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Melioidosis is an endemic disease in Southeast Asia and northern Australia. An increasing number of cases are being reported in nonendemic countries, making the diagnosis less obvious. We discuss the identification of Burkholderia pseudomallei using matrix-assisted desorption ionization–time of flight mass spectrometry on the occasion of recent cases of imported melioidosis in French travellers.

Objectives: Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods: We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results: Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions: Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Staphylococcus aureus induces severe infective endocarditis (IE) where embolic complications are a major cause of death. Risk factors for embolism have been reported such as a younger age or larger IE vegetations, while methicillin resistance conferred by the mecA gene appeared as a protective factor. It is unclear, however, whether embolism is influenced by other S. aureus characteristics such as clonal complex (CC) or virulence pattern. We examined clinical and microbiological predictors of embolism in a prospective multicentric cohort of 98 French patients with monomicrobial S. aureus IE. The genomic contents of causative isolates were characterized using DNA array. To preserve statistical power, genotypic predictors were restricted to CC, secreted virulence factors and virulence regulators. Multivariate regularized logistic regression identified three independent predictors of embolism. Patients at higher risk were younger than the cohort median age of 62.5 y (adjusted odds ratio [OR] 0.14; 95% confidence interval [CI] 0.05–0.36). S. aureus characteristics predicting embolism were a CC30 genetic background (adjusted OR 9.734; 95% CI 1.53–192.8) and the absence of pIB485-like plasmid-borne enterotoxin-encoding genes sed, sej, and ser (sedjr; adjusted OR 0.07; 95% CI 0.004–0.457). CC30 S. aureus has been repeatedly reported to exhibit enhanced fitness in bloodstream infections, which might impact its ability to cause embolism. sedjr-encoded enterotoxins, whose superantigenic activity is unlikely to protect against embolism, possibly acted as a proxy to others genes of the pIB485-like plasmid found in genetically unrelated isolates from mostly embolism-free patients. mecA did not independently predict embolism but was strongly associated with sedjr. This mecA-sedjr association might have driven previous reports of a negative association of mecA and embolism. Collectively, our results suggest that the influence of S. aureus genotypic features on the risk of embolism may be stronger than previously suspected and independent of clinical risk factors.

Background: Therapeutic drug monitoring requires a validated assay and appropriate conditions for sample shipment and storage based on the stability of the compound to be analyzed. This study evaluated the stability of 29 antimicrobial compounds in whole blood (WB) and plasma samples under various storage conditions., Methods: The pre-analytical stability of 22 antibiotics (amoxicillin, aztreonam, cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftobiprole, ceftolozane, ceftriaxone, ciprofloxacin, clindamycin, cloxacillin, daptomycin, levofloxacin, linezolid, meropenem, metronidazole, moxifloxacin, piperacillin, sulfamethoxazole, and trimethoprim), 2 beta-lactamase inhibitors (avibactam, tazobactam), and 5 antituberculosis drugs (ethambutol, isoniazid, pyrazinamide, rifabutin, and rifampicin) was assessed by WB for up to 24 hours at room temperature (RT) and 72 hours at +4°C. The stability in plasma was evaluated for up to 6 hours at RT, 24 hours at +4°C, 1 month at -20°C, and 6 months at -80°C., Results: Concerning WB stability, all investigated compounds were stable for 24 hours at RT, except meropenem and isoniazid, which were stable for 6 hours; however, for 24 hours at +4°C, all the compounds were stable. For storage durations of 48 and 72 hours at +4°C, all compounds were stable, except for ciprofloxacin, cotrimoxazole, and isoniazid. Concerning stability in plasma, all compounds were stable for 6 hours at RT, and all except isoniazid were stable for 24 hours at +4°C. All the tested compounds were stable for 7 days at -20°C, except isoniazid, for which a degradation of approximately 20% was observed. An important degradation was observed for beta-lactam antibiotics after 1 month at -20°C. All compounds were stable at -80°C for 6 months., Conclusions: The pre-analytical stabilities of several anti-infective compounds was described. The present results can be used to determine the appropriate conditions for shipping and storing samples dedicated to therapeutic drug monitoring of the investigated compounds., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We aimed to assess the feasibility and diagnostic performance of ultrasound-guided bone biopsies at the bedside of diabetic patients admitted for suspected foot osteitis not requiring surgery., Research Design and Methods: In this retrospective monocentric study, we compared the performance of ultrasound-guided (n = 29 consecutive patients, Dec.2020-Oct.2022) versus surgical (n = 24 consecutive patients, Jan.2018-Nov.2020) bone biopsies at confirming or ruling out diabetic foot osteitis (primary outcome)., Results: Patient characteristics were similar in the two intervention groups, including arteritis prevalence (62.3 %), SINBAD score, and wound location (phalanges 36 %, metatarsus 43 %, and calcaneus 21 %). However, the ultrasound-guided group was older (67 ± 11 versus 60 ± 13 years respectively, P = 0.047) and had more type 2 diabetes (97 % versus 75 %, P = 0.038). Diagnostic performance (i.e., capacity to confirm or rule out suspected osteitis) was similar for ultrasound-guided (28/29 cases: 25 confirmations, 3 invalidations) and surgical (24 confirmations/24) biopsies, P = 0.358. No biopsy-related side effect or complication was observed for either intervention, even for patients on antiaggregation and/or anticoagulation therapy. The mean (± standard deviation) time necessary to perform the biopsy was shorter in the ultrasound-guided group (2.6 ± 3.0 versus 7.2 ± 5.8 days, respectively, P < 0.001) and wound evolution at three months was more favorable (83.3 versus 41.2 %, P = 0.005) (94.4 % versus 66.7 %, respectively, patients with new surgical procedure within six months excluded; P = 0.055). Even though not statistically significant, healing rates in terms of wound and osteitis at six months were also better in the ultrasound-guided group (wound: 40.9 % versus 36.8 %; P = 0.790, and osteitis: 81.8 vs 55.6 % P = 0.071)., Conclusion: In diabetic patients with suspected foot osteitis not requiring surgery, bedside ultrasound-guided bone biopsies may constitute a promising alternative to surgical biopsies. This intervention provided excellent tolerance and microbiological documentation, short lead-times, and more favorable wound prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Data on the microbiological epidemiology of Intra-Abdominal Abscesses (IAAs) are very scarce. We aimed to study the microbiological epidemiology of these infections in order to optimize empirical antibiotic therapy., Patients and Methods: Between January 2015 and December 2020, we retrospectively analyzed all IAAs files in our hospital. Clinical and microbiological data such as antibiotic susceptibilities were collected., Results: We studied 243 IAA cases. All in all, 139 (57.2%) IAAs were healthcare-associated and 201 (82.7%) were drained. The highest risk situations for IAAs were appendicitis (n = 69) and diverticulitis (n = 37). Out of the 163 microbiologically documented infections, 136 (81.9%) were polymicrobial. Enterobacterales (n = 192, 36.1%), Enterococcus sp. (n = 84, 17.6%) and anaerobes (n = 66, 16.1%) were the most frequently identified bacteria. Gram-negative bacteria were susceptible to amoxicillin-acid clavulanic, piperacillin-tazobactam, cefotaxime, meropenem in 55.2%, 84.9%, 77.6% and 99.5% of cases, respectively. Concerning Gram-positive bacteria, the susceptibility rate was 81.8% for amoxicillin-clavulanic acid, piperacillin-tazobactam and meropenem, and decreased to 63.4% for cefotaxime., Conclusion: This study highlights the polymicrobial profile of IAAs and their low susceptibility to amoxicillin and clavulanic acid. The piperacillin-tazobactam association remained the most appropriate empirical antibiotic therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Therapeutic drug monitoring (TDM) of antibiotics (ATB) in patients with serious bacterial infections allows optimization of the efficacy of the treatment while reducing the risk of toxicity. Notably, early measurement of plasma beta-lactam concentration has been shown to be associated with reduced mortality in intensive care patients. In this context, a rapid, robust, and accurate assay method is essential for daily TDM. A fully automated procedure for quantification of the plasma concentrations of ten ATB was developed. The ATB were divided into two calibration pools, with Pool 1: aztreonam, ceftobiprole, cefoxitin, avibactam, tazobactam and Pool 2: metronidazole, ceftriaxone, daptomycin, ceftolozane, moxifloxacin. Sample preparation consisting of acetonitrile plasma protein precipitation and H20 dilution was applied to all analytes. This procedure was carried out by an automated sample preparation system directly coupled to a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. Since the instrument extracts sample n while sample n-1 is in the LC-MS/MS system, the delay between obtaining the results for two samples corresponds to the analytical run time, which is less than 7 min. The method was validated according to the Food and Drug Administration guidelines. The method was sensitive (lower limit of quantification 0.1-1 mg/L, depending on the ATB), accurate (intra/inter-assay bias -14.8 to 14.2 %) and precise (intra/inter-assay CVs 1.27 to 16.3 %). Application of the TDM assay was illustrated by the report of an intensive care patient treated with the ceftazidime/aztreonam/avibactam combination. Four assays were performed in 8 days with results returned within 24 h to quickly manage the dose regimen in this patient. An automated, simple, rapid, robust LC-MS/MS analysis was developed and validated for the simultaneous quantification of plasma concentrations of 10 ATB and was applied with success to perform TDM. This method provides a shorter turnaround time than classic sample batch-based analytical methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Patients lost to follow-up and treatment failure in tuberculosis disease (TB) are major public health issues. In the absence of appropriate treatment, approximately 70 % of smear-positive patients will die within 10 years of disease progression. This study, conducted in the French region with the highest incidence, aimed to assess tuberculosis treatment outcomes and its determinants., Patients and Methods: A prospective, multicenter cohort study (CO1TB) of adults and children treated for TB was conducted in four hospitals in the North of Paris. Treatment outcome at 1 year and associated socioeconomic and clinical factors were studied by multivariate logistic regression., Results: Among 145 TB cases included from May 2018 to January 2020, patients were mainly born abroad and most lived in difficult socioeconomic conditions. During treatment, 25/145 (17 %) patients experienced adverse effects, which were not significantly associated with discontinuation of treatment (p = 0.99). At 1 year, 114 (78 %) had completed treatments, 26 (19 %) were lost to follow-up, three (2.1 %) were still being treated and two (1.4 %) had died. In the multivariate analysis, a history of TB was significantly associated with unfavorable treatment outcome (aOR = 5.3, 95 %CI (1.5;18.6) and a trend towards significance (p < 0.2) was observed among patients aged under 24 years (aOR = 2.9, 95 %-CI 0.95;8.5)., Conclusion: In this precarious population, socioeconomic conditions were not found to be associated with unfavorable treatment outcome, whereas history of tuberculosis and young age played a role. Increased monitoring is thus required for these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Definitions of resistance in multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant tuberculosis (XDR TB) have been updated. Pre-XDR TB, defined as MDR TB with additional resistance to fluoroquinolones, and XDR TB, with additional resistance to bedaquiline or linezolid, are frequently associated with treatment failure and toxicity. We retrospectively determined the effects of pre-XDR/XDR TB resistance on outcomes and safety of MDR TB treatment in France. The study included 298 patients treated for MDR TB at 3 reference centers during 2006-2019. Of those, 205 (68.8%) cases were fluoroquinolone-susceptible MDR TB and 93 (31.2%) were pre-XDR/XDR TB. Compared with fluoroquinolone-susceptible MDR TB, pre-XDR/XDR TB was associated with more cavitary lung lesions and bilateral disease and required longer treatment. Overall, 202 patients (67.8%) had favorable treatment outcomes, with no significant difference between pre-XDR/XDR TB (67.7%) and fluoroquinolone-susceptible MDR TB (67.8%; p = 0.99). Pre-XDR/XDR TB was not associated with higher risk for serious adverse events.

Background: There are limited data comparing the efficacy and safety of raltegravir and dolutegravir to that of efavirenz in HIV-1/tuberculosis (TB) coinfected patients., Methods: We conducted a 10-year retrospective study in 4 centers in France. We included all HIV-1/tuberculosis coinfected patients starting antiretroviral therapy with a rifampicin-based regimen, with a plasma HIV RNA level (VL) > 1000 copies/mL. The primary endpoint was the proportion of patients with virological success that is, with VL <50 copies/mL at W48 using an Intention-To-Treat analysis, using last-observation-carried-forward to impute missing data. We also assessed antiretroviral therapy safety, analyzing treatment discontinuation for adverse events., Results: Between 2010 and 2020, 117 patients were included. Thirty-nine (33.3%) were treated with raltegravir and 2 nucleoside reverse transcriptase inhibitors (NRTIs), 19 (16.2%) with dolutegravir (and 2 NRTIs) and 59 (50.4%) with efavirenz (and 2 NRTIs). At W48, the primary endpoint was achieved in 24 patients (61.5%) in the raltegravir group, in 12 (63.2%) in the dolutegravir group, and in 41 (69.5%) in the efavirenz group using an Intention-To-Treat analysis ( P = 0.68). Emergence of drug resistance in patients with virological failure, defined as a VL >50 copies/mL, was observed in 3 patients with efavirenz and one patient with raltegravir. Rate of treatment discontinuation for drug-related adverse events was 10.3%, 10.6%, 16.9% for raltegravir, dolutegravir and efavirenz respectively ( P = 0.67)., Conclusions: In this retrospective cohort study, raltegravir and dolutegravir yielded similar efficacy and safety results to efavirenz for the treatment of HIV-1/TB coinfected patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs.

Phaeohyphomycoses comprise a heterogeneous group of fungal infections caused by dematiaceous fungi and have primarily been reported in patients with underlying acquired immunodeficiencies, such as hematological malignancies or solid-organ transplants. Over the past decade, a growing number of patients with phaeohyphomycosis but otherwise healthy were reported with autosomal recessive (AR) CARD9 deficiency. We report a 28-year-old woman who presented with invasive rhinosinusitis caused by Alternaria infectoria . Following a candidate gene sequencing approach, we identified a biallelic loss-of-function mutation of CARD9, thereby further broadening the spectrum of invasive fungal diseases found in patients with inherited CARD9 deficiency. In addition, we reviewed 17 other cases of phaeohyphomycosis associated with AR CARD9 deficiency. Physicians should maintain a high degree of suspicion for inborn errors of immunity, namely CARD9 deficiency, when caring for previously healthy patients with phaeohyphomycosis, regardless of age at first presentation.

SETTING: Migrants to Europe face a disproportionate burden of infections, including TB, yet little is known about the approach taken by primary and secondary care providers to screening and treatment. We therefore explored policy and practice relating to screening of active TB and latent TB infection (LTBI) in France. METHODS: We conducted an online national survey of French primary and secondary care physicians regarding their practices in relation to TB/LTBI screening among migrants. RESULTS: 367 physicians responded to the questionnaire among which 195 (53.1%) were primary care physicians, 126 (34.3%) were TB specialists in secondary care, and 46 (12.5%) other physicians; 303 (85.5%) were involved daily in the care of migrants. Most respondents recommended systematic TB screening with chest X-ray for migrants from medium and high-incidence countries (71.9%). Primary care physicians were less likely to offer screening than physicians in other settings (aOR 0.21, 95% CI 0.09-0.48). 220 (61.8%) offered LTBI screening for children (<15 years) and 34.0% for all migrants from high incidence countries. CONCLUSION: Improving awareness on TB screening is a critical next step to improve health outcomes in migrant groups and meet regional targets for tackling TB.

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [ 18 F]FDG-PET for this purpose. Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [ 18 F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment. Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUV max measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUV max (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment. Conclusions: [ 18 F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sarda-Mantel, Kaoutar, Alfaiate, Lopes, Paycha, Benali, Mikail, Soussan, Lemarignier, Méchaï, Nagat, Montravers, Deradji, Durand, Goulenok, Ponscarme, Yéni, Laouénan and Rioux.)

Objective: To identify tools that will result in faster diagnosis, making the current pulmonary tuberculosis strategy more efficient., Patients and Methods: A 4-year (2015-2018) retrospective study. The gold standard for diagnosis was a positive culture from a respiratory specimen. All sputum, fibroscopy and post-fibroscopy specimens (for smear negative patients) were collected. Each specimen was analyzed through smear examination and culture. All nucleic acid amplification testing results were included. Analyses looked at the incremental yield of positive cases of each successive specimen collection, and time to diagnosis., Results: A total of 354 patients had at least one positive culture. Sputum allowed a diagnosis in 92% of cases (including a gain in sensitivity of around 7% for the third sputum specimen), with 160 smear-positive patients (45%). Among smear-negative patients, 109 underwent a fibroscopy procedure (culture sensitivity of 75%), and 59 had a post-fibroscopy specimen collected, which together identified the rest of the patients (8%). Molecular testing was used in 237 specimens. Median time to diagnosis was 11 days, which was significantly reduced among smear-negative patients when molecular testing was used (P<0.001). Shortening the delay between sputum specimen collections did not alter procedure sensitivity., Conclusions: We identified several aspects of the French tuberculosis diagnosis algorithm that could be improved, and posed the basis for a prospective study. Centers in higher incidence areas could benefit from a dedicated, predefined procedure exploring suspicions of tuberculosis. A high suspicion score of tuberculosis could drive the reasoned use of molecular testing in such settings., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate and compare practices regarding the diagnosis, isolation measures, and treatment of tuberculosis (TB) in high-income countries and mainly in Europe. Materials and Methods: A survey was conducted from November 2018 to April 2019 within the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). The practices observed were compared to the main international guidelines. Results: Among 136 ESGMYC members, 64 (17 countries) responded to the questionnaire. In their practice, two (20.7%) or three sputum samples (79.3%) were collected for the diagnosis of pulmonary TB, alternatively induced sputum ( n = 37, 67.2%), bronchoscopy (34, 58.6%), and gastric aspirates (15, 25.9%). Nucleic acid amplification tests (NAATs) were performed by 41 (64%) respondents whatever the smear result and by 47 (73%) in case of smear-positive specimens. NAAT and adenosine deaminase measurement were used for extrapulmonary TB diagnosis in 83.6 and 40.4% of cases, respectively. For isolation duration, 21 respondents (42.9%) were keeping isolation until smear negativity. An initial treatment without ethambutol was offered by 14% ( n = 9) of respondents. Corticosteroid therapy, cerebrospinal fluid opening pressure testing, and repeated lumbar puncture were carried out for central nervous system TB by 79.6, 51.9, and 46.3% of the respondents, respectively. For patients with human immunodeficiency virus-TB coinfection, the preferred antiretroviral therapy included dolutegravir 50 mg twice a day (56.8%). Comparing with the recommendations of the main guidelines, the practices are not totally consistent. Conclusion: This study shows heterogeneous practices, particularly for diagnosis, and isolation, although rapid molecular testing is implemented in most centers. More standardization might be needed., (Copyright © 2020 Méchaï, Cordel, Guglielmetti, Aubry, Jankovic, Viveiros, Santin, Goletti and Cambau.)

Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis. In 2017, approximately 10 million people developed TB worldwide, of whom more than 100,000 new cases of TBM are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. GeneXpert represents the most significant advance in TBM diagnostics over the past decade, but it lacks sensitivity and cannot be used to rule out the diagnosis. Higher volume of cerebrospinal fluid (CSF) seems to be interesting to improve the diagnosis performances. New rapid and accurate diagnostic tools are necessary. Better advances have been made concerning the anti-tuberculosis chemotherapy of TBM, with the publication of clinical trials and pharmacokinetic studies exploring the use of higher rifampicin doses and fluoroquinolones. The rise of drug-resistant TBM is another challenge for management because TBM caused by multidrug resistant organisms results in death or severe disability in almost all sufferers., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: To describe the residual broncho-pulmonary lesions and evaluate the role of CT scanning at the end of treatment of pulmonary tuberculosis., Materials and Methods: Analysis of the initial and end of treatment CT scans of 56 patients with pulmonary tuberculosis according to a reading grid including parenchymatous and airways lesions. The CT data at the end of treatment were analysed in relation to the clinical and microbiological data, and the original CT scan., Results: Active lesions (thick walled cavities and/or centrilobular micronodules) persisted in 24 patients (43%) after a mean treatment period of 7 months. The persistence of these signs of activity was correlated with the initial presence of a cavitary syndrome (p=0.027), with predominant sub-segmentary bronchial involvement, with extensive micronodular spread (p=0.024) and with bronchiectasis (p=0.04). These residual lesions were not associated with an increased risk of relapse., Conclusion: The persistence of signs of activity on the CT scan at the end of treatment of tuberculosis do not necessarily correspond to an absence of cure but to a radiological delay. This imaging is nevertheless useful to make an assessment of any subsequent changes in the bronchial tree and to estimate the risk of later complications., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

The diagnosis of nocardiosis, a severe opportunistic infection, is challenging. We assessed the specificity and sensitivity of a 16S rRNA Nocardia PCR-based assay performed on clinical samples. In this multicenter study (January 2014 to April 2015), patients who were admitted to three hospitals and had an underlying condition favoring nocardiosis, clinical and radiological signs consistent with nocardiosis, and a Nocardia PCR assay result for a clinical sample were included. Patients were classified as negative control (NC) (negative Nocardia culture results and proven alternative diagnosis or improvement at 6 months without anti- Nocardia treatment), positive control (PC) (positive Nocardia culture results), or probable nocardiosis (positive Nocardia PCR results, negative Nocardia culture results, and no alternative diagnosis). Sixty-eight patients were included; 47 were classified as NC, 8 as PC, and 13 as probable nocardiosis. PCR results were negative for 35/47 NC patients (74%). For the 12 NC patients with positive PCR results, the PCR assay had been performed with respiratory samples. These NC patients had chronic bronchopulmonary disease more frequently than did the NC patients with negative PCR results (8/12 patients [67%] versus 11/35 patients [31%]; P = 0.044). PCR results were positive for 7/8 PC patients (88%). There were 13 cases of probable nocardiosis, diagnosed solely using the PCR results; 9 of those patients (69%) had lung involvement (consolidation or nodule). Nocardia PCR testing had a specificity of 74% and a sensitivity of 88% for the diagnosis of nocardiosis. Nocardia PCR testing may be helpful for the diagnosis of nocardiosis in immunocompromised patients but interpretation of PCR results from respiratory samples is difficult, because the PCR assay may also detect colonization., (Copyright © 2018 American Society for Microbiology.)

Objective: To evaluate the efficacy of amikacin on sputum conversion during initial sputum smear positive tuberculosis treatment., Material and Methods: Single-center observational cohort study (2012-2013) evaluating time to sputum smear conversion with standard treatment (ST) versus standard treatment+amikacin (IV 15mg/kg/day) for seven days (STamK)., Results: Forty-five patients were included. Median time to smear negative samples was 26.5 days (14-56) for the 30 (66.7%) patients included in the ST group and 48 days (19.5-69.5) for the 15 patients (33.3%) included in the STamK group (P=0.76). Time to negative culture was only known for 27 patients (61.4%): 47.5 days (26-58) for 18 patients in the ST group and 40 days (14-77) for nine patients in the STamK group., Conclusion: Despite our small sample size, the addition of amikacin in active tuberculosis treatment did not seem to impact time to smear conversion or period of contagiousness., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Vascular graft infections are infrequent complications with important morbidity and mortality rates. Pasteurella multocida, a Gram negative bacillus, is a normal oral commensal of many animals. For mankind, it is a pathogenous bacillus which is rarely implicated in vascular grafts., Case Report: We report hereafter the fourth case introduced in the international literature about vascular graft infections caused by P. multocida. The patient was successfully treated with a combination of a surgical graft change and a 6 weeks bi-antibiotic therapy., Discussion: There is fours case reported in litterature with quite different antibiotic drugs and duration., Conclusion: P. multicoda graft infection should be long with initial intravenous drug and mainteance traitement should not be required.

Objectives: To evaluate isolation practices and management of sputum smear-positive tuberculosis (TB) in France., Methods: A survey was conducted using a questionnaire e-mailed in 2011 and 2012 to physicians of the French Society of Infectious Diseases, the French Respiratory Society and the French National Society of Internal Medicine., Results: Of 311 responders, a quarter stated they treated more than 25 TB cases per year. A total of 87.8% declared they routinely used a four-drug regimen in the initial intensive phase. Of the 311 physicians who responded, 31.9% removed isolation precautions after three negative acid-fast bacilli (AFB) sputum results, 19.0% after 15 days of treatment and 34.1% only in case of clinical improvement. According to 71% of the responders, discharge from hospital despite positive AFB sputum smear results was 'possible'. A routine AFB sputum smear was performed after 2 months of treatment by only 21% of the responders., Conclusion: Despite recent national guidelines, the management of isolation precautions for sputum smear-positive TB remains heterogeneous, and a significant proportion of physicians use a three-drug regimen. Further efforts should be made to implement TB guidelines, mainly by raising awareness through national scientific institutions, but also by obtaining better evidence.

Objective: To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy., Methods: All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self-administered standardized questionnaire within 10 days after immunization. YF-specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids., Results: Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination., Conclusion: After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale studies are needed to confirm these results., (Copyright © 2013 by the American College of Rheumatology.)

Background: Fluoroquinolones are used with increasing frequency in children with a major risk of increasing the emergence of FQ resistance. FQ use has expanded off-label for primary antibacterial prophylaxis or treatment of infections in immune-compromised children and life-threatening multi-resistant bacteria infections. Here we assessed the prescriptions of ciprofloxacin in a pediatric cohort and their appropriateness., Methods: A monocenter audit of ciprofloxacin prescription was conducted for six months in a University hospital in Paris. Infected site, bacteriological findings and indication, were evaluated in children receiving ciprofloxacin in hospital independently by 3 infectious diseases consultants and 1 hospital pharmacist., Results: Ninety-eight ciprofloxacin prescriptions in children, among which 52 (53.1%) were oral and 46 (46.9%) parenteral, were collected. 45 children had an underlying condition, cystic fibrosis (CF) (21) or an innate or acquired immune deficiency (24). Among CF patients, the most frequent indication was a broncho-pulmonary Pseudomonas aeruginosa infection (20). In non-CF patient, the major indications were broncho-pulmonary (25), urinary (8), intra-abdominal (7), operative site infection (5) and bloodstream/catheter (2/4) infection. 62.2% were microbiologically documented. Twenty-three (23.4%) were considered "mandatory", 48 (49.0%) "alternative" and 27 (27.6%) "unjustified"., Conclusion: In our university hospital, only 23.4% of fluoroquinolones prescriptions were mandatory in children, especially in Pseudomonas aeruginosa healthcare associated infection. Looking to the ecological risk of fluoroquinolones and the increase consumption in children population we think that a control program should be developed to control FQ use in children. It could be done with the help of an antimicrobial stewardship team.

Background: Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe., Methods: A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine., Results: Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p < 0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group., Conclusions: This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.

Mycobacterium bovis (M. bovis) is a cause of zoonosis. It is rare in developed countries since cattle control. We report four cases of M. bovis infection in people aged more 60  years. They were probably infected during infancy, consuming unpasteurized milk. It is the main transmission mode in developing countries where veterinary controls aren't made. M. bovis infections clinical aspects are varied and treatment is complicated by natural pyrazinamide resistance. Recent diagnostic methods using molecular biology are quick and specific and facilitate identification.

Mycobacterium bovis is responsible for a zoonosis originating in cattle. This disease has rarely affected man in industrialised countries since the establishment of veterinary surveillance in cattle. We report the case of a young female patient who developed a Mycobacterium bovis primary infection revealed by erythema nodosum. Infection was probably due to the consumption of non-pasteurised milk in Morocco. This clinical manifestation is rare and physicians ought to be aware of this imported pathology.

Dengue is a common, mosquito borne, travel-related, viral infection in the tropical traveler caused by an arbovirus. This virus has 4 different serotypes and is responsible for approximately 50 to 100 million cases per year. Its incidence and geographic distribution are clearly increasing lately. Although occurring in tropical endemic areas, sporadic and autochthonous cases have been recently reported in temperate countries including France. The tropical influenza-like clinical presentation is not very specific except for rash. Diagnosis is facilitated by the existence of thrombocytopenia and the early detection of NS1 antigen using rapid test. Hemorragic forms with or without shock syndrome are rare in travelers and represent the severe manifestations especially in children. Their pathophysiology remains controversial. Management is essentially symptomatic. Aspirine should be avoided because of bleeding risk. Beyond individual (travel) or collective (endemic zone) vector control measures, the development of a quadrivalent vaccine seems about to succeed.

Candida species is the fourth most common cause of bloodstream infection and is the leading cause of invasive fungal infection among hospitalized patients. Acute disseminated candidiasis remains a life-threatening disease that now occurs mainly in intensive care units hospitalized patients. Delay in treatment of Candida bloodstream infections could be minimized by the development of more rapid and sensitive diagnostic techniques for the identification of Candida bloodstream infections. Current guidelines for the management of invasive candidiasis recommend fluconazole or an echinocandin as the primary therapeutic option. The optimal choice of the antifungal agent should depend on local epidemiology, prior antifungal therapy and patient's characteristics., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

A case of bladder toxoplasmosis in a 57-year-old male Caucasian patient was diagnosed with difficulty due to misleading clinical presentation. The patient presented with pollakiuria and urination burning. Imagery showed pseudotumoral thickening of the vesicle wall. Previously unknown status of HIV infection was found positive through the diagnosis of bladder toxoplasmosis. The patient died rapidly from neurological complications. This is the second published case in which bladder toxoplasmosis reveals an HIV infection., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Giant hydatid cyst located in the retroperitoneal space is rare. The purpose of this report is to present a case cured by surgery in an adult traveller., Case Report: In August 2009, a 67-year-old female who traveled frequently to Lebanon was admitted for assessment of a giant retroperitoneal hydatid cyst discovered coincidentally following palpation of an abdominal mass in 1997. From 1966 to 1975, the patient had undergone several surgical procedures for pulmonary and hepatic hydatidosis, complicated by vomica and anaphylactic shock. In 1997, computed tomography showed that the retroperitoneal cyst measured 100 mm at the widest point. At that time, the patient refused to undergo further surgery and was treated medically using albendazole initially in association with praziquantel. In 2009, the cyst had expanded to 180 mm at the widest point and the patient finally consented to perikystectomy. Excision was total and recovery was uneventful. Histology examination confirmed the viability of the cyst. Follow-up examination at 12 months indicated no relapse., Comments: The retroperitoneal space is a rare location for hydatidosis. Occurrence in this location is generally primary. In case of discovery of a liquid-filled retroperitoneal mass, a history of travel to an endemic area for hydatid disease should be elicited. Diagnosis relies on radiological findings and positive serology. Since retroperitoneal cysts are often giant, they respond poorly to medical treatment. Similarly radiological treatment is difficult due to retroperitoneal location. Surgery, preferably perikystectomy, is the treatment of choice.

Chloroquine-proguanil association is recommended for prophylaxis against falciparum malaria in countries with a low prevalence of chloroquine resistance. It is usually well tolerated with mild side effects consisting mainly of transient digestive discomfort and buccal manifestations (mouth sores or ulcers). The purpose of this report is to describe a case of duodenal ulcers presenting as epigastric pain with 10-kg weight-loss in a 32-year-old man taking chloroquine-proguanil for malaria prophylaxis during a stay in Haiti. No other causes of duodenal ulcers or weight-loss were found. Chloroquine-proguanil prophylaxis was discontinued and replaced by omeprazole for four weeks. Symptoms improved quickly and full recovery was observed within one month. To our knowledge, the occurrence of duodenal ulcers under chloroquine-proguanil association is quite rare, but possibly severe. Upper digestive endoscopy should be performed if a patient under chloroquine-proguanil develops abdominal pain especially in association with weight-loss. If endoscopy reveals duodenal ulcers, chloroquine-proguanil should be discontinued and replaced by another prophylactic regimen.

Purpose: To describe the epidemiological and clinical features of enteroviral meningitis as well as the biological profile of the cerebrospinal fluid (CSF)., Methods: A retrospective study conducted in a single centre between 2004 and 2008. All aseptic meningitis due to Enterovirus were included., Results: Fifty-nine patients were included. The triad including fever, headache and neck stiffness was reported in 62% of patients. Twelve patients (20%) had a neutrophilic leukocytosis and 23 (39%) an elevated CRP level. Twenty-eight patients (47%) had a prominent neutrophilic reaction in the CSF and nine (15.2%) had a low glucose concentration. A presumptive anti-bacterial treatment was initiated in 47 patients (80%) for an average of 3.2 days., Conclusion: Due to the lack of specificity of clinical features and biological manifestations of Enterovirus meningitis, the widespread use of real-time Enterovirus PCR is a priority for reducing the number of unnecessary anti-bacterial treatment. Guidelines based on clinical and biological features may be associated to help physicians in the differential diagnosis between bacterial and viral meningitides., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Yellow fever vaccine is produced from a live attenuated virus that is contraindicated in case of immunodeficiency and subject to restrictions for pregnant or breastfeeding women. The purpose of this review of available information on yellow fever vaccination during pregnancy and breastfeeding is to assist physicians in making recommendations prior to departure to yellow-fever endemic zones. Regarding pregnancy, there is no evidence to support a major risk of yellow-fever-vaccine-related complications in mothers or children. Although this finding is reassuring, it should be underlined that most reported series have been small. Regarding breastfeeding, the risk was recently confirmed by a report describing vaccine-induced encephalitis occurring in an infant 8 days after primary vaccination of the mother. The final decision to vaccinate depends on whether or not the trip can be postponed. If travel is mandatory, vaccination may be recommended in pregnant women preferably during the first trimester since the immunological response appears to be better at that time. Antibody titer should be checked following delivery. During breastfeeding, vaccination may be performed but breastfeeding must be stopped during the postvaccinal viremia phase. Breastfeeding can be resumed after a 10-day period of formula feeding.

Lymphogranuloma venereum (LGV) cases are currently re-emerging in the homosexual community, particularly in HIV-seropositive patients. The standard treatment for this infection, which is caused by Chlamydia trachomatis L1, L2 and L3 serotypes, is a 3-week doxycycline regimen. The case is reported of a male patient presenting with LGV, who was rapidly cured with moxifloxacin treatment after failure of extended treatment with cyclines. This fluoroquinolone is known to be highly active in vitro on the LGV pathogenic agent. Thus it may be a useful alternative when doxycycline treatment results in failure.

Chronic disseminated candidiasis is a complication of the intensive therapies of hematological malignancies revealed during hematopoietic recovery, a context reminiscent of the immune restoration inflammatory syndrome in human immunodeficiency virus patients receiving antiretroviral therapy. We report a case of severe exacerbation of chronic disseminated candidiasis after pegylated granulocyte-colony stimulating factor administration. We emphasize the major inflammatory substrate of the disease and suggest that immune-modulating strategies such as hematopoietic growth factors, should be used cautiously in such patients., (Copyright (c) 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.)

Amebiasis remains a major public health issue in most of the world. Amebic liver abscess is the most common extraintestinal manifestation. A complication such as venous obstruction associated with amebiais is rare. We report a thrombosis in hepatic veins associated with amebic hepatic abscess in a traveler.

Rhodococcus equi is a bacterial pathogen of domestic animals that can infect immunocompromised patients, especially those with impaired cellular immunity, such as transplant recipients. No standard treatment has been established, but therapy must be prolonged, as relapses are common and can occur at the initial site or distant locations. Here we report a case of R. equi-associated pulmonary abscess in a renal transplant recipient successfully treated with a combination of carbapenem and teicoplanin. This combination was shown to be synergistic. It has minimal side effects in transplant recipients and appears to be an effective initial treatment for this severe infection.

An ongoing outbreak of lymphogranuloma venereum (LGV) L2b proctitis, predominantly in HIV-positive men who have sex with men (MSM), has been reported in industrialised countries. A case of reactive arthritis after L2b proctitis is described. This case expands the spectrum of severe complications related to LGV L2b proctitis. Since this infection may be asymptomatic, this organism should be screened for in HIV-positive MSM with symptoms consistent with reactive arthritis.

African tick bite fever is caused by Rickettsia africae. The number of reported cases in international travelers has significantly increased recently. The gold standard treatment is doxycycline. Here, we present a case of R africae infection associated with quick complete resolution following the initiation of pristinamycin therapy.

Like other herpesviruses, human herpesvirus 6 (HHV-6) can reactivate in immunocompromised patients. A case is described of an HIV-1-infected patient who developed bilateral retrobulbar optic neuritis associated with HHV-6 infection. A 59-year-old woman, infected with HIV for 18 years, interrupted antiretroviral treatment because of therapeutic failure and severe metabolic complications. She presented subsequently with blurred vision and ophthalmological examination showed visual loss due to optic neuritis. Her CD4+ count was 285 cells/mm(3) and her plasma HIV-1 RNA level was 5.5 log(10) copies (cp)/ml. Magnetic resonance imaging of the brain was normal. HHV-6 loads were 3.2 log cp/ml in cerebrospinal fluid (CSF) and 6.3 log cp/10(6) peripheral blood mononuclear cells. Combined intravenous treatment was started with foscarnet and ganciclovir then changed to cidofovir and long-term valganciclovir. Her ocular condition improved gradually despite little decrease of the HHV-6 load in the CSF. Salvage antiretroviral treatment was then administered, with marked immunological and virological responses, contributing to further progressive ocular improvement. HHV-6-related optic neuritis has not been described previously in HIV-infected patients. Anti-HHV-6 treatment improved the patient's vision, but immune restoration seems to remain essential for long-term recovery.