Antibiotic use in children before, during and after hospitalisation.

PURPOSE: To investigate ambulatory antibiotic use in children during 1 year before and 1 year after in-hospital antibiotic exposure compared to children from the general population that had not received antibiotics in-hospital. METHODS: Explorative data-linkage cohort study from Norway of children aged 3 months to 17 years. One group had received antibiotics in-Hospital (H+), and one group had not received antibiotics in-hospital (H-). The H+ group was recruited during admission in 2017. Using the Norwegian Population Registry, 10 children from the H- group were matched with one child from the H+ group according to county of residence, age and sex. We used the Norwegian Prescription Database to register antibiotic use 1 year before and 1 year after the month of hospitalisation. RESULTS: Of 187 children in the H+ group, 83 (44%) received antibiotics before hospitalisation compared to 288/1870 (15%) in the H- group, relative risk (RR) 2.88 (95% confidence interval 2.38-3.49). After hospitalisation, 86 (46%) received antibiotics in the H+ group compared to 311 (17%) in the H- group, RR 2.77 (2.30-3.33). Comorbidity-adjusted RR was 2.30 (1.84-2.86) before and 2.25 (1.81-2.79) after hospitalisation. RR after hospitalisation was 2.55 (1.99-3.26) in children 3 months-2 years, 4.03 (2.84-5.71) in children 3-12 years and 2.07 (1.33-3.20) in children 13-17 years. CONCLUSIONS: Children exposed to antibiotics in-hospital had two to three times higher risk of receiving antibiotics in ambulatory care both before and after hospitalisation. The link between in-hospital and ambulatory antibiotic exposure should be emphasised in future antibiotic stewardship programs.

Are infants exposed to antimicrobials during the first 3 months of life at increased risk of recurrent use? An explorative data-linkage study.

OBJECTIVES: To investigate whether infants exposed to antimicrobials in hospital during the first 3 months of life had an increased risk of ambulatory antimicrobial use during the following year compared with infants not exposed to antimicrobials during the first 3 months of life. METHODS: Norwegian cohort study of infants less than 3 months consisting of one group exposed to antimicrobials recruited during hospitalization and one group not exposed to antimicrobials. Ten unexposed infants were matched with one exposed infant according to county of residence, birth year and month, and sex. The Norwegian Prescription Database was applied to register antimicrobial use from the month after discharge and 1 year onward. We defined comorbidity based on antimicrobials prescribed as reimbursable prescriptions due to underlying diseases. RESULTS: Of 95 infants exposed to antimicrobials during the first 3 months of life, 23% had recurrent use compared with 14% use in 950 unexposed infants [relative risk (RR) = 1.7 (95% CI = 1.1-2.5) and comorbidity-adjusted RR = 1.4 (95% CI = 0.9-2.2)]. The recurrence use rate in exposed term infants (≥37 weeks, n = 70) was 27% compared with 12% in their unexposed matches [RR 2.3 = (95% CI = 1.4-3.7) and comorbidity-adjusted RR = 1.9 (95% CI = 1.2-3.2). Of 25 exposed preterm infants, 3 (12%) had recurrent use. The total antimicrobial prescription rate was 674/1000 in the exposed group and 244/1000 in the unexposed group [incidence rate ratio = 2.8 (95% CI = 1.6-4.9)]. CONCLUSIONS: Infants exposed to antimicrobials during the first 3 months of life had an increased risk of recurrent use during the following year. This increased risk also appeared in term infants without infection-related comorbidity.

Identifying targets for antibiotic stewardship interventions through analysis of the antibiotic prescribing process in hospitals - a multicentre observational cohort study.

BACKGROUND: In order to change antibiotic prescribing behaviour, we need to understand the prescribing process. The aim of this study was to identify targets for antibiotic stewardship interventions in hospitals through analysis of the antibiotic prescribing process from admission to discharge across five groups of infectious diseases. METHODS: We conducted a multi-centre, observational cohort study, including patients with lower respiratory tract infections, exacerbation of chronic obstructive pulmonary disease, skin- and soft tissue infections, urinary tract infections or sepsis, admitted to wards of infectious diseases, pulmonary medicine and gastroenterology at three teaching hospitals in Western Norway. Data was collected over a 5-month period and included antibiotics prescribed and administered during admission, antibiotics prescribed at discharge, length of antibiotic therapy, indication for treatment and discharge diagnoses, estimated glomerular filtration rate (eGFR) on admission, antibiotic allergies, place of initiation of therapy, admittance from an institution, patient demographics and outcome data. Primary outcome measure was antibiotic use throughout the hospital stay, analysed by WHO AWaRe-categories and adherence to guideline. Secondary outcome measures were a) antibiotic prescribing patterns by groups of diagnoses, which were analysed using descriptive statistics and b) non-adherence to the national antibiotic guidelines, analysed using multivariate logistic regression. RESULTS: Through analysis of 1235 patient admissions, we identified five key targets for antibiotic stewardship interventions in our population of hospital inpatients; 1) adherence to guideline on initiation of treatment, as this increases the use of WHO Access-group antibiotics, 2) antibiotic prescribing in the emergency room (ER), as 83.6% of antibiotic therapy was initiated there, 3) understanding prescribing for patients admitted from other institutions, as this was significantly associated with non-adherence to guideline (OR = 1.44 95% CI 1.04, 2.00), 4) understanding cultural and contextual drives of antibiotic prescribing, as non-adherent prescribing differed significantly between the sites of initiation of therapy (between hospitals and ER versus ward) and 5) length of therapy, as days of antibiotic therapy was similar across a wide range of diagnoses and with prolonged therapy after discharge. CONCLUSIONS: Analysing the process of antibiotic prescribing in hospitals with patient-level data identified important targets for antibiotic stewardship interventions in hospitals.

The association between adherence to national antibiotic guidelines and mortality, readmission and length of stay in hospital inpatients: results from a Norwegian multicentre, observational cohort study.

Background: Clinical antibiotic prescribing guidelines are essential in defining responsible use in the local context. Our objective was to investigate the association between adherence to national antibiotic prescribing guidelines and patient outcomes across a wide range of infectious diseases in hospital inpatients. Methods: Over five months in 2014, inpatients receiving antibiotics under the care of pulmonary medicine, infectious diseases and gastroenterology specialties across three university hospitals in Western Norway were included in this observational cohort study. Patient and antibiotic prescribing data gathered from electronic medical records included indication for antibiotics, microbiology test results, discharge diagnoses, length of stay (LOS), comorbidity, estimated glomerular filtration rate (eGFR) on admission and patient outcomes (primary: 30-day mortality; secondary: in-hospital mortality, 30-day readmission and LOS). Antibiotic prescriptions were classified as adherent or non-adherent to national guidelines according to documented indication for treatment. Patient outcomes were analysed according to status for adherence to guidelines using multivariate logistic, linear and competing risk regression analysis with adjustments made for comorbidity, age, sex, indication for treatment, seasonality and whether the patient was admitted from an institution or not. Results: In total, 1756 patients were included in the study. 30-day-mortality and in-hospital mortality were lower (OR = 0.48, p = 0.003 and OR = 0.46, p = 0.001) in the guideline adherent group, compared to the non-adherent group. Adherence to guideline did not affect 30-day readmission. In linear regression analysis there was a trend towards shorter LOS when LOS was analysed for patients discharged alive (predicted mean difference - 0.47, 95% CI (- 1.02, 0.07), p = 0.081). In competing risk analysis of LOS, the adherent group had a subdistribution hazard ratio (SHR) of 1.17 95% CI (1.02, 1.34), p = 0.025 for discharge compared to the non-adherent group. Conclusions: Adhering to antibiotic guidelines when treating infections in hospital inpatients was associated with favourable patient outcomes in terms of mortality and LOS.

The effect of antibiotic stewardship interventions with stakeholder involvement in hospital settings: a multicentre, cluster randomized controlled intervention study.

Background: There is limited evidence from multicenter, randomized controlled studies to inform planning and implementation of antibiotic stewardship interventions in hospitals. Methods: A cluster randomized, controlled, intervention study was performed in selected specialities (infectious diseases, pulmonary medicine and gastroenterology) at three emergency care hospitals in Western Norway. Interventions applied were audit with feedback and academic detailing. Implementation strategies included co-design of interventions with stakeholders in local intervention teams and prescribers setting local targets for change in antibiotic prescribing behaviour. Primary outcome measures were adherence to national guidelines, use of broad-spectrum antibiotics and change in locally defined targets of change in prescribing behaviour. Secondary outcome measures were length of stay, 30-day readmission, in-hospital- and 30-day mortality. Results: One thousand eight hundred two patients receiving antibiotic treatment were included. Adherence to guidelines had an absolute increase from 60 to 66% for all intervention wards (p = 0.04). Effects differed across specialties and pulmonary intervention wards achieved a 14% absolute increase in adherence (p = 0.003), while no change was observed for other specialties. A pulmonary ward targeting increased use of penicillin G 2 mill IU × 4 for pneumonia and COPD exacerbations had an intended increase of 30% for this prescribing behaviour (p < 0.001). Conclusions: Pulmonary wards had a higher increase in adherence, independent of applied intervention. The effect of antibiotic stewardship interventions is dependent on how and in which context they are implemented. Additional effects of interventions are seen when stakeholders discuss ward prescribing behaviour and agree on specific targets for changes in prescribing practice.