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Stewardship / Resistance Scan for Oct 08, 2021

Stewardship / Resistance Scan for Oct 08, 2021

Narrow-spectrum antibiotics found safe, effective for moderate pneumonia

A clinical trial in the Netherlands found that an antimicrobial stewardship intervention safely reduced broad-spectrum antibiotic use in patients hospitalized with moderately severe pneumonia, Dutch researchers reported yesterday in The Lancet Infectious Diseases.

In the cross-sectional, stepped-wedge, cluster-randomized non-inferiority trial conducted in 12 Dutch hospitals, investigators enrolled immunocompetent adults who had a working diagnosis of moderately severe community-acquired pneumonia and were admitted to a non-intensive care unit ward. Every 3 months, a block of two hospitals would transition from the control period to the intervention period, with all hospitals eventually transitioning to the intervention period.

The antimicrobial stewardship intervention involved education, engaging local opinion leaders, and prospective audit and feedback of antibiotic use, with the aim of increasing the use of narrow-spectrum agents (benzylpenicillin and amoxicillin) for moderately severe pneumonia. The co-primary outcomes of the trial, which included 4,084 patients in the intention-to-treat analysis, were broad-spectrum days of therapy per patient and 90-day all-cause mortality.

The adjusted mean broad-spectrum days of therapy per patient were reduced from 6.5 days in the control period to 4.8 days in the intervention period, yielding an absolute reduction of 1.7 days (95% confidence interval [CI], 1.1 to 2.4) and a relative reduction of 26.6% (95% CI, 18.0 to 35.3). Crude 90-day mortality was 10.9% (242 of 2228 died) in the control period and 10.8% (199 of 1841) in the intervention period, yielding an adjusted absolute risk difference of 0.4% (90% CI, –2.7 to 2.4), indicating non-inferiority.

The study authors say the findings provide further evidence that antimicrobial stewardship interventions are efficacious in optimizing antibiotic use.

“In addition, our results add to the existing evidence base regarding the efficacy of narrow-spectrum beta-lactam monotherapy for patients with moderately severe community-acquired pneumonia, and thereby provide firm evidence to change clinical practice towards increased use of narrow-spectrum antibiotics, which will reduce antibiotic selective pressure for antimicrobial resistance,” they wrote.
Oct 7 Lancet Infect Dis


Molecular test for resistant TB shows high diagnostic accuracy

In another study published yesterday in the same journal, an international team of researchers reported that a rapid, sputum-based, molecular diagnostic test for drug-resistant tuberculosis (DR-TB) showed high diagnostic accuracy and met the World Health Organization’s criteria for a next-generation drug susceptibility test.

The prospective study involved individuals presenting with pulmonary TB symptoms and at least one risk factor for drug resistance at four sites in India, Moldova, and South Africa from Jul 31, 2019, through Jun 20, 2021. The Xpert MTB/XDR assay was used as a reflex test to detect resistance to isoniazid, fluoroquinolones, ethionamide, amikacin, kanamycin, and capreomycin in adults who had already tested positive for Mycobacterium tuberculosis complex on other assays. Diagnostic performance was evaluated against phenotypic drug-susceptibility testing and whole-genome sequencing.

Of the 710 patients enrolled, 611 had results from both Xpert MTB/XDR and the composite reference standard for any drug and were concluded in the analysis. Although performance of the assay varied among sites, overall, Xpert MTB/XDR had reasonable to high diagnostic accuracy. Sensitivity for detection of resistance was 94% (460 of 488; 95% CI, 92% to 96%) for isoniazid, 94% (222 of 235; 95% CI, 90% to 96%) for fluoroquinolones, 54% (178 of 328; 95% CI, 50% to 61%) for ethionamide, 73% (60 of 82; 95% CI, 62% to 81%) for amikacin, 86% (181 of 210; 95% CI, 81% to 91%) for kanamycin, and 61% (53 of 87; 95% CI, 49% to 70%) for capreomycin. Specificity was 98% to 100% for all drugs.

Performance was equivalent to that of line-probe assays. The non-determinate rate of Xpert MTB/XDR (ie, invalid M tuberculosis complex detection) was 2.96%.

“The Xpert MTB/XDR assay is an important method to identify and direct treatment of isoniazid-resistant, fluoroquinolone-resistant, and pre-extensively drug-resistant tuberculosis,” the authors wrote. “This rapid sputum-based assay has the potential to greatly improve diagnosis and management of DR-TB worldwide.”
Oct 7 Lancet Infect Dis abstract


Kids’ flu vaccine campaign has mixed impact on antibiotics for respiratory infections

Researchers with Public Health England found that a flu vaccine program for children had a mixed impact on antibiotic prescribing for respiratory infections, according to a study published yesterday in Vaccine.

To assess the impact of the United Kingdom’s live attenuated influenza vaccine (LAIV) program for children aged 2 to 3 years on antibiotic prescribing, the researchers calculated antibiotic prescribing incidence rates for respiratory tract infections (RTIs) and urinary tract infections (UTIs) at general practice (GP) levels by age category (children 10 years and younger and adults) and season in LAIV pilot areas from 2013 through 2016.

UTI prescriptions were used for baseline comparison. To estimate the LAIV intervention impact, a random effects model was fitted with factors for period, pilot area, and the interaction between period and pilot area.

RTI antibiotic prescribing rates for children 10 and under and adults showed clear seasonal trends and were lower in LAIV pilot areas and non-pilot areas after the introduction of the program in 2013. The reductions in RTI prescriptions for children were similar in all areas, but the researchers note the reduction may be linked to the start of the UK antimicrobial resistance (AMR) strategy.

The model also showed that, at the GP level, antibiotic prescribing for RTI was significantly inversely related to vaccine uptake in preschool children (2 to 3 years of age), with antibiotic prescribing being reduced by 2.7% (95% CI, 2.1% to 3.4%) for every 10% increase in flu vaccine uptake in pre-school children. 

“In summary, we did not find evidence of a population level impact of the live attenuated influenza vaccination programme for primary school age children on reducing GP antibiotic prescribing rates for respiratory infections for children or adults in England, though we did observe a significant reduction in respiratory antibiotic prescribing with increasing LAIV uptake in children 2–3 years of age at the primary care level,” the study authors wrote.

“Our paper highlights the importance of further work to investigate the apparent association between pre-school influenza vaccination and antibiotic prescribing.”
Oct 7 Vaccine abstract

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