In this episode, I’ll discuss antibiotic exposure and the emergence of multidrug-resistant bacteria in patients with liver cirrhosis.
Patients with advanced chronic liver disease and acute-on-chronic liver failure often have indications for antibiotic use, however this increases the risk of developing an infection with a multi-drug resistant organism (MDRO). But how much antibiotic use is too much? Is there a threshold where risk increases? That is what a group of authors sought to determine and they recently published their findings in Clinical Infectious Diseases.
The authors prospectively looked at 256 consecutive patients with advanced chronic liver disease at a single center and measured antibiotic exposure using defined daily doses (DDD) and antibiotic use density (AUD).
Almost all patients did not have a history of MDRO at admission but the authors found that acquisition of vancomycin-resistant enterococci (VRE) or Gram-negative MDR was strongly associated with cumulative antibiotic exposure.
The risk of a patient in this cohort acquiring VRE reached 20% once they were exposed to about 10 cumulative defined daily doses of any antibiotic. These thresholds dropped if the patients were exposed to β-lactam/β-lactamase inhibitor combinations, carbapenems, and glycopeptides.
De novo MDRO detection during follow-up, but not at baseline, was independently associated with increased 180-day mortality with a hazard ratio of 2.15.
The authors concluded:
In advanced cirrhosis, MDRO emergence is associated with cumulative antibiotic exposure beyond distinct, class-specific thresholds and carries excess mortality. These prospective findings identify cumulative antibiotic burden as a modifiable risk factor and support an exposure-aware approach to antimicrobial stewardship in this population.
The lower thresholds for specfic antibiotics to have a 20% chance a patient acquires VRE were quite different than the average of 10 for all antibiotics. For cephalosporins the number was 3 DDD, for β-lactam / β-lactamase inhibitor combinations the number was 5.1 DDD, carbapenems were 3.3, piperacillin-tazobactam was 3.6, and vancomycin was just 1.5.
The complete breakdown for higher thresholds like a 40% chance of VRE and also for gram negative MDROs can be found in the supplemenal data for the article here.
The article in this episode is a selection from my Hospital Pharmacy Academy’s weekly literature digest. Have you ever felt like your physician colleagues are one step ahead of you with new literature developments? Every week, Academy members are provided a summary curated and explained by me of the top hospital pharmacy-related articles published that week from over 20 major journals and sources to save you time and keep you up to date with the literature. To get immediate access, go to pharmacyjoe.com/academy.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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