SAN FRANCISCO — Drug resistance was a common cause of treatment failure in 26 patients with community-acquired pneumonia who developed bacteremia while being treated with macrolide antibiotics, Dr. Gavin Bayan Grant said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Of the 26 patients who developed bacteremia while on erythromycin, clarithromycin, or azithromycin therapy, 21 (81%) had resistant organisms, compared with 15 (44%) of 34 patients who developed bacteremia after recent use of one of the macrolides (defined as 16–90 days before the bacteremia diagnosis) and 14% of 721 patients who had not been taking any antibiotics and developed bacteremia.
Macrolide antibiotics are standard therapy for outpatient treatment of pneumonia, and evidence that significant macrolide resistance occurs has been inconclusive, said Dr. Grant of the Centers for Disease Control and Prevention, Atlanta. The current findings provide further evidence that resistance can lead to treatment failure with macrolides, which may inform clinical decisions to change antibiotics in some patients, he said at the meeting, sponsored by the American Society for Microbiology.
Dr. Grant has no association with the companies that make macrolides.
After patient age, immunosuppression, chronic comorbidities, and residence in a long-term care facility were controlled for, patients failing macrolide therapy were 5 times more likely to have resistant organisms, compared with patients who developed bacteremia after recent macrolide use, and 26 times more likely to have resistance than patients with bacteremia who had not been taking antibiotics.
The study also found that clinicians who define macrolide resistance using a cutoff of a minimum inhibitory concentration (MIC) of at least 16 mcg/mL will miss a significant percentage of the treatment failures. “Failures often occur at macrolide MICs less than 16 mcg/mL,” he said.
The laboratory-defined cutoff for pneumococcal resistance to erythromycin is 1 mcg/mL, but some researchers advocate the 16 mcg/mL cutoff as more likely to result in breakthrough bacteremia, he explained.
Comparison of isolates from all three patient groups found that breakthrough bacteremia occurred at a broad range of MIC values above 1 mcg/mL, not just at the higher levels of resistance, Dr. Grant said.
Among the patients who had MICs of 1 mcg/mL or greater, the distribution of MICs did not differ significantly between groups. An MIC of 16 mcg/mL or greater was seen in 39% of the group failing macrolide therapy and 6% of patients who developed bacteremia after recent macrolide therapy or not taking antibiotics.