Rapid Emergence of Quinolone Resistance in Cirrhotic Patients Treated with Norfloxacin to Prevent Spontaneous Bacterial Peritonitis

We carried out quantitative culturing of stools from 31 hospitalized alcoholic patients with cirrhosis and ascites, before treatment with 400 mg of norfloxacin per day, weekly for the first month, and then every 2 weeks thereafter for 15 to 229 days (median, 54 days). Members of the family Enterobacteriaceae virtually disappeared from the stools (< 10(2)/g), but treatment had little effect on enterococci. No selection of resistant organisms occurred in 15 patients, but the remaining 16 patients developed fecal organisms resistant to fluoroquinolones between days 14 and 43 of treatment (median, 25 days). Staphylococcus aureus was isolated four times, coagulase-negative Staphylococcus spp. were isolated six times, Citrobacter freundii was isolated four times, Enterobacter cloacae was isolated three times, Klebsiella oxytoca was isolated twice, Proteus rettgeri was isolated once, and untypeable streptococci were isolated six times. Some isolates persisted, while others were transient (one to seven consecutively positive cultures). The MICs of four quinolones (nalidixic acid, norfloxacin, ofloxacin, and ciprofloxacin) were determined by use of experimental microwell strips (ATB CMI; Biomerieux S.A.). All the strains isolated before treatment were susceptible to the four quinolones, with low MICs, whereas those isolated during norfloxacin treatment were highly resistant. Long-term norfloxacin administration thus carries a risk of disturbing the bacterial ecology in these patients, suggesting that digestive decontamination should no longer be prescribed routinely to cirrhotic patients with ascites.