RESUMEN
BACKGROUND: The antihypertensives reserpine and verapamil are also inhibitors of pneumococcal efflux pumps. We addressed the following questions: (i) Do verapamil and reserpine influence the mutation ratio of pneumococci in the presence of ciprofloxacin? (ii) At which concentrations does this occur? (iii) Is this limited to isolates with efflux phenotype? METHODS: 14 clinical isolates, nested in 6 genetically similar clusters, were used, 7 strains with efflux and 7 without. The mutation ratio in the presence of ciprofloxacin (3 × MIC) and increasing concentrations of reserpine and verapamil was determined and the quinolone-resistance determining regions (QRDR) of selected mutants were sequenced. Analysis of the efficacy was performed using a mixed linear model, supported by descriptive statistics. RESULTS: Reserpine and verapamil reduced the mutation ratio of QRDR in the presence of ciprofloxacin with the required concentration for a reduction ≥ 50% of 1mg/l for reserpine and 50mg/l for verapamil. The mutation prevention effect is not limited to, but is more pronounced in efflux positive phenotypes. CONCLUSION: Reserpine and verapamil can prevent the selection of ciprofloxacin resistant isolates by reduction of the mutation ratio, particularly in strain with an efflux phenotype. However, the required concentrations are too toxic for clinical use.
Asunto(s)
Antibacterianos/farmacología , Antihipertensivos/metabolismo , Farmacorresistencia Bacteriana/efectos de los fármacos , Fluoroquinolonas/farmacología , Tasa de Mutación , Streptococcus pneumoniae/efectos de los fármacos , Ciprofloxacina/farmacología , ADN Bacteriano/química , ADN Bacteriano/genética , Humanos , Infecciones Neumocócicas/microbiología , Reserpina/metabolismo , Análisis de Secuencia de ADN , Streptococcus pneumoniae/aislamiento & purificación , Verapamilo/metabolismoRESUMEN
We investigated the usage of fluoroquinolones and the prevalence of fluoroquinolone resistant pneumococci and their precursors (first step mutants and efflux expressing isolates) in patients with community-acquired pneumonia, who were enroled into the German CAPNETZ surveillance study from 2002 to 2006 before the introduction of the pneumococcal conjugate vaccine (n=5780). Thirty-eight percent of all outpatients received fluoroquinolones. Moxifloxacin accounted for 70%, levofloxacin for 19% and ciprofloxacin for 9% of all fluoroquinolone prescriptions. One hundred and sixty-three pneumococcal isolates from 556 patients with pneumococcal pneumonia were analyzed for fluoroquinolone resistance, efflux phenotype, prevalence of mutations within the quinolone-resistance determining regions and clonality. None of the isolates exhibited fluoroquinolone resistance, 1.2% of the isolates contained a first step mutation and 6.7% exhibited an efflux phenotype. There was no clonal relationship among these strains at increased risk for fluoroquinolone resistance. The absence of fluoroquinolone resistance in the context of high fluoroquinolone usage might be explained by the high proportion of third-generation fluoroquinolones with enhanced activity against pneumococci.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/microbiología , Farmacorresistencia Bacteriana , Utilización de Medicamentos/estadística & datos numéricos , Fluoroquinolonas/uso terapéutico , Neumonía Neumocócica/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Comunitarias Adquiridas/epidemiología , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neumonía Neumocócica/epidemiología , Prevalencia , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
Fluoroquinolone resistance in Streptococcus pyogenes has been reported only anecdotally, but a recent Belgian surveillance study found a rate of nonsusceptibility of 5.4%. From an analysis of these isolates, we show that interspecies horizontal gene transfer within the parC quinolone resistance-determining region is a frequent phenomenon that might contribute to fluoroquinolone resistance.