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Everett Rosa posted an update 2 months ago
mm Hg, because these recommendations differ from some other guidelines.Background Vancomycin is associated with nephrotoxicity and the mechanism may in part be related to oxidative stress. In vitro and preclinical studies suggest melatonin supplementation decreases oxidative stress. The objective of this study was to evaluate concomitant use of melatonin and vancomycin and the incidence of acute kidney injury (AKI). Methods We performed a retrospective cohort study at a large community medical center. All consecutive patients admitted to the medical center between January 2016 and September 2020 who received vancomycin therapy alone or concomitantly with melatonin as part of ordinary care were considered for inclusion. The primary endpoint was the development of AKI defined as an absolute increase in serum creatinine of ≥ 0.3 mg/dL or a ≥ 50% increase in serum creatinine. All data were analyzed using descriptive statistics. A multivariable logistic regression was constructed to account for potential confounding variables. Results A total of 303 adult patients meeting inclusion and exclusion criteria treated with vancomycin were identified, 101 of which received melatonin concomitantly. 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 , 0.37; 95% confidence interval , 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. ACY-738 price 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.