[Paradoxical tuberculosis reaction]. / Réaction paradoxale tuberculeuse.

Paradoxical tuberculosis reaction is defined as the aggravation of lesions present at diagnosis or the development of new lesions under anti-tuberculosis treatment, after exclusion of other alternate causes. It affects 5 to 30% of tuberculosis patients, with a variable prevalence depending on the site of infection and the clinical background. The diagnosis of paradoxical reaction is one of elimination, and requires having ruled out therapeutic failure, notably linked to poor compliance and/or to the presence of mycobacterial antibiotic resistance. The severity of paradoxical tuberculosis reaction lies in its neurological impairment. Despite its clinical importance, the mechanisms involved remain poorly understood and its management is not consensual. Corticosteroids are the cornerstone in the medical management. The role of anti-TNF agents, currently proposed in cases of corticodependence or corticoresistance, remains to be properly defined.

Probenecid, an old ß-lactams pharmacokinetic enhancer for a renewed use: A retrospective study.

BACKGROUND: Optimized antibiotic plasma predictor efficacy is essential in systemic infections. The uricosuric agent probenecid inhibits tubular excretion of antibiotics and may be used as ß-lactam pharmacokinetic enhancer (BLPKE), even though few data are currently available for this purpose. METHODS: We conducted a monocentric and retrospective observational study including all patients who received probenecid in combination with parenteral ß-lactam antibiotics for systemic infections from Jan 1, 2014 to Dec 31, 2019. Demographics, infection characteristics, treatment and ATC (antibiotics trough concentration) were investigated. RESULTS: All in all, 38 patients were included. Eight patients had a history of sickle cell disease. Hyperfiltration (defined as eGFR>130mL/min/1.73m2) was detected in twenty-one patients including six with sickle cell disease. Probenecid (500mg q6h orally) was added to antibiotics for a median (IQR) of 13 days (6.75-21.75), after a median (IQR) time lapse of 7 days (4-16) following the initiation of antibiotics. Probenecid was administered for low antibiotic trough concentration in 29 patients, for increased renal clearance in 5 patients and for persisting fever despite antibiotic therapy in 4 patients (including 1 infective relapse). A second plasma trough concentration, following probenecid administration, was available in 19 patients within a median (IQR) 3 days (2-5). Probenecid induced increased ATC in 18/19 patients (94.7%), with a median (IQR) change of +228.4% (IQR 38.7-633). No major adverse effects were reported. CONCLUSION: Probenecid could be a BLPKE. Our data suggest this drug should be used more often to optimize ß-lactam pharmacokinetics in clinical practice.

Tuberculosis in sickle cell disease patients.

OBJECTIVE: Tuberculosis (TB) disease has rarely been reported in patients with sickle cell disease, but it is associated with an increased risk of bacterial infections. In France, sickle cell disease is frequent in populations with the highest prevalence of TB disease. We aimed to highlight clinical aspects of TB disease in patients with sickle cell disease. PATIENTS AND METHODS: Over a 10-year period, we retrospectively included all adults with sickle cell disease who had a positive culture for Mycobacterium tuberculosis managed in the adult sickle cell center of Henri-Mondor hospital. Sickle cell patients with TB disease were matched for comparison to adults without hemoglobinopathy and with documented TB disease in a 1:2 ratio. Logistic regression mixed models were performed. RESULTS: Twelve patients with sickle cell disease and documented TB disease (median age: 29years; IQR [25-34]) were compared to 24 non-sickle cell patients (median age: 33years; IQR [27.5-38.5]). Baseline characteristics were similar between groups except for sickle cell disease. Ten of the 12 patients with sickle cell disease had pulmonary TB. TB disease characteristics were similar between sickle cell and non-sickle cell patients although sickle cell patients had fewer positive sputum smears for acid-fast bacilli (P=0.003) and fewer lung cavitations (P=0.03). CONCLUSIONS: TB disease in sickle cell patients was globally similar to non-sickle cell patients, even though less infectious. Regular follow-up in specialized centers might allow for earlier TB disease diagnosis in sickle cell patients.

Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series.

BACKGROUND: Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. METHODS: In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. RESULTS: Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N=8), encephalopathy (N=6), cerebrovascular events (ischemic strokes N=4 and vein thromboses N=2), other central nervous system (CNS) disorders (N=4), and Guillain-Barré syndrome (N=2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. CONCLUSIONS: Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a narrative review.

BACKGROUND: Anti-staphylococcal penicillins (ASPs) are recommended as first-line agents in methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Concerns about their safety profile have contributed to the increased use of cefazolin. The comparative clinical effectiveness and safety profile of cefazolin versus ASPs for such infections remain unclear. Furthermore, uncertainty persists concerning the use of cefazolin due to controversies over its efficacy in deep MSSA infections and its possible negative ecological impact. AIMS: The aim of this narrative review was to gather and balance available data on the efficacy and safety of cefazolin versus ASPs in the treatment of MSSA bacteraemia and to discuss the potential negative ecological impact of cefazolin. SOURCES: PubMed and EMBASE electronic databases were searched up to May 2017 to retrieve available studies on the topic. CONTENTS: Although described in vitro and in experimental studies, the clinical relevance of the inoculum effect during cefazolin treatment of deep MSSA infections remains unclear. It appears that there is no significant difference in rate of relapse or mortality between ASPs and cefazolin for the treatment of MSSA bacteraemia but these results should be cautiously interpreted because of the several limitations of the available studies. Compared with cefazolin, there is more frequent discontinuation for adverse effects with ASP use, especially because of cutaneous and renal events. No study has evidenced any change in the gut microbiota after the use of cefazolin. IMPLICATIONS: Based on currently available studies, there are no data that enable a choice to be made of one antibiotic over the other except in patients with allergy or renal impairment. This review points out the need for future prospective studies and randomized controlled trials to better address these questions.