Développement d’un modèle prédictif de tuberculose pulmonaire parmi des patients suspects de tuberculose en zone de faible prévalence : une étude cas-témoins

In low prevalence area for pulmonary tuberculosis infection (p-TB), predictive value of molecular-based detection method (PCR) might be low. The aim was to develop a predictive model of p-TB to identify patients at high risk of p-TB.Case-control study of consecutive patients hospitalized between 2009 and 2012, in a Parisian university hospital. Cases were patients with a culture-confirmed p-TB, regardless of smear result. Controls were patients with a suspected p-TB (direct exam and negative culture), matched to cases on a 1:1 ratio, by year and department of admission. Immunocompromised patients were not included. Factors associated with p-TB were screened using a stepwise conditional logistic regression. The score was developed using final’s model estimates. Discrimination (ROC curve, C - index / AUC), calibration (Hosmer-Lemeshow test) and internal validity using a bootstrap method were assessed. A sensitivity analysis which evaluated the score calibration in the subset of p-TB patients with negative direct exam was performed.Results: 354 patients were included. Age was forced in all analysis. Factors associated with p-TB in multivariate analysis were: age, diabetes, absence of cough +/- sputum, fever >15 days, chest X-rays findings. Score values were ranging from 0 to 8.4. The score was discriminant (0.84 C-index), well calibrated (p>0.05) and a score value higher than 3.3 can be used as a threshold (90% sensitivity, 50% specificity). The internal validity was good (0.79 corrected C-index). Score was well calibrated (p>0.05) in patients with negative direct exam. The developed score had good diagnostic performances and could be useful to determine when a PCR or a preventive respiratory isolation should be performed. An external validation is needed.La valeur prédictive des tests de détection moléculaire (PCR) peut être basse dans les pays de faible prévalence pour la tuberculose pulmonaire (p-TB). L’objectif était développer un score prédictif de p-TB pour identifier les patients à haut risque de p-TB. Étude cas-témoins monocentrique. Patients consécutifs hospitalisés entre 2009 et 2012 dans un CHU parisien. Les cas avaient une p-TB suspectée puis confirmée, les témoins avaient une TB suspectée puis infirmée. Les patients immunodéprimés n’ont pas été inclus. Appariement 1:1 sur l’année et le service d’hospitalisation. Modèle de régression logistique conditionnelle. Score construit à partir des coefficients du modèle multivarié. La discrimination (C-index), la calibration (test de Hosmer-Lemeshow) et la validité interne ont été évaluées. Analyse de sensibilité: calibration du modèle chez les cas avec examen direct négatif (ED-neg).354 patients majeurs inclus. Les facteurs associés à la p-TB étaient: âge, diabète, absence de toux +/- crachats, fièvre >15 jours, aspect radiologique. Les valeurs du score développé à partir des coefficients du modèle variaient de 0 à 8.4. Le score était discriminant (C-index 0.84), bien calibré (p>0.05) et une valeur seuil supérieur à 3.3 pouvait servir de seuil (sensibilité 90% et spécificité 50%). La validité interne était bonne (C-index corrigé 0.79). Chez les cas avec ED-neg, le score était bien calibré.Le score développé a de bonnes performances diagnostiques et peut être utile pour déterminer quand une PCR doit être réalisé. Une validation externe est nécessaire

Antibiotic susceptibilities of livestock isolates of leptospira

The authors wish to thank the consortium ‘Grupo de Trabajo Interinstitucional de Leptospirosis’ (Institut Pasteur Montevideo/UdelaR/INIA/MGAP, Uruguay) and Nicoletta Ponti for providing Leptospira strains. Thanks are also due to the technicians of the French National Reference Centre for Leptospirosis for culture and identification of strains.International audienceLeptospirosis is the most common zoonotic disease and is endemic worldwide. The antibiotic susceptibilities of Leptospira strains isolated from both humans and animals are poorly documented. This issue is particularly important for isolates from food-producing animals which are regularly exposed to antibiotic treatments. This study assessed the susceptibility of 35 leptospira strains isolated from food-producing animals of diverse geographical origins between 1936 and 2016 to the antimicrobial agents used most commonly in animals. A broth microdilution method was used to determine the susceptibilities of Leptospira strains isolated from livestock to 11 antibiotics. All isolates were susceptible to penicillin, amoxicillin, clavulanate, cephalexin, ceftriaxone, doxycycline, tetracycline, streptomycin, enrofloxacin and spectinomycin, but not polymyxin [minimum inhibitory concentration (MIC) ≥ 4 μg/L]. For tetracycline and doxycycline, the MIC was significantly higher for the recent isolates from Sardinia, Italy than for the other isolates. Antimicrobial susceptibilities were also determined with 10- and 100-fold higher inocula. High inocula significantly diminished the antibacterial effect by at least 10-fold for enrofloxacin (MIC ≥256 μg/L), streptomycin (MIC ≥16 μg/L) and tetracycline (MIC ≥32 μg/L), suggesting selection of resistant strains for high inocula. These findings contribute to the assessment of whether certain antibiotics are potentially useful for the treatment of leptospirosis, and point out the risk of failure for some antibiotics during infection with a high inoculum in both animals and humans. This study strengthens the need to detect and prevent the emergence of antimicrobial resistance of this major emerging zoonotic pathogen

Cervical Human Papillomavirus Infection (HPV) and High Oncogenic Risk Genotypes among Women Living with HIV in Asia: A Meta-Analysis

Women living with HIV (WLHIV) are prone to harbor several high-risk human papillomavirus (HR-HPV) genotypes and to develop cervical cancerous lesions. Data on HPV prevalence in these women are needed to inform immunization programs, especially in Asia where few data are available. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV and HR-HPV cervical infection in WLHIV in Asia and identify possible sources of heterogeneity for HR-HPV carriage. Pooled prevalence and its 95% confidence interval (95CI) were estimated using the inverse-variance weighting method. Linear regression weighted on study size was used to identify sources of heterogeneity. Among 7834 WLHIV (40 studies), the prevalence of HPV infection was 42.6% (95CI, 38.2% to 47.1%), and 34.6% (95CI, 30.3% to 39.1%) harbored HR-HPV genotypes, with significant heterogeneity across countries. In India, Thailand, and China, HPV-16 was the most frequent genotype (10.3%), followed by HPV-52 (5.4%), HPV-58 (5.0%), HPV-18 (4.1%), and HPV-33 (3.3%). In these women, most of whom were receiving antiretroviral therapy, we did not identify determinants of heterogeneity for HR-HPV infection. Our results underline the need for immunization programs based on nonavalent or new generation vaccines to prevent cervical cancer in WLHIV in Asia

Hospital admissions and mortality for acute exacerbations of COPD during the COVID-19 pandemic: A nationwide study in France

Background: A global reduction in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) was observed during the first months of the COVID-19 pandemic. Large-scale studies covering the entire pandemic period are lacking. We investigated hospitalizations for AECOPD and the associated in-hospital mortality at the national level in France during the first 2 years of the pandemic. Methods: We used the French National Hospital Database to analyse the time trends in (1) monthly incidences of hospitalizations for AECOPD, considering intensive care unit (ICU) admission and COVID-19 diagnoses, and (2) the related in-hospital mortality, from January 2016 to November 2021. Pandemic years were compared with the pre-pandemic years using Poisson regressions. Results: The database included 565,890 hospitalizations for AECOPD during the study period. The median age at admission was 74 years (interquartile range 65–83), and 37% of the stays concerned women. We found: (1) a dramatic and sustainable decline in hospitalizations for AECOPD over the pandemic period (from 8,899 to 6,032 monthly admissions, relative risk (RR) 0.65, 95% confidence interval (CI) 0.65–0.66), and (2) a concomitant increase in in-hospital mortality for AECOPD stays (from 6.2 to 7.6% per month, RR 1.24, 95% CI 1.21–1.27). The proportion of stays yielding ICU admission was similar in the pre-pandemic and pandemic years, 21.5 and 21.3%, respectively. In-hospital mortality increased to a greater extent for stays without ICU admission (RR 1.39, 95% CI 1.35–1.43) than for those with ICU admission (RR 1.09, 95% CI 1.05–1.13). Since January 2020, only 1.5% of stays were associated with a diagnosis of COVID-19, and their mortality rate was nearly three-times higher than those without COVID-19 (RR 2.66, 95% CI 2.41–2.93). Conclusion: The decline in admissions for AECOPD during the pandemic could be attributed to a decrease in the incidence of exacerbations for COPD patients and/or to a possible shift from hospital to community care. The rise in in-hospital mortality is partially explained by COVID-19, and could be related to restricted access to ICUs for some patients and/or to greater proportions of severe cases among the patients hospitalized during the pandemic

Effect of Professional and Extra-Professional Exposure on Seroprevalence of SARS-CoV-2 Infection among Healthcare Workers of the French Alps: A Multicentric Cross-Sectional Study

We aimed to report SARS-CoV-2 seroprevalence after the first wave of the pandemic among healthcare workers, and to explore factors associated with an increased infection rate. We conducted a multicentric cross-sectional survey from 27 June to 31 September 2020. For this survey, we enrolled 3454 voluntary healthcare workers across four participating hospitals, of which 83.4% were female, with a median age of 40.6 years old (31.8–50.3). We serologically screened the employees for SARS-CoV-2, estimated the prevalence of infection, and conducted binomial logistic regression with random effect on participating hospitals to investigate associations. We estimated the prevalence of SARS-CoV-2 infection at 5.0% (95 CI, 4.3%–5.8%). We found the lowest prevalence in health professional management support (4.3%) staff. Infections were more frequent in young professionals below 30 years old (aOR = 1.59, (95 CI, 1.06–2.37)), including paramedical students and residents (aOR = 3.38, (95 CI, 1.62–7.05)). In this group, SARS-CoV-2 prevalence was up 16.9%. The location of work and patient-facing role were not associated with increased infections. Employees reporting contacts with COVID-19 patients without adequate protective equipment had a higher rate of infection (aOR = 1.66, (95 CI, 1.12–2.44)). Aerosol-generating tasks were associated with a ~1.7-fold rate of infection, regardless of the uptake of FFP2. Those exposed to clusters of infected colleagues (aOR = 1.77, (95 CI, 1.24–2.53)) or intra-familial COVID-19 relatives (aOR = 2.09, (95 CI, 1.15–3.80)) also had a higher likelihood of infection. This report highlights that a sustained availability of personal protective equipment limits the SARS-CoV-2 infection rate to what is measured in the general population. It also pinpoints the need for dedicated hygiene training among young professionals, justifies the systematic eviction of infected personnel, and stresses the need for interventions to increase vaccination coverage among any healthcare workers

Hesitancy towards COVID-19 Vaccination among Healthcare Workers: A Multi-Centric Survey in France

Vaccination programs against COVID-19 are being scaled up. We aimed to assess the effects of vaccine characteristics on vaccine hesitancy among healthcare workers in a multi-center survey conducted within French healthcare facilities from 1 December 2020 to 26 March 2021. We invited any healthcare workers naïve of COVID-19 vaccination to complete an online self-questionnaire. They reported on their socio-demographic characteristics, as well as their perception and beliefs towards vaccination. We measured their willingness to get vaccinated in eight scenarios for candidates’ vaccines presented sequentially (1 to 4-point scale). Candidates’ vaccines varied for efficacy (25%, 50%, 100%), length of immunization (1 year or lifetime), frequency (<1/100, <1/10,000), and severity (none, moderate, severe) of adverse events. We analyzed 4349 healthcare workers’ responses with interpretable questionnaires. The crude willingness to get vaccinated was 53.2% and increased over time. We clustered the trajectories of responses using an unsupervised classification algorithm (k-means) and identified four groups of healthcare workers: those willing to get vaccinated in any scenario (18%), those not willing to get vaccinated at all (22%), and those hesitating but more likely to accept (32%) or reject (28%) the vaccination depending on the scenario. In these last two subgroups, vaccine acceptance was growing with age, educational background and was higher among men with condition. Compared to an ideal vaccine candidate, a 50% reduced efficacy resulted in an average drop in acceptance by 0.8 (SD ± 0.8, −23.5%), while it was ranging from 1.4 (SD ± 1.0, −38.4%) to 2.1 (SD ± 1.0, −58.4%) in case of severe but rare adverse event. The acceptance of a mandatory immunization program was 29.6% overall and was positively correlated to the willingness to get vaccinated, ranging from 2.4% to 60.0%. Even if healthcare workers represent a heterogeneous population, most (80%) could accept the vaccination against COVID-19. Their willingness to get the vaccine increased over time and as immunization programs became available. Among hesitant professionals, the fear of adverse events was the main concern. Targeted information campaigns reassuring about adverse events may increase vaccine coverage, in a population with a strong opinion about mandatory immunization programs

Temocillin versus carbapenems for urinary tract infection due to ESBL-producing Enterobacteriaceae: a multicenter matched case-control study.

International audienceObjectives: We aim to compare the efficacy of temocillin to carbapenems for ESBL-E UTI.Methods: We conducted a multicenter retrospective case-control study of adults with ESBL-E UTI between January-2015 and October-2019. Cases received temocillin ≥50% of the effective antibiotic therapy duration. Control exclusively received carbapenem. They were statistically matched (1:1 ratio) on period, sex, and age. The clinical cure at the end of antibiotic therapy was analyzed using conditional logistic regression.Results: We matched 72 temocillin cases to 72 carbapenem controls. Most (67%) were male, aged 69.4-years in median, 81 (56%) were immunocompromised, including 44 (31%) solid organ transplant recipients (SOT). There was no difference between cases and controls for baseline characteristics and microorganisms involved: K.pneumoniae in 59 (41%), E.coli in 57 (40%), and Enterobacter spp. in 24 (17%). The median time from admission to effective antibiotic therapy was 0-days [0-2]. Among cases, first-line antibiotic therapy (≤72 hours) was temocillin in 6 (8%) and carbapenems in 39 (54%). Temocillin was given at the median daily dose of 4g [2], [3], [4], after 3-days [2], [3], [4], [5] of carbapenems. Patients received temocillin for 81% [70-93] of the effective antibiotic course duration during 11-days [8], [9], [10], [11], [12], [13], [14]. The effective antibiotic duration was similar in cases and controls (p-value=0.067). Clinical cure at the end of the antibiotic therapy was 94% (68/72) in cases versus 99% (71/72) in controls (p-value=0.206), without difference among immunocompromised and SOT patients (p-value>0.050).Conclusions: Temocillin effectively relays beta-lactams, including carbapenems, to treat (complicated) ESBL-E UTI. Its efficacy is consistent among kidney transplant recipients

Computerized Decision Support System (CDSS) Use for Surveillance of Antimicrobial Resistance in Urinary Tract Infections in Primary Care

Abstract Background Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care. Objectives To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs. Methods We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections. Results We collected 43\mkern1mu591 Q-UTI, of which 10\mkern1mu192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%\textendash 42.2%) for amoxicillin, 16.6% (95% CI, 15.9%\textendash 17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%\textendash 7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%\textendash 6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value\mkern1mu=\mkern1mu0.004), and in EARS-NET (55.2%, P value\mkern1mu<\mkern1mu0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value\mkern1mu<\mkern1mu0.001) and EARS-NET (15.8%, P value\mkern1mu=\mkern1mu0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value\mkern1mu<\mkern1mu0.001), but lower than in EARS-NET (9.5%, P value\mkern1mu<\mkern1mu0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value\mkern1mu<\mkern1mu0.001). Conclusions CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC

Fosfomycin-trometamol (FT) or fluoroquinolone (FQ) as single-dose prophylaxis for transrectal ultrasound-guided prostate biopsy (TRUS-PB): A prospective cohort study

International audienceObjectives: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB.Methods: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression.Results: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602).Conclusions: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted