Comparative and Veterinary Pharmacology

Table 1

Relationship between drug, drug effects, and the PD surrogate most closely aligned to its clinical response (Martinez et al.

2006

; Chambers

2006

;

Steenbergen et al.

2005

; Safdar et al.

2004

)

Mechanism of action

Drug

Activity

Bacterial effect

Duration ofin vitro PAE

PDparameter

Agents affecting the function

of 30s and 50s ribosomalunits, resulting in areversible inhibition ofprotein synthesis (andtherefore generally arebacteriostatic)

Macrolide

StaticStatic and cidal (e.g. cidal

for

S. pneumoniae

,

S. pyogenes

)

Time-dependent

Erythromycin, etc.

Brief

a

T

>

MIC

Azalide

Prolonged

AUC

24

/

MIC

Lincosamides(Clindamycin)

Brief

AUC

24

/

MIC

Ketolide(Telithromycin)

Prolonged

AUC

24

/

MIC

ChloramphenicolFlorfenicolThiamphenicol

Primarily bacteriostatic,

but cidal against somepathogens. Exhibitboth Gram+ andGram– activity

Time-dependent

?

T>

MIC

TetracyclinesTraditional (e.g.

Chlortetracycline)

Static

Time-dependent

Prolonged

AUC

24

/

MIC

Atypical (e.g. Chelocardin and

Anhydrochlortetracycline)

Cidal

Time-dependent

Prolonged

AUC

24

/

MIC

Inhibition of cell wall

synthesis

Beta-LactamPenicillinCarbapenemMonobactams

Cidal

Time-dependent

Gm(–) none or

brief

Gm(+) may be

prolonged

T>

MIC

Glycopeptides(e.g. Vancomycin, Teicoplanin,

Bloodying )

Cidal (slower than beta

lactams)

Time-dependent

Prolonged

AUC

24

/

MIC

Agents that bind to the 30s

ribosomal subunit, inhibitingbacterial protein synthesis,leading to aberrant proteinsand eventually cell death

Aminoglycoside(e.g. Gentamicin andTobramycin)

Primarily cidal

Concentration-

dependent

Prolonged

AUC

24

/

MIC

Cmax

/ MIC

(continued

)

Antimicrobial Drug Resistance 231