Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae

In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here, we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter species from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM). We collected clinical data and screened all isolates for the presence of ampC alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at \u3e/=72 h from the time of treatment initiation. Of 493 patients with bacteremia, 165 patients met the inclusion criteria, of which 88 were treated with TZP and 77 with FEP or MEM. To minimize differences between covariates, we carried out propensity score matching, which yielded 41 matched pairs. Groups only differed by age, with patients in the TZP group significantly older (P = 0.012). There were no significant differences in 30-day mortality, persistent bacteremia, 7-day mortality, or treatment escalation between the two treatment groups, including in the propensity score-matched cohort. PCR amplification and sequencing of ampC genes revealed the presence of ampC in isolates with cefoxitin MICs below 16 mug/ml, in particular in Serratia spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC beta-lactamase-producing Enterobacteriaceae, diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings

Timing and clinical risk factors for early acquisition of gut pathogen colonization with multidrug resistant organisms in the intensive care unit

Background Microbiome restitution therapies are being developed to prevent gut pathogen colonization among patients in the intensive care unit (ICU) and in other select populations. If preventive therapies are to be effective, they must be administered prior to pathogen acquisition. The timing and risk factors for early acquisition of gut pathogen colonization (within 72 h) are currently unknown and could be helpful to guide ICU trial design. Methods This was a prospective cohort study. Patients in the ICU had deep rectal swabs performed within 4 h of ICU admission and exactly 72 h later. Early gut pathogen colonization was classified as the new presence (based on culture of rectal swabs) of one or more of the following organisms of interest: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant (VRE), and Gram-negative bacteria that showed multidrug resistance (MDR) or third generation Cephalosporin resistance (Ceph-R). Clinical risk factors for early acquisition of gut pathogen colonization were captured using the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scoring system. Findings Among 131 patients who were swabbed at ICU admission and 72 h later, the rates of gut pathogen colonization at ICU admission were 11.4%, 10.6%, 38.6%, and 8.3% for MRSA, VRE, MDR and Ceph-R Gram-negatives respectively. Among the patients who were negative for a given pathogen at ICU admission, the rates of early acquisition of gut pathogen colonization were 7.8% for MRSA (95% CI 3.6 to 14.2%), 7.7% for VRE (95% CI 3.6 to 14.1%), 11.3% for MDR Gram-negatives (95% CI 4.4 to 18.8%), and 4.2% for Ceph-R Gram-negatives (95% CI 1.4 to 9.5%). There were no clinical risk factors which independently predicted early acquisition of gut pathogen colonization. Interpretation Early gut pathogen colonization was common in the ICU, but our single-center study could not identify any clinical risk factors which were significantly associated with acquisition of gut pathogens

Respective impacts of Arctic sea ice decline and increasing greenhouse gases concentration on Sahel precipitation

The impact of climate change on Sahel precipitation is uncertain and has to be widely documented. Recently, it has been shown that Arctic sea ice loss leverages the global warming effects worldwide, suggesting a potential impact of Arctic sea ice decline on tropical regions. However, defining the specific roles of increasing greenhouse gases (GHG) concentration and declining Arctic sea ice extent on Sahel climate is not straightforward since the former impacts the latter. We avoid this dependency by analysing idealized experiments performed with the CNRM-CM5 coupled model. Results show that the increase in GHG concentration explains most of the Sahel precipitation change. We found that the impact due to Arctic sea ice loss depends on the level of atmospheric GHG concentration. When the GHG concentration is relatively low (values representative of 1980s), then the impact is moderate over the Sahel. However, when the concentration in GHG is levelled up, then Arctic sea ice loss leads to increased Sahel precipitation. In this particular case the ocean-land meridional gradient of temperature strengthens, allowing a more intense monsoon circulation. We linked the non-linearity of Arctic sea ice decline impact with differences in temperature and sea level pressure changes over the North Atlantic Ocean. We argue that the impact of the Arctic sea ice loss will become more relevant with time, in the context of climate change

Redirecting research efforts on the diversification-performance linkage: The search for synergy

We review the literature on the diversification-performance (D-P) relationship to a) propose that the time is ripe for a renewed attack on understanding the relationship between diversification and firm performance, and b) outline a new approach to attacking the question. Our paper makes four main contributions. First, through a review of the literature we establish the inherent complexities in the D-P relationship and the methodological challenges confronted by the literature in reaching its current conclusion of a non-linear relationship between diversification and performance. Second, we argue that to better guide managers the literature needs to develop along a complementary path – whereas past research has often focused on answering the big question of does diversification affect firm performance, this second path would focus more on identifying the precise micro-mechanisms through which diversification adds or subtracts value. Third, we outline a new approach to the investigation of this topic, based on (a) identifying the precise underlying mechanisms through which diversification affects performance; (b) identifying performance outcomes that are “proximate” to the mechanism that the researcher is studying, and (c) identifying an appropriate research design that can enable a causal claim. Finally, we outline a set of directions for future research

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks