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.

Anorectal lymphogranuloma venereum among men who have sex with men: a 3-year nationwide survey, France, 2020 to 2022.

BackgroundIn France, lymphogranuloma venereum (LGV) testing switched from universal to selective testing in 2016.AimTo investigate changes in LGV-affected populations, we performed a nationwide survey based on temporarily reinstated universal LGV testing from 2020 to 2022.MethodsEach year, during three consecutive months, laboratories voluntarily sent anorectal Chlamydia trachomatis-positive samples from men and women to the National Reference Centre for bacterial sexually transmitted infections. We collected patients' demographic, clinical and biological data. Genovars L of C. trachomatis were detected using real-time PCR. In LGV-positive samples, the ompA gene was sequenced.ResultsIn 2020, LGV positivity was 12.7% (146/1,147), 15.2% (138/907) in 2021 and 13.3% (151/1,137) in 2022 (p > 0.05). It occurred predominantly in men who have sex with men (MSM), with rare cases among transgender women. The proportion of HIV-negative individuals was higher than that of those living with HIV. Asymptomatic rectal LGV increased from 36.1% (44/122) in 2020 to 52.4% (66/126) in 2022 (p = 0.03). Among users of pre-exposure prophylaxis (PrEP), LGV positivity was 13.8% (49/354) in 2020, 15.6% (38/244) in 2021 and 10.9% (36/331) in 2022, and up to 50% reported no anorectal symptoms. Diversity of the LGV ompA genotypes in the Paris region increased during the survey period. An unexpectedly high number of ompA genotype L1 variant was reported in 2022.ConclusionIn rectal samples from MSM in France, LGV positivity was stable, but the proportion of asymptomatic cases increased in 2022. This underscores the need of universal LGV testing and the importance of continuous surveillance.

Food-borne botulism outbreak during the Rugby World Cup linked to marinated sardines in Bordeaux, France, September 2023.

In September 2023, a botulism outbreak affecting 15 individuals occurred in Bordeaux, France, during the Rugby World Cup. We report on eight individuals from four different countries on two continents admitted to the intensive care unit at our hospital, where six required invasive mechanical ventilation. Cases reported consuming locally produced canned sardines at a restaurant. This report highlights the importance of rapid, worldwide alerts from health authorities to prevent severe consequences of such outbreaks, particularly during events attracting international visitors.

The Mortality of Infective endocarditis with and without Surgery in Elderly (MoISE) Study.

BACKGROUND: Infective endocarditis (IE) is increasingly affecting older patients. However, data on their management are sparse, and the benefits of surgery in this population are unclear. METHODS: We included patients with left-sided IE (LSIE) aged ≥ 80 years enrolled in a prospective endocarditis cohort managed in Aquitaine, France, from 2013 to 2020. Geriatric data were collected retrospectively to identify factors associated with the 1-year risk of death using Cox regression. RESULTS: We included 163 patients with LSIE (median age, 84 years; men, 59%; rate of prosthetic LSIE, 45%). Of the 105 (64%) patients with potential surgical indications, 38 (36%) underwent valve surgery: they were younger, more likely to be men with aortic involvement, and had a lower Charlson comorbidity index. Moreover, they had better functional status at admission (ie, the ability to walk unassisted and a higher median activities of daily living [ADL] score; n = 5/6 vs 3/6, P = .01). The 1-year mortality rate in LSIE patients without surgical indications was 28%; it was lower in those who were operated on compared with those who were not despite a surgical indication (16% vs 66%, P < .001). Impaired functional status at admission was strongly associated with mortality regardless of surgical status. In patients unable to walk unassisted or with an ADL score <4, there was no significant surgical benefit for 1-year mortality. CONCLUSIONS: Surgery improves the prognosis of older patients with LSIE and good functional status. Surgical futility should be discussed in patients with altered autonomy. The endocarditis team should include a geriatric specialist.

Case Studies and Literature Review of Francisella tularensis-Related Prosthetic Joint Infection.

Tularemia is a zoonotic infection caused by Francisella tularensis. Its most typical manifestations in humans are ulceroglandular and glandular; infections in prosthetic joints are rare. We report 3 cases of F. tularensis subspecies holarctica-related prosthetic joint infection that occurred in France during 2016-2019. We also reviewed relevant literature and found only 5 other cases of Francisella-related prosthetic joint infections worldwide, which we summarized. Among those 8 patients, clinical symptoms appeared 7 days to 19 years after the joint placement and were nonspecific to tularemia. Although positive cultures are typically obtained in only 10% of tularemia cases, strains grew in all 8 of the patients. F. tularensis was initially identified in 2 patients by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; molecular methods were used for 6 patients. Surgical treatment in conjunction with long-term antimicrobial treatment resulted in favorable outcomes; no relapses were seen after 6 months of follow-up.

Effects of azithromycin and doxycycline on the vaginal microbiota of women with urogenital Chlamydia trachomatis infection: a substudy of the Chlazidoxy randomized controlled trial.

OBJECTIVES: Dysbiotic bacterial communities within the vagina are associated with Chlamydia trachomatis infection. We compared the effect of treatment with azithromycin and doxycycline on the vaginal microbiota in a cohort of women with a urogenital C. trachomatis infection randomly assigned to one of these treatments (Chlazidoxy trial). METHODS: We analysed vaginal samples from 284 women (135 in the azithromycin group and 149 in the doxycycline group) collected at baseline and 6 weeks after treatment initiation. The vaginal microbiota was characterized using 16S rRNA gene sequencing and classified into community state types (CSTs). RESULTS: At baseline, 75% (212/284) of the women had a high-risk microbiota (CST-III or CST-IV). A cross-sectional comparison 6 weeks after treatment showed that 15 phylotypes were differentially abundant, but this difference was not reflected at the CST (p 0.772) or diversity level (p 0.339). Between baseline and the 6-week visit, α-diversity (p 0.140) and transition probabilities between CSTs were not significantly different between the groups, and no phylotype was differentially abundant. DISCUSSION: In women with urogenital C. trachomatis infection, the vaginal microbiota does not seem to be affected by azithromycin or doxycycline 6 weeks after treatment. Because the vaginal microbiota remains susceptible to C. trachomatis infection (with CST-III or CST-IV) after antibiotic treatment, women remain at risk of reinfection, which could originate from unprotected sexual intercourse or untreated anorectal C. trachomatis infection. This last consideration advocates for the use of doxycycline instead of azithromycin because of its higher anorectal microbiological cure rate.

Genetic Diversity and Population Structure of Mycobacterium bovis at the Human-Animal-Ecosystem Interface in France: "A One Health Approach".

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.

Doxycycline versus azithromycin for the treatment of anorectal Chlamydia trachomatis infection in women concurrent with vaginal infection (CHLAZIDOXY study): a multicentre, open-label, randomised, controlled, superiority trial.

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.

An unexpected case of Borrelia garinii liver infection.

BACKGROUND: Lyme borreliosis is the most prevalent arthropod-borne infection in the Northern Hemisphere. In Europe, Borrelia afzelii is predominantly involved in cutaneous manifestations, Borrelia garinii and Borrelia bavariensis in neurological manifestations, and Borrelia burgdorferi sensu stricto in articular ones. Liver impairement is not classical in Lyme borreliosis. Diagnosis is currently mainly based on serological testing, and is challenging in immunocompromised patients. CASE PRESENTATION: We report the first case of B. garinii infection revealed by liver involvement in an immunocompromised man. A 73-year-old man with marginal zone lymphoma, treated with bendamustine and rituximab, developed intermittent fever and inflammatory syndrome. Microbial investigations were all negative and FDG-PET showed complete remission of the lymphoma. Three months later, liver biopsy was performed and histology revealed spirochetes-like bacteria. Microbial diagnosis was performed by 16S rDNA sequencing, flagellin (flaB) gene sequencing and multi-locus sequence typing and identified B. garinii. The patient recovered successfully after a three weeks course of antibiotics. Diagnosis was challenging because Borrelia hepatic involvement is unusual and no erythema migrans nor tick bite were notified. CONCLUSION: This case highlights that unexplained fever and inflammatory syndrome in immunocompromised patients warrants specific investigations to identify bacteria such as spirochetes.

Pulmonary tuberculosis and management of contact patients in a Department of Nephrology and Kidney Transplantation.

OBJECTIVES: To describe the investigation, follow-up, management, and outcomes in a cohort of chronic kidney disease (CKD) and kidney transplant recipients (KTR) exposed to a case of pulmonary tuberculosis (TB). METHODS: Contacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with evidence of latent TB infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay. RESULTS: A total of 130 patients with CKD and 180 KTR were identified as contacts and followed-up over a 2-year period. Few vulnerable high-priority contacts received anti-TB treatment, including the two (100%) highly exposed patients in circle 1, 11/78 (14.1%) CKD patients and 4/142 (2.8%) KTR in circle 2, and 10/52 (19.2%) CKD patients and 2/36 (5.6%) KTR in circle 3; all had a positive interferon-gamma release assay result. No incident cases of TB disease occurred. CONCLUSIONS: These findings suggest that latent TB treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2, with a negative interferon-gamma release assay and in countries with low prevalence of TB.

Spread of clonal genovar E Chlamydia trachomatis among men who have sex with men.

In a previous study, we developed a Multi-Locus VNTRs Analysis (MLVA) typing system, called MLVA-5, for the discrimination of Chlamydia trachomatis genovar E strain. The results suggested the clonal spread of a MLVA-5 type 21 strain among men who have sex with men (MSM). We applied the MLVA-5 typing method on 157 French anorectal genovar E specimens and 19 Swedish specimens collected between 2010 and 2015. A total of 29 MLVA-5 types was obtained, with three predominant types among French samples: 78 specimens belonged to MLVA-5 type 21, two other types, 11 and 13, included 9 and 14 specimens, respectively. In 15 cases, one unique MLVA-5 type was observed for a single patient, 7 of which were new types not previously described. The distribution of MLVA-5 types according to sexual orientation showed that the 7 anorectal specimens from heterosexual patients belonged to 6 genotypes, and the 12 anorectal specimens from bisexual patients comprised eight types. The 95 anorectal specimens from MSM were distributed into 22 types, but 55 (57.9%) of them belonged to MLVA-5 type 21. Among the Swedish specimens from MSM, eight were from MLVA-type 21 (4 urines and 4 anorectal specimens). The results support the hypothesis of the spread of clonal genovar E strain among MSM.

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.

Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum: exploring the genomic diversity of circulating strains.

Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.

A New SNP-Based Genotyping Method for C. psittaci: Application to Field Samples for Quick Identification.

Chlamydia (C.) psittaci is the causative agent of avian chlamydiosis and human psittacosis. In this study, we extracted single-nucleotide polymorphisms (SNPs) from the whole genome sequences of 55 C. psittaci strains and identified eight major lineages, most of which are host-related. A combined PCR/high-resolution melting (HRM) assay was developed to screen for eight phylogenetically informative SNPs related to the identified C. psittaci lineages. The PCR-HRM method was validated on 11 available reference strains and with a set of 118 field isolates. Overall, PCR-HRM clustering was consistent with previous genotyping data obtained by ompA and/or MLST analysis. The method was then applied to 28 C. psittaci-positive samples from animal or human cases. As expected, PCR-HRM typing results from human samples identified genotypes linked to ducks and pigeons, a common source of human exposure, but also to the poorly described Mat116-like genotype. The new genotyping method does not require time-consuming sequencing and allows a quick identification of the source of infection.

Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis.

OBJECTIVES: Tetracyclines are widely used for the treatment of bacterial sexually transmitted infections (STIs) and recently have been used successfully for post-exposure prophylaxis of STIs in MSM. We investigated the in vitro and in vivo development of tetracycline resistance in Chlamydia trachomatis and Mycoplasma genitalium and evaluated 16S rRNA mutations associated with acquired resistance in other bacteria. METHODS: In vitro selection of resistant mutants of reference strains of C. trachomatis and M. genitalium was undertaken by serial passage in medium containing subinhibitory concentrations of tetracycline or doxycycline, respectively. The 16S rRNA gene of the two microorganisms was amplified and sequenced at different passages, as were those of 43 C. trachomatis- and 106 M. genitalium-positive specimens collected in France from 2013 to 2019. RESULTS: No tetracycline- or doxycycline-resistant strains of C. trachomatis and M. genitalium, respectively, were obtained after 30 serial passages. The tetracycline and doxycycline MICs were unchanged and analysis of the 16S rRNA gene, the molecular target of tetracyclines, of C. trachomatis and M. genitalium revealed no mutation. No mutation in the 16S rRNA gene was detected in C. trachomatis-positive specimens. However, six M. genitalium-positive specimens harboured a mutation potentially associated with tetracycline resistance without known prior tetracycline treatment for patients. CONCLUSIONS: Tetracyclines did not select in vitro-resistant mutants of C. trachomatis or M. genitalium. However, 16S rRNA mutations either responsible for or associated with tetracycline resistance in other bacteria, including mycoplasma species, were identified in several M. genitalium-positive specimens.