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

Deposition velocities of airborne microbe-carrying particles

The deposition velocity of airborne microbe-carrying particles (MCPs) falling towards surfaces was obtained experimentally in operating theatres and cleanrooms. The airborne concentrations of MCPs, and their deposition rate onto surfaces, are related by the deposition velocity, and measurements made by a microbial air sampler and settle plates allowed deposition velocities to be calculated. The deposition velocity of MCPs was found to vary with the airborne concentration, with higher deposition rates occurring at lower airborne concentrations. Knowledge of the deposition velocity allows the deposition on surfaces, such as product or settle plates, by a known airborne concentration of MCPs to be predicted, as well as the airborne concentration that should not be exceeded for a specified product contamination rate. The relationship of airborne concentration and settle plate counts of MCPs used in Annex 1 of the EU Guidelines to Good Manufacturing Practice to specify grades of pharmaceutical cleanrooms was reassessed, and improvements suggested

Household screening and multidrug-resistant tuberculosis

Of the estimated half a million people who develop multidrug resistant (MDR) tuberculosis each year, less than 7% are diagnosed and only 1 in 5 of these have access to eff ective treatment.1 To control this epidemic, dramatically increased efforts are required to scale up case detection and treatment provision. In The Lancet, Mercedes Becerra and colleagues2 report the yield of additional MDR tuberculosis diagnoses that are found by screening household contacts of index cases in Lima, Peru. This study—the largest of its kind to date—found that more than 2% of 4503 household contacts had active tuberculosis at the time the index case was diagnosed. Incident tuberculosis was also found at a rate of 1624 cases per 100 000 person-years over 4 years follow-up. These results support recommendations for active screening of household contacts of people with MDR tuberculosis,3 and provide valuable lessons for other programmes striving to improve case detection and to reduce community transmission of MDR tuberculosis

Investigating bacteriophages targeting the opportunistic pathogen Acinetobacter baumannii

The multi-drug resistance of the opportunistic pathogen Acinetobacter baumannii is of growing concern, with many clinical isolates proving to be resistant to last resort as well as front line antibiotic treatments. The use of bacteriophages is an attractive alternative to controlling and treating this emerging nosocomial pathogen. In this study, we have investigated bacteriophages collected from hospital wastewater in Thailand and we have explored their activity against clinical isolates of A. baumannii. Bacteriophage vB_AbaM_PhT2 showed 28% host range against 150 multidrug resistant (MDR) isolates and whole genome sequencing did not detect any known virulence factors or antibiotic resistance genes. Purified vB_AbaM_PhT2 samples had endotoxin levels below those recommended for preclinical trials and were not shown to be directly cytotoxic to human cell lines in vitro. The treatment of human brain and bladder cell lines grown in the presence of A. baumannii with this bacteriophage released significantly less lactate dehydrogenase compared to samples with no bacteriophage treatment, indicating that vB_AbaM_PhT2 can protect from A. baumannii induced cellular damage. Our results have also indicated that there is synergy between this bacteriophage and the end line antibiotic colistin. We therefore propose bacteriophage vB_AbaM_PhT2 as a good candidate for future research and for its potential development into a surface antimicrobial for use in hospitals. View Full-Tex

Experimental phage therapy of burn wound infection : difficult first steps

Antibiotic resistance has become a major public health problem and the antibiotics pipeline is running dry. Bacteriophages (phages) may offer an ‘innovative’ means of infection treatment, which can be combined or alternated with antibiotic therapy and may enhance our abilities to treat bacterial infections successfully. Today, in the Queen Astrid Military Hospital, phage therapy is increasingly considered as part of a salvage therapy for patients in therapeutic dead end, particularly those with multidrug resistant infections. We describe the application of a well-defined and quality controlled phage cocktail, active against Pseudomonas aeruginosa and Staphylococcus aureus, on colonized burn wounds within a modest clinical trial (nine patients, 10 applications), which was approved by a leading Belgian Medical Ethical Committee. No adverse events, clinical abnormalities or changes in laboratory test results that could be related to the application of phages were observed. Unfortunately, this very prudent ‘clinical trial’ did not allow for an adequate evaluation of the efficacy of the phage cocktail. Nevertheless, this first ‘baby step’ revealed several pitfalls and lessons for future experimental phage therapy and helped overcome the psychological hurdles that existed to the use of viruses in the treatment of patients in our burn unit

Review of multidrug-resistant and extensively drug-resistant TB: global perspectives with a focus on sub-Saharan Africa

Tuberculosis (TB) remains a global emergency and is responsible for 1.7 million deaths annually. Widespread global misuse of isoniazid and rifampicin over three decades has resulted in emergence of the ominous spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) globally. These difficult to treat resistant forms of TB are increasingly seen in Asia, Eastern Europe, South America and sub-Saharan Africa, disrupting TB and HIV control programmes. We review the latest available global epidemiological and clinical evidence on drug-resistant TB in HIV-infected and uninfected populations, with focus on Africa where data are scanty because of poor diagnostic and reporting facilities. The difficult management and infection control problems posed by drug-resistant TB in HIV-infected patients are discussed. Given the increasing current global trends in MDR-TB, aggressive preventive and management strategies are urgently required to avoid disruption of global TB control efforts. The data suggest that existing interventions, public health systems and TB and HIV programmes must be strengthened significantly. Political and funder commitment is essential to curb the spread of drug-resistant TB

Investigation for the enrichment pattern of the element abundances in r+s star HE 0338-3945: a special r-II star?

The very metal-poor star HE 0338-3945 shows a double-enhanced pattern of the neutron-capture elements. The study to this sample could make people gain a better understanding of s- and r-process nucleosynthesis at low metallicity. Using a parametric model,we find that the abundance pattern of the neutron-capture elements could be best explained by a binary system formed in a molecular cloud, which had been polluted by r-process material. The observed abundance pattern of C and N can be explained by an AGB model(Karakas & Lattanzio 2007), . Combing with the parameters obtained from Cui & Zhang (2006), we suggest that the initial mass of the AGB companion is most likely to be about 2.5Msun, which excludes the possibility of forming a type-1.5 supernova. By comparing with the observational abundance pattern of CS 22892-052, we find that the dominating production of O should accompany with the production of the heavy r-process elements of r+s stars. Similar to r-II stars, the heavy r-process elements are not produced in conjunction with all the light elements from Na to Fe group. The abundance pattern of the light and r-process elements for HE 0338-3945 is very close to the pattern of the r-II star CS 22892-052. So, we suggest that this star HE 0338-3945 should be a special r-II star.Comment: 18 pages, 6 figures, published by Ap

Investigation for the puzzling abundance pattern of the neutron-capture elements in the ultra metal-poor star: CS 30322-023

The s-enhanced and very metal-poor star CS 30322-023 shows a puzzling abundance pattern of the neutron-capture elements, i.e. several neutron-capture elements such as Ba, Pb etc. show enhancement, but other neutron-capture elements such as Sr, Eu etc. exhibit deficient with respect to iron. The study to this sample star could make people gain a better understanding of s- and r-process nucleosynthesis at low metallicity. Using a parametric model, we find that the abundance pattern of the neutron-capture elements could be best explained by a star that was polluted by an AGB star and the CS 30322-023 binary system formed in a molecular cloud which had never been polluted by r-process material. The lack of r-process material also indicates that the AGB companion cannot have undergone a type-1.5 supernova, and thus must have had an initial mass below 4.0M$_\odot$, while the strong N overabundance and the absence of a strong C overabundance indicate that the companion's initial mass was larger than 2.0M$_\odot$. The smaller s-process component coefficient of this star illustrates that there is less accreted material of this star from the AGB companion, and the sample star should be formed in the binary system with larger initial orbital separation where the accretion-induced collapse (AIC) mechanism can not work.Comment: 13 pages, 2 figure