Antibiotic stewardship, and procalcitonin in Covid

 an effective and generalizable/scalable antibiotic stewardship program has been developed by the Agency for Healthcare Research and Quality Safety Program for decreasing antibiotic usage (see antibiotic stewardship program jama2021 in dropbox, or doi:10.1001/jamanetworkopen.2021.0235). 

Details:

--437 hospitals enrolled in the program, with 402 (92%) remaining in the program for the full year

    --28 academic medical center, 122 midlevel teaching hospitals, 167 community hospitals, and 85 critical access hospitals

    --43% of the hospitals did not have access to infectious disease (ID) specialists

--intervention: all clinical staff (clinicians, pharmacists, nurses) were encouraged to participate in 17 webinars over 12 months on antibiotic prescribing, along with some additional durable educational content (commitment posters, computer desktop backgrounds, pocket cards). topics of the webinars included antibiotic stewardship programs, science of safety, improving teamwork and communication, and best practices for the diagnosis and management of infectious processes

    --11,650 unique users participated in this program

--this was a quality Improvement (QI) initiative, not a randomized controlled trial, but they did compare antibiotic prescriptions with concurrent data from 614 nonparticipating hospitals in the Premier Healthcare Database, which has info on drug use in 1/4 of hospitalizations in the US

--sites were requested to complete and upload 10 Team Antibiotic Review Forms (TARFs) per month

--teams could access the AHRQ group to answer questions, and there were bimonthly office hours and availability to email the AHRQ group

--primary outcome: overall antibiotic use: days of antibiotic therapy (DOT) per 1000 patient days, from Jan-Feb 2018 until Nov-Dec 2018

--secondary outcome: quarterly hospital data on laboratory-documented C difficile infections per 10,000 patient days

--there was also a subgroup analysis of changes in fluoroquinolone prescribing

Results:

--91% of participants felt the content of the webinars was "excellent"

--adherence to key components of the antibiotic stewardship program improved from 8% to 74% over the 1-year period, p<0.01

--Antibiotic use decreased from 900.7 to 870.4 DOTs per 1000 patient-days (1000 PDs), a reduction of 30.3 DOT per 1000 PDs (-52.6 to -8.0), p=0.008

    --the largest decrease was in the first few months after the initiative started, but then was sustained for the remainder (!!!)

-- Premier Healthcare Database:

    -- nonsignificant decrease of 9.0 DOT per 1000 PD (-44.4 to 26.4), not statistically significant

    -- compared with the Jan-Feb decrease in the antibiotic stewardship programs (ASPs), the time period with the biggest change: antibiotic use increased in Premier data set from 648 to 660 DOT per 1000 PD

--fluoroquinolone use decreased from 105.0 to 84.6 DOT per 1000 PD, a decrease of 20.4 DOT (-25.4 to -15.5), p=0.009 (!!!)

--incidence in hospital-onset C. diff infections: decreased 19.5% (-33.5% to -2.4%), p=0.03 (!!!)

--decreases in DOT tracked with level of engagement with the program:

    --those completing <10 TARFs/month: decrease from 861 to 845 DOT per 1000 PD, decrease of 15.6 DOT

    --those averaging >10 TARFs/month: decrease from 912 to 877 DOT per 1000 PD, decrease of 34.2 DOT

Commentary:

--this study was really different from most prior approaches, which (to my knowledge) tended to focus on aggressive intra-hospital restrictions on prescribing certain antibiotics (eg see http://gmodestmedblogs.blogspot.com/2017/06/decreasing-antibiotic-resistance-by.html ), vs the current approach, a much larger-scale one which seemed to be minimally invasive and focused on education of prescribers

    --and, in this study a large number of hospitals were under-resourced: 41% with <100 beds, 43% had no access to ID specialists, 35% rural

--another study of other 549 hospitals focusing on fluoroquinolone prescribing reduction found that a 20% decrease, associated with an 8% decrease in C diff infections

--there was some concern in this AHRQ study that there were secular trends to decrease antibiotic prescribing during this time-period, resulting from the pretty aggressive identification of antibiotic overprescribing and antimicrobial resistance, microbiome changes, etc. But the analysis of 300 US hospitals using the Premier Healthcare Database from 2016-7 of 576 US hospitals did not find any significant difference in antibiotic prescribing from a decade earlier 

--it was impressive that there was both such a high uptake in clinical involvement and that this did not wane over the course of the 1-year study

Limitations:

--this was a quality improvement (QI) initiative, and not an RCT, so they did not have a control group and they did not have aggressive data collection and accuracy assessment (too onerous for a large, diverse study as this, with some very small hospitals likely without the resources for this type of data collection)

--this was a short-term study, 1 year. it would be important to know long-term data/sustainability of this QI initiative. one might expect that a year's worth of behavior change in prescribing would translate into long-term changes, but it would be important to know if this is true or if there needs to be occasional retunings.

--it would be useful to have a breakdown in the changes in antibiotic prescribing: was it solely in areas of unnecessary antibiotic prescribing (acute URIs, bronchitis, rhinosinusitis, etc), or were antibiotics actually withheld where they should have been prescribed??

--this QI initiative, as a publicly funded initiative, is available on-line (see below). it would be useful to know how often the direct access to AHRQ staff was emailed, or office hours utilized. Would access to the webinars, etc be sufficient to set up a successful program? Would there be help in under-resourced hospitals? would there be continued access to the AHRQ staff? Is there enough publicization of their quite impressive results that other hospitals might get involved?

--lots of inappropriate antibiotic prescribing happens in the outpatient setting. is this QI program useful for health centers and other outpatient sites?

so, this is a really impressive initiative with quite profound results, both in apparent decreases in antibiotic prescribing as well as the clear clinical outcome of decreased C diff infections. a few further comments:

--this approach has the huge advantage of being an inexpensive and widely applicable program to many different hospital settings, with and without infectious disease specialists in their mix,   ...

--the approach overall is not a top-down one, but one that releases the initiatives of those of us doing clinical care (ie, having us immersed in the program from the beginning as self-stewards and not being brow-beaten/having to call or be micromanaged by a hospital point person whenever we want to prescribe antibiotics or a selected group of antibiotics...)

--this Safety Program is now publicly available as part of the AHRQ Toolkit for improving Antibiotic Use (see https://www.ahrq.gov/antibiotic-use/acute-care/index.html ), including all webinars, slide sets, and detailed script material

--it was impressive/important that 92% of hospitals volunteering to participate in this program continued it for the whole year, and that their huge successes in the first couple of months persisted for the whole year.

--and it seems likely that the program is appropriate/useful in the outpatient setting.

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other recent info useful in decreasing the use of powerful antibiotics: 

--COVID: in a retrospective cohort study in New York (2443 patients, of whom 148 had bacterial coinfections), procalcitonin levels in patients with Covid-19 were higher in those with community-acquired bacterial infections (though this was not so clinically useful), but there was a pretty high negative predictive value, with a procalcitonin cutpoint of 0.25 or 0.50 ng/ml: 0.95 for bacteriuria, bacteremia, and bacterial pneumonia infections (see covid procalc for bact infec AnitmicAgents and CTX2021 in dropbox, or DOI: 10.1128/AAC.02167-20). so, lots of patients can forgo antibiotics with normal procalcitonin levels, assuming there can be adequate followup. and labs in outpatient settings may well have access to stat procalcitonin testing

--diverticulitis treatment: another recent article finding that amoxacillin/clavulanate was as good as metronidazole/fluroquinolones, and with less associated C. diff (see http://gmodestmedblogs.blogspot.com/2021/03/diverticulitis-rx-amoxacillinclavulanate.html )

--another recent one finding that short-course antibiotics for community-acquired pneumonia  (5 days of amoxacillin vs 10 days in 281 children aged 6 months to 10 years) had equivalent outcomes at 14 and 21 days after treatment (see pneumonia kids short course abx jamapeds2021 in dropbox, or doi:10.1001/jamapediatrics.2020.6735). similarly for strep (see  http://gmodestmedblogs.blogspot.com/2019/10/short-course-penicillin-for-strep.html )

--and an interesting argument that for most infections now, it may not be necessary to complete a full course of therapy, likely decreasing antibiotic resistance (see http://gmodestmedblogs.blogspot.com/2017/07/take-full-course-of-antibiotics.html)

geoff

 

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