OBJECTIVE:The Serratia marcescens ROT_R clinical isolate, which was resistant to almost all β-lactams, including cefiderocol (4 mg/L), was recovered from a neonate 2 months after the isolation of the S. marcescens ROT_S strain that was susceptible to extended-spectrum cephalosporins (ESCs). In this study, we attempted to decipher the mechanism of resistance displayed by the ROT_R isolate. METHODS:The genomes of ROT_S and ROT_R were sequenced using the Illumina and the Oxford Nanopore Technologies. Long and short reads were assembled together, giving rise to a circularized hybrid genome. RESULTS:Genomic comparison between ROT_S and ROT_R disclosed only one mutation (G98A) in the cpxA gene of ROT_R, which led to the Arg-33-His substitution in the histidine kinase of the two-component system CpxA/CpxR. The cpxA alleles of ROT_S and ROT_R were amplified and cloned, thus giving rise to the pCpxA_WT and pCpxA_R33H recombinant plasmids, respectively, which were subsequently introduced into the S. marcescens HatR recipient strain, which lacks functional CpxA. The S. marcescens HatR (pCpxA_R33H) recombinant clone, which produced the altered CpxA_R33H variant, differed from the S. marcescens HatR (pCpxA_WT) recombinant clone, which produced the wild-type CpxA, by enhanced MICs of carbapenems and ESCs, including cefiderocol (1 mg/L). CONCLUSIONS:This study demonstrates that CpxA alteration, such as Arg-33-His substitution, can contribute to cefiderocol resistance. Although it increases slightly the MIC of cefiderocol without resulting per se in clinical resistance, it can contribute, in combination with other additional mechanisms, to achieve a high level of resistance to this siderophore cephalosporin.

OBJECTIVES:Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. METHODS:We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. RESULTS:Overall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. CONCLUSIONS:Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.

Journal Article High-level expression of chromosomally encoded SHV-1 β-lactamase reduces the susceptibility to cefiderocol of clinical isolates of Klebsiella pneumoniae Get access Rym Charfi, Rym Charfi Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Asmaa Tazi, Asmaa Tazi Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, FranceUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France https://orcid.org/0000-0001-9531-9177 Search for other works by this author on: Oxford Academic PubMed Google Scholar Youssouf Sereme, Youssouf Sereme Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, Laboratory of Bacteriology, 75015 Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Céline Plainvert, Céline Plainvert Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, FranceUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Hélène Poupet, Hélène Poupet Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Alexandra Doloy, Alexandra Doloy Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Cécile Guyonnet, Cécile Guyonnet Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, FranceUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Philippe Morand, Philippe Morand Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, FranceUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Julien Loubinoux, Julien Loubinoux Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Claire Poyart, Claire Poyart Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, FranceUniversité de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Hedi Mammeri Hedi Mammeri Hôpitaux Universitaires Paris Centre, Site Cochin, Service de Bactériologie, Assistance Publique Hôpitaux de Paris, Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, Laboratory of Bacteriology, 75015 Paris, France Corresponding author. E-mail: hedi.mammeri@aphp.fr Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, dkae143, https://doi.org/10.1093/jac/dkae143 Published: 24 May 2024

Loss of endothelial integrity and vascular leakage are central features of sepsis pathogenesis; however, no effective therapeutic mechanisms for preserving endothelial integrity are available. Here we show that, compared to dermal microvessels, brain microvessels resist infection by Neisseria meningitidis, a bacterial pathogen that causes sepsis and meningitis. By comparing the transcriptional responses to infection in dermal and brain endothelial cells, we identified angiopoietin-like 4 as a key factor produced by the brain endothelium that preserves blood–brain barrier integrity during bacterial sepsis. Conversely, angiopoietin-like 4 is produced at lower levels in the peripheral endothelium. Treatment with recombinant angiopoietin-like 4 reduced vascular leakage, organ failure and death in mouse models of lethal sepsis and N. meningitidis infection. Protection was conferred by a previously uncharacterized domain of angiopoietin-like 4, through binding to the heparan proteoglycan, syndecan-4. These findings reveal a potential strategy to prevent endothelial dysfunction and improve outcomes in patients with sepsis. Therapeutic administration of angiopoietin-like 4 prevents shock during Neisseria meningitidis infection or lipopolysaccharide-induced sepsis in mice.

BACKGROUND:Pelvic bone and/or soft tissue sarcoma removal surgeries are associated with a high rate of surgical site infection (SSI). The recommended antibiotic prophylaxis (ABP) duration is 24-48 h. We aimed to assess the impact of extended ABP (5 days) on the SSI rate and describe the microbiology of SSI in bone and/or soft tissue pelvic sarcomas. METHODS:We retrospectively included all consecutive patients who underwent pelvic bone and/or soft tissue sarcoma removal surgery between January 2010 and June 2020. RESULTS:We analyzed 146 patients with pelvic bone (45, 31%) or soft tissue (101, 69%). Sixty patients (41%) developed SSI. SSI occurred in 13/28 (46.4%) in the extended ABP group versus 47/118 (39.8%) in the standard group (p = 0.53). In multivariable analysis, risk factors for SSI were surgery duration (OR: 1.94 [1.41-2.92] per h), stay in postoperative ICU for more than 2 days (12.0 [2.8-61.3]), and shred or autologous skin flap (39.3 [5.8-409.5]). Extended ABP was not associated with SSI. SSI were mainly polymicrobial with Enterobacterales (57.4%) and Enterococcus (45%). CONCLUSIONS AND DISCUSSION:Pelvic bone and/or soft tissue sarcoma removal surgery is highly prone to postoperative infection. Extending the ABP to 5 days does not reduce the level of SSI.

A 3-year-old male originating from Djibouti presented with a cervical mass evolving for 2 months. Tuberculous lymphadenopathy was suspected based on biopsy results, and he improved quickly on standard antituberculous quadritherapy. Subsequently some features of the mycobacterium that grew in culture were unusual. The isolate was eventually identified as Mycobacterium canettii , a peculiar species of the Mycobacterium tuberculosis complex.

Objectives This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). Methods From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). Results One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). Conclusions Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.

Zoonotic species of Capnocytophaga genus belong to the oral microbiota of dogs and cats. They may be responsible for serious human infections, mainly after animal bites, with a high mortality rate. In France, only few cases have been reported and no multicenter study has been conducted. Our aim was to describe the French epidemiology of Capnocytophaga zoonosis. We conducted a multicenter (21 centers) retrospective non-interventional, observational study in France describing the epidemiology of Capnocytophaga zoonosis (C. canimorsus, C. cynodegmi, C. canis) over 10 years with regard to clinical and bacteriological data. From 2009 to 2018, 44 cases of Capnocytophaga zoonotic infections were described (C. canimorsus, n = 41; C. cynodegmi, n = 3). We observed an increase (2.5 times) in the number of cases over the study period (from the first to the last 5 years of the study). The most frequent clinical presentations were sepsis (n = 37), skin and soft tissue infections (n = 12), meningitis (n = 8), osteoarticular infections (n = 6), and endocarditis (n = 2). About one-third of patients with sepsis went into septic shock. Mortality rate was 11%. Mortality and meningitis rates were significantly higher for alcoholic patients (p = 0.044 and p = 0.006, respectively). Other comorbidities included smoking, splenectomy, diabetes mellitus, and immunosuppressive therapy are associated to zoonotic Capnocytophaga infection. Eighty-two percent of cases involved contact with dogs, mostly included bites (63%). Despite all isolates were susceptible to the amoxicillin-clavulanic acid combination, three of them were resistant to amoxicillin.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2–6) for a mean duration of 20 months (range, 13–27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

In the context of increasing antimicrobial resistance in Enterobacterales, the management of these UTIs has become challenging. We retrospectively assess the prevalence of antimicrobial resistance in Enterobacterales isolates recovered from urinary tract samples in France, between 1 September 2017, to 31 August 2018. Twenty-six French clinical laboratories provided the susceptibility of 134,162 Enterobacterales isolates to 17 antimicrobials. The most frequent species were E. coli (72.0%), Klebsiella pneumoniae (9.7%), Proteus mirabilis (5.8%), and Enterobacter cloacae complex (2.9%). The overall rate of ESBL-producing Enterobacterales was 6.7%, and ranged from 1.0% in P. mirabilis to 19.5% in K. pneumoniae, and from 3.1% in outpatients to 13.6% in long-term care facilities. Overall, 4.1%, 9.3% and 10.5% of the isolates were resistant to cefoxitin, temocillin and pivmecillinam. Cotrimoxazole was the less active compound with 23.4% resistance. Conversely, 4.4%, 12.9%, and 14.3% of the strains were resistant to fosfomycin, nitrofurantoin, and ciprofloxacin. However, less than 1% of E. coli was resistant to fosfomycin and nitrofurantoin. We identified several trends in antibiotics resistances among Enterobacterales isolates recovered from the urinary tract samples in France. Carbapenem-sparing drugs, such as temocillin, mecillinam, fosfomycin, cefoxitin, and nitrofurantoin, remained highly active, including towards ESBL-E.

BACKGROUND Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. MATERIALS/METHODS In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection within a minimal follow-up of 12 months. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. RESULTS We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was two-stage exchange in 95 (50.8%), one-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%). Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted HR=2.15, p=0.03) and antibiotic treatment over 6 weeks (adjusted HR=0.29, p=0.0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment - though not statistically significant for treatment failure (adjusted HR=0.5, p=0.07) and not for relapses (adjusted HR=0.5, p=0.10). CONCLUSIONS We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI but a dedicated prospective multicenter study is needed.

Cutibacterium acnes (C. acnes) est une bactérie impliquée dans l’acné inflammatoire. Les traitements topiques existants sont variablement efficaces, et associés à des effets secondaires pouvant être responsables d’une mauvaise observance. Le but de cette étude est la mise au point d’un nouveau traitement pour l’acné inflammatoire modérée. Les kératinocytes et les monocytes ThP1 ont été pré-traités par la méclozine (0,39 à 50 μM) puis stimulés par C. acnes pendant 18 h. La production de CXCL8 et IL-1beta a été analysée par RT-qPCR et par ELISA. Les voies de signalisation ont été explorées par Western blot sur les kératinocytes pré-traités ou non. C. acnes a été injecté dans les 2 oreilles de souris (8 par groupe), traitées par des applications de méclozine topique ou par le véhicule seul, tous les jours pendant 4 jours. Le score inflammatoire mesuré correspondait à la présence de rougeur, de pustule et/ou de desquamation et à l’épaisseur des oreilles. Un essai clinique ouvert a été réalisé chez 27 volontaires (12 hommes, 15 femmes, de 20 à 40 ans) présentant une acné légère à modérée (grade 2-3) avec l’application d’un gel de méclozine à 1 %, 2 fois par jour, pendant 4 semaines. In vitro, la méclozine réduit la production de CXCL8 dans les kératinocytes et d’IL-1beta dans les ThP1, au niveau transcriptionnel et traductionnel avec des CI50 à 3 et 6 μM, respectivement. Aucune toxicité cellulaire mesurée à la CI50. La comparaison de l’efficacité de la méclozine avec les molécules couramment utilisées dans le traitement de l’acné montre que seul l’adapalène a un effet anti-CXCL8 mais associé à une forte cytotoxicité. La méclozine inhibe la dégradation de IkB et la phosphorylation de ERKs, p38, JNK, PKC, Akt, PPARalpha, PPARbeta et l’activation de Cox2. In vivo, la méclozine en application topique à 0,1, 0,5, 1, 2 et 4 %, réduit l’inflammation induite dans l’oreille des souris de 19 % (p = 0,04), 13 % (p = 0,14), 26 % (p = 0,01), 48 % (p = 0,002) et 56 % (p = 8,2 10−5), respectivement. En clinique, la méclozine à 1 %, montre une réduction de l’index de sévérité de l’acné de 34,5 à 27,2 (p = 0,002) après 4 semaines de traitement, sans aucun effet secondaire. La méclozine est un antiH1 et un antiémétique, utilisé dans les allergies et le mal des transports. Nous montrons qu’elle possède aussi une activité anti-inflammatoire dans des modèles in vitro et in vivo d’inflammation induite par C. acnes. L’étude clinique pilote montre une réduction significative du score clinique après 4 semaines de traitement, avec une absence totale de toxicité. Nous montrons ici que la méclozine pourrait représenter une nouvelle classe de molécule prometteuse pour le traitement de l’acné.

Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and meningitis. Since the first description of the epidemic nature of the illness at the dawn of the nineteenth century, the scientific knowledge of meningococcal infection has increased greatly. Major advances have been made in the management of the disease with the advent of antimicrobial therapy and the implementation of meningococcal vaccines. More recently, an extensive knowledge has been accumulated on meningococcal interaction with its human host, revealing key processes involved in disease progression and new promising therapeutic approaches.

The pathogenicity of the anaerobic bacteria Cutibacterium acnes (C acnes) is characterized by its ability to induce strong inflammatory response involving the TLRs receptors signaling pathway. Keratinocytes and ThP1 monocyte cells were pretreated with meclozine (0.39 to 50 μM) for 24 h and then stimulated for 18 h with C acnes suspension. Meclozine is able to inhibit the production of IL-1β and CXCL8 at the transcriptional level measured by RT-qPCR and at the protein level, measured by ELISA, in a dose-dependent manner with a IC50 at 3 and 6 μM, respectively. No cytotoxicity, evaluated by MTT assay, was measured at the IC50. When comparing the effect of meclozine with common commercial molecules (6 μM) used in acne treatment (erythromycine, clindamycine, benzoyl peroxide, isotretinoine, adapalene and retinoic acid) only adapalene shown comparable CXCL8 inhibition to meclozine but was associated with strong cytotoxicity. Western blot analysis shown that meclozine prevented the degradation of IκB and the phosphorylation of ERKs, p38, JNK, PKC, Akt, PPARα, PPARβ, Cox2 induced by C acnes. Meclozine-gel application reduced dose-dependently inflammation in a in vivo C acnes-induced ear inflammation model in mice by 19% (P = .04), 13% (P = .14), 26% (P = .01), 48% (P = .002), and 56% (P = 8.2 × 105) at 0.1, 0.5, 1, 2 and 4% concentrations, respectively. Therefore, meclozine appears to be a promising molecular compound to be tested clinically.

Significance Type IV pili (T4P) are among the most widespread adhesive factors in prokaryotes. In pathogenic Neisseria , the major pilin, which provides the structural framework for the filamentous T4P, undergoes antigenic variation allowing the bacteria to evade the humoral immune response without impacting host-cell adhesion. Here, we show that a minor pilin, PilV, is distributed throughout the pilus and contributes to Neisseria meningitidis adhesion and that antibodies to PilV block meningococcal adhesion in vivo. Our results provide a mechanism whereby N. meningitidis varies its immunodominant major pilin to escape antibody recognition while maintaining conserved sites throughout the pilus for host receptor binding. They further suggest a strategy to prevent or block deadly N. meningitidis infections by targeting this minor pilin.

Objectives. - One-stage replacement arthroplasty for treatment of periprosthetic joint infection (PJI) results in similar cure rate than two-stage (around 85-92%), but antibiotic therapy duration is not well established. The aim of this study was to evaluate the efficacy of a short six-week antibiotic course in periprosthetic joint infections after onstage exchange. Patients and methods. - Retrospective, observational study conducted at Orthopaedic Department of Cochin Hospital, Paris, between 1st January 2010 and 31 December 2015. Patients with a microbiologically proven PJI, treated with one-stage replacement and 6 weeks (+/1week) of antimicrobial therapy were included. Pearson's-chi(2) and Wilcoxon tests were used to compare categorical and continuous variables. Results. - Fifty patients with periprosthetic joint infections (42 hip, 8 knee PJI) treated with one-stage replacement arthroplasty were included. Median age was 69.3 years (IQR 24.5-97.4). Infections occurred after a mean of 36 months (IQR 1-216). Bone biopsy cultures were positive for Staphylococcus spp. in 29 patients (58%), Cutibacterium acnes in 19 (38%), Gram-negative bacilli in 6 (12%). Polymicrobial infections occurred in 12 (24%). Intravenous antibiotics were administered for a median of 11 days (IQR 4-45) and 46 patients (92%) were switched to an oral therapy. Medium follow-up was of 32 months (IQR 12-101). Overall remission rate was 90%. Conclusions. - A six-week course of antibiotics in knee and hip PJIs treated with one-stage RA has a satisfactory remission rate in this open study. (C) 2020 Elsevier Masson SAS. All rights reserved.

Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and meningitis. Interaction with both peripheral and cerebral microvascular endothelial cells is at the heart of meningococcal pathogenesis. During the last two decades, an essential role for meningococcal type IV pili in vascular colonisation and disease progression has been unravelled. This review summarises 20 years of research on meningococcal type IV pilus-dependent virulence mechanisms, up to the identification of promising anti-virulence compounds that target type IV pili.

The chromogenic βLACTA™ test was evaluated to detect ceftazidime resistance in P. aeruginosa isolates from patients with cystic fibrosis. Best results were obtained after one hour of incubation with low sensitivity (64.1%), high specificity (98.3%), and negative and positive predictive values of 80.3% and 96.2%, respectively.

En France, la prescription de daptomycine dans les infections ostéoarticulaires (IOA) est assez récente et encore peu étudiée. Dans un centre de référence des IOA, son utilisation est décidée après discussion en réunion de concertation pluridisciplinaire (RCP) en cas de : – reprise de prothèse avec suspicion ou documentation de saphylocoque résistant à la méticilline ; – pour une durée ≤ 15 jours. Dans le cadre du bon usage des antibiotiques, un audit de ces prescriptions a été mené après un an d’utilisation. Il s’agissait d’une étude rétrospective, descriptive de toutes les prescriptions de daptomycine faites en orthopédie entre le 1er janvier 2018 au 31 octobre 2018. La conformité aux recommandations a été étudiée par 2 référents en infectiologie, selon 2 critères : respect des indications et durée de traitement. Un total de 43 prescriptions de daptomycine ont été administrées chez 36 patients hospitalisés pour IOA (hanche (60 %) et genou (19 %)). Quatre vingt cinq pourcent d’entre eux ont bénéficié d’un changement de matériel, en 1 temps pour 23 patients (56 %) et en 2 temps pour 12 patients (29 %). La daptomycine était prescrite en probabiliste dans 75 % des cas, et dans 100 % des cas en bithérapie (avec rifampicine dans 46 % et lévofloxacine dans 22 % des cas). Les indications de la daptomycine étaient conformes aux recommandations des RCP dans 70 % des cas (n = 30/43). Les causes les plus fréquentes de non conformité aux recommandations étaient : un prélèvement préopératoire ayant isolé un germe autre que Staphylococcus. Spp (n = 5) ou ayant isolé un SAMS (n = 3). La durée médiane de daptomycine était de 10 jours (2–36). Parmi les 30 patients dont l’indication de la daptomycine était validée, 87 % (n = 26/30) avaient une durée conforme aux recommandations. Le seul motif de non conformité était l’absence de désescalade thérapeutique après positivité du prélèvement peropératoire. Au total, 60,5 % des prescriptions étaient conformes à 100 % pour les 2 critères étudiés. La daptomycine est un antibiotique coûteux à fort impact écologique potentiel. Des efforts sont à faire pour préserver cette molécule.

Bacterial virulence factors are attractive targets for the development of therapeutics. Type IV pili, which are associated with a remarkable array of properties including motility, the interaction between bacteria and attachment to biotic and abiotic surfaces, represent particularly appealing virulence factor targets. Type IV pili are present in numerous bacterial species and are critical for their pathogenesis. In this study, we report that trifluoperazine and related phenothiazines block functions associated with Type IV pili in different bacterial pathogens, by affecting piliation within minutes. Using Neisseria meningitidis as a paradigm of Gram-negative bacterial pathogens that require Type IV pili for pathogenesis, we show that piliation is sensitive to altered activity of the Na+ pumping NADH-ubiquinone oxidoreductase (Na+-NQR) complex and that these compounds probably altered the establishment of the sodium gradient. In vivo, these compounds exert a strong protective effect. They reduce meningococcal colonization of the human vessels and prevent subsequent vascular dysfunctions, intravascular coagulation and overwhelming inflammation, the hallmarks of invasive meningococcal infections. Finally, they reduce lethality. This work provides a proof of concept that compounds with activity against bacterial Type IV pili could beneficially participate in the treatment of infections caused by Type IV pilus-expressing bacteria.