Abstract
Bone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance. Lytic bacteriophages (phages for short) are ...natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms. Here we report on the management of a patient with a pandrug-resistant
Pseudomonas aeruginosa
spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting
P. aeruginosa
strain was resistant to the phages developed by private companies that were contacted, we set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time. After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy.
Antifungal resistance is a significant and emerging threat. Stewardship programmes (SPs) have been proposed as an opportunity to optimize antifungal use. While examples of antifungal SP ...implementation have been recently described, there is yet to be an overview of interventions and their impacts on performance measures.
We systematically reviewed published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses check-list 2009. MEDLINE was searched using the term 'antifungal stewardship' on 15 February 2017. Eligible studies were those that described an antifungal SP and included an intervention and an evaluation of performance measures.
A total of 97 studies were identified and 14 were included. Only five studies reported an antifungal stewardship team composed of all the recommended members. The main intervention was the formulation of recommendations to change treatment (12 of 14). The main performance measure collected was antifungal consumption (10 of 14), followed by antifungal expenditure (7 of 14), adherence to therapeutic advice (4 of 14) and impact on mortality (4 of 14). Antifungal consumption was reduced by 11.8% to 71% and antifungal expenditure by as much as 50%. Adherence to therapeutic advice ranged from 40% to 88%, whereas antifungal SPs had no impact on mortality.
All antifungal SPs had an impact, in particular on antifungal consumption and antifungal expenditure. Active intervention including a review of prescriptions seems to have more impact than implementation of treatment guidelines only. According to available published studies, antifungal consumption appears to be the most achievable performance measure to evaluate the impact of an antifungal SP.
The objective was to describe the trends in the consumption of narcotic drugs, substances related to narcotic drugs (SAS) and psychotropic drugs between a French hospital and a Quebec hospital ...between 2013 and 2017.
This is a retrospective descriptive study. The consumption data was obtained from the pharmacy management software and was extracted by financial year (January 1st, 2013 to December 31st, 2017 for the French hospital and April 1st, 2013 to March 31st, 2018 for the Quebec hospital). For each drug considered to be narcotics, SAS and psychotropic drugs in France or subject to the legislation on designated substances in Quebec, we identified the quantities consumed from 2013 to 2017. The data werepresented according to the following therapeutic classes: opioids (N02A), other analgesics (N02B), anxiolytics (N05B), hypnotics and sedatives (N05C), general anesthetics (N01A), psychostimulants (N06B), androgens (G03B) and antagonists peripheral opioid receptors (A06A). The data were expressed as a defined daily dose (DDJ) for 1000 patient-days (PDs).
In the French hospital, the consumption of narcotics, SAS and psychotropic drugs varied from 676 to 560 DDJ per 1000 PDs between 2013 and 2017. While it varied from 1019 to 756 DDJ per 1000 PDs between 2013 and 2017 in the Quebec hospital. In 2017, the most widely used therapeutic classes in French hospitals were, in decreasing order, anxiolytics (211 DDJ per 1000 PDs) (i.e. alprazolam), opioids (205 DDJ per 1000 PDs) (i.e. tramadol, morphine injectable) and hypnotics and sedatives (64 DDJ per 1000 PDs) (i.e. midazolam injectable). In Quebec hospitals, the three therapeutic classes the most used in 2017 were, in decreasing order, opioids (314 DDJ per 1000 PDs) (i.e. hydromorphone injectable, morphine injectable), anxiolytics (221 DDJ per 1000 PDs) (i.e. clobazam) and hypnotics and sedatives (108 DDJ per 1000 PDs) (i.e. midazolam injectable).
This study notes a decrease in the consumption of opioids and other substances in both the French and Quebec establishments between 2013-2017. More work is needed to better describe the differences observed between the profile of each establishment. This is why monitoring consumption trends, therapeutic indications and preventive measures are essential.
Urbanization is a major challenge for biodiversity conservation, yet the evolutionary processes taking place in urbanized areas remain poorly known. Human activities in cities set new selective ...forces in motion which need to be investigated to predict the evolutionary responses of animal species living in urban areas. In this study, we investigated the role of urbanization and parasites in the maintenance of melanin-based color polymorphism in the feral pigeon Columba livia. Using a correlative approach, we tested whether differently colored genotypes displayed alternative phenotypic responses to urbanization, by comparing body condition, blood parasite prevalence and parasite load between colored morphs along an urbanization gradient. Body condition did not vary with urbanization, but paler individuals had a higher body condition than darker individuals. Moreover, paler morphs were less often parasitized than darker morphs in moderately urbanized habitats, but their parasite prevalence increased with urbanization. In contrast, darker morphs had similar parasite prevalence along the urbanization gradient. This suggests that paler morphs did better than darker morphs in moderately urbanized environments but were negatively affected by increasing urbanization, while darker morphs performed equally in all environments. Thus, differently colored individuals were distributed non-randomly across the urban habitat and suffered different parasite risk according to their location (a gene-by-environment interaction). This suggests that melaninbased coloration might reflect alternative strategies to cope with urbanization via different exposure or susceptibility to parasites. Spatial variability of parasite pressures linked with urbanization may, thus, play a central role in the maintenance of plumage color polymorphism in this urban species.
Variation in genetic-based coloration is widespread among vertebrates, yet the underlying mechanisms explaining this polymorphism maintenance remain poorly known. Gene-by-environment interactions on ...fitness traits in a fluctuating environment are often invoked to explain the maintenance of such color diversity. According to this hypothesis, variation in coloration could signal alternative life-history strategies to cope with variable environmental conditions. However, empirical studies testing this hypothesis are still rare. Here, we aimed at comparing the variation of body mass maintenance behavior and reproductive traits between differently colored individuals in alternative environments. We exposed differently colored captive feral pigeons to different food conditions and immune challenges and measured their investment in body mass maintenance, egg laying, and offspring quality. Under food restriction, darker eumelanic females had a higher egg production, but darker adults tended to lose more body mass than paler conspecifics. Moreover, offspring reared in food-limited conditions had a higher body mass at fledging when sired by darker biological fathers, suggesting a positive genetic effect of a darker eumelanic coloration in harsh food conditions. In contrast, when food was abundant, pale- and dark-colored females had a similar egg production, but darker adults lost significantly less body mass than paler conspecifics. The immune challenge had no effect on adult body mass maintenance and reproduction. Differently colored individuals may thus display alternative reaction norms to different food conditions, suggesting that eumelanin-based coloration reflects how animals cope with variations in food availability. Spatiotemporal heterogeneity of food availability in natural systems may thus play a central role in the evolution of melanin-based coloration in wild animal populations.
Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support ...System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients.
This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications.
Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals.
The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS.
This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.
This study aims at evaluating fluconazole exposure in critically ill patients and identifying variables associated with the latter.
This was a 2-year (2018-2019) retrospective multicenter cohort ...study. Adult patients > 18 years-old with at least one fluconazole concentration measurement during their ICU stay were included.
Twenty patients were included. Only 11 patients had a fluconazole trough concentration (Cmin) within the target range (≥15 mg/L). According to bivariable analysis, SOFA score, GGT, fluconazole clearance, Ke, and Vd, were independently associated with a decrease in fluconazole Cmin. The median loading dose required to achieve the Cmin target appeared to be greater in patients with higher SOFA or GGT level and in patients undergoing renal replacement therapy.
This study supports recommendation for routine fluconazole therapeutic drug monitoring in ICU patients so as to avoid underexposure, especially if SOFA score is ≥ 7 and/or GGT is ≥ 100 U/L.
Females choose their mate on the basis of secondary sexual characters such as physical ornaments, courtship behaviours or vocalizations. In male birds, vocalizations are known to increase their ...attractiveness and consequently their probability of copulation. Moreover, male songs have been shown to shape maternal investment, particularly with regard to egg quality. Artificial manipulation of male attractiveness has been found to affect female sexual preferences and maternal investment. In this regard, supranormal stimuli are thought to increase such responses. The present study was designed to assess whether supranormal acoustic stimuli, known to induce high levels of sexual responsiveness in female canaries, Serinus canaria, could increase maternal investment beyond levels observed in birds exposed to natural songs. Exposure to supranormal songs (G phrases) increased maternal investment: compared to females exposed to moderately attractive (Control) or naturally attractive (A) phrases. Females exposed to supranormal songs laid bigger eggs (egg volume and mass, albumen mass); moreover, females in the G group laid eggs with heavier yolks than females in the Control group. In contrast, no differences were found between groups with regard to testosterone deposition in the eggs. Thus, the adjustment of females' investment in their brood seems to take various forms that appear to be related to different features of males' sexually selected traits, which raises the questions of how and why these different mechanisms have been selected.
► We measured the influence of song stimulation on maternal investment in canaries. ► We broadcast three types of songs (average, sexy and supranormal) to female canaries. ► Females exposed to supranormal stimuli laid bigger eggs than other females. ► We found no effect of the type of song on testosterone concentration in the eggs. ► It raises the question of how and why these different investment mechanisms evolved.
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