Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Trial supports shorter antibiotic course for Lyme symptoms
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.
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
Stewardship kit linked to reduced antibiotic use in UK hospitals
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
Study finds range of resistance in food animal E coli across Europe
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
BARDA to fund development of antibiotic for melioidosis
Originally published by CIDRAP News Oct 5
Venatorx Pharmaceuticals announced this week that it has received a contract from the US Department of Health and Human Services (HHS) Biomedical Advanced Research and Development Authority (BARDA) to develop the combination antibiotic cefipime-taniborbactam for treatment of melioidosis.
Under the terms of the agreement, Venatorx, of Malvern, PA, will receive $318 million to develop the drug, which combines a fourth-generation cephalosporin with a beta-lactamase inhibitor, to treat melioidosis, a respiratory disease caused by the bacterium Burkholderia pseudomallei. The contract includes funding for a completion of a clinical study and options to procure cefipime-taniborbactam for national preparedness efforts.
Venatorx has been developing cefipime-taniborbactam as a treatment option for patients with difficult-to-treat infections caused by multidrug-resistant bacteria, and recently completed a phase 3 clinical trial in patients with complicated urinary tract infections. The company expects to submit a New Drug Application for that indication to the Food and Drug Administration in 2023.
"The contract supports Venatorx's mission to address the devasting impact on patient lives from the growing multidrug-resistant bacterial infections in the US," Christopher J. Burns, PhD, president and CEO of Venatorx, said in a press release. "Venatorx and cefepime-taniborbactam can play an important role in helping to enhance the biodefense preparedness of our country, save lives and protect Americans."
B pseudomallei is most commonly found in soil and water in tropical regions, including South and South East Asia, northern Australia, and parts of Central and South America, Puerto Rico, and the US Virgin Islands. Most melioidosis cases in the United States have been linked to travel to and products imported from these regions. But the US Centers for Disease Control and Prevention (CDC) said in July that environmental sampling indicated the bacterium has been in soil and water in the Gulf Coast region of Mississippi since 2020 and is now considered locally endemic.
Often described as "the great mimicker" because it looks like other conditions, melioidosis symptoms can include fever, localized pain or swelling, cough, chest pain, respiratory distress, weight loss, muscle or joint pain, headache, and seizures. Melioidosis is fatal in anywhere from 10% to 50% of those infected.
Oct 3 Venatorx press release
Jul 27 CDC Health Alert Network advisory
Study: US children exposed to antibiotics frequently at an early age
Originally published by CIDRAP News Oct 5
An observational study of privately insured US preschoolers found a high volume of antibiotic prescribing, particularly in children with chronic medical conditions, researchers reported today in Clinical Infectious Diseases.
To address the evidence gap in pediatric antibiotic prescribing in the United States, and any links with chronic comorbidities, researchers from Harvard T.H. Chan School of Public Health and Harvard Medical School studied medical claims data from a cohort of 124,759 children under the age of 5 with private medical insurance. The primary outcomes were the cumulative number of antibiotics dispensed per child by age 5, and the proportion of children for whom at least one antibiotic was prescribed by age 5. The researchers also identified which chronic medical conditions predicted whether a child would be among the top 20% of antibiotic recipients.
Children in the cohort received a mean of 6.8 antibiotic courses by the age of 5, with 91% of children receiving at least one antibiotic course by 5. Most antibiotic courses (71%) were associated with respiratory tract infections. The presence of an underlying medical condition generally increased the odds that a child would be among the top 20% of antibiotic recipients, with pulmonary/respiratory conditions (odds ratio [OR], 2.64), otologic conditions (OR, 2.62), and immunological conditions (OR, 2.53) associated with the greatest increase in the odds of being in the highest consumption group. Children with at least one of these conditions received a mean of 10.5 antibiotic courses by age 5.
The study authors say the results are broadly consistent with studies that have measured cumulative antibiotic use in children in other high-income countries.
"Reducing rates of respiratory illness, through vaccination or other means, may be an effective way of achieving reductions in early pediatric antibiotic use, especially if these interventions are targeted in children with chronic conditions that predispose them to frequent receipt of antibiotics," they concluded.
Oct 5 Clin Infect Dis abstract
Antibiotic eye drops linked to shorter symptom duration for conjunctivitis
Originally published by CIDRAP News Oct 4
A randomized clinical trial and meta-analysis of previous trials found that topical antibiotics were associated with significantly shorter symptom duration in children with acute infective conjunctivitis, researchers reported today in JAMA Network Open.
The trial, conducted from October 2014 to February 2020, enrolled children ages 6 months to 7 years of age who had acute infective conjunctivitis, which is typically caused by bacteria, and randomized them to receive either moxifloxacin eye drops, placebo eye drops, or no intervention. The primary outcome of the trial was time to clinical cure. The trial also included a subsequent meta-analysis that included the results of the present trial, along with three previously conducted trials, and looked at the proportion of participants with conjunctival symptoms on days 3 to 6.
Of the 88 participants in the present trial, 30 received moxifloxacin eye drops, 27 received placebo eye drops, and 31 received no intervention. The time to clinical cure was significantly shorter in the children who received moxifloxacin eye drops compared with those in the no-intervention group (3.8 days vs 5.7 days; difference, –1.9 days; 95% CI, –3.7 to –0.1 days), but there was no difference between children who received moxifloxacin eye drops and those who received placebo drops (3.8 vs 4.0 days; difference, 0.2 days; 95% CI, –2.2 to 1.6 days). In the Kaplan-Meier survival analysis, both moxifloxacin and placebo eye drops significantly shortened the time to cure compared with no intervention.
In the meta-analysis, which compared 300 children who received topical antibiotics to 284 who received placebo, topical antibiotics were associated with a 41% reduction in conjunctival symptoms on day 3 and day 6 (OR, 0.59; 95% CI, 0.39 to 0.91).
"These findings suggest that topical antibiotic therapy should be considered for acute infective conjunctivitis in children because antibiotics were associated with significantly shorter recovery times," the investigators wrote. They add that the results of the present trial also suggest that lubricating eye drops may have some benefits for the management of acute infective conjunctivitis.
Oct 4 JAMA Netw Open study
Study: Hospital floors, healthcare workers' shoes may spread MRSA
Originally published by CIDRAP News Oct 3
A study conducted at a Veterans Affairs (VA) hospital in Ohio suggests that hospital floors and shoes of healthcare workers are potential sources for dissemination of methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated pathogens, researchers reported late last week in the American Journal of Infection Control.
Although hospital floors and shoes of healthcare workers are frequently contaminated, there is limited evidence of their potential to serve as a vector for pathogens. To assess the frequency of MRSA transmission from floors to adjacent rooms, researchers with Louis Stokes Cleveland VA Medical Center and Case Western Reserve University School of Medicine enrolled 12 MRSA-colonized patients at a long-term care facility and defined their rooms as the index rooms.
They then cleaned and disinfected the floors of two adjacent rooms, ensured that no MRSA was present immediately after cleaning, and had healthcare personnel (with disinfected shoes) walk first into the index rooms and then the two adjacent rooms. Three to four simulations were completed for each room, and afterward the researchers measured the number of MRSA colony-forming units (CFUs) on the floors of adjacent room 1 and 2.
The researchers also performed a similar experiment with water containing the bacteriophage MS2, looking at contamination of floors and high-touch surfaces in adjacent rooms and nursing stations.
Overall, MRSA was transferred in 47.4% (18 of 38) of assessments in adjacent room 1 and in 31.6% (12 of 38) of assessments in adjacent room 2. For both rooms, significantly greater numbers of MRSA CFUs were transferred from index rooms containing heavy MRSA contamination versus rooms with medium or light contamination. In addition, bacteriophage MS2 was recovered from more than half of floor cultures in adjacent rooms and nursing stations and was recovered from 33% to 70% of high-touch surfaces in index rooms, adjacent rooms, and nursing stations.
"These findings build upon evidence suggesting that contaminated floors and shoes could be an underappreciated source for pathogen dissemination in healthcare facilities," the study authors wrote. "Future studies are needed to assess the impact of interventions such as floor or shoe disinfection on transfer of pathogens."
Oct 1 Am J Infect Control abstract