Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections

Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. Its pharmacokinetic characteristics allow for a once-daily administration that leads to a more predictable efficacy and safety profile than those of linezolid. No hematological adverse effects have been reported associated with tedizolid when used at the therapeutic dose of 200 mg in Phase I, II, or III clinical trials of up to 3 weeks of tedizolid administration. Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need

Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections

Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. Its pharmacokinetic characteristics allow for a once-daily administration that leads to a more predictable efficacy and safety profile than those of linezolid. No hematological adverse effects have been reported associated with tedizolid when used at the therapeutic dose of 200 mg in Phase I, II, or III clinical trials of up to 3 weeks of tedizolid administration. Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need

Bacteriemias por cepas de Escherichia Coli y Klebsiella Pneumoniae productoras de beta-lactamasas de espectro extendido : epidemiología, factores de riesgo de adquisición, marcadores de evolución clínica e impacto de la adecuación del tratamiento antibiótico /

Descripció del recurs: 5 octubre 201

Evolution of Antimicrobial Consumption During the First Wave of COVID-19 Pandemic

Background: The first wave of COVID-19 pandemic may have significantly impacted antimicrobial consumption in hospitals. The objective of this study was to assess the evolution of antimicrobial consumption during this period. Methods : A retrospective quasi-experimental before-after study was conducted in a Spanish tertiary care hospital. The study compared two periods: pre-pandemic, from January 2018 to February 2020, and during the COVID-19 pandemic from March to June 2020. Antimicrobial consumption was analyzed monthly as defined daily doses (DDD)/100 bed-days and overall hospital and ICU consumption were evaluated. Results: An increase in the hospital consumption was noticed. Although only ceftaroline achieved statistical significance (p = 0.014), a rise was observed in most of the studied antimicrobials. A clear temporal pattern was detected. While an increase in ceftriaxone and azithromycin was observed during March, an increment in the consumption of daptomycin, carbapenems, linezolid, ceftaroline, novel cephalosporin/β-lactamase inhibitors or triazoles during April-May was noticed. In the ICU, these findings were more evident, namely ceftriaxone (p = 0.029), carbapenems (p = 0.002), daptomycin (p = 0.002), azithromycin (p = 0.030), and linezolid (p = 0.011) but followed a similar temporal pattern. Conclusion : An increase in the antimicrobial consumption during the first wave of COVID-19 pandemic was noticed, especially in the ICU. Availability of updated protocols and antimicrobial stewardship programs are essential to optimize these outcomes

Sex Differences in Multimorbidity, Inappropriate Medication and Adverse Outcomes of Inpatient Care : MoPIM Cohort Study

There is no published evidence on the possible differences in multimorbidity, inappropriate prescribing, and adverse outcomes of care, simultaneously, from a sex perspective in older patients. We aimed to identify those possible differences in patients hospitalized because of a chronic disease exacerbation. A multicenter, prospective cohort study of 740 older hospitalized patients (≥65 years) was designed, registering sociodemographic variables, frailty, Barthel index, chronic conditions (CCs), geriatric syndromes (GSs), polypharmacy, potentially inappropriate prescribing (PIP) according to STOPP/START criteria, and adverse drug reactions (ADRs). Outcomes were length of stay (LOS), discharge to nursing home, in-hospital mortality, cause of mortality, and existence of any ADR and its worst consequence. Bivariate analyses between sex and all variables were performed, and a network graph was created for each sex using CC and GS. A total of 740 patients were included (53.2% females, 53.5% ≥85 years old). Women presented higher prevalence of frailty, and more were living in a nursing home or alone, and had a higher percentage of PIP related to anxiolytics or pain management drugs. Moreover, they presented significant pairwise associations between CC, such as asthma, vertigo, thyroid diseases, osteoarticular diseases, and sleep disorders, and with GS, such as chronic pain, constipation, and anxiety/depression. No significant differences in immediate adverse outcomes of care were observed between men and women in the exacerbation episode

Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

Tedizolid phosphate has high activity against the Gram-positive microorganisms mainly involved in acute bacterial skin and skin structure infections, such as strains of Staphylococcus aureus (including methicillin-resistant S. aureus strains and methicillin-sensitive S. aureus strains), Streptococcus pyogenes, Streptococcus agalactiae, the Streptococcus anginosus group, and Enterococcus faecalis, including those with some mechanism of resistance limiting the use of linezolid. The area under the curve for time 0-24 hours/minimum inhibitory concentration (MIC) pharmacodynamic ratio has shown the best correlation with the efficacy of tedizolid, versus the time above MIC ratio and the maximum drug concentration/minimum inhibitory concentration ratio. Administration of this antibiotic for 6 days has shown its noninferiority versus administration of linezolid for 10 days in patients with skin and skin structure infections enrolled in two Phase III studies (ESTABLISH-1 and ESTABLISH-2). Tedizolid's more favorable safety profile and dosage regimen, which allow once-daily administration, versus linezolid, position it as a good therapeutic alternative. However, whether or not the greater economic cost associated with this antibiotic is offset by its shorter treatment duration and possibility of oral administration in routine clinical practice has yet to be clarified

Accidental Interruption of the Cold Chain for the Preservation of the Moderna COVID-19 Vaccine

Maintenance in restricted cold temperature conditions is a mandatory requirement to preserve the stability of mRNA vaccines [...