Yes / The cocrystal of nitrofurantoin with urea (C8H6N4O5)·(CH4N2O), a non-ionic supramolecular complex, has been studied. Nitrofurantoin (NF) is a widely used antibacterial drug for the oral treatment of infections of the urinary tract. Characterization of the cocrystal of nitrofurantoin with urea (NF–urea) was performed spectroscopically by employing FT-IR, FT- and dispersive-Raman, and CP-MAS solid-state 13C NMR techniques, along with quantum chemical calculations. With the purpose of having a better understanding of H-bonding (inter- and intra-molecular), two different models (monomer and monomer + 3urea) of the NF–urea cocrystal were prepared. The fundamental vibrational modes were characterized depending on their potential energy distribution (PED). A combined experimental and theoretical wavenumber study proved the existence of the cocrystal. The presence and nature of H-bonds present in the molecules were ascertained using quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. As the HOMO–LUMO gap defines the reactivity of a molecule, and this gap is more for the API than the cocrystal, this implies that the cocrystal is more reactive. Global descriptors were calculated to understand the chemical reactivity of the cocrystal and NF. Local reactivity descriptors such as Fukui functions, local softness and electrophilicity indices were analysed to determine the reactive sites within the molecule. The comparison between NF–urea (monomer) and NF showed that the cocrystal has improved overall reactivity, which is affected by the increased intermolecular hydrogen bond strength. The docking studies revealed that the active sites (C[double bond, length as m-dash]O, N–H, NO2, N–N) of NF showed best binding energies of −4.89 kcal mol−1 and −5.56 kcal mol−1 for MUL and 1EGO toxin, respectively, which are bacterial proteins of Escherichia coli. This cocrystal could potentially work as an exemplar system to understand H-bond interactions in biomolecules.

The efficacy of short term (3 day) oral amoxicillin therapy was compared to conventional (14 day) oral therapy in an experimental model of bacterial lower urinary tract infection (UTI) in the cat. Chemical cystitis was induced using an infusion solution of salicylic acid, 70% ethanol, and normal saline via transabdominal cystocentesis. Cats were challenged with a Staphylococcus intermedius inoculum twenty-four hours later introduced via urethral catheterization. Serial quantitative aerobic bacterial urine cultures obtained via cystocentesis were used to evaluate groups of cats. Eighteen adult cats (9 males and 9 females) were divided into 3 groups of 6 cats (3 males and 3 females): Group I = conventional amoxicillin therapy (14 day), Group II = control group (no treatment), and Group III = short term therapy (3 day). Results indicated the conventional therapy successfully eradicated infection, however, the short term therapy did not eradicate infection when compared to controls. During the study period the diuretic furosemide was used in some cats to facilitate cystocentesis procedures. Those cats were observed to exhibit less stranguria, which is a common sign of lower UTI. The second study evolved from observations made in the first study and evaluated the effect of furosemide on conventional antibiotic therapy in an experimental model of bacterial lower UTI in the cat. A similar experimental design was utilized with Group I = control group (no treatment), Group II = oral furosemide (14 day), and Group III = oral furosemide and oral amoxicillin (14 day). Statistical analysis failed to demonstrate the efficacy of the furosemide and amoxicillin combination, but showed furosemide alone was not an appropriate therapy when compared to controls. It was again observed that those cats receiving furosemide showed fewer secondary signs of lower UTI such as stranguria which suggests a possible role for furosemide as adjunct therapy in the treatment of lower UTI in the cat. / Master of Science

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

More than 13,000 deaths and $340 million in health care costs are the result of catheter-associated urinary tract infections (CAUTIs) annually in the United States. CAUTIs can also result in acute patient discomfort and potentially preventable exposure to antibiotics. The hospital for which this quality improvement project was developed was above the National Healthcare Safety Network CAUTI bench mark. Framed within the Iowa model of evidence-based practice, a multidisciplinary team of 8 hospital stakeholders guided the project (n=8). The purpose of the project was to develop an indwelling urinary catheter maintenance checklist using evidence-based practice guidelines related to preexisting inappropriate risk factors for catheterization and appropriate indications for catheterization, as well as evidence-based maintenance practices for care of the indwelling catheter. Each piece of evidence to be included in the checklist was evaluated by 4 content experts using a 10 item 5 point Likert scale ranging from 'strongly disagree' to 'strongly agree'. Descriptive analysis showed an average of 4.8/5 for all items with 'agree' being voiced in two of the items rather than 'strongly agree'. The checklist was completed and presented to hospital senior leadership who recommended that the checklist be incorporated into the hospital CAUTI prevention plan. All project team members (n=8) completed an 8 item 5 point Likert scale summative evaluation of the purpose, goal, objectives, and my leadership which averaged as 5 or 'strongly agree' supporting the development of the project. Implications for social change include improved patient outcomes, mindful stewardship of healthcare dollars, and increased patient and family satisfaction.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

The adhesion of bacteria to uroepithelial cells or urinary catheters is the first step in the development of biofilm formation and urinary tract infections (UTIs). Previous research has suggested that consumption of cranberry juice can prevent the recurrence of UTIs by decreasing bacterial adhesion since isolated compounds in cranberries, known as A-type proanthocyanidins (PACs), change the conformation of proteinaceous fimbriae that help attach bacteria to epithelial cell receptors. Most clinical and laboratory studies have shown the effects of cranberry juice cocktail (CJC) on large communities of bacteria; however, very few studies have evaluated how cranberry affects the adhesion forces of a single bacterium as well as effects on cellular composition and biofilm formation. We used atomic force microscopy (AFM) to investigate the effects of CJC and PACs on the adhesion forces between E. coli and a silicon nitride tip. Bacterial cultures were grown in tryptic soy broth (TSB), supplemented with 0 and 10 wt.% light cranberry juice cocktail (L-CJC) or 128 µg/mL PACs. E. coli bacteria were continuously cultured in the presence of cranberry products up to twelve times. Experiments were conducted at different scales to test bacterial attachment and adhesion forces. At the macroscale, bacteria were incubated with uroepithelial cells and the number of bacteria attached per uroepithelial cell was determined. In nanoscale experiments, the forces of adhesion between E. coli and a silicon nitride AFM tip were probed for bacteria grown in L-CJC or PACs for different numbers of culture times. Successive replacement of media and continued culture in L-CJC and PACs resulted in a significant decrease in adhesion forces for E. coli strains. Finally, during the continuous exposure of L-CJC to bacteria we examined the growth, morphology, and ability to form biofilms of E. coli. We found a decrease in growth rates related to changes in Gram staining with increasing number of cultures in L-CJC. Growth of bacteria in L-CJC or PACs inhibited the development of biofilms on polyvinyl-chloride, which can model biofilm formation on urinary catheters. We also determined that growth of E. coli in L-CJC results in prevention of the expression of indole which can be linked to the inhibition of biofilm formation. Our results help support the molecular mechanisms for the role of cranberry in preventing the adhesion of E. coli to biotic and abiotic surfaces, thus helping to scientifically validate the use of cranberry juice as a prophylactic treatment for the prevention of UTIs.