Antimicrobial treatment challenges in the era of carbapenem resistance

Infections due to carbapenem-resistant Gram-negative bacteria are burdened by high mortality and represent an urgent threat to address. Clinicians are currently at a dawn of a new era in which antibiotic resistance in Gram-negative bacilli is being dealt with by the availability of the first new antibiotics in this field for many years. Although new antibiotics have shown promising results in clinical trials, there is still uncertainty over whether their use will improve clinical outcomes in real world practice. Some observational studies have reported a survival benefit in carbapenem-resistant Enterobacteriaceae bloodstream infections using combination therapy, often including “old” antibiotics such as colistin, aminoglycosides, tigecycline, and carbapenems. These regimens, however, are linked to increased risk of antimicrobial resistance, and their efficacy has yet to be compared to new antimicrobial options. While awaiting more definitive evidence, antibiotic stewards need clear direction on how to optimize the use of old and novel antibiotic options. Furthermore, carbapenem-sparing regimens should be carefully considered as a potential tool to reduce selective antimicrobial pressure

Dexamethasone Prophylaxis in Pediatric Open Heart Surgery Is Associated with Increased Blood Long Pentraxin PTX3: Potential Clinical Implications

Glucocorticoid administration before cardiopulmonary bypass (CPB) can reduce the systemic inflammatory response and improve clinical outcome. Long pentraxin PTX3 is a novel inflammatory parameter that could play a protective cardiovascular role by regulating inflammation. Twenty-nine children undergoing open heart surgery were enrolled in the study. Fourteen received dexamethasone (1st dose 1.5 mg/Kg i.v. or i.m. the evening before surgery; 2nd dose 1.5 mg/kg i.v. before starting bypass) and fifteen children served as control. Blood PTX3, short pentraxin C-reactive protein (CRP), interleukin-1 receptor II (IL-1RII), fibrinogen and partial thromboplastin time (PTT) were assayed at different times. PTX3 levels significantly increased during CPB in dexamethasone-treated (+D) and dexamethasone-untreated (−D) subjects, but were significantly higher in +D than −D patients. CRP levels significantly increased both in +D and −D patients in the postoperative days, with values significantly higher in −D than +D patients. Fibrinogen and PTT values were significantly higher in −D than +D patients in the 1st postoperative day. IL-1RII plasma levels increased in the postoperative period in both groups. Dexamethasone prophylaxis in pediatric patients undergoing CPB for cardiac surgery is associated with a significant increase of blood PTX3 that could contribute to decreasing inflammatory parameters and improving patient clinical outcome

Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis

Background: Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infections associated with high mortality. Objectives: To perform a systematic review of currently available data on distribution, characteristics and outcome associated with carbapenem-resistant bloodstream infections in adult neutropenic patients. Methods: Included studies were identified through Medline, Embase and Cochrane databases between January 1995 and April 2016. Random effect meta-analysis was used to quantify the association between carbapenem resistance and mortality and between carbapenem exposure and resistance. Results: A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to 53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp. were reported in 18 (60%) studies showing high median resistance rates (44% of all carbapenem-resistant Gram-negatives and 19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream infections due to carbapenem-resistant Klebsiella spp. were mainly documented from endemic areas (Greece, Italy, Israel). Carbapenem resistance in Acinetobacter spp. was reported in 9 (30%) studies (median resistance 58% of Acinetobacter isolates). Mortality rates ranged from 33% to 71% (median 50%) in patients with carbapenem-resistant infections. Carbapenemresistance appeared to correlate with mortality (OR 4.89, 95% CI 3.30-7.26) and previous exposure to carbapenems (OR 4.63, 95% CI 3.08-6.96). Conclusions: Carbapenem resistance represents a threat to neutropenic patients. In this group, resistance is likely promoted by previous carbapenem use and leads to high mortality rates. The knowledge of resistance patterns is crucial and can direct clinicians in the use of alternatives to carbapenem-based regimens

Nitrogen but not phosphorus addition affects symbiotic N2 fixation by legumes in natural and semi‑natural grasslands located on four continents

The amount of nitrogen (N) derived from symbiotic N2 fixation by legumes in grasslands might be affected by anthropogenic N and phosphorus (P) inputs, but the underlying mechanisms are not known. Methods We evaluated symbiotic N2 fixation in 17 natural and semi-natural grasslands on four continents that are subjected to the same full-factorial N and P addition experiment, using the 15N natural abundance method. Results N as well as combined N and P (NP) addition reduced aboveground legume biomass by 65% and 45%, respectively, compared to the control, whereas P addition had no significant impact. Addition of N and/or P had no significant effect on the symbiotic N2 fixation per unit legume biomass. In consequence, the amount of N fixed annually per grassland area was less than half in the N addition treatments compared to control and P addition, irrespective of whether the dominant legumes were annuals or perennials. Conclusion Our results reveal that N addition mainly impacts symbiotic N2 fixation via reduced biomass of legumes rather than changes in N2 fixation per unit legume biomass. The results show that soil N enrichment by anthropogenic activities significantly reduces N 2 fixation in grasslands, and these effects cannot be reversed by additional P amendment.EEA Santa CruzFil: Vázquez, Eduardo. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: Vázquez, Eduardo. Swedish University of Agricultural Sciences. Department of Soil and Environment; SueciaFil: Schleuss, Per‑Marten. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: Borer, Elizabeth T. University of Minnesota. Department of Ecology, Evolution, and Behavior; Estados UnidosFil: Bugalho, Miguel N. University of Lisbon. Centre for Applied Ecology “Prof. Baeta Neves” (CEABN-InBIO). School of Agriculture; Portugal.Fil: Caldeira, Maria. C. University of Lisbon. Forest Research Centre. School of Agriculture; Portugal.Fil: Eisenhauer, Nico. German Centre for Integrative Biodiversity Research; AlemaniaFil: Eisenhauer, Nico. Leipzig University. Institute of Biology; AlemaniaFil: Eskelinen, Anu. German Centre for Integrative Biodiversity Research; AlemaniaFil: Eskelinen, Anu. Physiological Diversity, Helmholtz Centrefor Environmental Research; AlemaniaFil: Eskelinen, Anu. University of Oulu. Ecology & Genetics; FinlandiaFil: Fay, Philip A. Grassland Soil and Water Research Laboratory (USDA-ARS); Estados UnidosFil: Haider, Sylvia. German Centre for Integrative Biodiversity Research; AlemaniaFil: Haider, Sylvia. Martin Luther University. Institute of Biology. Geobotany and Botanical Garden; AlemaniaFil: Jentsch, Anke. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: Kirkman, Kevin P. University of KwaZulu-Natal. School of Life Sciences; SudáfricaFil: McCulley, Rebecca L. University of Kentucky. Department of Plant and Soil Sciences; Estados UnidosFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Price, Jodi. Charles Sturt University. Institute for Land, Water and Society; Australia.Fil: Richards, Anna E. CSIRO Land and Water. Northern Territory; Australia.Fil: Risch, Anita C. Swiss Federal Institute for Forest, Snow and Landscape Research WSL; SuizaFil: Roscher, Christiane. German Centre for Integrative Biodiversity Research; AlemaniaFil: Roscher, Christiane. Physiological Diversity, Helmholtz Centre for Environmental Research; AlemaniaFil: Schütz, Martin. Swiss Federal Institute for Forest, Snow and Landscape Research WSL; SuizaFil: Seabloom, Eric William. University of Minnesota. Dept. of Ecology, Evolution, and Behavior; Estados UnidosFil: Standish, Rachel J. Murdoch University. Harry Butler Institute; Australia.Fil: Stevens, Carly J. Lancaster University. Lancaster Environment Centre; Reino UnidoFil: Tedder, Michelle J. University of KwaZulu-Natal. School of Life Sciences; SudáfricaFil: Virtanen, Risto. University of Oulu. Ecology & Genetics; Finlandia.Fil: Spohn, Marie. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: Spohn, Marie. Swedish University of Agricultural Sciences. Department of Soil and Environment; Sueci

Nitrogen but not phosphorus addition affects symbiotic N-2 fixation by legumes in natural and semi-natural grasslands located on four continents

Background and aims: The amount of nitrogen (N) derived from symbiotic N-2 fixation by legumes in grasslands might be affected by anthropogenic N and phosphorus (P) inputs, but the underlying mechanisms are not known.Methods: We evaluated symbiotic N-2 fixation in 17 natural and semi-natural grasslands on four continents that are subjected to the same full-factorial N and P addition experiment, using the N-15 natural abundance method.Results: N as well as combined N and P (NP) addition reduced aboveground legume biomass by 65% and 45%, respectively, compared to the control, whereas P addition had no significant impact. Addition of N and/or P had no significant effect on the symbiotic N-2 fixation per unit legume biomass. In consequence, the amount of N fixed annually per grassland area was less than half in the N addition treatments compared to control and P addition, irrespective of whether the dominant legumes were annuals or perennials.Conclusion: Our results reveal that N addition mainly impacts symbiotic N-2 fixation via reduced biomass of legumes rather than changes in N-2 fixation per unit legume biomass. The results show that soil N enrichment by anthropogenic activities significantly reduces N-2 fixation in grasslands, and these effects cannot be reversed by additional P amendment

A global look at time: a 24-country study of the equivalence of the Zimbardo Time Perspective Inventory

In this article, we assess the structural equivalence of the Zimbardo Time Perspective Inventory (ZTPI) across 26 samples from 24 countries (N = 12,200). The ZTPI is proven to be a valid and reliable index of individual differences in time perspective across five temporal categories: Past Negative, Past Positive, Present Fatalistic, Present Hedonistic, and Future. We obtained evidence for invariance of 36 items (out of 56) and also the five-factor structure of ZTPI across 23 countries. The short ZTPI scales are reliable for country-level analysis, whereas we recommend the use of the full scales for individual-level analysis. The short version of ZTPI will further promote integration of research in the time perspective domain in relation to many different psycho-social processes

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements