Accuracy of gradient diffusion method for susceptibility testing of dalbavancin and comparators.

OBJECTIVES: This multicenter study aimed to assess the performances of gradient diffusion (GD) method in comparison to broth microdilution (BMD) method for susceptibility testing of dalbavancin, daptomycin, vancomycin, and teicoplanin. METHODS: Minimum Inhibitory Concentrations (MICs) were retrospectively determined concomitantly by BMD and GD methods, for 93 staphylococci and enterococci isolated from clinical samples. BMD was considered as the gold standard. Essential (EA) and categorical agreements (CA) were calculated. Discordant categorical results were categorized as major (ME) and very major errors (VME). RESULTS: EA and CA were 95.7% and 96.8%, 82.8% and 100%, 97.8% and 96.8%, and 94.6% and 95.7% for dalbavancin, daptomycin, vancomycin, and teicoplanin respectively. Concerning dalbavancin, 3 ME without any VME were observed and discrepancies were low (≤ to 2 two-fold dilutions) between both methods. VME were noted in 1 and 3 cases for vancomycin and teicoplanin, respectively, and resulted from 1 two-fold dilution discrepancy in each case. EA was lower for daptomycin. When they were discrepant, BMD MICs were systematically higher than GD ones. Nevertheless, no categorical discrepancy was noted. CONCLUSIONS: GD appears as an acceptable and convenient alternative for dalbavancin, vancomycin, and teicoplanin MICs determination. Our study also emphasizes how achieving accurate daptomycin MICs remains challenging.

Should we reconsider cefazolin for treating staphylococcal meningitis? A retrospective analysis of cefazolin and cloxacillin cerebrospinal fluid levels in patients treated for staphylococcal meningitis.

OBJECTIVES: To assess the meningeal penetration of cefazolin and cloxacillin in individuals treated for methicillin-susceptible staphylococcal meningitis. METHODS: We retrospectively identified individuals treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a validated assay of liquid chromatography coupled with mass spectrometry at the Nantes University Hospital between January 2009 and October 2019. Staphylococcus meningitis was defined by a compatible clinical presentation and a microbiological confirmation (positive CSF culture or positive specific PCR). Medical charts were retrospectively reviewed to collect microbiological and clinical data, and to assess therapeutic success. RESULTS: Among the 17 included individuals, eight (47%) were treated with cefazolin and nine (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 g (range 6-12 g) and 12 g (range 10-13 g), respectively. Cefazolin and cloxacillin were mainly administered by continuous infusion. Eleven individuals (65%) were men, median (interquartile range (IQR)) age was 54 years (50; 70), 14 (82%) had postoperative meningitis and 3 (18%) had haematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 mg/L (2.1; 5.2) and 0.66 mg/L (0.5; 0.9) for cefazolin and cloxacillin groups, respectively. Cloxacillin was discontinued in two individuals for therapeutic failure. CONCLUSIONS: Patients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of cefazolin achieved therapeutic concentrations in CSF. Cefazolin appears to be a therapeutic candidate that should be properly evaluated in this indication.

Multi-sectorial research is paramount for preventing and controlling emerging infectious diseases.

The social, economic and political consequences of emerging infectious disease (EID) may escape the sphere in which they first arise. In recent years, many EIDs have revealed the close links between human, animal and plant health, highlighting the need for multi-scale, multisectorial EID management. Human beings play a dual role in EID because they can promote their development through numerous human-environment interfaces and expanding international trade. On the other hand, their ability to analyze, interpret and act on the determinants of EID allows them to access the expertise necessary to control these EIDs. This expertise must be constantly adapted to remain relevant as the EID evolves, particularly in its virulence or transmission channels. Flexibility should become an inherent part of the expertise-based decision-making process even if it means going backwards. A certain degree of transparency and feedback to citizens is necessary for the acceptability of political decisions basing on expertise. A key step in the management of EID is the appropriate management of the early signal of infectious emergence. This step combines multidisciplinary skills allowing access to the best pathway for containing EID by implementing early countermeasures adapted to the situation. New digital technologies could significantly improve this early detection phase. Finally, experts have a fundamental role to play because they are located at the interface between operational actors and decision-makers, which allows multidirectional feedback, ideally in real time, between professional actors and decision makers. To combat current and future EIDs, expertise should be based on a multi-sectorial approach, promotion of collegiality and continuously adaptation to the evolving nature of EIDs.

[Update on leptospirosis]. / Mise au point sur la leptospirose.

Leptospirosis is a worldwide spirochetal zoonosis whose global incidence is increasing and is probably underestimated. Leptospirosis has long been associated with occupational contact with animals (rats and cattle) and has become in developed countries a pathology more related to recreational activities with exposure to fresh water (canoeing, swimming, canyoning) and to an environment contaminated by urine from leptospires excretory rodents. Leptospirosis should be one of the differential diagnoses to be considered when returning from travel to tropical areas, particularly Southeast Asia, and particularly during the rainy season. The clinical symptoms, particularly in the initial phase, are not specific and can limit to a flu-like syndrome or "dengue-like" making diagnosis often difficult. It is then necessary to look carefully for clinical (muscle pain, cough, conjunctival involvement, jaundice) and biological arguments (thrombocytopenia, cholestasis, rhabdomyolysis, frank elevation of CRP) that will help to diagnose leptospirosis and lead to quick antibiotic therapy before the progression to a severe icterohaemorrhagic (Weil's disease) or respiratory form associated with significant mortality. Treatment is based on injectable beta-lactams in severe forms (mainly cephalosporins) and amoxicillin, doxycycline or azithromycin in non-severe forms. Some atypical or delayed forms of leptospirosis occurring in the late immune phase of the disease are to know. Rapid diagnostic tools are currently being studied to improve diagnosis in remote areas and facilitate access to early treatment.

[Leptospirosis in French Guiana and the Guiana shield: Current knowledge in 2016]. / La leptospirose en Guyane française et sur le bouclier des Guyanes. État des connaissances en 2016.

Leptospirosis is a cosmopolitan zoonosis caused by bacteria of the genus Leptospira. Whether the distribution is worldwide, the hot and humid climate of the tropics is particularly conducive to its expansion. In most French overseas departments and territories, leptospirosis is considered as a public health problem. In French Guiana, a French department located in the northeastern part of the Amazon rainforest, it is supposed to be rare. The objective of this review was to make an inventory of the knowledge on human and animal leptospirosis in French Guiana and neighboring countries. A comprehensive search was conducted through the indexed and informal medical literature in English, French, Spanish and Portuguese. Thus, respectively ten and four publications were identified on human and animal leptospirosis in French Guiana, published between 1940 and 1995 in the form of case reports or case series. The publications concerning this disease in the other countries of the Guiana Shield, eastern Venezuela, Guyana, Suriname, and Brazilian state of Amapá, also scarce or nonexistent. However recent data from the French National Centre of leptospirosis showed a recent and sudden increase in the number of cases in the department, probably partly due to the development of diagnostic tools such as Elisa IgM serology. It is likely that leptospirosis is a neglected disease in the region, due to the lack of diagnostic tools readily available, the lack of knowledge of the local clinicians on this disease and the existence of many other pathogens with similar clinical presentation such as malaria, arboviruses and Q fever and Amazonian toxoplasmosis. The establishment of more large-scale studies on animal and human leptospirosis is necessary and urgent to know the true burden of this disease in our region.