Measuring broad-spectrum antibiotic use in hospitals with established versus new indicators. / Måling av bruk av bredspektrede antibiotika i sykehus med etablerte og nye indikatorer.

BACKGROUND: The target of a 30 % reduction in the use of broad-spectrum antibiotics in hospitals from 2012 to 2020 was not achieved, measured using the standard indicator of defined daily doses (DDD) per 100 bed days. We wished to investigate the reliability of the standard indicator and of selected alternative indicators for antibiotic use, and to determine the actual reduction in use. MATERIAL AND METHOD: We included ten DDD-based indicators with adjustment for combinations of activity marker, admission category (inpatient vs. all admissions), and case mix, and evaluated these according to how each indicator correlated with antibiotic resistance in a self-developed model. We then calculated use of broad-spectrum antibiotics in hospitals for the period 2012-20 with indicators deemed valid, and compared these indicators with regard to change in use and ranking of hospitals according to use. We used consumption rate (DDD per 1000 inhabitants per day) as an activity-neutral reference indicator (national and regional). RESULTS: All the indicators for antibiotic use showed a strong correlation with resistance. For five indicators the correlation was statistically significant. Of these, the indicator that combined adjustment for the total number of admitted patients and case mix accorded best with the consumption rate (35.6 %). The same indicator also showed the largest reduction in use (29.3 %) and gave the most hospitals that achieved a reduction of at least 30 % (13 of 22). INTERPRETATION: Combined adjustment for number of admitted patients and case mix represents a new, robust indicator for antibiotic use that is suitable for hospitals at all levels. The indicator can be used in parallel with the consumption rate, and consideration should be given to introducing the latter as the new standard indicator at national and regional level.

Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize.

Haemophilus influenzae is a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilus test medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 µg) with adjusted (+2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 µg cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 µg) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3 H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion.