Caracterización y seguimiento de la resistencia a linezolid en staphylococcus epidermidis en la unidad de cuidados intensivos del Hospital Clínico San Carlos tras la descripción del primer brote de staphylococcus aureus linezolid resistente

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Universidad Complutense de Madrid
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Linezolid is an oxazolidinone with antimicrobial activity against resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycinresistant enterococci, and Streptococcus species. The drug binds to domain V of the 23S ribosomal RNA (rRNA) of the 50S subunit of bacterial ribosomes, thus inhibiting protein synthesis. Three classes of oxazolidinone resistance mechanisms have been previously characterized: mutations in the domain V region of 23S rRNA genes, acquisition of the ribosomal methyltransferase gene cfr, and mutations in the rplD and rplC gene encoding the 50S ribosomal protein L4 and L3 respectively. The first reports of bacteria resistant to linezolid showed the presence of point mutations at the drug target site. The most frequent mutation is G2576T although other mutations have been found in clinical isolates and in vitro indicating that resistance was apparently generated de novo through spontaneous mutations rather than genetic exchange. Resistance develops slowly, because nearly all bacteria possess multiple copies of the 23S rRNA gene (S. aureus strains have 5 or 6 operons encoding 23S rRNA) and it is not transmisible between species. Subsequently, a new mechanism of linezolid resistance was reported in veterinary staphylococcal isolates. The mechanism is nonmutational and involves acquisition of a natural resistance gene, cfr (chloramphenicol-florfenicol resistance). The cfr gene was initially described in a bovine Staphylococcus sciuri isolate. It has been found primarily in plasmids and appears to be capable of horizontal transfer between staphylococci. The cfr gene, encodes methyltransferase, which induces posttranscriptional methylation of 23S rRNA at position A2503, thus affecting the binding of at least four antimicrobial classes of drugs (phenicols, lincosamides, pleuromutilins, and streptogramin A), conferring multidrug-resistant phenotype. In human isolates, the gene was located in the chromosome, unlike the animal isolates, but it was probably part of an integrated plasmid that was potentially capable of excision and mobilization. Therefore, the gene could be transmitted to other pathogenic strains and spread quickly...
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Medicina, leída el 25/01/2016