Synercid is a combination of 30 parts Quinupristin and 70 parts Dalfopristin, which are considered semisynthetic streptogramin antibiotics (macromolecular antibiotics produced by Streptomyces pristinaepiralis) and together, the compounds act synergistically as each is bacteriostatic, but Synercid is bactericidal. Synercid also inhibits the isoenzyme cytochrome P450-3A4. Synercid is derived from Pristinamycin (Quinupristin is derived from pristinamycin IA; dalfopristin from pristinamycin IIA). The compound was developed 1989 by Rhône-Poulenc (France).
Synercid is soluble in water.
| Mechanism of Action | Synercid acts as a synergistic protein synthesis inhibitor at different stages of ribosomal translation. Dalfopristin targets the early stages of protein synthesis by binding to the 23S portion of the 50S ribosomal subunit inhibiting peptidyl transferase, the enzyme involved in peptide bond formation. Quinupristin targets later stages of protein synthesis by binding to the 50S subunit near Dalfopristin, preventing polypeptide elongation and release. The synergistic effect is explained by the conformational change in the ribosome caused by Dalfopristin which allows Quinupristin to bind to the ribosome with higher affinity. Synercid inhibits the isoenzyme cytochrome P450-3A4. |
| Spectrum | Synercid is active against a range of Gram-positive bacteria including meticillin- and multidrug-resistant strains of Staphylococcus aureus and S. epidermidis, vancomycin-resistant Enterococcus faecium (but not E. faecalis), and penicillin- and macrolide-resistant Streptococcus pneumoniae. It is also active against the anaerobe Clostridium perfringens, and Gram-negative bacteria Legionella pneumophila, Moraxella catarrhalis (Branhamella catarrhalis), and Neisseria meningitidis. It is also active against Mycoplasma spp. including M. pneumoniae. |
| Microbiology Applications |
Synercid is commonly used in clinical in vitro microbiological antimicrobial susceptibility tests (panels, discs, and MIC strips) against Gram-positive microbial isolates. Medical microbiologists use AST results to recommend antibiotic treatment options. Representative MIC values include:
An in vitro susceptibility test study with more than 28,000 clinical isolates from 200 centers across North America found Synercid to be consistently active (≥90% susceptible) against major Gram-positive pathogens. It had an MIC of ≤1 µg per ml in 90% of strains in a wide variety of multidrug-resistant Gram-positive bacteria including E. faecium, MRSA, and S. epidermidis (Jones et al, 1998). |
| Molecular Formula | C87H117N13O19S2 |
| References |
Allington DR and Rivey MP (2001) Quinupristin/dalfopristin: A therapeutic review. Clin. Ther. 23:24 Chant C et al (1995) Quinupristin/dalfopristin (RP 59500): A new streptogramin antibiotic. Ann. Pharm. 29:1022 Delgado G., Neuhauser MM. Bearden DT, and Danziger LH (2000). Quinupristin-dalfopristin: An overview. Pharmacother. 20:1469–1485 Folcher M et al (2001). A transcriptional regulator of a Pristinamycin resistance gene in Streptomyces coelicolor. J. Biol. Chem. 276(2): 1479-1485 Jones RN, Ballow CH, Biedenbach DJ, Deinhart JA, and Schentag JJ. (1998) Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada. Diagn. Microbiol. Infect. Dis. 31:437–451 PMID 9635235 Manzella JP (2001) Quinupristin-dalfopristin: A new antibiotic for severe Gram-positive infections. Am. Fam. Physician 64(11):1863-1866 PMID 11764864 |
| MIC | Bacillus spp.| 0.5 － 8|| Bacillus spp.| 2|| Bacteroides distasonis| ≥8|| Bacteroides fragilis| 2 － 32|| Bacteroides ovatus| ≥8|| Bacteroides thetaiotaomicron| >8 － 32|| Bacteroides uniformis| 4 － 8|| Bacteroides vulgatus| 2 － >8|| Bifidobacterium adolescentis| 0.125 － 2|| Bifidobacterium bifidum| 0.125 － 2|| Bifidobacterium breve| 0.125 － 2|| Bifidobacterium catenulatum| 0.125 － 2|| Bifidobacterium dentium| 0.125 － 2|| Bifidobacterium longum| 0.125 － 2|| Bifidobacterium spp.| 0.12 － 16|| Clostridium aminovalericum| 0.125 － 8|| Clostridium baratii| 0.125 － 8|| Clostridium bifermentans| 0.125 － 1|| Clostridium butyricum| 0.125 － 8|| Clostridium cadaveris| 0.125 － 4|| Clostridium clostridioforme| 0.125 － 32|| Clostridium cochlearium| 0.125 － 8|| Clostridium difficile| ≤0.06 － 32|| Clostridium fallax| 0.125 － 0.5|| Clostridium glycolicum| 0.125 － 8|| Clostridium histolyticum | 0.25 － 1|| Clostridium innocuum| 0.125 － 4|| Clostridium leptum| 0.125 － 8|| Clostridium novyi| 0.125 － 8|| Clostridium oroticum| 0.125 － 0.5|| Clostridium paraputrificum| 0.125 － 8|| Clostridium perfringens| 0.125 － 4|| Clostridium ramosum| 0.125 － 8|| Clostridium sordellii| 0.25 － 1|| Clostridium sphenoides| 0.125 － 8|| Clostridium spp.| 0.25 － 2|| Clostridium subterminale| 0.125 － 8|| Clostridium symbiosum| 0.125 － 8|| Clostridium tertium| 0.25 － 8|| Collinsella aerofaciens| ≤0.03 － 8|| Corynebacterium| 0.06 － 2|| Corynebacterium accolens| 0.06 － 2|| Corynebacterium afermentans| 0.06 － 16|| Corynebacterium amycolatum| 0.06 － 2|| Corynebacterium aquaticum| 0.06 － 2|| Corynebacterium falsenii| 0.06 － 2|| Corynebacterium jeikeium| ≤0.12 － 2|| Corynebacterium minutissimum| 0.06 － 2|| Corynebacterium pseudodiphtheriticum| 0.03 － 2|| Corynebacterium striatum| 0.06 － 2|| Corynebacterium urealyticum| 0.06 － 2|| Corynebacterium xerosis| 0.06 － 2|| Dermabacter hominis| 0.06 － 2|| Diphtheroids| 2 － 32|| Eggerthella lenta| 0.25 － 2|| Enterococci| 0.25 － >8|| Enterococcus avium| ≤0.25 － 250|| Enterococcus casseliflavus| ≤0.25 － >8|| Enterococcus durans| ≤0.25 － >8|| Enterococcus faecalis| 0.125 － 128|| Enterococcus faecium| ≤0.06 － >32|| Enterococcus gallinarum| ≤0.25 － >8|| Enterococcus hirae| ≤0.25 － >2|| Enterococcus mundtii| ≤0.25 － >2|| Enterococcus raffinosus| ≤0.25 － >8|| Erysipelothrix rhusiopathiae| 1 － 2|| Eubacterium alactolyticum| ≤0.03 － 8|| Eubacterium brachy| 0.02 － 8|| Eubacterium combesii| 0.02 － 8|| Eubacterium contortum| ≤0.03 － 8|| Eubacterium lentum| 0.02 － 2|| Eubacterium limosum| ≤0.03 － 8|| Eubacterium moniliforme | ≤0.03 － 1|| Eubacterium saburreum| 0.02 － 4|| Eubacterium spp.| ≤0.03 － 1|| Eubacterium tenue| 0.02 － 4|| Eubacterium timidum| 0.02 － 4|| Eubacterium yurii| 0.02 － 4|| Finegoldia magna| 0.125 － 1|| Fusobacterium mortiferum| 4 － >8|| Fusobacterium necrophorum| 0.25 － 1|| Fusobacterium nucleatum| 0.5 － 8|| Fusobacterium spp.| 0.25 － >16|| Fusobacterium varium| ≥8|| Gemella morbillorum| 0.125 － 16|| Haemolytic streptococci| 0.12 － 1|| Haemophilus influenzae| 0.03 － 16|| Haemophilus influenzae | 0.12 － >8|| Haemophilus parainfluenzae| 2 － >16|| Lactobacillus acidophilus| 0.125 － 16|| Lactobacillus brevis| 0.125 － 16|| Lactobacillus casei| 0.125 － 16|| Lactobacillus catenaforme| 0.125 － 16|| Lactobacillus confusus| 0.125 － 16|| Lactobacillus delbrueckii| 0.125 － 16|| Lactobacillus fermentans| 0.125 － 2|| Lactobacillus fermentum| 0.125 － >32|| Lactobacillus gasseri| 0.125 － 4|| Lactobacillus jensenii| 0.125 － 16|| Lactobacillus lactis| 0.125 － 16|| Lactobacillus leichmannii | 0.125 － 4|| Lactobacillus minutus| 0.125 － 2|| Lactobacillus oris| 0.125 － 2|| Lactobacillus pentosus (PCD 101)| 4|| Lactobacillus plantarum| 0.125 － 16|| Lactobacillus rhamnosus| 0.125 － 16|| Lactobacillus spp.| 0.12 － 4|| Lactobacillus uli | 0.125 － 4|| Legionella spp.| 0.12 － 2|| Leuconostoc mesenteroides| ≥2|| Leuconostoc pseudomesenteroides| ≥1|| Leuconostoc spp.| 1 － 8|| Listeria spp.| 2 － >128|| Micromonas micros| 0.125 － 2|| Moraxella catarrhalis| ≤0.06 － 2|| Mycobacterium marinum| 8 － >32|| Mycoplasma hominis| ≥2|| Neisseria meningitidis| ≤0.12 － 0.5|| Neisseria spp.| 0.5 － >4|| Oerskovia spp.| 0.12 － 16|| Pediococcus pentosaceus| 2 － 4|| Pediococcus spp.| 0.5 － 16|| Peptoniphilus asaccharolyticus| 0.25 － 0.5|| Peptostreptococcus anaerobius| 0.06 － 16|| Peptostreptococcus asaccharolyticus| 0.125 － 2|| Peptostreptococcus magnus| ≤0.125 － 4|| Peptostreptococcus micros| ≤0.125 － 4|| Peptostreptococcus prevotii| 0.125 － 16|| Peptostreptococcus spp.| 0.25 － 4|| Peptostreptococcus tetradius| ≤0.125 － 2|| Pneumococci| 0.12 － 32|| Porphyromonas asaccharolytica| ≤0.0125 － 4|| Porphyromonas gingivalis| ≤0.0125 － 4|| Porphyromonas spp.| ≤0.0125 － 8|| Prevotella bivia| 2 － 8|| Prevotella buccae| ≤0.0125 － 4|| Prevotella corporis | ≤0.0125 － 4|| Prevotella disiens| ≤0.0125 － 4|| Prevotella intermedia| 0.25 － 2|| Prevotella loescheii| ≤0.0125 － 4|| Prevotella melaninogenica| 1 － 4|| Prevotella oralis (group)| ≤0.0125 － 4|| Prevotella oris| ≤0.0125 － 4|| Prevotella spp.| ≤0.0125 － 32|| Prevotella/Porphyromonas spp.| 0.125 － 4|| Propionibacterium acnes| ≤0.03 － 0.5|| Propionibacterium avidum| 0.06 － 1|| Propionibacterium granulosum| 0.06 － 1|| Propionibacterium propionicus| 0.06 － 0.25|| Pseudoramibacter alactolyticus | ≤0.03 － 1|| Rhodococcus equi| 0.12 － 8|| Rhodococcus spp.| 2 － 128|| Rothia sp.| 0.06 － 2|| Staphylococci| ≤0.06 － 16|| Staphylococcus aureus| ≤0.06 － >8|| Staphylococcus aureus| ≤0.06 － 32|| Staphylococcus auricularis| ≤0.25 － >8|| Staphylococcus capitis| ≤0.06 － >8|| Staphylococcus chromogenes | ≤0.06 － 1|| Staphylococcus cohnii| ≤0.25 － >8|| Staphylococcus epidermidis| ≤0.06 － 16|| Staphylococcus haemolyticus| ≤0.06 － >8|| Staphylococcus hominis| ≤0.06 － >8|| Staphylococcus intermedius| <0.06 － 2|| Staphylococcus lugdunensis| ≤0.25 － >8|| Staphylococcus saprophyticus| ≤0.06 － >8|| Staphylococcus sciuri| ≤0.25 － >8|| Staphylococcus simulans| ≤0.25 － >8|| Staphylococcus spp.| ≤0.12 － >8|| Staphylococcus warneri| 0.125 － >8|| Staphylococcus xylosus| ≤0.25 － >8|| Streptococcus agalactiae| ≤0.06 － 32|| Streptococcus anginosus| <0.06 － 2|| Streptococcus bovis| 0.25 － 4|| Streptococcus constellatus| <0.06 － 2|| Streptococcus intermedius| ≤0.25 － >8|| Streptococcus mitis| <0.06 － 2|| Streptococcus mutans| <0.06 － 2|| Streptococcus oralis| <0.06 － 4|| Streptococcus parasanguis| <0.06 － 2|| Streptococcus pneumonia| ≤0.03 － 8|| Streptococcus pyogenes| ≤0.06 － 4|| Streptococcus uberis| <0.06 － 2|| Turicella otitidis| 0.12 － 16|| |