Vaccines and monoclonal antibodies to prevent healthcare-associated bacterial infections.

SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridioides difficile, are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens. It is undeniable that complementary to infection prevention and control measures, prophylactic approaches by active or passive immunization are needed. Specific groups at-risk (elderly people, chronic condition as immunocompromised) and also healthcare workers are key targets. Medical procedures and specific interventions are known to be at risk of HAIs, in addition to hospital environmental exposure. Vaccines or monoclonal antibodies can be seen as attractive preventive approaches for HAIs. In this review, we present an overview of the vaccines and monoclonal antibodies in clinical development for prevention of the major bacterial HAIs pathogens. Based on the current state of knowledge, we look at the challenges and future perspectives to improve prevention by these means.

Pneumocystis jirovecii pneumonia in non-HIV patients: need for a more extended prophylaxis.

Background: Pneumocystis jirovecii pneumonia (PCP) has a significant mortality rate for non-HIV immunocompromised patients. Prevention is primarily based on combined trimethoprim and sulfamethoxazole (TMP-SMX) but guidelines on pneumocystosis prophylaxis are scattered and not consensual. Objectives: This study aims to describe PCP in non-HIV patients and to review case by case the prior indication of prophylaxis according to specific guidelines.We included patients with confirmed diagnosis of PCP admitted to one university hospital from 2007 to 2020. Prior indication for pneumocystis prophylaxis was assessed according to the specific guidelines for the underlying pathology or treatment. Results: Of 150 patients with a medical diagnosis of PCP, 78 were included. Four groups of underlying pathologies were identified: hematological pathologies (42%), autoimmune diseases (27%), organ transplantation (17%), and other pathologies at risk of PCP (14%). A small subgroup of 14 patients (18%) had received a prior prescription of pneumocystis prophylaxis but none at the time of the episode. Transfer to intensive care was necessary for 33 (42%) patients, and the mortality rate at 3 months was 20%. According to international disease society guidelines, 52 patients (59%) should have been on prophylaxis at the time of the pneumocystis episode. Lowest compliance with guidelines was observed in the hematological disease group for 24 patients (72%) without prescription of indicated prophylaxis. Conclusion: Infectious disease specialists should draw up specific prophylactic guidelines against pneumocystis to promote a better prevention of the disease and include additional criteria in their recommendations according to individual characteristics to prevent fatal cases.

Comparing ethanol lock therapy versus vancomycin lock in a salvation strategy for totally implantable vascular access device infections due to coagulase-negative staphylococci (the ETHALOCK study): a prospective double-blind randomized clinical trial.

OBJECTIVES: Little is known about efficacy and safety of ethanol lock therapy (ELT) to treat totally implantable venous access device (TIVAD) infections. The objective of this trial was to evaluate the effectiveness and safety profile of a local treatment with ELT without removal for TIVAD infection due to coagulase-negative staphylococci. METHODS: We performed a prospective, multicenter, double-blind, randomized clinical trial comparing the efficacy of 40% ELT versus vancomycin lock therapy (VLT) in TIVAD infections due to coagulase-negative staphylococci, complicated or not by bloodstream infection. RESULTS: Thirty-one patients were assigned to the ELT group and 30 to the VLT arm. Concomitant bacteremia was present in 41 patients (67.2%). Treatment success was 58.1 % (18 of 31) for the ELT arm and 46.7% (14 of 30) for the VLT arm (p = 0.37). The overall treatment success was 52.5% (32). The risk of treatment failure due to uncontrolled infections, superinfections, and mechanical complications did not differ significantly between participants receiving ELT (13 out of 31 [42%]) and those receiving VLT (16 out of 30 [53%]) with a hazard ratio of 0.70 (p = 0.343; 95% CI [0.34-1.46], Cox model). Catheter malfunctions were significantly more frequent in the ELT arm (11 patients versus 2 in the VLT group, p = 0.01). CONCLUSIONS: We found an overall high rate of treatment failure that did not differ between the ELT arm and the VLT arm. TIVAD removal must be prioritized to prevent complications (uncontrolled infections, superinfections, and catheter malfunctions) except in exceptional situations.

Costs associated with informal health care pathway for patients with suspected Lyme borreliosis.

OBJECTIVES: To compare the direct and indirect medical costs for patients with suspected Lyme borreliosis according to whether or not they had used an informal care pathway. PATIENTS AND METHODS: We retraced the care pathways of participating patients by a prospective questionnaire survey and a retrospective analysis of care records. Direct and indirect costs were estimated using a micro-costing method from different perspectives. We compared the costs of patients who had consulted a "Lyme Doctor" (informal care pathway) with those who had only used the formal care pathway. Non-parametric tests were appraised the significance of the differences between the two groups of patients. RESULTS: Out of 103 eligible patients, 49 (including 12 having used an informal health care pathway) agreed to be investigated. Five expenditure items entirely borne by patients were significantly higher for patients following an informal care pathway: productivity loss (3041 ± 6580 vs 194 ± 1177 euros, p = 0.01), alternative therapies (3484 ± 7308 vs 369 ± 956 euros), biological tests sent abroad (571 ± 1415 vs 17 ± 92 euros, p < 0.01), self-medication (918 ± 1998 vs 133 ± 689, p = 0.02) and transport (3 094 ± 3456 vs 1 123 ± 1903p = 0.01). CONCLUSIONS: From the patient's standpoint, the informal care pathway involving consultation with a Lyme Doctor is far more expensive than the formal care pathway. More specifically, the patient has to bear the costs of alternative treatments and repeated, non-recommended examinations.

[Lyme borreliosis]. / Borréliose de Lyme.

LYME BORRELIOSIS. Lyme borreliosis (LB) is the most common vector-borne disease in the Northern Hemisphere, caused by the bacterium Borrelia burgdorferi sensu lato, transmitted to humans by a bite of ticks Ixodes. Prevention is based on simple measures to evict ticks, and on their rapid extractionin the event of a bite. The diagnosis of LB is based on 3 arguments: an exposure to tick bites; clinically compatible symptoms (cutaneous, neurological or rheumatological manifestations, +/- functional symptoms such as fatigue or polyarthromyalgia), evolving in 3 stages (early localized or erythema migrans, early or late disseminated LB); a positive two-tier serological test (ELISA +/- Western-Blot). Serology can be negative for the first 6 weeks, without excluding the diagnosis. Since serology can remain positive for life, evolution is only evaluated clinically. LB treatment is mainly based on doxycycline for 14 to 28 days, depending on the clinical stage and manifestations, without demonstrated interest in prolonging it, even if symptoms persist. Nonetheless their management is crucial as often responsible for medical wandering. Attentive listening to the patient is essential. The prognosis of LB in the medium-term is favorable, especially if they beneficiate of an early management.

BORRÉLIOSE DE LYME. La borréliose de Lyme (BL) est la maladie vectorielle la plus fréquente de l'hémisphère Nord. Elle est due à la bactérie Borrelia burgdorferi sensu lato, transmise à l'homme lors d'une piqûre de tique infectée du genre Ixodes. La prévention repose sur des mesures simples d'éviction des tiques, et sur leur extraction rapide en cas de piqûre. Le diagnostic de la BL est basé sur un trépied : une exposition aux piqûres de tiques ; une clinique compatible (manifestations cutanées, neurologiques ou articulaires, éventuellement accompagnées de symptômes fonctionnels comme une fatigue, des polyarthromyalgies…), évoluant en trois phases (localisée précoce ou érythème migrant, disséminée précoce et tardive) ; une sérologie positive en deux temps (ELISA +/- western-blot). La sérologie peut être négative les 6 premières semaines, sans exclure le diagnostic. La sérologie pouvant rester positive à vie, l'évolution est uniquement évaluée cliniquement. Le traitement de la BL repose principalement sur la doxycycline, pendant 14 à 28 jours selon le stade clinique et le type d'atteinte. Il n'y a pas d'intérêt démontré à prolonger l'antibiothérapie, même en cas de persistance de symptômes. Néanmoins la prise en charge de ceux-ci (réadaptation physique, thérapies brèves, etc.) est fondamentale car ils sont souvent à l'origine d'une errance médicale. Une écoute attentive du patient est essentielle. Le pronostic des BL à moyen terme est favorable, ce d'autant que leur prise en charge est précoce.

Biofilm-coated microbeads and the mouse ear skin: An innovative model for analysing anti-biofilm immune response in vivo.

Owing to its ability to form biofilms, Staphylococcus aureus is responsible for an increasing number of infections on implantable medical devices. The aim of this study was to develop a mouse model using microbeads coated with S. aureus biofilm to simulate such infections and to analyse the dynamics of anti-biofilm inflammatory responses by intravital imaging. Scanning electron microscopy and flow cytometry were used in vitro to study the ability of an mCherry fluorescent strain of S. aureus to coat silica microbeads. Biofilm-coated microbeads were then inoculated intradermally into the ear tissue of LysM-EGFP transgenic mice (EGFP fluorescent immune cells). General and specific real-time inflammatory responses were studied in ear tissue by confocal microscopy at early (4-6h) and late time points (after 24h) after injection. The displacement properties of immune cells were analysed. The responses were compared with those obtained in control mice injected with only microbeads. In vitro, our protocol was capable of generating reproducible inocula of biofilm-coated microbeads verified by labelling matrix components, observing biofilm ultrastructure and confirmed in vivo and in situ with a matrix specific fluorescent probe. In vivo, a major inflammatory response was observed in the mouse ear pinna at both time points. Real-time observations of cell recruitment at injection sites showed that immune cells had difficulty in accessing biofilm bacteria and highlighted areas of direct interaction. The average speed of cells was lower in infected mice compared to control mice and in tissue areas where direct contact between immune cells and bacteria was observed, the average cell velocity and linearity were decreased in comparison to cells in areas where no bacteria were visible. This model provides an innovative way to analyse specific immune responses against biofilm infections on medical devices. It paves the way for live evaluation of the effectiveness of immunomodulatory therapies combined with antibiotics.