A validated clinical approach for the management of aspergillosis in critically ill patients: ready, steady, go!

The clinical relevance of recovering Aspergillus species in intensive care unit patients is unknown. Diagnosis of invasive pulmonary aspergillosis is extremely difficult because there are no specific tests sensitive enough to detect it. The rapidly fatal prognosis of this infection without treatment justifies early antifungal therapy. A clinical algorithm may aid clinicians to manage critically ill patients from whose respiratory specimens Aspergillus spp. have been isolated. This new tool needs to be validated in a large cohort of patients before it can be recommended

Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics. study protocol for a randomized controlled trial

Background: Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB. Methods/Design: The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed

European intensive care physicians’ experience of infections due to antibiotic-resistant bacteria

Background Antimicrobial resistance (AMR) compromises the treatment of patients with serious infections in intensive care units (ICUs), and intensive care physicians are increasingly facing patients with bacterial infections with limited or no adequate therapeutic options. A survey was conducted to assess the intensive care physicians' perception of the AMR situation in the European Union/European Economic Area (EU/EEA). Methods Between May and July 2017, physicians working in European ICUs were invited to complete an online questionnaire hosted by the European Society of Intensive Care Medicine. The survey included 20 questions on hospital and ICU characteristics, frequency of infections with multidrug-resistant (MDR) bacteria and relevance of AMR in the respondent's ICU, management of antimicrobial treatment as well as the use of last-line antibiotics in the six months preceding the survey. For the analysis of regional differences, EU/EEA countries were grouped into the four sub-regions of Eastern, Northern, Southern and Western Europe. Results Overall, 1062 responses from four European sub-regions were analysed. Infections with MDR bacteria in their ICU were rated as a major problem by 257 (24.2%), moderate problem by 360 (33.9%) and minor problem by 391 (36.8%) respondents. Third-generation cephalosporin-resistant Enterobacteriaceae were the most frequently encountered MDR bacteria followed by, in order of decreasing frequency, meticillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and vancomycin-resistant enterococci. Perception of the relevance of the AMR problem and the frequency of specific MDR bacteria varied by European sub-region. Bacteria resistant to all or almost all available antibiotics were encountered by 132 (12.4%) respondents. Many physicians reported not having access to specific last-line antibiotics. Conclusions The percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies. The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern

Biomarkers of fungal infection: Expert opinion on the current situation

The introduction of non-culture-based diagnostic techniques is revolutionizing the world of microbiological diagnosis and infection assessment. Fungi are no exception, and the introduction of biomarkers has opened up enormous expectations for better management of these entities. Biomarkers are diverse, their targets are also diverse and their evaluation has been done preferably in an individualized use and with deficient designs. Less is known about the value of the combined use of biomarkers and the impact of the negativity of two or more biomarkers on antifungal treatment decisions has been poorly studied. Given the paucity of prospective, randomized and definitive studies, we have convened experts from different fields, with an interest in invasive fungal infections, to answer some questions about the current relevant use of fungal biomarkers. This document summarizes the answers of these experts to the different questions

Clinical impact of a commercially available multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis

<p>Abstract</p> <p>Background</p> <p>Timely identification of pathogens is crucial to minimize mortality in patients with severe infections. Detection of bacterial and fungal pathogens in blood by nucleic acid amplification promises to yield results faster than blood cultures (BC). We analyzed the clinical impact of a commercially available multiplex PCR system in patients with suspected sepsis.</p> <p>Methods</p> <p>Blood samples from patients with presumed sepsis were cultured with the Bactec 9240™ system (Becton Dickinson, Heidelberg, Germany) and aliquots subjected to analysis with the LightCycler^®SeptiFast^®(SF) Test (Roche Diagnostics, Mannheim, Germany) at a tertiary care centre. For samples with PCR-detected pathogens, the actual impact on clinical management was determined by chart review. Furthermore a comparison between the time to a positive blood culture result and the SF result, based on a fictive assumption that it was done either on a once or twice daily basis, was made.</p> <p>Results</p> <p>Of 101 blood samples from 77 patients, 63 (62%) yielded concordant negative results, 14 (13%) concordant positive and 9 (9%) were BC positive only. In 14 (13%) samples pathogens were detected by SF only, resulting in adjustment of antibiotic therapy in 5 patients (7,7% of patients). In 3 samples a treatment adjustment would have been made earlier resulting in a total of 8 adjustments in all 101 samples (8%).</p> <p>Conclusion</p> <p>The addition of multiplex PCR to conventional blood cultures had a relevant impact on clinical management for a subset of patients with presumed sepsis.</p

Timing of antibiotic therapy in the ICU

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics

Intensive care in cancer patients in the age of immunotherapy and molecular therapies: SEOM-SEMICYUC’s commitment.

Cancer patients comprise a vulnerable collective exposed to numerous, serious risks, beyond the cancer itself. In recent years, these individuals’ prognosis has improved substantially thanks to several advances, such as immunotherapy, targeted molecular therapies, surgical techniques, or developments in support treatment. This coincides with the prolonged survival of oncological patients hospitalized in the ICU for critical complications. Thus, the time has come to revisit intensive care support for these patients, which poses new professional as well as organizational challenges. An agreement was therefore signed in 2017 between SEOM and SEMICYUC with the aim of improving the quality of care of cancer patients with critical complications. It seeks to aid in decision-making, standardize criteria, decrease subjectivity, generate channels of communication, and delve deeper into the ethical and scientific aspects of these situations. This document sets forth the most important reasons that have led us to undertake this initiative.pre-print653 K