BackgroundMethicillin susceptible Staphylococcus aureus (MSSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies.PurposeTo evaluate if the combination of daptomycin plus cloxacilin achieves higher clinical success rates in the treatment of MSSA bacteraemia than cloxacilin alone.Material and methodsA single centre, retrospective, observational, comparative study was performed between January 2015 and August 2015. The subjects were patients with MSSA bacteraemia who received cloxacilin as monotherapy (standard therapy group) or the combination cloxacilin plus daptomycin. A revision of the clinical history of each patient was carried out to asses clinical, laboratoy and microbiological data.The main outcome variable was 30 day all-cause mortality and 30 day all-cause hospital readmission. Secondary endpoints were: (i) percentage of patients who achieved a decrease in CRP levels to <50% of their initial value in the first 72 h of therapy; (ii) length of hospital stay (LOS); and (iii) percentage of patients with persistent bacteraemia after 72 h of initiation of therapy.Results14 patients met the study criteria. 7 (50%) patients received cloxacilin as monotherapy and 7 (50%) received the combination cloxacilin-daptomycin.No differences in 30 day all-cause mortality were observed (14% (1/7 in the standard therapy group vs 14% (1/7) in the combination group). No statistical differences between groups were observed in all-cause readmission at 30 days (14% (1/7) in the standard group vs 0/7 in the combination group (p = 0.337)). Similarly, there were no differences in the secondary endpoints: LOS (median 32 vs 37 days, p = 0.86) and a decrease in CRP levels to <50% of their initial value in the first 72 h of therapy (42% (3/7) in the combination group vs 28% (2/7) in the standard therapy group (p = 0.611)). The rate of persistent bacteraemia did not differ between the two groups.ConclusionOur data showed a benefit of adding daptomycin to cloxacilin in patients with MSSA bacteraemia. However, studies with a large number of patients are required to define the role of combination therapy in patients with MSSA bacteraemia.References and/or AcknowledgementsEmerg Infect Dis 2011;17:1099-102No conflict of interest.
BackgroundAdalimumab and ustekinumab have demonstrated a high level of efficacy in the treatment of moderate-severe psoriasis in randomised controlled trials. There are, however, no data available on the comparative effectiveness of ustekinumab and adalimumab in psoriasis patients switching from etanercept.PurposeTo evaluate the comparative effectiveness of adalimumab and ustekinumab in patients previously treated with etanercept.Material and methodsA single centre, retrospective, observational, comparative study was carried out from 1 November 2011 to 31 March 2013, with a follow-up of 2 years. Subjects were patients with moderate-severe psoriasis that after etanercept therapy were treated with adalimumab or ustekinumab. A revision of each patient’s clinical history was carried out to asses clinical data. The primary analysis compared the percentages of patients in each treatment group who achieved ≥75% improvement from baseline PASI score (PASI 75) at week 12. Secondary endpoints included the percentages of patients with PASI 75 at week 96. Statistical analysis was performed with the SPSS 22 software.Results28 psoriasis patients were included: 11 (39.3%) patients received adalimumab and 17 (60.7%) received ustekinumab as secondline therapy. Median age in the adalimumab and ustekinumab groups were 58 (SD 6.5) years and 49 years (SD 16.3), respectively (p = 00.08). After 12 weeks of study treatment, 76.5% of ustekinumab treated patients (13/17) achieved a PASI 75 response compared with 36.4% (4/11) in the adalimumab group (p = 0.034). At week 96, more patients had a PASI 75 in the ustekinumab group compared with the adalimumab group, but the difference was not statistically significant (70.6% vs 36.4%, p = 0.07).ConclusionPreviously studies have shown that adalimumab and ustekinumab are effective after anti-TNF inhibitor therapy. However, to our knowledge, the present study is the first to evaluate the comparative effectiveness of ustekinumab and adalimumab in psoriasis patients switching from etanercept. Our study suggests that ustekinumab is associated with a higher effectiveness compared with adalimumab as secondline treatment in patients previously treated with etanercept. Prospective, randomised studies with a large number of patients are required to establish the optimal treatment in psoriasis patients who have previously received etanercept.References and/or AcknowledgementsJ Dermatolog Treat 2015;26:217-22J Eur Acad Dermatol Venereol 2011;25:1037-40No conflict of interest.
BackgroundUGT1A1 polymorphisms have been relatated to interindividual variability effectiveness and toxicity in many drugs. In addition, the presence of mutated alleles in this gene has also been identified historically as Gilbert’s disease which exhibits high levels of unconjugated bilirubin.PurposeAnalysing the relationship between total serum bilirubin levels and rs8175347 (*28) polymorphism in the UGT1A1 gene.Material and methodsObservational, retrospective and unicentre study of 2 years was carried out. Patients with colorectal cancer who have been tested for gDNA determination of UGT1A1 genotype for clinical practice were included. Clinical data were obtained using the application SAP®.A high level of total-bilirrubine was considered as at least a 90% determination, with total-bilirubin higher than 1 mg/dL.Polymorphism *28 of UGT1A1 was established by analysing the genomic DNA of a peripheral blood sample. Genetic characterisation was carried out using the LightClycler® 480 platform and specific allele HybProbe fluorescent probes. The relationship between the UGT1A1 genotype and levels of total serum bilirrubine were determined by univariable statistical analysis. Patients were requested to sign an informed consent form prior to the inclusion.ResultsOne hundred and seventy-three patients were included in the study, with a median age of 62 years (81–27) and 62.3% were males. 46,2% of participants had WT genotype: 21.2% (n=17) of them showed high levels of total serum bilirubin.On the other hand, 53.7% of patients had mutant alleles (*1/*28. *28/28), of which 36.5% (n=34) showed high levels of bilirubin (p=0.003).ConclusionOur results show that the presence of *28 allele in UGT1A1 is associated with high levels of serum bilirubin. With these results, we feel that this finding could provide the clinician with a tool to detect patients with high risk of drug toxicity such as irinotecan or pazopanib, among others.No conflict of interest
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