Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
High levels of antibiotic-resistant urinary bacteria found in German men
Originally published by CIDRAP News Jul 28
An analysis of urine specimens from male patients in Germany found high levels of antibiotic resistance in the most frequent causes of urinary tract infections (UTIs), researchers reported today in Eurosurveillance.
The retrospective observational study analyzed routinely collected urine specimens from 102,736 adult men treated at outpatient practices across Germany from 2015 through 2020. Researchers focused on the distribution of bacteria and the resistance of the three most common bacteria to frequently used oral antibiotics for UTIs. A secondary aim was to identify risk factors for the occurrence UTIs caused by antibiotic-resistant Escherichia coli.
The three most frequent bacteria were E coli (38.4%), Enterococcus faecalis (16.5%), and Proteus mirabilis (9.3%). While E coli resistance to first-line, recommended antibiotics for uncomplicated UTIs (fosfomycin and nitrofurantoin) was low, resistance to amoxicillin (45.7%), TMP (26.6%), and ciprofloxacin (19.8%) was common, and multidrug resistance was high (22.9%). Resistance of E faecalis to ciproflxacin was also high (29.3%), as was P mirabilis resistance to TMP (41.3%) and ciprofloxacin (16.6%). Resistance to TMP and ciprofloxacin was significantly higher among bacteria derived from recurrent UTIs.
Multivariable logistic regression identified age (90 years or older) and recurrent UTI as independent risk factors for E coli UTIs with resistance to TMP and ciprofloxacin.
The study authors say the findings suggest urine culture should always be performed before therapy in men with suspected UTIs, and that the use of TMP and ciprofloxacin should be limited.
Jul 28 Eurosurveill study
New candidemia treatment could be on the horizon
Originally published by CIDRAP News Jul 28
San Diego-based biotechnology company Cidara Therapeutics announced yesterday that it has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for its novel antifungal candidate rezafungin.
The company submitted the NDA for rezafungin—an echinocandin antifungal—for the treatment of candidemia and invasive candidiasis based on positive results from the phase 3 ReSTORE and phase 2 STRIVE trial. In both trials, a once-weekly dose of rezafungin demonstrated statistical non-inferiority to once-daily caspafungin, meeting the primary endpoints for the FDA and the European Medicines Agency.
The FDA has granted rezafungin Qualified Infectious Disease Product designation, which confers priority review of the NDA. If the NDA is accepted, Cidara expects an FDA decision on approval of the drug could come in early 2023. No new therapies for candidemia and invasive candidiasis, which are caused by a yeast called Candida and are associated with high rates of morbidity and mortality, have been approved by the FDA in over a decade.
“If approved, rezafungin would represent an important new treatment option for patients at risk of these potentially deadly diseases," Cidara President and CEO Jeffrey Stein, PhD, said in a company press release.
Cidara also announced that it has entered into a license agreement with Melinta Therapeutics, of Morristown, New Jersey, under which Melinta will acquire an exclusive license to commercialize rezafungin in the United States.
Jul 27 Cidara Therapeutics press release
Study: Very short antibiotic course effective in pneumonia patients with normal oxygen levels
Originally published by CIDRAP News Jul 27
A study of patients hospitalized with pneumonia found that among those with normal oxygenation levels, an ultra-short course of antibiotics appeared to be as safe and effective as the standard course, researchers reported today in Clinical Infectious Diseases.
In the study, a team led by researchers from Harvard Medical School conducted a retrospective analysis of patients treated with antibiotics for possible pneumonia at four hospitals in Massachusetts from May 2017 through February 2021. They focused on a subset of patients with oxygen saturation levels of 95% or higher, which is associated with a lower probability of true infection, then compared those treated with a very short course of antibiotics (1 to 2 days) with those who received a standard course (5 to 8 days). The primary outcomes were hospital mortality and time-to-discharge. Secondary outcomes included readmissions, 30-day mortality, Clostridioides difficile infections, 30-day hospital-free days, and antibiotic-free days.
Among 39,752 patients treated for possible pneumonia, 10,012 had median oxygen saturation levels of 95% or higher without supplemental oxygen. Of these patients, 2,239 who received 1 to 2 days of antibiotics were propensity matched to 2,239 who received 5 to 8 days. There were no statistically significant differences in hospital mortality between the two groups (2.1% for short course vs 2.8% for standard course; subdistribution hazard ratio [SHR], 0.75; 95% confidence interval [CI], 0.51 to 1.09), but patients treated with 1 to 2 days of antibiotics were discharged sooner (6.1 days vs 6.6 days; SHR, 1.13; 95% CI, 1.07 to 1.19) and had more 30-day hospital-free days (23.1 vs 22.7; mean difference, 0.44; 95% CI, 0.09 to 0.78).
There were no significant differences in 30-day readmissions (16.0% vs 15.8%; odds ratio [OR], 1.01; 95% CI, 0.86 to 1.19), 30-day mortality (4.6% vs 5.1%; OR, 0.91; 95% CI, 0.69 to 1.19), or 90-day C difficile infections (1.3% vs 0.8%; OR, 1.67; 95% CI, 0.94 to
"This analysis suggests a potentially powerful strategy to help clinicians to easily identify a subset of patients with possible pneumonia in whom early discontinuation of antibiotics may be safe," the study authors wrote. They suggest the strategy merits testing in prospective randomized trials.
Jul 27 Clin Infect Dis abstract
European surveillance data show rise in carbapenem-resistant E coli, Klebsiella
Originally published by CIDRAP News Jul 26
New antimicrobial resistance (AMR) surveillance data from Europe shows concerning trends among the most common causes of clinical bacterial infections.
The 2020 European Antimicrobial Resistance Surveillance Network (EARS-Net) report, which includes data on eight bacterial species (E coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter species, Streptococcus pneumoniae, Staphylococcus aureus, E faecalis, and Enterococcus faecium) from 29 European Union/European Economic Activity (EU/EEA) countries, showed either significantly decreasing trends or no significant trends in population-weighted AMR percentages for most bacterial species-antibiotic combinations. But the situation varied by bacterial species, antibiotic class, and region.
In particular, invasive E coli and K pneumoniae isolates exhibited rising resistance to carbapenem antibiotics, with almost a quarter of EU/EEA countries reporting carbapenem-resistance percentages above 10% in K pneumoniae. In addition, more than half (54%) of the E coli isolates, and more than a third (38%) of K pneumoniae isolates, were resistant to at least one antibiotic under surveillance, and combined resistance to several antibiotics in both pathogens was a frequent occurrence.
The EARS-Net report noted that infections caused by resistant E coli proportionally contribute most to the burden of AMR in Europe, both in the number of cases and attributable deaths, while carbapenem-resistant K pneumoniae is associated with high mortality and is causing an increasing number of hospital outbreaks.
"This underlines the need for continuous close monitoring and greater efforts to respond efficiently to this public health threat," the report states.
The data also show that despite some declines, AMR among Acinetobacter and P aeruginosa—both considered critical-priority pathogens by the World Health Organization—remains high, particularly in southern and eastern Europe, while the percentage of vancomycin-resistant E faecium isolates rose from 11.6% in 2016 to 16.8% in 2020.
As in previous years, AMR patterns varied widely among European countries but often with a north-to-south and east-to-west gradient. In general, the lowest AMR percentages were reported by northern European countries, and the highest by countries in southern and eastern Europe.
Jun 25 2o20 EARS-Net surveillance report
VA intervention linked to better treatment for asymptomatic bacteriuria
Originally published by CIDRAP News Jul 25
An antibiotic stewardship intervention for asymptomatic bacteriuria (ASB) was associated with a reduction in urine cultures and antibiotic use at four Veterans Affairs (VA) hospitals, researchers reported today in JAMA Network Open.
To reduce unnecessary antibiotic treatment for ASB—the presence of bacteria in the urinary tract without related symptoms—clinicians and researchers at four geographically distant VA hospitals implemented the Less is More for ASB project, which encompassed case-based education to train clinicians who order urine cultures and dispense antibiotics how to use an algorithm to distinguish ASB from a urinary tract infection.
Previous research by the VA has shown that 72% of ASB patients at 25 VA hospitals received antibiotics unnecessarily. The program was implemented by a centralized coordinating center that provided coaching and troubleshooting to site champions at each hospital.
To assess the effectiveness of the intervention, researchers conducted an interrupted time series study at the four intervention hospitals and four comparison hospitals from October 2017 through April 2020. The main outcomes were the total number of urine cultures ordered, antibiotic days of therapy (DOT), and length of therapy (LOT).
A total of 11,299 patients were included in the study (94.7% men; mean age, 72.6 years). The decrease in urine cultures before and after the intervention was not significant in the intervention hospitals per segmented regression analysis, but a difference-in-differences analysis comparing intervention with comparison hospitals found that the number of urine cultures ordered fell by 3.24 urine cultures per 1,000 bed-days.
In the segmented regression analyses, the relative percentage decrease of antibiotic DOT in the postintervention period at the intervention sites was 21.7%, from 46.1 (95% CI, 28.8 to 63.4) to 37.0 (95% CI, 22.6 to 51.4) per 1,000 bed-days. The relative percentage decrease of antibiotic LOT in the postintervention period at the intervention sites was 21.0%, from 36.7 (95% CI, 23.2 to 50.2) to 29.6 (95% CI, 18.2 to 41.0) per 1,000 bed-days.
"Overall, our project led to the desired direction of change (decrease) in all 3 clinical outcomes: urine cultures, DOT, and LOT," the study authors wrote. "The success of this project implies that our external and internal facilitation is a viable implementation strategy for implementing stewardship at a distance."
Jul 25 JAMA Netw Open study
