#13 Dalbavancin Activity against Bacterial Isolates from Pediatric Patients: Results from the International Dalbavancin Evaluation of Activity (IDEA) Program for the United States and Europe (2019-2021)

Abstract

Abstract Background Dalbavancin is a lipoglycopeptide approved in the United States (US; 2014) and Europe (2015) to treat skin and skin structure infections in adults with a convenient parenteral administration of either a single dose of 1500 mg or a dose of 1000 mg followed by 500 mg a week later. We evaluated dalbavancin in vitro spectrum and potency against Gram-positive isolates from pediatric patients. Method 4,487 consecutive, unique pediatric patient isolates of clinical significance were collected from 32 US and 34 European medical centers and tested for susceptibility to dalbavancin and comparators by broth microdilution. The most common organisms were Staphylococcus aureus (n=2,633), Streptococcus pneumoniae (n=689), and beta-hemolytic streptococci (BHS; n=584). Susceptibility results were analyzed by patient age group: ≤1 years old (yo; n=1,459), 2-5 (1,106), 6-12 (1,164), and 13-17 (758). Results Dalbavancin showed complete activity against S. aureus (100% susceptibility), with a highest MIC value of 0.12 mg/L and consistent activity against all age groups (MIC50/90 of 0.03/0.03 mg/L for the US and Europe as well as the MSSA and MRSA subsets). MRSA rates were higher in the US (32.4% overall) than Europe (14.0%). In the US, MRSA rates were 38.7%, 34.2%, 28.4%, and 25.0% in the ≤1, 2-5, 6-12, and 13-17 yo groups, respectively; whereas, in Europe, it was slightly lower in the 2-5 yo group (11.5%) compared to the other age groups (14.1-14.8%). Ceftaroline was consistently active against S. aureus isolates from all age groups, with susceptibility rates ranging from 99.4% (13-17 yo) to 99.8% (2-5 yo) in the US and from 95.3% (≤1 yo) to 100.0% (2-5 yo) in Europe. Dalbavancin showed consistent activity against S. pneumoniae from all age groups (MIC50/90 of 0.008/0.015 mg/L for all age groups in the US and Europe) with a highest MIC value of 0.06 mg/L (1 isolate). All S. pneumoniae isolates were susceptible to ceftaroline, and susceptibility to ceftriaxone (at ≤1 mg/L; non-meningitis breakpoint) ranged from 92.7% (13-17 yo) to 100.0% (≤1 yo), or 97.8% overall. Dalbavancin was also highly active against BHS (n=584; MIC50/90, 0.008/0.015 mg/L; highest MIC, 0.06 mg/L), coagulase-negative staphylococci (n=240; MIC50/90, 0.03/0.06 mg/L; highest MIC, 0.25 mg/L), Enterococcus faecalis (n=200; MIC50/90, 0.03/0.06 mg/L; highest MIC, 0.06 mg/L), viridans group streptococci (n=102; MIC50/90, 0.008/0.03 mg/L; highest MIC, 0.12 mg/L), and vancomycin-susceptible E. faecium (n=26; MIC50/90, 0.03/0.12 mg/L; highest MIC, 0.25 mg/L), but showed limited activity against vancomycin-resistant E. faecium (VREFM; n=13 [0.3% of the organism collection]; MIC50/90, >2/>2 mg/L). Conclusion Dalbavancin showed potent in vitro activity against a large collection of Gram-positive isolates from pediatric patients, independent of patient age and geographic region (US and Europe). Only 13 of 4,487 (0.3%) isolates exhibited a dalbavancin MIC >0.25 mg/L, all of which were VREFM. These in vitro results support further clinical development of dalbavancin for treatment of Gram-positive infections in children.