The efficacy of fidaxomicin in the treatment of Clostridium difficile infection in a real-world clinical setting: a Spanish multi-centre retrospective cohort.

The objective of this study was to evaluate the efficacy and safety of fidaxomicin in the real-life clinical setting. This was a retrospective cohort of patients with Clostridium difficile infection (CDI) treated with fidaxomicin in 20 Spanish hospitals between July 2013 and July 2014. Clinical cure, 30-day recurrence, 30-day mortality, sustained cure, and factors associated with the failure to achieve sustained cure were analyzed. Of the 72 patients in the cohort 41 (56.9 %) had a fatal underlying disease. There were 44 (61.1 %) recurrent episodes and 26 cases (36.1 %) with a history of multiple recurrences. Most episodes were severe (26, 36 %) or severe-complicated (14, 19.4 %). Clinical cure rate was 90.3 %, recurrence rate was 16.7 % and three patients (4.2 %) died during the follow-up period. Sustained cure was achieved in 52 cases (72.2 %). Adverse events were reported in five cases (6.9 %). Factors associated with the lack of sustained cure were cardiovascular comorbidity (OR 11.4; 95 %CI 1.9-67.8), acute kidney failure (OR 7.4; 95 %CI 1.3-43.1), concomitant systemic antibiotic treatment (OR 6.2; 95 %CI 1.1-36.8), and C-reactive protein value at diagnosis (OR 1.2 for each 1 mg/dl increase; 95 %CI 1.03-1.3). Fidaxomicin is an effective and well tolerable treatment for severe CDI and for cases with elevated recurrence risk.

Community-onset bacteraemia of unknown origin: clinical characteristics, epidemiology and outcome.

Bacteraemia of unknown origin is prevalent and has a high mortality rate. However, there are no recent reports focusing on this issue. From 2005 to 2011, all episodes of community onset bacteraemia of unknown origin (CO-BSI), diagnosed at a 700-bed university hospital were prospectively included. Risk factors for Enterobactericeae resistant to third-generation cephalosporins (3GCR-E), Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus spp, and predictors of mortality were assessed by logistic regression. Out of 4,598 consecutive episodes of CO-BSI, 745 (16.2 %) were of unknown origin. Risk factors for S. aureus were male gender (OR 2.26; 1.33-3.83), diabetes mellitus (OR 1.71; 1.01-2.91) and intravenous drug addiction (OR 17.24; 1.47-202); for P. aeruginosa were male gender (OR 2.19; 1.10-4.37) and health-care associated origin (OR 9.13; 3.23-25.83); for 3GCR-E was recent antibiotic exposure (OR 2.53; 1.47-4.35), while for enterococci, it was recent hospital admission (OR 3.02; 1.64-5.55). Seven and 30-day mortality were 8.1 % and 13.4 %, respectively. Age over 65 years (OR 2.13; 1.28-3.55), an ultimately or rapidly fatal underlying disease (OR 4.15; 2.23-7.60), bone marrow transplantation (OR 4.07; 1.24-13.31), absence of fever (OR 4.45; 2.25-8.81), shock on presentation (OR 10.48; 6.05-18.15) and isolation of S. aureus (OR 2.01; 1.00-4.04) were independently associated with mortality. In patients with bacteraemia of unknown origin, a limited number of clinical characteristics may be useful to predict its aetiology and to choose the appropriate empirical treatment. Although no modifiable prognostic factors have been found, management optimization of S. aureus should be considered a priority in this setting.

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection.

OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.

Current time-to-positivity of blood cultures in febrile neutropenia: a tool to be used in stewardship de-escalation strategies.

OBJECTIVES: We aimed to describe the current time-to-positivity (TTP) of blood cultures in individuals with onco-haematological diseases with febrile neutropenia. We assessed the probability of having a multidrug-resistant Gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were taken, to use this information for antibiotic de-escalation strategies. METHODS: BSI episodes were prospectively collected (2003-2017). When a patient experienced more than one BSI, only one episode was randomly chosen. Time elapsed from the beginning of incubation to a positive reading was observed; TTP was recorded when the first bottle had a positive result. RESULTS: Of the 850 patient-unique episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%), Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%) episodes. Median TTP was 12 h (interquartile range 9-16.5 h). Within the first 24 h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over 24 h. Of the 67 (7.9%) episodes with a TTP ≥24 h, 25 (37.3%) occurred in patients who were already receiving active antibiotics against the isolated pathogen. Most common isolations with TTP ≥24 h were coagulase-negative staphylococci, candidaemia and a group of anaerobic GNB. CONCLUSIONS: Currently, the vast majority of BSI in individuals with onco-haematological diseases with febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB. Our results support reassessing empiric antibiotic treatment in neutropenic patients at 24 h, to apply antibiotic stewardship de-escalation strategies.

Hypoxia inhibits cold-induced huddling in rat pups.

We asked to what extent hypoxia would modify the huddling behaviour of young rats during cold exposure. Sets of five animals (postnatal age 9+/-1 days) were placed at predetermined positions in a chamber maintained at approximately 33 degrees C (warm) or approximately 15 degrees C (cold), in normoxia or hypoxia (10% inspired O2), and their movements monitored for 30 min by a video camera. The surface areas (SA) of each individual pup (SAi) and of the whole set of pups (SAset) was measured every 5 min. In warm, the rats spread out, and both SAi and SAset were the greatest, whether in normoxia or hypoxia. In hypoxia, the total travelled distance (TTD) was much greater than in normoxia. In cold, during normoxia, SAi and SAset were decreased because of postural changes and huddling, and body temperature, measured at the end of the exposure, was also decreased. In hypoxic-cold, compared to normoxic-cold, fewer pups were in contact with one another, SAi and SAset did not decrease and the drop in body temperature was larger. Differently from hypoxia, hypercapnia (5% CO2) did not modify the responses observed during breathing air, whether in warm or cold conditions. We conclude that hypoxia, in addition to inhibiting shivering and non-shivering thermogenesis, can also limit behavioural thermogenesis, with the effect of further lowering body temperature.