Design and study setting
The study consists in a two-year retrospective observational analysis of all the ID-cons provided in a large tertiary hospital in Milan, Italy. San Carlo Borromeo Hospital (HSC) is a non-teaching public hospital with 494 beds and 20,000 admissions/year. HSC does not feature a transplant or haematology-oncology unit but does have a neurosurgery unit. Thus, possible source and aetiology of infections might account for these characteristics. Additionally, HSC does not have an ID-unit but rather a consult service that is staffed by ID-specialists from the Unit of Infectious Diseases of San Paolo Hospital since 2016.
Infectious Diseases consultations were provided once a week from September 1, 2016 to August 31, 2017 (weekly ID-cons period); from September 1, 2017 onwards the service of ID-consultation is provided on a daily basis (daily ID-cons period). All the ID-cons were performed by the same team of ID-consultants. ID-cons is defined as any request by the treating non-ID physician for ID advice with bed-side evaluation of the patient resulting in a written statement by the ID consultant.
Study procedures and definitions
Demographics, clinical conditions and microbiological findings of all hospitalized patients for whom an ID consultation was required from September 1, 2016 to September 30, 2018 were collected in a dedicated database. Clinical charts were reviewed to identify risk factors of infections (alcoholism, radio-chemotherapy, use of steroids, injection drug use), and presence of comorbidities (cardiovascular disease, dementia, liver cirrhosis, cancer, chronic obstructive pulmonary disease, chronic renal failure, diabetes, hepatitis C virus (HCV) infection). Comorbidities were evaluated according to the age-adjusted Charlson comorbidity index (ACCI), a validated prognostic tool that predicts the risk of death in patients with several comorbidities .
Hospital units were grouped into three departments:
- Medical Department, which includes: Cardiology, Gastroenterology, Internal Medicine Units, Oncology, Nephrology, Neurology, Pulmonary, Psychiatry and Rehabilitation Unit;
- Surgical Department: General Surgery, Neurosurgery, Obstetrics/gynecology, Orthopedic Unit, Urology and Vascular Surgery;
- Emergency Department: Coronary Unit, Intensive care Unit (ICU) and Sub-intensive care Units, Emergency Room, Emergency Medicine Unit and Stroke Unit.
Infections were classified as: 1) healthcare-associated infections (HAI), in the case of infections associated with hospitalization or other medical treatment that appeared 48 hours or more after hospital admission; 2) community-acquired infections (CAI), in the case of patients admitted for an infection acquired before hospital admission or diagnosed within 48 hours of admission . Classification of an infection into one of the two groups, HAI or CAI, was made by the ID consultant by combining clinical presentation with radiological and microbiological findings.
At each consultation all the antimicrobial therapies were reviewed and discussed with the treating physician. Both intravenous and oral antimicrobials were included in the study.
Interventions on antibiotic therapies were collected into the database according to the following classification: start of ATB, no need of ATB, confirmation of ATB and modification of ATB (including dosage optimization, change of ATB, de-escalation, intensification and discontinuation of ATB). De-escalation therapy was defined as: i) switching from combination to monotherapy; ii) narrowing spectrum of activity. An opposite definition was applied to intensification therapy.
Treatment was considered appropriate in case of “confirmation of ATB” by the ID consultant in terms of dose, duration, penetrability and choice of regimen. In case of microbiological findings, appropriateness was assessed based on in vitro susceptibility data. Assessment of appropriateness was performed on the basis of internal guidelines that refer, in turn, to national and international guidelines. Conversely, “modification of ATB” was considered a marker of inappropriate therapy. In order to evaluate the appropriateness of antibiotics prescribed by the non-ID specialist physician, only first consultations per patient with an already ongoing antibiotic therapy were analyzed.
Inclusion/exclusion criteria and study period
All hospitalized patients for whom the treating physician required an ID consultation, from September 1, 2016 to September 30, 2018 were included in the study. All the ID-cons, both first-time and follow-up visits, were included. Age < 18 years was the only criteria for exclusion.
We evaluated the impact of a weekly service of ID-cons (September 1, 2016 - August 31, 2017) versus a daily service of ID-cons (September 1, 2017 – September 30, 2018).
Process outcomes estimate the performance of the study. Process outcomes of the study are: i) number-of-ID-cons per 100 bed-days (bd), ii) days-from-admission-to-first-ID-cons, iii) type of ATB -intervention and iv) appropriateness of ATB prescription (evaluated only on first ID evaluation).
Primary outcomes of the study are: (i) the reduction of overall ATB consumption and (ii) the reduction of ATB consumption by department and by ATB classes expressed as Defined Daily Dose (DDD)/100bd.
The secondary outcomes were the overall and sepsis-related in-hospital annual mortality rates (as death/patient’s admissions) evaluated from January 1st, 2017 to December 31st, 2018.
Categorical variables were analysed using absolute numbers and percentages while continuous variables were analysed using the median and interquartile range (IQR). Chi-square test was used for sex, comorbidities and characteristics of the infections while Mann-Whitney U test was used for age and ACCI. ATB consumption was expressed as DDD/100bd. The indicator 100 bed-days is widely applied in antimicrobial stewardship programs for analyses of in-hospital drug use according to World Health Organization (WHO) recommendations. DDD, defined as “the assumed average maintenance dose per day for a drug used for its main indication in adults”, were calculated using the Anatomical Therapeutic Chemical/DDD Index 2020 of the WHO Center for Drugs Statistics Methodology . In order to evaluate the impact of our intervention on the outcome, a sensitivity analysis including units with high number of ID cons/100bd (≥ 25th percentile of the ID-cons distribution) was performed. Differences in patient characteristics and process outcomes were evaluated by Mann-Whitney U and Chi-square tests. All comparisons were performed by time-period (before and after the implementation of daily ID-cons). Differences in antimicrobial consumption between the two time periods were evaluated by Wilcoxon test for paired data considering ATB consumption in every single unit. A p-value < 0.05 was considered statistically significant. Statistical analyses were performed with SAS software (version 9.2).