Time above MIC for AUC/MIC drug?

[Community managerKeymaster 18 July 2018 at 8:57 am Post count: 23]

#2650 |

In our recent webinar titled “PK-PD in support of accelerated programmes for antimicrobial development: how much is enough?” with William Hope, we received more questions from the audience than we could answer during the session. We will now follow up on some remaining questions in the forum and encourage our experts but also users to discuss these questions.

Please see find a recording of this webinar here.

One webinar participant asked: For an AUC/MIC drug, is there also a need to have some time above the MIC? Thinking about tigecycline which has blood levels below the breakpoint.

[Ursula TheuretzbacherExpert 18 July 2018 at 9:14 am Post count: 10]

#2651

Tigecycline is a specific example as its AUC is quite low due to a low dosage that is limited by adverse events. Randomized clinical trials with tigecyclin have been mainly undertaken in mild to moderate infections. In community acquired pneumonia there was no clear correlation between AUC/MIC and clinical cure. A correlation could only be found for time to fever resolution. For highly resistant Gram-negative bacteria the dosage is probably too low to be clinically effective. As the time above MIC is not correlated with outcome in non-clinical PK/PD models the relevant question is focused on the required AUC/MIC. Can it be achieved in the target patient population (In clinical practice: severely sick patients and extensively drug resistant Gram-negative bacteria) with the currently approved dosage. This may not be the case in many patients.

[François FranceschiExpert 30 July 2018 at 7:50 am Post count: 7]

#2701

As pointed above, the main problem here is that the therapeutic window does not allow for much higher doses.

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