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1.
Ther Adv Urol ; 7(4): 186-93, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26445598

ABSTRACT

OBJECTIVES: The aim of the study was to assess both the safety and the effectiveness of nitrofurantoin in male veterans treated for urinary tract infections (UTIs) with varying degrees of renal impairment in the outpatient setting. Nitrofurantoin is an important oral option for treating UTIs given increasing resistance to commonly used agents. Nitrofurantoin is currently contraindicated in patients with a creatinine clearance (CrCl) of < 60 ml/min, but the reason for this threshold has not been well documented. METHODS: Data were collected through a retrospective chart review from January 2004 to July 2013 of men who had received nitrofurantoin. Bivariate analyses followed by multivariate analyses were performed between patients experiencing clinical cure and those who did not, to determine factors significantly impacting effectiveness. RESULTS: The Gram stain of the organism causing the UTI and CrCl were significant factors impacting effectiveness. For every 1 ml/min increase in CrCl, the odds of clinical cure increased by 1.3%. Patients with Gram-negative UTIs predictably had 80% cure rates with CrCl around 60 ml/min. Patients with Gram-positive UTIs required higher CrCl, nearing 100 ml/min, to establish an 80% cure rate. Adverse effects did not vary with CrCl. CONCLUSIONS: The odds of clinical cure varied with CrCl and with the type of organism causing the UTI, while adverse events did not differ based on renal function. A minimum CrCl of 60 ml/min is suggested for men to achieve an 80% cure rate for UTIs with the most common urinary pathogens.

2.
Beilstein J Org Chem ; 8: 1814-8, 2012.
Article in English | MEDLINE | ID: mdl-23209516

ABSTRACT

Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl hydrogen to the copper core. This decreases the steric bulk above the copper center and limits the asymmetric control with this ligand.

3.
Bioorg Med Chem Lett ; 19(17): 4984-7, 2009 Sep 01.
Article in English | MEDLINE | ID: mdl-19660946

ABSTRACT

Due to the increasing number of strains of drug-resistant bacteria, the development of new antibiotics has become increasingly important. The antibacterial properties of quaternary amines and their derivatives on both Gram-positive and Gram-negative bacteria are well known. However, an encompassing study with specific emphasis on the role of the counter-anion has not been reported in the literature. By monitoring the Zone of Inhibition of various concentrations of tetrabutylammonium (TBA) salts, we observed that the counter anion plays a significant role in activity. We developed a novel method of reporting activity using zone of inhibition tests (ZI(MAX)/K(ZI)) and found it to be strongly correlated with the minimum inhibitory concentration (MIC).


Subject(s)
Anions/chemistry , Anti-Infective Agents/pharmacology , Quaternary Ammonium Compounds/chemistry , Anions/pharmacology , Anti-Infective Agents/chemistry , Disk Diffusion Antimicrobial Tests , Quaternary Ammonium Compounds/pharmacology , Structure-Activity Relationship
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