Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Linezolid”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2005

Serotonin toxicity associated with concomitant use of linezolid.

OBJECTIVE: To report 2 cases of serotonin toxicity (ST) associated with concomitant use of linezolid and serotonergic drugs and review previously published case reports. CASE SUMMARIES: Case 1. A 38-year-old white female with cystic fibrosis treated with venlafaxine 300 mg/day for one year was prescribed linezolid 600 mg intravenously every 12 hours for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pulmonary infection. She displayed symptoms of ST 8 days after the introduction of linezolid. The venlafaxine dosage was decreased to 150 mg/day, and symptoms gradually abated over 36 hours. Case 2. A 37-year-old male with multiple myeloma received citalopram 40 mg/day and trazodone 150 mg/day for anxiety-related disorders. Linezolid treatment with 600 mg orally twice daily was instituted for MRSA cellulitis. The following day, the patient developed anxiety, panic attacks, tremors, tachycardia, and hypertension that persisted throughout linezolid treatment. Symptoms finally waned 5 days after linezolid treatment was stopped. DISCUSSION: The symptoms observed in our patients were consistent with Sternbach's criteria for ST. A review of published case reports showed a short time to onset of symptoms following the introduction of linezolid, generally within 1-3 days. Also of note is the use of relatively high dosages of serotonergic drugs. Use of the Naranjo probability scale indicated a possible relationship between the use of linezolid and the occurrence of ST in both cases. CONCLUSIONS: Clinicians should pay special attention to patients treated with serotonergic drugs, especially those receiving dosages in the higher end of the normal range who are prescribed linezolid, and consider tapering or reducing the dosage of serotonergic drugs for the duration of antibiotic therapy.

Acetamides↗
PubMed2001

Linezolid--a review of the first oxazolidinone.

Linezolid is the first of a truly new class of antibiotics, the oxazolidinones. It acts as an inhibitor of bacterial protein synthesis by blocking the formation of the 70S ribosomal initiation complex. Its activity is bacteriostatic against some species (e.g., enterococci) and bactericidal against others (e.g., pneumococci). The antibacterial spectrum of linezolid includes Gram-positive pathogens and some Gram-negative anaerobic species but not Gram-negative aerobes. Importantly, multi-drug resistant organisms such as methicillin-resistant staphylococci, staphylococci with reduced susceptibility to vancomycin, penicillin- and macrolide-resistant pneumococci and vancomycin-resistant enterococci are fully susceptible to linezolid. Linezolid has almost 100% bioavailability and the area under the plasma concentration curve is identical after oral and iv. administration. This enables initial oral administration of linezolid in those patients who can absorb the drug normally and also an early step-down therapy from iv. to oral. Controlled, randomised clinical studies have documented efficacy and safety of linezolid in hospital- and community-acquired pneumonia, uncomplicated and complicated skin and soft tissue infections and infections caused by vancomycin-resistant enterococci. The safety and tolerability of linezolid are advantageous. Linezolid is a weak and reversible monoamine oxidase (MAO) inhibitor and although no increased frequency of adrenergic or serotonergic adverse events has been reported, it is recommended that linezolid is used with caution in patients treated with other MAO inhibitors.

Acetamides↗
PubMed2004

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.

Acetamides↗
PubMed2000

Linezolid.

Linezolid is an oxazolidinone antibacterial agent that acts by inhibiting the initiation of bacterial protein synthesis. Cross-resistance between linezolid and other inhibitors of protein synthesis has not been demonstrated. Linezolid has a wide spectrum of activity against gram-positive organisms including methicillin-resistant staphylococci, penicillin-resistant pneumococci and vancomycin-resistant Enterococcus faecalis and E. faecium. Anerobes such as Clostridium spp., Peptostreptococcus spp. and Prevotella spp. are also susceptible to linezolid. Linezolid is bacteriostatic against most susceptible organisms but displays bactericidal activity against some strains of pneumococci, Bacteroides fragilis and C. perfringens. In clinical trials involving hospitalised patients with skin/soft tissue infections (predominantly S. aureus), intravenous/oral linezolid (up to 1250 mg mg/day) produced clinical success in >83% of individuals. In patients with community-acquired pneumonia, success rates were >94%. Preliminary clinical data also indicate that twice daily intravenous/oral linezolid 600 mg is as effective as intravenous vancomycin 1 g in the treatment of patients with hospital-acquired pneumonia and in those with infections caused by methicillin-resistant staphylococci. Moreover, linezolid 600 mg twice daily produced >85% clinical/microbiological cure in vancomycin-resistant enterococcal infections. Linezolid is generally well tolerated and gastrointestinal disturbances are the most commonly occurring adverse events. No clinical evidence of adverse reactions as a result of monoamine oxidase inhibition has been reported.

Acetamides↗
PubMed2005

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.

Acetamides↗
PubMed2003

Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia.

BACKGROUND: The clinical efficacy and tolerability of linezolid were demonstrated in a previously published, randomized, double-blind, registration study comparing linezolid with vancomycin for the empiric treatment of 396 patients with nosocomial pneumonia. OBJECTIVES: The aims of this study were to obtain additional experience with linezolid and vancomycin in patients with nosocomial pneumonia and to satisfy international regulatory requirements. METHODS: Patients with pneumonia acquired after 48 hours in an inpatient facility were randomly assigned to receive either IV linezolid 600 mg or IV vancomycin 1 g every 12 hours for 7 to 21 consecutive days. Patients also received IV aztreonam 1 to 2 g every 8 hours, which could be discontinued if gram-negative pathogens were not identified. The primary efficacy variables were clinical and microbiologic outcomes in evaluable patients at the follow-up visit 15 to 21 days after the end of therapy. Results from the continuation study were analyzed separately and did not include patients from the previously reported study. RESULTS: A total of 623 patients were enrolled: 321 in the linezolid group and 302 in the vancomycin group. Mean (SD) ages were 63.1 (19.1) years and 61.9 (19.3) years, respectively. Mean (SD) Acute Physiology and Chronic Health Evaluation II scores were 14.1 (5.8) and 14.1 (6.2), respectively. There were no significant differences between the linezolid and vancomycin groups at the follow-up visit in clinical cure rates (114/168 [67.9%] and 111/171 [64.9%]) or microbiologic success rates (47/76 [61.8%] and 42/79 [53.2%]) in evaluable patients (excluding those who had indeterminate or missing outcomes). There were also no significant differences in the rates of all drug-related adverse events (14.0% and 14.0%) or those that occurred in > 1% of patients, including diarrhea (3.7% and 3.0%), nausea (0.3% and 1.3%), and rash (0.6% and 1.7%) in the linezolid and vancomycin groups, respectively. CONCLUSION: In the population studied, linezolid appeared to be as well tolerated and as effective as vancomycin, each in combination with aztreonam.

Acetamides↗
PubMed2002

Linezolid versus ceftriaxone/cefpodoxime in patients hospitalized for the treatment of Streptococcus pneumoniae pneumonia.

Intravenous (i.v.) to oral linezolid (600 mg twice daily for both, with optional aztreonam) and a cephalosporin regimen (i.v. ceftriaxone 1 g twice daily followed by oral cefpodoxime 200 mg twice daily) were compared for the treatment of community-acquired pneumonia (CAP), with emphasis on patients with Streptococcus pneumoniae. This multicenter, randomized, open-label trial was conducted in 27 countries in 6 continents. Efficacy was assessed 12-28 d following treatment. Clinical and laboratory safety assessments were evaluated; isolates for microbiologic assessments were identified primarily by sputum or blood culture. In all treated patients (linezolid, n = 381; ceftriaxone/cefpodoxime, n = 366), linezolid had a higher clinical cure rate than ceftriaxone/cefpodoxime (83.0% vs. 76.4%, respectively; p = 0.040). S. pneumoniae was isolated in 73.2% (186/254) of patients at baseline, with similar eradication rates in the linezolid and ceftriaxone/cefpodoxime groups (88.7% vs. 89.9%, respectively; p = 0.830). Linezolid had a superior clinical cure rate (93.1% vs. 68.2%; p = 0.021) in patients with S. pneumoniae bacteremia. Logistic regression analyses revealed that linezolid-treated patients with bacteremia, pleural effusion, cardiac comorbidities, diabetes or abnormal white blood cell counts had significantly better outcomes than cephalosporin-treated patients. Both regimens were well tolerated, although the incidence of drug-related adverse events was higher in the linezolid group than in the ceftriaxone/cefpodoxime group (21.3% vs. 11.2%, respectively; p = 0.0002). In summary, empiric i.v./oral linezolid was more effective than ceftriaxone/cefpodoxime in patients hospitalized with CAP, with comparable cure rates in S. pneumoniae pneumonia and higher cure rates in pneumonia complicated by bacteremia.

Acetamides↗
PubMed2006

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.

Acetamides↗
PubMed2005

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).

Acetamides↗
PubMed2002

A multicenter evaluation of linezolid antimicrobial activity in North America.

Overall, 141 centers in North America enrolled in this international surveillance study designed to evaluate the in vitro antimicrobial activity and spectrum of linezolid, a new oxazolidinone. Each participant tested the susceptibility of clinical isolates of staphylococcal species (n = 85) against 12 drugs, and enterococcal species (n = 40) against 6 drugs using reference broth microdilution trays; and of streptococcal species (n = 25) against 6 drugs using Etests (AB BIODISK, Solna, Sweden). Quality control testing was conducted using recommended strains, and verification of resistance to linezolid and select other agents was performed by a regional monitor. Of the 20,161 isolates collected from sites across the United States (US; n = 132) and Canada (n = 9), 18,307 were included in this analysis. Oxacillin resistance occurred in 38.7 and 70.6% of Staphylococcus aureus and coagulase-negative staphylococcal (CoNS) isolates, respectively. Vancomycin resistance was reported in 65.9 and 2.6% of Enterococcus faecium and E. faecalis, respectively. Penicillin resistance occurred in 37.2% of Streptococcus pneumoniae, 17.5% constituting high-level resistance (MIC, > or =2 microg/ml). The MIC(90) for linezolid was 1 microg/ml for streptococci, 2 microg/ml for enterococci and CoNS isolates, and 4 microg/ml for S. aureus. Using the US FDA-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance (i.e., MIC > or =8 microg/ml). The occurrence of linezolid MICs was unimodal and generally varied between, 1-4 microg/ml for staphylococci (94% of recorded results), 1-2 microg/ml for enterococci (93%), and 0.5-1 microg/ml for streptococci (85%). Susceptibility to linezolid was not influenced by susceptibility to other antiicrobials such as vancomycin, beta-lactams or macrolides. Only linezolid was universally active against essentially all tested Gram-positive specimens. The unimodal susceptibility pattern is indicative of excellent and near complete activity against key Gram-positive pathogens including multiply resistant strains, but surveillance for emerging resistances (rare) and the performance of routine susceptibility tests to guide patient therapy seems prudent.

Acetamides↗
PubMed2002

Multicentre assessment of linezolid antimicrobial activity and spectrum in Europe: report from the Zyvox antimicrobial potency study (ZAPS-Europe).

OBJECTIVE: To evaluate the in vitro spectrum and activity of linezolid, a recent oxazolidinone, according to well-controlled surveillance data from 42 medical centers in 13 countries throughout Europe. METHODS: Participants tested the susceptibility of 125 clinical strains of enterococcal and staphylococcal species against 13 drugs using reference broth microdilution trays or the standardized disk diffusion method of the National Committee for Clinical Laboratory Standards (NCCLS). Streptococcal species (n = 25 at each center) were tested against six drugs using E test (AB BIODISK, Solna, Sweden). Quality assurance testing was conducted using NCCLS-recommended strains and verification of resistance to linezolid and other selected agents was performed by retesting strains at the regional (Europe) and international (USA) monitor sites. RESULTS: A total of 5598 strains from throughout Europe (91% compliance) were tested. Vancomycin resistance was reported in only 0.6 and 3.0% of Enterococcus faecalis and E. faecium, respectively. Penicillin resistance occurred in 25.1% of Streptococcus pneumoniae; 4.9% at the high-level (> or =2 mg/L). The MIC90 for linezolid was 1 mg/L for streptococci and 2 mg/L for enterococci and staphylococci. Using the US FDA- and EUCAST-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance [minimum inhibitory concentration (MIC), > or =8 mg/L]. The distribution of linezolid MIC values was unimodal and varied between 0.25 and 1 mg/L for streptococci (>90% of isolates), and between 1 and 2 mg/L for staphylococci (>90%) and enterococci (>95%). There were no differences in linezolid susceptibility in the vancomycin-, oxacillin-, or penicillin-resistant subsets of strains when compared to susceptible organism populations. CONCLUSIONS: Compared to the North American component of this study, there was substantially less vancomycin resistance among E. faecium isolates (Europe 3.0% vs. North America 63.4%). While the occurrence of penicillin-resistant S. pneumoniae in Europe and North America was similar (25.1% vs. 29.7%), the recovery of high-level penicillin-resistant strains was nearly three-fold higher in North America (4.9% vs. 13.2%). Only linezolid was universally active against all the tested Gram-positive isolates at </=4 mg/L.

Acetamides↗
PubMed2006

Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer.

BACKGROUND: Gram-positive pathogens can cause serious infections in neutropenic patients with cancer, and vancomycin therapy is often initiated empirically. Linezolid may offer an option for these patients. METHODS: To compare the safety and efficacy of linezolid and vancomycin in febrile, neutropenic patients with cancer, we conducted a double-blind, multicenter equivalence study. Eligible patients with proven or suspected infection due to a gram-positive pathogen were randomized to receive linezolid or vancomycin. RESULTS: Clinical success rates 7 days after completion of therapy (primary end point) were equivalent between groups in the intent-to-treat (ITT) analysis (linezolid, 219 [87.3%] of 251 patients; vancomycin, 202 [85.2%] of 237 patients; 95% CI, -4.1 to 8.1; P=.52), modified ITT analysis, clinically evaluable analysis, and microbiologically evaluable analysis, as well as between subsets analyzed by malignancy and infection type. Mean time to defervescence was shorter for linezolid than vancomycin in the modified ITT (6.6 vs. 8.5 days; P=.04) and microbiologically evaluable subsets (5.9 vs. 9.1 days; P=.01), although post hoc analyses revealed delayed recovery of absolute neutrophil counts for linezolid in these subsets (P<.05). There were no between-group differences in microbiologic success rates in the modified ITT subset (41 [57.7%] of 71 patients vs. 29 [50.0%] of 58 patients; P=.38) and microbiologically evaluable subsets, as well as in mortality rates in the ITT subset (17 [5.6%] of 304 patients vs. 23 [7.6%] of 301 patients; P=.31) and all subsets. Distribution of adverse events, including reported hematologic events, was similar between groups, except that linezolid was associated with fewer drug-related adverse events (52 [17.2%] of 303 patients vs. 72 [24.0%] of 300 patients; P=.04) and fewer cases of drug-related renal failure (1 [0.3%] of 303 patients vs. 7 [2.3%] of patients; P=.04). CONCLUSIONS: Linezolid demonstrated efficacy and similar safety outcomes equivalent to those for vancomycin in febrile neutropenic patients with cancer.

Acetamides↗
PubMed2003

Safety, efficacy and pharmacokinetics of linezolid for treatment of resistant Gram-positive infections in cancer patients with neutropenia.

BACKGROUND: Linezolid is a recently approved oxazalidinone with extended activity against Gram-positive bacteria. We evaluated the results of linezolid therapy in neutropenic cancer patients with Gram-positive bacterial infections from a compassionate-use program. PATIENTS AND METHODS: This was a prospective, multicenter, open-label, non-comparative, non-randomized compassionate-use treatment program in patients with serious Gram-positive infections. To qualify for enrollment patients were required to have an infection resistant to available antimicrobial agents, or in whom available agents had failed or to which they were intolerant. Patients with absolute neutrophil counts (ANC) <500 cells/mm(3) or <1000 cells/mm(3) and expected to decrease to <500 cells/mm(3), and who received linezolid 600 mg twice daily were included. Plasma samples for population pharmacokinetic analysis were collected. Clinical and microbiological assessments of outcomes were made at the end of therapy and at short-term follow-up. RESULTS: Of the patients in the compassionate-use trial, 103 were neutropenic. The mean [standard deviation (SD)] age was 50.1 (17.5) years, 47% were female, and 47.6% had a baseline ANC </=100 cells/mm(3). The mean (SD) duration of linezolid therapy was 14.6 (11.4) days. The most common site of infection was the bloodstream (90.3%), and the most commonly identified pathogen was vancomycin-resistant Enterococcus faecium (83%). A total of 83 (80.5%) and 52 (50.4%) patients were evaluable for clinical and microbiological outcomes at the end of therapy, respectively. Clinical and microbiological cure rates in the evaluable patients were 79% and 86%, respectively. Linezolid was well-tolerated in this patient population, with an overall adverse event rate of 17.5%; 5% of patients required discontinuation of the drug due to side-effects. The pharmacokinetics of linezolid in patients with neutropenia did not differ from the overall compassionate-use population. CONCLUSIONS: Linezolid was safe and effective in treating resistant Gram-positive infections in neutropenic cancer patients. Comparative clinical trials to evaluate further the effectiveness and safety of linezolid in this patient population are warranted.

Acetamides↗
PubMed2005

Clinical audit of linezolid use in a large teaching hospital.

OBJECTIVES: Linezolid, the first available agent in the new class of oxazolidinone antibiotics, represents a significant advance in the management options available for combating methicillin-resistant Staphylococcus aureus (MRSA) infections. In the UK it was launched for clinical use in 2001. The aim of this study was to audit the clinical use of linezolid and compliance with the guidelines of the hospital antibiotic committee. METHODS: Our hospital antibiotic committee agreed clinical indications for linezolid use. We undertook an audit of compliance with these recommendations and also reviewed its use in terms of the source of infection, microbiology, duration of therapy, side-effects and choice of previous treatment. RESULTS: Seventy-seven inpatients prescribed linezolid in Ninewells Hospital in the 3 years between March 2001 and September 2003 were audited. Overall compliance with our local recommendations appears to be very good. The main justification for using linezolid is the presence of existing or worsening renal dysfunction or poor venous access (34%) or lack of tolerance or clinical failure following glycopeptide monotherapy or combination therapy (32%). Skin and soft tissue infections (26%) were the most frequently diagnosed infections, although an increasing number of patients appear to receive linezolid for the treatment of lower respiratory tract infections, primarily in the ICU for nosocomial or ventilator-associated pneumonia. MRSA organisms were the most common cause of microbiologically proven treated infections [n = 43 (56%)]. Disappointingly, only 34 out of 77 patients had case record documentation of prior approval by an infection specialist. CONCLUSIONS: The use of linezolid in our hospital appears to follow local guidelines, but the quality of information recorded in the notes could be optimized. Consequently, a linezolid mandatory order form to be completed by the attending prescribing clinician has been introduced, and will be subject to future evaluation. We recommend such specific antibiotic utilization reviews or audits of new agents introduced into clinical infection practice.

Acetamides↗
PubMed2005

In vitro selection of mutants of Streptococcus pneumoniae resistant to macrolides and linezolid: relationship with susceptibility to penicillin G or macrolides.

OBJECTIVES: To evaluate the rate of acquisition of resistance to linezolid and macrolides in Streptococcus pneumoniae isolates with different levels of susceptibility to penicillin and erythromycin. MATERIALS AND METHODS: Thirty strains of S. pneumoniae were tested by serial passages in subinhibitory concentrations of each antibiotic by the spiral method. The four copies of the 23S rRNA rrl gene of parent strains and linezolid-resistant mutants were amplified and sequenced. RESULTS: The rate of acquisition of macrolide resistance did not differ when C-14 and C-16 macrolides were tested. Resistance to linezolid in strains susceptible to penicillin and erythromycin was difficult to produce. For mutants with low-level resistance to linezolid the cut-off value of the MIC was between 6 and 8 mg/L depending on the strain. All linezolid-resistant mutants displayed a mutation in 2-4 copies of the 23S rRNA rrl gene, mainly the G2576U mutation (27/30) with an additional C2610U mutation observed in certain mutants. Two new mutations were also noted, namely C2612A and C2571G. In three linezolid-resistant mutants no mutation was identified within the studied domain, suggesting another mechanism of resistance. CONCLUSIONS: Linezolid resistance in pneumococcal strains susceptible to penicillin and macrolides was more difficult to obtain than with macrolides. Increased resistance to these agents may therefore influence the clinical use of linezolid.

Acetamides↗
PubMed2005

Linezolid versus vancomycin for Staphylococcus aureus bacteraemia: pooled analysis of randomized studies.

OBJECTIVES: To compare outcomes in patients with Staphylococcus aureus bacteraemia treated with linezolid with those of vancomycin-treated patients. METHODS: We pooled and analysed five randomized studies comparing linezolid with vancomycin, focusing on the 144 adults with S. aureus bacteraemia, which was secondary in >70% of patients. Efficacy variables were clinical cure of primary infection, microbiological success (eradication of S. aureus from blood or presumed eradication based on clinical cure of primary infection), survival, and outcome predictors identified by multivariate logistic regression. RESULTS: Of 99 clinically evaluable patients, primary infection was cured in 28 (55%) of 51 linezolid recipients and 25 (52%) of 48 vancomycin recipients [odds ratio (OR) for cure with linezolid versus vancomycin, 1.12; 95% confidence interval (CI), 0.51-2.47]. There were no between-group differences in the meta-analysis (OR, 1.16; 95% CI, 0.5-2.65). Of 53 evaluable patients with methicillin-resistant S. aureus (MRSA) bacteraemia, clinical cure occurred in 14 (56%) of 25 linezolid recipients and 13 (46%) of 28 vancomycin recipients (OR, 1.47; 95% CI, 0.50-4.34). Microbiological success occurred in 41 (69%) of 59 linezolid recipients and 41 (73%) of 56 vancomycin recipients (OR, 0.83; 95% CI, 0.37-1.87). Fifty-five (74%) of 74 linezolid recipients survived versus 52 (74%) of 70 vancomycin recipients (OR, 1.00; 95% CI, 0.47-2.12). In the multivariate analysis, treatment group was not a significant predictor of clinical cure or survival. CONCLUSIONS: Linezolid was associated with outcomes that were not inferior to those of vancomycin in patients with secondary S. aureus bacteraemia.

Acetamides↗
PubMed2000

Single dose pharmacokinetics of linezolid in infants and children.

BACKGROUND: Linezolid is an oxazolidinone antibiotic with excellent in vitro activity against a number of Gram-positive organisms including antibiotic-resistant isolates. The safety and pharmacokinetics of intravenously administered linezolid were evaluated in children and adolescents to examine the potential for developmental dependence on its disposition characteristics. METHODS: Fifty-eight children (3 months to 16 years old) participated in this study; 44 received a single 1.5-mg/kg dose and 14 received a single 10-mg/kg dose of linezolid administered by intravenous infusion. Repeated blood samples (n = 10 in children > or = 12 months; n = 8 in children 3 to 12 months) were obtained during 24 h after drug administration, and linezolid was quantitated from plasma by high performance liquid chromatography with mass spectrometry detection. Plasma concentration vs. time data were evaluated with a model independent approach. RESULTS: Linezolid was well-tolerated by all subjects. The disposition of linezolid appears to be age-dependent. A significant although weak correlation between age and total body clearance was observed. The mean (+/- SD) values for elimination half-life, total clearance and apparent volume of distribution were 3.0 +/- 1.1 h, 0.34 +/- 0.15 liter/h/kg and 0.73 +/- 0.18 liter/kg, respectively. Estimates of total body clearance and volume of distribution were significantly greater in children than historical values of adult data. As such maximum achievable linezolid plasma concentrations were slightly lower in children, and concentrations 12 h after a single 10-mg/kg dose were below the MIC90 for selected pathogens with in vitro susceptibility to the drug. CONCLUSION: Based on these data a linezolid dose of 10 mg/kg given two to three times daily would appear appropriate for use in pediatric therapeutic clinical trials of this agent.

Acetamides↗
PubMed2004

Successful treatment of chronic bone and joint infections with oral linezolid.

Linezolid is an attractive alternative for the treatment of chronic bone and joint infections because it is active against common pathogens including methicillin-resistant staphylococci and vancomycin-resistant enterococci and because its oral formulation is convenient for long-term administration. To evaluate the ability of linezolid to produce long-term remission, we prospectively monitored 11 consecutive adult patients who received linezolid for osteomyelitis (n = 9) or prosthetic joint infection (n = 2). Linezolid 600 mg was administered orally twice daily for a mean of 10 weeks (range, 6 to 19 weeks). Pathogens were methicillin-resistant Staphylococcus aureus (n = 5), methicillin-resistant coagulase-negative staphylococci (n = 4), vancomycin-resistant Enterococcus faecium (n = 1), and vancomycin-sensitive Enterococcus faecalis (n = 1). After a mean followup of 27 months (range, 17 to 41 months), all 11 patients had remission by clinical, laboratory, and radiographic criteria. During week 8 of linezolid treatment, one patient developed a gram-negative superinfection, which resolved with appropriate therapy. During week 6 of linezolid treatment, one patient developed mild thrombocytopenia and another patient developed mild anemia. Both episodes of myelosuppression were reversible within 10 days after completing the planned 6-week courses of linezolid. We recommend weekly complete blood counts to detect hematologic abnormalities. We conclude that oral linezolid seems to be a useful and convenient alternative for the treatment of bone and joint infections.

Acetamides↗