INTRODUCTIONIncreasing resistance in Escherichia coli and Klebsiella pneumoniae to firstline antibiotics makes therapeutic options for urinary tract infections (UTIs) challenging. This study investigated the in vitro efficacies of 6 antibiotics against multidrug resistant (MDR) uropathogens.

MATERIALS AND METHODSMinimum inhibitory concentrations to ceftibuten, cefpodoxime, fosfomycin, mecillinam, temocillin, and trimethoprim were determined against 155 MDR-isolates of E. coli and K. pneumoniae. The presence of extended-spectrum beta-lactamases (ESBL) and plasmid-borne AmpC enzymes was determined by phenotypic testing with genotyping performed by multiplex polymerase chain reaction.

RESULTSTemocillin demonstrated highest susceptibility rates for both E. coli (95%) and K. pneumoniae (95%) when breakpoints for uncomplicated UTIs were applied; however, temocillin susceptibility was substantially lower when "systemic infection" breakpoints were used. Fosfomycin demonstrated the best in vitro efficacy of the orally available agents, with 78% and 69% of E. coli and K. pneumoniae isolates susceptible, respectively. The next most effective antibiotics were ceftibuten (45%) and mecillinam (32%). ESBL and ampC genes were present in 47 (30%) and 59 (38%) isolates.

CONCLUSIONThis study demonstrated few oral therapeutic options for MDR-uropathogens, with fosfomycin demonstrating the best in vitro activity.

Amdinocillin ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; Ceftizoxime ; analogs & derivatives ; pharmacology ; Cephalosporins ; pharmacology ; Drug Resistance, Multiple, Bacterial ; genetics ; Escherichia coli ; drug effects ; genetics ; Escherichia coli Infections ; microbiology ; Fosfomycin ; pharmacology ; Genotype ; Humans ; In Vitro Techniques ; Klebsiella Infections ; microbiology ; Klebsiella pneumoniae ; drug effects ; genetics ; Microbial Sensitivity Tests ; Multiplex Polymerase Chain Reaction ; Penicillins ; pharmacology ; Singapore ; Trimethoprim ; pharmacology ; Urinary Tract Infections ; microbiology ; beta-Lactamases ; genetics

INTRODUCTIONIn end-stage heart failure (HF) that is not eligible for mechanical assist device or heart transplant, palliative care serves to maximise symptom control and quality of life. We sought to evaluate the impact of home-based advance care programme (ACP) on healthcare utilisation in end-stage HF patients.

MATERIALS AND METHODSProspectively collected registry data on all end-stage HF recruited into ACP between July 2008 and July 2010 were analysed. Chart reviews were conducted on HF database and hospital electronic records. Phone interview and home visit details by ACP team were extracted to complete data entry. HF and all-cause hospitalisations 1 year before, and any time after ACP inception were defined as events. For the latter analysis, follow-up duration adjustment to event episodes was performed to account for death less than a year.

RESULTSForty-four patients (mean age 79 years, 39% men) were followed up for 15±8 months. Fifty-seven percent had diabetes, 80% ischaemic heart disease, and 60% chronic kidney disease. All reported functional class III/IV at enrolment. Mean serum sodium was 136±6 mmol/L, and creatinine 186±126 mmol/L. Thirty (68%) died within the programme. Mean time to death was 5.5 months. Mean all-cause and HF hospitalisations were 3.6 and 2.0 per patient before enrolment, but improved to 1.0 and 0.6 respectively after ACP. Thirty-six (71%) patients had fewer HF hospitalisations. When only those who survived more than a year were considered (n = 14), 10 (71%) and 9 (64%) experienced reduced HF (mean: 1.4 episodes per patient) and all-cause hospitalisations (mean: 2.2 episodes per patient) respectively.

CONCLUSIONHome-based advance care programme is potentially effective in reducing healthcare utilisation of end-stage HF patients, primarily by reducing HF rehospitalisations, and in probably saving costs as well.

Aged ; Aged, 80 and over ; Diabetes Mellitus ; Female ; Health Care Costs ; Health Services ; economics ; utilization ; Heart Failure ; complications ; economics ; therapy ; Home Care Services, Hospital-Based ; economics ; Hospitalization ; economics ; statistics & numerical data ; Humans ; Male ; Myocardial Ischemia ; complications ; Palliative Care ; economics ; methods ; Prospective Studies ; Registries ; Renal Insufficiency, Chronic ; complications ; Tertiary Care Centers

The macrophage scavenger receptor SR-AI binds to host tissue debris to perform clearance and it binds to bacteria for phagocytosis. In addition, SR-AI modulates macrophage activation through cell signaling. However, investigation of SR-AI signaling on macrophages is complicated due to its promiscuous ligand specificity that overlaps with other macrophage receptors. Therefore, we expressed SR-AI on HEK 293T cells to investigate its ligand binding and signaling. On 293Tcells, SR-AI could respond to E. coli DH5α, leading to NF-κB activation and IL-8 production. However, this requires E. coli DH5α to be sensitized by fresh serum that is treated with heat-inactivation or complement C3 depletion. Anti-C3 antibody inhibits the binding of SR-AI to serum-sensitized DH5α and blocks DH5α stimulation of SR-AI signaling. Further analysis showed that SR-AI can directly bind to purified iC3b but not C3 or C3b. By mutagenesis, The SRCR domain of SR-AI was found to be essential in SR-AI binding to serum-sensitized DH5α. These results revealed a novel property of SR-AI as a complement receptor for iC3b-opsonized bacteria that can elicit cell signaling.
Amino Acid Sequence ; Carrier Proteins ; genetics ; metabolism ; Complement C3b ; metabolism ; Escherichia coli ; immunology ; HEK293 Cells ; Humans ; Macrophage Activation ; Molecular Sequence Data ; Mutagenesis ; NF-kappa B ; genetics ; metabolism ; Phagocytosis ; Serine-Arginine Splicing Factors ; Signal Transduction