Modification of antibiotic dosage with reduced renal or hepatobiliary functionMorrisSystem affectedHepatic function reducedBiliary obstructionRenal function reducedRenal function reducedRenal function reducedRenal function reduced Antibiotic affectedErythromycin, chloramphenicol, metronidazole,c1indamycin, lincomycin Ampicillin, fluoroquinolonesErythromycin, chloramphenicol, doxycyclineMost penicillins and cephalosporins,c1indamycin, lincomycin, trimethorpim,sulphonamides Aminoglycosides, carbenicillin, ticarcillin,vancomycin, metronidazole, fluoroquinolonesTetracyclines, cephaloridine. nitrofurantoin,polymixinEffect on doseReduce doseNormally excreted in the bile,biliary obstruction may reduceaccessto site of infectionGive usual doseConsider minor dose reductionConsider major dose reduction Avoid using these antibiotics Adapted from Prescott
could be metabolized to a different extentthan if given during the active dark phase,leading to differences in antibiotic plasmaconcentrations. This potential for differencesin plasma concentrations and even ineffectivetherapy would be increased if extrapolationof dose quantity or frequency was alsoinaccurate (see section below 'Extrapolationof antibiotic dose information betweenspecies'). In addition, antibacterials thatare eliminated via the kidney may have blood levels that vary depending on thetime of day of administration. For examplesulphonamides given during the active phase in chickens and calves are eliminatedtwice as fast compared to when givenduring the animal's resting phase [Heinze
1992). There is also evidence of strain differences within laboratory specieswith respect to the toxic effects of antibiotics. Tobramycin is more toxic inFischer rats than in Sprague-Dawley rats[Reinhard
et al. 1991).
Many species have adverse reactions to particular antibiotics at doses that arenormally safe therapeutic doses in other species. In rodents and rabbits this is oneof the most important considerations inantibiotic therapeutics (Tables 2 and 3). Itshould be emphasized that the single mostimportant mechanism of antibiotic toxicityin rodents and rabbits is the secondaryeffects from the disruption of the normalenteric flora. In the guinea pig and hamster the specific cause of death is often thetoxin produced by overgrowing
[Richard 1990, Fekety 1986,Manning
1984). In one study inguineapigs, aureomycin caused overgrowthof
which then ledto septicaemia and widely distributednecrotic lesions (Roine et
1953). In therabbit the toxins produced by C.
have been implicated inlincomycin [Rehg
Pakes 1982) andclindamycin (Katz
1978) inducedenteritis.The hamster is particularly sensitive totoxigenic C.
overgrowth caused bya very wide range of antibiotics (Bartlett
1978, Fekety 1986, Fekety
1979) and it has been suggested thattreatment of hamsters with any antibioticsshould be undertaken with caution sincemortality is high (Richard 1990).Tetracycline, metronidazole and to a lesser extent chloramphenicol are relatively poor inducers of enterocolitis in hamsters (seeTable 2) but the high incidence of renaldysfunction in older hamsters (Hubbard &Schmidt 1987) may even make tetracyclineadministration hazardous (see Table 1).Apart from severe enterocolitis caused byother antibiotics even the 'classical' guineapigtoxicity to penicillin most probably is notdue to 'allergy' (Anon 1992). Newborn andgerm-free guineapigs are not susceptibleto penicillin toxicity (Manning
1984), so deaths in normal animals after penicillin may simply be another example