Rash
  • Pruritus

• Endocrine & Metabolic:

  • Increased Lactate Dehydrogenase
  • Increased Gamma-Glutamyl Transferase
  • Hyperglycemia

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea

• Hematologic & Oncologic:

  • Anemia

• Neuromuscular & Skeletal:

  • Increased Creatine Phosphokinase

Contraindications to Quinupristin and Dalfopristin (Synercid):

• Hypersensitivity to quinupristin or dalfopristin, and other streptogramins (eg pristinamycin, virginiamycin) or any component in the formulation

Warnings and precautions

• Arthralgias/myalgias:

  • This can cause myalgias or arthralgias, which can sometimes be very severe but usually resolve with discontinuation. Some patients have seen improvement by reducing their dosing frequency.

• Hyperbilirubinemia:

  • May cause elevated bilirubin (>5x ULN; primarily conjugated Bilirubin), possibly due to competition for excretory pathways.

• Phlebitis:

  • It can cause pain and phlebitis if it is infused through a peripheral vein.

• Superinfection

  • Long-term antibiotic use can lead to fungal and bacterial superinfections, such as C. difficile-associated diarrhea or pseudomembranous collitis. CDAD is not uncommon after more than two months of treatment.

Quinupristin and dalfopristin: Drug Interaction

Monitoring parameters:

• Culture and sensitivity
• Conjugated bilirubin (only if indicated clinically)

How to administer Quinupristin and Dalfopristin (Synercid)?

IV:

• Flush the line with 5% dextrose in water prior to and following administration.
• Complete Infusion over 60 minutes (shorter infusion may increase toxicity).
• If peripheral administration results in severe venous irritation, quinupristin/dalfopristin may be further diluted (to 500 mL or 750 mL), infusion site changed, or infused by a central venous catheter.
• In general, administration by central venous catheter should be done to avoid phlebitis.

Intrathecal/Intraventricular (off-label route):

• Only preservative-free preparations should be used.
• When administered through a ventricular drain, the drain should be clamped for 15 to 60 minutes before opening the drain to allow the quinupristin-dalfopristin solution to equilibrate in the CSF.

Mechanism of action of Quinupristin and Dalfopristin (Synercid):

Quinupristin/dalfopristin causes inhibition of bacterial protein synthesis by binding to different sites on the 50S bacterial ribosomal subunit thereby causing protein synthesis inhibition.

Distribution:

• Quinupristin: 0.45 L/kg
• Dalfopristin: 0.24 L/kg

Metabolism: Quinupristin and glutathione are combined to make active metabolites. Dalfopristin hydrolyzes to create active metabolites.

Half-life elimination:

• Quinupristin: 0.85 hours
• Dalfopristin: 0.7 Hours (mean elimination halves-lives including metabolites: 3 & 1 respectively).

Excretion:

• Feces (75% to 77% as unchanged drug and metabolites)
• Urine (15% to 19%)

International Brand Names of Quinupristin and dalfopristin:

• Synercid
• Pyostacine

Quinupristin and dalfopristin Brand Names in Pakistan:

No Brands Available in Pakistan.