Burden of Antibiotic Resistance in Gram-Negative Infections in Dutch Hospitals (GRAND-ABC)

Sample (5/week/hospital) of all patients in a hospital that meet all of the following:

• meeting the criteria of at least one infection entity based on (modified) definitions of the Center for Disease Control and Infection Prevention (CDC; Am J Infect Control 2008;36:309-32) (restricted to infections that have septic potential);
• a culture with a gram-negative isolate (Enterobacteriaceae / Pseudomonas aeruginosa / Acinetobacter spp. / Stenotrophomonas maltophilia) with minimal inhibitory concentration (MIC) results from an automated system available that can be used to identify such an infection entity according to these criteria;
• receipt of antibiotics (oral, intravenous or intramuscular) for this infection, the choice of which is determined by the culture with the gram-negative (i.e. this isolate is seen as the causative pathogen);
• were admitted to the hospital during (part of) the infection episode.

Date of entry into cohort: date of index culture of infection episode

Matched sample of all patients that (1) were admitted to the hospital and (2) did not have a gram-negative infection according to the 4 criteria set out in the other group on the date used for matching. Selected by matching 1:1 to patients with gram-negative infections on (1) hospital, (2) length of hospital stay on the date the index culture for the infected patient was obtained, and (3) age.

Date of cohort entry: date of index culture of matched infected patient

Costs generated from societal perspective, including:

• Direct costs within healthcare sector, based on relating standard Dutch reference prices to (1) restricted chart review for all patients, (2) extensive collection of cost data in two of eight participating hospitals, (3) health care use after discharge, as recorded from medical files and reported by patients in questionnaires
• Other direct costs (own out-of-pocket expenses and time invested by caregivers), as reported by patients in questionnaires
• Indirect productivity losses, as reported by patients in questionnaires
• (possibly) Decision-analytic modelling of costs generated by sequelae not within 90 days of index culture date

Questionnaires are not available for the non-infected cohort, and therefore the costs for acquiring gram-negative infections can only be calculated from the hospital perspective.

Years of Life Lost (YLL) and Years Lived with Disability (YLD) attributable to infection as apparent from an outcome tree of health outcomes related to gram-negative infections. This tree is preconceived, but modifiable according to observed sequelae in the study. A mathematical model for this outcome will be constructed that incorporates, apart from the observed sequelae in the study, factors such as (1) preexisting decreased life expectancy and quality of life due to comorbidity, (2) known transition parameters between health outcomes from literature, (3) confounding effects of comorbidity on transition parameters, (4) sequelae not observed within the time frame of data collection for the study, (5) 'baseline' change in health outcomes during hospitalization as apparent from the non-infected cohort, and (6) occupancy of several health outcome simultaneously.

This outcome will not be calculated for the non-infected cohort.

Measured by EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) in questionnaires, as a confirmation of the DALY model results.

This outcome will not be calculated for the non-infected cohort.