 |
 |
 |
|
Healthcare-Associated Infections: CAP/VAP/MRSA Marin Kollef, MD Discussion Dr Napolitano: One of the features of broad empiric antimicrobial coverage and then deescalation when we get the cultures back is that we are using more antibiotics for a longer duration with the antibiotics we previously reserved for very ill patients. Is there any negative effect of that? Dr Kollef: Well, there is a negative effect, which is that carbapenem resistance is rising. The issue is: is carbapenem resistance rising because of more carbapenem use or is it because of more use of other agents, such as quinolones and cephalosporins, which are driving things like Klebsiella pneumoniae carbapenemase or other potential carbapenemases? I do not know that anyone really knows the answer to that. But we are seeing more resistance to these drugs. Dr Napolitano: Or is it related to the fact that when we use carbapenems, we are not using extended-infusion dosing? Dr Kollef: It would be interesting to know how many hospitals use a 500-mg dose of meropenem. Dr Karam: David Nicolau has talked about that a lot. David’s work has shown that 500 mg of meropenem every 6 hours is pharmacokinetically and pharmacodynamically the same as 1 g every 8 hours. Dr Kollef: I understand that hospitals always want it because of the cost involved, but my point would be that one should always give the highest dose of the drug, unless there is a toxicity issue. Dr Napolitano: Particularly because the mortality rate in hospital-acquired pneumonia (HAP) and ventilator-acquired pneumonia (VAP) is highest, at 30% to 50%. Dr Karam: They looked at the pharmacokinetics of meropenem 500 mg every 6 hours versus 1 g every 8 hours and said the time under the curve was the same. It is important to note, however that the 500-mg every-6-hour dose has not been studied in the treatment of infections such as HAP and VAP. It was for that reason that the 500-mg dose was not included in the 2005 American Thoracic Society guidelines for HAP/VAP/healthcare-associated pneumonia. Dr Kollef: The problem with those kinds of studies is that they are not clinical. Dr Owens: One aspect of antibiotic stewardship is using the maximum dose that provides the highest time above the minimum inhibitory concentration (MIC) for β-lactams. For meropenem, the 500-mg every-6-hours dose is equivalent, pharmacodynamically, in terms of time above the MIC, to 1 g every 8. We have used even higher doses, or 1 g every 6 in our cystic fibrosis population, and have even employed 2 g every 6, using the highest dose that we possibly can get away with for the higher MIC bugs we see there. Here is where prolonged infusion regimens of short half-life β-lactams are finding a niche. Doubling the dose of the carbapenems is very problematic. One half-life is 45 minutes, thus increasing the dose from 500 mg to 1g gives you 45 minutes of additional time above the MIC. That is not much time. Again, that is why giving these drugs over 3 to 4 hours makes the most sense. If we are going to extend their useful lifetime, that is how we should probably be giving them. We are currently employing this strategy with doripenem at our institution.
|