The History of Penicillin and a new QT Interaction

Just been catching up with Dr. Mark Crislip’s Puscast. Checked out a few of the references he linked to in the most recent one. Not really a reference I suppose, but there is a really interesting read about the history of Penicillin and other antibiotics. Many details you don’t usually hear about. I especially liked their conclusion, basically “look how much work goes into making an antibiotic… now stop wasting them!” The full article is available online here.

Another reference he mentioned is Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation from the Journal of the American College of Cardiology. I recognize one of the authors (Dr. Woosley) as the president of AZCERT, basically the best reference for QT prolongation information, so I’m pretty confident it’s a legit paper. It’s actually a really interesting read - essentially, the authors used advanced data mining techniques to scour databases looking for yet unrecognized drug-drug interactions leading to QT prolongation. They do this using methods like flagging ADR reporting of ADRs that often present alongside QT prolongation. From this data mining, the found the combination of Ceftriaxone and Lansoprazole lead to some pretty serious QT prolonging - especially interesting considering neither drug alone is known to have this effect! They compared against Cefuroxime and Lansoprazole combination and found it had no issues… so presumably it isn’t a class effect. They then validated the results in the lab using patch-clamp electrophysiology, and had results mirroring their data-mining findings.

This interaction could be significant in hospital given that lansprazole is our PPI of choice in tube-feed or crushed med patients, and ceftriaxone is our antibiotic of choice in… well, pretty much anything. That said, most of the patients who will be receiving this combination will be ICU patients, who are the most closely monitored and would be the easiest to spot a QT prolongation on.