Antibiotic stewardship programs have reduced the incidence of infections and colonization with multidrug-resistant (MDR) gram-negative bacteria in hospital patients by more than half, and cut methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile incidence by a third, according to a new review and meta-analysis in The Lancet Infectious Diseases.
The evidence also points to an increased effect when stewardship programs are combined with infection control measures, especially those targeting improved hand hygiene.
The review, by infectious disease expert David Baur, MD, and a team of researchers from Tubingen University Hospital in Germany, analyzed 32 studies, comprising more than 9 million patient-days, conducted from 1992 to 2014 in the United States, Europe, Asia, and Latin America. While previous reviews of stewardship programs at hospitals have focused on clinical outcomes, cost, incidence of antibiotic resistance, and C difficile infections, this appears to be the first to measure incidence of colonization or infections as a primary outcome.
Baur and his colleagues say the findings show that antibiotic stewardship programs play an essential role in combating the development of antibiotic resistance and should be promoted at the hospital level to prevent the spread of drug-resistant infections among patients.
"Implementation of these measures should be recommended not only on the basis of the well known cost benefits, but also because of the more relevant, patient-based clinical advantages," they write.
Significant reduction in resistance rates
In the 32 studies selected for analysis, the most frequent antibiotic stewardship interventions implemented were audits of physician prescribing practices and policies restricting use of certain antibiotics. Other interventions included antibiotic cycling, education, and use of implementing guidelines for stewardship programs.
In 10 of the studies, stewardship programs were implemented at the same time as infection control measures, most frequently hand hygiene and patient screening. Fifteen of the studies looked at interventions implemented throughout an entire hospital, while 17 analyzed interventions focused on a single hospital ward.
A pooled analysis of the 32 eligible studies showed that antibiotic stewardship implementation was associated with a 51% reduction in MDR gram-negative bacteria—defined as resistant to carbapenems or at least three anti-pseudomonal antibiotic classes—and an incidence ratio (IR) of 0.49. The incidence ratio was calculated as the ratio between the incidence of infection or colonization with the targeted antibiotic-resistant bacteria before and after implementation of the program.
When broken down by type of gram-negative bacteria, the analysis showed that reduction in incidence was greatest for carbapenem-resistant Acinetobacter baumannii (56% reduction, IR 0.44) and Pseudomonas aeruginosa (29% reduction, IR 0.71).
The analysis also showed that antibiotic stewardship was associated with a 48% reduction in the incidence of extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria (IR 0.52), a 37% reduction in incidence of MRSA (IR 0.63), and a 32% reduction in C difficile incidence (IR 0.68). The incidence of aminoglycoside-resistant (IR 0.82) and fluoroquinolone-resistant (IR 0.74) gram-negative bacteria was not significantly reduced.
When the reviewers further explored the results by study setting, type of stewardship intervention, and co-implementation with infection control measures, they found that stewardship programs implemented along with infection control measures were more effective at reducing incidence of drug resistance than stewardship programs alone (31% reduction, IR 0.69 vs. 19% reduction, IR 0.81), with programs emphasizing hand-hygiene associated with a 66% reduction in incidence of antibiotic resistance (IR 0.34) and those without hand-hygiene intervention associated with a 17% reduction (IR 0.83). Hand hygiene had the greatest impact when co-implemented with antibiotic cycling (51% reduction in resistance, IR 0.49).
"Our findings clearly show that antibiotic stewardship programmes, when implemented alongside infection control measures, are more effective than implementation of antibiotic stewardship alone," the authors write.
Another notable finding was that stewardship interventions had their greatest impact in hematology-oncology departments, where they were associated with a 59% reduction in incidence of drug-resistant infections (IR 0.41). "This finding is notable because of the serious outcomes of MDR infections in this setting and the scarcity of information about the effectiveness of antibiotic stewardship programmes in haematology-oncology patients," the authors write.
An 'advocacy tool' for stewardship
In an accompanying commentary, infectious disease and antibiotic stewardship experts Debbie Goff, PharmD, and Marc Mendelson, PhD, argue that the findings of the review are significant because while frontline providers can attest to the impact of antibiotic resistance on morbidity and mortality, many healthcare providers, managers, and policy makers continue to challenge the evidence that stewardship can have a beneficial effect on rates of antibiotic resistance.
But these results provide compelling evidence that stewardship favorably affects rates of resistance. As a result, Goff and Mendelson write, the findings are an important advocacy tool for antibiotic stewardship, one that should be used to convince "naysayers, policy makers, and stakeholders" that stewardship plays a leading role in the effort to decrease antibiotic resistance while preserving antibiotic effectiveness.
In particular, they note that the finding that the greatest benefit comes from implementing antibiotic stewardship programs alongside infection control measures "highlights the need for governments to develop national action plans that co-prioritise antibiotic stewardship and infection prevention."
"Such plans need to be converted into concrete action, which will require considerable financial input, especially in low-income and middle-income countries where health systems face substantial budgetary restrictions," they write.
In 2015, the World Health Organization (WHO) released a global action plan on antimicrobial resistance that called on all WHO member countries to have a national action plan in place by 2017. The WHO estimates that roughly two-thirds have managed to complete their plan or are in the process of developing one.
Jun 16 Lancet Infect Dis abstract
Jun 16 Lancet Infect Dis comment