quinupristin-dalfopristin and Sepsis

The pharmacodynamic and pharmacokinetic characteristics of antimicrobial agents are the two fundamental pharmacological components which provide a rationale for the choice of therapy for intraabdominal infections, and especially serious infections. The most important PK-PD parameters are well known which can potentiate therapeutic efficacy. Antimicrobial agents can be subdivided into categories based on whether their activity is dependent on concentration or exposure time. Therefore, a correct dosing regimen for the time-dependent molecules (i.e. beta-lactams, linezolid, tigecycline) should prolong the maximum exposure time to maintain serum levels over the minimum inhibitory concentration (MIC). The concentration-dependent molecules, on the other hand, which include aminoglycosides and fluoroquinolones, should be given in order to reach maximum concentrations, since they are bactericidal in direct proportion to their concentrations and possess a prolonged post-antibiotic effect.

Topics: Abdominal Abscess; Acetamides; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactams; Digestive System Diseases; Drug Therapy, Combination; Fluoroquinolones; Humans; Linezolid; Metronidazole; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Peritonitis; Sepsis; Tigecycline; Treatment Outcome; Virginiamycin

Quinupristin/dalfopristin is a semisynthetic parenteral streptogramin combination consisting of two components, quinupristin (RP 57669) and dalfopristin (RP 54476), in a 30:70 (w/w) ratio. These compounds act synergically against many Gram-positive bacteria that cause severe infections. Several animal models have been used to study the in-vivo efficacy and pharmacodynamics of quinupristin/dalfopristin against infections caused by Staphylococcus aureus and Streptococcus spp. Studies of its efficacy in animal models of septicaemia, thigh infection, pneumonia and aortic endocarditis have shown it to be as active as vancomycin against S. aureus, including some methicillin-resistant strains (MRSA), and as active as high doses of amoxycillin against penicillin-resistant and multi-resistant strains of Streptococcus pneumoniae. Thus, quinupristin/dalforpristin appears to have potential as an alternative to vancomycin in the management of severe staphylococcal and streptococcal infections, including those caused by MRSA and multi-resistant pneumococci.

Topics: Animals; Anti-Bacterial Agents; Chinchilla; Disease Models, Animal; Endocarditis, Bacterial; Lung Diseases; Mice; Rats; Sepsis; Virginiamycin