Analysis of antibiotic patterns of use

The initial antibiotic regimen was defined as the first new antibiotic(s) started within 24 h from baseline blood culture (including 3 h pre baseline culture). To structure the analysis and reporting of the multiple regimens used, a novel method of grouping antibiotics was derived, based on the Essential Medicine List for Children (EMLc) AWaRe classification (Access, Watch, Reserve) [24], with the “Watch” category divided into 3 distinct groups of “Low/Medium/High Watch” based on inclusion in current WHO guidelines (Low Watch) and likelihood of resistance generation with regimens outside WHO recommendations (Medium or High Watch) [25]. Antibiotic groups were defined by the main “stem” in the antibiotic combination: Group 1 antibiotics included a first-line WHO-recommended penicillin-based regimen (e.g., ampicillin and gentamicin) (Access), Group 2 included third-generation cephalosporin (e.g., cefotaxime/ceftriaxone)-based WHO regimens (“Low” Watch), Group 3 included regimens with partial anti-extended-spectrum beta-lactamase (ESBL) or pseudomonal activity (e.g., piperacillin-tazobactam/ceftazidime/fluoroquinolone-based) (“Medium” Watch), and Group 4 included carbapenems (e.g., meropenem) (“High” Watch). Group 5 antibiotics included Reserve antibiotics targeting carbapenem-resistant organisms (CROs) (e.g., colistin). Aminoglycosides (e.g., gentamicin/amikacin), glycopeptides (e.g., vancomycin/teicoplanin), and metronidazole used in combination regimens were classified as additional coverage and did not define the main antibiotic “stem” for the grouping. All antifungals and antivirals were excluded from the antimicrobial treatment data as these were not relevant to the analysis. Escalation of treatment was defined as a switch to a higher group antibiotic, and de-escalation was defined as switching to a lower group or discontinuation of the “stem” antibiotic while continuing with an additional coverage antibiotic.