Quinupristin‐Dalfopristin and Linezolid: Evidence and Opinion

Abstract

Quinupristin-dalfopristin and linezolid demonstrate in vitro activity against a wide range of gram-positive bacteria, including many isolates resistant to earlier antimicrobials. Quinupristin-dalfopristin is inactive against Enterococcus faecalis but has been effective for treatment of infections due to vancomycin-resistant Enterococcus faecium associated with bacteremia. In comparative trials, linezolid proved to be equivalent to comparator agents, resulting in its approval for several clinical indications. The almost-complete bioavailability of linezolid permits oral administration. Each agent can cause adverse effects that may limit use in individual patients. Resistance to these drugs has been encountered infrequently among vancomycin-resistant E. faecium. Resistance to quinupristin-dalfopristin is rare among staphylococci in the United States, and resistance to linezolid is very rare. Whether there is any benefit to use of these agents in combination regimens, and whether there are circumstances in which they might be alternatives to cell-wall active antibiotics for treatment of bone or endovascular infections, are questions that deserve further study.

Antimicrobial resistance of Enterococcus sp. isolated from the intestinal tract of patients from a university hospital in Brazil

“…In contrast, most isolates of E. faecium are susceptible to this agent. The mechanism of resistance to dalfopristin in E. faecalis is related with an efflux pump that appears to be intrinsic in this species (Eliopoulos 2003). Date obtained in this study are in concordance with those published because 13% of the E. faecalis were found to be resistant to quinupristin-dalfopristin.…”

“…Several hospitals located in São Paulo and some other Brazilian cities reported both outbreaks and isolated cases of VRE infection/colonization (Zanella et al 1999, 2003, Cereda et al 2001, Reis et al 2001, however the enterococci strains obtained in this study were van susceptible, indicating that vancomycin retains its therapeutic efficacy against E. faecalis and E. faecium in this hospital.…”

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

“…Individually the antibiotics are bacteriostatic but, in combination, bactericidal activity can be observed against staphylococci and streptococci, although not against E. faecium [50]. In vitro studies suggest that quinupristin-dalfopristin exhibits time-dependent killing but produces prolonged persistent effects against Gram-positive bacteria at concentrations above the MIC [48], allowing extended administration intervals of 8 h, despite the short half-lives of the two compounds (<1 h).…”

The Staphylococcus aureus “superbug”

“…The glycopeptide vancomycin was the last available drug to which this organism had remained uniformly sensitive until recent reports of low-level glycopeptide resistance (6) and, very recently, the transfer of high-level vancomycin resistance from Enterococcus to S. aureus (7). Although new drugs, including linezolid and synercid, have recently been introduced to treat MRSA infections (8), there is a worrying lack of novel drugs in the pipeline.…”