Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Study: Suboptimal antibiotic therapy common in US children's hospitals
More than a quarter of children in US children's hospitals are receiving suboptimal antibiotic therapy, and antibiotic stewardships programs (ASPs) miss a substantial portion of it, according to a study yesterday in Clinical Infectious Diseases.
In the cross-sectional analysis of antibiotic prescribing at 32 hospitals recruited from the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative, researchers looked at pooled data from single-day surveys of antibiotic use conducted at each hospital over six quarters in 2016 and 2017. For the surveys, ASP physicians and pharmacists collected data on patients with active antibiotic orders and evaluated the appropriateness of those orders. The primary outcome of the analysis was the percentage of antibiotics prescribed for infectious use that were classified as suboptimal, defined as either inappropriate or needing modification.
Of the 34,927 children hospitalized on survey days, 12,213 (35%) had more than one active antibiotic order, with infectious use accounting for 95.9% of all orders. Analysis of suboptimal antibiotic use found that 21% of antibiotic orders were suboptimal, with 25.9% of patients receiving one or more suboptimal antibiotic on a given day. Among the suboptimal orders considered inappropriate, the most common reasons for the classification were bug-drug mismatches (27.7%), surgical prophylaxis for more than 24 hours (17.7%), overly broad empiric therapy (11.2%), and unnecessary treatment (11%).
The analysis also found that bacterial lower respiratory tract infections accounted for the largest share of suboptimal orders (18%), followed by surgical prophylaxis (17%), and that oral third-generation cephalosporins, carbapenems, fluoroquinolones, broad-spectrum gram-positive agents, and vancomycin had the highest odd of suboptimal prescribing. ASPs would not have reviewed 46.1% of suboptimal antibiotics through routine ASP activities.
"This study highlights the need for ASPs to look beyond current practices to identify and intervene upon additional suboptimal use and denotes areas in which to potentially expand efforts," the authors of the study conclude. "Such evolution is imperative to ensure optimal antibiotic use for all hospitalized children."
Jan 16 Clin Infect Dis abstract
Pre–urine-culture antibiotics found appropriate in kids with superbug UTIs
A US study found that most children who had urinary tract infections (UTIs) resistant to third-generation cephalosporins and were started on discordant antibiotics (those administered before urine tests are available) experienced initial clinical improvement, suggesting that narrow-spectrum empiric therapy is appropriate while awaiting final urine culture results, according to findings published today in Pediatrics.
The study included 316 children with third-generation cephalosporin-resistant UTIs caused by Escherichia coli (98.7% of patients) or Klebsiella spp. treated from 2012 to 2017 at one of five children's hospitals or a large managed care organization. A strong majority (78%) were girls, and the patients' median age was 2.4 years. Seven children required escalation of care.
For the 230 children (73%) with clinical response recorded, 192 (83.5%) experienced clinical improvement. In children with repeat urine testing while on discordant therapy, pyuria (the presence of pus in the urine) improved or resolved in 16 of 19 (84%), and urine cultures were pathogen-free in 11 of 17 (65%). The authors say their results are similar to smaller studies conducted outside the United States.
They conclude, "These results suggest that current empiric regimens are reasonable even with concerns of increasing antimicrobial resistance."
In an accompanying commentary Tej Mattoo, MD, DCH, and Basim Asmar, MD, two pediatricians from Wayne State University who were not involved in the study, say caution is needed when prescribing discordant antibiotics for these patients, and treatment should be fine-tuned as soon as urine tests are available. "Prospective, comparative studies are needed to help answer some of the questions raised by patient response to discordant antibiotic therapy for UTI," they add.
Jan 17 Pediatrics abstract
Jan 17 Pediatrics commentary
Novel ceftazidime-avibactam resistance mechanism found in Greece
Greek scientists yesterday reported the identification of a novel extended-spectrum beta-lactamase enzyme in two Klebsiella pneumoniae isolates that confers resistance to ceftazidime-avibactam. A description of the isolates appeared in Eurosurveillance.
The K pneumoniae isolates were obtained from two hospitalized Greek patients and were among a collection of 118 isolates analyzed after the European Centre for Disease Prevention and Control issued a rapid risk assessment on the emergence of ceftazidime-avibactam resistance in carbapenem-resistant Enterobacteriaceae in July 2019. Neither patient, one of whom was infected and the other colonized, had received ceftazidime-avibactam before the resistant strains were isolated.
Whole-genome sequencing and conjugation experiments identified the source of resistance as Vietnamese extended-spectrum beta-lactamase (VEB) variation, designated as VEB-25. The enzyme was carried on self-transferable plasmids that harbor several other resistance genes and have been acquired by high-risk K pneumoniae clones.
Although the extent of dissemination of VEB-25 producers in Greek K pneumoniae hospital isolates in unclear, the authors of the study say the use of ceftazidime-avibactam will likely increase the clinical relevance of VEB-25–mediated resistance.
Jan 16 Eurosurveill rapid communication
Antifungal stewardship tied to drop in antifungal drugs, candidemia
Originally published by CIDRAP News Jan 16
A team of Spanish scientists reports that after they implemented an antimicrobial stewardship program (ASP) focused on antifungal use at their university hospital in Seville, use of antifungal drugs dropped 38%, according to their findings published yesterday in the Journal of Infection.
Over a 9-year period, the team quarterly assessed antifungal consumption, incidence of hospital-acquired candidemia, Candida distribution, antifungal resistance, and crude death rate per 1,000 occupied bed days (OBDs) of hospital-acquired candidemia.
They observed a trend of decreased antifungal consumption throughout the 9 years, with a sustained 0.87% reduction per quarter and a final reduction of 38.4% over the entire study period. Reduced fluconazole use accounted for the lion's share of the drop, with a sustained reduction of 1.37% per quarter.
In addition, hospital acquired candidemia decreased 5.06% cases per 1,000 OBDs per year, and the crude death rate dropped 6.36% per 1,000 OBDs per year (from 0.044 to 0.017).
The authors conclude, "This ASP has succeeded in optimizing the use of antifungal with a long-lasting reduction without increasing the incidence, neither the mortality, of hospital-acquired candidemia."
Jan 15 J Infect abstract
University of Leeds launches website for AMR in lower-resource countries
Originally published by CIDRAP News Jan 16
Yesterday the Community Engagement for Anti-microbial Resistance (CE4AMR) project at the University of Leeds in England launched its website, which showcases the network it's building to champion the use of community engagement and participatory and creative approaches to tackle antibiotic resistance in low- and middle-income countries (LMICs).
"CE4AMR believes that if communities are fully informed and engaged with the concept of antimicrobial resistance (AMR) then subsequent behaviour change will be meaningful and sustainable, allowing global AMR objectives to be met," said Jessica Mitchell, PhD, of the University of Leeds, in a CE4AMR blog post yesterday. "To achieve this vision the CE4AMR website provides a collaborative hub to showcase current research utilising community engagement methods to tackle AMR, plus resources and guidance for those wishing to branch into this area."
The website highlights interventions in LMICs, primarily in Southeast Asia and Africa. Projects range from small-scale programs to established, long-term interventions. The site hosts material to support the methodological development of community engagement projects, background information on AMR, evaluation and monitoring resources, and practical toolkits, infographics, reports, and reflections from CE4AMR's network.
The site will also feature workshops, webinars, and conferences on AMR geared toward LMICs.
Jan 15 CE4AMR blog post
Antibiotics obtained easily without prescription in China, study finds
Originally published by CIDRAP News Jan 15
Medical students posing as patients were able to obtain antibiotics without a prescription in 84% of Chinese retail pharmacies, Chinese researchers reported today in Antimicrobial Resistance and Infection Control.
For the cross-sectional survey, pairs of undergraduate medical students were sent to pharmacies in 13 provinces representing all three regions of China. The students were instructed to tell pharmacists they had a sore throat and a headache, then request antibiotics, following a three-step protocol in which the request became increasingly specific when antibiotics were not offered. They then recorded whether they were offered antibiotics, and at which step, along with the characteristics of the pharmacy and other details of their experience.
Overall, the students visited 1,106 pharmacies and obtained antibiotics without a prescription in 925 (83.6%; 95% confidence interval [CI], 81.5% to 85.8%). In 279 (25.2%) of the pharmacies, antibiotics were obtained at step 1, in which the students described their symptoms. More than half of the pharmacies (576, 52.1%) gave out antibiotics at step 2, when the students asked for antibiotics, and 70 (6.3%) gave out antibiotics when students specifically asked for penicillin or cephalosporins.
There were significant differences between provinces, with antibiotic access (at any stage) ranging from 57.0% (57/100) in Zhejiang (81/82) to 98.8% in Guizhou. However, there were no significant differences in access to antibiotics by level of city, county, township, or village (P = 0.25), whether the pharmacy was part of a chain or independent (P = 0.23), whether a licensed pharmacist was attending (P = 0.82) or whether there was a sign saying that prescriptions were required for antibiotics (P = 0.19).
Noting that previous studies have documented the ease of obtaining antibiotics from Chinese retail pharmacies, the authors of the study say these results are further evidence that little progress has been made toward the Chinese government's goal of prescription-only antibiotics by 2020. One study published in October 2019 found that 70% of patients reporting upper respiratory tract symptoms received antibiotics in Chinese pharmacies across six provinces.
"The very easy access to antibiotics in retail pharmacies in China needs to be addressed as a matter of urgency," the authors conclude. "This should be part of the wider anti-microbial stewardship effort."
Jan 15 Antimicrob Resist Infect Control study
Oct 7, 2019, CIDRAP News story on previous study
Study finds high rates of antimicrobial use in animals, people in Vietnam
Originally published by CIDRAP News Jan 15
Total antimicrobial usage in humans and animals in Vietnam reaches an estimated 3,842 tons a year, with usage in pigs far outpacing usage in people, according to a separate study yesterday in Antimicrobial Resistance and Infection Control.
The investigators used 2015 data to come up with their estimates. Of the 3,842 tons of antimicrobials used that year, 2,741 tons (71.7%) were used in animals and 1,086 tons (28.3%) in humans. The greatest use was in pigs (41.7% of the total), people (28.3%), aquaculture (21.9%), and chickens (4.8%).
Per kilogram of body weight, the results were similar: 261.7 milligrams (mg) of antimicrobials per kilogram (kg) in humans and 247.3 mg/kg in animals. That compares with 122.0 mg/kg in people and 151.1 mg/kg in Europe, the authors noted. They add that their data can help refine policies and interventions aimed at reducing antibiotic use in Vietnam.
Jan 14 Antimicrob Resist Infect Control study
CARB-X awards $3.2 million for monoclonal antibody against superbugs
Originally published by CIDRAP News Jan 13
CARB-X today said it has awarded Trellis Bioscience of Redwood City, California, up to $3.2 million to develop an innovative monoclonal antibody designed to disrupt the protective biofilm that makes bacteria resistant to antibiotics.
The monoclonal antibody, called TRL1068, disrupts the bacterial biofilm by extracting a key protein, thereby rendering the bacteria more susceptible to attack by the immune system and to antibiotics. TRL1068 has been shown to enhance antibiotic activity in highly drug-resistant strains of gram-positive and gram-negative bacteria, the company said in a news release.
Erin Duffy, PhD, chief of research and development for CARB-X, which is based at Boston University, said in the release, "The Trellis project is in early development but if successful and approved for use in patients, its promise for tackling challenging, biofilm-mediated infections including joint implants could be transformational for the success of many modern medical procedures."
Stefan Ryser, PhD, CEO of Trellis, said TRL 1068 is a potential game-changer in treating a broad range of antibiotic-resistant bacteria. "CARB-X funding will support the manufacture of the drug for clinical development and, in a potential second tranche of funding, support an initial trial in patients with an infected implant, a type of infection that is particularly hard to treat due to biofilm formation on the surface of the implant."
Trellis could be awarded up to an additional $3.8 million if it meets certain project milestones.
Since it began in 2016, CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), a public-private partnership, has announced 55 awards of more than $182.5 million total. It plans to invest $500 million for promising approaches to combat antibiotic resistance by the end of next year.
Jan 13 CARB-X news release
Lack of ID consult tied to higher death rates, inappropriate antibiotics
Originally published by CIDRAP News Jan 13
University of Minnesota researchers have discovered that having no infectious disease (ID) consultation is associated with more than a quadruple risk of death at 3 months, and a sixfold increased risk of death in the hospital among patients with bloodstream infections caused by methicillin-resistant Staphylococcus aureus (MRSA), Candida fungi, and Pseudomonas bacteria, according to their study in Open Forum Infectious Diseases.
ID consultation was also tied to a much higher rate of receiving appropriate antibiotics or antifungals.
The retrospective cohort study included 229 bloodstream infections in 2016 through 2018 (99 from MRSA, 69 Candida, and 61 Pseudomonas). All told, 181 patients had an ID consultation and 48 did not.
Overall 3-month mortality was 36%, but it was 4.5-fold higher in those who received no ID consult. Likewise, the risk of dying while still in the hospital was 5.9 times higher in those who had no ID consult. The investigators also determined that patients who received ID consultation were 9 times more likely to receive appropriate antibiotics or antifungals, 6 times more likely to have central lines removed, and 4 times more likely to have echocardiography to evaluate for endocarditis.
The authors conclude, "Automatic ID consultation may have the potential to improve patient survival; prospective evaluation of such an intervention is warranted."
Jan 11 Open Forum Infect Dis abstract
C difficile carriage tied to living near livestock farms
Originally published by CIDRAP News Jan 13
A single-center study published in JAMA Network Open found that living near a livestock farm is tied to a higher rate of Clostridioides difficile carriage at hospital admission, among other risk factors such as having been treated in a hematology-oncology unit and recent hospitalization in general.
Scientists examined data on 3,043 adults consecutively treated at Medical College of Wisconsin in Milwaukee from May 1, 2017, through Jun 30, 2018. All patients underwent C difficile screening using a nucleic acid amplification test at hospital admission. In addition to assessing typical C difficile risk factors, the investigators also noted the distance from patients' residence to the nearest livestock farm, meat processing plant, raw materials services, and sewage facilities.
Among the cohort, 318 (10.4%) tested positive for C difficile. Patients admitted to hematology-oncology units were 35% more likely to be colonized with C difficile, and the risk quadrupled among these patients if they had co-morbidities. The researchers also found that having been hospitalized in the preceding months raised the likelihood of colonization by 70%. Both these risk factors have been identified before.
The authors also found, however, that regardless of previous healthcare exposure, the probability of C difficile colonization more than doubled for those living 1 mile from a livestock farm compared with those living 50 miles from a livestock farm. They wrote, "Although we found an inverse association between C difficile colonization and the distance from a patient's residence to livestock farms, we did not find similar associations with water treatment plants, meat processing plants, or farm raw material plants."
They conclude, "Knowledge of the epidemiology of C difficile in the community surrounding the hospital is important, as it has potential implications for the incidence of hospital-onset C difficile infection."
Jan 10 JAMA Netw Open study