Binding to and antibacterial effect of aztreonam, temocillin, gentamicin and tobramycin on human faeces

Hazenberg, M. P.; Pennock-Schröder, A.M.; Merwe, J. P. van de

doi:10.1017/s0022172400062689

Cited by 11 publications

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References 18 publications

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“…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.…”

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Norfloxacin binds to human fecal material

Edlund

Lindqvist

Nord

1988

Antimicrob Agents Chemother

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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.

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confidence: 99%