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Aurélien Dinh, Benjamin Davido, Frédérique Bouchand, Clara Duran, Jacques Ropers, Anne-Claude Crémieux, Honey, I Shrunk the Antibiotic Therapy, Clinical Infectious Diseases, Volume 66, Issue 12, 15 June 2018, Pages 1981–1982, https://doi.org/10.1093/cid/ciy047
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To the editor—We have read with great interest the retrospective study by Yi et al. about the length of antibiotic therapy (LOT) among 152874 adult patients hospitalized for community-acquired pneumonia (CAP) in 2012–13 in the United States [1].
The median LOT was 9.5 days. It should be noted that most patients with underlying conditions or complications, possibly requiring longer LOT, were excluded from the analysis.
Thus, comparing their results to guidelines [2], the authors concluded that LOT exceeded the recommended duration in more than 70% of patients.
In a context of dramatic emergence of bacterial resistance, shortened antibiotic therapy duration is necessary to lower selective pressure on patients’ endogenous flora [4, 5].
As CAP is a frequent cause of antibiotic therapy [3], it is therefore urgently needed to determine the shortest possible treatment regimen. Recently, Uranga et al. evaluated discontinuation of antibiotic therapy 48 h after reaching clinical stability in CAP, with a minimum 5-day treatment duration [6]. Previously, El Moussaoui et al. evaluated 3 days versus 8 days of amoxicillin for patients with nonsevere CAP, mostly belonging to outpatient population [7]. In both trials, noninferiority was demonstrated suggesting that shortening treatment duration to 3–5 days could be effective and sufficient for CAP among specific populations.
We are currently conducting a randomized double blind noninferiority trial comparing 3 days versus 8 days of beta-lactams, among hospitalized patients with CAP [8]. Patients are included in case of favorable response after 3 days of beta-lactam, defined by the presence of clinical stability criteria (temperature ≤37.2° C; heart rate ≤100 beats/min; respiratory rate ≤24 breaths/min; systolic blood pressure ≥90 mmHg; oxygen saturation ≥90%; or arterial oxygen tension ≥60 mmHg) [9].
The primary endpoint is cure at day 15. Secondary endpoints are cure at day 30 and adverse events.
At this time, 281 patients have been included (mean age: 69.2; sex ratio: 112 F/169 M).
Main comorbidities are: cardiac insufficiency (n = 58; 20.6 %), diabetes mellitus (n = 52; 18.5 %), and chronic obstructive pulmonary disease (n = 65; 23.1 %). Mean PSI Score is 81.4 ± 31.9 (range 15–181, median of 82.0), and mean temperature is 38.9 ± 0.6° C (range 38.1–41° C, median of 38.9° C).
A safety analysis conducted by the Data Safety Monitoring Board (DSMB) has reviewed the first 131 patients included in the trial.
Global cure rate was 84%, with 11 failures, among whom 2 patients died. Distribution of failures was 5 and 6 in each arm.
The DSMB concluded that no safety issue prevented the trial to proceed. Overall, 39 severe adverse events were reported among 35 patients, and 5 died with 2 deaths related to pneumonia.
Should noninferiority be demonstrated and the trial achieves its objective, these results could justify reducing treatment duration in this frequent disease. Hence, antimicrobial stewardship teams should challenge physicians to apply shorter duration in every day practice.
Moreover, we can hypothesize that, if a shorter 3-day treatment duration is recommended, it could lead to a 5- to 7-day antibiotic therapy in real practice, substantially shorter than in the study of Yi et al.
Notes
Financial support. This work was supported by the French Department of Health.
Potential conflicts of interest. All authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
