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Objectives: Determining the best available therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is a challenge. Cefiderocol is an attractive alternative drug effective against many resistance mechanisms in Gram-negative bacteria. However, its place in the treatment of Acinetobacter baumannii infections remains unclear and much debated, with contradictory results., Methods: We describe here the case of a 37-year-old man with ventilator-associated bacteraemic CRAB pneumonia in an intensive care unit. He was initially treated with a combination of colistin and tigecycline, and was then switched onto colistin and cefiderocol. We then used a new accessible protocol to test 30 CRAB isolates (OXA-23/OXA-24/OXA-58/NDM-1) for adaptive resistance to cefiderocol (ARC) after exposure to this drug., Results: After clinical failure with the initial combination, we noted a significant clinical improvement in the patient on the second combination, leading to clinical cure. No ARC was detected in the two OXA-23 case-CRAB isolates. All NDM-1 CRAB isolates were resistant to cefiderocol in standard tests; the OXA-23, OXA-24 and OXA-58 CRAB isolates presented 84.2 %, 50 % and 0 % ARC, respectively., Conclusions: ARC is not routinely assessed for CRAB isolates despite frequently being reported in susceptible isolates (69.2 %). Subpopulations displaying ARC may account for treatment failure, but this hypothesis should be treated with caution in the absence of robust clinical data. The two main findings of this work are that (i) cefiderocol monotherapy should probably not be recommended for OXA-23/24 CRAB infections and (ii) the characterisation of carbapenemases in CRAB strains may be informative for clinical decision-making., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: In May 2020, the French Ministry of Health funded the creation of regional antimicrobial stewardship (AMS) coordination centres (CRAtb) in preparation for the new national framework for the prevention of antimicrobial resistance. This study aimed to assess through qualitative methods the implementation process, the activities carried out, and the interactions with other regional stakeholders of the newly created CRAtb., Methods: We conducted a mixed-method study based on a cross-sectional survey and semi-structured interviews by French regions among implemented CRAtb. Of the eight eligible French regions with an existing CRAtb, seven participated to the online survey. Regional partners involved in AMS from the eight regions were interviewed between September 2021 and April 2022. The survey questionnaire addressed, through closed questions, the organization of the CRAtb, articulation with other regional actors involved in AMS and infection prevention and control (IPC), and AMS activities. The semi-structured interviews approached the implementation and the role of CRAtb, and the collaboration of other AMS and IPC stakeholders. Interview transcripts were analysed using thematic content analysis methodology., Results: AMS activities carried out by CRAtb were mainly focusing on hospitals (n = 3), primary care (n = 2) and nursing homes (n = 1). Education mostly relied on training days and AMS help lines, communication on websites and newsletters. CRAtb members reported still being more engaged in providing advice to professionals for individual antibiotic treatments rather than collective-level AMS activities. Interactions were frequent between CRAtb, IPC regional centres and health authorities, but rarely involved other stakeholders. Interviews were performed with 28 professionals involved in AMS from eight regions. Pre-existing networks and working relationships in AMS and more broadly facilitated the implementation of CRAtb. Streamlining and decompartmentalizing IPC and AMS regional activities were considered a way to optimise the prevention of antimicrobial resistance across sectors. The engagement with liberal health professionals was identified as a significant obstacle for CRAtb., Conclusions: Two years after the launch of a new national framework, the implementation of CRAtb appeared complex in most regions. An integrative model joining IPC and AMS efforts, relying on existing networks, with engagement from liberal health profession organisations may be the next pivotal step., (© 2023. The Author(s).)

Background: Automated molecular panels are attractive tools for improving early meningitis diagnosis. This study assessed the Eazyplex ® CSF direct M panel (EP), a multiplex real-time Loop-Mediated Isothermal Amplification assay. Methods: From December 2016 to December 2019, cerebrospinal fluid (CSF) samples were routinely tested with the EP V1.0. CSF parameters and microbiological and clinical data were retrospectively collected. Results: Out of 230 CSF samples, the EP yielded positive, negative, and invalid results for 32 (13.9%) (16 N. meningitidis , nine S. pneumoniae , two S. agalactiae , two E. coli , two H. influenzae , one L. monocytogenes ), 182 (79.1%), and 16 (7%) samples, respectively. Among the positive samples, 14 (44%) remained negative in culture (antibiotic therapy before lumbar puncture ( n = 11), meningococcal meningitis ( n = 3)). High CSF protein concentrations and cellularity were associated with LAMP inhibition, counteracted by centrifugation. The automated software yielded 13 false positive and five false negative results. Amplification curve analysis was necessary and enabled the attainment of positive (PPA) and negative percentage agreement and positive and negative predictive values of 91.4%, 100%, 100%, and 98.3%. Three false negative results remained (two E. coli and one N. meningitidis ). E. coli presented the poorest PPA (50%). Conclusion : This work confirms the strong performance of the EP, of particular interest in cases of antibiotic therapy before lumbar puncture.

Objectives: Current guidelines recommend cefazolin as an alternative to antistaphylococcal penicillins (ASPs) in methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis despite the lack of comparative study. The objective of this study was to evaluate the comparative outcomes of cefazolin vs. ASPs in MSSA infective endocarditis., Methods: This was a retrospective analysis of an observational multicentre cohort study using prospectively collected data from patients with MSSA endocarditis confirmed by endocarditis team and treated either with cefazolin or ASPs between July 2013 and December 2018. Patients were excluded if they received both treatments. The primary outcome was 90-day all-cause mortality., Results: Of 210 patients included, 53 patients (25.2%) received cefazolin and 157 (74.8%) received ASPs. The overall 90-day mortality rate was 27.6% (58/210 patients), 24.5% (13/53) in the cefazolin group vs. 28.7% (45/157) in the ASP group (p 0.561). Premature antimicrobial discontinuation due to adverse events occurred less frequently with cefazolin than with ASPs (0/53 vs. 13/157 patients; p 0.042). In multivariate analysis, there was no difference in 90-day mortality between cefazolin and ASPs (adjusted odds ratio (aOR), 1.2; 95% confidence interval (CI), 0.49-2.91; p 0.681), while age (aOR, 1.06; 95% CI, 1.03-1.09; p < 0.001), Charlson comorbidity index (aOR, 1.18; 95% CI, 1.02-1.36 p 0.023), cerebral embolism (aOR, 2.83; 95% CI, 1.33-6.14; p 0.007) and intensive care unit admission (aOR, 4.16; 95% CI, 1.89-9.59; p 0.001) were factors significantly associated with higher mortality., Conclusions: Cefazolin seems to be a possible alternative to ASPs in MSSA endocarditis. More studies are needed to confirm these results and determine which treatment should be recommended as first-line therapy., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Resections of primary pelvic bone tumors are frequently complicated by surgical site infections (SSIs), thereby impairing the functional prognosis of patients, especially in case of implant removal. Although prophylactic antibiotics play an essential role in preventing SSIs, there are presently no recommendations that support their appropriate use. This study aimed to assess the impact of a 24 h prophylactic protocol on the bacterial ecology, the resistance pattern, and the SSI healing rate. We hypothesized that this protocol not only limits the emergence of resistance but also results in a good cure rate with implant retention in case of SSI. A retrospective study was performed that included all patients with an SSI following a pelvic bone tumoral resection between 2005 and 2017 who received a 24 h antibiotic prophylaxis protocol. Twenty-nine patients with an SSI were included. We observed a 75.9% rate of polymicrobial infection, with a high prevalence of digestive flora microorganisms and a majority of wild-type phenotypes. We confirmed that there was no significant emergence of resistant flora. After first-line debridement, antibiotics (DA) if any implant was used, or debridement, antibiotics, and implant retention (DAIR) whenever possible, we obtained a 79.3% cure rate, with implant removal in 20% of cases. The absence of an implant was significantly associated with SSI healing. Early infection management and low resistance profiles may also have a positive effect, but this needs to be confirmed in a larger cohort. In light of this, the use of a 24 h prophylactic protocol in primary pelvic bone tumor resections is associated with a favorable infection cure rate and implant retention in case of SSI, and minimal selection of resistant microorganisms.

Azithromycin (AZM) is a 15-membered-ring macrolide that presents a broad-spectrum antimicrobial activity against Gram-positive bacteria and atypical microorganisms but suffers from a poor diffusion across the outer-membrane of Gram-negative bacilli, including Pseudomonas aeruginosa (PA). However, AZM has demonstrated clinical benefits in patients suffering from chronic PA respiratory infections, especially cystic fibrosis patients. Since the rise of multidrug-resistant PA has led to a growing need for new therapeutic options, this macrolide has been proposed as an adjunctive therapy. Clinical trials assessing AZM in PA acute pneumonia are scarce. However, a careful examination of the available literature provides good rationales for its use in that context. In fact, 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. Furthermore, growing evidence supports a downregulation of PA virulence dependent on direct interaction with the ribosomes, and based on the modulation of several key regulators from the Quorum Sensing network. First highlighted in vitro , these interesting properties of AZM have subsequently been confirmed in the animal models. In this review, we systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects. In vitro and in vivo studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Leroy, Caillon, Caroff, Broquet, Corvec, Asehnoune, Roquilly and Crémet.)

Diabetes is marked by a range of complications, including chronic infections that can lead to limb amputation. The treatment of infected wounds is disrupted by arteriopathies that reduce tissue perfusion as well as by the critical development of bacterial resistance. We evaluated the impact of a local application of bacteriophages compared to that of a per os administration of amoxicillin-clavulanic acid in a mouse model of Staphylococcus aureus wound infection. We found that phage treatment resulted in improved clinical healing and a reduction in local bacterial load at 7 and 14 days postinfection. Unlike antibiotics, phage therapy did not deplete the intestinal microbiota of treated animals. Amoxicillin resulted in a reduction of alpha and beta diversities of the murine microbiota and disturbed architecture even 7 days after the end of treatment, whereas phage treatment did not impinge on the microbiota. IMPORTANCE The management of diabetic foot infections is frequently a dead end for surgeons and infectious disease specialists. When the pathogen to be treated is not resistant to conventional antibiotics, the latter tend to unbalance the intestinal microbiota, which is linked to multiple pathologies. A local treatment with bacteriophages, in addition to being as much or even more effective than antibiotics from a clinical and microbiological point of view, makes it possible to respect the patient's microbiota. These results suggest that the use of this therapeutic alternative is a major avenue and that the introduction of recommendations for their use is now necessary., (Copyright © 2020 Huon et al.)

Objectives: To assess the meningeal penetration of cefazolin and cloxacillin in individuals treated for methicillin-susceptible staphylococcal meningitis., Methods: We retrospectively identified individuals treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a validated assay of liquid chromatography coupled with mass spectrometry at the Nantes University Hospital between January 2009 and October 2019. Staphylococcus meningitis was defined by a compatible clinical presentation and a microbiological confirmation (positive CSF culture or positive specific PCR). Medical charts were retrospectively reviewed to collect microbiological and clinical data, and to assess therapeutic success., Results: Among the 17 included individuals, eight (47%) were treated with cefazolin and nine (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 g (range 6-12 g) and 12 g (range 10-13 g), respectively. Cefazolin and cloxacillin were mainly administered by continuous infusion. Eleven individuals (65%) were men, median (interquartile range (IQR)) age was 54 years (50; 70), 14 (82%) had postoperative meningitis and 3 (18%) had haematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 mg/L (2.1; 5.2) and 0.66 mg/L (0.5; 0.9) for cefazolin and cloxacillin groups, respectively. Cloxacillin was discontinued in two individuals for therapeutic failure., Conclusions: Patients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of cefazolin achieved therapeutic concentrations in CSF. Cefazolin appears to be a therapeutic candidate that should be properly evaluated in this indication., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: The diagnosis of prosthetic joint infections (PJIs) can be difficult in the chronic stage and is based on clinical and paraclinical evidence. A minimally invasive serological test against the main pathogens encountered during PJI would distinguish PJI from mechanical loosening. Methods: We performed a prospective, multicentre, cross-sectional study to assess the contribution of serology in the diagnosis of PJI. Over a 2-year period, all patients undergoing prosthesis revision were included in the study. A C-reactive protein assay and a serological test specifically designed against 5 bacterial species ( Staphylococcus aureus , S. epidermidis , S. lugdunensis, Streptococcus agalactiae , Cutibacterium acnes ) were performed preoperatively. Five samples per patient were taken intraoperatively during surgery. The diagnosis of PJI was based on clinical and bacteriological criteria according to guidelines. Results: Between November 2015 and November 2017, 115 patients were included, 49 for a chronic PJI and 66 for a mechanical problem. Among patients with PJI, a sinus tract was observed in 32.6% and a C-reactive protein level ≥10 mg/L in 74.5%. The PJI was monomicrobial in 43 cases (targeted staphylococci, 24; S. agalactiae , 1; C. acnes , 2; others, 16), and polymicrobial in 6 cases (12.2%). Sensitivity, specificity, positive predictive value and negative predictive value were 75.0%, 82.1%, 58.3% and 90.8%, respectively, for targeted staphylococci. Specificity/negative predictive value was 97.3%/100% for S. agalactiae and 83.8% /96.9% for C. acnes . Conclusions: The serological tests are insufficient to affirm the diagnosis of PJI for the targeted bacteria. Nevertheless, the excellent NPV may help clinicians to exclude PJI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: Prosthetic joint infections (PJI) are responsible for significant morbidity and mortality and their number continues to rise. Their management remains complex, especially the microbiological diagnosis. Besides 'homemade' tests developed by several teams, new molecular biology methods are now available with different analytical performance and usability., Methods: We studied the performances of one of these tests: ITI ® multiplex PCR (mPCR) by the Curetis ® company and compared it to either 'optimized' culture or 16S rRNA PCR. We performed a retrospective multicentre study to assess the contributions of mPCR in the diagnosis of PJI. We randomly selected 484 intraoperative specimens among 1252 of various types (biopsy, bone, tissue around the prosthesis, synovial fluid) from 251 patients in seven different hospitals. Each sample was treated according to the recommendations of the manufacturer., Results: In all, 154 out of 164 (93.9%) samples negative in culture were negative with the mPCR. Among the 276 positive samples in culture, 251 (90.9%) were monomicrobial, of which 119 (47.4%) were positive with the mPCR, and 25 (9.1%) were polymicrobial, of which 12 (48%) were positive with the mPCR. The concordance rate of mPCR with culture was 58.1% (53.6%-62.7%) and the concordance rate with 16S rRNA PCR was 70.1% (65.5%-74.6%)., Conclusion: This new standardized molecular test showed a lack of detection when the bacterial inoculum was low (number of positive media per sample and number of colonies per media) but can be useful when patients have received antibiotic therapy previously., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)