Rapid emergence of quinolone resistance in cirrhotic patients treated with norfloxacin to prevent spontaneous bacterial peritonitis

Abstract

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 (<102/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, KlebsieUla 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.

Prevalência e prognóstico da peritonite bacteriana espontânea: experiência em pacientes internados em um hospital geral de Porto Alegre, RS, Brasil (1991-2000)

“…Por outro lado, quanto à bacteriologia, embora sem haver diferença estatística, houve predomínio de bactérias Gram-positivas, o que vai ao encontro dos trabalhos que referem ser freqüente o surgimento destas no grupo que recebe antibiótico profilático (6,10,11,26,36) .…”

Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures and norfloxacin prophylaxis

“…11 The development of QR-GNB in the feces of cirrhotic patients receiving long-term norfloxacin prophylaxis has been increasingly described. 12,13 Moreover, a high incidence of urinary tract infections caused by QR-GNB in these patients has been reported. 43,46 It is interesting to remark, however, that despite the widespread use of quinolones in cirrhosis, only 3 cases of SBP caused by QR-GNB have so far been reported.…”

“…It is well known that patients submitted to long-term selective intestinal decontamination with norfloxacin develop QR-GNB in the fecal flora. 12,13 However, whether these bacteria are invasive, translocate to the systemic circulation, and produce SBP is not known. This is an important subject because if infections caused by QR-GNB were a frequent event in patients on long-term selective intestinal decontamination, new methods for prophylaxis of bacterial infections in cirrhosis should be developed.…”

Trimethoprim-sulfamethoxazole versus norfloxacin in the prophylaxis of spontaneous bacterial peritonitis in cirrhosis

“…The greatest concern at present is the shifting range of causative agents of SBP and the development of bacterial resistance (6,11,12,13,31,32,33) .…”