Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Strain of extensively drug-resistant gonorrhea identified in Austria
Researchers in Austria are reporting the identification of a second strain of extensively drug-resistant (XDR) gonorrhea.
In a case report published yesterday in Eurosurveillance, researchers described the strain, which was detected in a heterosexual man from Austria who had unprotected sex with a female commercial sex worker in Cambodia. The patient was treated with the standard gonorrhea treatment regimen (an intramuscular dose of ceftriaxone plus an oral dose of azithromycin), and symptoms had resolved at the 2-week follow-up visit, but a polymerase chain reaction (PCR) test found the patient was still positive for Neisseria gonorrhoeae.
The case was considered a treatment failure, and additional antibiotic treatment was prescribed.
Subsequent antimicrobial susceptibility testing of N gonorrhoeae isolates from the patient found high-level resistance to azithromycin and resistance to ceftriaxone, cefixime, cefotaxime, ciprofloxacin, and tetracycline. Molecular investigation found genetic mutations that are similar to those detected in a strain of XDR N gonorrhoeae identified in three patients in the United Kingdom and Australia in 2018. The researchers say the strains belong to the same sublineage, which they warn could make gonorrhea untreatable if it establishes sustained transmission.
"XDR N. gonorrhoeae strains, including those with resistance to all available treatment options, are a major global public health concern," the researchers wrote. "They pose a risk of treatment failure and serious complications/sequelae on the individual level but also compromise the management and control of gonorrhoea on the public health level."
They add that antimicrobial susceptibility surveillance, both nationally and internationally but particularly in Asia, where many strains of ceftriaxone-resistant gonorrhea have emerged, is necessary, and that new antibiotics for effective gonorrhea treatment are needed.
Jun 16 Eurosurveill rapid communication
Study notes antibiotic overuse for respiratory infections in primary care
A study conducted in a large healthcare system in the Upper Midwest found that unnecessary antibiotic prescribing for upper respiratory infections (URIs) was common among all primary care providers, but worse among older, rural clinicians and those in high-volume specialties, researchers reported today in Open Forum Infectious Diseases.
In the analysis of electronic medical records from Sanford Health, which serves patients in South Dakota, North Dakota, and Minnesota, researchers looked at all patients 18 and older who were seen by a primary care provider for a URI (acute bronchitis, pharyngitis, nonspecific acute respiratory tract infection, and uncomplicated acute rhinosinusitis) from June 2017 through May 2018. They then compared individual provider rates of unnecessary antibiotic prescribing for primary care providers practicing in the departments of internal medicine, family medicine, and urgent care, and identified patient and provider characteristics associated with unnecessary prescribing.
Of the 49,463 patient encounters included in the study, antibiotics were prescribed unnecessarily for 42.2%. Acute bronchitis had the highest rate of unnecessary prescribing, with antibiotics prescribed in 74.2% of encounters. Men and older patients were more likely to be prescribed unnecessary antibiotics.
Provider characteristics associated with higher rates of unnecessary prescribing included being in a rural practice (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.20 to 1.84), having more years in practice (OR, 1.09; 95% CI, 1.01 to 1.06 for every 5 years), and being in a high-volume specialty such as urgent care (OR, 1.43; 95% CI, 1.08 to 1.89).
"Despite multiple public health initiatives and professional society guidelines aimed at producing more judicious use of antibiotics for URIs in the outpatient setting, overuse remains quite common," the study authors conclude. "Targeting higher volume clinicians may be particularly impactful."
They add, "Health systems should be encouraged to engage these, as well as novel strategies, to promote necessary and appropriate antibiotic usage as an urgent priority for their quality improvement initiatives."
Jun 17 Open Forum Infect Dis abstract
Antibiotic resistance app certified for low-resource settings
Global humanitarian organization Doctors Without Borders/Medecins Sans Frontieres (MSF) announced this week that a mobile application it helped develop to aid the diagnosis of antibiotic-resistant infections in low- and middle-income countries (LMICs) has been certified in Europe and is one step closer to being widely available.
Antibiogo, which is available as a free, open source and offline application for Android devices, allows non-expert laboratory technicians in LMICS to measure and interpret antibiograms—the lab tests that determine whether bacteria cultured from patients is susceptible to antibiotics—with a smart phone. Using image processing and artificial intelligence technology, the app processes an uploaded photo of the cultured bacteria and selected antibiotics in a petri dish, summarizes and interprets the results based on rules from European and American microbiology societies, and recommends an antibiotic.
MSF says the test was specifically developed for low-resource settings, which often lack the equipment necessary to carry out antibiograms, don't have enough microbiologists to interpret them, or are not well-suited for automated diagnostic tests that require reliable electricity sources. Field tests have shown a high level of concordance with the interpretation made by qualified microbiologists.
"Thanks to Antibiogo, any microbiology laboratory technician anywhere will be able to read and interpret an antibiogram directly on their telephone—online or offline—and know the resistance profile of the bacteria responsible for a patient's infection," Nada Malou, PhD, head of the Antibiogo program, said in an MSF press release.
"Properly used, it is a fantastic new diagnostic tool which will help to ensure wider access to high-quality bacteriological tests even in the absence of microbiologists. This will make it possible not only to treat patients with the most appropriate antibiotics but also to reduce antibiotic resistance."
The app will be used first in MSF laboratories in Mali, Central African Republic, Yemen, and Jordan this summer, which will allow MSF to collect user feedback and performance data under real-world conditions.
Jun 15 MSF press release
Urgent care stewardship linked to fewer inappropriate antibiotics
Originally published by CIDRAP News Jun 16
Pediatric urgent care (UC) centers involved in a multisite quality improvement (QI) study saw significant reductions in inappropriate antibiotics for three target diagnoses, a team of US researchers reported yesterday in Pediatrics.
The study involved 157 participants from 20 pediatric urgent care centers who responded to an invitation from the Society of Pediatric Urgent Care Centers to participate in a QI collaborative aimed at improving antibiotic prescribing for acute otitis media (AOM, or ear infection), otitis media with effusion (OME), and pharyngitis.
From June 2019 to December 2019, participating sites completed multiple intervention cycles from a menu of publicly available antibiotic stewardship intervention tools, including provider and patient education, provider communication training, delayed prescribing, and social media. The primary outcome was the rate of inappropriate antibiotic prescriptions for all target diagnoses.
Data from 3,833 patient encounters showed that the rate of inappropriate prescribing for all encounters fell from 60.3% at the beginning of the intervention to 27.8% at the end, for a relative reduction of 53.9%. The biggest reductions in inappropriate prescription rates were observed for AOM (57% to 36.6%) and pharyngitis (66.9% to 11.7%), which were the two most common encounters, accounting for 52% and 40.9% of all diagnoses, respectively. Inappropriate prescribing for OME, which accounted for only 7.1% of patient encounters, fell from 54.6% to 48.4%.
The study authors say that while the interventions are affordable, accessible, and easy to implement, they also have low reliability, and the changes can be difficult to maintain "because new people enter the system, and humans fall back on old habits."
"Future work is needed to embed these changes into the UC system by incorporating antibiotic stewardship initiatives into local onboarding processes, annual mandatory education, audits, and national benchmarking," they concluded.
Jun 15 Pediatrics abstract
England's NHS set to begin subscription-style payments for 2 antibiotics
Originally published by CIDRAP News Jun 16
England's National Health Service (NHS) announced yesterday it has agreed on reimbursement contracts for the two antibiotics selected for its pioneering, subscription-style payment model, and will soon make them available to patients.
Under the first-of-its-kind payment model, the NHS will pay an annual fee of up to £10 million ($12.4 million US) a year for up to 10 years for access to cefiderocol and ceftazidime-avibactam, manufactured by Shionogi and Pfizer, respectively. The hope is that paying an annual fee to the drugmakers based on the public health value of the two drugs, rather than reimbursing them based on the quantity of antibiotics sold, will incentivize funding for research into new antibiotics.
Although the two antibiotics are critical for patients with severe, multidrug-resistant infections like sepsis, hospital- or ventilator-acquired pneumonia, and bloodstream infections, they are used sparingly to avoid development of resistance, and the people who need them are relatively few. The low sales and lack of return on investment for these and other new antibiotics have led many pharmaceutical companies and investors to abandon antibiotic development, resulting in a weak pipeline of new products.
NHS and the UK National Institute for Health and Care Excellence selected cefiderocol and ceftazidime-avibactam as the first antibiotics to be bought through the pilot program in December 2020. The NHS says around 1,700 patients a year with severe bacterial infections will be eligible for the drugs, and the agreement ensures they will be used only when necessary.
"This world-leading agreement not only provides a template for other countries to follow, incentivising antimicrobial drug innovation globally, as we collectively deal with this threat to modern medicine and public health, but also gives new hope to thousands of patients who previously had no treatment options left," NHS Chief Executive Amanda Pritchard said in a press release.
Jun 15 NHS press release
Study: Not-susceptible urinary tract infections costlier, higher-impact
Originally published by CIDRAP News Jun 16
A study of electronic medical record data found that female patients with uncomplicated urinary tract infections (uUTIs) caused by not-susceptible urinary bacteria had higher healthcare costs and were more likely to develop a more serious infection compared with patients with susceptible bacteria, researchers reported this week in Antimicrobial Resistance and Infection Control.
Using data from an integrated delivery network that serves patients in mid-Atlantic states, researchers analyzed all female patients ages 12 years and older who received an antibiotic for a uUTI from July 2016 through March 2020 and had at least one urine culture within 5 days of diagnosis. The primary outcome was the difference in healthcare use and costs among patients with susceptible versus not-susceptible isolates during the 6 months after the primary diagnosis. Secondary outcomes included hospital and emergency department visits and the probability of progressing to a complicated urinary tract infection (cUTI).
A total of 2,018 women were included in the final analysis, with an average age of 44 years for both groups. The most commonly prescribed antibiotics were nitrofurantoin (60.8%), trimethoprim-sulfamethoxazole (19.4%), and ciprofloxacin (14.6%).
In the 6 months post-index uUTI event, patients with not-susceptible isolates had significantly higher numbers of prescriptions (+ 1.41) and UTI-specific prescriptions (+ 0.26) versus patients with susceptible isolates. They also had a higher probability of all-cause outpatient (+ 6.1%), UTI-related outpatient (+ 3.7%), and all-cause inpatient (+ 1.4%) visits. The predicted probability of disease progression to cUTI was more than double for patients with not-susceptible versus susceptible isolates (OR, 2.35; 95% confidence interval, 1.66 to 3.33). Over 6 months, patients with not-susceptible isolates had significantly higher all-cause costs (+ $426) and UTI-related costs (+ $157) than those with susceptible isolates.
The study authors say that, with antibiotic resistance increasing in community-acquired uUTIs in the United States, clinicians should transition away from purely empiric antibiotic prescribing.
"By treating these patients without specific knowledge of the pathogen or antibiotic susceptibility, there is a possibility that patients might be prescribed an antibiotic therapy to which their isolate is not-susceptible, leading to a higher probability of treatment failure and subsequent infections with antibiotic-resistant uropathogens," they wrote.
Jun 14 Antimicrob Resist Infect Control study
Study ties rotavirus vaccination to fewer antibiotics for gastroenteritis
Originally published by CIDRAP News Jun 13
A study of data from insured US children found that rotavirus vaccination was associated with reduced antibiotic prescribing for acute gastroenteritis, researchers reported last week in Open Forum Infectious Diseases.
Using data from a large commercial database of people with employer-sponsored health insurance coverage, researchers from Oregon Health and Science University and Emory University School of Medicine constructed a cohort of children born from 2007 through 2018 and followed those children for 5 years. They then estimated the cumulative incidence of antibiotic prescriptions associated with acute gastroenteritis—which is frequently treated with antibiotics even when caused by rotavirus or other viruses—among children who had completed a full rotavirus vaccination series by 8 months and those who had not received any dose of rotavirus vaccine. The investigators adjusted for receipt of pneumococcal vaccine, provider type, and rural/urban status.
Of the 2,136,136 children in the data set, 69.9% completed the rotavirus vaccination series by 8 months, and 15.7% had no rotavirus vaccination. Overall, 17,318 children (1.7%) received an antibiotic following an acute gastroenteritis diagnosis.
At 5 years of age, the adjusted relative cumulative incidence of antibiotic prescription following an acute gastroenteritis diagnosis was 0.793 (95% CI, 0.761 to 0.827) among children with complete rotavirus vaccination compared with children without rotavirus vaccination—or 21% lower. Additionally, the adjusted relative cumulative incidence of receiving a second, unique antibiotic prescription within 28 days was 0.820 (95% CI, 0.750 to 0.905), or 18% lower.
Using annual US trends in rotavirus vaccination, the researchers estimated that rotavirus vaccination has averted 67,045 antibiotic prescriptions nationally among children born from 2007 through 2018.
"These results demonstrate an additional important, non-targeted benefit of rotavirus vaccination and bolster evidence for the use of rotavirus vaccines for reducing antibiotic prescribing for acute gastroenteritis," the study authors wrote. "The reduction of antibiotic prescribing likely contributes to the broader effort of reducing antimicrobial resistance. Thus, increasing rotavirus vaccination coverage should be encouraged both for its intended and non-targeted effects."
Jun 9 Open Forum Infect Dis abstract
Encouraging results found for MDR-TB treatment in pregnant women
Originally published by CIDRAP News Jun 13
A systematic review and analysis of studies on pregnant women with multidrug-resistant tuberculosis (MDR-TB) found some encouraging results, researchers reported late last week in JAMA Network Open.
A total of 10 studies containing 275 pregnant patients with available data were reviewed by a team of researchers from Australia, Ethiopia, and the United States to quantify treatment and pregnancy outcomes among pregnant women with MDR-TB, who currently have limited treatment options because of the potential harmful effects that second-line TB drugs can have on embryonic and fetal development. Their meta-analysis found that the pooled estimate was 72.5% (95% CI, 63.3% to 81.0%) for treatment success, 6.8% (95% CI, 2.6% to 14.2%) for death, 18.4% (95% CI, 13.1% to 24.2%) for loss to follow-up, and 0.6% (95% CI, 0.0% to 2.9%) for treatment failure.
Treatment success was significantly higher in studies in which the proportion of patients taking linezolid was greater than the median (20.1%) compared with studies in which this proportion was lower than the median (odds ratio, 1.22; 95% CI, 1.05 to 1.42). More than half of patients (54.7%; 95% CI, 43.5% to 65.4%) experienced at least one adverse event, most commonly liver function impairment, kidney function impairment, and hearing loss.
The pooled proportion of favorable pregnancy outcomes was 73.2% (95% CI, 49.4% to 92.1%). The most common types of adverse pregnancy outcomes were preterm birth (9.5%; 95% CI, 0.0% to 29.0%), pregnancy loss (6.0%; 95% CI, 1.3% to 12.9%), low birth weight (3.9%; 95% CI, 0.0% to 18.7%), and stillbirth (1.9%; 95% CI, 0.1% to 5.1%).
The study authors note that the treatment success rate of 72.5% is close to the World Health Organization's target of 75%, and higher than that found among non-pregnant adults with MDR-TB in previous studies (60% to 69%). They suggest that increasing use of recently recommended novel drugs like linezolid, bedaquiline, and pretomanid among pregnant women with MDR-TB could further improve the treatment success rate.
"Given the limited drug options available to treat individuals with MDR-TB, especially pregnant patients, the high proportion of patients with treatment success in our study compared with previously reported findings in the general adult population is encouraging," they wrote.
Jun 10 JAMA Netw Open study
Antibiotic use fell in South Korea after national action plan
Originally published by CIDRAP News Jun 13
An analysis of health insurance claims data in South Korea found a decline in overall antibiotic use after implementation of a national action plan (NAP) on antimicrobial resistance (AMR), researchers reported yesterday in the International Journal of Infectious Diseases.
For the retrospective, population-based study, researchers looked at data from the Korean National Health Insurance claims database from 2011 to 2020. South Korea established its first NAP on AMR in 2016, and it included guidelines for antibiotic use for several types of infection and stronger monitoring of antibiotic use. Total antibiotic consumption over the study period, both inpatient and outpatient, was measured using defined daily doses per 1,000 inhabitants per day (DID), and data were analyzed for each year, dimension, and category of the WHO's AWaRe (Access, Watch, and Reserve) antibiotic classification system.
Overall, the consumption of antibiotics increased from 25.78 DID in 2011 to 28.02 DID in 2016, then decreased in 2017 following the implementation of the NAP on AMR and fell to 26.35 DID in 2019.
Consumption of Access antibiotics increased from 12.51 DID in 2011 to 13.83 in 2016, followed by a decrease in 2017. In the Watch group, antibiotic use continuously increased over the study period, from 13.24 DID in 2011 to 15.69 DID in 2019, while the Reserve group showed a small downward trend beginning in 2017. Analysis of the most frequently used antibiotics found that, after implementation of the NAP, use of amoxicillin and beta-lactamase inhibitors fell from 7.18 DID in 2016 to 4.84 DID in 2017 , use of ciprofloxacin fell from 0.81 DID to 0.7 DID, and consumption of levofloxacin declined from 0.81 DID to 0.65 DID.
An interrupted time series analysis showed that the level and the slope of the trend of total antibiotic use decreased by 0.17 and 0.001, respectively.
The study authors say the findings are in line with similar studies in Japan and Italy, and suggest the NAP could further cut antibiotic use in South Korea by improving the understanding and awareness of AMR, strengthening AMR surveillance and research, and optimizing the use of antimicrobials.
Jun 12 Int J Infect Dis study