mecanismos de resistencia de quinolonas

7/31/2019 Mecanismos de Resistencia de Quinolonas

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MECANISMOS DERESISTENCIA DE

QUINOLONAS


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MECANISMOS DE RESISTENCIA A

LAS QUINOLONAS

MECANISMO DE ACCION

INGRESO POR PORINAS

SITIO DE ACCION

DNA GIRASA (SUBUNIDAD GRUPO A GRUPO

BTOPOISOMERASA IV SUBUNIDAD GRUPO C

GRUPO E

CAMBIOS EN EL SUPERENROLLAMIENTO


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LAS QUINOLONAS

MECANISMO DE RESISTENCIA

IMPERMEABILIDAD POR ALTERACIN DEUNA PORINA

EFLUJO

ALTERACIN DEL SITIO DE ACCIN(GIRASA, TOPOISOMERASA)

CROMOSOMICAS NO PLASMIDICASDEPENDE DEL USO DEL ATB


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LAS QUINOLONASMUTACIONES POR PASOS

1ERA MUTACIONR A ACIDO NAL.

S A CIPRO

FRACASO DE

TTO

2DA MUTACION R ACIDO NAL

R A CIPRO


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LAS QUINOLONASBACILOS GRAM NEGATIVOS

PUNTO DE CORTE ACIDONALIDIXICOSENSIBLE > 19 mm RESISTENTE < 13 mm

PUNTO DE CORTE PARA CIPROFLOXACINO

SENSIBLE > 21mm RESISTENTE < 15 mm

Criterio farmacocintico NCCLS

Disco de acido nalidixico < 13 mm Sensibilidaddisminuda a ci rofloxacino


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. - .

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 thanin 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 gram-

positive 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.


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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 highMIC 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 thenalidixic acid susceptibility test may be incorporated in a clinical bacteriology laboratory to alert the treating physicians of
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubmed&from_uid=12138664http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubmed&from_uid=12138664


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