tedizolid and Soft-Tissue-Infections

An increase of skin and soft tissue infections involving Staphylococcus aureus has been reported in community and hospital settings. Methicillin resistance in S. aureus is associated with treatment failure and increased mortality. Recently, new antimicrobials with enhanced activity against methicillin-resistant Staph. aureus have been approved for the treatment of skin and soft tissue infections. Among these, novel oxazolidinones and lipoglycopeptides represent options with favorable pharmacokinetic characteristics and safety profiles.. Newly approved compounds include tedizolid, characterized by the availability of both oral and intravenous formulation and once daily administration and dalbavancin, a long-acting antimicrobial allowing for weekly administration. These new molecules present advantages, such as enhanced activity against multidrug-resistant Gram-positive bacteria and favorable safety profiles.. We have reviewed the pharmacokinetic characteristics and the implications for use in skin and soft tissue infections of tedizolid and dalbavancin. Advantages associated with the use of these compounds include the possibility for early patient discharge, reduced hospital length of stay, and outpatient treatment, with potential impact on morbidity, mortality, and overall health-care costs.

Topics: Administration, Intravenous; Administration, Oral; Anti-Infective Agents; Community-Acquired Infections; Cross Infection; Humans; Lipoglycopeptides; Oxazolidinones; Soft Tissue Infections; Staphylococcal Skin Infections; Teicoplanin; Tetrazoles

Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, including MRSA isolates resistant to linezolid. Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI. The comparison of adverse events is favorable to tedizolid under the circumstances of the clinical trials. This is a review of recent literature on tedizolid, its use in special populations and potential adverse effects.. Findings suggest that tedizolid can be used in SSTI in adolescents, those older than 65 years, obese individuals and patients with diabetic foot infections. Forthcoming research to determine the future uses of this drug in other clinical syndromes requires demonstration of tolerance whenever tedizolid is administered for longer than 6 days.We also speculate on missing data and potential future indications of tedizolid in the highly competitive field of the treatment of severe Gram-positive infections other than SSTI.. Tedizolid is a second-generation oxazolidinone, very convenient for treatment of SSTI, in search for other indications including nosocomial pneumonia and bone and joint infections. VIDEO ABSTRACT.

Topics: Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Gram-Positive Bacterial Infections; Humans; Oxazolidinones; Skin Diseases, Infectious; Soft Tissue Infections; Tetrazoles; Treatment Outcome

Methicillin-resistant Staphylococcus aureus (MRSA)is a common pathogen in acute bacterial skin and soft tissue infections (ABSSSIs), nosocomial pneumonia, bacteremia, endocarditis, as well as diabetic foot, bone, and joint infections. Areas covered: This review summarizes the randomized controlled trials that evaluated the clinical efficacy of tedizolid in ABSSSIs, which is currently the only United States Food and Drug Administration-labeled indication for tedizolid. Expert opinion: Tedizolid has several potential advantages over linezolid including once-daily dosing, shorter duration of therapy, and increased tolerability. However, its cost will likely limit its adoption for ABSSSIs with MRSA because other oxazolidinone antibiotics are available in less costly generic versions. Tedizolid is also currently being investigated for its use in other MRSA infections including nosocomial pneumonia as well as diabetic foot, bone, and joint infections and tedizolid's use in these disease states appears more promising. Potential indications for future clinical investigation of tedizolid's efficacy and safety include bacteremia and meningitis.

Topics: Anti-Bacterial Agents; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Randomized Controlled Trials as Topic; Soft Tissue Infections; Staphylococcal Infections; Tetrazoles

Tedizolid phosphate is an oxazolidinone prodrug approved in 2014 for treatment of adults with acute bacterial skin and skin structure infections (ABSSSIs); however, efficacy has not previously been evaluated in children. This study compared the safety and efficacy of tedizolid (administered as tedizolid phosphate) with active antibacterial comparators for the treatment of ABSSSIs in adolescents.. This was a randomized, assessor-blind, global phase 3 study of tedizolid versus active comparators for the treatment of Gram-positive ABSSSIs in adolescents (12 to <18 years of age; NCT02276482). Enrolled participants were stratified by region and randomized 3:1 to receive tedizolid phosphate 200 mg (oral and/or intravenous) once daily for 6 days or active comparator, selected by investigator from an allowed list per local standard of care, for 10 days. The primary endpoint was safety; blinded investigator's assessment of clinical success at the test-of-cure visit (18-25 days after the first dose) was a secondary efficacy endpoint. Statistical comparisons between treatment groups were not performed.. Of the 121 participants enrolled, 120 were treated (tedizolid, n = 91; comparator, n = 29). Treatment-emergent adverse events were balanced between treatment groups (tedizolid, 14.3%; comparator, 10.3%). Overall, 3 participants (3.3%) in the tedizolid group and 1 (3.4%) in the comparator group experienced a single drug-related TEAE. Clinical success rates were high in both treatment groups: 96.7% and 93.1% at the test-of-cure visit for the tedizolid and comparator groups, respectively.. Tedizolid demonstrated safety and efficacy similar to comparators for the treatment of ABSSSIs in adolescents.

Topics: Abscess; Adolescent; Anti-Bacterial Agents; Female; Global Health; Humans; Male; Oxazolidinones; Skin Diseases, Bacterial; Soft Tissue Infections; Tetrazoles; Wound Infection

We evaluated the microbiological efficacy of tedizolid compared with that of linezolid against common and emerging pathogens using pooled data from 2 phase 3 trials (NCT01170221 and NCT01421511) in patients with acute bacterial skin and skin structure infections. Patients received tedizolid 200 mg once daily for 6 days (n = 664) or linezolid 600 mg twice daily for 10 days (n = 669). Favorable microbiological outcome in both treatment groups, defined as eradication or presumed eradication at the end of treatment and at the posttherapy evaluation, exceeded 85% for most pathogens, including methicillin-resistant Staphylococcus aureus. Favorable microbiological response was observed for staphylococci and streptococci at tedizolid minimal inhibitory concentration values ≤0.5 mg/L and 0.25 mg/L, respectively. The studies demonstrated positive microbiological outcomes against common pathogens with a 6-day, once-daily regimen of tedizolid phosphate in patients with acute bacterial skin and skin structure infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Clinical Trials, Phase III as Topic; Double-Blind Method; Female; Gram-Positive Bacterial Infections; Humans; Linezolid; Male; Middle Aged; Oxazolidinones; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Soft Tissue Infections; Tetrazoles; Treatment Outcome; Young Adult

Skin and soft tissue infections (SSTI) are among the most commonly occurring infections and evidence suggests that these are increasing world-wide. The aetiology is diverse, but Staphylococcus aureus predominate and these are often resistant to antimicrobials that were previously effective. Tedizolid is a new oxazolidinone-class antibacterial indicated for the treatment of adults with SSTI caused by Gram-positive pathogens, including S. aureus. The aim of this study was to evaluate the in vitro efficacy of tedizolid in comparison to other clinically used antibacterials against antibiotic sensitive- and resistant-staphylococci, grown in planktonic cultures and as biofilms reflecting the growth of the microorganism during episodes of SSTI. Against a panel of 66 clinical staphylococci, sensitivity testing revealed that a lower concentration of tedizolid was required to inhibit the growth of staphylococci compared to linezolid, vancomycin and daptomycin; with the tedizolid MIC

Topics: Anti-Bacterial Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus; Tetrazoles

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) causes severe skin and soft tissue infections in hospitals and, more recently, in the community. Tedizolid is a new second-generation oxazolidinone derivative having greater in vitro potency than linezolid against this type of microorganism.\ Objectives: To evaluate the antimicrobial activity of tedizolid and other comparator antibiotics in MRSA isolates causing skin and soft tissue infections in Colombian hospitals.\ Materials and methods: We conducted a prospective, multi-center descriptive study in seven tertiary-level hospitals in Colombia along a 12-month period. MRSA isolates were collected from adult patients with skin and soft tissue infections. Tedizolid, linezolid, vancomycin, daptomycin, trimethoprim-sulfamethoxazole, and clindamycin minimum inhibitory concentration (MIC) was determined by ETEST® (bioMérieux).\ Results: MRSA isolates were obtained from 102 patients with an average age of 46.8 years of whom 56 (54.9%) were men. Infection was community-acquired in 77 cases (75.4%). Abscess-related samples predominated (69 patients: 67.6%). All isolates were susceptible to tedizolid, linezolid, daptomycin, trimethoprim-sulfamethoxazole, and vancomycin. Tedizolid had greater in vitro activity than linezolid. Tedizolid MIC intervals ranged from 0.125 μg/mL to 0.5 μg/mL while those of linezolid ranged from 1μg/mL to 2μg/mL.\ Conclusions: MRSA strains circulating in Colombia are highly susceptible to tedizolid and can be considered a therapeutic alternative for hospitals and/or community-acquired skin and soft tissue infections.. Introducción. Staphylococcus aureus resistente a meticilina (SARM) causa infecciones graves de la piel y los tejidos blandos en los hospitales y, en los últimos años, en la comunidad. El tedizolid es una nueva oxazolidinona cuya potencia in vitro ha demostrado ser mayor que la del linezolid frente a este microorganismo.Objetivo. Conocer la actividad antimicrobiana del tedizolid y de algunos antibióticos de comparación en aislamientos de SARM causante de infecciones de piel y tejidos blandos en hospitales de Colombia.Materiales y métodos. Se hizo un estudio multicéntrico prospectivo y descriptivo a lo largo de doce meses en siete hospitales de tercer nivel de Colombia. Se recolectaron aislamientos de SARM de pacientes adultos con infección de piel y tejidos blandos. Se determinó la concentración inhibitoria mínima (CIM) mediante la técnica de ETEST® (bioMérieux) del tedizolid, el linezolid, la vancomicina, la daptomicina, el trimetoprim-sulfametoxazol y la clindamicina.Resultados. Se obtuvieron aislamientos de SARM de 102 pacientes, de los cuales 56 (54,9 %) eran hombres; el promedio de edad fue de 46,8 años. La infección tuvo origen en la comunidad en 77 casos (75,4 %). El tipo de muestra que predominó fue el absceso (69 pacientes: 67,6 %). Todos los aislamientos fueron sensibles a tedizolid, linezolid, daptomicina, trimetoprim-sulfametoxazol y vancomicina. La actividad in vitro del tedizolid fue mayor que la del linezolid. Los intervalos de la CIM del tedizolid oscilaron entre 0,125 μg/ml y 0,5 μg/ml en tanto que los del linezolid fluctuaron entre 1 μg/m y 2 μg/ml.Conclusiones. Las cepas circulantes de SARM en Colombia presentaron una gran sensibilidad al tedizolid, por lo cual sería una alternativa terapéutica para las infecciones de piel y tejidos blandos en nuestro medio.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colombia; Female; Hospitals; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Prospective Studies; Soft Tissue Infections; Staphylococcal Skin Infections; Tetrazoles; Young Adult

Topics: Anti-Bacterial Agents; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Soft Tissue Infections; Staphylococcal Infections; Tetrazoles