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: Ninety-five 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. M. 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.

Amoxicillin and Ceftriaxone: A Synergistic Association Against Listeria monocytogenes.

Among 15 strains of Listeria monocytogenes tested, a synergy between amoxicillin and ceftriaxone was observed in 14 (93%) according to minimal inhibitory concentration strips and 12 (80%) per the checkerboard methods, as well as for 2 of the 3 strains tested by the time-killing curve. This association may be an alternative treatment for listeriosis in the future.

Apyrexia improves the prognostic value of quick SOFA in older patients with acute pneumonia or bacteremic urinary tract infection.

PURPOSE: Apyrexia is increasingly recognized as an indicator of inadequate inflammatory response in older patients with suspected infection. We aimed to evaluate whether temperature at admission could improve the prognostic value of the Quick Sequential Organ Failure Assessment (qSOFA) for predicting in-hospital mortality after acute infection. METHODS: We created a new score, named qSOFAGE (qSOFA in GEriatrics), by adding apyrexia as an item to the existing qSOFA (+ 1 point if temperature at admission ≤ 38 °C). We compared the prognostic value of the qSOFA, the qSOFAGE and temperature at admission for predicting in-hospital mortality after acute infection in two cohorts including older patients with acute pneumonia (AP) or bacteremic urinary tract infection (UTI). RESULTS: 217 consecutive patients aged ≥ 75 hospitalized for AP (first cohort) and 105 for bacteremic UTI (second cohort) were recorded. Temperature at admission was strongly inversely correlated with in-hospital mortality in both cohorts (Odds Ratios per °C (95% Confidence Interval): 0.60 (0.45-0.80) and 0.46 (0.27-0.79) for AP and UTI. respectively). Adding the temperature ≤ 38 °C item to the qSOFA markedly improved its predictive value for in-hospital mortality in the two groups: C-statistics for qSOFAGE vs. qSOFA: 0.63 (0.53-0.73) vs. 0.56 (0.46-0.67) in AP cohort; 0.74 (0.58-0.89) vs. 0.69 (0.53-0.85) in UTI cohort. For patients with qSOFAGE ≥ 3, in-hospital mortality reached 37% after AP and 55% after bacteremic UTI. CONCLUSION: Temperature at admission was strongly correlated with mortality in these two cohorts of older patients hospitalized for acute infection. The next step will be to validate this score in cohorts of older patients with suspected infection.

Distribution of Achromobacter Species in 12 French Cystic Fibrosis Centers in 2020 by a Retrospective MALDI-TOF MS Spectrum Analysis.

Achromobacter spp. are nonfermenting Gram-negative bacilli mainly studied among cystic fibrosis (CF) patients. The identification of the 19 species within the genus is time-consuming (nrdA-sequencing), thus data concerning the distribution of the species are limited to specific studies. Recently, we built a database using MALDI-TOF mass spectrometry (MS) (Bruker) that allows rapid and accurate species identification and detection of the multiresistant epidemic clones: A. xylosoxidans ST137 spreading among CF patients in various French and Belgium centers, and A. ruhlandii DES in Denmark. Here, we first assessed whether species identification could be achieved with our database solely by analysis of MS spectra without availability of isolates. Then, we conducted a multicentric study describing the distribution of Achromobacter species and of the clone ST137 among French CF centers. We collected and analyzed with our local database the spectra of Achromobacter isolates from 193 patients (528 samples) from 12 centers during 2020. In total, our approach enabled to conclude for 502/528 samples (95.1%), corresponding to 181 patients. Eleven species were detected, only five being involved in chronic colonization, A. xylosoxidans (86.4%), A. insuavis (9.1%), A. mucicolens (2.3%), A. marplatensis (1.1%) and A. genogroup 3 (1.1%). This study confirmed the high prevalence of A. xylosoxidans in chronic colonizations and the circulation of the clone A. xylosoxidans ST137 in France: four patients in two centers. The present study is the first to report the distribution of Achromobacter species from CF patients samples using retrospective MALDI-TOF/MS data. This easy approach could enable future large-scale epidemiological studies.

Evaluation of the relevance of use of the BD-BACTEC®MycosisIC/F, BD-BACTEC®PlusAerobic/F, BD-BACTEC®Lytic/10 anaerobic/F and BD-BACTEC®PedsPlus/F culture bottle system for fungemia detection: A 4-year retrospective study at the Dijon university hospital, France.

INTRODUCTION: Fungemia is a severe invasive fungal infection that combines rapid progression and a high mortality rate. This type of infection is a vital emergency, and early diagnosis is crucial. Currently, only the BD-BACTEC® Automated Blood Culture System (Becton Dickinson, New Jersey, USA) has a medium specifically dedicated to the detection of fungal agents: the BD-BACTEC®MycosisIC/F bottle. GAP STATEMENT: Thus, it is important to assess the performance of the different bottles offered by the BD-BACTEC® Automated Blood Culture System for the diagnosis of fungemia. AIM: The aim of this study was to evaluate the performance of the BD-BACTEC® MycosisIC/F culture medium in comparison to bacteriologic culture bottle media for the detection of fungemia in different clinical situations. METHODOLOGY: This retrospective study was conducted over a period of 4 years at the Dijon University Hospital. Three hundred and thirty-one pairs of blood cultures (i.e. a BD-BACTEC® MycosisIC/F culture bottle associated with at least one bacteriologic culture media bottle) were included in this study. RESULTS: We showed that the BD-BACTEC® MycosisIC/F culture bottles performed significantly better (i.e. diagnostic advantage either because it was the only positive bottle of the pair or time to positive result was shorter) than the bacteriological culture bottles in 57.7% (191/331) of cases (p <0.01). Multivariate analysis revealed that BD-BACTEC®MycosisIC/F bottles had better diagnostic performance than BD-BACTEC®Bacteriologic bottles in the context of: (i) the initial versus follow-up diagnostic subgroup, (ii) venipuncture or arterial sampling versus other sampling methods, and (iii) detection of filamentous versus yeast fungi. CONCLUSION: We concluded that the use of BD-BACTEC® MycosisIC/F culture bottles is a relevant addition to media optimized for routine bacterial detection.

Role of AxyABM overexpression in acquired resistance in Achromobacter xylosoxidans.

BACKGROUND: Acquired antimicrobial resistance among Achromobacter isolates from cystic fibrosis (CF) patients is frequent. Data concerning the mechanisms involved are scarce. The role of the AxyXY-OprZ and AxyEF-OprN Resistance Nodulation Division (RND) efflux systems has been demonstrated, but not that of AxyABM. OBJECTIVES: To explore the role of efflux systems in the acquired multiresistance observed in a one-step mutant selected after ofloxacin exposure. METHODS: The in vitro resistant mutant NCF-39-Bo2 and its parental strain NCF-39 (MICs of meropenem of 8 and 0.19 mg/L, of ceftazidime of 12 and 3 mg/L, of cefiderocol of 0.094 and 0.032 mg/L and of ciprofloxacin of 8 and 1.5 mg/L, respectively) were investigated by RNA-seq and WGS. Gene inactivation and reverse transcription quantitative PCR (RT-qPCR) were used to explore the role of the efflux systems of interest. RESULTS: RNA-seq showed that the AxyABM efflux system was overproduced (about 40-fold) in the in vitro mutant NCF-39-Bo2 versus its parental strain NCF-39. A substitution in AxyR, the putative regulator of AxyABM, was detected in NCF-39-Bo2. Gene inactivation of axyB (encoding the transporter component) in NCF-39-Bo2 led to a decrease in MICs of ciprofloxacin (5-fold), meropenem (64-fold), ceftazidime (12-fold) and cefiderocol (24-fold). Inactivation of axyB in the clinical isolate AXX-H2 harbouring a phenotype of resistance close to that of NCF-39-Bo2 enhanced the activity of the same molecules, especially meropenem. CONCLUSIONS: AxyABM overproduction is involved in acquired resistance of Achromobacter to ciprofloxacin, meropenem and ceftazidime, antibiotics widely used in CF patients, and increases the MIC of the new promising antibiotic cefiderocol.

Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study.

BACKGROUND: Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. METHODS: To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). RESULTS: 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. CONCLUSION: These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.

Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Rapid Detection of Isolates Belonging to the Epidemic Clones Achromobacter xylosoxidans ST137 and Achromobacter ruhlandii DES from Cystic Fibrosis Patients.

Achromobacter spp. are increasingly reported among cystic fibrosis patients. Genotyping requires time-consuming methods such as multilocus sequence typing or pulsed-field gel electrophoresis. Therefore, data on the prevalence of multiresistant epidemic clones, especially A. xylosoxidans ST137 (AxST137) and the Danish epidemic strain A. ruhlandii (DES), are lacking. We recently developed and published a database for Achromobacter species identification by matrix-assisted laser desorption-ionization-time of flight mass spectrometry (MALDI-TOF MS; Bruker Daltonics). The aim of this study was to evaluate the ability of the MALDI-TOF MS to distinguish these multiresistant epidemic clones within Achromobacter species. All the spectra of A. xylosoxidans (n = 1,571) and A. ruhlandii (n = 174) used to build the local database were analyzed by ClinProTools, MALDI Biotyper PCA, MALDI Biotyper dendrogram, and flexAnalysis software for biomarker peak detection. Two hundred two isolates (including 48 isolates of AxST137 and 7 of DES) were tested. Specific biomarker peaks were identified: absent peak at m/z 6,651 for AxST137 isolates and present peak at m/z 9,438 for DES isolates. All tested isolates were well typed by our local database and clustered within distinct groups (ST137 or non-ST137 and DES or non-DES) no matter the MALDI-TOF software or only by simple visual inspection of the spectra by any user. The use of MALDI-TOF MS allowed us to identify isolates of A. xylosoxidans belonging to the AxST137 clone that spread in France and Belgium (the Belgian epidemic clone) and of A. ruhlandii belonging to the DES clone. This tool will help the implementation of segregation measures to avoid interpatient transmission of these resistant clones.

Atypical Presentation of Bacteremic Urinary Tract Infection in Older Patients: Frequency and Prognostic Impact.

In older patients, urinary tract infection (UTI) often has an atypical clinical presentation, making its diagnosis difficult. We aimed to describe the clinical presentation in older inpatients with UTI-related bacteremia and to determine the prognostic impact of atypical presentation. This cohort study included all consecutive patients older than 75 years hospitalized in a university hospital in 2019 with a UTI-related gram-negative bacillus (GNB) bacteremia, defined by blood and urine cultures positive for the same GNB, and followed up for 90 days. Patients with typical symptoms of UTI were compared to patients with atypical forms. Among 3865 inpatients over 75 with GNB-positive urine culture over the inclusion period, 105 patients (2.7%) with bacteremic UTI were included (mean age 85.3 ± 5.9, 61.9% female). Among them, UTI symptoms were reported in only 38 patients (36.2%) and 44 patients (41.9%) had no fever on initial management. Initial diagnosis of UTI was made in only 58% of patient. Mortality at 90 days was 23.6%. After adjustment for confounders, hyperthermia (HR = 0.37; IC95 (0.14-0.97)) and early UTI diagnosis (HR = 0.35; IC95 (0.13-0.94)) were associated with lower mortality, while UTI symptoms were not associated with prognosis. In conclusion, only one third of older patients with UTI developing bacteremia had UTI symptoms. However, early UTI diagnosis was associated with better survival.

In vitro antimicrobial activity of daptomycin alone and in adjunction with either amoxicillin, cefotaxime or rifampicin against the main pathogens responsible for bacterial meningitis in adults.

OBJECTIVES: As daptomycin adjunction is currently under clinical evaluation in the multicentre phase II AddaMAP study to improve the prognosis of pneumococcal meningitis, the present work aimed at evaluating the in vitro antimicrobial activity of daptomycin-based combinations against some of the most frequent species responsible for bacterial meningitis. METHODS: Clinically relevant strains of Streptococcus pneumoniae, Listeria monocytogenes, Haemophilus influenzae and Neisseria meningitidis were obtained from National Reference Centers. The antimicrobial activity of amoxicillin, cefotaxime and rifampicin, either alone or in association with daptomycin, was explored through the determination of minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) as well as time-kill assay (TKA) using the broth microdilution method. RESULTS: All species taken together, the adjunction of daptomycin had no deleterious impact on the antimicrobial activity of amoxicillin, cefotaxime or rifampicin in vitro. Regarding Gram-positive bacteria, FICI and TKA analysis confirmed a global improvement of growth inhibition and bactericidal activity due to the adjunction of daptomycin. The synergistic effect prevailed for L. monocytogenes as demonstrated by FICI mainly <0.5 and a dynamic TKA-based synergy rate >50%. In addition, daptomycin-based associations did not modify the activity of ß-lactam antibiotics or rifampicin against Gram-negative bacteria, notably N. meningitidis. CONCLUSION: These results bring comforting evidence towards the clinical potential of daptomycin adjunction in the treatment of bacterial meningitis, which supports the ongoing AddaMAP clinical trial.

Fluoroquinolone resistance in Achromobacter spp.: substitutions in QRDRs of GyrA, GyrB, ParC and ParE and implication of the RND efflux system AxyEF-OprN.

BACKGROUND: Achromobacter are emerging pathogens in cystic fibrosis patients. Mechanisms of resistance to fluoroquinolones are unknown in clinical isolates. Among non-fermenting Gram-negative bacilli, fluoroquinolone resistance is mostly due to amino acid substitutions in localized regions of the targets (GyrA, GyrB, ParC and ParE) named QRDRs, but also to efflux. OBJECTIVES: To explore quinolone resistance mechanisms in Achromobacter. METHODS: The putative QRDRs of GyrA, GyrB, ParC and ParE were sequenced in 62 clinical isolates, and in vitro one-step mutants obtained after exposure to fluoroquinolones. An in vitro mutant and its parental isolate were investigated by RNASeq and WGS. RT-qPCR and gene inactivation were used to explore the role of efflux systems overexpression. RESULTS: We detected seven substitutions in QRDRs (Q83L/S84P/D87N/D87G for GyrA, Q480P for GyrB, T395A/K525Q for ParE), all in nine of the 27 clinical isolates with ciprofloxacin MIC ≥16 mg/L, whereas none among the in vitro mutants. The RND efflux system AxyEF-OprN was overproduced (about 150-fold) in the in vitro mutant NCF-39-Bl6 versus its parental strain NCF-39 (ciprofloxacin MICs 64 and 1.5 mg/L, respectively). A substitution in AxyT (putative regulator of AxyEF-OprN) was detected in NCF-39-Bl6. Ciprofloxacin MIC in NCF-39-Bl6 dropped from 64 to 1.5 mg/L following gene inactivation of either axyT or axyF. Substitutions in AxyT associated with overexpression of AxyEF-OprN were also detected in seven clinical strains with ciprofloxacin MIC ≥16 mg/L. CONCLUSIONS: Target alteration is not the primary mechanism involved in fluoroquinolone resistance in Achromobacter. The role of AxyEF-OprN overproduction was demonstrated in one in vitro mutant.

Impact of a Diagnosis-Centered Antibiotic Stewardship on Incident Clostridioides difficile Infections in Older Inpatients: An Observational Study.

In 2015, a major increase in incident hospital-onset Clostridioides difficile infections (HO-CDI) in a geriatric university hospital led to the implementation of a diagnosis-centered antibiotic stewardship program (ASP). We aimed to evaluate the impact of the ASP on antibiotic consumption and on HO-CDI incidence. The intervention was the arrival of a full-time infectiologist in the acute geriatric unit in May 2015, followed by the implementation of new diagnostic procedures for infections associated with an antibiotic withdrawal policy. Between 2015 and 2018, the ASP was associated with a major reduction in diagnoses for inpatients (23% to 13% for pneumonia, 24% to 13% for urinary tract infection), while median hospital stays and mortality rates remained stable. The reduction in diagnosed bacterial infections was associated with a 45% decrease in antibiotic consumption in the acute geriatric unit. HO-CDI incidence also decreased dramatically from 1.4‱ bed-days to 0.8‱ bed-days in the geriatric rehabilitation unit. The ASP focused on reducing the overdiagnosis of bacterial infections in the acute geriatric unit was successfully associated with both a reduction in antibiotic use and a clear reduction in the incidence of HO-CDI in the geriatric rehabilitation unit.

Clostridioides difficile infection after pneumonia in older patients: Which antibiotic is at lower risk?

BACKGROUND: Clostridioides difficile infection (CDI) is a frequent and severe complication of antibiotic treatment in older patients hospitalized for acute pneumonia (AP). AIMS: We aimed to assess the burden and risk factors of CDI and to determine which of the usual antibiotics regimens is at lower risk for post-AP CDI incidence. METHODS: Among patients aged >75y hospitalized for AP in all departments of a university hospital between 2007 and 2017, all the 92 patients developing a CDI were compared with 213 patients without CDI. Factors associated with 1) in-hospital and one-year mortality, 2) CDI incidence were assessed using logistic regression models. FINDINGS: In patients with and without CDI after AP, mortality rates were respectively at 34% vs 20% in hospital and 63% vs 42% at one-year. After adjustment for confounders, CDI was associated with a two-fold risk of in-hospital and one-year mortality after pneumonia (Respective Odds Ratio (95% Confidence Interval), OR (95%CI): 1.95 (1.06-3.58) and 2.02 (1.43-7.31)). High number of antibiotics (Per antibiotic, OR (95%CI): 1.89 (1.18-3.06)), rather than antibiotics duration (Per day, OR 95%CI): 1.04 (0.96-1.11)) was associated with a higher risk of CDI. Compared with other antibiotics, use of penicillin + beta-lactamase inhibitors was associated with a lower risk of CDI (OR (95%CI): 0.43 (0.19 -0.99)) CONCLUSION: In older inpatients, CDI highly increase the burden of AP at both short and long term. If confirmed, these results suggest the preferential use of penicillin + beta-lactamase inhibitors for a lower incidence of CDI in older inpatients with AP.

Adhering to the procalcitonin algorithm allows antibiotic therapy to be shortened in patients with ventilator-associated pneumonia.

PURPOSE: Ventilator-associated pneumonia (VAP) increases exposure to antibiotics. Physicians are however reluctant to shorten treatment, arguing this could lead to failures and worse outcome. Monitoring procalcitonin (PCT) has proven effective for decreasing exposure to antibiotics in randomized controlled trials, but additional "real-life" studies are needed. MATERIALS AND METHODS: All patients with VAP in whom ABT was stopped before death or discharge were included in this 5-year prospective cohort study. Patients in whom ABT was stopped in accordance with the algorithm ("PCT-guided" group: ABT withdrawal strongly encouraged if PCT < 0.5 ng/mL or < 80% peak value) were compared to those with ABT continuation despite PCT decrease ("not PCT-guided" group). The primary endpoint was ABT duration. The secondary endpoint was unfavorable VAP outcome (i.e. death or relapse). RESULTS: We included 157 of the 316 patients with microbiologically-proven VAP. The algorithm was overruled in 81 patients (51.6%). ABT duration was significantly longer in these patients than in the PCT-guided group (9.5 vs. 8.0 days; p = .02), although baseline and VAP characteristics did not differ. The rate of unfavorable outcomes was comparable (46.9% vs. 51.3%; p = .69). CONCLUSIONS: PCT-guided ABT adherence appears safe for patients with VAP and is likely to reduce exposure to antibiotics.

Study of 109 Achromobacter spp. isolates from 9 French CF centres reveals the circulation of a multiresistant clone of A. xylosoxidans belonging to ST 137.

We previously reported the distribution of Achromobacter spp. (species and Sequence Types (ST)) in our French Cystic Fibrosis (CF) centre. In the present study we collected 109 Achromobacter isolates (1/patient) from 9 other French CF Centres for species identification, antimicrobial susceptibility testings and Multilocus-Sequence-Typing (MLST) analysis. Ten species were detected, A. xylosoxidans being the most predominant one (73.4% of the isolates). Piperacillin-tazobactam, ceftazidime, imipenem, meropenem and ciprofloxacin were respectively active against 88, 70, 79, 72 and 23% of the isolates. Among the 79 A. xylosoxidans isolates, 46 STs were detected. Interestingly, ST 137, recovered in 4 centres (5 patients), was previously detected in our centre (2 patients). The strains from the 7 patients belonged to the same pulsotype (pulsed-field-gel-electrophoresis analysis) and harboured acquired resistance to meropenem, ceftazidime, ciprofloxacin, and except for 2 isolates, to imipenem and piperacillin-tazobactam. This is the first description in France of a circulating multiresistant A. xylosoxidans strain.

Pneumonia-Specific Escherichia coli with Distinct Phylogenetic and Virulence Profiles, France, 2012-2014.

In a prospective, nationwide study in France of Escherichia coli responsible for pneumonia in patients receiving mechanical ventilation, we determined E. coli antimicrobial susceptibility, phylotype, O-type, and virulence factor gene content. We compared 260 isolates with those of 2 published collections containing commensal and bacteremia isolates. The preponderant phylogenetic group was B2 (59.6%), and the predominant sequence type complex (STc) was STc73. STc127 and STc141 were overrepresented and STc95 underrepresented in pneumonia isolates compared with bacteremia isolates. Pneumonia isolates carried higher proportions of virulence genes sfa/foc, papGIII, hlyC, cnf1, and iroN compared with bacteremia isolates. Virulence factor gene content and antimicrobial drug resistance were higher in pneumonia than in commensal isolates. Genomic and phylogenetic characteristics of E. coli pneumonia isolates from critically ill patients indicate that they belong to the extraintestinal pathogenic E. coli pathovar but have distinguishable lung-specific traits.

Two new Salmonella genomic islands 1 from Proteus mirabilis and description of blaCTX-M-15 on a variant (SGI1-K7).

Objectives: To characterize the structure of Salmonella genomic islands 1 (SGI1s) from two clinical Proteus mirabilis isolates: one producing an ESBL and the other a penicillinase. Methods: WGS completed by PCR and Sanger sequencing was performed to determine sequences of SGI1s from Pm2CHAMA and Pm37THOMI strains. Results: Two new variants of SGI1 named SGI1-Pm2CHAMA (53.6 kb) and SGI1-K7 (55.1 kb) were identified. The backbone of SGI1-Pm2CHAMA shared 99.9% identity with that of SGI1. Its MDR region (26.3 kb) harboured two class 1 integrons (an In2-type integron and an In4-type integron) containing in particular a qacH cassette (encoding a quaternary ammonium compound efflux pump). These two integrons framed a complex region (harbouring among others blaCARB-4) resulting from transposon insertions mediated by IS26 and successive transposition events of ISs (ISAba14 isoform and the new ISPmi2). The second variant (SGI1-K7) had the same backbone as SGI1-K. Its MDR region (29.7 kb) was derived from that of SGI1-K and was generated by three events. The two main events were mediated by IS26: inversion of a large portion of the MDR region of SGI1-K and insertion of a structure previously reported on plasmids carried by prevalent and successful MDR clones of Enterobacteriaceae. This last event led to the insertion of the blaCTX-M-15 gene into SGI1-K7. Conclusions: This study confirmed the great plasticity of the MDR region of SGI1 and its potential key role for the dissemination of clinically significant antibiotic resistance among Enterobacteriaceae.

"Does the Salmonella Genomic Island 1 (SGI1) confer invasiveness properties to human isolates?"

BACKGROUND: In the eighties, a multidrug resistant clone of Salmonella Typhimurium DT104 emerged in UK and disseminated worldwide. This clone harbored a Salmonella genomic island 1 (SGI1) that consists of a backbone and a multidrug resistant region encoding for penta-resistance (ampicillin, chloramphenicol/florfenicol, streptomycin/spectinomycin, sulphonamides and tetracycline (ACSSuT)). Several authors suggested that SGI1 might have a potential role in enhancement of virulence properties of Salmonella enterica. The aim of this study was to investigate whether nontyphoidal S. enterica isolates carrying SGI1 cause more severe illness than SGI1 free ones in humans. METHODS: From 2011 to 2016, all patients infected with nontyphoidal S. enterica in our hospital were retrospectively included. All nontyphoidal S. enterica isolates preserved in our University Hospital (Dijon, France) were screened for the presence of SGI1. Clinical and biological data of patients were retrospectively collected to evaluate illness severity. Statistical analysis of data was performed by Kruskal-Wallis test or Fisher's exact test for univariate analysis, and by logistic regression for multivariate analysis. RESULTS: A total of 100 isolates of S. enterica (22 serovars) were collected. Twelve isolates (12%) belonging to 4 serovars harbored SGI1: S. Typhimurium, S. Infantis, S. Kentucky, S. St Paul. The severity of the disease was age-related (for invasive infection, sepsis and inflammatory response) and was associated with immunosuppression (for invasive infection, sepsis and bacteremia) but not with the presence of SGI1 or with antimicrobial resistance. CONCLUSION: A rather high proportion (12%) of human clinical isolates belonging to various serovars (for the first time serovar St Paul) and harboring various antimicrobial resistance profile carried SGI1. Diseases due to SGI1-positive S. enterica or to antimicrobial resistant isolates were not more severe than the others. This first clinical observation should be confirmed by a multicenter and prospective study.