At our institution, the prevalence of clinical isolates of Clostridium difficile with resistance to metronidazole is 6.3%. We observed that initial metronidazole MICs of 16 to 64 mg/liter against ...toxigenic, primary fresh C. difficile isolates, as determined by agar dilution, decreased to 0.125 mg/liter after the isolates were thawed. In this study, we examined the possibility of heterogeneous or inducible resistance. Totals of 14 metronidazole-resistant and 10 metronidazole-susceptible clinical isolates of toxigenic C. difficile were studied. The isolates were investigated for the presence of nim genes by PCR. After the isolates were thawed, susceptibility testing was done by agar dilution, by disc diffusion using a 5-μg metronidazole disc, and by the Etest method. An experiment for determining the effect of prolonged exposure to metronidazole was applied to all resistant isolates and to susceptible control strains. None of the isolates presented the nim genes. All initially metronidazole-resistant C. difficile isolates became susceptible after thawing; however, they presented slow-growing subpopulations within the inhibition zones of both the disk and the Etest strip. All metronidazole-susceptible isolates remained homogeneously susceptible by both methods. After prolonged exposure in vitro to metronidazole, no zone of inhibition was found around the 5-μg disk in any of the metronidazole-resistant isolates, and the MICs as determined by the Etest method ranged from 0.125 to >256 mg/liter, with colonies growing inside the inhibition zone. Our results indicate that (i) resistance to metronidazole was not due to the presence of nim genes, (ii) resistance to metronidazole in toxigenic C. difficile isolates is heterogeneous, and (iii) prolonged exposure to metronidazole can select for in vitro resistance. We recommend routine performance of the disk diffusion method (5-μg metronidazole disk) with primary fresh C. difficile isolates in order to ensure that metronidazole-heteroresistant populations do not go undetected.
A multicenter study of
Clostridium difficile
infection (CDI) performed during 2008 in Spain revealed that two of every three episodes went undiagnosed or were misdiagnosed owing to nonsensitive ...diagnostic tests or lack of clinical suspicion and request. Since then, efforts have been made to improve the diagnostic tests used by laboratories and to increase the awareness of this disease among both clinicians and microbiologists. Our objective was to evaluate the impact of these efforts by assessing the current magnitude of underdiagnosis of CDI in Spain using two point-prevalence studies performed on one day each in January and July of 2013. A total of 111 Spanish laboratories selected all unformed stool specimens received for microbiological diagnosis on these days, and toxigenic culture was performed at a central reference laboratory. Toxigenic isolates were characterized both pheno- and genotypically. The reference laboratory detected 103 episodes of CDI in patients aged 2 years or more. Half (50.5 %) of the episodes were not diagnosed in the participating laboratories, owing to insensitive diagnostic tests (15.5 %) or the lack of clinical suspicion and request (35.0 %). The main ribotypes were 014, 078/126, 001/072, and 106. Ribotype 027 caused 2.9 % of all cases. Despite all the interventions undertaken, CDI remains a highly neglected disease because of the lack of sensitive diagnostic tests in some institutions and, especially, the absence of clinical suspicion, mainly in patients with community-associated CDI. Toxigenic
C. difficile
should be routinely sought in unformed stools sent for microbiological diagnosis, regardless of their origin.
SUMMARY
We propose a method for defining the optimal locations of a network of tsunameters in view of near real-time tsunami forecasting using sea surface data assimilation in the near and middle ...fields, just outside of the source region. The method requires first the application of the empirical orthogonal function analysis to identify the potential initial locations, followed by an optimization heuristic that minimizes a cost-benefit function to narrow down the number of stations. We apply the method to a synthetic case of the 2015 Mw8.4 Illapel Chile earthquake and show that it is possible to obtain an accurate tsunami forecast for wave heights at near coastal points, not too close to the source, from assimilating data from three tsunameters during 14 min, but with a minimum average time lag of nearly 5 min between simulated and forecasted waveforms. Additional tests show that the time lag is reduced for tsunami sources that are located just outside of the area covered by the tsunameter network. The latter suggests that sea surface data assimilation from a sparse network of stations could be a strong complement for the fastest tsunami early warning systems based on pre-modelled seismic scenarios.
The present work proposes a morphological evolution model for sandy cuspate beaches, which depends on two parameters, swash excursion (S) and offshore wave steepness (H0/L0). The model was derived ...from observations of morphology and wave climate at Reñaca Beach in central Chile, comprising in-situ instrumentation, topographic surveys, wave modeling, and optical imagery. It was found that wave steepness alone was unable to explain the morphological changes observed on the beach. Rather, results indicate that swash excursion is better to distinguish between erosive and accretionary events, with swash excursion exceeding 29.5 m for more than 12 h being indicative of erosive events. While morphological changes are led by S, wave steepness correlates with the erosive potential of waves, especially when H0/L0 is greater than 0.017. Although derived for a specific beach under a limited range of conditions, this work adds to the understanding of the dynamic behavior of beaches exposed to persistent high-energy swells.
Display omitted
•Horizontal swash excursion is determinant in controlling erosion of a cuspate beach under persistent high-energy swells.•All erosion events occur when swash excursion exceeds 29.5 m for over 12 h.•Erosion events are driven by swash excursion, with wave steepness enhancing erosive potential.•The magnitude of accretion and erosion is conditioned by the antecedent state.
Although the study of thermoregulation in insects has shown that infected animals tend to prefer higher temperatures than healthy individuals, the immune response and energetic consequences of this ...preference remain unknown. We examined the effect of environmental temperature and the energetic costs associated to the activation of the immune response of Tenebrio molitor larvae following a lipopolysaccharide (LPS) challenge. We measured the effect of temperature on immune parameters including phenoloxidase (PO) activity and antibacterial responses. Further as proximal and distal costs of the immune response we determined the standard metabolic rate (SMR) and the loss of body mass (mb), respectively. Immune response was stronger at 30°C than was at 10 or 20°C. While SMR at 10 and 20°C did not differ between immune treatments, at 30°C SMR of LPS-treated larvae was almost 25–60% higher than SMR of PBS-treated and naïve larvae. In addition, the loss in mb was 1.9 and 4.2 times higher in LPS-treated larvae than in PBS-treated and naïve controls. The immune responses exhibited a positive correlation with temperature and both, SMR and mb change, were sensitive to environmental temperature. These data suggest a significant effect of environmental temperature on the immune response and on the energetic costs of immunity.
The clinical significance of prolonged viral shedding (PVS) and viral load (VL) dynamics has not been sufficiently assessed in hospitalized patients with pandemic 2009 influenza A(H1N1). We performed ...a prospective study of adults with confirmed influenza A(H1N1) virus infection admitted to our hospital from 20 September 2009 to 31 December 2009. Consecutive nasopharyngeal swabs were collected every 2 days during the first week after diagnosis, and then every week or until viral detection was negative. Relative VL was measured on the basis of haemagglutinin and RNaseP gene analysis. PVS was defined as positive detection of influenza A(H1N1) virus by real-time RT-PCR at day 7 after diagnosis. We studied 64 patients: 16 (25%) presented PVS. The factors associated with PVS were admission to the intensive-care unit (69% vs. 33%, p 0.02), purulent expectoration (75% vs. 44%, p 0.04), higher dosage of oseltamivir (62.5% vs. 27%, p 0.016), corticosteroid treatment (50% vs. 21%, p 0.05), mechanical ventilation (MV) (50% vs. 12.5%, p 0.004), and longer stay (34 vs. 7 median days, p 0.003). Multivariate analysis revealed the factors independently associated with PVS to be immunosuppression (OR 5.15; 95% CI 1.2–22.2; p 0.03) and the need for MV (OR 11.7; 95% CI 2.5–54.4; p 0.002). VL at diagnosis correlated negatively with age and septic shock. VL dynamics of patients with acute respiratory distress syndrome and/or mortality were very different from those of other patients. PVS was detected in 25% of hospitalized patients with pandemic 2009 influenza A(H1N1) and was strongly associated with immunosuppression and the need for MV. Diagnostic VL and viral clearance varied with the clinical course.
Obstructive sleep apnoea (OSA) is a risk factor for stroke, but little is known about the effect of OSA and continuous positive airway pressure (CPAP) on the incidence of long-term, nonfatal ...cardiovascular events (CVE) in stroke patients. A prospective observational study was made in 223 patients consecutively admitted for stroke. A sleep study was performed on 166 of them. 31 had an apnoea/hypopnoea index (AHI) <10 events · h(-1); 39 had an AHI between 10 and 19 events · h(-1) and 96 had an AHI ≥ 20 events · h(-1). CPAP treatment was offered when AHI was ≥ 20 events · h(-1). Patients were followed up for 7 yrs and incident CVE data were recorded. The mean ± SD age of the subjects was 73.3 ± 11 yrs; mean AHI was 26 ± 16.7 events · h(-1). Patients with moderate-to-severe OSA who could not tolerate CPAP (AHI ≥ 20 events · h(-1); n = 68) showed an increased adjusted incidence of nonfatal CVE, especially new ischaemic strokes (hazard ratio 2.87, 95% CI 1.11-7.71; p = 0.03), compared with patients with moderate-to-severe OSA who tolerated CPAP (n = 28), patients with mild disease (AHI 10-19 events · h(-1); n = 36) and patients without OSA (AHI <10 events · h(-1); n = 31). Our results suggest that the presence of moderate-to-severe OSA is associated with an increased long-term incidence of nonfatal CVE in stroke patients and that CPAP reduces the excess of incidence seen in these patients.
Following the construction introduced by Antoniadis and Savvidy in Refs. 1–3, we study metric-independent topological invariants on a (2n+1)-dimensional space–time. These invariants allow us to show ...that Chamseddine's even-dimensional topological gravity corresponds to a Chern–Simons–Antoniadis–Savvidy form. Starting from this result, more general four-dimensional topological gravity actions are explicitly constructed.
Apart from the overwhelming cases of allopolyploidization, the impact of speciation through homoploid hybridization is becoming more relevant than previously thought. Much less is known, however, ...about the impact of climate changes as a driven factor of speciation. To investigate these issues, we selected Festuca picoeuropeana, an hypothetical natural hybrid between the diploid species F. eskia and F. gautieri that occurs in two different mountain ranges (Cantabrian Mountains and Pyrenees) separated by more than 400 km. To unravel the outcomes of this mode of speciation and the impact of climate during speciation we used a multidisciplinary approach combining genome size and chromosome counts, data from an extensive nuclear genotypic analysis, plastid sequences and ecological niche models (ENM). Our results show that the same homoploid hybrid was originated independently in the two mountain ranges, being currently isolated from both parents and producing viable seeds. Parental species had the opportunity to contact as early as 21000 years ago although niche divergence occurs nowadays as result of a climate-driven shift. A high degree of niche divergence was observed between the hybrid and its parents and no recent introgression or backcrossed hybrids were detected, supporting the current presence of reproductive isolation barriers between these species.
Influenza virus infection remains a major cause of morbidity and mortality during winter seasons. Bacterial and virus co-infection is a commonly described situation in these patients. However, data ...on co-infection by influenza A and B viruses are lacking. In this study, we present the cases of co-infection by influenza A and B viruses during the winter season of 2014–2015 in our institution. We analyzed 2759 samples from 2111 patients and found that 625 samples corresponding to 609 patients were positive for influenza A or B virus. A total of 371 patients had influenza A, 228 had influenza B, and 10 (1.6 %) had influenza A and B virus detection in the same sample. The median age of co-infected patients was 78.6 years, and only one of the co-infected patients died because of the infection. Comparison with a control group of mono-infected patients revealed that co-infection was significantly associated with nosocomial acquisition odds ratio (OR) = 4.5, 95 % confidence interval (CI) = 1.05–19.25,
p
= 0.042. However, co-infection was not associated with worse outcome, previous underlying condition, or vaccination status. Multivariate analysis revealed that co-infection was not an independent risk factor for death and that no single risk factor could predict co-infection.