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.

The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

Bacterial chondritis complications following ear piercing.

BACKGROUND: Body piercing has become widespread and is associated with increased complications. Post-piercing chondritis may lead to severe residual deformity. We aimed to report case patients presenting with post-piercing chondritis in our department and to describe clinical features and treatment. PATIENTS AND METHODS: We conducted a retrospective study of patients presenting with post-piercing chondritis in the infectious disease department of Tenon Hospital, Paris, France. RESULTS: We included 21 patients. Fifteen bacteriological cultures were positive (7 Pseudomonas aeruginosa, 5 Staphylococcus aureus, and three other). Dual intravenous antibiotic therapy was administered to 13 patients for a median duration of six days [2-8], replaced by an oral antibiotic therapy for a median duration of 15 days [7-40]. Eight patients received oral antibiotic monotherapy for 10 days [7-30]. Median duration of antibiotic therapy was 16 days. Earring removal was performed for 18 patients. No ear deformity or general complication was reported. CONCLUSION: Transcartilaginous ear piercing may lead to infectious complications or deformity. In case of chondritis, early administration of an antibiotic therapy active against P. aeruginosa and S. aureus is recommended. Specific guidelines are needed.

Role of a NSAID in the apparent cure of a fungal mycetoma.

UNLABELLED: We report the case of a fungal mycetoma due to Madurella mycetomatis that failed to respond to surgery and antifungal treatment but responded strongly to the addition of a non-steroidal anti-inflammatory drug (NSAID). This African patient was born in Mauritania in 1972. He was a herdsman, living close to the Senegal River. The first nodules appeared on the left foot at the age of 13years (1985). The patient suffered frequent flare-ups with the appearance of black grains and underwent surgery in 1988 and 1992 in Senegal. After remission for several months after surgery, new fistulae occurred. The patient emigrated to France in 1995 and underwent a third surgical intervention in 1996. M. mycetomatis was cultured from the black grains. The patient was otherwise in good health, with no diabetes, and HIV tests were negative. We saw the patient for the first time in 2005, at which time he had flare-ups every two to three months. Imaging disclosed an absence of bone involvement. The patient underwent a fourth operation in October, 2005, and voriconazole treatment was initiated. A new flare-up occurred in February, 2006. CT, MRI, and PET scans revealed calcaneus and tarsal involvement, and posaconazole then replaced voriconazole. Flucytosine was added four months later, due to an absence of improvement. New flares-ups occurred and a fifth surgical intervention was performed in September, 2006. The pain, which had been present for three years, worsened; the patient had to stop working and was no longer able to walk without crutches. Amputation of the foot was considered. Empiric treatment with a NSAID, diclofenac (Voltaren(®); 100mg/day), was added to the antifungal treatment in November 2006, to treat the patient's pain and inflammation. A major improvement was observed within one week. The patient was able to walk without crutches one month later. After two months, clinical examination was normal: no pain, inflammation, nodules or fistulae. Flucytosine was stopped after six months of treatment, in January 2007, diclofenac after 10months, in October 2007, and posaconazole after 18.5months, also in October 2007. No relapse has occurred during the eight years of follow-up since treatment ended. The patient seems to have been cured and has normal CT, MRI, and PET scans. IN SUMMARY: This eumycetoma, which had progressed over 20years despite surgery and antifungal treatments, seems to have been cured by the addition of a NSAID. This observation suggests that inflammation plays a major role in the pathogenesis of fungal mycetoma. Clinical studies of treatments including an NSAID should be conducted to confirm this finding.

The features of infectious diseases departments and anti-infective practices in France and Turkey: a cross-sectional study.

The aim of this study was to assess the infectious diseases (ID) wards of tertiary hospitals in France and Turkey for technical capacity, infection control, characteristics of patients, infections, infecting organisms, and therapeutic approaches. This cross-sectional study was carried out on a single day on one of the weekdays of June 17-21, 2013. Overall, 36 ID departments from Turkey (n = 21) and France (n = 15) were involved. On the study day, 273 patients were hospitalized in Turkish and 324 patients were followed in French ID departments. The numbers of patients and beds in the hospitals, and presence of an intensive care unit (ICU) room in the ID ward was not different in both France and Turkey. Bed occupancy in the ID ward, single rooms, and negative pressure rooms were significantly higher in France. The presence of a laboratory inside the ID ward was more common in Turkish ID wards. The configuration of infection control committees, and their qualifications and surveillance types were quite similar in both countries. Although differences existed based on epidemiology, the distribution of infections were uniform on both sides. In Turkey, anti-Gram-positive agents, carbapenems, and tigecycline, and in France, cephalosporins, penicillins, aminoglycosides, and metronidazole were more frequently preferred. Enteric Gram-negatives and hepatitis B and C were more frequent in Turkey, while human immunodeficiency virus (HIV) and streptococci were more common in France (p < 0.05 for all significances). Various differences and similarities existed in France and Turkey in the ID wards. However, the current scene is that ID are managed with high standards in both countries.

Upgraded Cobas Ampliprep-Cobas TaqMan version 2.0 HIV-1 RNA quantification assay versus first version: correction of underestimations.

The large underestimations of HIV RNA quantification observed in 17 patients with the first version of Cobas TaqMan assay have been successfully corrected in the upgraded version 2.0. In comparison with the Abbott RealTime assay, the mean difference that was 1.18 log(10) copies/ml is now zero. The discrepancies have disappeared.

Fetal death as a result of placental immune reconstitution inflammatory syndrome.

A 26-year-old woman was HIV-1 diagnosed at 11 weeks of pregnancy (CD4 = 7/mm(3), HIV-1 RNA = 108,000 copies/mL) with immunity against toxoplasmosis (Toxoplasma IgG = 1800 UI/mL). A fetal death was diagnosed 7 weeks after starting HAART (CD4 = 185/mm(3), HIV-1 RNA = 391 copies/mL) with a positive Toxoplasma PCR on fetal tissues and amniotic fluid. The absence of severe toxoplasmic foetopathy, the very exaggerated and atypical placental inflammation and the immune restoration context led to the diagnosis of placental IRIS associated with Toxoplasma gondii reactivation. This outcome remains undescribed and could represent an issue in resource-limited settings where HIV-pregnant patients are often severely immunodeficient and infected with opportunistic pathogens.

[Prevalence of skin disorders in HIV patients in Senegal and relationship to degree of immunosuppression]. / Prévalence des manifestations dermatologiques chez les malades infectés par le VIH au Sénégal et association avec le degré d'immunodépression.

BACKGROUND: The aim was to evaluate the association between dermatological findings in HIV-infected patients in Senegal and degree of immunosuppression and HIV stage. PATIENTS AND METHODS: All consecutive HIV infected patients followed up at three dermatology centres in Senegal from 01 January 2004 to 01 January 2006 were evaluated retrospectively regarding dermatological findings, CD4 cell count and HIV stage. PATIENTS AND METHODS: One hundred and forty-nine patients with 331 skin diseases were evaluated. The most common forms of dermatosis were oral candidiasis (53%), herpes zoster (24%), prurigo (24%) and dermatophytosis (16%). An increasing number of skin diseases was significantly associated with CD4 counts of below 200 per cubic millimeter and Aids diagnosis. A significant association (p<0.05) was found between two types of dermatosis (oral candidiasis and chromonychia) and CD4 counts of below 200 per cubic millimeter and between four types of dermatosis (straightened hair, herpes, oral candidiasis and xerosis) and Aids diagnosis. CONCLUSION: Dermatological findings are of great diagnostic and prognostic significance. We found some features specific to black skin: longitudinal melanonychia and blue ungueal pigmentation potentially related to immunosuppression and straightened hair, associated with Aids, probably resulting from denutrition.

[Antibiotherapy for early localized Lyme disease]. / Antibiothérapie de la phase primaire de la borréliose de Lyme.

OBJECTIVE: The aim of this article is to provide clinicians with guidelines for the antibiotherapy of early-localized Lyme disease. The outcome measures are the clearance of erythema migrans and associated symptoms of early localized Lyme disease and the prevention rate of late complications, with a low risk of adverse effects. Design. The reviewed studies were selected by Medline with the keywords: "erythema migrans, treatment". Sixteen studies comparing treatment or duration of treatment were analyzed. RESULTS: Amoxicillin, doxycycline, and cefuroxim axetil are equally efficacious for early-localized Lyme disease. Azithromycin is an alternative. Most patients respond completely and less than 10% fail to respond. All antibiotics are associated with a low frequency of adverse effects, with the exception of Jarisch Herxheimer reaction which occurs in about 15% of the patients. CONCLUSIONS: We recommend treating adults with amoxicillin (50 mg/kg/day in 3 intakes) or doxycycline (100 mg bid) for 14 days (erythema migrans) to 21 days (early localized Lyme disease with associated symptoms). For children, we recommend amoxicillin (50 mg/kg/day in 3 intakes) or doxycycline (4 mg/kg/day in 2 intakes, maximum 100 mg/dose) above 8 years of age. Cefuroxim axetil (500 mg twice daily for adults or 30 mg/kg/day in 2 intakes, maximum 500 mg/dose, for children), and azithromycin (500 mg/day for adults and 20 mg/kg/day for children for 7-10 days) are second line treatment.

[Surgery of type A acute aortic dissection. Past, present and future]. / Cirugía de la disección aórtica aguda tipo A. Pasado, presente y futuro.

Type A Aortic Dissection is a medical-surgical emergency which requires prompt diagnosis and adequate treatment. Since its inception--more than 40 years ago--the surgical treatment has evolved up until now, when it offers an immediate solution to the high mortality rate due to complications, with acceptable morbidity and mortality rates. This improvement is due also to better diagnostic techniques, postoperative management and profound hypothermia with circulatory arrest. The basic techniques to achieve this consist of resection of the entry tear and closure of the false lumen and repair of the aortic regurgitation when present. Failure of them--proximally or distally--leads to persistence of the false lumen and the possibility of complications or late reoperations. The long-term follow-up, monitorized by non-invasive methods, is mandatory to decide the proper management.