Breakpoint to MIC quotient: A parameter to rapidly evaluate the in vitro bactericidal activity of ß-lactams on Enterobacteriaceae.

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) do not completely predict the bactericidal nature of the antimicrobial agent. Patients with pathogens having MICs near the clinical breakpoint experience a higher risk of clinical failure. This study defined an indicator, breakpoint to MIC quotient (BMQ), that incorporates MIC and the European Committee on Antimicrobial Susceptibility Testing breakpoint. The BMQ was inversely correlated with MBC in antibiotic combinations against Enterobacteriaceae strains (Spearman coefficient ≤ -0.96). This new parameter may provide timely additional insight for choosing an antibiotic for a severe bacterial infection.

Sequence Variation in Amplification Target Genes and Standards Influences Interlaboratory Comparison of BK Virus DNA Load Measurement.

International guidelines define a BK virus (BKV) load of ≥4 log10 copies/ml as presumptive of BKV-associated nephropathy (BKVN) and a cutoff for therapeutic intervention. To investigate whether BKV DNA loads (BKVL) are comparable between laboratories, 2 panels of 15 and 8 clinical specimens (urine, whole blood, and plasma) harboring different BKV genotypes were distributed to 20 and 27 French hospital centers in 2013 and 2014, respectively. Although 68% of the reported results fell within the acceptable range of the expected result ±0.5 log10, the interlaboratory variation ranged from 1.32 to 5.55 log10. Polymorphisms specific to BKV genotypes II and IV, namely, the number and position of mutations in amplification target genes and/or deletion in standards, arose as major sources of interlaboratory disagreements. The diversity of DNA purification methods also contributed to the interlaboratory variability, in particular for urine samples. Our data strongly suggest that (i) commercial external quality controls for BKVL assessment should include all major BKV genotypes to allow a correct evaluation of BKV assays, and (ii) the BKV sequence of commercial standards should be provided to users to verify the absence of mismatches with the primers and probes of their BKV assays. Finally, the optimization of primer and probe design and standardization of DNA extraction methods may substantially decrease interlaboratory variability and allow interinstitutional studies to define a universal cutoff for presumptive BKVN and, ultimately, ensure adequate patient care.

[A case of dysfibrinogenemia without hemorrhagic diathesis or thromboembolism linked to a new mutation p.H103N in fibrinogen γ chain]. / Un cas de dysfibrinogénémie sans complication hémorragique ni thrombotique lié à une nouvelle mutation p.H103N de la chaîne γ du fibrinogène.

This work describes a dysfibrinogenemia linked to a new mutation in the gene coding for fibrinogen γ chain. Dysfibrinogenemia was fortuitously discovered in a 9-year old boy consulting for symptoms suggesting meningitis. DNA was extracted from blood, the fibrinogen genes coding for Aα, Bß and γ chains were sequenced, and compared with consensus sequences. Apart from the patient, dysfibrinogenemia and the mutation p.H103N in the γ chain of fibrinogen with heterozygous status were found in his mother, without any symptom. This mutation is unknown in fibrinogen variant databases and seems to affect mostly fibrin polymerisation. The reporting of this new p.H103N mutation in the γ chain has a great interest for improving the knowledge of the fibrinogen gene and its expression. Even if no haemorrhage was observed in this case, the expression of this mutation impaired the function of the molecule, particularly polymerisation, and could induce bleeding during an important surgery.