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The results of a randomized clinical trial in Slovenia suggest that a 7-day course of antibiotics for a rash caused by Lyme disease is noninferior to a 14-day course, researchers reported yesterday in The Lancet Infectious Diseases. Gentamicin
The randomized, open-label trial enrolled patients with a solitary erythema migrans rash—the most common manifestation of early Lyme disease—at University Medical Center in Ljubljana, Slovenia, from July 2017 to October 2018. Participants were randomized 1:1 to receive 100 milligrams of oral doxycycline twice a day for 7 or 14 days (10 to 14 days of doxycycline is the standard treatment).
The primary efficacy end point was the difference in the proportion of patients with treatment failure in the per-protocol analysis. The noninferiority margin was 6 percentage points.
Of the 300 patients enrolled, 295 completed antibiotic therapy as per protocol, and 294 were able to be evaluated 2 months post-enrollment. Five of 147 patients (3.4%) in the 7-day treatment group and 3 of 147 patients (2.0%) in the 14-day treatment group had treatment failure manifesting as persistent erythema at the 2-month visit (difference, 1.4 percentage points; upper limit of one-sided 95% confidence interval [CI], 5.1 percentage points). Results of the intention-to-treat analysis and the analysis that included only patients who attended the 2-month follow-up visit were similar to the per-protocol analysis.
No patients developed new objective manifestations of Lyme borreliosis during follow-up or had positive repeat skin biopsies. Two of 150 patients (1.3%) in the 7-day and one of 150 patients (0.7%) in the 14-day group discontinued therapy due to adverse events.
The trial investigators say the minimal decrease in efficacy in the 7-day group is acceptable because no patients developed objective signs of persistent or progressive infection.
"The 7-day regimen appears to fulfill the fundamental treatment goals of preventing progression to more advanced disease while limiting antibiotic exposure," they wrote. "We propose similar studies in other Lyme borreliosis endemic regions where disease characteristics and response to treatment could differ." Oct 6 Lancet Infect Dis abstract
In another study published this week in The Lancet Infectious Diseases, British researchers report that an antibiotic review kit intervention was tied to sustained reductions in antimicrobial use in adult acute general medical patients.
The four-component antibiotic review kit (ARK) for hospitals, which aims to help prescribers make appropriate decisions to stop or continue antibiotics at prescription review, includes a novel prescribing decision aid, an online training tool, guidance for implementing audit and feedback, and a patient leaflet.
To evaluate the impact of the program, a team of researchers performed a trial in which clusters of hospitals were randomized to an implementation date occurring at 1- to 2-week intervals. The co-primary outcomes of the trial, assessed using data from electronic health records, were monthly antibiotic defined daily doses (DDDs) per adult acute general medicine admission and 30-day all-cause mortality.
Thirty-nine UK hospitals (13 large, 14 medium, and 12 small) were followed for at least 13 months. Hospitals contributed a median of 23 months of antibiotic data after implementation of the ARK intervention. Adjusting for the effects of the COVID-19 pandemic, the intervention was associated with a –1.0% (95% CI, –4.0 to 2.1) immediate change in total antibiotic DDDs per admission and a sustained –4.8% (95% CI, –9.1% to –0.2%) change per year. No overall relationship between fidelity of implementation and the effect of the intervention was observed.
Among 7,160,421 acute general medical admissions, the ARK intervention was associated with an immediate change of –2.7% (95% CI, –5.7% to 0.3%) and sustained change of 3.0% (95% CI, –0.1% to 6.2%) in 30-day mortality. The analysis of all-cause mortality was also adjusted to account for the COVID-19 pandemic.
The study authors note that while the ARK intervention did not result in an immediate impact on prescribing, the sustained reductions in antibiotic use are significant, and the intervention appears to be safe.
"Acute hospital providers should consider embedding the ARK-Hospital toolkit in their staff training, prescribing processes, and stewardship work to reduce antibiotic overuse in acute general medical inpatients," they concluded. Oct 4 Lancet Infect Dis abstract
An analysis of Escherichia coli from food-producing animals in Europe found that antibiotic susceptibility varied widely among antibiotics, animal species, and countries, with some signs of decline in recent years, a team of European researchers reported today in the Journal of Antimicrobial Chemotherapy.
To describe the susceptibility of food-animal E coli to medically important antibiotics, researchers randomly sampled intestinal contents from healthy cattle, pigs, and broiler chickens at slaughter in five or six European Union countries over four periods (2004-2006, 2008-2009, 2013-2014, and 2017-2018). They conducted susceptibility tests for 11 antibiotics deemed medically important by the World Health Organization (WHO) and screened for the presence of the colistin-resistance genes MCR-1 to MCR-10.
A total of 10,613 E coli strains were recovered. Generally, the occurrence of resistance was lower among E coli isolates from cattle than among those from pigs and broilers. In broilers, resistance percentages were the lowest in 2017-2018. Resistance to meropenem and tigecycline was absent, and resistance to azithromycin was 0.2% to 2.0%. Also, low resistance to third-generation cephalosporins (1.1% to 7.4%) was detected in broilers. Resistance to colistin varied from 0.1% to 4.8%.
E coli from broilers showed high resistance to ciprofloxacin (7.3% to 23.3%), whereas for cattle and pigs it was 0.2% to 2.5%. Low/moderate resistance to chloramphenicol (9.3% to 21.3%) and gentamicin (0.9% to 7.0%) was observed in pigs and broilers. The highest resistance was noted for ampicillin (32.7% to 65.3%), tetracycline (41.3% to 67.5%), trimethoprim (32.0% to 35.7%) and trimethoprim/sulfamethoxazole (27.5% to 49.7%) from pigs and broilers, with marked country differences.
Overall pooled values for multidrug-resistance (MDR) were 3.5% for cattle, 23.7% for pigs, and 25.9% for broilers. A significant decrease in MDR over time was also observed for broilers and a tendency for a decrease for pigs, while no consistent trend was found in cattle.
The researchers say the decline in resistance in broilers in several countries, particularly for antibiotics most commonly used in veterinary medicine, is likely influenced by the decline in overall veterinary antibiotic use since 2011. Oct 7 J Antimicrob Chemother abstract
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