Improving linezolid use decreases the incidence of resistance among Gram-positive microorganisms

Abstract

Surveillance studies have shown the emergence of infections with linezolid-resistant bacteria. The relationship between appropriate linezolid use and the spread of linezolid resistance among Gram-positive microorganisms in a single tertiary referral centre was evaluated. In an initial observational study, a prospective prescription-indication study was conducted on intensive care areas and haematology, neurosurgery, vascular surgery and nephrology wards during 2009. An intervention through follow-up feedback on audit results from May–June 2010 was then conducted. From July–December 2010, a second drug-use study of linezolid was conducted, with the same objectives and methodology. To assess the antimicrobial pressure of linezolid, an ecological study was conducted from 2006–2010 in the same hospital wards. Indications for linezolid in the initial study were considered suitable in 38.5% of cases, whilst in the second study the rate was 51.2% (33% increase). Linezolid consumption fell by 57% in the second half of 2010. A significant correlation was found between its inadequate use (DDD/1000 patient-days) and the incidence of linezolid-resistant strains/1000 patient-days (r = 0.93; P = 6.9e-024); 85% of the variability in the incidence of linezolid resistance was predicted by its inadequate use. Its partial correlations were significant for Enterococcus faecium (r = 0.407; P = 0.049), Staphylococcus epidermidis (r = 0.874; P = 2.3e-008) and Staphylococcus haemolyticus (r = 0.406; P = 0.049) but not Staphylococcus aureus (r = 0.051; P = 0.704). A relationship was found between appropriate linezolid use and the incidence of linezolid-resistant strains of E. faecium, S. epidermidis and S. haemolyticus.

Introduction

Linezolid is a member of the oxazolidinone class of antibiotics, which were licensed by Spain's health authority in July 2001. Linezolid exerts antibacterial activity by inhibiting formation of the 70S initiation complex, ultimately preventing the translation and replication of bacterial proteins.

The LEADER surveillance programme monitors linezolid resistance in US hospitals and has reported an increase in linezolid resistance from 1% in 2004 to 2.11% in 2009 [1], whilst rates as low as 0.1% have been described among Gram-positive isolates at non-US medical sites [2]. Resistance to linezolid has been observed, particularly among enterococci (Enterococcus faecium and Enterococcus faecalis) and coagulase-negative staphylococci (CoNS) species [3]. These resistance events have usually been associated with recognised risk factors such as prolonged therapeutic exposure and/or indwelling infective devices [4]. A number of resistant strains have appeared in patients with no prior drug exposure. Each occurrence is probably attributable to endemic spread from other patients in the same healthcare environment. Furthermore, Scheetz et al. found a link between genetically proven linezolid resistance among vancomycin-resistant E. faecium strains and linezolid consumption [5]. Mulanovich et al. found that increased linezolid use preceded the appearance of a linezolid-resistant CoNS [6].

In this study, the relationship between appropriate use of linezolid and the spread of linezolid resistance among Gram-positive microorganisms in a single tertiary referral centre in Spain was evaluated.