The VADS system approach to pharmacodynamics of sulfonamides

 

In the event that pharmacodynamic relationships have been shown with experimental data generated in domestic species with veterinary pathogens using veterinary-approved antimicrobials, those relationships will be used to generate dose recommendations.  In the absence of that information, data from laboratory animal and human retrospective and prospective studies (including neutropenic models), as well as in vitro models such as time kill studies will be used to extrapolate the relationship.

 

There is a paucity of in vivo data related to the pharmacodynamics of sulfonamides.  It is often stated in review articles that agents that inhibit protein synthesis, such as sulfonamides, most likely require serum concentrations above the MIC for long portions of the dosing interval, but no specifics on percentages have been tested.  In vitro microbiological factors such as the static or cidal nature of antimicrobials are also often used as justification for the importance of T>MIC.  However, the in vitro/in vivo correlation is not 100%, the property may change depending on organism, and the cidal or static nature may not guarantee success. (Pankey 2004)  For example, it has been assumed by clinicians that a cidal drug was required for meningitis, when in fact therapy has been successful with chloramphenicol and tetracycline.  (Pankey 2004)  The presence of a prolonged postantibiotic effect is often used as justification for longer intervals between dosing, but no information could be found on postantibiotic effect and sulfonamides, so it is assumed that there is none. 

 

Drug	Pathogen	Results	RefID
sulfamethoxazole	Dermatophilus congolensis	MBC:MIC=indeterminate, since MIC and MBC of most resistant strain was >64	375

 

Pyrimidine-sulfonamide combinations

 

Drug	Pathogen	Results	RefID
Trimethoprim-sulfamethoxazole	Salmonella spp.	MBC:MIC ≥ 10 for 52% of S. enteritidis, and 12% of S. typhi	8084
Trimethoprim-sulfamethoxazole	Listeria		6840
Trimethoprim-sulfamethoxazole	Listeria	MBC:MIC = 1 (at 48 hrs after inoculation)	8105
Trimethoprim-sulfamethoxazole	Glycopeptide-intermediate Staph. aureus	Possible concentration-dependent action (Cmax important) in vitro time-kill study; 1X MIC bacteriostatic, whereas 9-39 X MIC was bactericidal in 2/3 strains	6841

 

 

For all pathogens treated with sulfonamides, the time that serum concentration of the antimicrobial needs to remain above the MIC of the pathogen will be assumed to be 100% of the dosing interval.