[New treatment option for gram-positive infections in critically ill patients - overview over linezolid].

INTRODUCTION

During the last decade, there has been an emergence of multiresistant Gram-positive bacteria in intensive care units. Oxazolidinones are a new class of antibiotics without cross-resistance to other antimicrobial agents, and linezolid was recently introduced as first oxazolidinone on the German market. In this overview, we summarize important data and discuss possible indications for linezolid in the treatment of infections in critically ill patients. ANTIMICROBIAL ACTIVITY AND PHARMACOLOGY: The antimicrobial spectrum comprises mainly Gram-positive bacteria, especially Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, enterococci, and streptococci. Linezolid is mostly bacteriostatic and inhibits the bacterial protein synthesis at an early stage. Adults may receive 600 mg b.i.d. intravenously or p. o. About 30 % of the dose are excreted by the kidneys as mother compound and 50 % as metabolites. Dosage reductions are not necessary, even in severe renal impairment, but about one third of the dose is eliminated during dialysis. Overall, linezolid is well tolerated, but approximately 5 % of the patients may suffer from diarrhea or nausea and there have been a few reports about reversible myelosuppressive side effects.

CLINICAL STUDIES

Linezolid has been compared to vancomycin for treatment of Gram-positive nosocomial pneumonia, and the clinical cure rates were 66.4 % and 68.1 %, respectively. Linezolid is highly active and bactericidal against pneumococci. The clinical cure rates for treatment of skin and soft tissue infections were 88.1 % with linezolid and 86.1 % with penicillinase-stable penicillins. MRSA were excluded in this study, but it may be assumed from data in vitro that linezolid is equally effective against these bacteria. Data for the treatment of catheter-associated and other forms of bacteremias are mainly derived from the compassionate-use-program, where linezolid has been used in complicated cases, mainly after failure of standard therapy. The majority of infections was caused by multiresistant Enterococcus faecium and the clinical cure rates were approximately 80 %.

COMMENT

The currently available data suggest that linezolid will serve as useful agent in the treatment of severe infections caused by multiresistant staphylococci and enterococci. Further studies are necessary to define the role of linezolid as first-line agent, e. g. in the treatment of central venous catheter infections. In light of the severe prognosis of pneumonias caused by MRSA, studies on the combination of linezolid and vancomycin are warranted. Despite the low level of resistance, it seems prudent not to use linezolid as first line agent in the treatment of uncomplicated infections, as long as effective standard antibiotics are available.