Antibiotics in vitro : Which properties do we need to consider for optimizing our therapeutic choice?

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1 Antibiotics in vitro : Which properties do we need to consider for optimizing our therapeutic choice? With the support of Wallonie-Bruxelles-International 1-1

2 In vitro evaluation of antibiotics : the antibiogram semi-quantitative evaluation Disk loaded with antibiotic incubation at 37 C Agar inoculated with bacteria susceptible intermediate resistant 1-2

3 In vitro evaluation of antibiotics : the antibiogram semi-quantitative evaluation Disk loaded with antibiotic incubation at 37 C Agar inoculated with bacteria But where is the limit? But where is the limit? susceptible intermediate resistant 1-3

4 In vitro evaluation of antibiotics : MIC quantitative evaluation 1. inoculation Minimal Inhibitory Concentration Known amount of bacteria Increasing antibiotic concentrations 1-4

5 In vitro evaluation of antibiotics : MIC quantitative evaluation 2. incubation MIC = minimal antibiotic concentration able to prevent bacterial growth 1-5

6 In vitro evaluation of antibiotics : MIC quantitative evaluation 3. interpretation The most active is the drug, the smallest is the MIC 1-6

7 Susceptibilities of bacteria populations : MIC 50 and MIC «susceptible» «intermediate» «resistant» 20 % strains MIC (µg/ml) 1-7

8 Susceptibilities of bacteria populations : MIC 50 and MIC 90 «susceptible» «intermediate» «resistant» 1-8

9 Susceptibilities of bacteria populations : MIC 50 and MIC «susceptible» «intermediate» «resistant» MIC 50 = 0.25 µg/ml MIC 90 = 4 µg/ml % strains MIC (µg/ml) 51 % 93% 1-9

10 MIC distributions : unimodal populations 50% 90% MIC (µg/ml) MIC 50 MIC

11 MIC distributions : unimodal populations 50% 90% But is the same amount of antibiotic needed to eradicate these two bugs? MIC (µg/ml) MIC 50 MIC

12 MIC distribution : bimodal populations 50% 90% MIC 50 MIC

13 MIC distribution : bimodal populations 50% 90% And to eradicate those ones? MIC 50 MIC

14 MIC distribution : bimodal populations 50% 90% MIC 50 MIC

15 bacteriostatic >< bactericidal activity Bacteriostatic : prevents bacterial growth Bactericidal : kills bacteria Telithromycin vs S. aureus Moxifloxacin vs S. aureus MIC Serum peak MIC Serum peak Seral et al, AAC (2003) 47:

16 bacteriostatic >< bactericidal activity Bacteriostatic : prevents bacterial growth Bactericidal : kills bacteria Telithromycin vs S. aureus Moxifloxacin vs S. aureus MIC No bacterial growth Serum peak sterilization MIC Serum peak Seral et al, AAC (2003) 47:

17 bacteriostatic >< bactericidal activity Bacteriostatic : prevents bacterial growth Bactericidal : kills bacteria cooperation with host defences needed able to eradicate infection by itself! Immunosuppressed patients macrolides tetracyclines glycopeptides fluoroquinolones aminoglycosides -lactams 1-17

18 narrow >< broad spectrum Narrow spectrum : active on a small number of bacterial species Broad spectrum : active on a large number of bacterial species Targetted treatment of documented infections Empiric treatment of non documented infections! Risk for selection of resistance some -lactams glycopeptides macrolides aminoglycosides fluoroquinolones tetracyclines sulfamides some -lactams 1-18

19 Conclusions: how to choose an antibiotic on the basis of its microbiological properties? 1. Antibiotic with a spectrum as narrow as possible (depending on the suspected pathogens) 2. Bactericidal antibiotic preferred to bacteriostatic ones 3. Within a family, antibiotic with the lowest MIC of the most probable pathogens 1-19

20 But how shall we adapt the dosis to the MIC? Concentration Pharmacokinetics do describe this curve... MIC Section Time (h) 1-20

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