Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study.

OBJECTIVE: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance. METHODS: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion. RESULTS: Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (κ test=0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p <0.001), and even when the latter were continued over 30 days (19/101 (19%), p 0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, 95% CI 0.95-1). CONCLUSIONS: Untargeted next-generation sequencing has a high negative predictive value and detects more clinically relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults.

Aspergillus spp. invasive external otitis: favourable outcome with a medical approach.

Aspergillus spp. invasive external otitis (IEO) is a rare infection. We performed a seven-year, single-centre retrospective study from 2007 to 2014 including all patients with proven Aspergillus spp. IEO. Twelve patients were identified. All patients had a poorly controlled diabetes mellitus and one underwent solid organ transplant. The most frequently isolated species was Aspergillus flavus (n = 10) and voriconazole was the first-line therapy in all cases, with a median length of treatment of 338.5 days (158-804 days). None of the patients underwent extensive surgery. The clinical outcome was excellent. However, otological sequelae were reported, including hearing impairment (n = 7) and facial palsy (n = 3).

Induction therapy with linezolid/clarithromycin combination for Mycobacterium chelonae skin infections in immunocompromised hosts.

BACKGROUND: The optimal management of Mycobacterium chelonae disease in immunocompromised patients remains unclear. A combination of antimicrobial agents is recommended as monotherapy with clarithromycin has been associated with clinical failures due to acquired resistance. OBJECTIVES: We aim to report the efficacy and tolerability of linezolid in association with clarithromycin for the treatment of M. chelonae infections in immunocompromised patients. METHODS: We describe four immunocompromised patients treated by linezolid and clarithromycin for cutaneous M. chelonae disease. RESULTS: This combination was associated with rapid clinical efficacy in all patients with no relapse observed after a median follow-up of 2.25 years (1.4 years). However, this treatment was responsible for frequent adverse events including thrombocytopaenia, myalgia and mitochondrial toxicity. All adverse effects were reversible after linezolid discontinuation. CONCLUSIONS: We therefore suggest linezolid/clarithromycin combination as the initial therapeutic strategy for M. chelonae skin infections in immunocompromised patients.

Postprescription review improves in-hospital antibiotic use: a multicenter randomized controlled trial.

Although review of antibiotic therapy is recommended to optimize antibiotic use, physicians do not always perform it. This trial aimed to evaluate the impact of a systematic postprescription review performed by antimicrobial stewardship program (ASP) infectious disease physicians (IDP) on the quality of in-hospital antibiotic use. A multicenter, prospective, randomized, parallel-group trial using the PROBE (Prospective Randomized Open-label Blinded Endpoint) methodology was conducted in eight surgical or medical wards of four hospitals. Two hundred forty-six patients receiving antibiotic therapy prescribed by ward physicians for less than 24 hours were randomized to receive either a systematic review by the ASP IDP at day 1 and days 3 to 4 (intervention group, n = 123) or no systematic review (usual care, n = 123). The primary outcome measure was appropriateness of antimicrobial therapy, a composite score of appropriateness of antibiotic use at days 3 to 4 and appropriate treatment duration, adjudicated by a blinded committee. Analyses were performed on an intention-to-treat basis. In the intervention group, appropriateness of antimicrobial therapy was more frequent (55/123, 44.7% vs. 35/123, 28.5%; odds ratio 2.03, 95% confidence interval 1.20-3.45). Antibiotic treatment duration was lower in the intervention group (median (interquartile range) 7 (3-9) days vs. 10 (7-12) days; p 0.003). ASP IDP counseling to change therapy was more frequent at days 3 to 4 than at day 1 (114/123; 92.7% vs. 24/123; 19.5%, p <0.001). Clinical outcome was similar between groups. This study suggests that a systematic postprescription antibiotic review performed at days 1 and 3 to 4 results in higher quality of antibiotic use and lower antibiotic duration. This trial was registered at ClinicalTrials.gov (NCT01136200).

Dramatic improvement of severe cryptococcosis-induced immune reconstitution syndrome with adalimumab in a renal transplant recipient.

In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.

[Update on infective endocarditis]. / Les actualités dans l'endocardite infectieuse.

Infective endocarditis has continuously evolved since its first clinical description by William Osler in the late 19th century. The epidemiological and microbiological profile of the disease has changed as the result of the progress of the medical care and demographic mutation in industrialized countries. Furthermore, advances in anti-infective therapy and in cardiovascular surgery have contributed to an improvement in the management and the prognosis of this severe infectious disease. During the past decade, the recommendations on antibiotic prophylaxis against infective endocarditis have changed dramatically. Guidelines on management of infective endocarditis and state-of-the-art articles have been published recently and this work aims to outline current recommendations about this evolving disease.

[Autoimmune autonomic ganglionopathy: a case series of six patients and literature review]. / Ganglionopathie autonomique auto-immune : une série de six observations et revue de la littérature.

PURPOSE: Auto-immune autonomic ganglionopathy is a recently described clinical entity within the spectrum of autonomic neuropathies. Patients with auto-immune autonomic ganglionopathy typically present with rapid onset of severe autonomic failure. Acetylcholine receptor ganglionic antibodies, directed against ganglionic synapsis, disrupt synaptic transmission in autonomic ganglia and lead to autonomic failure. These antibodies are specific for auto-immune autonomic ganglionopathy and are present in 50% of patients. METHODS: Descriptive retrospective study. We report six French patients who presented with auto-immune autonomic ganglionopathy diagnosed between 1996 and 2002. RESULTS: Four patients were men and the median age at diagnosis was 45 years. All patients presented with a subacute autonomic failure with constant severe orthostatic hypotension. Serological testing of acetylcholine receptor ganglionic antibodies was performed in four out of the six patients and was found positive in three. All the patients received intravenous immunoglobulin and a clinical improvement was observed in four of them. CONCLUSION: Auto-immune autonomic ganglionopathy is an unusual and overlooked disorder. However, this autonomic neuropathy deserves to be better known as most of the patients respond to immunomodulatory therapy.