Clinical features and treatment outcomes of bone and joint nontuberculous mycobacterial infections according to immune status: a 9-year retrospective observational cohort.

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.

Impact of revised breakpoints on the categorization of susceptibility of Enterobacterales to temocillin.

Background: To harmonize with the EUCAST breakpoints, the French Society of Microbiology introduced a change in the inhibition diameter breakpoint (17 mm versus 20 mm previously) of temocillin. We assessed the impact of the new breakpoints on categorizing susceptibility of Enterobacterales to temocillin. Methods: This was a multicentric retrospective study including all Enterobacterales isolates routinely tested for temocillin susceptibility with the disc diffusion method between 1 January 2016 and 31 July 2022 in four centres. Categorization using the breakpoints of 20 mm (French guidelines CA-SFM/EUCAST 2020 v.1.1) and 17 mm (French guidelines CA-SFM/EUCAST 2021 v1.0 and EUCAST guidelines v11.0) was performed. Results: Overall, 36 416 Enterobacterales isolates were included. The overall rate of temocillin resistance decreased from 11.3% to 4.7% (relative difference of 58.5%) when using the 17 mm breakpoint instead of the 20 mm breakpoint, respectively. The relative change ranged from -44.0% in Klebsiella aerogenes to -72.7% in Klebsiella oxytoca. The median inhibition diameter was 23 mm (IQR 21-25). The isolates with a diameter of 20 mm appeared overrepresented, whereas those with a diameter of 18 and 19 mm were underrepresented. We therefore reviewed the diameters between 18 and 21 mm of 273 isolates. Thirty-two (11.7%) of them categorized as susceptible at first measure were controlled resistant at second measure. Conclusions: The new breakpoint induced a decrease in the rate of isolates categorized as resistant to temocillin, increasing therapeutic choice including for Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). We suggest the bias in measuring the inhibition diameter is probably related to the fact that temocillin is considered remarkably stable against broad-spectrum ß-lactamases.

Apelin is expressed in intimal smooth muscle cells and promotes their phenotypic transition.

During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium-binding protein. We investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. We found that apelin was highly expressed in R-SMCs compared with S-SMCs. We observed a nuclear expression of apelin in SMCs within experimentally-induced intimal thickening of the porcine coronary artery and rat aorta. Plasmids targeting apelin to the nucleus (N. Ap) and to the secretory vesicles (S. Ap) were transfected into S-SMCs where apelin was barely detectable. Both plasmids induced the SMC transition towards a R-phenotype. Overexpression of N. Ap, and to a lesser degree S. Ap, led to a nuclear localization of S100A4. Stimulation of S-SMCs with platelet-derived growth factor-BB, known to induce the transition toward the R-phenotype, yielded the direct interaction and nuclear expression of both apelin and S100A4. In conclusion, apelin induces a SMC phenotypic transition towards the synthetic phenotype. These results suggest that apelin acts via nuclear re-localization of S100A4, raising the possibility of a new pro-atherogenic relationship between apelin and S100A4.

Xpert MTB/RIF Ultra Trace Results: Decision Support for the Treatment of Extrapulmonary Tuberculosis in Low TB Burden Countries.

OBJECTIVES: Extrapulmonary tuberculosis (EPTB) can be difficult to diagnose, especially in severe forms. The Xpert MTB/RIF Ultra test introduced an additional category called trace to reference very small amounts of Mycobacterium tuberculosis complex (MTBC) DNA. The objective of our multicenter study was to evaluate whether the trace result on an extrapulmonary (EP) sample is a sufficient argument to consider diagnosing tuberculosis and starting treatment, even in severe cases. METHODS: A retrospective, multicenter cohort study was conducted from 2018 to 2022. Patients strongly suspected of EPTB with a trace result on an EP specimen were included. Hospital records were reviewed for clinical, treatment, and paraclinical data. RESULTS: A total of 52 patients were included, with a severe form in 22/52 (42.3%) cases. Culture was positive for MTBC in 33/46 (71.7%) cases. Histological analysis showed granulomas in 36/45 (80.0%) cases. An Ultra trace result with a presumptive diagnosis of TB led to the decision to treat 41/52 (78.8%) patients. All patients were started on first-line anti-TB therapy (median duration of 6.1 months), with a favorable outcome in 31/35 (88.6%) patients. The presence of a small amount of MTBC genome in EPTB is a sufficient argument to treat patients across a large region of France.

Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales.

OBJECTIVES: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020. METHODS: First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum ß-lactamase [ESBL] production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), including 170 carbapenemase producers (CPE). Then, 1632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by E-test® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison. RESULTS: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs. 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80% of OXA-48-like producers were susceptible to C/T, whereas all metallo-ß-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1632 clinical isolates demonstrated 99% of categorization agreement between MIC to C/T determined by E-test® in comparison with the BMD (reference) and only 74% of essential agreement. CONCLUSION: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers, and ESBL-producing Escherichia coli but is less active against ESBL-producing Klebsiella pneumoniae, and CRE. E-test® led to an underestimation of the MICs in comparison to the BMD reference.

Multiplex PCR assay targeting Trichomonas vaginalis: need for biological evaluation and interpretation.

In a retrospective study, we used sequencing to investigate Trichomonas vaginalis-positive specimens (genital, rectal and pharyngeal) with the Allplex™ STI Essential or the Anyplex™-II-STI-7 assays. Our results confirm that majority of T. vaginalis-positive genital and pharyngeal specimens contained T. vaginalis DNA and actually T. tenax DNA, respectively.

Geohistorical dataset of ten plant species introduced into Occitania (France).

Background: The original dataset presented here is the result of the first near-exhaustive analysis performed on historical data concerning ten plant species introduced in and around Occitania (south-western France) since 1651. Research was carried out on the following species: Alnusincana, Buddlejadavidii, Castaneasativa, Helianthustuberosus, Impatiensglandulifera, Prunuscerasifera, Prunuslaurocerasus, Reynoutriajaponica, Robiniapseudoacacia and Spiraeajaponica.The data file contains 199 occurrence data exclusively based on historical observations and records made between 1651 and 2004 that were retrieved from 111 of the 640 literary sources consulted. All the records are associated with a year and 61% of them have associated spatial coordinates. Initially, the EI2P-VALEEBEE research project focused on the introduction of these species into Occitania (95 occurrences, 47.7%), but mentions found of introductions beyond this territory - mainly in metropolitan France - are also reported.The creation of this dataset involved five stages: (1) selection of species, (2) consultation of historical sources, (3) recording of occurrences in the dataset, (4) dataset standardisation/enrichment and Darwin core mapping and (5) data publication. Quality controls were conducted at each step.The dataset is available on the platform of the Global Biodiversity Information Facility (GBIF) at https://doi.org/10.15468/3kvaeh. It respects the internationally recognised FAIR Data Principles (Findable, Accessible, Interoperable and Reusable). New information: The dataset will be progressively enriched by new data during the EI2P-VALEEBEE research project and future projects on invasive plant species conducted by the team.

Contribution of the anaerobic blood culture vial for the recovery of Candida glabrata: A retrospective multicentric study.

Although Candida spp are aerobic microorganisms, some Candida strains, mainly Candida glabrata, can be recovered from anaerobic blood culture vials. We assessed the contribution of the anaerobic vials for the diagnosis of candidemia, especially for C. glabrata. We conducted a multicenter retrospective study including eight university or regional hospitals. A single episode of monomicrobial candidemia per patient was included from September 1st, 2016, to August 31st, 2019. The characteristics of all aerobic and anaerobic blood culture vials sampled within 2 h before and after the first positive blood culture vials were recorded (type of vials, result, and for positive vials time-to-positivity and Candida species). Overall, 509 episodes of candidemia were included. The main species were C. albicans (55.6%) followed by C. glabrata (17.1%), C. parapsilosis (4.9%), and C. tropicalis (4.5%). An anaerobic vial was positive in 76 (14.9%) of all episodes of which 56 (73.8%) were due to C. glabrata. The number of C. glabrata infections only positive in anaerobic vials was 1 (2.6%), 1 (11.1%), and 15 (37.5%) with the BACT/ALERT 3D the BACT/ALERT VIRTUO and the BACTEC FX instrument, respectively (P < 0.01). The initial positivity of an anaerobic vial was highly predictive of the isolation of C. glabrata with the BACTEC FX (sensitivity of 96.8%). C. glabrata time-to-positivity was shorter in anaerobic vial than aerobic vial with all instruments. Anaerobic blood culture vials improve the recovery of Candida spp mainly C. glabrata. This study could be completed by further analyses including mycological and pediatric vials. LAY SUMMARY: Although Candida spp are aerobic microorganisms, C. glabrata is able to grow in anaerobic conditions. In blood culture, the time-to-positivity of C. glabrata is shorter in anaerobic than aerobic vials. Only the anaerobic vial was positive in up to 15 (37.5%) C. glabrata bloodstream infections.

Antimicrobial Resistance in Enterobacterales Recovered from Urinary Tract Infections in France.

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.

Capnocytophaga zoonotic infections: a 10-year retrospective study (the French CANCAN study).

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.

High Prevalence of OXA-23 Carbapenemase-Producing Proteus mirabilis among Amoxicillin-Clavulanate-Resistant Isolates in France.

In this multicentric study performed in 12 French hospitals, we reported that 26.9% (14/52) of the amoxicillin-clavulanate-resistant Proteus mirabilis isolates produced the OXA-23 carbapenemase. We found that an inhibition zone diameter of <11 mm around the amoxicillin-clavulanate disc was an accurate screening cutoff to detect these OXA-23 producers. We confirmed by whole-genome sequencing that these OXA-23-producers all belonged to the same lineage that has been demonstrated to disseminate OXA-23 or OXA-58 in P. mirabilis.

Host Immunity and Francisella tularensis: A Review of Tularemia in Immunocompromised Patients.

Tularemia, caused by the bacterium Francisella tularensis, is an infrequent zoonotic infection, well known in immunocompetent (but poorly described in immunocompromised) patients. Although there is no clear literature data about the specific characteristics of this disease in immunocompromised patients, clinical reports seem to describe a different presentation of tularemia in these patients. Moreover, atypical clinical presentations added to the fastidiousness of pathogen identification seem to be responsible for a delayed diagnosis, leading to a" loss of chance" for immunocompromised patients. In this article, we first provide an overview of the host immune responses to Francisella infections and discuss how immunosuppressive therapies or diseases can lead to a higher susceptibility to tularemia. Then, we describe the particular clinical patterns of tularemia in immunocompromised patients from the literature. We also provide hints of an alternative diagnostic strategy regarding these patients. In conclusion, tularemia should be considered in immunocompromised patients presenting pulmonary symptoms or unexplained fever. Molecular techniques on pathological tissues might improve diagnosis with faster results.

Dual Ureaplasma parvum arthritis: a case report of U. parvum septic arthritis following contralateral reactive arthritis in an immunosuppressed patient.

BACKGROUND: Ureaplasma parvum is usually part of the normal genital flora. Rarely can it cause invasive infections such as genitourinary infections, septic arthritis, or meningitis. CASE PRESENTATION: Here we present the first description of chronic ureterocystitis in a 56-year-old immunocompromised patient, complicated first by reactive arthritis and secondarily by contralateral septic arthritis due to U. parvum infection. U. parvum was detected in synovial fluid and in a urine sample. Treatment consisted of double-J stenting and targeted antibiotic therapy. Evolution showed resolution of urinary symptoms and clinical improvement of arthritis despite functional sequelae. CONCLUSIONS: Given the high prevalence of U. parvum colonisation, this diagnosis should remain a diagnosis of exclusion. However, because of the difficulty in detecting this microorganism, it should be considered in unexplained subacute urethritis or arthritis, including reactive arthritis, especially in immunosuppressed patients. Real-time PCR positivity in the absence of a differential diagnosis should not be overlooked.

Temocillin susceptibility among Enterobacterales strains recovered from blood culture in France.

Temocillin is used for several years in some European countries but, only since 2015 in France. We assessed the susceptibility of Enterobacterales strains isolated from blood culture 1 year before (2014) and 2 years after (2017) its use in France. 1,387 strains were included by 17 clinical laboratories located throughout France: 363 in 2014 and 1,024 in 2017. The rate of resistance to temocillin was 4.6% and 26.7% in 3rd generation cephalosporin (3GC) susceptible and resistant strains respectively. Cephalosporinase-overproducer (COPE) strains were significantly more resistant to temocillin (37.7%) than ESBL-producer (ESBL-PE) (23.5%) (P < 0.01). The rate of temocillin resistance was correlated to the number of inactive beta-lactams. The rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01). Temocillin remains highly active against Enterobacterales but the trend in resistance should be assessed over time.

[Mycoplasma genitalium: Prevalence of macrolide and fluoroquinolone resistance at the University Hospital of Tours, and check of the S-DiaMGRes® (Diagenode Diagnostics) assay]. / Mycoplasma genitalium : prévalence de la résistance aux macrolides et fluoroquinolones au CHRU de Tours, et vérification de la trousse commerciale S-DiaMGRes® (Diagenode Diagnostics).

Mycoplasma genitalium is an emerging agent of sexually transmitted infections, associated with urethritis, cervicitis, and pelvic inflammatory disease. Over the past decade, a remarkable increase in macrolide-resistant M. genitalium, the first-line treatment, is observed all over the world. In some regions, an increase in fluoroquinolone-resistance, the second-line treatment, is also noticed. It therefore seems important to have a knowledge of the local epidemiology as well as the means of detecting these resistances in order to best adapt the treatment. Our study aimed to determine the prevalence of macrolide and fluoroquinolone-resistant Mycoplasma genitalium at the University Hospital of Tours in 2018, using a real-time PCR technique followed by Sanger sequencing. The prevalence of macrolide resistance in our population was 15.4 %. No FQ resistance-conferring mutations were observed in our study. Furthermore, we evaluated the performance of the commercial kit S-DiaMGRes® (Diagenode Diagnostics, Belgium), allowing the detection of 23S rRNA mutations conferring resistance to macrolides.

Challenging diagnosis of chronic cerebral fungal infection: Value of (1→3)-ß-D-glucan and mannan antigen testing in cerebrospinal fluid and of cerebral ventricle puncture.

Primary fungal infection of the central nervous system (CNS) is rare but often associated with severe prognosis. Diagnosis is complicated since cerebrospinal fluid (CSF) samples obtained from lumbar puncture usually remain sterile. Testing for fungal antigens in CSF could be a complementary diagnostic tool. We conducted such measurements in CSF from patients with CNS fungal infection and now discuss the usefulness of ventricular puncture. Mannan and (1→3)ß-D-glucan (BDG) testing were retrospectively performed in CSF samples from three patients with proven chronic CNS fungal infection (excluding Cryptococcus), and subsequently compared to 16 controls. Results from lumbar punctures and those from cerebral ventricles were confronted. BDG detection was positive in all the CSF samples (from lumbar and/or ventricular puncture) from the three confirmed cases. In case of Candida infection, mannan antigen measurement was positive in 75% of the CSF samples. In the control group, all antigen detections were negative (n = 15), except for one false positive. Faced with suspected chronic CNS fungal infection, measurement of BDG levels appears to be a complementary diagnostic tool to circumvent the limitations of mycological cultures from lumbar punctures. In the event of negative results, more invasive procedures should be considered, such as ventricular puncture.

Contribution of a molecular test for the diagnosis of genital infection with Trichomonas vaginalis and Mycoplasma genitalium.

In the present study, we assessed a recently-marketed molecular test, the S-DiaMGTV™ kit (Diagenode), which provides simultaneous detection of Mycoplasma genitalium and Trichomonas vaginalis in urogenital samples. Performance characteristics of the S-DiaMGTV™ kit were compared to an in-house PCR for detection of M. genitalium and, for first time, with direct observation of genital secretions in wet mounting microscopy for T. vaginalis, a routine laboratory method. For M. genitalium, out of 66 samples, two negative with the in-house PCR were found positive with the S-DiaMGTV™ kit and two positive with the in-house PCR were found negative with the kit. For T. vaginalis, four samples were found positive by the molecular test. Among them, two were previously tested by the wet mounting observation and only one was positive. The kit allows an increase of T. vaginalis detection even in a low incidence country. Performances of the kit are in favor of its use in routine laboratory practice.

Seven Years Leptospirosis Follow-Up in a Critical Care Unit of a French Metropolitan Hospital; Role of Real Time PCR for a Quick and Acute Diagnosis.

(1) Background: Leptospirosis infection can lead to multiple organ failure, requiring hospitalization in an intensive care unit for supportive care, along with initiation of an adapted antibiotic therapy. Achieving a quick diagnosis is decisive in the management of these patients. (2) Methods: We present here a review of leptospirosis cases diagnosed in the intensive care unit of our hospital over seven years. Clinical and biological data were gathered, and we compared the differences in terms of diagnostic method. (3) Results: Molecular biology method by Polymerase Chain Reaction (PCR) allowed quick and reliable diagnosis when performed in the first days after the symptoms began. Moreover, we identified that sampling blood and urine for PCR was more efficient than performing PCR on only one type of biological sample. (4) Conclusions: Our results confirm the efficiency of PCR for the quick diagnosis of leptospirosis and suggest that testing both blood and urine early in the disease might improve diagnosis.

Molecular basis of macrolide-lincosamide-streptogramin (MLS) resistance in Finegoldia magna clinical isolates.

Of 69 clinical isolates of Finegoldia magna tested, 36% presented high-level MICs of erythromycin (>256 µg/ml), harboring erm(A) (n = 20) or erm(B) (n=5). Of nine isolates exhibiting an inducible resistance phenotype to macrolides-lincosamides-streptogramins B, four (44%) were susceptible with a potential risk of treatment failure due to emergence of resistant mutants.

Severe infections due to Francisella tularensis ssp. holarctica in solid organ transplant recipient: report of two cases and review of literature.

BACKGROUND: Tularemia is a rare zoonotic infection caused by bacterium Francisella tularensis. It has been well described in immunocompetent patients but poorly described in immunocompromised patients notably in solid organ transplant recipients. CASE PRESENTATIONS: We report here two cases of tularemia in solid organ transplant recipients including first case after heart transplant. We also carried out an exhaustive review of literature describing characteristics of this infection in solid organ transplant recipients.