OBJECTIVES:Bacillus cereus sensu lato (s.l.) or B. cereus group increasingly causes severe infections in preterm neonates. However, species-level identification and virulence characterization remain limited. This study aimed to identify B. cereus group species responsible for invasive infections in preterm neonates and to correlate genomic virulence profiles with clinical outcomes. METHODS:We conducted a retrospective, multicentre study across 13 French hospitals (2010-2021), including 40 B. cereus group isolates from blood or cerebrospinal fluid of preterm neonates with invasive infections. Clinical data were extracted from patient records. Whole-genome sequencing (WGS) (Illumina and Oxford Nanopore) with hybrid assemblies enabled species identification using digital DNA-DNA hybridization and average nucleotide identity. Virulence genes were screened against a curated database of 65 virulence genes, and associations with clinical outcomes were analysed. RESULTS:Forty isolates were analysed, 42.5% (17 of 40) of patients developed septic shock, and 37.5% (15 of 40), died, usually after rapid clinical deterioration. WGS identified seven species, predominantly Bacillus paranthracis (47.5%, 19 of 40) and B. cereus sensu stricto (20%, 8 of 40). Virulence gene content varied by species. The presence of hblCDAB (60%, 9 of 15), nprB (46.5%, 7 of 15), asbABCDEF (80%, 12 of 15), and essC-cereus/esxA (66.7%, 10 of 15) genes correlated with mortality (p 0.00015, 0.002, 0.0027, and 0.02, respectively). B. cereus sensu stricto carried more virulence determinants and was associated with higher mortality than B. paranthracis and other species, at day 7 (p 0.05) and at day 28 (p 0.0065). The cesH gene (60%, 15 of 25) is significantly associated with survival (p 0.007), particularly with B. paranthacis, the predominant species in our cohort. CONCLUSIONS:Invasive B. cereus group infections in preterm neonates are associated with high mortality, particularly in cases due to B. cereus sensu stricto. WGS enables precise species identification and virulence profiling, which are essential insights for diagnostic refinement, outbreak control, and risk stratification in neonatal intensive care settings.

BACKGROUND:Nontuberculous mycobacterial (NTM) adenitis is increasingly recognized in children; however, optimal management strategies remain debated. The aim of this study was to describe the clinical characteristics, management and outcomes of pediatric NTM lymphadenitis in France. METHODS:We conducted a multicenter retrospective descriptive study of culture-confirmed NTM lymphadenitis cases in children across 15 French hospitals participating in the MYCOMED network between 2010 and 2019. RESULTS:A total of 279 patients were included, with a progressive increase in diagnoses over the study period, from 11 cases in 2010 to 33 in 2019, with peaks of 38 observed in 2015 and 2018. Most patients were female (64%) with a median age of 3 years. Mycobacterium avium was the most frequently isolated species (71%). Histologic examination revealed necrotizing granulomatous lymphadenitis in two-third of cases (71%, 112/115), and acid-fast bacilli staining was positive in 24.6% (68/276) of the cases. Of the 250 patients with available therapeutic data, 34.8% were treated with surgery alone, 24.8% with antibiotics alone, 28% with combined therapy and 12.4% received no treatment. Overall, 104 children were lost to follow-up. Among 175 patients with follow-up data, the overall cure rate was 96%, with no significant differences between therapeutic strategies. Relapse occurred in 6 children (3.4%). No cases of facial nerve palsy were reported; however, cosmetic sequelae related to scarring were observed. CONCLUSIONS:The incidence of pediatric NTM adenitis has increased over the last decade in France, with M. avium as the predominant species. The clinical outcome was favorable in most cases, irrespective of the management strategy. Surgery with complete excision should be considered when technically feasible and safe, while antibiotics or a "wait and see" strategy remain acceptable alternatives.

Invasive Escherichia coli disease (IED) is associated with high hospitalization and mortality rates, particularly among adults aged ≥60 years. O-antigens are virulence factors required for E. coli survival. To inform EXPEC9V development, a novel glycoconjugate vaccine targeting E. coli O-antigens that is no longer in active clinical development, this retrospective observational study describes O-serotype prevalence among E. coli isolates from IED patients. Eligible patients were identified from medical record databases (9 January 2018-8 November 2019) across 17 tertiary care hospitals in Europe, North America, and Asia. To estimate vaccine serotype coverage of EXPEC9V, E. coli isolates were O-serotyped using whole-genome sequencing and agglutination. Antimicrobial susceptibility testing was also performed. Nine hundred and two patients were enrolled, of whom 690 (76.5%) were aged ≥60 years. Common serotypes were O25, O2, O6, O1, O15, O75, O16, O4, and O18, with O25 being the most reported (17.3%). In patients aged ≥60 years, 422/637 E. coli isolates were EXPEC9V O-serotypes. EXPEC9V O-serotype prevalence did not substantially differ when stratified according to sex, presence of a positive blood culture, sepsis, fatality, or multidrug resistance. Consistent with previous studies, serotype O25 was most prevalent and associated with ~20% of cases. An EXPEC9V vaccine serotype coverage of 66.2% was observed for IED patients aged ≥60 years.

In recent years, novel β-lactam-inhibitor combinations (imipenem-relebactam (I/R), meropenem-vaborbactam (M/V), aztreonam-avibactam (A/A)) have been commercialized and some are not yet on the market (cefepime-zidebactam (C/Z)). The objective of this study was to evaluate the efficacy of these β-lactam-β-lactamase inhibitors (BL/BLIs) combinations against a wide collection of French clinical multiresistant Enterobacterales isolates and to assess the performance of the E-test MIC method for I/R and M/V. BL/BLIs MICs were determined by broth microdilution on a collection of 200 ESBL-producing and 414 carbapenem-resistant clinical Enterobacterales (K. pneumoniae (271), E. coli (245), E. cloacae complex (48), other species (50)) including 292 carbapenemase-producing isolates. E-test method was evaluated for the determination of I/R and M/V MICs using 131 isolates from this collection. All the combinations were active against most ESBL-producing isolates (99-100 %), but C/Z and A/A MIC90 were lower than that of I/R and M/V (2mg/L and 2mg/L versus 8mg/L and 8mg/L). The M/V and I/R E-tests performances were close to those required by the FDA recommendations: Categorical agreement (CA) and Essential agreement (EA) ≥ 90 %, Major discrepancy (MD) and Very major discrepancy (VMD) < 3 %): 96.9 % (CA), 92.4 % (EA), 1.2 % (MD), 6.1 % (VMD) for I/R and 94.7 % (CA), 96.9 % (EA), 4.1 % (MD), 8.8 % (VMD) for M/V. This work confirmed the interest of C/Z and A/A combinations against carbapenem-resistant Enterobacterales isolates compared with M/V and I/R. Additionally, the findings indicate that the E-test method can be used for the determination of M/V and I/R MIC for E. coli and K. pneumoniae strains.

Streptococcus pneumoniae infection is considered an uncommon cause of arthritis in adults. To determine the clinical and microbiological characteristics of pneumococcal septic arthritis, we retrospectively studied a large series of cases among adult patients during the 2010-2018 conjugate vaccine era in France. We identified 110 patients (56 women, 54 men; mean age 65 years), and cases included 82 native joint infections and 28 prosthetic joint infections. Most commonly affected were the knee (50/110) and hip (25/110). Concomitant pneumococcal infections were found in 37.2% (38/102) and bacteremia in 57.3% (55/96) of patients, and underlying conditions were noted for 81.4% (83/102). Mortality rate was 9.4% (8/85). The proportion of strains not susceptible to penicillin was 29.1% (32/110). Of the 55 serotyped strains, 31 (56.4%) were covered by standard pneumococcal vaccines; however, several nonvaccine serotypes (mainly 23B, 24F, and 15A) had emerged, for which susceptibility to β-lactams was low.

CRISPR-Cas9 immune systems protect bacteria from foreign DNA. However, immune efficiency is constrained by Cas9 off-target cleavages and toxicity. How bacteria regulate Cas9 to maximize protection while preventing autoimmunity is not understood. Here, we show that the master regulator of virulence, CovR, regulates CRISPR-Cas9 immunity against mobile genetic elements in Streptococcus agalactiae, a pathobiont responsible for invasive neonatal infections. We show that CovR binds to and represses a distal promoter of the cas operon, integrating immunity within the virulence regulatory network. The CovR-regulated promoter provides a controlled increase in off-target cleavages to counteract mutations in the target DNA, restores the potency of old immune memory, and stimulates the acquisition of new memory in response to recent infections. Regulation of Cas9 by CovR is conserved at the species level, with lineage specificities suggesting different adaptive trajectories. Altogether, we describe the coordinated regulation of immunity and virulence that enhances the bacterial immune repertoire during host-pathogen interaction.

BackgroundCerebral infection with the opportunistic pathogen Bacillus cereus can lead to severe lesions, especially in premature newborns. Early diagnosis would be highly beneficial. The aim of this study was to describe the imaging findings associated with B. cereus infections.Materials and methodsWe included all newborns with a positive B. cereus blood culture and transfontanellar ultrasound between 2012 and 2022 at the Tours University Hospital. Imaging was assessed by both a junior and a senior radiologist to differentiate between hemorrhages, leukomalacia, and lesions attributed to B. cereus.ResultsNineteen patients were enrolled (12 girls), of whom 18 were premature. Three patients did not survive. Six patients had normal ultrasound and brain magnetic resonance imaging (MRI) scans. Thirteen patients had ultrasound-detected lesions: 7 hemorrhages, 1 case of leukomalacia, 1 focal ischemic lesion, and 5 lesions attributed to B. cereus. The B. cereus lesions appeared as irregular (5/5), bilateral (4/5), asymmetric (5/5), and hyperechoic patches in the subcortical white matter. They were extensive, asynchronous, and rapidly progressive over a few days (central necrosis with peripheral enhancement, referred to as the "bear scratch sign"), while respecting the cortex and basal ganglia.ConclusionThe presence of rapidly evolving white matter lesions should raise suspicion of B. cereus infection in newborns' brains. Imaging plays a crucial role in estimating the progression of this pathology.

Bacteria exhibit remarkable adaptability in response to selective pressures encountered during infection and antibiotic treatment. We characterize four Yersinia enterocolitica clonal isolates from successive bacteremia episodes that evolved within an elderly patient over 14 years. Their common evolution is characterized by a genome size reduction resulting in the loss of about a hundred genes and a so far undescribed deletion in the DNA gyrase gene gyrA conferring quinolone resistance. Third-generation cephalosporin resistance of the last isolate correlates with a truncation of OmpF in synergy with an increased production of BlaA and AmpC β-lactamases. A strong proteome remodeling of the isolates reveals a perturbed stringent response, as well as impaired metabolism which substantiate their severe growth defects in vitro, accounting for antibiotics tolerance and possibly therapeutic failure. This study documents previously unreported genetic and phenotypic changes associated with in-host adaptation of a pathogenic Yersinia species under antibiotic pressure.

CRISPR-Cas9 immune systems protect bacteria from foreign DNA. However, immune efficiency is constrained by Cas9 off-target cleavages and toxicity. How bacteria regulate Cas9 to maximize protection while preventing autoimmunity is not understood. Here, we show that the master regulator of virulence, CovR, regulates CRISPR-Cas9 immunity against mobile genetic elements in Streptococcus agalactiae , a pathobiont responsible for invasive neonatal infections. We show that CovR binds to and represses a distal promoter of the cas operon, integrating immunity within the virulence regulatory network. The CovR-regulated promoter provides a controlled increase in off-target cleavages to counteract mutations in the target DNA, restores the potency of old immune memory, and stimulates the acquisition of new memory in response to recent infections. Regulation of Cas9 by CovR is conserved at the species level, with lineage specificities suggesting different adaptive trajectories. Altogether, we describe the coordinated regulation of immunity and virulence that enhances the bacterial immune repertoire during host-pathogen interaction. ### Competing Interest Statement The authors have declared no competing interest.

Streptococcus agalactiae is among the few pathogens that have not developed resistance to ß-lactam antibiotics despite decades of clinical use. The molecular basis of this long-lasting susceptibility has not been investigated, and it is not known whether specific mechanisms constrain the emergence of resistance. In this study, we first report ß-lactam tolerance due to the inactivation of the c-di-AMP phosphodiesterase GdpP. Mechanistically, tolerance depends on antagonistic regulation by the repressor BusR, which is activated by c-di-AMP and negatively regulates ß-lactam susceptibility through the BusAB osmolyte transporter and the AmaP/Asp23/GlsB cell envelope stress complex. The BusR transcriptional response is synergistic with the simultaneous allosteric inhibition of potassium and osmolyte transporters by c-di-AMP, which individually contribute to low-level ß-lactam tolerance. Genome-wide transposon mutagenesis confirms the role of GdpP and highlights functional interactions between a lysozyme-like hydrolase, the KhpAB RNA chaperone and the protein S immunomodulator in the response of GBS to ß-lactam. Overall, we demonstrate that c-di-AMP acts as a turgor pressure rheostat, coordinating an integrated response at the transcriptional and post-translational levels to cell wall weakening caused by ß-lactam activity, and reveal additional mechanisms that could foster resistance.

Group B Streptococcus is the leading bacterium responsible for maternal and neonatal infections worldwide, also involved in preterm birth, stillbirth, and fetal death. In this study, we determined the clonal complex of all GBS isolates responsible for neonatal diseases (early- and late-onset diseases) and maternal invasive infections, including chorioamnionitis associated with in utero fetal death.

Introduction. Group B Streptococcus (GBS) remains the leading cause of bacterial neonatal infections worldwide, despite the spread of recommendations on vaginal screening and antibiotic prophylaxis.Hypothesis/Gap Statement. There is a need to evaluate the potential changes in GBS epidemiology over time following the introduction of such guidelines.Aim. Our aim was to perform a descriptive analysis of the epidemiological characteristics of GBS by conducting a long-term surveillance of strains isolated between 2000 and 2018, using molecular typing methods.Methodology. A total of 121 invasive strains, responsible for maternal infections (20 strains), fetal infections (8 strains) and neonatal infections (93 strains), were included in the study, representing all the invasive isolates during the period; in addition, 384 colonization strains isolated from vaginal or newborn samples were randomly selected. The 505 strains were characterized by capsular polysaccharide (CPS) type multiplex PCR assay and the clonal complex (CC) was assigned using a single nucleotide polymorphism PCR assay. Antibiotic susceptibility was also determined.Results. CPS types III (32.1 % of the strains), Ia (24.6 %) and V (19 %) were the most prevalent. The five main CCs observed were CC1 (26.3 % of the strains), CC17 (22.2 %), CC19 (16.2 %), CC23 (15.8 %) and CC10 (13.9 %). Neonatal invasive GBS diseases were predominantly due to CC17 isolates (46.3 % of the strains), which mainly express CPS type III (87.5 %), with a very high prevalence in late-onset diseases (76.2 %).Conclusion. Between 2000 and 2018, we observed a decrease in the proportion of CC1 strains, which mainly express CPS type V, and an increase in the proportion of CC23 strains, mainly expressing CPS type Ia. Conversely, there was no significant change in the proportion of strains resistant to macrolides, lincosamides or tetracyclines. The two molecular techniques used in our study provide almost as much information as classical serotyping and multilocus sequence typing, but are quicker, easy to perform, and avoid long sequencing and analysis steps.

Abstract Background Escherichia coli is a common Gram-negative bacterium that can infect normally sterile body sites and cause invasive E. coli disease (IED) including bacteremia, sepsis and septic shock. E. coli surface O-antigens are important virulence factors that contribute to pathogenicity, making them promising targets for the development of multivalent conjugate vaccines to protect against IED. Here, we describe the prevalence of O-serotypes and O-genotypes of clinical E. coli isolates across a multinational cohort of patients with IED. Methods This was a retrospective, multicenter, noninterventional study across 17 tertiary care hospitals in Europe, North America and Asia. Patients with an IED diagnosis in the 12 months prior to data collection were included. IED was defined as E. coli presence in cultures from any normally sterile body site or urine in patients exhibiting clinical criteria of invasive disease (i.e., systemic inflammatory response syndrome [SIRS], sepsis, or septic shock) and no other identifiable site of infection. O-serotyping (agglutination) and O-genotyping (whole genome sequencing [WGS]) were conducted. Subgroup analyses were performed in isolates from patients with bacteremic vs nonbacteremic IED and in patients ≥60 years old. Results 902 patients with IED were identified (median age at initial IED diagnosis, 71.0 years; 51.6% male). The most common O-serotypes (prevalence ≥5%) based on O-genotyping were O25 (17.3% [95% CI, 14.82–20.06%]), O2 (11.7% [95% CI, 9.61–14.08%]), O6 (9.3% [95% CI, 7.44–11.49%]), O1 (6.3% [95% CI, 4.78–8.20%]), O15 (5.3% [95% CI, 3.85– 6.99%]) and O75 (5.0% [95% CI, 3.64–6.72%]) (Table 1). Collectively, these 6 most prevalent serotypes accounted for 55.0% of total isolates. A similar pattern of O-serotypes was observed in the subgroup of patients ≥60 years old (Table 2), with serotypes O25, O2 and O6 most common in both bacteremic and nonbacteremic IED isolates. Conclusion The most predominant O-serotype among IED isolates from hospitalized patients with IED was O25, followed by O2, O6, O1, O15 and O75. Such epidemiological data could inform the development of an effective prophylactic vaccine against IED. Disclosures Jeroen Geurtsen, PhD, Janssen: Employee|Janssen: Stocks/Bonds Joachim Doua, MD, MPH, Janssen: Employee|Janssen: Stocks/Bonds Patricia Ibarra de Palacios, MD, Janssen: Employee at the time of analysis Matthew Sims, MD, PhD, Astra-Zeneca: Investigator for company-sponsored studies|ContraFect: Investigator for company-sponsored studies|Crestone: Investigator for company-sponsored studies|Finch: Investigator for company-sponsored studies|Janssen: Investigator for company-sponsored studies|Leonard-Meron: Investigator for company-sponsored studies|Merck and Co: Investigator for company-sponsored studies|OpGen Inc: Advisor/Consultant|OpGen Inc: Investigator for company-sponsored studies|Pfizer: Investigator for company-sponsored studies|Prenosis: Advisor/Consultant|Prenosis: Investigator for company-sponsored studies|QIAGEN Sciences LLC: Investigator for company-sponsored studies|Roche: Investigator for company-sponsored studies|Seres Therapeutics: Investigator for company-sponsored studies Peter Hermans, PhD, Janssen: Employee at the time of analysis Joshua T. Thaden, MD, PhD, Resonantia Diagnostics, Inc: Advisor/Consultant Oscar Go, PhD, Janssen: Employee|Janssen: Stocks/Bonds Bart Spiessens, PhD, Janssen: Employee|Janssen: Stocks/Bonds Darren Abbanat, PhD, Janssen: Employee at the time of analysis Florian Wagenlehner, MD, Achaogen: Advisory Board member, study participation|Astellas: Honoraria|AstraZeneca: Honoraria|AstraZeneca: Advisory Board member|Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Bionorica: Honoraria|Bionorica: Meeting/travel support, study participation|Deutsches Zentrum für Infektionsforschung (DZIF): Study participation|Enteris BioPharma: Study participation|Everest Medicines: Grant/Research Support|German S3 guideline Urinary tract infections: Board Member|Glaxo Smith Kline: Advisor/Consultant|Glaxo Smith Kline: Honoraria|Glaxo Smith Kline: Consulting fees, meeting/travel support, advisory board member, principal investigator in a GSK-sponsored study|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Guidelines European Association of Urology: Infections in Urology: Board Member|Helperby Therapeutics: Study participation|Janssen: Honoraria|Janssen: Advisory Board member|Klosterfrau: Honoraria|LeoPharma: Advisory Board member|MerLion: Advisory Board member|MIP Pharma: Honoraria|MSD: Advisory Board member|OM Pharma/Vifor Pharma: Advisory Board member, study participation|OM-Pharma: Honoraria|Pfizer: Honoraria|Pfizer: Advisory Board member|RosenPharma: Advisory Board member|Shionogi: Advisory Board member, study participation|Speaker research group German research foundation (DFG) Bacterial Renal Infections and Defense (FOR 5427): Study participation|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Consulting fees|University Hospital Giessen and Marburg GmbH, and Justus Liebig University, Germany: Employee|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Consulting fees, Advisory Board member Tetsuya Matsumoto, MD; PhD, member of the international study steering committee for the E.mbrace study and reports payment: Board Member Marc Bonten, MD, PhD, chair of the international study steering committee for the E.mbrace study (Janssen Vaccines), with payments made to UMC Utrecht: Board Member Michal Sarnecki, MD, Janssen: Employee|Janssen: Stocks/Bonds Jan Poolman, PhD, Janssen: Employee|Janssen: Stocks/Bonds

PURPOSE:Streptococcus agalactiae remains a major pathogen in human health, especially in neonatal infection. Detection in pregnant women is essential to initiate intrapartum antibiotic prophylaxis. This study compared the HiberGene loop-mediated isothermal amplification (LAMP) assay to culture, the reference method, for the detection of group B Streptococcus (GBS) in pregnant women.METHODS:This was a prospective multicenter study conducted in four French hospitals. Three hundred fifty-four non-redundant routine care vaginal swabs were analyzed by both methods, LAMP assay and culture. Clinicians and patients were blinded to the results of the LAMP assay.RESULTS:Three hundred thirty-seven samples presented concordant results, 15 presented discordant results, and 2 were invalid using the LAMP assay (excluded from the study). Compared to culture, the LAMP assay had a sensitivity of 87.7%, a specificity of 98%, a negative predictive value of 97.6%, and a positive predictive value of 89.3%.CONCLUSION:The HiberGene GBS LAMP assay is an easy test that possesses good performances compared with the reference method, culture. It could be used in case of emergency when a quick result is needed.

Mycobacterium bovis infects cattle and wildlife, and also causes a small proportion of tuberculosis cases in humans. In most European countries, M. bovis infections in cattle have been drastically reduced, but not eradicated. Here, to determine the M. bovis circulation within and between the human, cattle, and wildlife compartments, we characterized by spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing the genetic diversity of M. bovis isolates collected from humans, cattle, and wildlife in France from 2000 to 2010. We also assessed their genetic structure within and among the different host groups, and across time and space. The M. bovis genetic structure and its spatiotemporal variations showed different dynamics in the human and animal compartments. Most genotypes detected in human isolates were absent in cattle and wildlife isolates, possibly because in patients, M. bovis infection was contracted abroad or was the reactivation of an old lesion. Therefore, they did not match the genetic pool present in France during the study period. However, some human-cattle exchanges occurred because some genotypes were common to both compartments. This study provides new elements for understanding M. bovis epidemiology in France, and calls for increased efforts to control this pathogen worldwide.

BACKGROUND:Anorectal infections with Chlamydia trachomatis are commonly found in women. Although the efficacy of doxycycline and azithromycin is comparable in the treatment of urogenital infection, their efficacies toward anorectal infection remain unclear. We therefore aimed to compare a single dose of azithromycin with a 7-day course of doxycycline for the treatment of anorectal C trachomatis infection in women with concurrent vaginal infection. METHODS:We did a multicentre, open-label, randomised, controlled, superiority trial involving four sexually transmitted infection screening centres and three pregnancy termination centres in France. We included sexually active adult women (≥18 years) with a positive C trachomatis vaginal swab who agreed to provide self-collected anorectal swabs for C trachomatis detection. Participants were randomly assigned (1:1), using block sizes of six and eight and stratification by each investigating centre, to orally receive either azithromycin (a single 1-g dose, with or without food) or doxycycline (100 mg in the morning and evening at mealtimes for 7 days [ie, 100 mg of doxycycline twice per day for 7 days]). All laboratory staff who did the bacteriological analyses, but not the participants and the investigators, were masked to the treatment groups. The primary outcome was the microbiological anorectal cure rate defined as a C trachomatis-negative nucleic acid amplification test (NAAT) result in anorectal specimens 6 weeks after treatment initiation among women who had a baseline C trachomatis-positive anorectal NAAT result. The primary analysis was done in the modified intention-to-treat population, with multiple imputation, which included all women who underwent randomisation and had a C trachomatis-positive vaginal and anorectal NAAT result at baseline. Adverse events were reported in all women who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT03532464. FINDINGS:Between Oct 19, 2018, and April 17, 2020, we randomly assigned a total of 460 participants to either the doxycycline group (n=230) or the azithromycin group (n=230). Four (1%) of 460 participants were excluded because they refused to take doxycycline or were found to be ineligible after randomisation. Among the 456 participants, 357 (78%) had a concurrent C trachomatis-positive anorectal NAAT result at baseline; 184 (52%) of 357 were in the doxycycline group and 173 (48%) were in the azithromycin group (ie, the modified intention-to-treat population). Microbiological anorectal cure occurred in 147 (94%) of 156 participants in the doxycycline group (28 missing values) versus 120 (85%) of 142 in the azithromycin group (31 missing values; adjusted odds ratio with imputation of missing values 0·43 [95% CI 0·21-0·91]; p=0·0274). Reported adverse events possibly related to treatment were notified in 53 (12%) of 456 women: 24 (11%) of 228 in the doxycycline group and 29 (13%) of 228 in the azithromycin group. Gastrointestinal disorders were the most frequently occurring, in 43 (9%) of 456 women: 17 (8%) of 228 in the doxycycline group and 26 (11%) of 228 in the azithromycin group. INTERPRETATION:The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women. FUNDING:French Ministry of Health. TRANSLATION:For the French translation of the abstract see Supplementary Materials section.

Streptococci form a wide group of bacteria and are involved in both human and animal pathologies. Among pathogenic isolates, differences have been highlighted especially concerning their adaptation and virulence profiles. CRISPR-Cas systems have been identified in bacteria and many streptococci harbor one or more systems, particularly subtypes I-C, II-A, and III-A. Since the demonstration that CRISPR-Cas act as an adaptive immune system in Streptococcus thermophilus, a lactic bacteria, the diversity and role of CRISPR-Cas were extended to many germs and functions were enlarged. Among those, the genome editing tool based on the properties of Cas endonucleases is used worldwide, and the recent attribution of the Nobel Prize illustrates the importance of this tool in the scientific world. Another application is CRISPR loci analysis, which allows to easily characterize isolates in order to understand the interactions of bacteria with their environment and visualize species evolution. In this review, we focused on the distribution, diversity and roles of CRISPR-Cas systems in the main pathogenic streptococci.

Abstract Background Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Pooling samples is a promising technique, but no data are available when pooled screening also includes Mycoplasma genitalium (MG). The main objective of this study was to examine the sensitivity of pooled samples for detecting CT, NG, and MG in MSM using nucleic acid amplification versus single-site testing. Methods In this multicenter study, MSM with a positive result for CT, NG, or MG were recalled to the clinic for treatment and were asked to participate in this study. Separate samples were sent to a central virological department that proceeded to form the pooled samples. Testing was performed using the multiplex real-time polymerase chain reaction Allplex STI Essential Assay (Seegene, Seoul, Korea), which can simultaneously detect 7 pathogens. Results A total of 130 MSM with at least 1 positive test for CT, NG, or MG were included. A total of 25.4% had a coinfection. The sensitivities of pooled-sample testing were 94.8% for CT, 97.0% for NG, and 92.3% for MG. Pooling failed to detect 8 infections, but pooled-sample analysis missed detecting only samples with a low bacterial load (cycle threshold >35). Conclusions Pooling samples from MSM to detect CT, NG, and MG is as sensitive as individual-site testing for these 3 pathogens using the Allplex assay. Missed infections with a very low bacterial load could have a low impact on further transmission. Clinical Trials Registration. NCT03568695.

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.