Exploratory Cost-Effectiveness Analysis for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: Is Linezolid or Daptomycin Favored Over Vancomycin?

BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality, and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. Our objective was to compare the cost-effectiveness of vancomycin and other antibiotic regimens against MRSAB. METHODS: We estimated the cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin) for Veterans Health Administration patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure at 7 days and adverse drug event (ADE)-related discontinuation after at least 7 days. RESULTS: In base-case analyses, intravenous linezolid was the least expensive regimen at 4 and 6 weeks. Daptomycin was more expensive and more effective than linezolid, with an incremental cost-effectiveness ratio (ICER) of ~$13,000 (4 weeks) per composite failure avoided. With 6 weeks of treatment, daptomycin was more expensive and more effective than vancomycin (ICER ~$21,000 per composite failure avoided). Vancomycin and ceftaroline/daptomycin were dominated strategies at both 4 and 6 weeks. In one-way sensitivity analyses, vancomycin was favored when its microbiological failure risk was less than 20.1% (base-case: 27.2%), assuming a willingness to pay (WTP) threshold of $40,000/composite treatment failure avoided. In two-way sensitivity analyses, intravenous linezolid was favored if linezolid microbiological failure and ADE-related discontinuation rates were < 22.5% and < 17.3%, respectively. Daptomycin, vancomycin, and linezolid were favored in 50%, 31%, and 17% of 4-week probabilistic iterations, respectively, at $40,000 WTP. CONCLUSION: Daptomycin is likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed on the safety of linezolid against MRSAB.

Agomelatine Drug Utilisation Study in Selected European Countries: A Multinational, Observational Study to Assess Effectiveness of Risk-Minimisation Measures.

BACKGROUND: Hepatotoxic reactions are an important identified risk listed in the agomelatine risk management plan. This post-authorisation safety study evaluated the effectiveness of additional risk-minimisation measures (aRMMs) for agomelatine. OBJECTIVE: The objective of this study was to evaluate, among physicians prescribing agomelatine and their patients, liver function monitoring adherence, compliance with contraindications and patients' reasons for non-compliance with liver monitoring. METHODS: A non-interventional cohort study was conducted among adults initiating agomelatine in routine clinical practice in Denmark, France, Germany and Spain through a retrospective medical record abstraction (MRA) before and after implementation of aRMMs and a cross-sectional patient survey. RESULTS: Fifty-four sites contributed data on 437 and 404 patients in the before- and after-RMM periods, and 237 patients completed the survey. No patient had cirrhosis in either study period; 98.2% of patients in the before- and 98.0% in the after-RMM period had no active liver disease reported at initiation or during treatment. Compliance to contraindicated medications was > 99% in both periods. The adherence to the liver-monitoring regimen was similar in both periods (15.1% before RMM and 16.3% after RMM). In the after-RMM period, 25.2% of patients had a liver test before or at treatment initiation; 61.5% had a liver test during treatment. Among patients surveyed who did not have a blood test before treatment initiation or during treatment, the most frequently cited reason was a test ordered but not yet performed. CONCLUSIONS: The overall adherence to liver-monitoring recommendations remained weakly influenced by aRMMs. However, patients treated with agomelatine are in compliance with relevant contraindications.

Pharmacokinetic/pharmacodynamic research on three different infusion time regimens of linezolid in healthy Chinese volunteers.

OBJECTIVE: To evaluate the pharmacokinetic and pharmacodynamic (PK/PD) results of three different infusion time regimens of single doses of 600 mg linezolid in healthy Han Chinese volunteers. METHODS: We conducted a clinical trial involving 6 male and 6 female healthy Chinese volunteers. They were randomized to receive intravenous linezolid infusion (600 mg/0.5 hours, 600 mg/2 hours, or 600 mg/4 hours) in three periods with washout periods of 7 days between each dosage. Serum linezolid concentration was measured in each subject at pre-dose (at 0 hours) until 24 hours after each dose. The ratio of the area under the serum concentration-time curve (AUC) to the minimum inhibitory concentration (MIC), AUC/MIC, was adopted as the major relevant parameter. Monte Carlo simulation was used to evaluate the probability of target attainment (PTA) of these three linezolid regimens. RESULTS: One subject in 600 mg/0.5 hours regimen complained of mild pain at the injection site. No significant difference was found in pharmacokinetic parameters among the three different infusion regimens. When AUC/MIC was applied as parameter, PTA of 4 hours infusion regimen was much lower than that of the 0.5 hours and 2 hours infusion regimens (55.65% vs. 74.91% and 72.03%, respectively). Especially at higher MIC (2 µg/mL), the PTAs of the 0.5 hours and 2 hours infusion regimens decreased to 57.2% and 50.1%, respectively, while that of the 4 hours infusion regimen dropped sharply to only 25.95%. When T>MIC was applied as a parameter, PTA of the 0.5 hours regimen was higher than 90%, while the 2 hours and 4 hours regimens remained 100%. CONCLUSION: Our findings suggest that 2 hours infusion of linezolid at a fixed dose (600 mg) regimen is appropriate to achieve the safety and efficacy against MRSA-caused infections in Chinese adults.

Assessment of the effects of lacosamide on sleep parameters in healthy subjects.

PURPOSE: Seizures and antiepileptic drugs (AED) may disrupt sleep patterns in patients with epilepsy, thus evaluation of lacosamide effects on objective and subjective sleep measures is warranted. METHODS: A multicenter, interventional, open-label study (NCT01530386) was conducted in healthy subjects without confounding effects of concomitant AED use, co-morbidities, or disease state to determine whether lacosamide impacts sleep parameters after 22 days of lacosamide exposure. After overnight polysomnography (PSG) to assess baseline parameters, lacosamide was initiated at 100mg/day (50mg twice daily) and increased by 100mg/day weekly to 300 mg/day (the mid-range maintenance dose for adjunctive therapy). The primary variable was change from baseline to post-treatment in wake after sleep onset (WASO). Secondary variables included additional objective sleep measures, subject-reported measures of sleep quality, daytime sleepiness, and tolerability. Change from baseline in WASO was analyzed using the Wilcoxon rank-sum test. RESULTS: A total of 27 subjects received ≥1 dose of lacosamide and 25 subjects completed the study. For WASO, median change from baseline was a 6-min reduction (95% confidence interval: -38, 77.5; p=0.1074) after lacosamide treatment; this was considered not clinically relevant. No clinically relevant changes were observed in any secondary variables. Thirteen subjects (48%) reported a treatment-emergent adverse event, none of which was severe or led to study discontinuation. CONCLUSION: Lacosamide 300 mg/day had no effect on objective or subjective sleep parameters in healthy subjects and was generally well tolerated.

Formulation development for the orexin receptor antagonist almorexant: assessment in two clinical studies.

Almorexant, a dual orexin receptor antagonist, was investigated for the treatment of insomnia. The following observations initiated further formulation development: the active pharmaceutical ingredient (API) was sticking to the apparatus used during tablet compression; almorexant has an absolute bioavailability of 11.2%; and almorexant modestly decreased the latency to persistent sleep by 10.4 minutes in patients. Two randomized crossover studies were performed to investigate the pharmacokinetics of several new formulations in healthy subjects. In study I, the old "sticky" tablet was compared to two new formulations developed to prevent sticking: a qualitatively similar tablet but with a larger API crystal size and a tablet with 30% more excipients as well as a larger API crystal size. This latter formulation was available in two strengths. The geometric mean ratios and 90% confidence interval of the area under the curve (AUC) were within the bioequivalence range of 0.80-1.25 for the different comparisons between formulations. In study II, 100 mg of the reference tablet was compared to 25 and 50 mg of a liquid-filled hard gelatin capsule developed to increase the bioavailability of almorexant. The geometric mean ratios of the maximum concentration and AUC comparing the new 25 and 50 mg capsule formulations to the reference tablet did not exceed 0.25 and 0.50, respectively, indicating that the new capsule formulation did not increase the maximum concentration of or the total exposure to almorexant. In conclusion, a new tablet was developed but formulation development aimed at increasing the bioavailability of almorexant failed.

Weight-adjusted versus fixed dose of linezolid for Chinese healthy volunteers of higher and lower body weight: a Phase I pharmacokinetic and pharmacodynamic study.

OBJECTIVES: The objective was to evaluate the pharmacokinetic and pharmacodynamic properties of a single intravenous fixed dose compared with a weight-adjusted dose of linezolid. METHODS: A Phase I, comparative clinical trial was conducted involving 20 healthy male Chinese volunteers, assigned into low weight (LW) (50 kg < weight ≤ 55 kg) and high weight (HW) (≥ 80 kg) groups. All subjects were administrated single dose of linezolid (600 mg/30 min) and, after 72 h washout period, another single-dose (10 mg/kg/30 min). Plasma linezolid concentrations were measured by liquid chromatography-tandem mass spectrometry. A Monte Carlo simulation was used to evaluate the probability of pharmacodynamic target attainment (PTA). RESULTS: With 600 mg dose, plasma concentrations in LW group were much higher than that in HW group. A persistent serum inhibitory activity was observed in LW group; the inhibitory activity was lower in HW group. The PTA in HW group was lower than in LW group. For 10 mg/kg dose, both HW and LW groups had similar plasma concentrations. The HW and LW groups had similar serum inhibitory effects. The PTA in HW and LW groups also showed no difference. CONCLUSIONS: Our findings suggest that a weight-adjusted, 10 mg/kg regimen of linezolid may be more appropriate than fixed dosing for patients of different body weight.

Linezolid-containing regimens for the treatment of drug-resistant tuberculosis in South African children.

BACKGROUND: Treatment options for drug-resistant tuberculosis (DR-TB) are limited. Linezolid has been successfully used to treat DR-TB in adults, but there are few case reports of its use in children for TB. The reported rate of adverse events in adults is high. METHODS: We conducted a retrospective review of children with DR-TB treated with linezolid-containing regimens from February 2007 to March 2012 at two South African hospitals. RESULTS: Seven children (three human immunodeficiency virus [HIV] infected) received a linezolid-containing regimen. All had culture-confirmed DR-TB; five had previously failed second-line anti-tuberculosis treatment. Four children were cured and three were still receiving anti-tuberculosis treatment, but had culture converted. None of the non-HIV-infected children experienced adverse events while receiving linezolid. Three HIV-infected children had adverse events, one of which was life-threatening; linezolid was permanently discontinued in this case. Adverse events included lactic acidosis (n = 1), pancreatitis (n = 2), peripheral neuropathy (n = 1) and asymptomatic bone marrow hypoplasia (n = 1). CONCLUSION: Linezolid-containing regimens can be effective in treating children with DR-TB even after failing second-line treatment. Adverse events should be monitored, especially in combination with medications that have similar adverse effects. Linezolid remains costly, and a reduced dosage and duration may result in fewer adverse events and lower cost.

Linezolid: an effective, safe and cheap drug for patients failing multidrug-resistant tuberculosis treatment in India.

Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB.

Lacosamide as adjunctive therapy for partial-onset epileptic seizures: a review of the clinical and economic literature.

OBJECTIVE: This article provides a short but comprehensive pharmacotherapeutic update of adjunctive therapy with lacosamide for partial-onset seizures in adult patients. RESEARCH DESIGN AND METHODS: PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, EconLit were searched from January 1999 to September 2010. Studies evaluating intravenous lacosamide were excluded because this article focuses on chronic adjunctive therapy. RESULTS: Three randomised, multicentre, double-blind, placebo-controlled trials have investigated the efficacy of lacosamide in 1300 adults with epilepsy. The median percent reduction in seizure frequency per 28 days from baseline to maintenance was 18.4% for placebo, 33.3% for lacosamide 200 mg/day (p < 0.01), 36.8% for 400 mg/day (p < 0.001), 39.4% for 600 mg/day. The percentage of patients attaining a seizure frequency reduction of ≥50% was 22.6% with placebo, 34.1% with lacosamide 200 mg/day (p < 0.05), 39.7% with lacosamide 400 mg/day (p < 0.001), 39.6% with lacosamide 600 mg/day. Three open-label extension studies showed that long-term treatment with lacosamide produced sustained efficacy in and was well-tolerated by patients. Three economic evaluations used a similar design to determine the cost effectiveness of lacosamide from the healthcare payer perspective in Sweden, Finland and Belgium. These studies showed that standard anti-epileptic drug therapy plus lacosamide is likely to constitute a cost-effective alternative. The budget impact of introducing lacosamide is likely to be limited. CONCLUSIONS: The evidence on lacosamide was limited and studies suffered from a number of methodological limitations. Lacosamide appears to be a safe, efficacious and cost-effective adjunctive therapy for partial-onset epileptic seizures in adult patients. However, these results need to be validated by studies that explore the impact of lacosamide in real-life clinical practice.

Linezolid interaction with serotonin reuptake inhibitors: report of two cases and incidence assessment.

BACKGROUND: Prompted by the advent of potentially life-threatening neuromuscular symptoms following initiation of linezolid therapy in two patients receiving treatment with a serotonin reuptake inhibitor antidepressant, an evaluation was conducted to determine the incidence and characteristics of symptomatic serotonin toxicity among hospitalized patients receiving combined treatment with these medications. METHODS: Patients admitted between January 1, 2006 and August 30, 2008 who received linezolid concurrently with citalopram or escitalopram were identified and their medical records were examined. Patients were judged to have serotonin toxicity if their records contained documentation of clinical evidence adequate to fulfill requisites of the Hunter Serotonin Toxicity Criteria. Severity of serotonin-related symptoms was graded according to previously established criteria. RESULTS: During the period of observation, 24 patients received concurrent treatment with linezolid and citalopram or escitalopram. Of these, one patient (4%) treated with citalopram met evidentiary requirements for diagnosis of serotonin toxicity. The severity of symptoms in this patient was graded as mild. No evidence of serious harm related to a possible drug interaction was identified. CONCLUSIONS: Severe symptoms associated with serotonin toxicity were shown to be uncommon in patients receiving linezolid and selected serotonin reuptake inhibitors. Nonetheless, serious interaction-related toxicity has been observed at our institution and reported in detail by others. Accordingly, concurrent use of these medications is categorized as contraindicated. Alternative antimicrobial therapy should be instituted in most cases. If no suitable alternative is available, recipient patients should be hospitalized for expectant observation and rigorous monitoring.

Benefit-risk assessment of linezolid for serious gram-positive bacterial infections.

Linezolid is an oxazolidinone, a new class of antibacterial with a unique mechanism of action, namely inhibition of the formation of a functional 70S initiation complex in the 50S bacterial ribosomal subunit. Linezolid is highly active against multidrug-resistant Gram-positive cocci, including meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate and vancomycin-resistant S. aureus, and vancomycin-resistant enterococci; its spectrum of activity also includes some anaerobic bacteria. Linezolid has been studied in several randomized controlled trials for the treatment of patients with community-acquired and nosocomial pneumonia, skin and soft tissue infections (SSTIs), urinary tract infections and bacteraemia. The available evidence suggests that linezolid is at least as effective as vancomycin for patients with nosocomial pneumonia, and there are some retrospective analyses supporting its superiority in comparison with vancomycin for MRSA nosocomial pneumonia, including ventilator-associated pneumonia. Linezolid is more effective than glycopeptides, macrolides and beta-lactams for SSTIs. The limited available data for the treatment of patients with bacteraemia suggest that it may be a better treatment option than vancomycin and beta-lactams for these patients, but questions have arisen regarding patients with catheter-related bacteraemias. Compared with other antibacterials, linezolid is associated with a greater frequency of adverse events, mainly nausea, vomiting, diarrhoea and headaches. Thrombocytopenia also occurs more frequently in patients taking linezolid but there is no increased frequency of anaemia. Other adverse events potentially related to linezolid therapy include fungal infections (moniliasis), hypertension and serotonin-like syndrome, tongue discolouration and taste alterations, dizziness, insomnia, rash and Clostridium difficile-related diarrhoea. The majority of adverse events develop after prolonged administration (i.e. >2 weeks) and subside shortly after discontinuation of linezolid. Peripheral or optic neuropathy, another possible adverse effect, is associated with an even longer duration of treatment (3-6 months). In conclusion, linezolid is an important treatment option for the treatment of patients with multidrug-resistant, Gram-positive bacterial infections. However, in order to reduce the possibility of development of resistance and preserve its activity, the use of linezolid should be restricted to treatment of patients with infections associated with high morbidity and mortality, particularly those caused by multidrug-resistant bacteria.

Linezolid for the treatment of Nocardia spp. infections.

OBJECTIVE: To review the available evidence regarding the use of linezolid for the treatment of Nocardia spp. infections. DATA SOURCES: Data were identified through a search of MEDLINE (1966-May 2007), American Search Premier (1975-May 2007), International Pharmaceutical Abstracts (1960-2007), Science Citation Index Expanded (1996-2007), and Cochrane Databases (publications archived until May 2007) using the terms linezolid and Nocardia. STUDY SELECTION AND DATA EXTRACTION: Prospective and retrospective studies, case reports, case series, and in vitro studies were eligible for inclusion if they used linezolid for nocardiosis regardless of site of infection and outcome. DATA SYNTHESIS: We identified 11 published cases of linezolid use for Nocardia spp. infections. The predominant species isolated were N. asteroides (n = 4; 36%) and N. farcinica (n = 3; 27%). Nocardiosis with central nervous system involvement (n = 7; 64%) or disseminated disease (n = 4; 36%) were most common. The main reason for discontinuation of previous antimicrobials was most often related to adverse effects (n = 5; 45%), followed by clinical failure (n = 3; 27%). Linezolid was associated with cure or improvement in all cases (n = 11; 100%). However, the majority of patients developed serious complications that may have led to premature discontinuation of therapy with linezolid, including myelosuppression (n = 5; 45%) or possible/confirmed peripheral neuropathy (n = 2; 18%). CONCLUSIONS: The limited published data suggest that linezolid appears to be an effective alternative to trimethoprim/sulfamethoxazole for the treatment of nocardiosis. Unfortunately, the high cost and potentially serious long-term toxicities of linezolid appear to limit its use and relegate it to salvage therapy alone or in combination with other antimicrobials.

Role of linezolid in the treatment of complicated skin and soft tissue infections.

Staphylococcus aureus is the most common cause of complicated skin and soft tissue infections (cSSTIs). Antibiotic choices for these infections continue to evolve. History has seen penicillin progress to antistaphylococcal penicillins and cephalosporins, but these drugs are now giving way to drugs that are effective against methicillin-resistant S. aureus (MRSA). While vancomycin has been the gold standard to treat MRSA infections, newer therapeutic options have been developed over the last 5 years. These include quinupristin-dalfopristin, daptomycin, tigecycline and linezolid, which is the focus for this review. Linezolid is efficacious in the treatment of cSSTIs (including diabetic foot infections) caused by Gram-positive organisms (including MRSA), with a well-defined safety profile and straightforward dosing. It is also approved for nosocomial pneumonia, community-acquired pneumonia and uncomplicated skin and skin structure infections. Linezolid has an oral and parenteral formulation, which are equivalent. The oral formulation has the potential to offer economic benefits as compared with other therapies. Currently, there are only a few new antibiotics in development with MRSA activity. The proper use of all antibiotics, including these newer agents, is increasingly important if we are to slow the evolution of microbial resistance.

A multicentre, randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population.

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir treatment in a population at high risk for influenza. RESEARCH DESIGN AND METHODS: This was a randomized, open-label, controlled trial involving Chinese patients with chronic respiratory diseases (chronic bronchitis, obstructive emphysema, bronchial asthma or bronchiectasis) or chronic cardiac disease. Patients showing symptoms of influenza were randomly assigned to receive oral oseltamivir 75 mg twice daily for 5 days (oseltamivir group), or symptomatic treatment (control group) within 48 h after symptom onset. MAIN OUTCOME MEASURES: The main outcome measures were duration and severity of illness in influenza-infected patients. Other outcome measures included incidence of complications, antibiotic use, hospitalization and total medical cost. RESULTS: Of the 118 recruited patients, 56 were identified as influenza-infected through laboratory tests (oseltamivir, N = 27; control, N = 29). Relative to symptomatic treatment, oseltamivir significantly reduced the duration of influenza symptoms by 36.8% (p = 0.0479), and the severity by 43.1% (p = 0.0002). In addition, oseltamivir significantly reduced the duration of fever by 45.2% (p = 0.0051), and the time to return to baseline health status by 5 days (p = 0.0011). The incidence of complications (11% vs. 45%, p = 0.0053) and antibiotic use (37% vs. 69%, p = 0.0167) were also significantly lower in the oseltamivir group compared with the control group. The cost of treating influenza and its complications was comparable between the two groups (p = 0.2462). CONCLUSIONS: Oseltamivir is effective and well tolerated in high-risk patients with chronic respiratory or cardiac diseases. It can reduce the duration and severity of influenza symptoms and decrease the incidence of secondary complications and antibiotic use, without increasing the total medical cost.

Why do we need new and better antidepressants?

The range of available antidepressants is reviewed in relation to mechanisms of action and the evidence of efficacy in general and efficacy in severe depression in particular. In studies investigating efficacy in major depressive disorder, not all antidepressants have been shown to have clear-cut efficacy in severe depression. Here, the minimum standards for the necessary methodology to investigate efficacy in severe depression are reviewed and the methods that are needed to establish efficacy as a superior antidepressant or as an antidepressant with a faster than expected response are suggested. A review of the mechanisms of action of different antidepressants is accompanied by a critical review of the properties of an antidepressant likely to achieve either efficacy in severe depression or the status of a superior antidepressant.

Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections.

Linezolid (Zyvox), the first available oxazolidinone antibacterial agent, has good activity against Gram-positive pathogens, including multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Randomised multicentre trials in patients with various types of serious Gram-positive infections showed that clinical cure rates with linezolid were similar to those with vancomycin or teicoplanin. In some subgroup analyses, which must be interpreted with a degree of caution, clinical advantages were noted for linezolid (e.g. versus vancomycin in confirmed MRSA nosocomial pneumonia and MRSA-complicated skin and soft tissue infections). Although generally well tolerated, gastrointestinal adverse effects are relatively common with linezolid and it has been associated with thrombocytopenia and myelosuppression. The oral bioavailability of linezolid is approximately 100%, thus allowing sequential intravenous-to-oral administration without changing the drug or dosage regimen. Healthcare resource use data from various countries indicate that this practical advantage translates into at least a trend towards reduced length of hospital stay compared with vancomycin, which may offset its several-fold higher acquisition cost. Modelled analyses from the US, despite some limitations, indicate that, compared with vancomycin, linezolid is associated with lower total hospitalisation costs for the treatment of patients with cellulitis and has a favourable incremental cost-effectiveness ratio of approximately US30,000 dollars per QALY gained (2001 value) for patients with ventilator-associated pneumonia. Broadly similar results have also been reported in modelled analyses from other countries. In conclusion, for patients with serious Gram-positive infections, including those caused by suspected or proven multidrug-resistant pathogens such as MRSA, linezolid is an effective and generally well tolerated therapeutic option. Linezolid is currently the only antibacterial agent with good activity against MRSA that can be administered orally (as well as intravenously). It may be particularly useful as an alternative to vancomycin in patients who have impaired renal function, poor or no intravenous access, require outpatient therapy, or who have been unable to tolerate glycopeptides. Healthcare resource use studies and pharmacoeconomic analyses generally support the use of linezolid in some subgroups of patients, although results should be interpreted with due consideration of the study limitations.