Clinical update on linezolid in the treatment of Gram-positive bacterial infections.

Department of Microbiology, Newcastle upon Tyne Hospitals Trust, Freeman Hospital, High Heaton, Newcastle upon Tyne, UK.
Infection and Drug Resistance 01/2012; 5:87-102. DOI: 10.2147/IDR.S25890
Source: PubMed

ABSTRACT Gram-positive pathogens are a significant cause of morbidity and mortality in both community and health care settings. Glycopeptides have traditionally been the antibiotics of choice for multiresistant Gram-positive pathogens but there are problems with their use, including the emergence of glycopeptide-resistant strains, tissue penetration, and achieving and monitoring adequate serum levels. Newer antibiotics such as linezolid, a synthetic oxazolidinone, are available for the treatment of resistant Gram-positive bacteria. Linezolid is active against a wide range of Gram-positive bacteria and has been generally available for the treatment of Gram-positive infections since 2000. There are potential problems with linezolid use, including its bacteriostatic action and the relatively high incidence of reported adverse effects, particularly with long-term use. Long-term use may also be complicated by the development of resistance. However, linezolid has been shown to be clinically useful in the treatment of several serious infections where traditionally bacteriocidal agents have been required and many of its adverse effects are reversible on cessation. It has also been shown to be a cost-effective treatment option in several studies, with its high oral bioavailability allowing an early change from intravenous to oral formulations with consequent earlier patient discharge and lower inpatient costs.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose To identify the spectrum and susceptibility pattern of pathogens responsible for culture-positive endophthalmitis referred to a single institution and investigate possible trends in both pathogens and antibiotic sensitivities over the past 25 years. Design A retrospective, laboratory-based study of consecutive microbiological isolates. Participants A total of 988 consecutive culture-positive endophthalmitis isolates from 911 eyes. Methods All culture-positive endophthalmitis isolates collected from 1987 to 2011 were identified. Susceptibility rates to a variety of antibiotics were calculated. Chi-square test for trend was used to detect changes in spectrum or susceptibility over time. Main Outcome Measures Microbial spectrum and susceptibility pattern over time. Results A total of 988 isolates were identified from 911 eyes. The average patient age was 67±18 years, and 55% of the patients were female. The most prevalent pathogens were coagulase-negative staphylococcus (39.4%), followed by Streptococcus viridans species (12.1%) and Staphylococcus aureus (11.1%). Gram-negative organisms and fungi accounted for 10.3% and 4.6% of all isolates, respectively. With the exception of 2 isolates, Enterococcus faecium and Nocardia exalbida, all the other 725 (99.7%) gram-positive bacteria tested were susceptible to vancomycin. Of the 94 gram-negative organisms tested against ceftazidime, 2 were of intermediate sensitivity and 6 were resistant. For 8 antibiotics, increasing microbial resistance over time was observed: cefazolin (P = 0.02), cefotetan (P = 0.006), cephalothin (P<0.0001), clindamycin (P = 0.04), erythromycin (P<0.0001), methicillin/oxacillin (P<0.0001), ampicillin (P = 0.01), and ceftriaxone (P = 0.006). For 3 antibiotics, increasing microbial susceptibility was observed: gentamicin (P<0.0001), tobramycin (P = 0.005), and imipenem (P<0.0001). Conclusions Coagulase-negative staphylococcus remains the most frequently identified cause of endophthalmitis. Vancomycin and ceftazidime seem to be excellent empiric antibiotics for treating endophthalmitis. Although a statistically significant trend toward increasing microbial resistance against a variety of antibiotics, including cephalosporins and methicillin, was observed, a significant trend toward decreasing microbial resistance against aminoglycosides and imipenem also was detected.
    Ophthalmology 01/2014; · 5.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The increasing prevalence of bacterial resistance necessitates appropriate use of antimicrobial agents, which can be only achieved by a better understanding of their pharmacokinetics (PK) and pharmacodynamics (PD). In particular, soft-tissue infections should be treated with antibiotics that penetrate well not only healthy, but also infected tissues. In clinical practice, the treatment of soft-tissue infections in patients with diabetes poses a real challenge.
    The Journal of Clinical Pharmacology 03/2014; · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genome level analysis of bacterial strains provides information on genetic composition and resistance mechanisms to clinically relevant antibiotics. To date, whole genome characterization of linezolid-resistant Enterococcus faecalis isolated in the clinic is lacking. In this study, we report the entire genome sequence, genomic characteristics and virulence factors of a pathogenic E. faecalis strain, DENG1. Our results showed considerable differences in genomic characteristics and virulence factors compared with other E. faecalis strains (V583 and OG1RF). The genome of this LZD-resistant E. faecalis strain can be used as a reference to study the mechanism of LZD resistance and the phylogenetic relationship of E. faecalis strains worldwide.
    Archives of Microbiology 05/2014; · 1.86 Impact Factor


Available from