Notes

Dielectric properties associated with calamansi (Lemon or lime microcarpa) beneath high-temperature therapy.
Overall baseline characteristics were similar between the two groups except for the incidence of bactremia/sepsis. After controlling for vancomycin area under the curve, baseline creatinine clearance, and intensive care unit admission in multivariable logistic regression, melatonin use was associated with a 63% decrease in AKI (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14 - 0.96; p =0.041). Conclusions Melatonin use was associated with a significant reduction in vancomycin-related AKI. Although this was a retrospective study with a small sample size, given the magnitude of the difference seen, further large prospective studies are warranted.Voriconazole (VRC), a first-line agent for the treatment of invasive fungal infections, is mainly metabolized by human cytochrome P450 (CYP) 2C19. In this study, a retrospective analysis was performed to investigate the key factors which influence the plasma trough concentration (Cmin) of VRC, and an appropriate dosing regimen for pediatric patients was drafted subsequently. Overall, the factors such as age, CYP2C19 phenotype and combination medication with proton pump inhibitors accounted for 23.4% of variability in dose-normalized Cmin values of VRC by a multiple linear regression analysis. Dose-normalized Cmin values in the poor metabolizers (PMs) and intermediate metabolizers (IMs) were significantly higher than those in extensive metabolizers (EMs) (P less then 0.001). To achieve therapeutic Cmin, for CYP2C19 ultra-rapid metabolizers (UMs) or EMs, patients aged no more than 12 and more than 12 years required doses of 6.53 ± 2.08 and 3.95 ± 0.85 mg/kg twice daily (P = 0.007). For CYP2C19 PMs or IMs, patients aged under 12 and over 12 years required dose of 5.75 ± 1.73 and 4.23 ± 0.76 mg/kg twice daily, respectively (P = 0.019). Furthermore, co-administration of rifamycin sodium or omeprazole exhibited significant effects on VRC Cmin. Taken together, it is necessary to pay attention to the impact of CYP2C19 phenotype and drug-drug interactions to achieve an optimal therapy.Aliarcobacter butzleri is an emergent enteropathogen for which resistance to several classes of antimicrobial agents has been described, although the underlying mechanisms have been poorly addressed. We aimed to evaluate the contribution of the resistance-nodulation-division-type (RND) efflux system, AreABC, to drug resistance in A. butzleri. A. butzleri strains were first tested against several antimicrobials, with and without an efflux pump inhibitor. Then, erythromycin resistant strains were screened for the presence of a premature stop codon in a putative transcriptional regulator of the AreABC system, areR. Lastly, antimicrobial susceptibility and ethidium bromide (EtBr) accumulation were evaluated using an areB-knockout strain and a strain overexpressing the AreABC system through areR truncation. The presence of the efflux pump inhibitor resulted in increased susceptibility to most of the antimicrobials tested. A correlation between erythromycin resistance and the presence of premature stop codons in areR was observed. The truncation of areR resulted in increased expression of the AreABC system and decreased susceptibility to various antimicrobials. In contrast, areB inactivation resulted in increased susceptibility and a higher intracellular accumulation of EtBr. In conclusion, the AreABC efflux pump plays a role in the resistance of A. butzleri to multiple drugs and is regulated by a putative transcriptional repressor areR. Our results support the importance of efflux pumps in this bacterium's resistance to major classes of antibiotics and other antimicrobials.An effective strategy to control blood-borne diseases and prevent outbreak recrudescence involves targeting conserved metabolic processes that are essential for pathogen viability. One such target for Plasmodium and Babesia, the infectious agents of malaria and babesiosis, respectively, is the mitochondrial cytochrome bc1 protein complex, which can be inhibited by endochin-like quinolones (ELQ) and atovaquone. We used the tick-transmitted and culturable blood-borne pathogen Babesia duncani to evaluate the structure-activity relationship, safety, efficacy and mode of action of ELQs. We identified a potent and highly selective ELQ prodrug (ELQ-502), which, alone, or in combination with atovaquone, eliminates B. microti and B. duncani infections in vitro and in mouse models of parasitemia and lethal infection. The strong efficacy at low dose, excellent safety, bioavailability and long half-life of this experimental therapy makes it an ideal clinical candidate for the treatment of human infections caused by Babesia and its closely related apicomplexan parasites.Antibiotic combinations including ceftazidime/avibactam are frequently employed to combat KPC-producing Klebsiella pneumoniae (KPC-Kp), though such combinations have not been rationally optimized. Clinical KPC-Kp isolates with common genes encoding aminoglycoside modifying enzymes (AMEs), aac(6')-Ib' or aac(6')-Ib, were used in static time-kill assays (n=4 isolates) and the hollow fiber infection model (HFIM) (n=2 isolates) to evaluate the activity of gentamicin, amikacin, and ceftazidime/avibactam alone and in combinations. A short course, one-time aminoglycoside dose was also evaluated. Gentamicin plus ceftazidime/avibactam was then tested in a mouse pneumonia model. Synergy with ceftazidime/avibactam was more common with amikacin for aac(6')-Ib' containing KPC-Kp but more common with gentamicin for aac(6')-Ib containing isolates in time-kills. In the HFIM, although the isolates were aminoglycoside-susceptible at baseline, aminoglycoside monotherapies displayed variable initial killing followed by regrowth and resistance emergence. Ceftazidime/avibactam combined with amikacin or gentamicin resulted in undetectable counts 50h sooner than ceftazidime/avibactam monotherapy against KPC-Kp with aac(6')-Ib'. Ceftazidime/avibactam monotherapy failed to eradicate KPC-Kp with aac(6')-Ib and a combination with gentamicin led to undetectable counts 70h sooner than with amikacin. A one-time aminoglycoside dose with ceftazidime/avibactam provided similar killing to aminoglycosides dosed for 7 days. In the mouse pneumonia model (n=1 isolate), gentamicin and ceftazidime/avibactam achieved a 6.0 log10CFU/lung reduction at 24h, which was significantly greater than either monotherapy (P less then 0.005). Aminoglycosides in combination with ceftazidime/avibactam were promising for KPC-Kp infections; this was true even for a one-time aminoglycoside dose. Selecting aminoglycosides based on AME genes or susceptibilities can improve the pharmacodynamic activity of the combination.Drug resistance is a worldwide problem affecting all pathogens. The human fungal pathogen Aspergillus fumigatus coexists in the environment with other fungi targeted by crop protection compounds being unintentionally exposed to the selective pressure of multiple antifungal classes leading to the selection of resistant strains. A. fumigatus azole resistant isolates are emerging in both the clinical and environmental setting. Since their approval, azole drugs have dominated the clinical treatment for aspergillosis infections, and the agriculture fungicide market. However, other antifungal classes are used for crop protection including benzimidazoles (MBC), strobilurins (QoIs) and succinate dehydrogenase inhibitors (SDHIs). Mutations responsible for resistance to these fungicides have been widely researched in plant pathogens, but it has not been explored in A. see more fumigatus. In this work, the genetic basis underlying resistance to MBCs, QoIs and SDHIs were studied in azole susceptible and resistant A. fumigatus strains. E198A/Q and F200Y mutations in the β-tubulin conferred resistance to MBCs, G143A and F129L substitutions in the Cytochrome b to QoIs and H270R/Y mutations in SdhB to SDHIs. Characterization of the susceptibility to azoles showed a correlation between strains resistant to these fungicides and the ones with TR-based azole resistance mechanisms. Whole genome sequencing analysis showed a genetic relationship among fungicide multi resistant strains, which grouped together into subclusters that only included strains carrying the TR-based azole resistance mechanisms, indicating a common ancestor/evolution pattern and confirming the environmental origin of this type of azole resistant A. fumigatus.Antibiotic resistance genes exist naturally in various environments far from human usage. Here, we investigated multidrug-resistant Klebsiella pneumoniae, a common pathogen of chimpanzees and humans. We screened antibiotic-resistant K. pneumoniae from 48 chimpanzee stools and 38 termite mounds (N=415 samples) collected in protected areas in Senegal. The microsatellite method was used to identify chimpanzee individuals (N=13). Whole genome sequencing was performed on K. pneumoniae complex isolates to identify antibiotic-resistant genes and characterize clones. We found a high prevalence of carbapenem-resistant K. pneumoniae among chimpanzee isolates (18/48 samples from 7/13 individuals) and ceftriaxone resistance among both chimpanzee individuals (19/48) and termite mounds (7/415 termites and 3/38 termite mounds). The blaOXA-48 and the blaKPC-2 genes were carried by international pOXA-48 and pKPC-2 plasmids respectively. The ESBL plasmid carried blaCTX-M-15, blaTEM-1B and blaOXA-1 genes. Genome sequencing of 56 isolates identified two major clones associated with hospital-acquired infections of K. pneumoniae (ST307 and ST147) in chimpanzees and termites, suggesting circulation of strains between the two species, as chimpanzees feed on termites. The source and selection pressure of these clones in this environment need to be explored.Nafithromycin (13 WCK 4873) is a novel lactone ketolide under clinical development as an orally administrated antibiotic for treatment of community acquired pneumonia (CAP) caused by Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, and methicillin susceptible Staphylococcus aureus.….Sporotrichosis has become an important zoonosis in Brazil and Sporothrix brasiliensis is the primary species transmitted by cats. Improvement of animal treatment will help control and limit the spread and geographic expansion of sporotrichosis. Accordingly, buparvaquone, an antiprotozoal hydroxynaphthoquinone agent marketed as Butalex®, was evaluated in vitro and in vivo against feline-borne isolates of S. brasiliensis. Buparvaquone inhibited in vitro fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for S. brasiliensis than mammalian cells. Yeasts treated with a subinhibitory concentration of buparvaquone exhibited mitochondrial dysfunction, ROS and neutral lipid accumulation, and impaired plasma membranes. Also, scanning electron microscopy images revealed buparvaquone altered cell wall integrity and induced cell disruption. In vivo experiments in a Galleria mellonella model revealed that buparvaquone (single dose of 5 mg/kg) is more effective than itraconazole against infections with S. brasiliensis yeasts. Combined, our results indicate that buparvaquone has a great in vitro and in vivo antifungal activity against S. brasiliensis, revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.
Here's my website: https://www.selleckchem.com/products/cathepsin-Inhibitor-1.html