By Drayton Hammond, PharmD, MBA, BCPS, BCCCP

Clinical Pharmacy Specialist, Adult Critical Care, Rush University Medical Center, Chicago

Dr. Hammond reports no financial relationships relevant to this field of study.

SYNOPSIS: Excess antibiotic therapy did not improve mortality or morbidity outcomes, although each additional antibiotic day was associated with 3% increased odds of antibiotic-associated adverse drug events.

SOURCE: Vaughn VM, et al. Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: A multihospital cohort study. Ann Intern Med 2019;171:153-163.

In acutely ill patients with community-acquired pneumonia (CAP), multiple randomized, controlled trials have shown similar or improved patient outcomes with three- to five-day antibiotic courses compared to seven- to 14-day courses.1 Although data are less prevalent for the duration of treatment for healthcare-associated pneumonia (HCAP), the last guidelines published in 2004 suggested a shorter duration of antibiotic therapy (seven to eight days).2 However, a lack of explicit recommendations for using the shortest course of antibiotics possible for CAP and HCAP may affect antibiotic prescribing practices in the general medicine population. Vaughn et al performed a multicenter cohort study to examine the predictors of and outcomes associated with excess duration of antibiotics in CAP and HCAP across 43 hospitals in Michigan.3

Adult patients admitted to a general medicine service in one of 43 participating hospitals were included if they were admitted for CAP or HCAP treatment and were discharged from the hospital between January 2017 and April 2018. Those who were admitted to an ICU or were severely immunocompromised were not included. Approximately 60% of patients had severe pneumonia (pneumonia severity index class IV or V), with 55% having uncomplicated CAP, 19% having complicated CAP, and 27% having HCAP. Overall, 67.8% of patients received excess antibiotics based on guideline recommendations. The median durations for both CAP and HCAP were eight days, with median excess durations of two days for CAP and one day for HCAP. In total, this resulted in 2,526 excess antibiotic days per 1,000 patients hospitalized with CAP or HCAP. The vast majority of these excess days (93.2%) occurred after hospital discharge, with an additional five days of treatment after discharge most common despite patients frequently needing zero or one additional day of therapy based on guideline recommendations. Patients from all hospitals were affected, with a range of patient discharges affected between 38.1% and 95.0%, depending on the hospital.

Variables associated with excess antibiotic treatment duration on multivariable regression analysis included positive respiratory culture result (predicted excess days per patient 3.2, adjusted rate ratio [aRR], 1.49; 95% confidence interval [CI], 1.33-1.68), each day of hospital stay (excess days, 0.2; aRR, 1.02; 95% CI, 1.02-1.02), receipt of high-risk antibiotics in the 90 days prior to admission (excess days, 2.9; aRR, 1.17; 95% CI, 1.10-1.25), and CAP diagnosis (excess days, 3.2; aRR, 1.43; 95% CI, 1.32-1.55). Documentation of total antibiotic treatment duration in the hospital discharge summary was predictive for excess antibiotic duration (aRR, 0.78; 95% CI, 0.70-0.87). Most outcomes were similar at 30 days between the appropriate duration and excess duration groups, including mortality (1.9% vs. 2.0%; adjusted odds ratio [aOR] per excess day, 1.01; 95% CI, 0.97-1.05), readmission (14.1% vs. 11.3%; aOR, 1.00; 95% CI, 0.98-1.03), and ED visit (11.4% vs. 10.9%; aOR, 0.98; 95% CI, 0.95-1.01). However, antibiotic-associated adverse drug events (ADEs) occurred more frequently in the excess duration group (3.4% vs. 4.8%; aOR, 1.03; 95% CI, 1.00-1.06).

COMMENTARY

Two-thirds of general medicine patients with pneumonia received excess antibiotic therapy, with 93.2% of the unnecessary duration occurring after hospital discharge. Although the reasons for these practices were not recorded, the authors hypothesized the most likely culprits affecting these durations were implied rather than explicitly stated recommendations for antibiotic durations in pneumonia guidelines, the wait for finalized culture results to be available, and a lack of national policy efforts focused on treatment durations. Since patient outcomes did not improve because of excess antibiotic durations, providers may be more comfortable aligning their treatment durations with more contemporary data for shorter courses. In fact, it may be possible to use one- to five-day antibiotic courses for CAP in many cases, which may allow for further reductions in antibiotic use.4 Furthermore, each additional antibiotic day was associated with a 3% increased odds of an antibiotic-associated ADE. The most common ADE was diarrhea; however, the short study duration precluded the authors from evaluating the effect of antibiotic days on resistance development. In a recent study of more than 7,000 critically ill adults, researchers observed that each additional day of broad-spectrum beta-lactam therapy beyond day 3 was associated with a 4% increased risk of new resistance development.5 Consequently, the long-term implications of excessive antibiotic durations in CAP and HCAP are uncertain and likely are worse than those reported in this study. A particular emphasis may be placed on leveraging the electronic health record to guide providers to an appropriate treatment duration based on days of therapy already received in the hospital and the treatment indication. This may help allay concerns about treatment duration while streamlining the discharge process.

REFERENCES

  1. Wald-Dickler N, Spellberg B. Short-course antibiotic therapy — replacing Constantine units with “shorter is better.” Clin Infect Dis 2019;69:1476-1479.
  2. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388-416.
  3. Vaughn VM, et al. Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: A multihospital cohort study. Ann Intern Med 2019;171:153-163.
  4. Royer S, et al. Shorter versus longer courses of antibiotics for infection in hospitalized patients: A systematic review and meta-analysis. J Hosp Med 2018;13:336-342.
  5. Teshome BF, et al. Duration of exposure to antipseudomonal β-lactam antibiotics in the critically ill and development of new resistance. Pharmacotherapy 2019;39:261-270.