Secular Trend and Risk Factors for Antimicrobial Resistance in Escherichia coli Isolates in Switzerland 1997-2007

Abstract : Background: : Antibacterial resistance in Escherichia coli isolates of urinary infections, mainly to fluoroquinolones, is emerging. The aim of our study was to identify the secular trend of resistant E. coli isolates and to characterize the population at risk for colonization or infections with these organisms. Patients and Methods: : Retrospective analysis of 3,430 E.coli first isolates of urine specimens from patients admitted to the University Hospital Basel in 1997, 2000, 2003, and 2007. Results: : Resistance to ciprofloxacin, trimethoprim/sulfamethoxazole, and amoxicillin/clavulanate has increased over the 10-year study period (from 1.8% to 15.9%, 17.4% to 21.3%, and 9.5% to 14.5%, respectively). A detailed analysis of the 2007 data revealed that independent risk factors for ciprofloxacin resistance were age (5.3% 75 years; odds ratio [OR] 1.29 per 10 years, 95% confidence interval [CI] 1.15-1.45, p < 0.001) and male gender (OR 1.59, 95% CI 1.05-2.41, p = 0.04). In contrast, nosocomial E. coli isolates were associated with lower odds of ciprofloxacin resistance (OR 0.51, 95% CI 0.28-0.67, p < 0.001). The frequency of resistant isolate rates was not influenced by the clinical significance (i.e., colonization vs urinary tract infection, UTI) or by whether the urine was taken from a urinary catheter. Importantly, the increase in ciprofloxacin resistance paralleled the increase in ciprofloxacin consumption in Switzerland (Pearson's correlation test R2= 0.998, p = 0.002). Of note, resistance was less frequent in isolates sent in by general practitioners. However, after adjustment for age and gender, only resistance against amoxicillin/clavulanate was found to be less frequent (OR 0.34, 95% CI 0.16-0.92, p = 0.03). Conclusion: : Our study reveals that resistance rates have been increasing during the last decade. Published resistance rates may lack information due to important differences regarding age, gender, and probable origin of the isolates. Empirical therapy for UTI should be guided more on individual risk profile and local resistance data than on resistance data bank

Significant increases in global weathering during Oceanic Anoxic Events 1a and 2 indicated by calcium isotopes

Calcium-isotope ratios (δ44/42Ca) were measured in carbonate-rich sedimentary sections deposited during Oceanic Anoxic Events 1a (Early Aptian) and 2 (Cenomanian-Turonian). In sections from Resolution Guyot, Mid-Pacific Mountains; Coppitella, Italy; and the English Chalk at Eastbourne and South Ferriby, UK, a negative excursion in δ44/42Ca of ~0.20‰ and ~0.10‰ is observed for the two events. These δ44/42Ca excursions occur at the same stratigraphic level as the carbon-isotope excursions that define the events, but do not correlate with evidence for carbonate dissolution or lithological changes. Diagenetic and temperature effects on the calcium-isotope ratios can be discounted, leaving changes in global seawater composition as the most probable explanation for δ44/42Ca changes in four different carbonate sections. An oceanic box model with coupled strontium- and calcium-isotope systems indicates that a global weathering increase is likely to be the dominant driver of transient excursions in calcium-isotope ratios. The model suggests that contributions from hydrothermal activity and carbonate dissolution are too small and short-lived to affect the oceanic calcium reservoir measurably. A modelled increase in weathering flux, on the order of three times the modern flux, combined with increased hydrothermal activity due to formation of the Ontong-Java Plateau (OAE1a) and Caribbean Plateau (OAE2), can produce trends in both calcium and strontium isotopes that match the signals recorded in the carbonate sections. This study presents the first major-element record of a weathering response to Oceanic Anoxic Events. © 2011 Elsevier B.V

Secular trend and risk factors for antimicrobial resistance in Escherichia coli isolates in Switzerland 1997-2007

BACKGROUND: : Antibacterial resistance in Escherichia coli isolates of urinary infections, mainly to fluoroquinolones, is emerging. The aim of our study was to identify the secular trend of resistant E. coli isolates and to characterize the population at risk for colonization or infections with these organisms. PATIENTS AND METHODS: : Retrospective analysis of 3,430 E.coli first isolates of urine specimens from patients admitted to the University Hospital Basel in 1997, 2000, 2003, and 2007. RESULTS: : Resistance to ciprofloxacin, trimethoprim/sulfamethoxazole, and amoxicillin/clavulanate has increased over the 10-year study period (from 1.8% to 15.9%, 17.4% to 21.3%, and 9.5% to 14.5%, respectively). A detailed analysis of the 2007 data revealed that independent risk factors for ciprofloxacin resistance were age (5.3% > 35 years of age to 21.9% in patients 0.001) and male gender (OR 1.59, 95% CI 1.05-2.41, p = 0.04). In contrast, nosocomial E. coli isolates were associated with lower odds of ciprofloxacin resistance (OR 0.51, 95% CI 0.28-0.67, p > 0.001). The frequency of resistant isolate rates was not influenced by the clinical significance (i.e., colonization vs urinary tract infection, UTI) or by whether the urine was taken from a urinary catheter. Importantly, the increase in ciprofloxacin resistance paralleled the increase in ciprofloxacin consumption in Switzerland (Pearson's correlation test R(2)= 0.998, p = 0.002). Of note, resistance was less frequent in isolates sent in by general practitioners. However, after adjustment for age and gender, only resistance against amoxicillin/clavulanate was found to be less frequent (OR 0.34, 95% CI 0.16-0.92, p = 0.03). CONCLUSION: : Our study reveals that resistance rates have been increasing during the last decade. Published resistance rates may lack information due to important differences regarding age, gender, and probable origin of the isolates. Empirical therapy for UTI should be guided more on individual risk profile and local resistance data than on resistance data banks

Safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 spinal muscular atrophy: a randomised, double-blind, placebo-controlled phase 2 trial

Background Spinal muscular atrophy (SMA) is a progressive motor neuron disease causing loss of motor function and reduced life expectancy, for which limited treatment is available. We investigated the safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 SMA. Methods This randomised, double-blind, placebo-controlled, phase 2 study was done in 22 neuromuscular care centres in Belgium, France, Germany, Italy, Netherlands, Poland, and the UK. Safety and efficacy of olesoxime were assessed in patients aged 3\u201325 years with genetically confirmed type 2 or non-ambulatory type 3 SMA. A centralised, computerised randomisation process allocated patients (2:1 with stratification by SMA type and centre) to receive olesoxime (10 mg/kg per day) in an oral liquid suspension or placebo for 24 months. Patients, investigators assessing outcomes, and sponsor study personnel were masked to treatment assignment. The primary outcome measure was change from baseline compared with 24 months between the two treatment groups in functional domains 1 and 2 of the Motor Function Measure (MFM D1 + D2) assessed in the full analysis population. A shorter, 20-item version of the MFM, which was specifically adapted for young children, was used to assess patients younger than 6 years. Safety was assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01302600. Findings The trial was done between Nov 18, 2010, and Oct 9, 2013. Of 198 patients screened, 165 were randomly assigned to olesoxime (n=108) or placebo (n=57). Five patients in the olesoxime group were not included in the primary outcome analysis because of an absence of post-baseline assessments. The change from baseline to month 24 on the primary outcome measure was 0\ub718 for olesoxime and 121\ub782 for placebo (treatment difference 2\ub700 points, 96% CI 120\ub725 to 4\ub725, p=0\ub70676). Olesoxime seemed to be safe and generally well tolerated, with an adverse event profile similar to placebo. The most frequent adverse events in the olesoxime group were pyrexia (n=34), cough (n=32), nasopharyngitis (n=25), and vomiting (n=25). There were two patient deaths (one in each group), but these were not deemed to be related to the study treatment. Interpretation Olesoxime was safe at the doses studied, for the duration of the trial. Although the primary endpoint was not met, secondary endpoints and sensitivity analyses suggest that olesoxime might maintain motor function in patients with type 2 or type 3 SMA over a period of 24 months. Based on these results, olesoxime might provide meaningful clinical benefits for patients with SMA and, given its mode of action, might be used in combination with other drugs targeting other mechanisms of disease, although additional evidence is needed. Funding AFM T\ue9l\ue9thon and Trophos SA