In vitro susceptibility of methicillin-resistant Staphylococcus aureus isolates from skin and soft tissue infections to vancomycin, daptomycin, linezolid and tedizolid

Abstract Introduction Treatment of multidrug-resistant Gram-positive infections caused by Staphylococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently approved for skin and soft tissues infections. We conducted a study to determine in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in MRSA clinical isolates from adult patients with skin and soft tissue infections. Material and methods Methicillin-resistant S. aureus isolates were collected in three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June 2010 as part of a previous study. Clinical characteristics were assessed by medical records and MIC values were determined by Epsilometer test. Genotypic analysis included spa typing, MLST, and SCCmec typing. Results A total of 150 MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in vitro activity than other antimicrobials, with MIC values ranging from 0.13 µg/mL to 0.75 µg/mL and lower values of MIC50 and MIC90 (0.38 µg/mL and 0.5 µg/mL). In contrast, vancomycin and linezolid had higher MIC values, which ranged from 0.5 µg/mL to 2.0 µg/mL and from 0.38 µg/mL to 4.0 µg/mL, respectively. Tedizolid MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics showed high previous antimicrobial use and hospitalization history. The majority of the strains belong to the CC8 harboring the SCCmec IVc and were associated with the spa t1610 (29.33%, n = 44). Conclusion In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.

[Cytotoxic effects of selective inhibitor 'Aurora Kinase B' on viability and metabolic features of human promyelocytic leukemia cell line]

A goal of modern cancer research is to reach targeted therapies with drugs having fewer side effects. AZD1152 is a highly specific inhibitor of Aurora Kinase B, which leads to the programmed cell death by different mechanisms. The aim of this study was to evaluate the effects of AZD1152 on viability and metabolic activity of NB4 cells [APL derived cell line]. The cells were treated with various concentrations of AZD1152. After 24, 48 and 72h treatments, the metabolic activity and viability of inhibitor-treated NB4 cells were assessed using MTT and trypan blue dye exclusion assays, respectively. Data were analyzed by applying student's t-test [Microsoft Excel]. At 25, 50 and 100 nM, AZD1152 reduced the metabolic activity by 9.2, 15.5 and 56.2% [after 24h], 10.3, 19.5 and 59.9% [after 48h], and 17.1, 28.4 and 64.8% [after 72h], respectively. Meanwhile, the percentage of viability was decreased to about 51, 45 and 40% [after 24h], 39, 36 and 30% [after 48h], and 34, 32 and 28% [after 72h], respectively. According to the results, AZD1152 has substantial efficacy on APL cell line and may be applied in some cases, e. g., for patients who have relapse or who become refractory to the conventional chemotherapy. Further studies are needed to show the molecular mechanisms regulating effects of this anti-cancer agent

Acaricide resistance mechanisms in Rhipicephalus (Boophilus) microplus / Mecanismos de resistência aos acaricidas em Rhipicephalus (Boophilus) microplus

Acaricide resistance has become widespread in countries where cattle ticks, Rhipicephalus (Boophilus) microplus, are a problem. Resistance arises through genetic changes in a cattle tick population that causes modifications to the target site, increased metabolism or sequestration of the acaricide, or reduced ability of the acaricide to penetrate through the outer protective layers of the tick’s body. We review the molecular and biochemical mechanisms of acaricide resistance that have been shown to be functional in R. (B.) microplus. From a mechanistic point of view, resistance to pyrethroids has been characterized to a greater degree than any other acaricide class. Although a great deal of research has gone into discovery of the mechanisms that cause organophosphate resistance, very little is defined at the molecular level and organophosphate resistance seems to be maintained through a complex and multifactorial process. The resistance mechanisms for other acaricides are less well understood. The target sites of fipronil and the macrocyclic lactones are known and resistance mechanism studies are in the early stages. The target site of amitraz has not been definitively identified and this is hampering mechanistic studies on this acaricide.

A resistência aos acaricidas tornou-se amplamente difundida nos países onde os carrapatos bovinos, Rhipicephalus .Boophilus. microplus, são um problema. A resistência surge por meio de alterações genéticas em umapopulação de carrapatos que causam modificações no local de ação, aumento do metabolismo ou sequestro do acaricida, ou ainda redução na capacidade do acaricida em penetrar através das camadas protetoras do corpo do carrapato. Neste artigo, foram revisados os mecanismos moleculares e bioquímicos da resistência aos acaricidas que ocorrem em R. (B.) microplus. A partir de um ponto de vista dos mecanismos envolvidos, a resistência aos piretróides tem sido caracterizada em maior grau do que em qualquer outra classe de acaricida. Embora uma grande quantidade de pesquisas têm sido direcionada para a descoberta de mecanismos que causam resistência aos organofosforados, muito pouco é conhecido ao nível molecular, e essa resistência parece ser mantida por intermédio de um processo multifatorial e complexo. Os mecanismos de resistência para os demais acaricidas são bem menos compreendidos. Os alvos de ação do fipronil e das lactonas macrocíclicas são conhecidos, e os estudos dos mecanismos de ação envolvidos estão ainda em estágios iniciais. O alvo de ação do amitraz ainda não foi definitivamente identificado, e isso é limitante aos estudos dos mecanismos envolvidos na resistência a esse acaricida.

Fluconazole-loaded liposomes for ocular delivery: characterization and antifungal activity

Fluconazole loaded liposomes were prepared using reverse phase evaporation technique for ocular delivery of the drug. Characterization of fluconazole liposomes including; particle size and physical morphology were studied. The effects of different variables [cholesterol weight ratio and charge type] on the loading efficiency of liposomes as well as particle size were determined. Inclusion of cholesterol in liposomal formulations improved the encapsulation of fluconazole into liposomes at certain Phosphatidylcholine: Cholesterol [PC: Ch] weight ratios further increase in cholesterol content resulted in a decrease in the encapsulation percent of the drug. A significant increase in the encapsulation at ratio 7:3 was noticed. At ratio 7:6, the encapsulation significantly decreased. Incorporation of stearylamine [SA] into liposomes decreased the loading efficiency of fluconazole at ratio [PC: Ch: SA] 5: 5: 0.25 followed by insignificant increase in the entrapment of the drug into liposomes at ratio 5: 5: 0.5. On the other hand, addition of dicetyl phosphate [DP] into liposomes resulted in a significant increase in fluconazole encapsulation into liposomes at all tested [PC: Ch: DP] ratios. The loading efficiency of the neutral liposomes was found to be in between those of positively and negatively charged liposomes. The particle size studies showed that, increasing cholesterol amount, led to an increase in the particle size. While increasing stearylamine and dicetyl phosphate led to decrease in the particle size of liposomes. An in-vitro study was done to know the effect of fluconazole loaded liposomes on different fungi isolated from eye

Use of sedation analgesia for pediatric dentistry.

26 healthy children between the ages of 36 and 60 months (mean 35 months) who satisfied the selection criteria during a screening visit participated in this double blind study. The subjects were assigned randomly to receive either 75 mg/kg Triclofos elixir (Regimen I-21 children) or 50 mg/1kg Trichlofos elixir combined with 1 mg/kg promethazine elixir (Regimen II-22 children). All medications were given orally 45 minutes before treatment. During operative procedures all subjects received nitrous oxide/oxygen at a concentration of 35%. All the patients were restrained in a papoose board (Indigenous). The subjects were monitored for vital signs and evaluated for sedation and sleep, movement, crying and overall behaviour before, during and after the operative procedure. Regimen II was found to be superior to Regimen I with regard to behaviour management of difficult young children. However extremely apprehensive children were not good subjects for this sedation technique.