Drusano GL, Craig WA

Language: Spanish
References: 11
Page: 191-197
PDF size: 62.45 Kb.

ABSTRACT

The pharmacodynamic principles that link the concentrations of antibiotics within body systems and their effects have been elucidated only recently. Animal work, now confirmed by clinical studies, has shown that for β-lactam antibiotics, the time that the serum, concentration exceeds the minimum inhibitory concentration (MIC) value of the pathogen is a key parameter in predicting a successful clinical and bacteriological outcome. The situation with the macrolides is less clear; time above MIC is the dynamic variable likely to be most closely linked to efficacy for erythromycin and clarithromyc1n but for azithromycin it appears to be the area under the plasma concentration-time curve: MIC ratio. Different antibiotics are appropriate for the key pathogens in community-acquired respiratory tract infections. For Streptococcus pneumoniae, amoxycillin/clavulanate is effective with varying dosage regimens providing around 40% time above the MIC,₉₀ in contrast to the oral cephalosporins and the macrolides for which serum concentrations do not exceed the MIC.₉₀ For Haemophilus influenzae, amoxycillin/clavulanate and cefixime are suitable antibiotics whereas macrolides have limited activity. With the exception of amoxycillin, all the β-lactam and macrolide antibiotics reviewed here perform better against Moraxella catarrhalis than against the other two principal community-acquired respiratory tract pathogens and there is a wide choice of appropriate agents. Knowledge of the pharmacodynamically-linked variables for different antibiotics allows optimization of dosage regimens and direct comparisons across agents for the same variables.

REFERENCES

1. Soriano F, García-Corbeira P, Ponte C, Fernández-Roblas R, Gadea 1. Correlation of pharmacodynamic parameter of five b-lactam antibiotics with therapeutic efficacies in an animal model. Antimicrob Agents Chemother 1996; 40: 2686-90.

2. Vogelman B, Gudmundsson S, Leggett J, Tumidge J, Ebert S, Craig WA, Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model J Infect Dis 1988; 158: 831-47.

3. Craig WA. Antimicrobial resistance issues of the future. Diagn Microbiol Infect Dis 1996; 25: 213-7.

4. Walker R, Andes D, Conkin R, Ebert S, Craig W Pharmacodynamic activities of meropenem in an animal infection model. Program and Abstracts of the 34‘ Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, FL p 147, Abstract A91, American Society of Microbiologists, Washington DC, 1994.

5. Craig WA, Andes D. Pharmacokinetics and pharmacodynamics of antibiotics in acute otitis media. Pediatr Infecl Dis J 1996; 15(suppl 3): 255-9.

6. Gerber AU. Role of pharmacokinetics on the outcome of infections. Scand J Infect Dis 1990; 74(suppl): 147-54.

7. Craig WA. Postantibiotic effects and dosing of macrolides, azalides and streptogramins. In: Zinner S, Young L, Acar J eds. New macrolides, azalides and streptogramins in clinical practice (ICMAS III) (in press).

8. Schentag JJ, Smith IL, Swanson DJ, et al, Role of individualization with cefmenoxima. Am J Med 1984; 77(suppl 6a): 43-50.

9. Garrison MW, Malone CL, Eiland JE, Anderson DE. Utilizing an in vitro pharmacodynamic chamber model (PDCM) to assess the influence of pH on the activity of Augmentin (A), Clarithromycin (C), and Clarithromycin plus its 14-OH metabolite (C+OH), versus Haemophilus influenzae. Abstract 1216. European Congress of Clinical Microbiology and Infections Diseases, 1995, Vienna.

10. Schito GC, Mannelli S, Pesce A and the Alexander Project Group. Trends in the activity of macrolide and b-lactam antibiotics and resistance development J Chemother 1997; 9(suppl 3): 18-283.

11. Poulsen RL Knudsen JD, Petersen MB, et al. In vitro activity of six macrolides, clindamycin and tetracycline on Streptococcus pneumoniae with different penicillin susceptibilities. APMIS 1996; 104: 227-33.