Safety and efficacy of linezolid in 16 infants and children in Japan

Linezolid, an oxazolidinone antibiotic, exhibits a broad spectrum of activity against Gram-positive bacteria. It has been licensed for adult use in Japan since 2006 for MRSA infections, and has also been used off-label for pediatric patients. At our university hospital, a total of 16 infants and children (including one non-Japanese Asian) were administered linezolid owing to infection with multidrug-resistant Gram-positive bacteria, after consent had been provided. All patients had severe underlying diseases or indications for surgery. Eighty-eight percent of the causal microorganisms were methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus and all were sensitive to linezolid. Linezolid was administered because the antecedent anti-MRSA medications were ineffective or contraindicated, or intravenous-to-oral switch therapy was requested owing to cardiac or orthopedic surgical-site infections. The median duration of administration was 13 days (range 3-31 days). The overall efficacy was 91 % (10/11) in those for whom efficacy could be evaluated. Only two patients (both teen-aged) encountered linezolid-related adverse effects (13 %, 2/16). One patient showed elevation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), requiring that administration be withdrawn, but enzyme levels returned to normal after the patient had been switched to vancomycin. The other patient showed transiently decreased platelet counts. Linezolid is considered generally safe and effective for children in Japan, especially for those who cannot use other anti-MRSA medications or those who require oral antibiotics for infections with multidrug-resistant Gram-positive bacteria.     

Role of linezolid in the treatment of orthopedic infections

Gram-positive organisms, particularly staphylococci and streptococci, are responsible for the majority of bone and joint infections. The rising incidence of antimicrobial resistance among Staphylococcus aureus, coagulase-negative staphylococci and enterococci means that novel antibiotics with unique mechanisms of antimicrobial activity are needed, especially in orthopedic infections. Linezolid is the first of the oxazolidinones, a new class of antibacterial agents particularly effective against Gram-positive infections including methicillin- and vancomycin-resistant strains. With an excellent oral bioavailability and acceptable safety profile, linezolid offers a valuable alternative to more traditional therapies, such as glycopeptides. No large randomized trials have been published on its use in patients with orthopedic infections, but early results are encouraging. Reported adverse events, especially bone marrow suppression and optic neuropathy seen with prolonged administration, mean that treatment of such patients must be undertaken with careful follow-up of laboratory tests. Until now, little resistance has been reported.     

Linezolid therapy for orthopedic infections

OBJECTIVE: To assess the clinical and bacteriological efficacy and the safety and tolerability profile of linezolid when used as the primary component of a combined surgical and antimicrobial treatment strategy for orthopedic infections. PATIENTS AND METHODS: We retrospectively reviewed medical records to obtain clinical, bacteriological, and safety outcomes of 20 consecutive patients who took linezolid for the treatment of orthopedic infections between April 1, 2000, and November 30, 2002. RESULTS: Twenty patients received linezolid therapy for microbiologically confirmed orthopedic infections due to gram-positive cocci during the 32-month study period. Fifteen patients (75%) had infections involving orthopedic hardware; in 10 of these patients, the hardware was removed. All 20 patients underwent surgical débridement. At a mean follow-up of 276 days, 11 patients (55%) achieved clinical cure, 7 (35%) had clinical improvement but received long-term antimicrobial suppressive therapy, 1 (5%) had clinical relapse after discontinuing linezolid treatment, and 1 (5%) died of a cause unrelated to linezolid treatment. Bacterial persistence was documented in 3 patients (15%), all of whom were Infected with methicillin-resistant Staphylococcus aureus. Eight patients (40%) developed reversible myelosuppression, 1 (5%) had irreversible peripheral neuropathy, and 2 (10%) discontinued linezolid treatment because of pancytopenia or urticaria. CONCLUSION: Oral linezolid may be an effective alternative therapy for orthopedic infections due to linezolid-susceptible gram-positive bacteria in patients who are unable to take other antimicrobial drugs because of drug allergy or Intolerance or antimicrobial resistance.     

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.     

Successful treatment and cerebrospinal fluid penetration of oral linezolid in a patient with coagulase-negative Staphylococcus ventriculitis

OBJECTIVE: To describe a case of coagulase-negative Staphylococcus ventriculitis successfully treated with oral linezolid, for which good cerebrospinal fluid (CSF) penetration was observed. CASE SUMMARY: A 69-year-old man had an extraventricular drain inserted following a right cerebellar infarct. On day 6, the CSF culture was positive for coagulase-negative staphylococci; intravenous vancomycin 1 g daily was initiated to treat ventriculitis. A ventriculoperitoneal shunt, inserted on day 35 to manage communicating hydrocephalus, was subsequently removed as symptoms suggesting infection presented. Coagulase-negative Staphylococcus was isolated from shunt reservoir aspirate, and intrathecal vancomycin 10 mg daily was added to the treatment regimen. On day 61, vancomycin was stopped and oral linezolid 600 mg twice daily was started. Linezolid was discontinued 22 days later, with no evidence of ongoing infection. Four blood samples were collected around the seventh dose of linezolid and 5 CSF samples were collected on separate days during treatment. Linezolid concentrations were measured in plasma and CSF by HPLC. Using an ADAPT II maximum a priori Bayesian estimator module, a 2 compartment pharmacokinetic model was fitted to the plasma linezolid concentration data and CSF:predicted plasma concentration ratios (ranging from 0.27 to 1.02) were derived. All CSF concentrations exceeded the reported 90% minimum inhibitory concentration of 2 mg/L for linezolid against coagulase-negative staphylococci. DISCUSSION: Evidence of the effectiveness of linezolid against central nervous system infections is growing; however, limited data exist describing its CSF penetration. Oral linezolid exhibited good CSF penetration in this patient, which corresponded to positive clinical response. CONCLUSIONS: Oral linezolid may play a valuable role in the treatment of multiresistant gram-positive central nervous system infections.     

In vitro activities of linezolid against important gram-positive bacterial pathogens including vancomycin-resistant enterococci.

The emergence of resistance in gram-positive bacteria has necessitated a search for new antimicrobial agents. Linezolid is an oxazolidinone, a new class of antibacterial agents with enhanced activity against pathogens. We compared the activity of linezolid to those of other antimicrobial agents against 3,945 clinical isolates. Linezolid demonstrated potent activity against all isolates tested. For all vancomycin-susceptible enterococci, staphylococci, and streptococci, the activity of linezolid was comparable to that of vancomycin. Against oxacillin-resistant staphylococci and vancomycin-resistant enterococci, linezolid was the most active agent tested. In summary, linezolid appears to be a promising new antimicrobial agent for the treatment of gram-positive infections.     

Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study

BACKGROUND: Linezolid is an oxazolidinone agent which is apparently well designed for treating chronic osteomyelitis, but data on effectiveness and tolerability as prolonged therapy is currently lacking. OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of linezolid in the treatment of chronic osteomyelitis. METHODS: The charts of hospitalized patients who had been treated with linezolid for >4 weeks because of chronic osteomyelitis and were followed up for > or =12 months after the end of treatment were retrospectively reviewed for clinical outcome and tolerability. Cure was defined as the absence of clinical, biological, or radiological evidence of infection throughout the posttreatment follow-up. Linezolid tolerability was assessed on the basis of hematologic properties during treatment. RESULTS: Of the 66 patients included, all were white (mean [SD] age, 67.7 [18.1] years; 41 men and 25 women; mean [SD] weight, 80.7 [18.6] kg). Thirty-seven (56.1%) patients had infection due to implants including 27 prosthetic joints. Pathogens were predominantly methicillin-resistant staphylococci (49/72 strains, 68.1 %). Every patient was administered N linezolid (600 mg BID) treatment for 6 to 8 days as inpatients, and then, as outpatients, they were switched to PO treatment. Fifty (75.8%) patients received a combination of linezolid and other antimicrobial agents, including rifampin (32 [48.5%]). Surgery was performed in 52 (78.8%) patients. The median hospital stay was 14 days (mean [SD], 19 [11.4] days [range, 7-70 days] ). The median duration of treatment was 13 weeks (mean [SD], 14.3 [8.2] weeks [range, 5-36 weeks]). At the end of treatment, 56 (84.8%) patients were cured, and during the post-treatment follow-up (median duration, 15 months [range, 12-36 months]), 4 relapses occurred, resulting in an overall successful cure for 52 (78.8%) patients. Reversible anemia was reported in 21 patients (31.8%), of whom 16 (24.2%) required blood transfusions. Median time from treatment initiation to anemia onset was 7.3 weeks (range, 4-12 weeks). Peripheral neuropathy was reported in 6 (9.1%) patients, of whom 4 remained symptomatic for up to 24 months after linezolid discontinuation. Other reported adverse events included nausea (6 [9.1%]), diarrhea (1 [1.5%]), and headache (2 [3.0%]), although none of these patients discontinued treatment. CONCLUSIONS: In this retrospective chart review, treatment with linezolid as monotherapy or in combination with antimicrobials and/or surgery was associated with cure of chronic osteomyelitis in 84.8% of subjects at 12 weeks after the end of treatment and 78.8% at follow-up. Adverse events were reported in 51.5% of subjects, and 34.8% of subjects discontinued the study because of adverse events. The potential for severe complications justifies close monitoring of these patients.     

The Emergence of Linezolid Resistance among Enterococci in Intestinal Microbiota of Treated Patients Is Unrelated to Individual Pharmacokinetic Characteristics

Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. We assessed the impact of linezolid on the microbiota and the emergence of resistance and investigated its relationship with plasma pharmacokinetics of the antibiotic. Twenty-eight patients were treated for the first time with linezolid administered orally (n = 17) or parenterally (n = 11) at 600 mg twice a day. Linezolid plasma pharmacokinetic analysis was performed on day 7. Colonization by fecal enterococci, pharyngeal streptococci, and nasal staphylococci were assessed using selective media with or without supplemental linezolid. The resistance to linezolid was characterized. The treatment led to a decrease of enterococci, staphylococci, and streptococci in the fecal (P = 0.03), nasal, and pharyngeal (P < 0.01) microbiotas. The appearance of resistant strains was observed only in enterococci from the fecal microbiota between the 7th and 21st days of treatment in four patients (14.3%). The resistance was mainly due for the first time to the mutation G2447T in the 23S rRNA gene. No pharmacokinetic parameters were significantly different between the patients, regardless of the appearance of resistance. The emergence of linezolid resistance during treatment was observed only in the intestinal microbiota and unrelated to pharmacokinetic parameters. However, colonization by Gram-positive bacteria was reduced as a result of treatment in all microbiotas.     

Worldwide assessment of linezolid's clinical safety and tolerability: comparator-controlled phase III studies

Linezolid, an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens including multidrug-resistant staphylococci, enterococci, and pneumococci. Safety assessments were conducted for 2,046 linezolid-treated patients and 2,001 comparator drug-treated patients from seven controlled clinical trials comparing the activities of linezolid and comparator drugs against nosocomial and community-acquired pneumonia, skin and skin structure infections, and methicillin-resistant staphylococcal infections. Drug-related adverse events were primarily transient. The most frequent (> or = 2%) adverse events caused by linezolid and the comparator drugs were diarrhea (4.3 and 3.2%, respectively; P = 0.074), nausea (3.4 and 2.3%, respectively; P = 0.036), and headache (2.2 and 1.3%, respectively; P = 0.047). Treatment discontinuations due to drug-related events (2.4 and 1.9%, respectively), serious adverse events (11.4 and 10.6%, respectively), and deaths (4.8 and 4.9%, respectively) were similar. No clinically significant drug-related hematologic events were reported, and laboratory safety data were comparable. In the first 6 months of postmarketing surveillance, hematologic abnormalities were reported in 0.1% of linezolid-treated patients, but no irreversible blood dyscrasias were documented. The risk for transient, reversible hematologic effects from treatment with linezolid should be considered together with the clinical benefits associated with its use.     

Comparative activity of linezolid and other new agents against methicillin-resistant Staphylococcus aureus and teicoplanin-intermediate coagulase-negative staphylococci.

The activity of linezolid was determined against 225 recently isolated methicillin-resistant Staphylococcus aureus (MRSA) and 20 methicillin-resistant coagulase-negative staphylococci (CoNS) with decreased levels of susceptibility to teicoplanin. Linezolid activity was compared with other new agents (quinupristin-dalfopristin, trovafloxacin, moxifloxacin, levofloxacin and telithromycin) and six other antimicrobials (erythromycin, clindamycin, gentamicin, vancomycin, teicoplanin and rifampicin). The in vitro activity of linezolid was similar to that of vancomycin. Linezolid inhibited all MRSA strains at between 0.1 and 2 mg/L and all CoNS strains tested at between 0.2 and 0.5 mg/L. These results suggest that linezolid would be useful for the treatment of infections involving these organisms.     

Increased copy number of 23S ribosomal RNA gene with point mutation in MRSA associated with linezolid resistance in a patient treated with long-term linezolid

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) infection is one of the most difficult infections we have to treat. Linezolid is one of the effective treatment options for refractory MRSA infections. There are cases where we are forced to use long-term linezolid treatment for refractory MRSA infections.ObjectiveTo discuss the evolution of Linezolid resistance factors in clinical isolates of MRSA.MethodsWe investigated 16 MRSA isolated from a patient treated with linezolid for a long period of 75 days. We performed antibiotic susceptibility test, 23S rRNA genes sequencing analysis, Pulsed-field gel electrophoresis.ResultsMRSA isolates were susceptible to linezolid before the start of treatment, but became less susceptible by prolonged treatment. The 23S rRNA sequencing analysis of linezolid-resistant strains that appeared 17 days after the start of treatment with linezolid revealed that all resistant MRSA had the G2576T substitution (Escherichia coli 23S rRNA gene number). The number of copies of this mutation increased with the use of linezolid.ConclusionLong-term use of linezolid in a patient or reuse of linezolid in a patient who has been previously treated with linezolid can lead to the emerging of linezolid-resistant MRSA in the host.     

Activity of linezolid against multi-resistant gram-positive bacteria from diverse hospitals in the United Kingdom

The in vitro activity of linezolid, an oxazolidinone, was assessed against 374 gram-positive cocci, with an emphasis on testing multi-resistant, epidemiologically unrelated isolates. MICs of linezolid for staphylococci, pneumococci and streptococci had a narrow range, from 0.5 to 2 mg/L, whereas MICs for enterococci were uniformly 4 mg/L. For all the species tested, the MICs of linezolid were unrelated to those of other antimicrobials. Linezolid appears to be a potentially useful drug for infections caused by gram-positive cocci.     

Trends in linezolid susceptibility patterns in 2002: report from the worldwide Zyvox Annual Appraisal of Potency and Spectrum Program

Oxazolidinones have become reliable clinical and candidate antimicrobial agents to be utilized for infections caused by multidrug-resistant Gram-positive cocci, especially vancomycin-resistant enterococci and methicillin-resistant staphylococci. However, mutational resistance of the ribosomal target has been described for several species. Longitudinal surveillance remains necessary to monitor for this evolving linezolid resistance pattern. A survey of linezolid and several comparison Gram-positive focused agents was initiated in 2002 (7971 strains, >99.0% compliance) for 54 participating sites in the United States, Canada, Europe (6 nations), Latin America (2 nations), and the Asia Pacific (2 nations). The 5 and 25 sites in Canada and the United States, respectively, submitted 200 strains each to a central laboratory for organism identification/confirmation and reference MIC processing. The 10 remaining nations had 200 strain samples from 1 to 4 separate institutions. Linezolid resistance (MIC >/= 8 microg/mL) was confirmed by alternative susceptibility testing methods (Etest, AB BIO Disk, Solna, Sweden; disk diffusion method) and target mutation characterization by PCR and sequence analysis. Linezolid activity against the 6 major organism groups did not vary between geographic areas. A total of 98.1% of linezolid MIC values were between 0.5 and 2 microg/mL, and only 0.5% of results were at 4 microg/mL, which included 32 Staphylococcus aureus (0.9%) and 5 (0.5%) enterococcal isolates. Linezolid resistance was detected in only 4 isolates (0.05%): 1 each Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, and a viridans group Streptococcus. All 4 isolates had a G2576U mutation in the 23S rRNA target. Linezolid activity as outlined by these Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program results demonstrate sustained, near complete activity against contemporary Gram-positive isolates on 4 monitored continents and in centers utilizing oxazolidinones. Rare linezolid-resistant strains were identified in the United States only (0.05% resistance overall).     

In vitro activity of linezolid against multiply resistant Gram-positive clinical isolates

The in vitro activity of the oxazolidinone linezolid was compared with the activities of vancomycin and teicoplanin against 450 Gram-positive clinical isolates, including a variety of multiply resistant strains. Linezolid inhibited all microorganisms tested at < or = 4 mg/L, including methicillin- and teicoplanin-resistant staphylococci, glycopeptide-resistant enterococci, penicillin- and multiply resistant pneumococci and viridans streptococci, and erythromycin-resistant beta-haemolytic streptococci. The MIC(90) of linezolid for all isolates was 2 mg/L.     

Linezolid penetration into osteo-articular tissues

Penetration of linezolid into osteo-articular tissue and fluid was studied in 10 patients undergoing primary total knee replacement. Linezolid 600 mg 12 hourly was given orally over the 48 h before operation and intravenously 1 h before induction of anaesthesia. Mean concentrations of linezolid at 90 min after the final dose, in serum, synovial fluid, synovium, muscle and cancellous bone, assayed by HPLC, were at least twice the MIC(90) for staphylococci and streptococci. The concentrations obtained indicate good penetration of this antibiotic and support its use in the management of multidrug-resistant Gram-positive bone, joint and deep-seated soft-tissue infections.     

In vivo efficacy of continuous infusion versus intermittent dosing of linezolid compared to vancomycin in a methicillin-resistant Staphylococcus aureus rabbit endocarditis model

Linezolid is the first drug issued from the oxazolidinones, a novel class of antimicrobial agents with potent activity against gram-positive pathogens. A rabbit endocarditis model was used to compare the in vivo activities of different linezolid regimens mimicking intermittent dosing of 10 mg/kg of body weight every 12 h for 5 days or continuous (constant-rate) infusion of a daily dose of 20 mg/kg (for 5 days) or 40 mg/kg (for 3 and 5 days) and the activities of intermittent dosing and continuous infusion of vancomycin (for 5 days). The in vivo activities of these regimens were tested against three strains of methicillin-resistant Staphylococcus aureus. A human-like pharmacokinetic simulation was used for linezolid in order to improve the extrapolation of the results to human therapy. All linezolid regimens significantly reduced the numbers of S. aureus cells in aortic valve vegetations compared to the numbers in the control groups. Linezolid intermittent dosing had an in vivo bacteriostatic effect. Switching from intermittent dosing to continuous infusion (at the same dose) led to in vivo bactericidal activity, with a decrease of at least 3 log(10) CFU/g of vegetation compared to the counts for the controls. After 5 days of treatment, continuous infusion of linezolid (corresponding to a daily dose of 40 mg/kg in humans) seemed to be at least as effective as vancomycin against the three strains. No resistant variant was isolated from the vegetations during any of the treatments. These data suggest that continuous infusion of linezolid could be an appropriate alternative to the use of glycopeptides for the treatment of severe methicillin-resistant S. aureus infections.     

Linezolid versus teicoplanin in the treatment of Gram-positive infections in the critically ill: a randomized, double-blind, multicentre study

OBJECTIVES: Linezolid, the only commercially available oxazolidinone, is indicated for the treatment of Gram-positive infections, although little has been published specifically on its use in the critically ill. A randomized, prospective study was therefore performed to compare linezolid with the glycopeptide antibiotic, teicoplanin, for the treatment of suspected or proven Gram-positive infections in an intensive care population. METHODS: Using a double-blind, double-dummy, prospective design, patients were randomized to (i) intravenous linezolid (600 mg/12 h) plus teicoplanin dummy [one dose/12 h for three doses then every 24 h intravenously (iv)] or (ii) teicoplanin (400 mg/12 h for three doses then 400 mg/24 h iv) plus linezolid dummy (one dose/12 h iv). Other antibiotics were used in combination with the trial agents in empirical treatment. Clinical and microbiological assessments were made daily in the first week, and at 8 and 21 days after treatment. RESULTS: One hundred patients received linezolid plus placebo-teicoplanin, whereas 102 received teicoplanin plus placebo-linezolid. Population baseline characteristics were similar in both groups. At end of treatment, clinical success [71 (78.9%) linezolid versus 67 (72.8%) teicoplanin] and microbiological success [49 (70.0%) versus 45 (66.2%)] rates were similar, as were adverse effects, intensive care unit mortality, and success rates at short- and long-term follow-up. Linezolid was superior at initial clearance of methicillin-resistant Staphylococcus aureus (MRSA) colonization (end of treatment, 51.1% versus 18.6%, P = 0.002). Two MRSA isolates showed reduced susceptibility to teicoplanin. CONCLUSIONS: Linezolid has similar safety and efficacy to teicoplanin in treating Gram-positive infections in the critically ill. Short-term MRSA clearance achieved with linezolid suggests better skin and mucosal penetration.     

Prospective, randomized study comparing quinupristin-dalfopristin with linezolid in the treatment of vancomycin-resistant Enterococcus faecium infections

OBJECTIVES: Quinupristin-dalfopristin and linezolid have been shown to be efficacious in the treatment of vancomycin-resistant Enterococcus faecium (VREF) infections. However, the two antibiotics have not been compared in terms of safety and efficacy in a prospective randomized study. The objective of this study was to compare the safety and efficacy of the two drugs in the treatment of VREF infections in cancer patients. PATIENTS AND METHODS: Forty cancer patients with VREF infection were randomized to receive linezolid 600 mg every 12 h or quinupristin-dalfopristin 7.5 mg/kg every 8 h. All patients were followed up for 30 days after discontinuation of study drugs. RESULTS: Linezolid and quinupristin-dalfopristin had comparable clinical responses (58% and 43%, respectively, P = 0.6). Myalgias and/or arthralgias occurred at a frequency of 33% in patients who received quinupristin-dalfopristin, but were not observed in the linezolid group (P = 0.03). In contrast, drug-related thrombocytopenia occurred in 11% of patients who received linezolid, but was not observed in the quinupristin-dalfopristin group (P = 0.2). CONCLUSION: In cancer patients, quinupristin-dalfopristin treatment is associated with a relatively high frequency of myalgias/arthralgias; however, profound thrombocytopenia might limit the choice of linezolid in a subpopulation of cancer patients.     

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.