Expert rules for aminoglycosides, macrolides and lincosamides

Abstract number: 1732_253

Leclercq R.

Resistance to aminoglycosides is mostly related to production of modifying enzymes, phosphorylases, nucleotidyltransferases or acetyltransferases. The enzymes vary in their substrate ranges which are often broad and each enzyme is characterised by a particular profile of resistance which allows its putative identification from the conferred phenotype. The enzymes from Gram-positive cocci generally differ from the enzymes detected in Gram-negative bacteria. Generally, the presence of an enzyme confers to the host frank resistance to the antibiotics modified in vitro. However, there are some exceptions, both in Gram-negative and in Gram-positive bacteria. For instance, resistance of Gram-positive organisms to the kanamycin–neomycin group of antibiotics is due to the synthesis of an APH(3')-III enzyme. The enzyme catalyzes efficient phosphorylation of amikacin in cell-free extracts but does not always determine resistance to this antibiotic. However, bactericidal synergism of amikacin with b-lactams or vancomycin is always abolished. Therefore, the test of kanamycin better predicts the activity of amikacin against Gram-positive organisms. In this case and several others, interpretive reading of susceptibility tests based on identification of resistance phenotypes may help to identify impaired activity of aminoglycosides.

Interpretive reading may also allow to identify some pitfalls in the detection of resistance to macrolide and lincosamide antibiotics. Staphylococci may be resistant to macrolides by production of a ribosomal methylase encoded by erm genes conferring the MLSB phenotype or by production of an efflux pump encoded by the msr(A) gene. In case of inducible MLSB resistance, clindamycin that is not an inducer remains active. However, constitutively resistant mutants can be selected by clindamycin and clinical failure during treatment by clindamycin have been reported in a few occasions. The use of clindamycin is probably best avoided in severe infections or infections with heavy bacterial inocula. In case of resistance by efflux, clindamycin is not substrate for the pump and the risk for selection of resistant mutants is not greater than that for erythromycin-susceptible isolates. By a disk diffusion test, the inducible MLSB phenotype can be identified by the flattening of the clindamycin zone facing the erythromycin disk.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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