Case report: Continuous infusions of ceftazidime-avibactam and aztreonam in combination through elastomeric infusors for 12 weeks for the treatment of bone and joint infections due to metallo-β-lactamase producing Enterobacterales

Among carbapenem-resistant Enterobacterales, metallo-beta-lactamase producing strains represent a growing therapeutic challenge. While the association of aztreonam and ceftazidime-avibactam has been investigated in recent years for the treatment of infections involving these strains, little to no clinical data support the use of this association for the treatment of bone and joint infections. We report two cases of complex bone and joint infections involving metallo-beta-lactamase-producing Enterobacterales, successfully treated at our referral center with aztreonam and ceftazidime-avibactam for 12 weeks in continuous infusions through elastomeric infusors

Persistence and Diffusion of mecC-Positive CC130 MRSA Isolates in Dairy Farms in Meurthe-et-Moselle County (France)

Background: Methicillin resistance in Staphylococcus aureus (MRSA) is classically conferred by the acquisition of the mecA gene encoding an additional penicillin binding protein with low affinity for beta-lactams. A mecA variant, named mecC, was described in 2011. MRSA isolates harboring mecC of both animal and human origin have since been collected in different European countries. In France, animal cases were reported in 4 dairy farms between 2008 and 2013 in the Meurthe-et-Moselle county, all located in a 30 km perimeter, suggesting a possible dissemination of mecC-positive MRSA strains. We performed a prospective study to evaluate the local epidemiology of such strains in terms of (i) dissemination among animals, humans and in the environment, and (ii) persistence in Meurthe-et-Moselle dairy cattle farms.Methods: The 4 French dairy farms with previous reports of mecC-positive MRSA strains and 14 farms in the same perimeter were included in this study. In each farm, nasal swabs, rectal swabs and milk samples were collected from 10 randomly selected cows, as well as nasal samples from family pets, volunteer farmers and veterinarians. One farm (E0), in which mecC-MRSA isolates were detected, was selected to study more deeply the dissemination of mecC-positive strains within the farm. After pre-enrichment of swabs and milk, they were subcultured on MSSA/MRSA chromogenic selective agar plates. S. aureus colonies were tested with a multiplex PCR to detect the mecA and mecC genes. The mecC-positive strains were characterized using DNA microarray.Results:mecC-positive strains were recovered in four farms, corresponding to the ones with previous reports of mecC-positive MRSA strains, and originated only from dairy cow samples. The screening in the E0 farm showed that 22% of the dairy cows carried mecC-positive MRSA. Three strains were also isolated from the environmental samples. All mecC-positive strains belonged to the clonal complex CC130 and harbored the same spa-type t1736.Conclusion: This study found that mecC-positive MRSA isolates are able to persist within the same farms for several years after being introduced in this setting and are able to widely disseminate but only among dairy cows suggesting that milking machines might be a key player

Olfactory cleft infection revealed by anosmia

No abstract availabl

Implementation of a complex bone and joint infection phage therapy centre in France: lessons to be learned after 4years' experience

Phage therapy is a promising option in patients with bacterial infection, especially in the worldwide context of resistance. It was totally abandoned in Western countries, but continued to be used in Eastern Europe. Recently, the FDA's position was modified in the light of the Tom Patterson case, leading to the emergence of dedicated phage therapy centres such as the Innovative Phage Applications and Therapeutics (IPATH) [1]. In 2020, the WHO classified phages as non-traditional antibacterial agents. Now that phages of pharmaceutical quality are available, the perspective of a ?phage 2.0 era' is open, and it becomes necessary to identify relevant indications and to assess efficacy in these indications through clinical trials. The ultimate aim is to demonstrate in which clinical settings phage therapy provides medical benefit

Interdisciplinary Systems-Based Intervention to Improve IV Hydration during Parenteral Administration of Acyclovir

ABSTRACTBackground: Intravenous (IV) hydration is considered a protective factor in reducing the incidence of acyclovir- induced nephrotoxicity. A systems based review of cases of acyclovir-associated acute kidney injury can be used to examine institution-, care provider-, and task-related factors involved in administering the drug and can serve as a basis for developing a quality improvement intervention to achieve safer administration of acyclovir.Objectives: To explore the effectiveness of the study institution’s inter - disciplinary quality improvement intervention in increasing the dilution of acyclovir before IV administration.Methods: After conducting a systems-based review for intervention development, a retrospective analysis was undertaken to compare IV administration of acyclovir in the 6-month periods before and after implementation of the intervention. The study population was a sequential sample of all patients over 18 years of age who were seen in the emergency department or admitted to a ward and who received at least one IV dose of acyclovir at the study institution. The primary outcome was the volume in which each acyclovir dose was delivered. The secondary outcomes were the hourly rate of fluid administration, the frequency of an increase in hourly hydration rate, and the incidence of acute kidney injury.Results: Eighty-four patients (44 in the pre-intervention period and 40 in the post-intervention period) received IV acyclovir and had evaluable data for the primary outcome. The median volume in which the acyclovir dose was administered was significantly higher in the post-intervention group (250 mL versus 100 mL, p < 0.001).Conclusions: In this study, an easily implemented intervention significantly increased the volume of IV fluid administered to patients receiving acyclovir. Adequately powered prospective studies are suggested to investigate the effectiveness of this intervention on the clinically relevant incidence of acyclovir-induced nephrotoxicity.RÉSUMÉContexte : L’hydratation par voie intraveineuse est considérée comme un facteur de protection aidant à réduire l’incidence des cas de néphrotoxicité associés à l’acyclovir. Une analyse de systèmes des cas d’insuffisance rénale aiguë associés à l’acyclovir peut servir à examiner les facteurs liés aux établissements, aux fournisseurs de soins et aux tâches qui touchent l’administration du médicament et à générer ainsi une mesure visant l’amélioration de la qualité qui rendra l’administration d’acyclovir plus sûre.Objectif : Étudier l’efficacité de la mesure interdisciplinaire visant l’amélioration de la qualité qui a été mise en oeuvre dans l’établissement de l’étude et qui encourageait à diluer davantage l’acyclovir avant son administration par voie intraveineuse.Méthodes : Après avoir procédé à une analyse de systèmes pour générer une mesure d’intervention, une analyse rétrospective a été réalisée afin de comparer l’administration d’acyclovir par voie intraveineuse au cours des six mois précédant et suivant la mise en oeuvre de la mesure. La population de l’étude était composée d’un échantillon progressif de tous les patients de plus de 18 ans ayant séjourné aux urgences ou dans un service intra-hospitalier et ayant reçu au moins une dose d’acyclovir par voie intraveineuse dans l’établissement concerné. Le principal parameter d’évaluation était le volume de liquide contenant chaque dose d’acyclovir administrée. Les paramètres d’évaluation secondaires comprenaient : le débit horaire de liquide administré, la fréquence d’ajustement à la hausse du débit liquidien horaire et la fréquence des cas d’insuffisance rénale aiguë.Résultats : Quatre-vingt-quatre patients (44 dans la période précédant l’application de la mesure et 40 dans la période la suivant) ont reçu de l’acyclovir par voie intraveineuse et présentaient des données évaluables pour le paramètre principal. Le volume médian avec lequel chaque dose d’acyclovir était administrée était significativement supérieur dans le groupe suivant l’application de la mesure (250 mL contre 100 mL, p < 0,001).Conclusions : Cette étude montre qu’une mesure facile à mettre en place augmentait de façon significative le volume  de liquides intraveineux administré aux patients recevant de l’acyclovir. L’on suggère de réaliser des études prospectives d’une puissance suffisante pour évaluer l’efficacité de cette mesure en ce qui a trait à la fréquence cliniquement significative des cas de néphrotoxicité associés à l’acyclovir

Les virus au service de la santé : les bactériophages

International audienceLes bactériophages sont des virus naturels très répandus dans l’environnement qui ciblent spécifiquement les bactéries. Leur utilisation en médecine, connue sous le terme phagothérapie, consiste à les isoler, les caractériser, les cultiver, puis les purifier pour traiter des infections bactériennes. Il existe actuellement un renouveau pour la thérapie phagique, et sa mise en œuvre présuppose de disposer de phages actifs de qualité pharmaceutique. D’un point de vue réglementaire, le statut des phages n’est pas encore clairement défini par les autorités, mais la mise à disposition de phages produits par l’industrie pharmaceutique et les programmes de développement académiques, comme le programme PHAGEinLYON, constituent un tournant dans le déploiement de la phagothérapie

Evaluation of the Activity of a Combination of Three Bacteriophages Alone or in Association with Antibiotics on Staphylococcus aureus Embedded in Biofilm or Internalized in Osteoblasts

Staphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm and to be internalized and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections, but data on its activity against the specific bacterial lifestyles presented above remain scarce. We evaluated the activity of a combination of three bacteriophages, recently used for compassionate treatment in France, against S. aureus HG001 in a model of staphylococcal biofilm and a model of osteoblasts infection, alone or in association with vancomycin or rifampin. The activity of bacteriophages against biofilm-embedded S. aureus was dose dependent. In addition, synergistic effects were observed when bacteriophages were combined with antibiotics used at the lowest concentrations. Phage penetration into osteoblasts was observed only when the cells were infected, suggesting a S. aureus-dependent Trojan horse mechanism for internalization. The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages as well as with vancomycin was significantly higher than in cells treated with lysostaphin, used as a control condition, owing to the absence of intracellular activity and the rapid killing of bacteria released after the death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalized in infected osteoblasts and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment, which avoids preventing them from infecting other osteoblasts. The combination of bacteriophages tested was highly active against S. aureus embedded in biofilm but showed no activity against intracellular bacteria in the cell model used

Case report: Continuous infusions of ceftazidime-avibactam and aztreonam in combination through elastomeric infusors for 12 weeks for the treatment of bone and joint infections due to metallo-β-lactamase producing Enterobacterales

Among carbapenem-resistant Enterobacterales , metallo-beta-lactamase producing strains represent a growing therapeutic challenge. While the association of aztreonam and ceftazidime-avibactam has been investigated in recent years for the treatment of infections involving these strains, little to no clinical data support the use of this association for the treatment of bone and joint infections. We report two cases of complex bone and joint infections involving metallo-beta-lactamase-producing Enterobacterales , successfully treated at our referral center with aztreonam and ceftazidime-avibactam for 12 weeks in continuous infusions through elastomeric infusors

Experience With the Use of the MicroDTTect Device for the Diagnosis of Low-Grade Chronic Prosthetic Joint Infections in a Routine Setting

Background: In prosthetic joint infections (PJIs), identification of the causative microorganisms is critical to successfully adapt and optimize treatment. However, microbiological diagnosis of PJIs remains a challenge notably because bacteria are embedded in biofilm adhered to the prosthetic material. Recently, dithiothreitol (DTT) treatment of prosthesis has been proposed as a new strategy to release bacteria from biofilm and to improve the yield of microbiological diagnosis. In this study, we evaluated the interest of a commercial device using DTT, the MicroDTTect system (Heraeus, Hanau, Germany), for the diagnosis of low-grade chronic PJIs, compared to the conventional culture of periprosthetic tissue (PPT) samples. Methods: Twenty patients undergoing a surgery procedure for removal of prosthetic material because of a suspicion of low-grade PJI without pre-operative microbiological documentation were included (NCT04371068). Bacteriological results using the fluid obtained after prosthesis treatment with the MicroDTTect system were compared to results obtained with conventional culture of PPT samples. Results: All the bacteria considered as responsible for PJIs recovered from culture of PPT samples were also detected using the MicroDTTect device. For one patient, an additional bacterial isolate (Staphylococcus haemolyticus) suspected to be involved in a polymicrobial PJI was identified using DTT treatment. Time to positivity of the cultures was also reduced using the MicroDTTect system, notably in case of Cutibacterium acnes infection. However, probable bacterial contaminants were found (MicroDTTect system, n = 5; PPT samples, n = 1). Conclusion: This study showed that DTT treatment of the prosthetic component using the MicroDTTect device could improve the microbiological diagnosis of low-grade PJIs