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Preliminary experience with the use of oral linezolid in infants for the completion of antibiotic therapy in the outpatient setting after admission to the pediatric intensive care unit.

Advances in medical technology have led to improved survival after catastrophic illnesses. Many of the survivors require ongoing care including tracheostomy, mechanical ventilation, tube feedings, and indwelling venous catheters. Repeated hospitalizations may be necessary to treat infectious complications resulting from resistant organisms requiring intravenous antibiotic therapy. Because prolonged intravenous access may be difficult or even impossible in these patients, alternative means of therapy are necessary. Linezolid is the first of a new class of antimicrobial agents known as the oxazolidinones with activity against gram-positive bacteria similar to that of vancomycin and yet its oral bioavailability allows for enteral administration. We present our retrospective experience with oral linezolid in a cohort of pediatric intensive care unit patients. Primary infectious disease issues included endocarditis, tracheitis, pneumonia, or central line sepsis resulting from Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus, and Enterococcus. Treatment was initiated with vancomycin and changed to enteral linezolid (10 mg/kg every 12 hours). The duration of therapy with linezolid varied from 7 days to 6 weeks. All of the patients were discharged home to complete their course of enteral linezolid. No complications related to linezolid therapy were noted, and all of the patients completed their prescribed course of therapy without the need for rehospitalization. Our preliminary experience suggests that oral linezolid offers an effective alternative to intravenous vancomycin for the treatment of infections resulting from gram-positive bacteria and avoids the need for prolonged vascular access.

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Clinical experience with linezolid in conjunction with wound coverage techniques for skin and soft-tissue infections and postoperative osteomyelitis.

Gram-positive organisms are emerging as possibly the most important nosocomial pathogens during the past decade. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infection in the postoperative patient. Burn victims are at high risk for developing vancomycin-resistant Enterococcus (VRE) and other multidrug-resistant microbial infections as a result of the immunocompromising effects of burn injury, prolonged intensive care unit stays, and broad-spectrum antibiotic therapy. To prevent serious and dreaded complications such as skin graft breakdown, delayed wound healing, loss of a limb, and even death, these infections require a combination of extensive antibiotic therapy and plastic surgical intervention. The objectives of this study were to report clinical experience with linezolid in addition to wound care, debridement, and wound coverage techniques for the treatment of S. aureus (including MRSA) and VRE infections. Forty patients received linezolid for infections of wound coverage such as an infected graft or flap, or received linezolid in conjunction with wound coverage techniques for a S. aureus or VRE infection. The median patient age was 53 years (range, 14-85 years), 55% were female, 28% of patients received intravenous (i.v.) linezolid only, 45% received i.v. with a switch to the oral formulation, and 28% received the oral formulation only. The clinical success rate of linezolid with adjuvant wound coverage techniques was 90.0% for osteomyelitis and was 100% for skin and soft-tissue infections. For infections of wound coverage, the clinical success rate was 83.3%. In conclusion, linezolid was an effective antibiotic for the treatment of S. aureus (including MRSA) and VRE infections in conjunction with wound coverage techniques. In addition, linezolid offers the option of treating these infections with an oral agent that is 100% bioavailable.

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Activity of linezolid against Gram-positive cocci isolated in French hospitals as determined by three in-vitro susceptibility testing methods.

In total, 844 strains of Gram-positive cocci were collected from six university hospitals in France between September 1999 and January 2000. MICs of linezolid were determined: (i) for all strains by agar dilution (method A); (ii) by broth microdilution (method B) for staphylococci and enterococci; (iii) by Etest (method E) for beta-haemolytic streptococci and Streptococcus pneumoniae. Susceptibility to other antibiotics was determined by the disk diffusion method. MIC50 and MIC90 values were identical (2 mg/L) for methicillin-susceptible Staphylococcus aureus (n = 179) by methods A and B. Linezolid was active against methicillin-resistant S. aureus (n = 117), with an MIC90 of 2 mg/L (methods A and B), but with a lower MIC50 of 1 mg/L by method A. Of the 200 coagulase-negative staphylococci, 56.5% were methicillin-resistant and 43.5% were methicillin-susceptible. Linezolid had similar in-vitro activity by methods A and B (MIC50 and MIC90 values of 1-2 mg/L), irrespective of methicillin susceptibility. The MIC90 of linezolid for all enterococci (150 Enterococcus faecalis and 50 Enterococcus faecium) was 2 mg/L by both methods. MICs of linezolid for beta-haemolytic streptococci had a narrow range of 0.5-2 mg/L (method A) and 0.125-2 mg/L (method E). Pneumococci (n = 118), including 67 penicillin G-intermediate and -resistant strains, were all inhibited by linezolid 2 mg/L (MIC90 of 2 mg/L by methods A and E). No strain had an MIC of > 2 mg/L by agar dilution or Etest, or of > 4 mg/L by broth microdilution. Overall, the study confirmed the good in-vitro activity of linezolid and the very narrow range of MICs for Gram-positive cocci susceptible or resistant to other antibiotics, irrespective of the method used.

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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.

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Subinhibitory concentrations of linezolid reduce Staphylococcus aureus virulence factor expression.

The influence of the antibiotic linezolid on the secretion of exotoxins by Staphylococcus aureus was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry and Western blot analysis. S. aureus suspensions were treated with grading subinhibitory concentrations of linezolid (12.5, 25, 50, and 90% of MIC) at different stages of bacterial growth (i.e., an optical density at 540 nm [OD(540)] of 0.05 or 0.8). When added to S. aureus cultures at an OD(540) of 0.05, linezolid reduced in a dose-dependent manner the secretion of specific virulence factors, including staphylococcal enterotoxin A (SEA) and SEB, bifunctional autolysin, autolysin, protein A, and alpha- and beta-hemolysins. In contrast, other presumably nontoxic exoproteins remained unchanged or even accumulated in supernatants in the presence of linezolid at a 90% MIC. Similarly, when added at OD(540) of 0.8, that is, after quorum sensing, linezolid reduced the release of virulence factors, whereas the relative abundance of nontoxic exoproteins such as triacylglycerol lipase, glycerol ester hydrolase, DnaK, or translation elongation factor EF-Tu was found to be increased. Consistently, linezolid reduced in a dose-dependent manner the tumor necrosis factor-inducing activity secreted by S. aureus into the culture supernatants. The results of our study suggest that the expression of virulence factors in S. aureus is especially sensitive to the inhibition of protein synthesis by linezolid, which should be an advantage in the treatment of infections with toxin-producing S. aureus.

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In vitro and in vivo synergistic activities of linezolid combined with subinhibitory concentrations of imipenem against methicillin-resistant Staphylococcus aureus.

Indifference or moderate antagonism of linezolid combined with other antibiotics in vitro and in vivo have mainly been reported in the literature. We have assessed the in vitro activities of linezolid, alone or in combination with imipenem, against methicillin-resistant Staphylococcus aureus (MRSA) strains using the dynamic checkerboard and time-kill curve methods. Linezolid and low concentrations of imipenem had a synergistic effect, leading us to evaluate the in vivo antibacterial activity of the combination using the rabbit endocarditis experimental model. Two MRSA strains were used for in vivo experiments: one was a heterogeneous glycopeptide-intermediate clinical S. aureus strain isolated from blood cultures, and the other was the S. aureus COL reference strain. Animals infected with one of two MRSA strains were randomly assigned to one of the following treatments: no treatment (controls), linezolid (simulating a dose in humans of 10 mg/kg of body weight every 12 h), a constant intravenous infusion of imipenem (which allowed the steady-state concentration of about 1/32 the MIC of imipenem for each strain to be reached in serum), or the combination of both treatments. Linezolid and imipenem as monotherapies exhibited no bactericidal activity against either strain. The combination of linezolid plus imipenem showed in vivo bactericidal activity that corresponded to a decrease of at least 4.5 log CFU/g of vegetation compared to the counts for the controls. In conclusion, the combination exhibited synergistic and bactericidal activities against two MRSA strains after 5 days of treatment. The combination of linezolid plus imipenem appears to be promising for the treatment of severe MRSA infections and merits further investigations to explore the mechanism underlying the synergy between the two drugs.

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Linezolid-induced optic neuropathy: a mitochondrial disorder?

We report a case of bilateral mitochondrial optic neuropathies secondary to long-term linezolid treatment, show the nature of recovery, review the findings in the literature and propose a potential mitochondrial mechanism for linezolid-induced mitochondrial optic neuropathy. This is an observational case report and literature review with presentation of the clinical course of linezolid mitochondrial optic neuropathies through clinical and psychophysical documentation. Main outcome measures included: visual acuity, funduscopical examinations and peripapillary retinal nerve fibre layer (PRNFL) optical coherence tomography (OCT). A 6-year-old boy presented with bilateral optic neuropathies secondary to 1 year of linezolid treatment for osteomyelitis of the mandible. On presentation, visual acuities were 20/400 in both eyes, with considerable optic disc oedema, hyperaemia and PRNFL swelling confirmed by OCT. 2 weeks after the discontinuation of linezolid, visual acuities returned to 20/25 in both eyes, with reduction in the optic disc oedema, hyperaemia and PRNFL swelling. 3 months after the discontinuation of linezolid treatment, visual acuities were stable at 20/20 in both eyes, with a marked decrease in PRNFL swelling confirmed by OCT, and the development of mild temporal optic disc pallor in both eyes. Doctors should be aware of impairments of vision among patients on long-term linezolid treatment and promptly discontinue treatment to prevent irreversible vision loss. The development and resolution of bilateral optic neuropathies with considerable PRNFL swelling in this patient provide insight into the more general rubric of mitochondrial optic neuropathies.

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Linezolid, a novel oxazolidinone antibiotic: assessment of monoamine oxidase inhibition using pressor response to oral tyramine.

The primary objective of this study was to compare the effects of oral linezolid with moclobemide and placebo on the pressor response to oral tyramine. Secondary objectives were to determine possible mechanisms of the effect based on changes in the pharmacokinetics of tyramine and to evaluate alternative methods for quantifying the pressor effect. Subjects received linezolid (625 mg bid orally), moclobemide (150 mg tid orally), or placebo for up to 7 days. Using the oral tyramine dose producing a >30 mmHg increase in systolic blood pressure (SBP) (PD>30), a positive pressor response was defined as a PD>30 index (pretreatment/treatment ratio of PD>30) of > or = 2. There were 8/10, 11/11, and 1/10 responders with linezolid, moclobemide, and placebo, respectively. Responses returned to baseline within 2 days of drug discontinuation. The ratio of mean greatest SBP and heart rate at the time of greatest SBP (GSBP/HR) increased linearly with tyramine dose both pretreatment and during treatment with linezolid and moclobemide. During treatment, responses to tyramine when subjects took linezolid or moclobemide were significantly different from placebo. Both drugs significantly decreased tyramine oral clearance compared with placebo. Urinary excretion of catecholamines and metabolites was consistent with MAOI activity of the drugs, but results were variable. The MAOI activity of linezolid is similar to that of moclobemide, a drug used clinically without food restrictions. Restrictions to normal dietary intake of tyramine-containing foods are not warranted when taking linezolid.

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Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr.

Linezolid is a novel oxazolidinone antibiotic with mild reversible monoamine oxidase inhibitor (MAOI) activity. The potential for interaction with over-the-counter (OTC) medications requires quantification. The authors present data evaluating the pharmacokinetic and pharmacodynamic responses to coadministration of oral linezolid with sympathomimetics (pseudoephedrine and phenylpropanolamine) and a serotonin reuptake inhibitor (dextromethorphan). Following coadministration with linezolid, minimal but statistically significant increases were observed in pseudoephedrine and phenylpropanolamine plasma concentrations; a minimal but statistically significant decrease was observed in dextrorphan (the primary metabolite of dextromethorphan) plasma concentrations. Increased blood pressure (BP) was observed following the coadministration of linezolid with either pseudoephedrine or phenylpropanolamine; no significant effects were observed with dextromethorphan. None of these coadministered drugs had a significant effect on linezolid pharmacokinetics. Minimal numbers of adverse events were reported. Potentiation of sympathomimetic activity by linezolid was judged not to be clinically significant, but patients sensitive to the effects of increased BP due to predisposing factors should be treated cautiously. No restrictions are indicated for the coadministration of dextromethorphan and linezolid.

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A pharmacokinetic evaluation of concomitant administration of linezolid and aztreonam.

Linezolid, a new oxazolidinone antimicrobial agent, has a spectrum of activity encompassing a wide variety of Grampositive bacteria. The purpose of this study was to evaluate the pharmacokinetics of linezolid and aztreonam, an antimicrobial agent with selective activity against Gram-negative bacteria, when given alone and in combination. Healthy subjects were randomized to receive single, 30-minute intravenous infusions of (1) linezolid 375 mg, (2) aztreonam 1000 mg, and (3) linezolid 375 mg plus aztreonam 1000 mg in an open-label, crossover manner. The only statistically significant differences observed with combination treatment relative to each drug alone were an increase in the maximum plasma concentration of linezolid (approximately 18%) and an approximate 7% decrease in the apparent elimination rate of aztreonam, neither of which are expected to be clinically significant. In healthy subjects, the combination of linezolid and aztreonam was safe and well tolerated compared with each agent used alone. Pharmacokinetic data demonstrate that coadministration of linezolid and aztreonam does not alter the disposition of either agent under single-dose conditions. Therefore, it is not expected that a dose alteration of either agent will be necessary in a clinical setting.

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Elimination of linezolid by an in vitro extracorporeal circuit model.

Linezolid is an oxazolidinone antibiotic with activity against important grampositive aerobic bacteria, including nosocomial pathogens. It is not known whether dosage adjustments are necessary in patients treated with continuous renal replacement therapies. This in vitro study was conducted to investigate the elimination of linezolid in an in vitro continuous hemo(dia)filtration model using different filter materials (polysulfone, polyacrylonitrile, polyamide), surface areas, and different modes of renal replacement therapies. Linezolid was measured using HPLC with UV-detection. No adsorption of linezolid to any of the tested membranes was detected. Recovery of linezolid in the ultrafiltrate was 98.2 +/- 10.5% in the filtration mode. During dialysis, recovery was significantly less (87.6 +/- 16.1%; p = 0.02). Linezolid elimination was not altered by filter size, when polysulfone filters with surface areas of 0.7 m2 and 1.3 m2 were tested. In conclusion, the dosage recommendations for linezolid are independent of the filter materials. However, the elimination is significantly higher during hemofiltration compared to dialysis.

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Comparative in vitro activity of PH-027 versus linezolid and other anti-anaerobic antimicrobials against clinical isolates of Clostridium difficile and other anaerobic bacteria.

PH-027 is a new 5-triazole oxazolidinone synthesized in our laboratories, which shows strong activity against gram-positive aerobic bacteria including clinical isolates. The objective of this study was to investigate the in vitro activity of this compound in comparison with linezolid and other antibiotics against gram-positive and gram-negative anaerobes. The in vitro activity of PH-027 in comparison with those of linezolid and other antimicrobial agents was evaluated against 201 clinical isolates of gram-positive and gram-negative anaerobic bacteria by agar dilution and Etest methods. PH-027 showed excellent activity, with minimum inhibitory concentrations (MIC) in the range of 0.12-4.0 microg/ml against all isolates; MIC90s being 4.0, 1.0, 2.0, 2.0 and 2.0 microg/ml against Clostridium difficile, Peptostreptococcus spp., Bacteroides fragilis, Prevotella bivia and Fusobacterium spp. respectively. In comparison, linezolid had MIC in the range of 0.5-4.0 microg/ml against all isolates, with MIC90s of 2.0, 4.0, 4.0, 4.0 and 2.0 microg/ml against the same set of bacteria respectively. PH-027 demonstrated excellent in vitro activity that is superior to linezolid against Peptostreptococcus spp., B. fragilis and P. bivia. However, against C. difficile and Fusobacterium spp, PH-027 and linezolid showed comparable in vitro activity. Against all anaerobes, metronidazole, PH-027 and, to a lesser extent, linezolid had the most potent activity. From the results of in vitro susceptibility testing, both linezolid and PH-027 show promise in the treatment of anaerobic infections.

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The effectiveness and safety of oral linezolid for the primary and secondary treatment of osteomyelitis.

The pharmacokinetic profile of oral linezolid makes it an attractive alternative for the treatment of osteomyelitis. Few studies have described the efficacy of linezolid in the treatment of osteomyelitis. A retrospective, observational analysis was conducted at Edward Hines, Jr. VA Hospital. Patients who received oral linezolid from June 2000 to December 2002 were identified from pharmacy records. Forty-two patients who received oral linezolid for osteomyelitis at our institution were identified. Only patients who had received at least six weeks of linezolid therapy were evaluated for clinical effectiveness. Patients were also evaluated for adverse drug reactions due to linezolid. The clinical cure rate was 55% for the 20 patients who received at least six weeks of therapy. Adverse events included gastrointestinal disturbances (15%), thrombocytopenia (10%), anemia (10%), neutropenia (5%) and rash (5%). The authors conclude that oral linezolid is an alterative to intravenous antibiotics for the treatment of osteomyelitis.

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Mechanisms for linezolid-induced anemia and thrombocytopenia.

BACKGROUND: Linezolid has been associated with anemia and thrombocytopenia. Mechanisms for neither have been elucidated. OBJECTIVE: To propose mechanisms for linezolid-induced anemia and thrombocytopenia. CASE SUMMARY: A 78-year-old white woman with Staphylococcus epidermidis endocarditis was treated with linezolid after developing resistance to multiple antibiotic regimens. After 7 days of linezolid therapy, she developed thrombocytopenia, while an anemia present since admission remained unchanged. A bone marrow biopsy was performed, primarily looking for a mechanism for the thrombocytopenia. Histopathology revealed adequate megakaryocytes, ringed sideroblasts, and vacuolated pronormoblasts. A course of immune globulin (IVIG) was administered, with slowing in the rate of decline in platelets. She died 24 hours after her last dose of IVIG of congestive heart failure. DISCUSSION: The presence of ringed sideroblasts and vacuolated pronormoblasts suggests that linezolid-induced anemia is secondary to a chloramphenicol-like suppression of erythropoiesis. The presence of adequate, normal-appearing megakaryocytes suggests immune-mediated thrombocytopenia, not marrow suppression. Although the response to IVIG is difficult to interpret because of the patient's death, there was a slowing in the rate of decline of the platelet count, further supporting immune-mediated thrombocytopenia. An objective causality assessment indicated that the adverse drug event was probably due to linezolid. CONCLUSIONS: There appear to be 2 distinct mechanisms for linezolid-induced cytopenias. While anemia is reversible and manageable with transfusions, thrombocytopenia can be a treatment-limiting toxicity. The ability to treat through an immune-mediated cytopenia with IVIG may be beneficial for critically ill patients with few therapeutic options.

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Linezolid resistance since 2001: SENTRY Antimicrobial Surveillance Program.

BACKGROUND: The oxazolidinone class of antimicrobials has demonstrated remarkable activity against gram-positive cocci. Linezolid has proven to be a first-line therapeutic option for vancomycin-resistant strains. Linezolid clinical trial results and subsequent published case reports cite rare resistance emerging in patients receiving prolonged therapy. OBJECTIVE: To report the initial linezolid-resistant organisms from cases obtained through the SENTRY Antimicrobial Surveillance Program, after screening >40,000 gram-positive cocci without resistance between 1998 and 2000. METHODS: During 2001-2002, 8 resistant strains (from 8 different patients) located in 6 states from 7 different participating SENTRY institutions in the US were identified among bloodstream, respiratory, skin and soft tissue, and urinary tract infection isolates of Enterococcus faecalis, Enterococcus faecium, Staphylococcus epidermidis, and Streptococcus oralis. Resistance was detected by reference broth microdilution methods and confirmed by identical results using Etest (AB BIODISK, Solna, Sweden) and the standardized disk diffusion method. RESULTS: Minimum inhibitory concentration (MIC) and disk diffusion tests showed elevated MICs (> or =8 microg/mL) and small inhibitory zone diameters (< or =15 mm) for all strains to both linezolid and the investigational oxazolidinone AZD2563. Vancomycin resistance was detected in 2 of the 8 linezolid-resistant strains. All enterococci and the viridans-group streptococcus (S. oralis) strain showed resistance to erythromycin. E. faecium strains were resistant to penicillins, but susceptible to quinupristin/dalfopristin. Only 3 of the patients had previously received the drug. CONCLUSIONS: Linezolid resistance remains rare, with only 8 isolates among 9833 (0.08%) monitored isolates identified between January 1, 2001, and June 30, 2002. Resistance, however, was no longer limited to enterococci. Clinical laboratories should test linezolid more widely to detect emerging resistance, especially for patients receiving oxazolidinone therapy. Longitudinal surveillance programs are warranted to detect a trend in the development of resistance, determine the molecular mechanism of resistance, and recommend alternative therapies or epidemiologic interventions.

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Impact of linezolid on economic outcomes and determinants of cost in a clinical trial evaluating patients with MRSA complicated skin and soft-tissue infections.

BACKGROUND: In clinical trials, linezolid has demonstrated higher clinical cure rates and shorter hospital duration for patients than has vancomycin for the treatment of complicated skin and soft-tissue infections (cSSTIs). OBJECTIVE: To assess economic outcomes of linezolid versus vancomycin and evaluate determinants of treatment costs for cSSTIs. METHODS: Economic data were obtained from US subjects enrolled in a multinational, open-label, clinical trial of cSSTIs caused by suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects were randomized to receive intravenous or oral linezolid or intravenous vancomycin for 7-21 days. Costs for each patient were evaluated by applying nationally representative per diem hospital costs by hospital ward. Intravenous administration costs were applied to the duration of intravenous treatment. Factors contributing to the cost of therapy were evaluated using multivariate regression analysis. RESULTS: Seven hundred seventeen US patients were included in the study. Demographics were similar between treatment groups. Length of stay and duration of intravenous therapy were shorter for linezolid-treated patients. Mean +/- SD cost for intent-to-treat population patients treated with linezolid versus vancomycin was 4865 US dollars +/- 4367 versus 5738 US dollars +/- 5190, respectively (p = 0.017), and in the MRSA population was 4881 US dollars +/- 3987 versus 6006 US dollars +/- 5039, respectively (p = 0.041). Factors significantly associated with increased cost included vancomycin therapy, age, and comorbidities, including diabetes. After adjusting for all other factors, treatment with linezolid was associated with significantly lower treatment costs compared with vancomycin. CONCLUSIONS: Linezolid therapy was associated with improved clinical outcomes and significantly lower treatment costs than was vancomycin. The largest cost advantage was demonstrated in patients with documented MRSA cSSTIs.

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Update on linezolid: the first oxazolidinone antibiotic.

Linezolid is the first of an entirely new class of antibiotics, the oxazolidinones, in decades. It has a spectrum of activity against virtually all important Gram-positive pathogens. The unique mechanism of action of linezolid makes cross-resistance with other antimicrobial agents unlikely. Linezolid has both intravenous and oral formulations and the latter is 100% bioavailable. Since its first approval and marketing in March 2000 in the US, linezolid has gained approval for use in many other countries for the treatment of community-acquired and nosocomial pneumonia, complicated and uncomplicated skin and soft-tissue infections, and infections caused by methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, including cases with concurrent bacteraemia. Several earlier comprehensive reviews summarised the chemistry, mechanism of action, pharmacokinetics, clinical efficacy and safety profile of linezolid. The present review provides an update on the latest data regarding the antimicrobial activity of linezolid versus other commonly used agents, the clinical and health-economic outcomes of linezolid versus vancomycin and teicoplanin, and safety issues.

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Cost-effectiveness of linezolid versus vancomycin in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant staphylococcus aureus.

UNLABELLED: Linezolid, an oxazolidinone-class antimicrobial agent, is a new drug; its use has frequently been questioned due to its high price. However, recent trials have demonstrated that the use of linezolid in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (VAP-MRSA) may be justified due to its improved efficacy compared to vancomycin. Price and cost have different magnitudes, and clinical efficacy should always be considered in the decision-making process. Our objective was to determine whether linezolid treatment was more cost-effective than vancomycin for treating VAP-MRSA. METHODOLOGY: Elaboration of an economic model from a metanalysis of previous clinical trials comparing both drugs, through a cost-effectiveness analysis. Costs of the treatments were calculated using Brazilian parameters and were compared to the results obtained in the metanalysis. In order to compare the results with real life conditions, costs were calculated for both name brand and for generic vancomycin. RESULTS: The cost (May/2004) per unit (vial, ampoule or bag) was R$ 47.73 for the name-brand vancomycin, R$ 14.45 for generic vancomycin and R$ 214.04 for linezolid. Linezolid's efficacy in VAP-MRSA according to the metanalysis was 62.2% and vancomycin's efficacy was 21.2%. The total cost per cured patient was R$ 13,231.65 for the name-brand vancomycin, R$ 11,277.59 for generic vancomycin and R$ 7,764.72 for linezolid. CONCLUSION: Despite the higher price per unit, linezolid was more cost-effective than vancomycin.

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