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Question
Could you provide a list of antibiotics that are time-dependent and concentration-dependent, including the new agent
tigecycline? Can tigecycline be administered once daily instead of every 12 hours?
Response From the Expert

Laura S. Lehman, PharmD
Clinical Coordinator, Pharmacy, Carroll Hospital Center, Westminster, Maryland
The pharmacology of antibiotics involves both pharmacokinetic and pharmacodynamic (PD) properties. Pharmacokinetics
pertains to drug concentration and time in the host, while pharmacodynamics describes the concentration- and
time-dependent interactions of antibiotics against pathogens in the host.
[1]
We typically think of 2 major PD categories of
antibiotics: those with time-dependent bactericidal effect and those with concentration-dependent bactericidal effect. However,
a third category has also been described, consisting of antibiotics with both time-dependent and concentration-dependent
effects ( Table ).
[2]
The time-dependent antibiotics exert optimal bactericidal effect when drug concentrations are maintained above the minimum
inhibitory concentration (MIC). Typically, concentrations are maintained at 2 to 4 times the MIC throughout the dosing interval.
[1]
For these agents, higher concentrations do not result in greater kill of organisms. Furthermore, they tend to have minimal to no
postantibiotic effect (PAE).
[2]
Concentration-dependent antibiotics achieve increasing bacterial kill with increasing levels of drug. In addition, these agents
have an associated concentration-dependent PAE in which bactericidal action continues for a period of time after the antibiotic
level falls below the MIC. The peak concentration and area under the concentration curve (AUC) determine efficacy of these
antibiotics.
[2]
For this group of drugs, concentrations of at least 10 times the MIC are needed for optimal bactericidal effect.
[3]
The third PD category consists mainly of bacteriostatic antibiotics that have prolonged PAEs. Some of these agents have
been classified elsewhere as time-dependent;
[1,3]
however, because of the presence of PAE, they also have concentration-
dependent features. Efficacy of this group is determined by the 24-hour AUC to MIC ratio (AUC/MIC).
[2]
From Medscape Pharmacists > Ask the Experts > Pharmacotherapy
Which Antibiotics Are Time- or Concentration-Dependent?
Laura S. Lehman, PharmD
Published: 10/24/2007
Table 1. Antibiotic Pharmacodynamic Categories
[2]
Time-Dependent (with minimal or
no PAE)
Concentration-Dependent
(with PAE)
Time-Dependent, Concentration-Enhanced
(with PAE)
Beta-lactams
Vancomycin
Aminoglycosides
Daptomycin
Fluoroquinolones
Metronidazole
Azithromycin
Ketolides
Clarithromycin
Clindamycin
Erythromycin
Linezolid
Streptogramins
Tetracyclines
Tigecycline
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Tigecycline (Tygacil) is a derivative of minocycline, and it is the first glycylcycline antibiotic. There are currently 2 approved
indications, for complicated skin and soft tissue infections, and for complicated intra-abdominal infections. An off-label use of
tigecycline is the treatment of bronchial secretions in pneumonia.
Tigecycline has a reported mean terminal half-life of 37 to 38 hours.
[4]
Its PD properties have not yet been fully elucidated, but
it appears to have both time- and concentration-dependent characteristics. Its PAE in vivo has been reported as 8.9 hours for
Staphylococcus pneumoniae and 4.9 hours for Escherichia coli.
[5]
Intuitively, on the basis of its long half-life and prolonged
PAE, it seems reasonable to question whether tigecycline could be given less often than twice daily. However, according to
the manufacturer, a study of the drug's serum and intrapulmonary PD effects in 30 healthy subjects supported a twice-daily
regimen for the organisms studied (written communication, Wyeth Pharmaceuticals; August 6, 2007). A literature search
revealed no published studies of daily dosing of tigecycline. Daily dosing cannot be recommended at this time.

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References
Barger A, Fuhst C, Wiedemann B. Pharmacological indices in antibiotic therapy. J Antimicrob Chemother.
2003;52:893-898. Abstract
1.
Levison ME. Pharmacodynamics of antimicrobial drugs. Infect Dis Clin North Am. 2004Sep;18:451-465. 2.
Quintiliani R. Using pharmacodynamic and pharmacokinetic concepts to optimize treatment of infectious diseases.
Infect Med. 2004;21:219-233.
3.
Stein GE, Craing WA. Tigecycline: a critical analysis. Clin Infect Dis. 2006;43:518-524. Abstract 4.
Slover CM, Rodvold KA, Danziger LH. Tigecycline: a novel broad-spectrum antimicrobial. Ann Pharmacother.
2007;41:965-972. Abstract
5.
Authors and Disclosures
Laura S. Lehman, PharmD, Clinical Coordinator, Pharmacy, Carroll Hospital Center, Westminster, Maryland
Disclosure: Laura S. Lehman, PharmD, has disclosed no relevant financial relationships.
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