STREPTOGRAMINS

(QUINUPRISTIN/ DALFOPRISTIN)

Tejal Khade
KGRDCP & RI
 Quinupristin/dalfopristin (SYNERCID)

quinupristin, a streptogramin B (30 %)

dalfopristin, a streptogramin A (70 %)

• semisynthetic derivatives of naturally occurring

pristinamycins, produced by Streptomyces
pristinaespiralis
 Antimicrobial Activity
• active against gram-positive cocci, including S.
pneumoniae, beta- and alphahemolytic strains of
streptococci, E. faecium (but not E. faecalis),
• The combination is largely inactive against gram-
negative organisms, although Moraxella catarrhalis
and Neisseria spp. are susceptible.
• active against organisms responsible for atypical
pneumonia, M. pneumoniae, Legionella spp., and
Chlamydia pneumoniae.
• combination is bactericidal against streptococci and
many strains of staphylococci but bacteriostatic
against E. faecium.
Mechanism of Action
streptogramin A binds synergistic binding of
to peptidyltransferase these two molecules
of 50S subunit same to the ribosome is
as macrolides bactericidal activity

Prevent elongation of
Conformational
peptide chain changes in 50S
ribosomal subunit

Also causes Increases ribosomal

conformational binding activity of
changes streptogramin B
Resistance to Streptogramins
• Ribosomal methylase that prevents binding of drug
to its target;
• lactonases that inactivate type B streptogramins
• Resistance to dalfopristin is mediated by
acetyltransferases that inactivate type A
streptogramins
• ATP-binding efflux proteins that pump type A
streptogramins out of the cell
• Methylase can rendser the combination
bacteriostatic instead of bactericidal, making it
ineffective in certain infections in which bactericidal
activity is necessary for cure, such as endocarditis.
Absorption, Distribution, and
Excretion
• administered only by intravenous infusion over at
least 1 hour.
• incompatible with saline and heparin and should be
dissolved in 5% dextrose in water.
• t1/2 is 0.85 hour for quinupristin and 0.7 hour for
dalfopristin.
• volume of distribution is 0.87 L/kg for quinupristin
and 0.71 L/kg for dalfopristin.
• 80% of an administered dose eliminated by biliary
excretion.
• No dosage adjustment is necessary for renal
insufficiency.
Therapeutic Use
• vancomycin-resistant strains of E. faecium
• complicated skin and skin-structure infections
caused by methicillin-susceptible strains of S.
aureus or S. pyogenes
• nosocomial pneumonia
• infections caused by methicillin-resistant strains of
S. aureus
• serious infections caused by multiple-drug-resistant
gram-positive organisms such as vancomycin-
resistant E. faecium.
Untoward Effects
pain and
phlebitis at the
infusion site
Phlebitis and pain
can be minimized
by infusion of
drug through a
central venous
catheter.
• Arthralgias and myalgias.
• Arthralgias and myalgias, which are
more likely to be a problem in
patients with hepatic insufficiency
and may be due to accumulation of
metabolites, are managed by
reducing the infusion frequency to
every 12 hours