Methicillin-resistant Staphylococcus Aureus Nosocomial Pneumonia Research Articles

Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia.

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

The effect of diabetes mellitus on outcomes of patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: data from a prospective double-blind clinical trial comparing treatment with linezolid versus vancomycin.

BackgroundThe presence of diabetes mellitus increases the risk of several severe infections, but data on its effect on treatment outcomes in patients with nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA) are limited.MethodsWe retrospectively analyzed data from a double-blind, randomized, multi-center, international clinical trial of culture-confirmed MRSA NP that compared treatment with linezolid to vancomycin. Specifically, we evaluated the clinical and microbiologic outcomes of patients with and without diabetes in the modified intent to treat population at end-of-treatment (EOT) and end-of-study (EOS, 7–30 days post-EOT).ResultsAmong 448 enrolled patients 183 (40.8 %) had diabetes mellitus, 87 (47.5 %) of whom received linezolid and 96 (52.5 %) vancomycin. Baseline demographic and clinical characteristics were similar for the two treatment groups. Clinical success rates at EOS were 57.6 % with linezolid and 39.3 % with vancomycin, while microbiological success rates were 58.9 % with linezolid and 41.1 % with vancomycin. Among diabetic patients, rates of mortality and study drug-related adverse effects were similar between the treatment groups. Overall day 28 mortality rates were higher among diabetic patients compared to non-diabetic patients (23.5 vs 14.7 %, respectively: RD = 8.8 %, 95 % CI [1.4, 16.3]).ConclusionsAmong diabetic patients with MRSA NP, treatment with linezolid, compared to vancomycin, was associated with higher clinical and microbiologic success rates, and comparable adverse event rates.Trial registrationNCT00084266.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1779-5) contains supplementary material, which is available to authorized users.

Methicillin-resistant Staphylococcus aureus nosocomial pneumonia: role of linezolid in the People's Republic of China.

The burden of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia in the People’s Republic of China is high, with methicillin-resistance rates greater than 80% reported for patients with S. aureus pneumonia treated in intensive care units. Historically, vancomycin was the treatment of choice for patients with hospital-acquired MRSA infections. Recent evidence suggests that the minimum inhibitory concentration for vancomycin is increasing. Additionally, patients treated with vancomycin require monitoring of vancomycin trough concentrations and can develop nephrotoxicity. Linezolid is a treatment option for patients with hospital-acquired MRSA infections that can be administered either intravenously or orally. Analysis of data from a worldwide linezolid surveillance program initiated in the year 2004 shows no evidence of increasing linezolid minimum inhibitory concentrations. The clinical efficacy of linezolid for patients with gram-positive, including MRSA, nosocomial pneumonia, was evaluated in numerous studies. In general, results from these studies show higher or similar clinical success with no mortality difference for linezolid compared to vancomycin treated patients. Results from a Phase IV study enrolling patients with MRSA-confirmed nosocomial pneumonia suggest higher clinical cure rates for linezolid compared to vancomycin treated patients. Although acquisition costs are higher for linezolid compared to vancomycin therapy, evidence suggests similar overall medical costs. Cost-analysis results from a Chinese perspective show that linezolid dominated vancomycin therapy for MRSA nosocomial pneumonia in ∼35% of bootstrap simulations whereas vancomycin dominated linezolid in less than 2% of bootstrap simulations. In summary, results from both clinical and economic studies, including studies conducted from a Chinese perspective, support the use of linezolid for the treatment of patients with MRSA nosocomial pneumonia.

Estimating the cost-effectiveness of linezolid for the treatment of methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Taiwan.

Methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) is associated with higher resource utilization, increased hospital stays, and mortality. We present a health economics model to understand the impact of using linezolid as the first-line treatment of MRSA NP in Taiwan. We developed a cost-effectiveness model to estimate the costs and clinical outcomes of using linezolid 600mg b.i.d. versus vancomycin 15mg/kg b.i.d. as the first-line treatment of MRSA NP in Taiwan. The model is a decision-analytic analysis in which a MRSA-confirmed patient is simulated to utilize one of the treatments, using data from a clinical trial. Within each treatment arm, the patient can or cannot achieve clinical cure. Regardless of whether the clinical cure was achieved or not, the patient may or may not have experienced an adverse event. The per-protocol results for clinical cure were 57.6% and 46.6% for linezolid and vancomycin, respectively. The total cost of linezolid was $376 more per patient than that of vancomycin. Drug costs were higher for linezolid than for vancomycin ($1108 vs. $233), and hospitalization costs were lower ($4998 vs. $5496). With higher cost and higher cure rates for linezolid, the incremental cost per cure was $3421. This study projects linezolid to have higher drug costs, lower hospital costs, and higher overall costs compared with vancomycin. This is balanced against the higher clinical cure rate for linezolid. Depending on the willingness to pay for clinical cure, linezolid could be cost effective as the first-line treatment of NP in Taiwan.

Linezolid Versus Vancomycin in the Empiric Treatment of Nosocomial Pneumonia: A Cost-Utility Analysis Incorporating Results from the ZEPHyR Trial

ObjectiveTo examine the cost-effectiveness of vancomycin versus linezolid in the empiric treatment of nosocomial pneumonias incorporating results from a recent prospective, double-blind, multicenter, controlled trial in adults with suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. MethodsA decision-analytic model examining the cost-effectiveness of linezolid versus vancomycin for the empiric treatment of nosocomial pneumonia was created. Publicly available cost, efficacy, and utility data populated relevant model variables. A probabilistic sensitivity analysis varied parameters in 10,000 Monte-Carlo simulations, and univariate sensitivity analyses assessed the impact of model uncertainties and the robustness of our conclusions. ResultsResults indicated that the cost per quality-adjusted life-year (QALY) increased 6% ($22,594 vs. $23,860) by using linezolid versus vancomycin for nosocomial pneumonia. The incremental cost per QALY gained by using linezolid over vancomycin was $6,089, and the incremental cost per life saved was $68,615 with the use of linezolid. Vancomycin dominated linezolid in the subset of patients with documented MRSA. The incremental cost per QALY gained using linezolid if no mortality benefit exists between agents or a 60-day time horizon was analyzed was $19,608,688 and $443,662, respectively. ConclusionsLinezolid may be a cost-effective alternative to vancomycin in the empiric treatment of patients with suspected MRSA nosocomial pneumonia; however, results of our model were highly variable on a number of important variables and assumptions including mortality differences and time frame analyzed.

Linezolid versus vancomycin for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a systematic review employing meta-analysis.

The optimal therapy involving linezolid or vancomycin for suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) remains controversial. This study compared the efficacy and safety of linezolid and vancomycin therapies in patients with NP. A systematic review of randomized controlled trials with meta-analyses performed by searching PubMed, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials. We screened for relevant randomized controlled studies in which patients with NP were enrolled and linezolid and vancomycin therapies were compared. Nine trials involving 2618 pneumonia patients were reviewed. Linezolid was not found to be superior to vancomycin for clinical cure when categories of pathogen were not considered and in a subgroup of NP patients with MRSA infection [relative risk (RR)=1.16, 95 % confidence interval (CI)=0.95-1.43, P=0.15]. Compared with vancomycin, linezolid has no difference in the overall microbiological eradication rate (RR=1.12, 95 % CI=0.96-1.30, P=0.15) and specific MRSA eradication rate (RR=1.16, 95 % CI=0.93-1.45, P=0.19) in NP patients. In addition, nephrotoxicity was more frequent with vancomycin (RR=0.50, 95 % CI=0.31-0.81, P=0.005), but no differences between the treatments were found for all-cause mortality, thrombocytopenia, gastrointestinal effects, and drug discontinuation due to adverse events. These results suggest that linezolid is not superior to vancomycin with respect to both clinical and microbiological cure rates in patients with MRSA NP.

An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany.

BackgroundAcross Europe, methicillin-resistant Staphylococcus aureus (MRSA) is considered to be the primary cause of nosocomial pneumonia (NP). In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system.MethodsA 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros) was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival), failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days) or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10).ResultsThe model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with marginally lower costs (by €123) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP). Approximately 85%–87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). Sensitivity analysis yielded similar results.ConclusionThe model results show that linezolid is a cost-effective alternative to vancomycin for MRSA-confirmed NP, largely attributable to the higher clinical response rate of patients treated with linezolid.

Health Economic Evaluation of Patients Treated for Nosocomial Pneumonia Caused by Methicillin-resistant Staphylococcus aureus: Secondary Analysis of a Multicenter Randomized Clinical Trial of Vancomycin and Linezolid

PurposeResults from studies comparing health care resource use (HCRU), costs of treatment, and cost-effectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated. MethodsWe performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparator-controlled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-to-treat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental cost-effectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial. FindingsOverall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly higher total costs. The point estimate incremental cost-effectiveness ratio for linezolid compared with vancomycin was $16,516 per treatment success, with linezolid dominant in 24% and dominated in <2% of bootstrapped samples. ImplicationsThis phase 4 clinical trial conducted in patients with MRSA-confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycin-treated patients had similar HCRU and total overall costs. Fewer patients developed renal failure during the study while taking linezolid compared with vancomycin, and patients with a documented MSAE or renal failure had increased HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy in MRSA-confirmed nosocomial pneumonia.

Consensus statement on the management of methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Asia.

Nosocomial pneumonia (NP; encompassing hospital-acquired, health care-associated and ventilator-associated pneumonia) is one of the most common nosocomial infections and is associated with a mortality rate of 18.7%-40.8% in Asian countries. The burden of methicillin-resistant Staphylococcus aureus (MRSA) infections in Asia is high, and approximately 13% of NP cases in Asia are caused by this pathogen. Evidence regarding optimal management of MRSA NP continues to evolve and is complicated by the fact that a significant proportion of cases are likely to be caused by isolates with reduced susceptibility to the main therapeutic agent, vancomycin. The Asian Consensus Taskforce on MRSA Nosocomial Pneumonia has developed this statement to provide consensus points on diagnosis, antimicrobial treatment and prevention strategies for MRSA NP in the Asian context, based on our review of Asian data, previous international guidelines and recent scientific evidence.

Methicillin-resistant Staphylococcus aureus nosocomial pneumonia patients treated with ceftaroline: retrospective case series of 10 patients

Background:Methicillin-resistant Staphylococcus aureus (MRSA) is a common nosocomial pneumonia (NP) pathogen in US ICUs. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA.Methods:We retrospectively reviewed patients (pts) who received ceftaroline therapy for MRSA NP.Results:A total of 10 pts received ceftaroline from September 2011 to September 2012 for MRSA NP. Nine pts received prior anti-MRSA therapy before initiation of ceftaroline. Ceftaroline duration of therapy ranged from 4 to 28 days. Three pts pursued palliative care prior to completion of therapy and expired off antibiotics. Of the remaining seven pts, six pts were considered to have clinical cure or improvement either at the end of therapy with ceftaroline or total antibiotic treatment. One pt had a relapse 1 week after ceftaroline treatment.Conclusions:This case series suggests the potential of ceftaroline as an alternative agent for the treatment of MRSA NP and warrants further investigation.

Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study

Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia. This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated. Of 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.

Linezolid vs Glycopeptide Antibiotics for the Treatment of Suspected Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Meta-analysis of Randomized Controlled Trials

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial pneumonia. Societal guidelines suggest linezolid may be the preferred treatment of MRSA nosocomial pneumonia. We investigated the efficacy of linezolid compared with glycopeptide antibiotics (vancomycin or teicoplanin) for nosocomial pneumonia. This was a systematic review and meta-analysis of English language, randomized, controlled trials comparing linezolid to glycopeptide antibiotics for suspected MRSA pneumonia in subjects > 12 years of age. A highly sensitive search of PubMed MEDLINE and Cochrane Central Register of Controlled Trials databases identified relevant studies. Eight trials encompassing 1,641 subjects met entry criteria. Linezolid was not superior to glycopeptide antibiotics for end points of clinical success (relative risk [RR] linezolid vs glycopeptide, 1.04; 95% CI, 0.97-1.11; P = .28), microbiologic success (RR, 1.13; 95% CI, 0.97-1.31; P = .12), or mortality (RR, 0.91; 95% CI, 0.69-1.18; P = .47). In addition, clinical success in the subgroup of subjects with MRSA-positive respiratory tract culture (RR, 1.23; 95% CI, 0.97-1.57; P = .09) was not significantly different from those without MRSA (RR, 0.95; 95% CI, 0.83-1.09; P = .48), P for interaction, 0.07. The risk for adverse events was not different between the two antibiotic classes (RR, 0.96; 95% CI, 0.86-1.07; P = .48). Randomized controlled trials do not support superiority of linezolid over glycopeptide antibiotics for the treatment of nosocomial pneumonia. We recommend that decisions between linezolid or glycopeptide antibiotics for empirical or MRSA-directed therapy of nosocomial pneumonia depend on local availability, antibiotic resistance patterns, preferred routes of delivery, and cost, rather than presumed differences in efficacy.

Relationship between the MIC of vancomycin and clinical outcome in patients with MRSA nosocomial pneumonia

The objective of this study is to assess the distribution of vancomycin minimum inhibitory concentrations (MICs) in methicillin-resistant Staphylococcus aureus (MRSA) isolates and evaluate the efficacy of vancomycin relative to vancomycin MICs in adult patients with MRSA nosocomial pneumonia. This retrospective cohort study involved adults with MRSA nosocomial pneumonia treated with vancomycin. Vancomycin MICs were determined using Etest. Patients with MRSA and vancomycin MICs ≥ 1.5 μg/mL and those with MRSA and MICs ≤ 1 μg/mL were placed in the high- and low-MIC group, respectively. The primary outcomes assessed were clinical response and relapse of MRSA pneumonia within 28 days after vancomycin discontinuation. Secondary outcomes included 28-day mortality, in-hospital mortality and length of hospital stay. Seventy patients met the inclusion criteria. Mean age and mean Acute Physiological and Chronic Health Evaluation (APACHE) II score upon intensive care unit (ICU) admission of these patients were 67.0 years and 25.9, respectively. Thirty-four (48.6%) isolates had high vancomycin MICs, and 36 (51.4%) had low MICs. There were no significant differences in baseline characteristics between the two groups. Early clinical response rates in the low- and high-MIC groups were 63.9% and 35.3%, respectively (p = 0.031). The high-MIC group had an 8% lower final clinical response rate, but this difference was not significant (p = 0.609). The relapse rate within 28 days was significantly higher in the high-MIC group than in the low-MIC group (29.6% versus 6.9%, p = 0.038). On multivariate analysis, infection by high-MIC strains was an independent predictor of early clinical response failure. About half of the MRSA isolates had high vancomycin MIC. Patients infected with these strains showed slower clinical response and higher relapse rate than patients infected with low vancomycin MIC isolates.

Infectious Diseases: Pharmacologic Treatment Options for Nosocomial Pneumonia Involving Methicillin-Resistant Staphylococcus aureus

To discuss current and potential treatment options for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). A MEDLINE search (1966-January 2007) was conducted to identify English-language literature on pharmacotherapy of nosocomial pneumonia and the bibliographies of pertinent articles. Programs and abstracts from infectious disease meetings were also searched. Search terms included MRSA, nosocomial pneumonia, pulmonary infections, vancomycin, quinupristin/dalfopristin, linezolid, daptomycin, tigecycline, dalbavancin, oritavancin, and ceftobiprole. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all pertinent information was included in this review. Vancomycin has been the drug of choice for MRSA infections for many years. Recent data suggest that linezolid may be superior to vancomycin in the treatment of MRSA nosocomial pneumonia. However, there are limitations to the available data. Therefore, prospective, randomized studies are needed before linezolid is recommended as the preferred first-line therapy. Other approved agents for nosocomial MRSA infections, such as quinupristin/dalfopristin and daptomycin, should not be used in the treatment of MRSA pneumonia, as they were inferior in clinical trials. Tigecycline has excellent activity against MRSA in vitro, but should not be routinely used for the treatment of MRSA pneumonia, as clinical data are lacking. In a Phase III clinical trial, an anti-MRSA cephalosporin, ceftobiprole, is being evaluated for effectiveness against nosocomial pneumonia. Investigational glycopeptides may eventually have a role in the treatment of nosocomial pneumonia, but data are currently lacking. Vancomycin is still the drug of choice for treatment of MRSA pneumonia, and linezolid should be used as an alternative agent. Linezolid should carry strong consideration for patients with vancomycin-induced nephrotoxicity or a documented lack of response to vancomycin. Tigecycline and investigational agents with activity against MRSA may be future options for nosocomial pneumonia due to MRSA.

Linezolid

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.