Evaluation of Ertapenem use with Impact Assessment on Extended-Spectrum Beta-Lactamases (ESBL) Production and Gram-Negative resistance in Singapore General Hospital (SGH)

BACKGROUND: Ertapenem (preferred choice for ESBL-producing organisms) use exhibited an increasing trend from 2006 to 2008. As extensive use of ertapenem might induce the mutation of resistant bacteria strains to ertapenem, we aimed to assess the appropriateness and impact of ertapenem-use, on ESBL production, the trends of gram-negative bacterial resistance and on the utilization of other antibiotics in our institution. METHODS: Inpatients who received a dose of ertapenem during 1 January 2006 to 31 December 2008, were reviewed. Pertinent patient clinical data was extracted from the pharmacy databases and assessed for appropriateness based on dose and indication. Relevant data from Network for Antimicrobial Resistance Surveillance (Singapore) (NARSS) was extracted, to cross-correlate with ertapenem via time series to assess its impact on hospital epidemiology, trends of gram-negative resistance and consumption of other antibiotics from 2006 to mid-2010. RESULTS: 906 cases were reviewed. Ertapenem therapy was appropriate in 72.4% (93.7% success rate). CNS adverse events were noted in 3.2%. Readmission rate (30-day) due to re-infection (same pathogen) was 5.5%. Fifty cases had cultures growing Pseudomonas aeruginosa within 30 days of ertapenem initiation, with 25 cases growing carbapenem-resistant Pseudomonas aeruginosa. Ertapenem use increased from 0.45 DDD/100 patient days in 2006 to 1.2 DDD/100 patient days in mid-2010. Overall, the increasing trend of ertapenem consumption correlated with 1) increasing incidence-densities of ciprofloxacin-resistant/cephalosporin-resistant E. coli at zero time lag; 2) increasing incidence-densities of ertapenem-resistant Escherichia. coli and Klebsiella spp. at zero time lag; 3) increasing incidence-density of carbapenem-resistant Pseudomonas aeruginosa, at zero time lag. Increasing ertapenem consumption was significantly correlated with decreasing consumption of cefepime (R(2) = 0.37344) 3 months later. It was significantly correlated with a decrease in imipenem consumption (R(2) = 0.31081), with no time lag but was correlated with subsequent increasing consumption of meropenem (R(2) = 0.4092) 6 months later. CONCLUSION: Ertapenem use was appropriate. Increasing Ertapenem consumption did not result in a decreasing trend of ESBL producing enterobacteriaceae and could result in the selection for multi-drug resistant bacteria

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Femtocell/Macrocell Interference Analysis for Mobile WiMAX System

Femtocell can provide better indoor coverage and capacity of cellular systems. In order to operate femtocell appropriately, RF interference analysis between femtocells and macrocells is needed. In this paper, we discussed the impact of interference by the introduction of femtocell in Mobile WiMAX system. Performance degradation was evaluated for the downlink case by system level simulation. Simulation results shows that the impact of interference from macrocell to femtocell is more severe than from femtocell to macrocell. By allocating different frequency bands for femtocell and macrocell, performance degradation can be negligible.This work was partly supported by the Brain Korea 21 project and the IT R&D program of MKE/IITA. [2007-S-029-02, Development of Indoor WiBro System for Home and Enterprise

Outcome of donors with a remnant liver volume of less than 35% after right hepatectomy

To overcome the barrier of size match, right lobe graft has been widely used in living donor liver transplantation (LDLT). We assessed donor outcome, with a focus on remnant liver volume (RLV) after right hepatectomy based on the experiences of 2 LDLT centers, as a means of guiding the establishment of safe RLV limits for donor right hepatectomy. Between January 2002 and December 2003, a consecutive 146 liver donors who underwent right hepatectomy with at least 12 months of follow-up were enrolled in this study. Donors were grouped into 2 groups according to RLV: group 1 (n = 74), or = 35% (35.0-46.8). No donors died or suffered a life-threatening complication. Mean peak serum postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (IU/L) levels were 219.5 +/- 79.9 and 231.5 +/- 83.3 in group 1 and 210.3 +/- 81.6 and 225.8 +/- 93.0 in group 2 (P = 0.497 and 0.699), respectively. Mean peak serum total bilirubin (TB) (mg/dL) level in group 1 (3.4 +/- 1.6) was higher than in group 2 (2.8 +/- 1.4; P = 0.023). Overall 23 (15.8%) major morbidities, 10 in group 1 (13.5%) and 13 in group 2 (18.1%), occurred according to Clavien's system (P = 0.939). These included bleeding (n = 3 in group 1 and n = 6 in group 2; P = 0.282), ileus (n = 3 and 1; P = 0.324), biliary leakage (n = 4 and 4; P = 0.968), and pneumonia (n = 0 and 2; P = 0.149). Minor morbidities were also comparable in the 2 groups. In conclusion, the outcome of donors with an RLV of or = 35%, with the exception of transient cholestasis. Therefore, a remnant RLV of <35% does not appear to be a contraindication for right liver procurement in living donors