Norfloxacin binds to human fecal material

Abstract

Earlier studies have reported very high (120 to 2,700 mg/kg) concentrations of norfloxacin in feces after therapeutic doses. MICs for fecal microorganisms are with few exceptions far below these levels. Nevertheless, clinical investigations show that the main part of the aerobic gram-positive and the anaerobic microflora remains unaffected after norfloxacin administration. In Previous studies on the newer quinolones have shown that administration of these agents causes selective ecological disturbances in the gastrointestinal flora (11,20). Several investigations including healthy volunteers as well as different categories of patients on the impact of norfloxacin on the normal gastrointestinal microflora showed uniform results (2, 9, 17, 18). The aerobic gram-negative microorganisms are eliminated or strongly suppressed during administration, while the aerobic gram-positive and the anaerobic microfloras are unaffected. These favorable ecological properties of norfloxacin contribute to a preservation of "colonization resistance" (25) and thus make norfloxacin suitable for long-term prophylactic treatment of urinary tract infections, selective decontamination in immunocompromised patients, and treatment of bacterial intestinal infections.However, very high concentrations of norfloxacin are achieved in feces. Peak fecal concentrations of norfloxacin of 120 to 2,700 mg/kg after therapeutic doses have been reported (5, 9, 18). MICs for both aerobic and anaerobic microorganisms are with few exceptions far below these levels (10,19,22). Thus, despite the high levels of norfloxacin in feces, the main part of the aerobic gram-positive and the anaerobic flora remains unaffected after norfloxacin administration. Different theories have been raised to explain this paradox. Differences in anaerobiosis of the colon environment in vivo compared with the in vitro conditions have been suggested to influence the sensitivity of anaerobic bacteria. An inoculum effect on the activity of norfloxacin has been shown for anaerobic strains (12). At an inoculum of 109 CFU/ml, norfloxacin concentrations greater than 512 ,ug/ ml are required to reduce most gram-positive and gramnegative fecal anaerobes to less than 103 CFU/ml. The third * Corresponding author. theory suggests that there is a binding between norfloxacin and fecal material. Reversible binding to feces has been seen for other antimicrobial agents (13,14). The influence of feces on the antimicrobial activity of norfloxacin has been studied (26), but to our knowledge no study has characterized the binding of quinolones to feces.

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

“…Furthermore, polycations such as poly-myxin-colistin and aminoglycosides bind to DNA, so they are inactivated in the presence of, e.g., pus and cell debris (192,193). Fluoroquinolones also bind to DNA and cell debris (194)(195)(196)(197). In addition, infected areas with poor ventilation may be protected from aerosolized agents.…”

Effect of Parenteral Fluoroquinolone Administration on Persistence of Vancomycin-Resistant Enterococcus faecium in the Mouse Gastrointestinal Tract

“…Fluoroquinolones are actively secreted into the human and rodent intestinal tract, resulting in intestinal concentrations that are typically 100 to 1,000 times higher than serum concentrations after oral or parenteral dosing (12,16). These agents inhibit susceptible facultative gram-negative organisms in the intestinal tract but have much less effect on intestinal anaerobes than would be predicted based on the drug levels achieved (10,17). For example, the MIC at which 90% of isolates are inhibited of ciprofloxacin for Bacteroides species is 1 to 32 g/ml (18), but this agent achieves concentrations of 185 to 2,220 g/g in stool (3,14).…”

“…For example, the MIC at which 90% of isolates are inhibited of ciprofloxacin for Bacteroides species is 1 to 32 g/ml (18), but this agent achieves concentrations of 185 to 2,220 g/g in stool (3,14). The minimal impact of the fluoroquinolone antibiotics on intestinal anaerobes has been attributed to high degrees of reversible binding of these agents to fecal matter, reduced susceptibility of anaerobic bacteria to fluoroquinolones under strictly anaerobic conditions, and an inoculum effect for inhibition of anaerobes (10,17).…”

Susceptibility of anaerobic bacteria isolated from intra-abdominal infections to ofloxacin and interaction of ofloxacin with metronidazole

“…Some studies have suggested that ofloxacin be used for selective decontamination of the gastrointestinal tract in neutropenic patients (1,2,7,13). Even though ofloxacin exhibited moderate activity against many fecal anaerobic bacteria, several studies have noted that ofloxacin did not alter the anaerobic fecal flora in healthy volunteers (7,11).…”