Abstract
Objectives
To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel β-lactam/β-lactamase inhibitor combinations.
...Material and methods
Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project).
Results
Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10–1.31, P < 0.001) and Pitt score (HR 1.33; 95% CI 1.15–1.55, P < 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74–2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50–2.29, P = 0.866).
Conclusions
Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp.
Introduction
Inhaled low-dose methoxyflurane is approved in Europe for emergency relief of moderate-to-severe trauma-related pain in adults, but data versus active comparators are sparse. The phase ...IIIb Methoxyflurane in Emergency Department in ITAly (MEDITA) trial investigated the analgesic efficacy, practicality and safety of methoxyflurane versus standard analgesic treatment (SAT) for acute trauma pain.
Methods
This was a randomised, active-controlled, parallel-group, open-label trial conducted in 15 Italian emergency units. Adults with limb trauma and pain score ≥ 4 on numerical rating scale (NRS) were randomised 1:1 to inhaled methoxyflurane 3 mL or SAT intravenously administered (IV) morphine 0.1 mg/kg for severe pain (NRS ≥ 7); IV paracetamol 1 g or IV ketoprofen 100 mg for moderate pain (NRS 4–6). The primary endpoint was overall change in visual analogue scale (VAS) pain intensity from baseline (time of randomisation) to 3, 5 and 10 min. Non-inferiority and superiority of methoxyflurane versus SAT were concluded if the upper 95% confidence interval (CI) for the treatment comparison (methoxyflurane–SAT) was less than 1 and less than 0, respectively.
Results
Between 8 February 2018 and 8 February 2019, 272 patients were randomised (136 per treatment group). A total of 270 patients (mean age 51 years; 49% male; 34% with severe pain; mean baseline VAS 67 mm) were treated and analysed for efficacy and safety. Superiority of methoxyflurane was demonstrated for moderate-to-severe pain (adjusted mean treatment difference − 5.94 mm; 95% CI − 8.83, − 3.06 mm), moderate pain (− 5.97 mm; 95% CI − 9.55, − 2.39 mm) and severe pain (− 5.54 mm; 95% CI − 10.49, − 0.59 mm). Median onset of pain relief was 9 min for methoxyflurane and 15 min for SAT. Practicality of methoxyflurane treatment was rated “Excellent”, “Very Good” or “Good” by 90% of clinicians vs. 64% for SAT. Adverse events (all non-serious) were reported by 17% of methoxyflurane-treated patients and 3% of SAT-treated patients.
Conclusion
Methoxyflurane provided superior pain relief to SAT in patients with moderate-to-severe trauma pain and may offer a simple, fast, effective non-opioid treatment option.
Trial registration
Trial registered with EudraCT (2017-001565-25) on 2 March 2018 and ClinicalTrials.gov (NCT03585374) on 13 July 2018.
Funding
Mundipharma Pharmaceuticals S.r.l.
Background
In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with ...polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice.
Methods
The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP.
Results
Septic shock was diagnosed in 305 (85.4 %) patients. The most common source of infection was abdominal (44.0 %) followed by pulmonary (17.6 %). Gram negative bacteria represented 60.6 % of the pathogens responsible of infection. After 72 h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16 ± 1.77 from 3.32 ± 1.29,
p
< 0.0001), respiratory (1.95 ± 0.95 from 2.40 ± 1.06,
p
< 0.001) and renal (1.84 ± 1.77 from 2.23 ± 1.62,
p
= 0.013). Overall 28-day survival rate was 54.5 % (60.4 % in abdominal and 47.5 % in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24 h from the diagnosis of septic shock had a 28-day survival rate of 64.5 %. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75 % in comparison to the 39 % of patients who did not (
p
< 0.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5 %,
p
= 0.003), ICU (59 vs. 36.7 %,
p
= 0.006) and hospital survival rate (53.2 vs. 35 %,
p
= 0.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission.
Conclusion
The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique.
The main source of systematic uncertainty on neutrino cross section measurements at the GeV scale is represented by the poor knowledge of the initial flux. The goal of cutting down this uncertainty ...to 1% can be achieved through the monitoring of charged leptons produced in association with neutrinos, by properly instrumenting the decay region of a conventional narrow-band neutrino beam. Large angle muons and positrons from kaons are measured by a sampling calorimeter on the decay tunnel walls (tagger), while muon stations after the hadron dump can be used to monitor the neutrino component from pion decays. This instrumentation can provide a full control on both the muon and electron neutrino fluxes at all energies. Furthermore, the narrow momentum width (<10%) of the beam provides a O(10%) measurement of the neutrino energy on an event by event basis, thanks to its correlation with the radial position of the interaction at the neutrino detector. The ENUBET project has been funded by the ERC in 2016 to prove the feasibility of such a monitored neutrino beam and is cast in the framework of the CERN neutrino platform (NP06) and the Physics Beyond Colliders initiative. In our contribution, we summarize the ENUBET design, physics performance and opportunities for its implementation in a timescale comparable with next long baseline neutrino experiments.
Epidemiological models are relevant to study and analyze clinical as well as environmental and behavioural data, useful to support health studies. The target is to perform epidemiological analysis ...producing fast and reliable data access useful to guide prevention and curing processes. This is currently true in pandemic emergency as the current Covid-19 context. Epidemiological models should support in the early identification of pandemic phenomena and in making available data set for studying more accurate drug-based strategy for vaccines or virus containment.In this contribution we present an epidemiology database which integrates different types of clinical data to support research, follow-up and patient monitoring. The idea starts from an hospital databases cooperation integration where virus available data have been integrated to support statistical based studies. Starting from an available database containing 5 years data of infection related viruses (such as HPC, hepatitis) and patient anonymous data, the proposed system provide an integrated data access able to (i) extracting data filtered by means of clinical hypothesis based on patient profiles, environment and drugs and (ii) allowing to build large scale geographical data mappings in order to study correlations among chronic infection diseases and their relations with upcoming pandemic phenomena. Even if the application is in its infancy, the application is relevant with high very important applications.
After incubation of equimolar amounts of cisplatin (CDDP) and glutathione (GSH) in phosphate buffer pH 7.4 at 37°C, we detected two CDDP-GSH adducts whose structures, characterized by LC-MS, ...corresponded to
cis-Pt(NH
3)
2Cl(SG) and
cis-{Pt(NH
3)
2Cl
2( μ-SG)}
+. The latter is a new CDDP-GSH adduct, which was postulated but never structurally characterized so far. Rats and patients were given a 15-min intravenous infusion of CDDP (10 mg/kg to rats and 25 mg/m
2 to patients) preceded by a GSH intravenous administration (200 mg/kg to rats as a bolus and 1.5 g/m
2 to patients as a 15-min infusion). After the administrations, CDDP-GSH adducts were absent in rat and human plasma ultrafiltrates. The discrepancy between in vitro and in vivo findings can be explained based on pharmacokinetic considerations.
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