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Background Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes. Methods A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. Results There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6–8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were bla CTX-M-15 (34/94, 36%) and bla SHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6–6.4). Conclusions GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials. [ABSTRACT FROM AUTHOR]

Background: Urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened.Objectives: This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates.Methods: E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days.Results: Piperacillin/tazobactam regimens attained ∼4-5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h.Conclusions: Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome. [ABSTRACT FROM AUTHOR]

Background: Skin microorganisms may contribute to the development of vascular access device (VAD) infections. Baseline skin microorganism type and quantity vary between body sites, yet there is little evidence to inform choice of VAD site selection. Objective: To compare microorganisms present at different body sites used for VAD insertions and understand the effect of transparent dressings on skin microflora. Methods: The ESCAPE observational study consisted of three phases: (1) skin swabs of four sites (mid-neck, base neck, chest, upper arm) from 48 hospital patients; (2) skin swabs of five body sites (mid-neck, base neck, chest, upper arm, lower arm) from 10 healthy volunteers; and (3) paired skin swabs (n = 72) under and outside of transparent dressings from 36 hospital patients (16 mid/base neck, 10 chest, upper arm). Specimens were cultured for 72 h, species identified and colony-forming units (CFU) counted. Ordinal logistic regression compared CFU categories between variables of interest. Results: The chest and upper arm were significantly associated with fewer microorganisms compared to neck or forearm (odds ratio [OR] = 0.40, 95% confidence interval [CI] = 0.25–0.65, P < 0.05). CFU levels under transparent dressings were not significantly different from outside (OR = 0.57, 95% CI = 0.22–1.45). Staphylococci were predominant at all sites. Other significant (P < 0.05) predictors of higher CFU count included prolonged hospitalisation and medical/surgical patient status. Discussion: Skin microorganism load was significantly lower at the upper arm or chest, compared to the mid- or base neck. This may impact VAD site selection and subsequent infection risk. [ABSTRACT FROM AUTHOR]