Retrospective studies have shown that outdoor temperature influences the prevalence of detectable brown adipose tissue (BAT). Prospective studies use acute cold exposure to activate BAT. In prospective studies, BAT might be preconditioned in winter months leading to an increased BAT response to various stimuli. Therefore the aim of this study was to assess whether outdoor temperatures and other weather characteristics modulate the response of BAT to acute cold. To assess metabolic BAT activity and sympathetic outflow to BAT, 64 (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) and 56 additional (123)I-meta-iodobenzylguanidine ((123)I-mIBG) single-photon emission computed tomography-CT (SPECT-CT) scans, respectively, of subjects participating in previously executed trials were retrospectively included. BAT activity was measured in subjects after an overnight fast, following 2 h of cold exposure (∼17°C). The average daytime outdoor temperatures and other weather characteristics were obtained from the Dutch Royal Weather Institute. Forty-nine subjects were BAT positive. One week prior to the scan, outdoor temperature was significantly lower in the BAT-positive group compared with the BAT-negative group. Higher outdoor temperatures on preceding days resulted in lower stimulated metabolic BAT activity and volume (all P < 0.01). Outdoor temperatures did not correlate with sympathetic outflow to BAT. In conclusion, outdoor temperatures influence metabolic BAT activity and volume, but not sympathetic outflow to BAT, in subjects exposed to acute cold. To improve the consistency of the findings of future BAT studies in humans and to exclude bias introduced by outdoor temperatures, these studies should be planned in periods of similar outdoor temperatures.

Objectives: Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands. Methods: In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to noninfected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection. Results: We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66e3.09) and 1.32 (1.06e1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48e2.41). Conclusions: In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections.

Background: The prophylactic use of antimicrobial agents to prevent infections in non-surgical situations has hardly been investigated. We investigate the extent, indications and appropriateness of antimicrobial prophylaxis given outside the operating room in a tertiary care hospital. Methods: Four point-prevalence surveys were conducted in which all inpatients on that day were screened for the use of prophylactic antimicrobials: medical prophylaxis, prophylaxis around non-surgical interventions and surgical prophylaxis given on the ward. The primary endpoint was the extent of prophylaxis relative to the total number of antimicrobial prescriptions. We also investigated per prescription the presence of a (local) protocol and adherence to these protocols. Results: We registered in total 1020 antimicrobial prescriptions, of which 317 (31.1%) were given as prophylaxis. 827/ 1020 were antibiotic prescriptions. Of these antibiotic prescriptions, 17.0% was medical prophylaxis, 2.7% prophylaxis around non-surgical interventions and 6.9% surgical prophylaxis administered on a ward. For medical antibiotic prophylaxis, a protocol was present in 125 of 141 prescriptions (88.7%); the protocol was followed in 118 cases (94.4%). For prophylaxis around non-surgical interventions and surgical prophylaxis on the wards, protocol presence and adherence rates were 59.1% and 92.3%, and 73.3% and 97.6% respectively. Of the 96 antiviral and 97 antifungal prescriptions, 42.7% and 57.8%, respectively, were medical prophylaxis, of which 95.1 and 96.3% were prescribed according to protocols respectively. Conclusions: Antimicrobial prophylaxis outside the operating theatre is responsible for a considerable part of total in-hospital antimicrobial use. For most prescriptions there was a protocol and adherence to the protocols was high. The main targets for improvement were prophylaxis around non-surgical interventions and surgical prophylaxis given on the ward.

Objective: Short-course aminoglycosides as adjunctive empirical therapy to b-lactams in patients with a clinical suspicion of sepsis are used to broaden antibiotic susceptibility coverage and to enhance bacterial killing. We quantified the impact of this approach on 30-day mortality in a subset of sepsis patients with a Gram-negative bloodstream infection. Methods: From a prospective cohort study conducted in seven hospitals in the Netherlands between June 2013 and November 2015, we selected all patients with Gram-negative bloodstream infection (GN-BSI). Short-course aminoglycoside therapy was defined as tobramycin, gentamicin or amikacin initiated within a 48-hour time window around blood-culture obtainment, and prescribed for a maximum of 2 days. The outcome of interest was 30-day all-cause mortality. Confounders were selected a priori for adjustment using a propensity score analysis with inverse probability weighting.Results: A total of 626 individuals with GN-BSI who received b-lactams were included; 156 (24.9%) also received aminoglycosides for a median of 1 day. Patients receiving aminoglycosides more often had septic shock (31/156, 19.9% versus 34/470, 7.2%) and had an eight-fold lower risk of inappropriate treatment (3/156, 1.9% versus 69/470, 14.7%). Thirty-day mortality was 17.3% (27/156) and 13.6% (64/470) for patients receiving and not receiving aminoglycosides, respectively; yielding crude and adjusted odds ratios for 30-day mortality for patients treated with aminoglycosides of 1.33 (95% CI 0.80e2.15) and 1.57 (0.84e2.93), respectively.Conclusions: Short-course adjunctive aminoglycoside treatment as part of empirical therapy with blactam antibiotics in patients with GN-BSI did not result in improved outcomes, despite better antibiotic coverage of pathogens.

a , k , on behalf of the ISIS-AR study group l , 1