Instructions of ?Pristinamycin

Pristinamycin is a mixture of water-insoluble pristinamycin IA (PIA, 90–97%) and pristinamycin IIA (PIIA, 3–10%), derived from S. pristinaespiralis. The former is a group B streptogramin (a peptidic macrolactone or depsipeptide), whereas the latter is a group A streptogramin (a macrolide: polyunsaturated macrolactone). It is structurally similar to virginiamycin, derived from Streptomyces virginiae, composed of virginiamycin S and virginiamycin M, widely used in animals. Group A and group B streptogramins are bacteriostatic by reversible binding of the 50S subunit of 70S bacterial ribosomes. Pristinamycin has been available in Europe for over 30 years. The commercially available oral formulation is marketed by Sanofi-Aventis under the trade name Pyostacines in two tablet dosages: 250 and 500 mg of pristinamycin. Oral pristinamycin is not currently available in the USA.

ANTIMICROBIAL ACTIVITY

Pristinamycin is active mainly against Gram-positive bacteria, specifically staphylococci and streptococci. Enterococci are typically resistant to group A streptogramins and consequently have reduced susceptibility to streptogramin combinations, such as oral pristinamycin. Despite the macrolide component, pristinamycin is effective against strains showing either type of resistance to erythromycin (constitutive or inducible), as only the type B component (in this case, pristinamycin I) is affected, and synergy is maintained. Pristinamycin is active against a wide range of methicillin-resistant Staphylococcus aureus (MRSA), a distinction shared among clinically available systemic antibiotics only by vancomycin and teicoplanin. Against MRSA, vancomycin and prisitinamycin had the highest rates of susceptible strains, greater than 93% for the latter antibiotic. More than 92% of oxacillin-susceptible or -resistant strains of coagulase negative staphylococci were sensitive to pristinamycin.

MECHANISM OF DRUG ACTION

The conformational change induced by the binding of group A streptogramins to 50S produces an increased affinity for group B streptogramins that consequently bind irreversibly. In the resulting complex, the group A streptogramin prevents peptide bond formation during the chain elongation step of protein synthesis, whereas the group B streptogramin causes the incomplete peptide chain to dissociate from the 50S ribosomal subunit.

TOXICITY

One comparative study evaluated the adverse effects of oral pristinamycin. Adverse effects reported with the comparator regimen (penicillin G) are shown in Table 72.3. A more recent study found similar rates of adverse events for pristinamycin (20.5%) and the comparator (amoxicillin, 15.7%; p = 0.21). Most of the adverse events concerned the gastrointestinal tract, such as vomiting and diarrhea of mild–moderate intensity. Similarly, in noncomparative trials, pristinamycin was generally well tolerated and its most common side-effects were gastrointestinal disturbance (anorexia, nausea, vomiting, epigastric discomfort, and diarrhea), glossitis, and rash. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including pristinamycin, and may range in severity from mild to life-threatening. The use of pristinamycin is contraindicated in patients with known hypersensitivity to these compounds or to other streptogramins (e.g. virginiamycin).

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