Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin

Objective To assess the effect of baseline variables, including treatment, on clinical cure and survival rates in patients with Gram-positive, ventilator-associated pneumonia (VAP).Design Retrospective analysis of two randomized, double-blind studies.Setting Multinational study with 134 sites.Patients 544 patients with suspected Gram-positive VAP, including 264 with documented Gram-positive VAP and 91 with methicillin-resistant S. aureus (MRSA) VAP.Interventions Linezolid 600 mg or vancomycin 1 g every 12 h for 7–21 days, each with aztreonam.Measurements and results Clinical cure rates assessed 12–28 days after the end of therapy and excluding indeterminate or missing outcomes significantly favored linezolid in the Gram-positive and MRSA subsets. Logistic regression showed that linezolid was an independent predictor of clinical cure with odds ratios of 1.8 for all patients, 2.4 for Gram-positive VAP, and 20.0 for MRSA VAP. Kaplan-Meier survival rates favored linezolid in the MRSA subset. Logistic regression showed that linezolid was an independent predictor of survival with odds ratios of 1.6 for all patients, 2.6 for Gram-positive VAP, and 4.6 for MRSA VAP.Conclusions Initial linezolid therapy was associated with significantly better clinical cure and survival rates than was initial vancomycin therapy in patients with MRSA VAP.This study was supported by a grant from Pharmacia Corporation, Peapack, N.J., USAAn editorial regarding this article can be found in the same issue ()     

In Vivo Antibacterial Activity of MRX-I,a New Oxazolidinone

MRX-I is a potent oxazolidinone antibiotic against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), penicillin-intermediate S. pneumoniae (PISP), and vancomycin-resistant enterococci (VRE). In this study, the in vivo efficacy of orally administered MRX-I was evaluated using linezolid as a comparator. MRX-I showed the same or better efficacy than linezolid in both systemic and local infection models against the tested strains.     

Ceftaroline fosamil: a new cephalosporin active against resistant Gram-positive organisms including MRSA

The growing prevalence of resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus continues to pose a dilemma to clinicians. With strains developing reduced susceptibility to vancomycin, effective and well-tolerated antibiotics to combat these resistant pathogens are needed. Ceftaroline is a new parenteral cephalosporin that has been available in the USA for almost 2 years. Similar to other cephalosporins, it is well tolerated with mostly mild adverse events; however, compared with existing parenteral cephalosporins, ceftaroline has the unique attribute of being bactericidal against resistant Gram-positive aerobes including both hospital- and community-acquired methicillin-resistant S. aureus, S. aureus strains with reduced susceptibility or complete resistance to vancomycin, and resistant Streptococcus pneumoniae including multidrug-resistant strains. Current indications in the USA and Europe include treatment of adults with complicated skin, skin-structure infections and community-acquired pneumonia. This paper will review the properties of ceftaroline, its spectrum of activity, clinical use, safety profile and future role.     

Efficacy of linezolid versus comparator therapies in Gram-positive infections

Treatment of Gram-positive bacterial infections is currently a therapeutic challenge because many of these pathogens are now resistant to standard antimicrobial agents. The emergence of multidrug-resistant, Gram-positive pathogens emphasizes the need for new antimicrobial therapy. Linezolid is an oxazolidinone antibiotic with a novel mechanism of action that works by inhibiting bacterial protein synthesis by blocking formation of the initiation complex. It is active against Gram-positive organisms resistant to other antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci (VRE). Results are encouraging from several large-scale, randomized, Phase III trials comparing the efficacy and safety of linezolid with standard comparator agents for the treatment of nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and infections due to MRSA and VRE. Intravenous/oral linezolid is a promising antimicrobial agent and provides the clinician with an additional treatment option, particularly among the limited therapies for resistant Gram-positive bacterial infections.     

Update on prevalence and treatment of methicillin-resistant Staphylococcus aureus infections

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is characterized by variations (sometimes extreme) by country and geographic region. The conventional association of MRSA with healthcare settings has been upset by the emergence of community-associated MRSA infections in many areas. With this surge in MRSA comes a renewed interest in alternative agents to vancomycin for treatment of MRSA infections, including older drugs, such as clindamycin, doxycycline and trimethoprim– sulfamethoxazole. Newer agents, such as linezolid and daptomycin, are aiming to improve on the poor cure rates found with vancomycin in serious MRSA infections, but definitive studies showing superiority of these drugs are not yet available. Finally, the drug-development pipeline contains a number of agents for the treatment of MRSA infections, including enhanced glycopeptides (dalbavancin, oritavancin and telavancin) and anti-MRSA cephalosporins (ceftobiprole). As MRSA becomes the ‘new normal’ in many areas, clinicians will have to sort out the proper role of a dozen or more anti-MRSA drugs.     

In Vitro Activity and Microbiological Efficacy of Tedizolid (TR-700) against Gram-Positive Clinical Isolates from a Phase 2 Study of Oral Tedizolid Phosphate (TR-701) in Patients with Complicated Skin and Skin Structure Infections

Tedizolid (TR-700, formerly torezolid) is the active moiety of the prodrug tedizolid phosphate (TR-701), a next-generation oxazolidinone, with high potency against Gram-positive species, including methicillin-resistant Staphylococcus aureus (MRSA). A recently completed randomized, double-blind phase 2 trial evaluated 200, 300, or 400 mg of oral tedizolid phosphate once daily for 5 to 7 days in patients with complicated skin and skin structure infections. This report examines the in vitro activity of tedizolid and Zyvox (linezolid) against Gram-positive pathogens isolated at baseline and describes the microbiological and clinical efficacy of tedizolid. Of 196 isolates tested, 81.6% were S. aureus, and of these, 76% were MRSA. The MIC(50) and MIC(90) of tedizolid against both methicillin-susceptible S. aureus (MSSA) and MRSA were 0.25 μg/ml, compared with a MIC(50) of 1 μg/ml and MIC(90) of 2 μg/ml for linezolid. For coagulase-negative staphylococci (n = 7), viridans group streptococci (n = 15), and beta-hemolytic streptococci (n = 3), the MICs ranged from 0.03 to 0.25 μg/ml for tedizolid and from 0.12 to 1 μg/ml for linezolid. The microbiological eradication rates at the test-of-cure visit (7 to 14 days posttreatment) in the microbiologically evaluable population (n = 133) were similar in all treatment groups, with overall eradication rates of 97.7% for all pathogens, 97.9% for MRSA, and 95.7% for MSSA. The clinical cure rates for MRSA and MSSA infections were 96.9% and 95.7%, respectively, across all dose groups. This study confirms the potent in vitro activity of tedizolid against pathogenic Gram-positive cocci, including MRSA, and its 4-fold-greater potency in comparison with linezolid. All dosages of tedizolid phosphate showed excellent microbiological and clinical efficacy against MRSA and MSSA.     

In vitro susceptibility of Gram-positive pathogens to linezolid and teicoplanin and effect on outcome in critically ill patients

OBJECTIVES: To determine the prevalence of teicoplanin and linezolid resistance amongst Gram-positive pathogens isolated in the intensive care unit (ICU) and the impact of any resistance on clinical outcome. METHODS: Gram-positive isolates were collected from two critical care units over 1 year. All patients were screened weekly for methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to teicoplanin and linezolid was tested by Etest. The length of hospital and critical care unit stay and the use of antibiotics in each patient were recorded. RESULTS: Reduced susceptibility to teicoplanin (MIC>or=16 mg/L) was found in 21 [3.3% (95% CI 2.0-5.0%) 6 patients] of 643 strains of MRSA versus none of 374 methicillin-susceptible S. aureus (MSSA) [<0.3% (95% CI 0-0.9%)]. Of 49 enterococci 3 were teicoplanin-resistant. All Gram-positive isolates were susceptible to linezolid. The length of treatment with teicoplanin and outcome of patients infected with these strains were similar to that of susceptible strains. MRSA was a more common cause of infection than MSSA but a less frequent colonizer. CONCLUSIONS: Resistance to teicoplanin remains at a comparatively low level and there was no clear relationship between susceptibility and outcome in this critically ill population. There was no resistance in Gram-positives to linezolid but this should be kept as a reserve antibiotic to maintain its activity.     

Immunomodulatory Effect of Linezolid on Methicillin-Resistant Staphylococcus aureus Supernatant-Induced MUC5AC Overexpression in Human Airway Epithelial Cells

Linezolid is the first member of the oxazolidinones and is active against drug-resistant Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). Additionally, linezolid shows an immunomodulatory effect, such as inhibition of inflammatory cytokine production. In this study, we examined the effect of linezolid on MRSA-induced MUC5AC overexpression in airway epithelial cells. In this study, an MRSA supernatant was used to avoid the direct effect of linezolid on MRSA. MUC5AC protein production was significantly increased with a 40-fold dilution of MRSA supernatant. At the mRNA level, MUC5AC gene expression was significantly increased 6 and 9 h after stimulation. In an inhibition study, linezolid significantly reduced MRSA-induced MUC5AC protein and mRNA overexpression at concentrations of 5 and 20 μg/ml, which were the same as the trough and peak concentrations in human epithelial lining fluid. In an analysis of cell signaling, among the mitogen-activated protein kinase inhibitors, only the extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor reduced the MUC5AC protein production to the same level as that of the control; on Western blot analysis, only ERK1/2 was phosphorylated by the MRSA supernatant. In addition, the ERK1/2 phosphorylation was inhibited by linezolid. MUC5AC and MUC5B are the major barrier that traps inhaled microbial organisms, particulates, and foreign irritants. However, in patients with chronic respiratory diseases, pathogen-induced MUC5AC overexpression causes many problems, and control of the overexpression is important. Thus, this study revealed that linezolid showed a direct immunomodulatory effect in airway epithelial cells.     

In Vivo Efficacy of Ceftaroline Fosamil in a Methicillin-Resistant Panton-Valentine Leukocidin-Producing Staphylococcus aureus Rabbit Pneumonia Model

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with broad-spectrum in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae (MDRSP), and common Gram-negative pathogens. This study investigated the in vivo activity of ceftaroline fosamil compared with clindamycin, linezolid, and vancomycin in a severe pneumonia model due to MRSA-producing Panton-Valentine leukocidin (PVL). A USA300 PVL-positive clone was used to induce pneumonia in rabbits. Infected rabbits were randomly assigned to no treatment or simulated human-equivalent dosing with ceftaroline fosamil, clindamycin, linezolid, or vancomycin. Residual bacterial concentrations in the lungs and spleen were assessed after 48 h of treatment. PVL expression was measured using a specific enzyme-linked immunosorbent assay (ELISA). Ceftaroline, clindamycin, and linezolid considerably reduced mortality rates compared with the control, whereas vancomycin did not. Pulmonary and splenic bacterial titers and PVL concentrations were greatly reduced by ceftaroline, clindamycin, and linezolid. Ceftaroline, clindamycin, and linezolid were associated with reduced pulmonary tissue damage based on significantly lower macroscopic scores. Ceftaroline fosamil, clindamycin, and, to a lesser extent, linezolid were efficient in reducing bacterial titers in both the lungs and spleen and decreasing macroscopic scores and PVL production compared with the control.     

A review of linezolid: the first oxazolidinone antibiotic

Resistance of Gram-positive bacterial pathogens, such as Staphylococcus aureus and Enterococcus faecium, to existing antibiotics continues to increase, and new antibiotics with activity against these pathogens are in demand. Linezolid (Zyvox^®, Pharmacia and Upjohn) is the first agent of a new class of antibiotics called the oxazolidinones. Linezolid possesses excellent microbial activity against a wide variety of Gram-positive pathogens including those resistant to methicillin and vancomycin (Vancocin^®, Eli Lilly). Linezolid is available for intravenous and oral administration and possesses excellent bioavailability. It exhibits good penetration into pulmonary, as well as skin and related structure tissues, and does not require dosage adjustment in hepatic or renal dysfunction. Linezolid is generally well-tolerated, with the predominant adverse effect manifesting as a duration dependent, reversible thrombocytopenia. Linezolid possesses monoamine oxidase inhibitor activity and caution is warranted with coadministration of adrenergic or seritonergic medications. Clinical trials conducted with linezolid in skin and structure infections, lower respiratory tract infections and vancomycin-resistant enterococcal infections demonstrate that linezolid is an effective therapy. Recent data suggest that linezolid may be superior to vancomycin for the treatment of infections caused by methicillin-resistant S. aureus. Linezolid is an excellent and promising new antibiotic for the treatment of resistant Gram-positive pathogens.     

A comparison of linezolid with glycopeptides in severe MRSA pneumonia

Evaluation of: Luna CM, Bruno DA, García-Morato J et al. Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets. Chest 135(6), 1564–1571 (2009).

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen in nosocomial infections and accounts for a large proportion of nosocomial pneumonia. However, there are limited antibiotics available for the treatment of this serious and potentially lethal infection. Until recently, the only effective antibiotic was vancomycin, but the oxazolidinones, such as linezolid, have been shown to be a valuable addition to the arsenal of antimicrobial agents that can be used for MRSA pneumonia. Clinical trials have been conducted to compare vancomycin and linezolid head-to-head in pneumonia and, in post hoc subgroup analyses, showed that linezolid use was associated with improved survival. The ensuing debate over these results was dominated by two opinions; there were those who speculated on the mechanism by which linezolid achieved this benefit, namely attributing it to pharmacodynamics and pharmacokinetics, and others who criticized the methodology of the studies and questioned the validity of the results altogether. This study by Luna and colleagues was designed with several goals in mind. The first was to attempt to generate an animal model of MRSA pneumonia in piglets by duplicating techniques used in animal models of Gram-negative pneumonia. Then they studied the effect of three antibiotics (vancomycin, linezolid and teicoplanin) on outcomes in the same model, while simultaneously measuring antibiotic levels in the serum, bronchoalveolar lavage fluid and lung tissue, in an attempt to attribute differences in survival to pharmacological properties of the drugs used. Their results showed a survival benefit only for linezolid, despite the fact that all three antibiotics had levels above MIC in all the compartments sampled, leading them to speculate that linezolid may have improved outcomes by mechanisms not directly related to its antimicrobial actions.     

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.     

Dalbavancin: a novel antimicrobial

The increasing incidence of serious infections because of Gram-positive pathogens and the rising cost in parenteral administration of antimicrobials has inspired the development of a novel antibiotic. Dalbavancin is the first once a week antibiotic with activity against a broad range of Gram-positive pathogens. A large multicentre, pivotal, Phase III clinical trial, which included 854 patients with complicated skin and skin structure infections, compared 1-2 doses of dalbavancin vs. linezolid. The results demonstrated non-inferiority and a comparable safety profile. With its unique pharmacokinetic profile, ease of use and excellent safety profile, dalbavancin should provide a valuable addition to the armamentarium used to treat infections because of Gram-positive cocci.     

Linezolid in the treatment of Gram-positive prosthetic joint infections

OBJECTIVES: To investigate the clinical efficacy and safety of linezolid in the treatment of Gram-positive prosthetic hip and knee infections. MATERIALS AND METHODS: A retrospective evaluation of patients hospitalized in the Department of Infectious Diseases of San Martino Hospital in Genoa with the diagnosis of Gram-positive prosthetic joint infection and treated with intravenous and/or oral linezolid. Primary end points were the patient clinical outcome at the end of treatment and at long-term follow-up (up to 12 months after the end of treatment). RESULTS: Between May 1999 and September 2003, 20 patients with prosthetic joint infection were treated with linezolid. Pathogens isolated were: methicillin-resistant Staphylococcus aureus (MRSA), 14 strains; methicillin-resistant coagulase-negative staphylococci, five strains; and Enterococcus spp., one strain. The overall duration of treatment was 7.2 +/- 2 weeks (range 6-10 weeks). Patients were given intravenous therapy for 3-7 days as inpatients, then were changed as outpatients to oral therapy under weekly laboratory testing. At long-term follow-up (1 year), we observed four cases of failure due to relapsing infections. The other 16 patients treated with linezolid did not need further surgical substitution of prosthesis or surgical joint revision. Linezolid was well tolerated, and no drug-related events leading to discontinuation of treatment were recorded. CONCLUSIONS: Our data indicate that linezolid may be an effective alternative therapy for orthopaedic infections caused by Gram-positive resistant pathogens and that a prospective and comparative evaluation of linezolid in this setting is necessary.     

Community-Associated MRSA Infections in Women

Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital pathogen, but now its prevalence in the community is increasing. Community-associated MRSA (CA-MRSA) is the causative agent in many outpatient skin and soft tissue infections. Within the women's health population, CA-MRSA infection can result in a variety of genital skin infections, including boils, furuncles, and abscesses. Antibiotic-resistant strains, reinfection, and transmission among close contacts contribute to difficulty in controlling the spread of this pathogen. This article provides an overview of CA-MRSA, its clinical presentation, diagnosis, treatment, and implications for clinical practice in women's healthcare settings.     

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

The prevalence of skin and soft tissue infections (SSTIs) has been increasing in the United States. These infections are associated with an increase in hospital admissions. Hospitalists play an increasingly important role in the management of these infections and need to use hospital resources efficiently and effectively. When available, observation units are useful for treating low-risk patients who do not require hospital admission. Imaging tools may help to exclude abscesses and necrotizing soft tissue infections; however, surgical exploration remains the principal means of diagnosing necrotizing soft tissue infections. The most common pathogens that cause SSTIs are streptococci and Staphylococcus aureus. Methicillin-resistant S aureus (MRSA) is a prevalent pathogen, and concerns are increasing regarding the unclear distinctions between community-acquired and hospital-acquired MRSA. Other less frequent pathogens that cause SSTIs include Enterococcus species, Escherichia coli, Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa. Cephalexin and clindamycin are suitable options for infections caused by streptococcal species and methicillin-susceptible S aureus. The increasing resistance of S aureus and Streptococcus pyogenes to erythromycin limits its use in these infections, and better alternatives are available. Parenteral cefazolin, nafcillin, or oxacillin can be used in hospitalized patients with nonpurulent cellulitis caused by streptococci and methicillin-susceptible S aureus. When oral MRSA therapy is indicated, clindamycin, doxycycline, trimethoprim-sulfamethoxazole, or linezolid is appropriate. Vancomycin, linezolid, daptomycin, tigecycline, telavancin, and ceftaroline fosamil are intravenous options that should be used in MRSA infections that require patient hospitalization. In the treatment of patients with SSTIs, hospitalists are at the forefront of providing proper patient care that reduces hospital costs, duration of therapy, and therapeutic failures. This review updates guidelines on the management of SSTIs with a focus on infections caused by S aureus, particularly MRSA, and outlines the role of the hospitalist in the effective management of SSTIs.     

康替唑胺体外抗菌作用研究

目的 评价唑烷酮类新药康替唑胺对临床分离菌的体外抗菌作用.方法 收集全国19所医院1321株的临床分离菌,以琼脂对倍稀释法测定康替唑胺对分离菌的最低抑菌浓度(MIC)并与有关抗菌药物进行比较,测定康替唑胺的杀菌活性、抗菌药物后效应(PAE)以及不同培养条件对康替唑胺抗菌作用的影响.结果 康替唑胺对革兰阳性菌中葡萄球菌...     

Chronic liver disease increases the risk of linezolid-related thrombocytopenia in methicillin-resistant Staphylococcus aureus-infected patients after digestive surgery

Linezolid is an effective antibiotic for treatment of infections caused by resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). However, thrombocytopenia has been reported in a certain proportion of patients receiving linezolid treatment. We investigated the risk factors for linezolid-related thrombocytopenia in MRSA-infected patients after digestive surgery. Forty-three patients who were treated with linezolid for postoperative MRSA infection were enrolled. We compared the characteristics of the patients who developed thrombocytopenia during linezolid therapy with those of the patients who did not. Thrombocytopenia was defined as a platelet ratio (post/pre-treatment with linezolid) of <0.7. Twenty-one (48.8%) patients developed thrombocytopenia. In univariate analysis, long treatment duration, high pre-treatment levels of total-bilirubin and transaminases, and the coexistence of chronic liver disease (CLD) were found to be significant risk factors for development of thrombocytopenia. Other factors, for example pre-treatment platelet count, serum creatinine and albumin levels, and previous hepatic resection were not associated with thrombocytopenia. In the multivariate regression analysis, only CLD remained as an independent factor associated with thrombocytopenia. In addition, thrombocytopenia was more common among patients with indocyanine green retention at 15 min (ICG-R15) of more than 10% than in those with an ICG-R15 of 10% or less. Our results suggest that patients with CLD are at high risk of developing linezolid-related thrombocytopenia. Therefore, they should be targeted for more intense platelet count monitoring during linezolid therapy.     

Surveillance of iclaprim activity: In vitro susceptibility of gram-positive pathogens collected from 2012 to 2014 from the United States,Asia Pacific,Latin American and Europe

Iclaprim is a diaminopyrimidine, which inhibits bacterial dihydrofolate reductase, and it is highly active against Gram-positive pathogens including emerging drug-resistant pathogens. In vitro activity of iclaprim and comparators against 2814 Gram-positive clinical isolates from the United States, Asia Pacific, Latin American and Europe collected between 2012 and 2014 were tested. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. MIC₅₀/MIC₉₀ for all S. aureus, methicillin susceptible S. aureus, methicillin resistant S. aureus, beta-hemolytic streptococci, and Streptococcus pneumoniae were 0.06/0.12, 0.06/0.12, 0.06/0.5, 0.06/0.25, and 0.06/2 μg/mL, respectively. Iclaprim was 8 to 32-fold more potent than trimethoprim, the only FDA approved dihydrofolate reductase inhibitor, against all Gram-positive isolates including resistant phenotypes. The MIC₉₀ of iclaprim was also lower than most of the comparators including linezolid and vancomycin against Gram-positive pathogens. Iclaprim demonstrated potent activity against a contemporary collection (2012–2014) of Gram-positive clinical isolates from the United States, Asia Pacific, Latin America and Europe.     

Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States

This study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980 Staphylococcus aureus isolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.