Antibiotics in vitro : Which properties do we need to consider for optimizing our therapeutic choice? With the support of Wallonie-Bruxelles-International 1-1
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
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
In vitro evaluation of antibiotics : MIC quantitative evaluation 1. inoculation Minimal Inhibitory Concentration Known amount of bacteria 0 0.25 0.5 1.0 2.0 4.0 8.0 16 Increasing antibiotic concentrations 1-4
In vitro evaluation of antibiotics : MIC quantitative evaluation 2. incubation 0 0.25 0.5 1.0 2.0 4.0 8.0 16 MIC = minimal antibiotic concentration able to prevent bacterial growth 1-5
In vitro evaluation of antibiotics : MIC quantitative evaluation 3. interpretation 0 0.25 0.5 1.0 2.0 4.0 8.0 16 The most active is the drug, the smallest is the MIC 1-6
Susceptibilities of bacteria populations : MIC 50 and MIC 90 25 «susceptible» «intermediate» «resistant» 20 % strains 15 10 5 0 0.01 0.02 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 MIC (µg/ml) 1-7
Susceptibilities of bacteria populations : MIC 50 and MIC 90 «susceptible» «intermediate» «resistant» 1-8
Susceptibilities of bacteria populations : MIC 50 and MIC 90 25 20 «susceptible» «intermediate» «resistant» MIC 50 = 0.25 µg/ml MIC 90 = 4 µg/ml % strains 15 10 5 0 0.01 0.02 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 MIC (µg/ml) 51 % 93% 1-9
MIC distributions : unimodal populations 50% 90% 0.03 0.06 012 0.25 0.5 1 2 4 8 MIC (µg/ml) MIC 50 MIC 90 1-10
MIC distributions : unimodal populations 50% 90% But is the same amount of antibiotic needed to eradicate these two bugs? 0.03 0.06 012 0.25 0.5 1 2 4 8 MIC (µg/ml) MIC 50 MIC 90 1-11
MIC distribution : bimodal populations 50% 90% 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 MIC 50 MIC 90 1-12
MIC distribution : bimodal populations 50% 90% And to eradicate those ones? 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 MIC 50 MIC 90 1-13
MIC distribution : bimodal populations 50% 90% 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 MIC 50 MIC 90 1-14
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) 47:228 3-2292 1-15
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) 47:228 3-2292 1-16
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
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
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
But how shall we adapt the dosis to the MIC? Concentration Pharmacokinetics do describe this curve... MIC Section 2 0 6 12 18 24 Time (h) 1-20