No abstract

Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4 th European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient's risk factors for resistant bacteria and for a complicated clinical course. An 'escalation' approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A 'deescalation' approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72-96 h should be based on the patient's clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n 2 0 1 3 increasing resistance. The draft of these guidelines was discussed by the Expert Group at the ECIL-4 meeting in September 2011 and considers: i) bacterial epidemiology in neutropenic patients; ii) risk factors for resistance; iii) escalation and deescalation approaches; iv) the appropriate duration of empirical therapy; iv) non-conventional therapies against multi-resistant pathogens; and v) other issues on the management of bacterial infections in these patients. Up-dated slide sets from ECIL-4 covering these aspects are available on the websites of the four organizations involved in ECIL: the European Group for Blood and Marrow Transplantation, the European Organisation for Research and Treatment of Cancer, the Immunocompromised Host Society (ECIL), and the European Leukaemia Net. 12,13 This article summarizes the main ECIL recommendations on the initial empirical therapy of bacterial infections, but will also be valuable for the management of the many nonneutropenic but severely-immunosuppressed hematology patients. MethodsThe methodology of the ECIL conferences has been described previously. 11A working group of experts in the field of infectious diseases, microbiology or hematology was constituted, and reviewed the published literature in order to prepare proposals covering the following aspects: 1) empirical antibiotic therapy for...

Background

The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram-positive agents. Data on the use of these agents in leukemic patients are scanty, with only linezolid subjected to formal trials. The Expert Group of the 4 th European Conference on Infections in Leukemia has developed guidelines for their use in these patient populations. Targeted therapy should be based on (i) in vitro susceptibility data, (ii) knowledge of the best treatment option against the particular species or phenotype of bacteria, (iii) pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk-benefit balance. For infections due to resistant Gram-negative bacteria, these agents should be preferably used in combination with other agents that remain active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs in the near future should lead us to limit the use of these drugs to situations where no alternative exists. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o n 2 0 1 3organizing committee and experts were solicited to form the working group. The group reviewed the published English-language literature and prepared proposals on treatment options for infections due to resistant bacteria. Papers for review were sought using PubMed with the terms "linezolid", "daptomycin", "quinupristin/ dalfopristin", "colistin or polymyxin", "tigecycline", "fosfomycin", "telavancin", "ceftaroline" AND "stem cell transplantation or bone marrow transplant or leukemia or hematological malignancy or cancer". References cited in the articles identified were also considered. In respect of 'Duration of therapy', the main search terms used were "antibiotic therapy"; "stem cell transplantation or bone marrow transplantation or hematological malignancy or cancer"; "febrile neutropenia" and "duration therapy", "discontinuation antibiotics" and "microbiologically documented infection". Definitions of resistanceA bacterial isolate was considered non-susceptible if it was categorized resistant, intermediate or non-susceptible when using clinical breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), Clinical and Laboratory Standards Institute (CLSI) or the US Food and Drug Administration (FDA). Definitions of 'MDR' vary among authors and usually presume resistance to at least two antibiotics used in empiric therapy (3 rd 4 th -generation cephalosporins, carbapenems or piperacillin/tazobactam) or resistance to at least three of the following antibiotic classes: antipseudomonal penicillins, cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. [11][12][13][14][15] According to the recent definition of the European Centre for Disease Prevention and Control...

Background First-line antifungal treatment for invasive mucormycosis (IM) consists of liposomal amphotericin B. Salvage treatment options are limited and often based on posaconazole oral suspension. With the approval of posaconazole new formulations, patients could benefit from improved pharmacokinetics, safety and tolerability. Objectives Our aim was to assess the effectiveness of posaconazole new formulations for IM treatment. Methods We performed a case-matched analysis with proven or probable IM patients from the FungiScope® Registry. First-line posaconazole new formulations (1st-POSnew) and first-line amphotericin B plus posaconazole new formulations (1st-AMB+POSnew) cases were matched with first-line amphotericin B-based (1st-AMB) treatment controls. Salvage posaconazole new formulations (SAL-POSnew) cases were matched with salvage posaconazole oral suspension (SAL-POSsusp) controls. Each case was matched with up to three controls (based on severity, haematological/oncological malignancy, surgery and/or renal dysfunction). Results Five patients receiving 1st-POSnew, 18 receiving 1st-AMB+POSnew and 22 receiving SAL-POSnew were identified. By day 42, a favourable response was reported for 80.0% (n = 4/5) of patients receiving 1st-POSnew, for 27.8% (n = 5/18) receiving 1st-AMB+POSnew and for 50.0% (n = 11/22) receiving SAL-POSnew. Day 42 all-cause mortality of patients receiving posaconazole new formulations was lower compared with controls [20.0% (n = 1/5) in 1st-POSnew versus 53.3% (n = 8/15) in 1st-AMB; 33.3% (n = 6/18) in 1st-AMB+POSnew versus 52.0% (n = 26/50) in 1st-AMB; and 0.0% (n = 0/22) in SAL-POSnew versus 4.4% (n = 2/45) in SAL-POSsusp]. Conclusions Posaconazole new formulations were effective in terms of treatment response and associated mortality of IM. While posaconazole new formulations may be an alternative for treatment of IM, the limited sample size of our study calls for a cautious interpretation of these observations.