Episode 50- Public service announcement: Don’t forget to redose your antibiotics!

Hello and welcome to Episode 50 of ER-Rx. In this week’s Fresh Fruit series, we review a study showing the importance of giving that second antibiotic dose in a timely manner to patients that are in your ER. This study is entitled “Delays in antibiotic redosing: association with inpatient mortality and risk factors for delay.” This article was published in the American Journal of Emergency Medicine on March 1st of 2021.

We all know the strong emphasis that multiple quality control guidelines put on timely antibiotic administration. The most common example of this is in the setting of severe sepsis and septic shock. Timely antibiotic administration has also been recommended in the settings of neutropenic fever, bacteremia, and meningitis. Largely, the focus has been on time to initial antibiotic, but the second and subsequent doses have received little attention. Given increased ER boarding, busier ERs overall, and frequent transitions of care between ER and admitting services, it can be very hard to ensure subsequent antibiotic doses are given on time- sometimes it’s hard enough to ensure that they are ordered and given at all.

The authors of this trial attempted to add to the relatively small amount of published literature on this topic (there are only two other smaller studies addressing this). They sought to use larger, more diverse patients to determine if there was a link between time to second antibiotic dose administration and in-hospital mortality.

This was a retrospective study of patients in the ER across five hospitals within a single healthcare system during the year 2018. They included patients who received 2 or more doses of the same IV antibiotic, the first of which had to have been given in the ER. They included patients with antibiotic indications of severe sepsis and neutropenic fever along with respiratory, urinary, intra-abdominal, bone/joint, CNS, and skin infections. They excluded patients with end-stage renal disease, cirrhosis, or those patients with extremes of weight (BMI > 40 kg/m2, weight > 120 kg, weight < 40 kg) given the fact that these criteria impact pharmacokinetics/ pharmacodynamics and don’t have standardized dosing frequency recommendations.

Their analysis included 4904 ER visits, the mean patient age was ~62 years, and ~50% were male. The most common antibiotic indication was respiratory tract infections (35%) followed by abdomen/pelvic infections (23.5%), sepsis/septic shock (13.9%) and urinary tract infections (13.4%). Of the 4904 visits, 21% had a delay in the second antibiotic dose administered greater than 25% of the recommended frequency. This means that if a drug was to be given every 6 hours, the second dose was given more than 1.5 hours late. If it was an every 24-hour drug, it was given more than 6 hours late, and so on.

They found that delay in receiving the second antibiotic dose was associated with a significantly increased risk of mortality (OR 1.51, 95% CI 1.06-2.15, P= 0.022). This remained true even after adjusting for patients who were boarders in the ER- which has been shown to increase the risk of mortality by itself in previous studies (but not this study).

Secondary analysis showed that shorter antibiotic redosing frequencies were a risk factor for delayed administration, with 4-hour intervals showing only 25% compliance, and 24-hour intervals showing 100% compliance. This isn’t very surprising. The longer the re-dosing interval, the more time the ER and admitting teams and the clinical pharmacists have to recognize the antibiotic needs to be re-dosed. They also found that boarders (OR 1.47, 95% CI 1.27-1.71, P <0.0001), higher acuity presentations (OR 1.54, 95% CI 1.30-1.81, P <0.0001), and patients with multiple medical comorbidities (OR 1.84, 95% CI 1.36-2.51, P <0.001) had a higher risk for antibiotic delays. They found that 16% (n= 932) of the second antibiotic doses were due prior to the patient being admitted- meaning in the ER we have a fantastic opportunity to prevent these mistakes from happening.

They also found that using standing antibiotic orders with redosing intervals was not more effective in promoting compliance than just one-time orders- meaning that resolving this issue will take more than just standardizing hospitals to use a standing antibiotic order for all doses given in the ER.

In conclusion, this study showed that a delay in getting the second antibiotic dose was associated with a higher risk of mortality. Predictors of delay included boarding status, higher acuity, and using antibiotics with more frequent dosing intervals.

I was disappointed, but not overly surprised that this study didn’t mention the pharmacist role in these situations. At my site, we have a relatively simple solution to this problem. Every time a one-time dose of an antibiotic is ordered, the pharmacist enters a “pharmacist alert intermittent dosing” reminder order in EPIC and leaves it unverified. In the comments of this order, we write which antibiotic was given and when. Given that all of our ER orders are STAT, this reminder order stays on top of the verification queue and reminds other pharmacists that this patient got an antibiotic in the ER at a certain time and to ensure subsequent doses are ordered. If they aren’t ordered by the time the next dose is due, it’s the pharmacists’ responsibility to call the admitting team to ask if they want antibiotics to continue. At this time, the standing antibiotic order can be entered and the reminder can be discontinued. We also use this reminder order for any intermittent orders that are due within 24 hours- including not only antibiotics but for example twice daily proton pump inhibitor orders for GI bleeders. I would recommend that your ER implements a similar order, which will greatly reduce the risk of missing or delaying subsequent antibiotic doses. Feel free to reach out to me on errxpodcast.com if you want an example of this reminder order.

As always, thank you so much for your time. We are nearing the 52nd episode of ER-Rx and our one-year anniversary. To celebrate, we’ll be doing another small prize giveaway. To enter, simply leave a review of the podcast on Apple Podcasts, then send me a message on errxpodcast.com with your review and email address.