[First-line management of infertile couple. Guidelines for clinical practice of the French College of Obstetricians and Gynecologists 2022]. / Prise en charge de première intention du couple infertile : mise à jour des RPC 2010 du CNGOF.

OBJECTIVE: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples. MATERIALS AND METHODS: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts. RESULTS: The fertility work-up is recommended to be prescribed according to the woman's age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple's initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery. CONCLUSION: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

Association of Healthcare and Aesthetic Procedures with Infections Caused by Nontuberculous Mycobacteria, France, 2012‒2020.

We describe nontuberculous mycobacteria (NTM) infections during 2012-2020 associated with health care and aesthetic procedures in France. We obtained epidemiologic data from the national early warning response system for healtcare-associated infections and data on NTM isolates from the National Reference Center for Mycobacteria. We compared clinical and environmental isolates by using whole-genome sequencing. The 85 original cases were reported after surgery (48, 56%), other invasive procedures (28, 33%) and other procedures (9, 11%). NTM isolates belonged to rapidly growing (73, 86%) and slowly growing (10, 12%) species; in 2 cases, the species was not identified. We performed environmental investigations for 38 (45%) cases; results for 12 (32%) were positive for the same NTM species as for the infection. In 10 cases that had environmental and clinical samples whose genomes were similar, the infection source was probably the water used in the procedures. NTM infections could be preventable by using sterile water in all invasive procedures.

Impact of a 24/7 multiplex-PCR on the management of patients with confirmed viral meningitis.

Objectives: The relevance of syndromic multiplex-PCR for the etiological diagnosis of meningitis or meningoencephalitis is still a matter of debate. Here, we studied the impact of a 24/7 multiplex-PCR on the management of patients consulting in the emergency department for suspicion of community-acquired meningitis. Methods: We conducted a single-center retrospective study at the Emergency department of Lariboisière University Hospital (Paris, France) including all patients suspected of meningitis. During period 1 (April 2014-March 2017), the molecular assays used for the detection of infectious agents in the cerebrospinal fluid (CSF) were performed during the daytime. During period 2 (April 2017-March 2019), multiplex-PCR (BioFire® Filmarray® Meningitis/Encephalitis Panel [ME], bioMérieux) was performed 24/7. Results: During the periods 1 and 2, 4 100 and 3 574 patients were included and 284 (6.9%) and 308 (8.6%) meningitis were diagnosed, respectively. During the periods 1 and 2, the most common causes of meningitis were enterovirus (23.9% and 29.5%), varicella zoster virus (10.2% and 6.8%) and herpes simplex virus-2 (4.2% and 8.1%). For patients with confirmed viral meningitis, a significant decrease was found between period 1 and period 2, respectively for the rate of hospitalization (73.9% vs 42.0%; p < 0.05), the length of stay (3[2­5] vs 2[1­3] days; p < 0.05), the empirical antiviral (26.1% vs 14.5%) and antibacterial administrations (29.3% vs 14.5%; p < 0.05). Conclusions: Multiplex-PCR is an important tool in the diagnosis of infectious meningitis in the emergency department and is relevant in the management of meningitis by screening for patients who do not require hospitalization and antibacterial therapy.

SARS-CoV-2 variants of concern are associated with lower RT-PCR amplification cycles between January and March 2021 in France.

SARS-CoV-2 variants raise concern regarding the mortality caused by COVID-19 epidemics. We analyse 88,375 cycle amplification (Ct) values from variant-specific RT-PCR tests performed between January 26 and March 13, 2021. We estimate that on March 12, nearly 85% of the infections were caused by the Alpha variant and that its transmission advantage over wild type strains was between 38 and 44%. We also find that tests positive for Alpha and Beta/Gamma variants exhibit significantly lower cycle threshold (Ct) values.

Rapid spread of the SARS-CoV-2 Delta variant in some French regions, June 2021.

We analysed 9,030 variant-specific RT-PCR tests performed on SARS-CoV-2-positive samples collected in France between 31 May and 21 June 2021. This analysis revealed rapid growth of the Delta variant in three of the 13 metropolitan French regions and estimated a +79% (95% confidence interval: 52-110%) transmission advantage compared with the Alpha variant. The next weeks will prove decisive and the magnitude of the estimated transmission advantages of the Delta variant could represent a major challenge for public health authorities.

Mycobacterium chimaera Genomics With Regard to Epidemiological and Clinical Investigations Conducted for an Open Chest Postsurgical Mycobacterium chimaera Infection Outbreak.

BACKGROUND: Postsurgical infections due to Mycobacterium chimaera appeared as a novel nosocomial threat in 2015, with a worldwide outbreak due to contaminated heater-cooler units used in open chest surgery. We report the results of investigations conducted in France including whole-genome sequencing comparison of patient and heater-cooler unit isolates. METHODS: We sought M. chimaera infection cases from 2010 onwards through national epidemiological investigations in health care facilities performing cardiopulmonary bypass, together with a survey on good practices and systematic heater-cooler unit microbial analyses. Clinical and heater-cooler unit isolates were subjected to whole-genome sequencing analyzed with regard to the reference outbreak strain Zuerich-1. RESULTS: Only 2 clinical cases were shown to be related to the outbreak, although 23% (41/175) of heater-cooler units were declared positive for M. avium complex. Specific measures to prevent infection were applied in 89% (50/56) of health care facilities, although only 14% (8/56) of them followed the manufacturer maintenance recommendations. Whole-genome sequencing comparison showed that the clinical isolates and 72% (26/36) of heater-cooler unit isolates belonged to the epidemic cluster. Within clinical isolates, 5-9 nonsynonymous single nucleotide polymorphisms were observed, among which an in vivo mutation in a putative efflux pump gene was observed in a clinical isolate obtained for 1 patient on antimicrobial treatment. CONCLUSIONS: Cases of postsurgical M. chimaera infections have been declared to be rare in France, although heater-cooler units were contaminated, as in other countries. Genomic analyses confirmed the connection to the outbreak and identified specific single nucleotide polymorphisms, including 1 suggesting fitness evolution in vivo.

The SARS-CoV-2 B.1.351 lineage (VOC ß) is outgrowing the B.1.1.7 lineage (VOC α) in some French regions in April 2021.

To assess SARS-CoV-2 variants spread, we analysed 36,590 variant-specific reverse-transcription-PCR tests performed on samples from 12 April-7 May 2021 in France. In this period, contrarily to January-March 2021, variants of concern (VOC) ß (B.1.351 lineage) and/or γ (P.1 lineage) had a significant transmission advantage over VOC α (B.1.1.7 lineage) in Île-de-France (15.8%; 95% confidence interval (CI): 15.5-16.2) and Hauts-de-France (17.3%; 95% CI: 15.9-18.7) regions. This is consistent with VOC ß's immune evasion abilities and high proportions of prior-SARS-CoV-2-infected persons in these regions.

Detecting Rapid Spread of SARS-CoV-2 Variants, France, January 26-February 16, 2021.

Variants of severe acute respiratory syndrome coronavirus 2 raise concerns regarding the control of coronavirus disease epidemics. We analyzed 40,000 specific reverse transcription PCR tests performed on positive samples during January 26-February 16, 2021, in France. We found high transmission advantage of variants and more advanced spread than anticipated.

Impact of a 24/7 Rapid Molecular Assay for Influenza Detection on the Prescription of Oseltamivir.

We assessed the impact of a rapid molecular assay for influenza detection whether outsourced or performed onsite 24/7 in a University Hospital in Paris, France. Shorter median time-to-results (16.8 vs 2.3 hours, P < .05) and an increased rate of adequate prescription of oseltamivir (76.6% vs 95.3%, P < .05) were observed.

Disseminated Mycobacterium chimaera Following Open-Heart Surgery, the Heater-Cooler Unit Worldwide Outbreak: Case Report and Minireview.

Invasive cardiovascular infections by Mycobacterium chimaera associated with open-heart surgery have been reported worldwide since 2013. Here, we report a case of a 61 year old man, without any other particular medical background, who underwent cardiac surgery for replacing part of the ascending aorta by a bio-prosthetic graft. Eighteen months later, the patient was painful at the lower back with fever. A pyogenic vertebral osteomyelitis due to M. chimaera associated to graft infection was diagnosed after 6 months of sub-acute infection. The patient presented a disseminated disease with cerebral lesions, chorioretinitis, and chronic renal failure. Despite adequate antimicrobial treatment and graft explantation, the patient died after 6 years. We reviewed the literature on M. chimaera infections associated with open-heart surgery. The worldwide outbreak has been explained by airborne bioaerosol generated by the 3T heater-cooler unit (HCU) used during cardiac by-pass surgical procedures. These infections are difficult to diagnose because of a long latency period (up to several years), with no specific symptoms and a highly specialized microbiological diagnosis. The treatment is based on antibiotics and surgery. These infections are also difficult to treat, since the mortality rate is high around 50%. Prevention is necessary by modifying the use of HCUs in operating rooms.

Population Genomics of Mycobacterium leprae Reveals a New Genotype in Madagascar and the Comoros.

Human settlement of Madagascar traces back to the beginning of the first millennium with the arrival of Austronesians from Southeast Asia, followed by migrations from Africa and the Middle East. Remains of these different cultural, genetic, and linguistic legacies are still present in Madagascar and other islands of the Indian Ocean. The close relationship between human migration and the introduction and spread of infectious diseases, a well-documented phenomenon, is particularly evident for the causative agent of leprosy, Mycobacterium leprae. In this study, we used whole-genome sequencing (WGS) and molecular dating to characterize the genetic background and retrace the origin of the M. leprae strains circulating in Madagascar (n = 30) and the Comoros (n = 3), two islands where leprosy is still considered a public health problem and monitored as part of a drug resistance surveillance program. Most M. leprae strains (97%) from Madagascar and Comoros belonged to a new genotype as part of branch 1, closely related to single nucleotide polymorphism (SNP) type 1D, named 1D-Malagasy. Other strains belonged to the genotype 1A (3%). We sequenced 39 strains from nine other countries, which, together with previously published genomes, amounted to 242 genomes that were used for molecular dating. Specific SNP markers for the new 1D-Malagasy genotype were used to screen samples from 11 countries and revealed this genotype to be restricted to Madagascar, with the sole exception being a strain from Malawi. The overall analysis thus ruled out a possible introduction of leprosy by the Austronesian settlers and suggests a later origin from East Africa, the Middle East, or South Asia.

Cause Analysis of an Infection in Facelift Surgery Due to Mycobacterium chelonae.

We report a post-facelift infection due to Mycobacterium chelonae. An environmental strain recovered from the water supply network of the surgical clinic and the clinical strains were considered non-differentiable using whole genome sequencing. After the unhealed wound's exposure to M. chelonae while showering early at the clinic after surgery, a lasting exposure of the colonized wound to the warm and moist working conditions of a bakery may have been favorable to the infection's development.

Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence.

Drug resistance in Mycobacterium leprae is assumed to be due to genetic alterations in the drug targets and reduced cell wall permeability. However, as observed in Mycobacterium tuberculosis, drug resistance may also result from the overactivity of efflux systems, which is mostly unexplored. In this perspective, we discuss known efflux pumps involved in M. tuberculosis drug resistance and virulence and investigate similar regions in the genome of M. leprae. In silico analysis reveals that the major M. tuberculosis efflux pumps known to be associated with drug resistance and virulence have been retained during the reductive evolutionary process that M. leprae underwent, e.g., RND superfamily, the ABC transporter BacA, and the MFS P55. However, some are absent (DinF, MATE) while others are derepressed (Mmr, SMR) in M. leprae reflecting the specific environment where M. leprae may live. The occurrence of several multidrug resistance efflux transporters shared between M. leprae and M. tuberculosis reveals potential implications in drug resistance and virulence. The conservation of the described efflux systems in M. leprae upon genome reduction indicates that these systems are potentially required for its intracellular survival and lifestyle. They potentially are involved in M. leprae drug resistance, which could hamper leprosy treatment success. Studying M. leprae efflux pumps as new drug targets is useful for future leprosy therapeutics, enhancing the global efforts to eradicate endemic leprosy, and prevent the emergence of drug resistance in afflicted countries.