quinupristin-dalfopristin and Abscess

Intravenous administration of quinupristin/dalfopristin outside the hospital setting has not been reported previously. We describe 37 outpatients receiving quinupristin/dalfopristin iv for infections including osteomyelitis, bacteraemia, abscesses and cellulitis. The most frequent aetiological pathogens found were Enterococcus faecium, Staphylococcus aureus and coagulase-negative staphylococci. Patients received an average of 9 days therapy as inpatients and 22 days as outpatients. Quinupristin/dalfopristin was administered using various access devices, most commonly peripherally inserted central catheters and tunnelled central catheters. The bacteriological and clinical success rates were both 89.2%. Five patients were readmitted to hospital; one patient developed catheter-related bacteraemia. The most frequently reported non-venous adverse events were nausea (18.9% of patients), myalgia (18.9%) and arthralgia (13.5%). Sixteen patients experienced venous access-related events, most commonly infusion pain, oedema and phlebitis. In this group of patients, for those who had difficult-to-treat infections, intravenous quinupristin/dalfopristin therapy was generally effective and safe outside the hospital setting.

Topics: Abscess; Adult; Aged; Aged, 80 and over; Ambulatory Care; Bacteremia; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Middle Aged; Osteomyelitis; Treatment Outcome; Virginiamycin

RP 59500 is a new semisynthetic injectable streptogramin antibiotic composed of two compounds which interact synergically, RP 57669 and RP 54476, derived from pristinamycin IA and pristinamycin IIB, respectively. The bacteristatic and bactericidal activities of RP 57669 and RP 54476 alone or combined in various proportions were tested by the chequerboard dilution technique. The fractional inhibitory concentration (FIC) index was determined for 14 Staphylococcus aureus isolates (including methicillin- and macrolide-resistant strains) and one culture collection strain. The FIC index was found to be much lower than 0.5, indicating the presence of synergy for all strains tested, whatever their resistance pattern. The ED50 of RP 57669 and RP 54476 in various combinations were also determined in three experimental murine models of septicaemia, caused by either S. aureus or Streptococcus pneumoniae, and a thigh abscess model caused by S. aureus. The combinations which performed best in the model of septicaemia were those in which the RP 57669: RP 54476 ratio ranged from 16:84 to 92:8, while those active against the thigh abscess model had ratios ranging from 8:92 to 84:16. That the drugs were active over a wide range of ratios suggests that synergy will be maintained even if one drug is cleared more rapidly than the other. The combination of 30:70, referred to as RP 59500, was selected for further studies, both in vitro and in various experimental models of infections.

Topics: Abscess; Animals; Drug Resistance, Microbial; Drug Synergism; Humans; In Vitro Techniques; Mice; Microbial Sensitivity Tests; Pneumococcal Infections; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae; Thigh; Virginiamycin