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Antimicrobial Agents and Chemotherapy, April 1998, p. 749-754, Vol. 42, No. 4
Department of Medical Microbiology and
Infectious Diseases, University Hospital Rotterdam, Dijkzigt,
Rotterdam, The Netherlands,1 and
Department of Clinical Microbiology, Statens Serum Institut,
Copenhagen, Denmark2
Received 28 January 1997/Returned for modification 27 July
1997/Accepted 23 December 1997
The influence of half-life on the postantibiotic effect (PAE) of
tobramycin against Pseudomonas aeruginosa and
Staphylococcus aureus was investigated during one dosing
interval. Tobramycin half-lives of 0.5 to 2.5 h were simulated in
an in vitro model, and the PAE was determined by an enzymatic
inactivation method at different time points, i.e., when the tobramycin
concentrations were 20×, 5×, and 1× the MIC. At the time point
during therapy when the tobramycin concentrations had declined to 1×
the MIC, at a tobramycin half-life of 0.5 h, the times of the PAEs
were approximately 0.7 and 1.7 h for P. aeruginosa and
S. aureus, respectively, and the PAE disappeared completely
at half-lives corresponding to those found in humans (i.e., 2 to
2.5 h). The PAE itself cannot be fully explained by the presence
of free intrabacterial tobramycin or the emergence of resistant
subpopulations. The explanation for the disappearance of the PAE during
the dosing interval may therefore be explained by the repair of
sublethal damage. Since the standard method of determining the PAE in
animal models is somewhat different from the method used for
measurement of the PAE in vitro, the conditions under which the PAE is
measured in vivo were also simulated in the in vitro model. This
resulted in PAEs longer than those found by the standard method of
obtaining in vitro PAE measurements. We conclude that the PAE of
tobramycin, as determined by conventional in vitro methods, has
virtually no clinical importance. PAEs determined in vivo may have some clinical relevance, but they are probably primarily caused by sub-MIC
effects.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Duration and Clinical Relevance of Postantibiotic
Effect in Relation to the Dosing Interval
*
Corresponding author. Present address: Department of
Internal Medicine, Zuiderziekenhuis, Groene Hilledijk 315, 3075 EA
Rotterdam, The Netherlands. Phone: 31-10-2903000, ext. 109. Fax:
31-10-2903361.
Antimicrobial Agents and Chemotherapy, April 1998, p. 749-754, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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