Tuberculous meningitis: Challenges in diagnosis and management.

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.

Intra-abdominal abscesses: Microbiological epidemiology and empirical antibiotherapy.

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.

Treatment With a Three-Drug Regimen for Pulmonary Tuberculosis Based on Rapid Molecular Detection of Isoniazid Resistance: A Noninferiority Randomized Trial (FAST-TB).

Background: The rationale behind the use of ethambutol in the standard tuberculosis treatment is to prevent the emergence of resistance to rifampicin in case of primary resistance to isoniazid. We evaluated whether early detection of isoniazid resistance using molecular testing allows the use an ethambutol-free regimen. Methods: FAST-TB, a phase 4, French, multicenter, open-label, non-inferiority trial, compared 2 strategies: (1) polymerase chain reaction (PCR)-based detection of isoniazid and rifampicin resistance at baseline using Genotype MTBDRplus version 2.0 followed by ethambutol discontinuation if no resistance was detected (PCR arm) and (2) a standard 4-drug combination, pending phenotypic drug-susceptibility results (C arm). Adult patients with smear-positive pulmonary tuberculosis were enrolled. The primary endpoint was the proportion of patients with treatment success defined as bacteriological or clinical cure at the end of treatment. A non-inferiority margin of 10% was used. Results: Two hundred three patients were randomized, 104 in the PCR arm and 99 in the C arm: 26.6% were female, median age was 37 (interquartile range, 28-51) years, 72.4% were born in Africa, and 5.4% were infected with human immunodeficiency virus. Chest x-ray showed cavities in 64.5% of the cases. Overall, 169 patients met criteria of treatment success: 87 of 104 (83.7%) in the PCR arm and 82 of 99 (82.8%) in the C arm with a difference of +0.8% (90% confidence interval, -7.9 to 9.6), meeting the noninferiority criteria in the intention-to-treat population (P = .02). Conclusions: In a setting with low prevalence of primary isoniazid resistance, a 3-drug combination with isoniazid, rifampicin, and pyrazinamide, based on rapid detection of isoniazid resistance using molecular testing, was noninferior to starting the recommended 4-drug regimen.

Tuberculosis treatment outcomes among precarious patients in France.

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.

[Performances of the Amplified Mycobacterium Tuberculosis Direct Test in non respiratory specimens (study about 1538 samples)]. / Performances du test "Amplified Mycobacterium Tuberculosis Direct Test" sur les échantillons extrarespiratoires (étude sur 1538 échantillons).

From March 1998 to August 2009, 1538 non-respiratory samples collected from 1182 patients, were tested using the Gen-Probe Amplified Mycobacterium Direct Test™ (AMTD). After decontamination procedure, every sample was tested by AMTD and by culture on solid and liquid media. The "Gold-standard" was considered by the combination of culture results and clinical diagnosis. Tuberculosis was present in 17,59 % (208 patients). For theses 1538 non-respiratory samples (225 culture positive samples, 248 AMTD positive), 279 corresponded to tuberculosis. After resolving the discordant results, the sensitivity, specificity, positive and negative values were 89, 99, 99,6 and 97,3 %.

[Evaluation of the SD BIOLINE TB Ag MPT64 Rapid® for the diagnosis of tuberculosis]. / Évaluation du kit SD BIOLINE TB Ag MPT64 Rapid® dans le cadre du diagnostic de la tuberculose.

The purpose of this study was to evaluate the SD Bioline Ag MPT64 Rapid(®) for identification of the Mycobacterium tuberculosis complex. The method uses an immunochromatographic assay and needs 100 µl of sample taken from liquid culture or colonies suspended. The sensitivity was determined using 99 strains of M. tuberculosis complex and the specificity using 10 nontuberculous mycobacteria and 85 strains other than mycobacteria genus. The test showed excellent sensitivity (99%) and specificity (100%). This technique displays several advantages and is destined to spread in all laboratories and particularly in endemic areas.

[Giant retroperitoneal hydatid cyst in a traveller]. / Kyste hydatique rétropéritonéal géant chez un voyageur.

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.

Screening for active and latent TB among migrants in France.

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.

Pulmonary tuberculosis: Evaluation of current diagnostic strategy.

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.

[Should yellow fever vaccination be recommended during pregnancy or breastfeeding?]. / Vaccin amaril au cours de la grossesse ou de l'allaitement: que conseiller?

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.

[Duodenal ulcers caused by chloroquine-proguanil association]. / Ulcérations duodénales dues à l'association chloroquine-proguanil.

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.

[Acute myelitis related to hepatitis A after travel to Senegal]. / Myélite aiguë transverse révélatrice d'une hépatite virale aiguë A au retour du Sénégal.

Neurological complications are rare following hepatitis A. Acute myelitis is even more uncommon. The purpose of this report is to describe a case of acute myelitis related to hepatitis A virus (HAV) in a 43-year-old-woman returning from Senegal. Diagnosis of myelitis was confirmed by spinal MRI and detection of anti-HAV Ig M antibodies in serum. The patient made a spontaneous clinical recovery in one month. Spinal MRI findings were normal at three months. Hepatitis A should be considered in the diagnostic approach to acute myelitis in returning travelers and patients living in highly endemic countries where prophylactic vaccination is unavailable.

Reactive arthritis associated with L2b lymphogranuloma venereum proctitis.

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.

Microsporidiosis in solid organ transplant recipients: two Enterocytozoon bieneusi cases and review.

Microsporidiosis first came to prominence as an opportunistic infection in patients with acquired immunodeficiency syndrome. Microsporidia are now emerging pathogens responsible for severe diarrhea during solid organ transplantation. Two main clinical entities can be identified: infection by Enterocytozoon bieneusi, causing diarrhea with limited treatment options; and infection by Encephalitozoon intestinalis, which may disseminate and usually responds to albendazole treatment. We describe here 2 cases of microsporidiosis caused by E. bieneusi in a renal and a liver transplant recipient, respectively, in whom complete clinical efficacy of a short course of fumagillin therapy was obtained. Long-term microbiological eradication was assessed using classical methods and monitored using a real-time quantitative polymerase chain reaction-based method. Both patients experienced drug-induced thrombocytopenia, which resolved after withdrawal of the treatment. We also review the 18 other previously reported cases of microsporidiosis in transplant recipients. In case of persistent diarrhea in solid organ transplant patients, microsporidiosis should be considered. Based on the present experience, treating E. bieneusi infection with 7 days of fumagillin therapy is adequate to eradicate E. bieneusi in this context.

Synergistic effect of carbapenem-teicoplanin combination during severe Rhodococcus equi pneumonia in a kidney transplant recipient.

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.

[Pulmonary tuberculosis: Radiological evolution of broncho-pulmonary lesions at the end of treatment]. / Tuberculose pulmonaire : évolution radiologique des lésions broncho-pulmonaires en fin de traitement.

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.

[Systemic granulomatosis of infectious origin]. / Les granulomatoses systémiques d'origine infectieuse.

PURPOSE: Granulomatous diseases are defined by specific histological features, following the local recruitment of macrophages and lymphocytes. Many infections can lead to the development of granuloma. CURRENT KNOWLEDGE AND KEY POINTS: Microorganisms responsible for granuloma include mainly mycobacteria, many viral and fungal species, as well as schistosoma in endemic areas. Nevertheless, almost all microorganisms can lead to granuloma, especially if their clearance needs macrophages pathway. New immunosuppressive drugs such as tumor necrosis factor antagonists are associated with a high risk of infectious granulomatous complications. All patients with granuloma must be carefully screened to find a potential underlying infection, since an immunosuppressive therapy could be otherwise considered. We here review the general diagnostic process with a specific glance to the main organs. FUTURE PROSPECTS AND PROJECTS: Without clinical or epidemiological clue, diagnosis can be very tedious. New molecular tools now assist classical microbiological and histological techniques. Their specificity and sensitivity have recently been better characterized, and their use will probably increase in the near future for the diagnosis of infectious granuloma. They may also lead to discover new infectious aetiologies of granulomatous diseases formerly considered as idiopathic. We describe here the main microorganisms that can be responsible for granuloma, with a specific focus on the use of new diagnostic tools.

Active pulmonary tuberculosis: Role for amikacin in early treatment.

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.

MALDI-TOF MS contribution to diagnosis of melioidosis in a nonendemic country in three French travellers.

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.