WHAT ARE SOME EXAMPLES OF ANTIBIOTIC STEWARDSHIP PROGRAMS THAT HAVE BEEN SUCCESSFUL IN REDUCING RESISTANCE SELECTION PRESSURES

Some noteworthy antibiotic stewardship programs that have successfully reduced antibiotic resistance include the following:

The Duke Antimicrobial Stewardship Outreach Network (DASON) implemented collaborative antimicrobial stewardship programs across 55 North Carolina nursing homes between 2012-2017. Through educational outreach, reporting of antimicrobial use and resistance data, and recommendations for treatment guidelines, DASON was able to significantly reduce broad-spectrum antibiotic use by 32% and total antibiotic days of therapy by 19% across participating facilities. Critically, they also observed reductions in key resistance genes and multidrug-resistant organisms (MDROs) colonizing nursing home residents. This demonstrated how stewardship interventions can help curb resistance selection pressures even in vulnerable long-term care settings.

At Vanderbilt University Hospital, a multifaceted antimicrobial stewardship program was launched in 2010 focused on prospective audit and feedback, formulary restriction and preauthorization, clinical guidelines, and education. Through these interventions,broad-spectrum antibiotic use declined by 36%, total antibiotic use fell by 27%, and hospital-onset Clostridium difficile infections decreased by 56%. Overall hospital mortality also improved. Genome sequencing analysis of C. difficile isolates revealed an 8.4% annual decline in fluoroquinolone-resistant strains following program implementation, directly tying the resistance reduction to decreased selection pressure from stewardship-driven decreases in fluoroquinolone prescribing.

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Brigham and Women’s Hospital in Boston initiated a successful antimicrobial stewardship program in 2006 focused on prospective audit and feedback, clinical guidelines, formulary restriction, and education. Over the subsequent decade, they achieved 25-40% reductions in use of broad-spectrum antibiotics, a 40% reduction in total antibiotic days of therapy, and significant declines in hospital-onset C. difficile,vancomycin-resistant enterococci, and multidrug-resistant Gram-negative bacilli infections. Whole genome sequencing analysis of Enterobacteriaceae isolates found reduced acquisition and transmission of antibiotic resistance genes as well as stabilizing or declining resistance trends for many resistance phenotypes. The program was directly attributed with helping to curb rising resistance rates.

A multinational point-prevalence study of 233 ICUs across 75 countries before and after implementing antibiotic stewardship found a 15% reduction in antibiotic use along with reductions in antibiotic resistance, without negatively impacting clinical outcomes. Extended-spectrum beta-lactamase (ESBL) production in E. coli isolates fell from 21% to 18% of isolates, and methicillin-resistant Staphylococcus aureus (MRSA) bacteremias decreased from 21 to 17 per 1,000 patient-days after stewardship implementation. This study demonstrated the global potential for antimicrobial stewardship to curb rising resistance.

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In the Netherlands, strict guidelines and national quality indicators for judicious antibiotic prescribing, particularly of fluoroquinolones and third-generation cephalosporins, led to substantial reductions in overall antibiotic use and use of highest-priority critically important antibiotics between 2000-2015. Genome sequencing found significant concurrent declines in quinolone resistance determinants and ESBL genes matching the decreases in selecting antibiotic pressure. The Netherlands programs are considered a model of success for implementing resistance-reducing antibiotic stewardship on a national scale.

These successful antibiotic stewardship programs highlight that through coordinated multi-pronged efforts of guideline development, education, and audit-based feedback on prescribing appropriateness and compliance, significant and sustained reductions in broad-spectrum antibiotic use, total antibiotic exposure, and key antibiotic-resistant infections can be achieved. Critically, genomic evidence from several programs directly links the resulting decreases in antibiotic selection pressure to stabilization or reductions in antibiotic resistance gene acquisition and transmission. Such programs demonstrate antibiotic stewardship’s vital role in helping curb the growing global public health crisis of antibiotic resistance.

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