The antibiotic classes that are recommended for tularaemia treatment are the aminoglycosides, the fluoroquinolones and the tetracyclines. However, cure rates vary between 60 and 100% depending on the antibiotic used, the time to appropriate antibiotic therapy setup and its duration, and the presence of complications, such as lymph node suppuration. Thus, antibiotic susceptibility testing (AST) of F. tularensis strains remains of primary importance for detection of the emergence of antibiotic resistances to first-line drugs, and to test new therapeutic alternatives. However, the AST methods reported in the literature were poorly standardized between studies and AST data have not been previously evaluated in a comprehensive and comparative way. The aim of the present review was to summarize experimental data on antibiotic susceptibilities of F. tularensis obtained in acellular media, cell models and animal models since the introduction of fluoroquinolones in the treatment of tularaemia in 1989. We compiled MIC data of 33 antibiotics (including aminoglycosides, fluoroquinolones, tetracyclines, macrolides, β-lactams, chloramphenicol, rifampicin, and linezolid) against 900 F. tularensis strains (504 human strains), including 107 subsp. tularensis (type A), 789 subsp. holarctica (type B) and four subsp. mediasiatica strains, using various AST methods. Specific culture media were identified or confirmed as unsuitable for AST of F. tularensis. Overall, MICs were the lowest for ciprofloxacin (≤ 0.002–0.125 mg/L) and levofloxacin, and ranged from ≤ 0.016 to 2 mg/L for gentamicin, and 0.064 to 4 mg/L for doxycycline. No resistant strain to any of these antibiotics was reported. Fluoroquinolones also exhibited a bactericidal activity against intracellular F. tularensis and lower relapse rates in animal models when compared with the bacteriostatic compound doxycycline. As expected, lower MIC values were found for macrolides against type A and biovar I type B strains, compared to biovar II type B strains. The macrolides were more effective against F. tularensis grown in phagocytic cells than in acellular media.

Up to 15% of patients infected by SARS-CoV-2 present severe forms requiring hospitalisation in intensive care units and which are associated with high mortality. The prevalence of bacterial infections in these patients is not well established and more data are needed to guide empiric antibiotic therapy and improve patient outcomes. In this prospective multicenter study, we assessed bacterial co-infections identified in culture from 99 French patients infected by SARS-Cov-2 and hospitalized in intensive care units. We concomitantly evaluated the value of the use of an innovative molecular diagnostic technologies, the BioFire® FilmArray® Pneumonia Panel plus (FA-pneumo) assay, to early identify these co-infections in these patients and the concordance with conventional culture. We showed that a bacterial co-infection was detected in 15% of patients based on conventional culture. S. aureus and H. influenzae were the most prevalent pathogens. The sensitivity of FA-pneumo compared to culture was 100%. Conversely, the specificity varied between 88.4 and 100% according to the pathogen and our results highlighted that 60.5% of bacterial targets reported using this assay were not recovered by culture; 76.9% of discordant results corresponded to bacteria belonging to commensal oral flora and/or reported with ≤ 10 5 copies/mL of bacterial nucleic acids. Based on its excellent sensitivity, the FA-pneumo assay is useful to rule out bacterial co-infections in the context of severe SARS-CoV-2 infection and avoid the inappropriate prescription of antibiotics. However, positive tests should be interpreted carefully taking into consideration DNA bacterial load, all clinical and biological signs.