Short-course antibiotic therapy is safe for most clinically stable patients hospitalized for community-acquired pneumonia, according to findings from a multicenter, randomized trial conducted in Spain.
Among patients who did not require intensive care unit (ICU) treatment, around 70% of those in the short-treatment arm of the study met the criteria for clinical stability after five antibiotic treatment days. Treatment was stopped in these patients, and their outcomes were similar to patients treated with a longer course of antibiotics (seven to 14 days).
The findings support recommendations from the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), calling for shorter treatment courses in patients with community-acquired pneumonia (CAP) who achieve clinical stability after a minimum of five antibiotic treatment days, researcher Ane Uranga, MD, of Galdakao-Usansolo Hospital, Galdakao, Biscay, Spain, and colleagues wrote in JAMA Internal Medicine, published online July 25.
"This is the first study, to our knowledge, to validate the IDSA/ATS guideline recommendations for duration of antibiotic treatment," the researchers wrote. "Determining the duration of antibiotic treatment based on clinical response appears to be a better strategy than using arbitrary treatment lengths."
The shorter treatment course was also associated with less antimicrobial resistance, fewer adverse effects, lower cost and improved adherence to treatment, the researchers wrote.
They noted that despite these widely recognized benefits and the 2007 IDSA/ATS recommendations, reducing the duration of antibiotic treatment has remained a challenge in clinical practice, "probably because of physicians feeling a false sense of security with longer treatments."
Their clinical trial, designed to validate the IDSA/ATS recommendations, was conducted at four teaching hospitals in Spain from Jan. 1 of 2012 to Aug. 31 of 2013. The study included 312 patients with CAP treated outside of ICUs during this period, including 162 and 150, respectively, randomized to the intervention and control groups.
Patients were randomized at day five, with the intervention group treated with antibiotics for a minimum of 5 days. Treatment was stopped on day five in patients with body temperatures of 37.8°C or less for at least 48 hours and no more than one CAP-associated sign of clinical instability (hypotension, tachycardia, tachypnea, or hypoxia).
Duration of antibiotic treatment in the control group was determined by the patients' physicians.
Main study outcomes included clinical success rate at days 10 and 30 following admission and CAP-related symptoms at days five and 10, measured using the 18-item CAP symptom questionnaire score of 0-90 (higher score indicates more severe symptoms).
Patients in the two groups were similar in age, sex distribution, and other baseline demographics and characteristics.
A total of 70.1% of patients in the intervention group were treated with antibiotics for just five days, compared with 2.9% of patients in the control usual-care group (P<0.001).
Among the main study findings:
-
In the intent-to-treat analysis, clinical success was 48.6% in the control group and 56.3% in the intervention group at day 10 (P=0.18) and 88.6% in the control group and 91.9% in the intervention group at day 30 (P=0.33).
-
Mean (SD) CAP symptom questionnaire scores were 24.7 (11.4) vs 27.2 (12.5) at day five (P=0.10) and 18.6 (9.0) versus 17.9 (7.6) at day 10 (P=0.69).
-
In the per-protocol analysis, clinical success was 50.4% in the control group and 59.7% in the intervention group at day 10 (P=0.12) and 92.7% in the control group and 94.4% in the intervention group at day 30 (P=0.54).
-
Mean (SD) CAP symptom questionnaire scores were 24.3 (11.4) versus 26.6 (12.1) at day five (P=0.16) and 18.1 (8.5) versus 17.6 (7.4) at day 10 (P=0.81).
"No significant differences were found between groups in time until clinical improvement and days to return to normal activity measured at day 30, radiographic resolution at day 30, or adverse effects by day 30," the researchers wrote. "Furthermore, no significant differences were found between groups using Kaplan-Meier survival curves and return to normal activity until day 30."
In an editorial published with the study, Brad Spellberg, MD, of the University of Southern California Keck School of Medicine, Los Angeles, noted that the efficacy and safety of short-course antibiotics was recognized soon after the drugs were introduced, but misdirected fear of patient relapse led to the dogma still held today that patients must finish a predetermined course of treatment, even when symptoms have resolved.
"There is no evidence that taking antibiotics beyond the point at which a patient's symptoms are resolved reduces antibiotic resistance," he wrote. "To the contrary, specifically for pneumonia, studies have shown that longer courses of therapy result in more emergence of antibiotic resistance."
Spellberg said it is time to abandon the predetermined antibiotic course model, which, "is likely a major source of selective pressure that drives antibiotic resistance in society."
"Patients should no longer be told to keep taking the antibiotic," he wrote. "Patients should be told that if their symptoms resolve before completing the antibiotic they should communicate with their physician to determine if they can stop therapy early. Healthcare professionals should be encouraged to allow patients to stop antibiotic treatment as early as possible on resolution of symptoms of infection. Ultimately, we should replace the old dogma of continuing therapy past resolution of symptoms with a new, evidence-based dogma of 'shorter is better.'"
This study was funded by grants from the Department of Basque Country government, the Pharmacy Department of the Spanish government, and the Spanish Pulmonary and Thoracic Surgery Society.
The researchers declared no relevant relationships with industry. Editorial writer Brad Spellberg reported receiving consulting fees from Cempra, The Medicines Company, MedImmune/AstraZeneca and others.
Aucun commentaire:
Enregistrer un commentaire