virginiamycin 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

Over recent years gram-positive bacterial pathogens have become dominant in many forms of nosocomial infections. The principal pathogens in severe infections are Staphylococcus aureus and enterococci. The utility of the traditional antibiotics used for nosocomial sepsis, particularly beta-lactam agents, has been severely compromised by the spread of resistance and there was, often, no therapeutic alternative to the glycopeptide antibiotics, vancomycin and teicoplanin, for empirical (and often also the specific) therapy of infections caused by methicillin-resistant S. aureus (MRSA) and Enterococcus spp. This reliance on glycopeptides, however, is now also threatened by acquired resistance. Vancomycin-resistant enterococci (VRE), particularly E. faecium, have become a therapeutic problem in many European cities and are now endemic in some hospital wards. The recent reports from several continents of MRSA with reduced glycopeptide-susceptibility (GISA) is of grave concern. New agents are needed to meet these threats and several classes of compounds are under development. One class is the streptogramins and the combination of quinupristin/dalfopristin (Synercid) is nearing licensing. Clinical trials and a compassionate use programme have already shown it to have considerable promise for the treatment of the most problematic forms of gram-positive nosocomial sepsis, including MRSA and vancomycin-resistant E. faecium infections that had failed therapy with other antibiotics.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Microbial; Gram-Positive Bacterial Infections; Humans; Sepsis; Staphylococcal Infections; 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

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Dermatologic Agents; Sepsis; Staphylococcal Infections; Virginiamycin