A European Organization for Research and Treatment of Cancer-International Antimicrobial Therapy Group Study of secondary infections in febrile, neutropenic patients with cancer

BACKGROUND: Neutropenic patients with cancer may develop several episodes of fever and infection during chemotherapy-induced myeloaplasia. METHODS: To identify risk factors for secondary infectious episodes among patients who responded to initial antibiotic therapy, we retrospectively analyzed 2 consecutive, prospective, randomized clinical trials performed by the International Antimicrobial Therapy Group of the European Organization for Research and Treatment of Cancer during 1991-1994. RESULTS: Of 1720 patients with their first episode of febrile neutropenia, 836 responded to the initial antibiotic regimen and were therefore suitable for our analysis. A secondary infection was observed in 129 (15%) of 836 patients that occurred at a median of 10 days (range, 1-28 days) after the onset of the primary febrile episode. Factors at both baseline and day 4 were analyzed. Age of >16 years (odds ratio [OR], 3.46; P<.001), acute leukemia in first induction (OR, 3.17; P<.001), presence of intravenous line (OR, 1.88; P=.04), severe neutropenia (defined as an absolute granulocyte count of <100 cells/mm(3)) on day 4 (OR, 2.72; P<.001), and type of documentation of the primary episode (i.e., microbiologically documented cause or unexplained fever; OR, 2.56; P=.001) were found to be risk factors for secondary infection. The risk of death was higher among patients who developed a secondary infectious episode than among those who did not (5.4% vs. 1.4%; P<.01). CONCLUSIONS: The clinical parameters described above may help to identify neutropenic patients at risk of developing secondary infection

Clinical efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum β-lactamase- producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospect observational study (BICAR).

Introduction: Bloodstream infection (BSI) due to extended-spectrum β-lactamase-producing Gram- negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although β-lactam/β- lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. Methods and analysis: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case- fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case- fatality rates, microbiological failure, colonisation/ infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. Sample size: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. Ethics and dissemination: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).Ministerio de Economía y Competitividad REIPI RD12/001

Re: "Comparison of antipseudomonal betalactams for febrile neutropenia empiric therapy: systematic review and network metaanalysis" by Horita et al

Item does not contain fulltex

The global threat of antimicrobial resistance: science for intervention

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance

On the isoperimetric problem for the Laplacian with Robin and Wentzell boundary conditions

Doctor of PhilosophyWe consider the problem of minimising the eigenvalues of the Laplacian with Robin boundary conditions $\frac{\partial u}{\partial \nu} + \alpha u = 0$ and generalised Wentzell boundary conditions $\Delta u + \beta \frac{\partial u}{\partial \nu} + \gamma u = 0$ with respect to the domain $\Omega \subset \mathbb R^N$ on which the problem is defined. For the Robin problem, when $\alpha > 0$ we extend the Faber-Krahn inequality of Daners [Math. Ann. 335 (2006), 767--785], which states that the ball minimises the first eigenvalue, to prove that the minimiser is unique amongst domains of class $C^2$. The method of proof uses a functional of the level sets to estimate the first eigenvalue from below, together with a rearrangement of the ball's eigenfunction onto the domain $\Omega$ and the usual isoperimetric inequality. We then prove that the second eigenvalue attains its minimum only on the disjoint union of two equal balls, and set the proof up so it works for the Robin $p$-Laplacian. For the higher eigenvalues, we show that it is in general impossible for a minimiser to exist independently of $\alpha > 0$. When $\alpha < 0$, we prove that every eigenvalue behaves like $-\alpha^2$ as $\alpha \to -\infty$, provided only that $\Omega$ is bounded with $C^1$ boundary. This generalises a result of Lou and Zhu [Pacific J. Math. 214 (2004), 323--334] for the first eigenvalue. For the Wentzell problem, we (re-)prove general operator properties, including for the less-studied case $\beta 0$ establish a type of equivalence property between the Wentzell and Robin minimisers for all eigenvalues. This yields a minimiser of the second Wentzell eigenvalue. We also prove a Cheeger-type inequality for the first eigenvalue in this case

Activity of ceftolozane/tazobactam against surveillance and ‘problem’ Enterobacteriaceae, Pseudomonas aeruginosa and non-fermenters from the British Isles

Background: We assessed the activity of ceftolozane/tazobactam against consecutive isolates collected in the BSAC Bacteraemia Surveillance from 2011 to 2015 and against ‘problem’ isolates sent to the UK national reference laboratory from July 2015, when routine testing began. Methods: Susceptibility testing was by BSAC agar dilution with resistance mechanisms identified by PCR and interpretive reading. Results: Data were reviewed for 6080 BSAC surveillance isolates and 5473 referred organisms. Ceftolozane/tazobactam had good activity against unselected ESBL producers in the BSAC series, but activity was reduced against ertapenem-resistant ESBL producers, which were numerous among reference submissions. AmpC-derepressed Enterobacter spp. were widely resistant, but Escherichia coli with raised chromosomal AmpC frequently remained susceptible, as did Klebsiella pneumoniae with acquired DHA-1-type AmpC. Carbapenemase-producing Enterobacteriaceae were mostly resistant, except for ceftazidime-susceptible isolates with OXA-48-like enzymes. Ceftolozane/tazobactam was active against 99.8% of the BSAC Pseudomonas aeruginosa isolates; against referred P. aeruginosa it was active against 99.7% with moderately raised efflux, 94.7% with strongly raised efflux and 96.6% with derepressed AmpC. Resistance in P. aeruginosa was largely confined to isolates with metallo-β-lactamases (MBLs) or ESBLs. MICs for referred Burkholderia spp. and Stenotrophomonas maltophilia were 2–4-fold lower than those of ceftazidime. Conclusions: Ceftolozane/tazobactam is active against ESBL-producing Enterobacteriaceae; gains against other problem Enterobacteriaceae groups were limited. Against P. aeruginosa it overcame the two most prevalent mechanisms (up-regulated efflux and derepressed AmpC) and was active against 51.9% of isolates non-susceptible to all other β-lactams, rising to 80.9% if ESBL and MBL producers were excluded