Use of Gentamicin for Sepsis and Septic Shock in Anaesthesia-Intensive Care Unit: A Clinical Practice Evaluation.

OBJECTIVE: Numerous cases of gentamicin underdosing have been described in the literature in the context of sepsis and septic shock in anaesthesia-intensive care units (ICU). A survey of clinical practice was conducted with the aim to rationalise the use of gentamicin in the unit. The secondary objective was to propose a corrective formula for adjusting individual dosage. METHODS: A single-centre survey was used to determine the initial dose of gentamicin administered, in an anaesthesia-ICU, during the first hours of sepsis/septic shock. An initial retrospective phase allowed focusing on the points of improvement in terms of prescription. A second prospective phase enabled the evaluation of benefits following the implemented changes. RESULTS: Fifty-one patients were included during the retrospective phase (2014-2015) and 28 patients during the prospective phase (2016-2017). Out-of-guideline prescriptions significantly decreased between these two study periods (i.e., pulmonary infections decreased from 70.5% to 18%, p<0.001) and the mean±standard deviation administered dosage increased from 7.3±1.2 mg kg-1 to 9.5±1.5 mg kg-1 (p<0.001). Nevertheless, the proportion of Cmax (peak plasma concentration) ≥30 mg L-1 and the mean Cmax did not change significantly. A significant association (p<0.05) was found between Cmax, body mass index, haematocrit and creatinine, enabling a corrective formula to be proposed. CONCLUSION: The present study allowed improvement in gentamicin prescription in an anaesthesia-ICU. A Cmax ≥30 mg L-1 remains difficult to achieve, but a Cmax ≥16 mg L-1 could be considered relevant for community infections and would be more attainable. A corrective formula could be used to adjust the dosage.

A novel multiple locus variable number of tandem repeat (VNTR) analysis (MLVA) method for Propionibacterium acnes.

Propionibacterium acnes plays a central role in the pathogenesis of acne and is responsible for severe opportunistic infections. Numerous typing schemes have been developed that allow the identification of phylotypes, but they are often insufficient to differentiate subtypes. To better understand the genetic diversity of this species and to perform epidemiological analyses, high throughput discriminant genotyping techniques are needed. Here we describe the development of a multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) method. Thirteen VNTRs were identified in the genome of P. acnes and were used to genotype a collection of clinical isolates. In addition, publically available sequencing data for 102 genomes were analyzed in silico, providing an MLVA genotype. The clustering of MLVA data was in perfect congruence with whole genome based clustering. Analysis of the clustered regularly interspaced short palindromic repeat (CRISPR) element uncovered new spacers, a supplementary source of genotypic information. The present MLVA13 scheme and associated internet database represents a first line genotyping assay to investigate large number of isolates. Particular strains may then be submitted to full genome sequencing in order to better analyze their pathogenic potential.

Yersinia pseudotuberculosis ST42 (O:1) Strain Misidentified as Yersinia pestis by Mass Spectrometry Analysis.

We report here the draft sequence of strain CEB14_0017, alias HIAD_DUP, recovered from a human patient and initially identified as Yersinia pestis by mass spectrometry analysis. Genotyping based on tandem repeat polymorphism assigned the strain to Yersinia pseudotuberculosis sequence type 42 (ST42). The total assembly length is 4,894,739 bp.

[Autochtonous hepatitis E, an emerging infection: case report]. / Hépatite E autochtone, une pathologie émergente: à propos d'un cas.

Hepatitis E is rare in France but its increasing frequency makes it an emerging infection. Autochtonous hepatitis E is prevalent, largely confined to older men and currently caused by gentotype 3f. Patients with unexplained hepatitis should be tested by hepatitis E, even in the absence of travel from endemic areas. The diagnosis is based on serological testing (including detection of specific antibodies IgM and IgG, and sometimes by determination of antibody avidity) and nucleic acid amplification techniques which might used first.

False-negative serologies in amebic liver abscess: report of two cases.

Amebiasis, the parasitic disease caused by Entamoeba histolytica, may result in extra-intestinal diseases among which liver abscess is the most common manifestation. We report two cases of amebic liver abscess illustrating the inequal sensitivity of serologic tests detecting anti-amebic antibodies.

Assessment of total- and partial-body irradiation in a baboon model: preliminary results of a kinetic study including clinical, physical, and biological parameters.

This biodosimetry study used irradiated baboons to investigate the efficacy of a kinetic multiparameter (clinical, physical, and biological) approach for discriminating partial-body irradiation (PBI) and total-body irradiation (TBI). Animals were unilaterally (front) exposed to 60Co gamma rays (8 to 32 cGy min) using either TBI or vertical left hemi-body irradiation (HBI), as follows: 2.5 Gy TBI (n = 2), 5 Gy TBI (n = 2), 5 Gy HBI (n = 2), and 10 Gy HBI (n = 2). Midline tissue doses were measured at the anterior iliac crest level with an ionization chamber, and body dosimetry was performed using thermoluminescent dosimeters. Blood samples were collected before exposure and from 1 h until 200 d after irradiation. Clinical status, complete blood cell count, biochemical parameters, and cytogenetic analysis were evaluated. The partial least square discriminant analysis chosen for statistical analysis showed that the four groups of irradiated baboons were clearly separated. However, the dicentric chromosome assay may not distinguish HBI from TBI in confounding situations where equivalent whole-body doses are similar and the time of exposure is sufficient for peripheral blood lymphocyte homogenization. Interestingly, as bone marrow shielding in HBI animals prevented aplasia from happening, hematologic parameters such as the platelet count and Flt-3 ligand level helped to distinguish HBI and TBI. Moreover, the ratio of neutrophil to lymphocyte counts, creatine kinase, and citrulline levels may be discriminating biomarkers of dose or injury. Both early and delayed clinical signs and bioindicators appear to be useful for assessment of heterogeneous irradiation.

Diversity of Acinetobacter baumannii in four French military hospitals, as assessed by multiple locus variable number of tandem repeats analysis.

BACKGROUND: Infections by A. calcoaceticus-A. baumannii (ACB) complex isolates represent a serious threat for wounded and burn patients. Three international multidrug-resistant (MDR) clones (EU clone I-III) are responsible for a large proportion of nosocomial infections with A. baumannii but other emerging strains with high epidemic potential also occur. METHODOLOGY/PRINCIPAL FINDINGS: We automatized a Multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) protocol and used it to investigate the genetic diversity of 136 ACB isolates from four military hospitals and one childrens hospital. Acinetobacter sp other than baumannii isolates represented 22.6% (31/137) with a majority being A. pittii. The genotyping protocol designed for A.baumannii was also efficient to cluster A. pittii isolates. Fifty-five percent of A. baumannii isolates belonged to the two international clones I and II, and we identified new clones which members were found in the different hospitals. Analysis of two CRISPR-cas systems helped define two clonal complexes and provided phylogenetic information to help trace back their emergence. CONCLUSIONS/SIGNIFICANCE: The increasing occurrence of A. baumannii infections in the hospital calls for measures to rapidly characterize the isolates and identify emerging clones. The automatized MLVA protocol can be the instrument for such surveys. In addition, the investigation of CRISPR/cas systems may give important keys to understand the evolution of some highly successful clonal complexes.

[Update on Mycobacterium bovis infections in France: 4 cases reports]. / Actualités de l'infection à Mycobacterium bovis en France : à propos de 4 cas.

Mycobacterium bovis (M. bovis) is a cause of zoonosis. It is rare in developed countries since cattle control. We report four cases of M. bovis infection in people aged more 60 years. They were probably infected during infancy, consuming unpasteurized milk. It is the main transmission mode in developing countries where veterinary controls aren't made. M. bovis infections clinical aspects are varied and treatment is complicated by natural pyrazinamide resistance. Recent diagnostic methods using molecular biology are quick and specific and facilitate identification.

[Acute appendicitis due to both Klebsiella pneumoniae and serotype 35B Streptococcus pneumoniae, an emergent serotype]. / Appendicite aiguë à Klebsiella pneumoniae et Streptococcus pneumoniae de sérotype 35B, un sérotype émergent.

Streptococcus pneumoniae has been rarely considered as an infectious agent in appendicitis. We report a case of a 47-year-old woman with acute appendicitis caused both by serotype 35B S. pneumoniae and Klebsiella pneumoniae. The pathway of the appendix colonisation remains unclear. It could be explain by direct infection via mucosal translocation or by hematogenous spread. Pneumococcal appendicitis could progress to perforation more frequently. The use of intraoperative samples for management of appendicitis is controversial. But, culture with appropriate media is the only mean to isolate bacteria not very often encountered in appendicitis and to identify species of epidemiologic interest as serotype 35B S. pneumoniae, a non vaccinal serotype resistant to penicillin which is considered as a potential emergent pathogen. In the case of S. pneumoniae appendicitis, it could be recommended to take complementary directed samples to understand its pathophysiology.

How to improve the implementation of guidelines on cancer-related thrombosis.

Venous thromboembolism (VTE; defined by deep-vein thrombosis, central venous catheter-related thrombosis or pulmonary embolism) is a major therapeutic issue in cancer patients. VTE is reported in 15-20% of patients with cancer and is an independent prognostic factor and a leading cause of death. In this population, low-molecular-weight heparins have been shown to be superior to vitamin K antagonists. The Italian Association of Medical Oncology, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the French 'Institut National du Cancer', the European Society of Medical Oncology and the American College of Chest Physicians have all published specific guidelines, but their implementation is still low in clinical practice. Methodological assessment of these guidelines was performed using the Appraisal of Guidelines Research & Evaluation Instrument. None of the guidelines on thrombosis and cancer have sought for patients' preferences, nor were they tested among target users. VTE in cancer patients requires a multidisciplinary approach but downstream of the guidelines publication, the potential organisational barriers in applying the recommendations have not been discussed. Tolerance and cost-effectiveness of long-term use of low-molecular-weight heparin may account for the large heterogeneity seen in daily clinical practice. Homogenization of guidelines in international consensus working groups followed by educational and active implementation strategies would be very valuable in order to improve the care of VTE in cancer patients.

Frequency of anticardiolipin, antinuclear and anti beta2GP1 antibodies is not increased in unselected epileptic patients: a case-control study.

UNLABELLED: In order to determine whether auto antibodies were restricted to some subtypes of epilepsy, we included 81 unselected epileptic patients and 81 controls, studied clinical data, EEG, neuroimaging, measured antinuclear (ANA), anticardiolipin (aCL) and beta2GP1 antibodies. RESULTS: Epilepsy was active in 74 patients, generalised in 78 and partial in 9. Auto antibodies were positive at the same frequency and the same level among patients and controls (ANA+ 17% vs. 11%; aCL+ 4% vs. 7%; beta2GP1 antibodies+ 5% vs. 6%). There was no increased frequency of auto antibodies among subgroups of epileptic patients except ANA which were more frequent when patients had more than 10 seizures per year. CONCLUSIONS: Positivity of ANA, aCL and beta2GP1 antibodies is not increased in all types of epilepsy and further studies are needed to determine exactly which kind of seizure is immune-mediated.

Integron-located oxa-32 gene cassette encoding an extended-spectrum variant of OXA-2 beta-lactamase from Pseudomonas aeruginosa.

Pseudomonas aeruginosa clinical isolate CY-1, which was resistant to ceftazidime, harbored a conjugative ca. 250-kb plasmid that contained a class 1 integron with two gene cassettes encoding OXA-32, an OXA-2- type beta-lactamase, and the aminoglycoside acetyltransferase AAC(6')Ib(9). OXA-32 differed from OXA-2 by an Leu169Ile amino acid substitution (class D numbering). Site-directed mutagenesis established that Ile169 is responsible for resistance to ceftazidime but not to cefotaxime.