MECANISMOS DE RESISTENCIA DE QUINOLONAS

MECANISMOS DE RESISTENCIA A LAS QUINOLONAS

MECANISMO DE ACCION INGRESO POR PORINAS

SITIO DE ACCION
DNA GIRASA (SUBUNIDAD GRUPO A GRUPO B

TOPOISOMERASA IV SUBUNIDAD GRUPO C GRUPO E

CAMBIOS EN EL SUPERENROLLAMIENTO

MECANISMOS DE RESISTENCIA A LAS QUINOLONAS

MECANISMO DE RESISTENCIA IMPERMEABILIDAD POR ALTERACIN DE UNA PORINA EFLUJO ALTERACIN DEL SITIO DE ACCIN (GIRASA, TOPOISOMERASA) CROMOSOMICAS NO PLASMIDICAS DEPENDE DEL USO DEL ATB

MECANISMOS DE RESISTENCIA A LAS QUINOLONAS

MUTACIONES POR PASOS
1ERA MUTACION R A ACIDO NAL. S A CIPRO FRACASO DE TTO

2DA MUTACION

R ACIDO NAL
R A CIPRO

MECANISMOS DE RESISTENCIA A LAS QUINOLONAS

BACILOS GRAM NEGATIVOS PUNTO DE CORTE ACIDONALIDIXICO SENSIBLE > 19 mm RESISTENTE < 13 mm

PUNTO DE CORTE PARA CIPROFLOXACINO SENSIBLE > 21mm RESISTENTE < 15 mm Criterio farmacocintico NCCLS Disco de acido nalidixico < 13 mm Sensibilidad disminuda a ciprofloxacino

Germany. schmitfj@uni-duesseldorf.de

The quinolones are a potent class of antimicrobial agents that target two essential enzymes of bacterial cells: DNA gyrase and topoisomerase IV. Resistance is mediated chiefly through stepwise mutations in the genes that encode these enzymes, leading to alterations of the target site. These mutations occur in an area called the "quinolone resistance determining region". In gram-positive organisms, mutations occur more often in topoisomerase IV than in DNA gyrase. This target preference appears to depend upon two factors: the species of organism and the selecting drug. Resistance can be enhanced by a decrease in intracellular drug concentration, which is mediated through efflux pumps. The newer generation of fluoroquinolones and non-fluorinated quinolones exhibits enhanced activity against grampositive organisms compared to the older members of this drug class, although development of resistance to these drugs has been demonstrated in vitro. This review gives a chronological perspective of the literature on the action of DNA gyrase and topoisomerase IV and the mechanisms of resistance to quinolones in staphylococci, streptococci and enterococci.

2002 Feb;115:49-54

Related Articles, Links

Nalidixic acid susceptibility test to screen ciprofloxacin resistance in Salmonella typhi. Kapil A, Renuka, Das B. Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.

BACKGROUND & OBJECTIVES: Clinical non response to ciprofloxacin therapy in enteric fever is increasingly being encountered in endemic areas possibly due to the increase in the levels of resistance to ciprofloxacin in Salmonella typhi. The antimicrobial susceptibility tests for S. typhi performed by the disc diffusion method using NCCLS breakpoints fail to detect the increasing MIC of ciprofloxacin, leading to the inappropriate treatment of enteric fever with ciprofloxacin. We explored the possibility of testing S. typhi strains for their susceptibility to nalidixic acid by disc diffusion method as a marker for high MIC to ciprofloxacin. METHODS: Isolates (94) of S. typhi were tested for in vitro susceptibility to nalidixic acid (30 micrograms) and ciprofloxacin (5 micrograms) by disc diffusion method using NCCLS guidelines. The MIC of these strains to ciprofloxacin was also determined by E-test. RESULTS: Of the 94 strains tested, 56 were NARST (nalidixic acid resistant S. typhi) and 34 were NASST (nalidixic acid sensitive S. typhi). MIC of ciprofloxacin in the NASST strains varied from 0.002-0.125 microgram/ml while that for NARST strains varied from 0.023-0.38 microgram/ml, which is about 10-folds higher than that of NASST strains. INTERPRETATION & CONCLUSION: Our study shows that resistance to nalidixic acid is associated with a high MIC to ciprofloxacin in S. typhi. These strains would have been interpreted as ciprofloxacin sensitive by routine antimicrobial susceptibility testing by disc diffusion method. Hence screening of S. typhi isolates by the nalidixic acid susceptibility test may be incorporated in a clinical bacteriology laboratory to alert the treating physicians of