Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Study: Hospital patients allergic to penicillin twice as likely to receive beta-lactam alternatives
Originally published by CIDRAP News Jul 1
Hospitalized patients with a documented penicillin allergy are nearly twice as likely to receive a potentially harmful beta-lactam antibiotic alternative, US researchers reported in JAMA Internal Medicine.
In a cross-sectional study of 10,992 patients receiving antibiotics at 106 US hospitals, a team led by researchers from Massachusetts General Hospital (MGH) found that 1,741 patients (16%) had a documented penicillin allergy. Compared with patients without a documented penicillin allergy, those with a documented allergy had higher beta-lactam alternative antibiotic use (1,114 of 1,741 [64%] vs 4,438 of 9,251 [48%]) and lower narrow-spectrum beta-lactam use (227 of 1,741 [13%] vs 2,811 of 9,251 [30%]).
In the fully adjusted model, the adjusted odds ratio (aOR) for receiving beta-lactam alternative antibiotics was 1.94 (95% confidence interval [CI], 1.74 to 2.17) for patients with a documented penicillin allergy, with especially high odds of clindamycin use (aOR, 5.34; 95% CI, 3.99 to 7.13), which is associated with an increased risk of Clostridioides difficile infection. Patients with a documented allergy also had lower odds of receiving a narrow-spectrum beta-lactam (aOR, 0.35; 95% CI, 0.31 to 0.40).
The association between a documented penicillin allergy and alternative antibiotic use was stronger among patients receiving prophylactic antibiotics for surgery (aOR, 7.31; 95% CI, 5.01 to 10.69) and those receiving antibiotics for urinary tract infection (aOR, 2.07; 95% CI, 1.51 to 2.85).
The authors of the study note that since studies have found that only a small percentage of patients with documented penicillin allergies are truly allergic, at least 90% of the alternative antibiotic recommendations were likely unnecessary.
"Unfortunately, antibiotic decisions are often made based on limited information or without a thorough investigation," senior author Rochelle Walensky, MD, MPH, chief of infectious diseases at MGH, said in a press release. "We learned from our study that antibiotic prescribing without full allergy information can ultimately do the patient more harm than good."
Walensky and her colleagues suggest hospitals should conduct inpatient penicillin allergy interventions on patients prescribed clindamycin and those with planned surgical procedures.
Jun 29 JAMA Internal Med research letter
Jun 30 MGH press release
WHO experts urge antimicrobial stewardship during pandemic response
Originally published by CIDRAP News Jul 1
Antimicrobial resistance (AMR) experts from the World Health Organization (WHO) are urging that antimicrobial stewardship activities be integrated into the COVID-19 pandemic response.
In an editorial published in the Bulletin of the World Health Organization, scientists with the WHO's Department of Global Coordination and Partnership on Antimicrobial Resistance note that while the WHO's interim guidance on COVID-19 treatment incorporates antibiotic stewardship principles with specific recommendations, a broader strategy to address antimicrobial use during the pandemic is needed. They call for five specific measures to be integrated into the pandemic response across the broader health system.
The first measure they recommend is increased training for healthcare workers treating COVID-19 patients, with a focus on improving the recognition of signs of severe COVID-19 and superimposed bacterial or fungal infections, eliminating unnecessary antibiotic use, evaluating the need for medical devices that may increase the risk of bacterial infections, and implementing strict infection prevention and control measures.
The other recommended measures include improving COVID-19 testing to reduce turnaround time and the urge to initiate empiric antibiotics; ensuring the continuity of essential health services that, if interrupted, could lead to increased use of antibiotics; exercising maximum caution on the use of biocides for environmental and personal disinfection; using biocides with a low selection pressure for antibiotic resistance; and addressing research gaps to ensure that antimicrobial stewardship activities become an integral part of the pandemic response.
"These measures would stem the emergence of untreatable drug-resistant infections and diseases that could potentially lead to another public health emergency," the authors write.
July 2020 Bull World Health Organ editorial
CARB-X to fund its first CRISPR-based phage project
Originally published by CIDRAP News Jun 30
CARB-X announced an award today of up to $1.82 million to French biotechnology company Eligo Bioscience to develop CRISPR- and bacteriophage-based therapeutics to prevent multidrug-resistant infections in transplant patients.
Eligo's EB004 project takes bacteriophages, which are viruses that selectively infect and kill bacteria, and designs them to inject synthetic DNA into targeted bacterial populations—extended-spectrum beta-lactamase-producing and carbapenem-resistant Escherichia coli and Klebsiella pneumoniae—in a patient's digestive tract. The DNA is designed to circumvent bacterial defense systems and enable the expression of a CRISPR-Cas system that creates double strand DNA breaks only in the antibiotic resistance genes carried by the targeted bacteria, selectively killing the bacteria carrying these genes and leaving those that don't carry antibiotic-resistance genes alone.
The idea behind the project is to eliminate these multidrug-resistant pathogens from a transplant patient's microbiome before the procedure to prevent the onset of life-threatening post-operative infections, without disrupting any beneficial bacteria.
"Eligo is developing a new class of targeted biotherapeutics to selectively eliminate certain multidrug-resistant bacteria by combining the specificity of CRISPR and the ability of bacteriophages to deliver DNA into bacteria," CARB-X chief of research and development Erin Duffy, PhD, said in a press release. "This innovative approach, if successful, offers additional benefits in that it can prevent multi-drug-resistant infections while not harming bacteria in the microbiome."
This is the first CRISPR-based phage project funded by CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator). Eligo could receive up to $7.05 million in funding if certain project milestones are met.
Jun 30 CARB-X press release
Antimicrobial stewardship helps Saudi hospitals cut antibiotic use, expenses
Originally published by CIDRAP News Jun 30
Implementation of antimicrobial stewardship programs at four private hospitals in Saudi Arabia resulted in reduced antibiotic use and expenditures and lowered incidence of healthcare-associated infections, Saudi researchers reported yesterday in Antimicrobial Resistance and Infection Control.
In a pre-post quasi-experimental study, the researchers aimed to measure the impact of the antibiotic stewardship program implemented at four Al Habib Medical Group hospitals by comparing the 1-year baseline period prior to implementation (2015) with 4 years of post-implementation data (2016 through 2019). Patients were included on the pre- and post-implementation arms if they were on any of 10 selected broad-spectrum antibiotics (imipenem/cilastatin, piperacillin/tazobactam, colistin, tigecycline, cefepime, meropenem, ciprofloxacin, moxifloxacin, teicoplanin, and linezolid).
A total of 409,403 subjects were included in the study, with 79,369 in the pre-implementation period and 330,034 in the post-implementation arm. Average consumption of the targeted antibiotics, in defined daily doses (DDDs), was lower from 2016 through 2019 than in the pre-implementation period (233 vs 320 DDDs per 1,000 patient-days, P = 0.689), and antibiotic expenditures decreased by 28.45% in the first years of the program and remained relatively stable in subsequent years, with an estimated overall cumulative cost savings estimated at US $1,676,514.
Rates of healthcare-associated infections also fell, with incidence of C difficile declining by 86.17%, ventilator-associated pneumonia falling by 75%, and central line-associated bloodstream infections falling by 94.12%.
The authors of the study note that many indirect expenses are also expected to decrease proportionally, including those associated with antibiotic resistance, antibiotic side effects, hospital-acquired infections, and increased length of hospital stay and readmission.
Jun 29 Antimicrob Resist Infect Control study
Rapid ID, susceptibility test aids stewardship, study finds
Originally published by CIDRAP News Jun 30
Implementation of a rapid identification (ID) and antimicrobial susceptibility test (AST) combined with pharmacy-driven antimicrobial stewardship in patients with gram-negative bacteremia and candidemia was associated with decreased use of broad-spectrum antibiotics, shortened time to targeted therapy, and fewer days in the hospital, researchers reported yesterday in Antimicrobial Agents and Chemotherapy.
In a pre-post quasi-experimental study conducted at a 288-bed community hospital in Maryland, researchers investigated the impact of the Accelerate Pheno system and Accelerate PhenoTest BC kit (AXDX), which can produce ID results in 2 hours and AST results in an additional 5 hours, on antimicrobial stewardship and clinical outcomes when compared with rapid genotypic testing.
The study included 200 patients (100 pre-AXDX implementation and 100 post-AXDX implementation) with positive blood cultures with gram-negative rods or candida species. The primary endpoints were time to first antibiotic intervention, time to targeted antibiotic therapy, and 14-day hospital mortality. Secondary endpoints included hospital and intensive care unit (ICU) length of stay (LOS), antibiotic intensity score at 96 hours, and 30-day readmission rates.
The final analysis included 84 patients in the pre-implementation group and 89 in the post-AXDX group. The results showed that time to first antibiotic intervention was significantly shorter in the post-AXDX group compared with the pre-AXDX group (8 vs 26.3 hours, P = .003), as was the median time to targeted therapy (9 vs 14.4 hours, P = .03). In addition, hospital LOS was shorter in the post-AXDX group compared with the pre-AXDX patients (6 vs 8 days, P = .002), and the antibiotic intensity score was lower (12 vs 16, P = .0002). Both groups had a comparable 14-day mortality (0% vs 3.6%, P = .11).
"Our results demonstrate that in a resource-limited community hospital setting, fast ID and AST via AXDX can be used in conjunction with clinical pharmacy services to positively impact patient care," the authors of the study wrote.
Jun 29 Antimicrob Agents Chemother abstract
Delayed URTI antibiotics tied to higher risk of hospitalization
Originally published by CIDRAP News Jun 29
Waiting to treat upper respiratory tract infections (URTIs) with antibiotics was associated with an increased risk of hospital admission in a large population-based study examining the safety of delayed antibiotic prescribing in URTI patients, researchers from the University of Manchester reported today in Clinical Infectious Diseases.
Using two large databases of electronic health records from primary care practices linked to hospital admission records in the United Kingdom and Wales, the researchers looked specifically at patients with a URTI diagnosis and a prescription for amoxicillin, clarithromycin, doxycycline, erythromycin, or phenoxymethylpenicillin. Antibiotic prescribing among patients was classified as either immediate or delayed, with immediate defined as a prescription on the same day as diagnosis and delayed defined as a URTI diagnosis 1 to 30 days before the prescription. The primary outcome was hospital admission for infection-related complications in the 30 days after the prescription.
Between the two databases, 1.82 million with a URTI and an antibiotic prescription were identified, with 91.7% receiving an immediate antibiotic and 8.3% receiving a delayed antibiotic. When the results of both data sets were combined, delayed antibiotic prescribing was associated with 52% increased risk of infection-related hospital admission (adjusted hazard ratio [HR], 1.52; 95% CI, 1.43 to 1.62). The effects of delayed prescribing were lowest in children (adjusted HR, 1.36; 95% CI, 1.25 to 1.47) and highest in adults aged 18 to 59 years (adjusted HR, 1.61; 95% CI, 1.42 to 1.84). The probability of delayed antibiotic prescribing was unrelated to the predicted risks of hospital admission.
Analyses of Numbers Needed to Harm (NNH) showed considerable variability across different patient groups. The median NNH with delays in prescribing was 1,357, 2.5% percentile 295 and 97.5% percentile 3,366.
The findings are noteworthy because UK treatment guidelines recommend no antibiotic or a delayed antibiotic in URTIs except in more severe cases.
"There is an important need to better target delayed antibiotic prescribing to URTI patients with moderate risks of complications and immediate antibiotic to those with higher risks," the authors of the study concluded. "Further research on the cost effectiveness of the most optimal threshold is needed to establish the treatment thresholds."
Jun 29 Clin Infect Dis abstract
