Patients in last spring's outbreak of severe Escherichia coli infection who were treated with azithromycin were more likely to clear the organism compared with patients who did not receive antibacterial therapy, German investigators reported.
The rate of carriage of Shiga toxin-producing enteroaggregative E. coli O104:H4 at one month was only 4.5% (95% CI 0 to 13.3) for treated patients compared with 81.4% (95% CI 69.8 to 93, P<0.001) for those not given antibiotics, according to Johannes K.M. Knobloch, MD, of University Hospital of Schleswig-Holstein in Lübeck, and colleagues.
Action Points
- Explain that patients in last spring's outbreak of severe Escherichia coli infection who were treated with azithromycin were more likely to clear the organism compared with patients who did not receive antibacterial therapy.
- Note that by day 35 there were no carriers in the treated group, while carriage persisted in 57.7% (95% CI 40.5 to 75) of the untreated patients at day 42.
Moreover, by day 35 there were no carriers in the treated group, while carriage persisted in 57.7% (95% CI 40.5 to 75) of the untreated patients at day 42, the researchers reported in the March 14 Journal of the American Medical Association.
Currently, most recommendations advise against the use of antibiotics for treatment of Shiga toxin-producing E. coli out of concerns for an increased risk for the development of the potentially deadly complication of hemolytic uremic syndrome.
However, during the large German outbreak some patients were given the monoclonal antibody eculizumab (Soliris), which had shown benefits in a few case reports of severe hemolytic uremic syndrome.
This antibody blocks a complement protein thought to be involved in the kidney damage associated with that syndrome. However, this treatment raises patients' risk for serious infections with meningococci, so prophylactic azithromycin is given along with the monoclonal antibody.
Knobloch's group followed a cohort of 65 patients with confirmed E. coli infection for a mean of 43.5 days. Two-thirds were women, and mean age was 47.
A total of 22 patients in the group received azithromycin, and compared with untreated patients they had a significantly lower probability of being Shiga toxin-producing E. coli carriers (HR 0.095, 95% CI 0.041 to 0.218, P<0.001).
Because of this significant difference, the investigators then decided to try azithromycin (Zithromax) treatment for 15 previously untreated patients with persistent symptoms.
The treatment was offered to these patients because the German health authorities restrict the activities of individuals carrying enteropathogenic bacteria, which can place a significant burden on the affected.
The duration of colonization in these patients ranged from 30 to 63 days before they received the antibiotic, and five days later they were confirmed to be negative.
None of the patients showed signs of developing hemolytic uremic syndrome such as changes in serum creatinine and lactate dehydrogenase levels. Also, azithromycin resistance did not develop.
The persistence of colonization with this enteroaggregative strain of E. coli is likely a result of its ability to create a protective biofilm, the investigators explained.
They concluded that three days of treatment with azithromycin cleared the pathogen, and that larger studies are warranted to clarify the possible role for antibiotic therapy in this and other strains of Shiga toxin-producing E. coli.
The study was limited by being conducted at a single site and with a small number of patients, as well as a lack of randomization.
Disclosures
The authors received funding from multiple sources, including Novartis, Genzyme, Roche, Bayer, Gilead, and Merck Sharpe & Dohme, as well as from the German Research Foundation and the German Ministry of Education and Research.
Primary Source
Journal of the American Medical Association
Nitschke M, et al "Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4" JAMA 2012; 307: 1046-1052.