Antimicrobial Stewardship Interventions to Combat Antibiotic Resistance: an Update on Targeted Strategies

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Penicillin is the most common drug "allergy" noted at hospital admission, although it is often inaccurate. We sought to determine total hospital days, antibiotic exposures, and the prevalence rates of Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) in patients with and without penicillin "allergy" at hospital admission. We performed a retrospective, matched cohort study of subjects admitted to Kaiser Foundation hospitals in Southern California during 2010 through 2012. It was possible to match 51,582 (99.6% of all possible cases) unique hospitalized subjects with penicillin "allergy" to 2 unique discharge diagnosis category-matched, sex-matched, age-matched, and date of admission-matched control subjects each. Cases with penicillin "allergy" averaged 0.59 (9.9%; 95% CI, 0.47-0.71) more total hospital days during 20.1 ± 10.5 months of follow-up compared with control subjects. Cases were treated with significantly more fluoroquinolones, clindamycin, and vancomycin (P < .0001) for each antibiotic compared with control subjects. Cases had 23.4% (95% CI, 15.6% to 31.7%) more C difficile, 14.1% (95% CI, 7.1% to 21.6%) more MRSA, and 30.1% (95% CI, 12.5% to 50.4%) more VRE infections than expected compared with control subjects. A penicillin "allergy" history, although often inaccurate, is not a benign finding at hospital admission. Subjects with a penicillin "allergy" history spend significantly more time in the hospital. Subjects with a penicillin "allergy" history are exposed to significantly more antibiotics previously associated with C difficile and VRE. Drug "allergies" in general, but most those notably to penicillin, are associated with increased hospital use and increased C difficile, MRSA, and VRE prevalence. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Summary Background Unnecessary antibiotic prescribing contributes to antimicrobial resistance. In this trial, we aimed to reduce unnecessary prescriptions of antibiotics by general practitioners (GPs) in England. Methods In this randomised, 2 × 2 factorial trial, publicly available databases were used to identify GP practices whose prescribing rate for antibiotics was in the top 20% for their National Health Service (NHS) Local Area Team. Eligible practices were randomly assigned (1:1) into two groups by computer-generated allocation sequence, stratified by NHS Local Area Team. Participants, but not investigators, were blinded to group assignment. On Sept 29, 2014, every GP in the feedback intervention group was sent a letter from England's Chief Medical Officer and a leaflet on antibiotics for use with patients. The letter stated that the practice was prescribing antibiotics at a higher rate than 80% of practices in its NHS Local Area Team. GPs in the control group received no communication. The sample was re-randomised into two groups, and in December, 2014, GP practices were either sent patient-focused information that promoted reduced use of antibiotics or received no communication. The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population, controlling for past prescribing. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN32349954, and has been completed. Findings Between Sept 8 and Sept 26, 2014, we recruited and assigned 1581 GP practices to feedback intervention (n=791) or control (n=790) groups. Letters were sent to 3227 GPs in the intervention group. Between October, 2014, and March, 2015, the rate of antibiotic items dispensed per 1000 population was 126·98 (95% CI 125·68–128·27) in the feedback intervention group and 131·25 (130·33–132·16) in the control group, a difference of 4·27 (3·3%; incidence rate ratio [IRR] 0·967 [95% CI 0·957–0·977]; p<0·0001), representing an estimated 73 406 fewer antibiotic items dispensed. In December, 2014, GP practices were re-assigned to patient-focused intervention (n=777) or control (n=804) groups. The patient-focused intervention did not significantly affect the primary outcome measure between December, 2014, and March, 2015 (antibiotic items dispensed per 1000 population: 135·00 [95% CI 133·77–136·22] in the patient-focused intervention group and 133·98 [133·06–134·90] in the control group; IRR for difference between groups 1·01, 95% CI 1·00–1·02; p=0·105). Interpretation Social norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes. Funding Public Health England.