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.

Invasive group B streptococcal infections in adults, France (2007-2010).

Group B streptococcus (GBS) has emerged as an important cause of invasive infection in adults. Here, we report the clinical and microbiological characteristics of 401 non-redundant GBS strains causing adult invasive infections collected during a 4-year period (2007-2010). Bacteraemia without focus (43.4%) and bone and joint infections (18.7%) were the main clinical manifestations. The distribution of capsular polysaccharide (CPS) type showed that types Ia, III, and V accounted for 71.8% of all strains. Resistance to erythromycin increased from 20.2% in 2007 to 35.3% in 2010, and was mainly associated with CPS type V harbouring the erm(B) resistant determinant.

The adhesive property of the type IV pilus-associated component PilC1 of pathogenic Neisseria is supported by the conformational structure of the N-terminal part of the molecule.

Neisserial PilC proteins are key elements in type IV pili biogenesis and adhesion. Two pilC alleles are usually present in Neisseria meningitidis. At least one of the PilC proteins is required for pilus assembly and competence for transformation. In addition, meningococcal PilC1, but not PilC2, modulates adhesiveness, whereas, in N. gonorrhoeae, both alleles are adhesive. The meningococcal pilC genes are differently regulated, and it was shown that the expression of pilC1, but not that of pilC2, is transiently induced by bacteria-cell contact. The aim of this work was to determine whether, besides regulation, PilC1-mediated adhesion was conferred by some specific protein pattern not present in the meningococcal PilC2 protein. We demonstrate first that differences within the primary sequence of the meningococcal PilC1 and PilC2 are responsible for different adhesion phenotypes, thus eliminating the regulation of transcription being solely responsible for the adhesive phenotype of PilC1. To identify the regions of PilC1 responsible for adhesion, we engineered meningococcal strains expressing various PilC1-PilC2 hybrids at the pilC1 locus. Our data demonstrate that the specific PilC1 adhesion-promoting regions are located in the amino-terminal part of the molecule and that several domains within this region probably interact with each other to promote adhesion to human cells.

Pilus-mediated adhesion of Neisseria meningitidis: the essential role of cell contact-dependent transcriptional upregulation of the PilC1 protein.

Pilus-mediated adherence makes an essential contribution to the pathogenesis of Neisseria meningitidis by allowing the initial localized adherence. Pili are assembled from a protein subunit called pilin. Two proteins, PilC1 and PilC2, are also key elements in the formation of pili as the production of at least one PilC protein is required for pilus assembly. In addition, PilC1 but not PilC2 modulates adhesiveness, most probably by being the adhesin. Recently, both genes have been demonstrated to be controlled by different promoters, pilC2 is expressed from a single transcription starting point (TSP), whereas pilC1 has three TSPs. One of these, PC1.1, corresponds to the unique TSP of pilC2, and two others, PC1.2 and PC1.3, are located in a region upstream of pilC1 but not pilC2. This suggests that both genes may be under the control of separate regulatory pathways. In this work, by engineering pilC1-lacZ and pilC2-lacZ transcriptional fusions, we provide evidence that expression of pilC1, but not that of pilC2, is transiently induced by bacterial cell contact. This induction required viable cells, did not need the presence of pili and relied on the expression of pilC1 from PC1.3. Destruction of this TSP by site-directed mutagenesis did not significantly diminish the piliation level or the basal expression of PilC1, but led to the loss of cell contact-dependent upregulation of pilC1 and to a dramatic decrease in bacterial adhesiveness. Taken together, these data demonstrate that cell contact-dependent upregulation of the transcription of pilC1 at PC1.3 is essential for meningococcal pilus-mediated adhesion.

Improved fluorometric determination of malonaldehyde.

Lipoperoxidation is implicated in various pathological conditions. Malonaldehyde (MDA) is the most commonly used marker of this process. We propose simple modifications to Yagi's fluorometric assay for MDA determinations, to avoid long and tedious manipulations by eliminating the first precipitation and washing steps, analogous to HPLC methods, and to increase both the sensitivity and the specificity of the assay by measuring synchronous fluorescence. The proposed technique is easier, faster, and more sensitive than Yagi's method (Academic Press, 1982: Lipid peroxides in biology and medicine). The results obtained with the novel method correlate with those from the HPLC method described by Therasse and Lemonnier (J Chromatogr Biomed Appl 1987;413:237-41).