Treatment of Vancomycin-ResistantEnterococcus faeciumInfections With an Investigational Streptogramin Antibiotic (Quinupristin/Dalfopristin): A Report of Fifteen Cases

Abstract

New therapies for vancomycin-resistant Enterococcus faecium (VREF) infections are urgently needed. We describe the treatment of 15 patients with VREF infection with quinupristin/dalfopristin (RP 59500), a new injectable streptogramin antibiotic. Primary infections treated were bacteremia (4), urinary tract (4), intraabdominal (5), otitis externa (1), and meningitis (1). Minimum inhibitory concentrations for quinupristin/dalfopristin ranged from 0.5 microgram/ml or less to 2 micrograms/ml, and minimum bactericidal concentrations were greater than 64 micrograms/ml for all VREF isolates tested. Peak serum inhibitory titers following infusion of quinupristin/dalfopristin ranged from 1:8 to 1:64; all bactericidal titers were less than 1:2. Development of resistance to quinupristin/dalfopristin during therapy was not observed. The only drug-related adverse effect noted was phlebitis in 4 patients; all had received quinupristin/dalfopristin by peripheral venous infusion. Three patients had clinical and bacteriologic cures. Relapses occurred in 5 patients with recovery of VREF from infected sites in post-treatment cultures. Ten patients died of severe underlying disease; VREF was believed to contribute directly to the death of only 1 patient. While evaluation of clinical efficacy was complicated by the severity of underlying disease in patients with VREF infection, our experience suggests that quinupristin/dalfopristin is a safe and potentially useful agent for the treatment of VREF infections.

Quinupristin‐Dalfopristin: An Overview

“…Finally, case reports support quinupristindalfopristin as a possible alternative for methicillin-resistant S. epidermidis and VREF endocarditis, 53,103,104 VREF osteomyelitis, 105 polymicrobial peritonitis, 106 urinary tract infections, 107 intraabdominal infections, 107 otitis externa, 107 and meningeal infections. 107…”

Occurrence of satA and vgb Genes in Streptogramin-Resistant Enterococcus faecium Isolates of Animal and Human Origins in The Netherlands

“…Despite the fact that VRE infections are a hospital problem and the human usage of glycopeptides is in hospitals, VRE have been isolated from the fecal flora of healthy humans without a known hospital connection, from animals, and from the environment (1,5,9). One of the few options for treatment of vancomycinresistant Enterococcus faecium infection is quinopristin-dalfopristin, a mixture (30:70 ratio) of two streptogramins: dalfopristin (streptogramin A) and quinopristin (streptogramin B) (6). A related mixed compound virginiamycin has been used in Europe for many years as a feed additive to enhance growth in food animals.…”

Mechanisms of Resistance to Quinupristin-Dalfopristin among Isolates of Enterococcus faecium from Animals, Raw Meat, and Hospital Patients in Western Europe

“…Quinupristin-dalfopristin is a semisynthetic, injectable mixture of streptogramin A and B compounds which has recently been licensed for clinical use in the United States and in Europe for the treatment of infections caused by multiresistant gram-positive pathogens, including glycopeptide-resistant Enterococcus faecium (9,17,18). Virginiamycin, another streptogramin A and B combination, has been used as a growth promoter in animal feed for many years.…”