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Antimicrobial susceptibility testing (AST) of bacteria isolated in blood cultures is critical for optimal management of patients with sepsis. This review describes new and emerging phenotypic and genotypic AST methods and summarizes the evidence that implementation of these methods can impact clinical outcomes of patients with bloodstream infections.

Background. The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs. Methods. A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost. Results. Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost. Conclusions. rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation. Clinical Trials Registration. NCT01898208.

Background Children hospitalized with viral lower respiratory tract infections (LRTIs) are often prescribed antibiotics due to concern for bacterial co-infection, although most do not have concurrent bacterial infections. This unnecessary antibiotic treatment can lead to bacterial resistance and adverse events. The extent of antibiotic overuse in hospitalized children with community-onset viral LRTIs has not been described in recent years. To identify antibiotic stewardship opportunities in this population, we quantified the extent of antibiotic overtreatment and determined predictors of antibiotic use among children hospitalized with influenza, respiratory syncytial virus (RSV), or SARS-CoV-2 (COVID-19). Methods We performed a single-center retrospective study evaluating antibiotic use and culture-confirmed bacterial co-infection among children and adolescents hospitalized with influenza, RSV, or COVID-19 between April 2020 and May 2023. Predictors of antibiotic treatment were determined using logistic regression. Results We included 1,718 patients (influenza: 188; RSV: 1,022; COVID-19: 535). Patients with RSV were younger and more likely to be in intensive care. While only 8% of patients had culture-confirmed bacterial co-infection, the proportion receiving antibiotics was high and varied by virus (influenza: 60.6%, RSV:41.2%, COVID-19: 48.6%, p  < 0.001). Independent predictors for receipt of > 3 days of antibiotics were elevated inflammatory markers, comorbidities, mechanical ventilation, intensive care unit admission, influenza infection, and a concurrent non-respiratory infection. Conclusions In children hospitalized with community-onset viral LRTIs, antibiotic treatment is substantially higher than the burden of culture-confirmed bacterial infection, especially for influenza, suggesting antibiotic overuse and antibiotic stewardship opportunities.

Antimicrobial resistance (AMR) disproportionately affects people who are immunocompromised due to their frequent encounters with the health-care system and repeated, prolonged exposure to antibiotics. AMR threatens to undermine continued advances in cancer care, haematopoietic cell transplantation, and solid organ transplantation by severely restricting therapeutic options. The convergence of several factors in the diagnostic evaluation of infection among individuals with immunocompromising conditions contributes to excess and inappropriate antibiotic use. Diagnostic and antimicrobial stewardship are key complementary strategies to address these challenges with shared goals of improving patient outcomes, reducing harm, and mitigating the risk of AMR. In this Series paper, we discuss opportunities to enhance use of existing diagnostic tools (eg, culture-based diagnostics, molecular diagnostics, and other tools such as antibiotic allergy delabelling), emerging diagnostic tools (eg, metagenomic sequencing and host response profiling), and digital innovation, to optimise antibiotic use, and the potential for precision medicine approaches to combat AMR in people who are immunocompromised.

Escherichia coli sequence type 131 (ST131) is a major cause of community-onset, multidrug-resistant extraintestinal infections. The transmission and carriage dynamics associated with E. coli ST131’s global prevalence remain poorly understood. Here, we identify a group of persistent, high-density carriers of E. coli ST131 in the community. In this prospective cohort study in Singapore, we enrolled index patients with prior extraintestinal E. coli infections (17 with ST131, 17 with other sequence types) and their household coresidents. We collected sequential stool samples from 135 human participants and six companion animals and environmental swabs from 34 households. We identified nine carriers that persistently carried E. coli ST131 in high densities (57.79% of E. coli isolates per sample) for a median carriage duration of 86.35 days (80% credible interval (CrI) 30.03 to 188.80). Persistent carriers and their coresidents carried genetically similar E. coli ST131 isolates (median single nucleotide polymorphism distance 2, interquartile range 2 to 7), but persistent carriers harboured greater diversity, suggesting that they were the source of inter-individual transmissions. Our results highlight asymptomatic, persistent carriers as potential reservoirs sustaining community E. coli ST131 transmissions, offering a potential target for public health interventions such as vaccination to limit the spread of multidrug resistance. E. coli sequence type 131 is a significant cause of community-onset infection. Here, the authors perform a prospective household-based cohort study in Singapore including samples from humans, companion animals, the environment, and food, to characterise transmission and carriage dynamics.

Antibiotics are frequently prescribed for children in the outpatient setting. Although sometimes necessary, antibiotic use is associated with important downstream effects including the development of antimicrobial resistance among human and environmental microorganisms. Current outpatient stewardship efforts focus on guiding appropriate antibiotic prescribing practices among providers, but little is known about parents’ understanding of antibiotics and appropriate disposal of leftover antibiotics. To help bridge this gap, we conducted a qualitative study to assess parental understanding of their children’s antibiotics, their adherence to antibiotic instructions, and their disposal practices. We conducted a semi-structured interview with parents of 13 children diagnosed with acute respiratory illnesses and prescribed antibiotics in an urban outpatient clinic. We found that parents had limited understanding of how antibiotics work. Although they received instructions about antibiotic use during the healthcare visit, adherence to the prescription and appropriate disposal of antibiotics was suboptimal. Limited baseline understanding of antibiotics, their prior experiences with antibiotics, perceptions about their social networks’ antibiotic use, and information provided to them by healthcare providers may influence these behaviors. Our findings can inform educational efforts of outpatient stewardship programs to help optimize parental understanding of how to use and dispose of their children’s antibiotics.

Background: Antibiotic prescribing for children is highest in rural areas. Tele-stewardship allows for implementation of antimicrobial stewardship (AS) via telecommunication with providers. This study addresses need for better AS in rural areas by implementing and evaluating bundled outpatient AS interventions using tele-stewardship in rural pediatric primary care (PC) clinics and emergency departments (EDs) affiliated with Vanderbilt University Medical Center. Methods: The bundle includes (1) patient/guardian educational materials, (2) antibiotic use commitment posters (3) provider education through quarterly teaching pearls and app-based microlearning modules (QuizTime), and (4) quarterly audit/feedback with peer comparison on guideline-concordant antibiotic use via tele-meeting and email. Participants are pediatric prescribers (physician, physician assistant, nurse practitioner). We compared antibiotic prescription data for children < 1 8 years collected during the baseline period (Jan–Dec 2022) to the intervention period (Jan-Sept 2023). Two academic PC clinics and one ED where interventions were not implemented were included as “controls”. The primary outcome is percent of encounters that result in an antibiotic prescription. Secondary outcomes include (1) percent of encounters with guideline-concordant antibiotic choice for otitis media (AOM), streptococcal pharyngitis (GAS), sinusitis, and community-acquired pneumonia (CAP); (2) percent of encounters with 5-day antibiotic duration for AOM, sinusitis, and CAP; and (3) percent of encounters with rapid GAS testing. ED sinusitis data not analyzed due to small N. Significance was determined by calculating 95% confidence intervals for the difference of proportions. Results: There were 139,474 PC encounters (91,706 baseline and 47,768 intervention) and 94,205 ED encounters (54,138 baseline and 40,067 intervention) among 20 PC prescribers and 38 ED prescribers from January 2022-September 2023. Compared to baseline, the antibiotic prescription rate decreased 1.1% in intervention PCs but increased 0.9% in control PCs (Figure 1). Compared to baseline, the antibiotic prescription rate decreased by 0.4% in the intervention EDs but increased 3.1% in the control ED (Figure 1). Secondary outcomes showed significantly increased proportions of guideline concordant ED AOM prescriptions, 5-day PC AOM prescriptions (Figure 2), guideline concordant ED streptococcal pharyngitis prescriptions (Figure 3), and guideline concordant PC sinusitis prescriptions (Figure 4). There was a decrease in GAS tests in intervention PCs and EDs (Figure 6). Conclusions: Interim analysis shows bundled implementation strategies using tele-AS led to significantly decreased overall antibiotic use in rural PC clinics compared to control sites. The study is ongoing and will continue to evaluate outcomes over a longer intervention period to reduce seasonal bias. Disclosure: Sophie Katz: Research Grant - Pfizer; Research Grant - Dolly Parton Pediatric Infectious Diseases Research Fund; Consultant - Optum

It is not established whether diagnostic testing and antimicrobial treatment are warranted in well-appearing neonates without other signs or symptoms who have hypothermia identified incidentally at a routine visit with their primary care provider. This was a retrospective observational study of well-appearing neonates who were noted at a routine visit to be hypothermic (<97.7°F or <36.5°C) and referred to a pediatric emergency department over an 8.5-year period. Excluded were those transferred from an outside hospital and those with signs of illness, including apnea, bradycardia, fever, hypoglycemia, ill appearance, lethargy, poor feeding, respiratory distress, tachycardia, or vomiting. Patient characteristics, laboratory results, antimicrobial treatment, and clinical outcomes were recorded. Among a final cohort of 212 neonates with incidental hypothermia, no urine (n = 195) or blood (n = 198) culture grew a bacterial pathogen. No CSF culture (n = 168) grew a bacterial pathogen and no CSF PCR test (n = 142) was positive for herpes simplex virus. Contaminants were isolated in 3 urine and 3 blood cultures. Well-appearing neonates with incidentally noted hypothermia at a routine visit are at low risk for serious infection and may not warrant a full sepsis evaluation.

Developing, implementing, and evaluating the effectiveness of outpatient pediatric antimicrobial stewardship interventions via tele-stewardship. Baseline data collected between January and December 2022. Intervention data collected from February 2023 to December 2024. Interrupted time series with regression discontinuity analysis used to compare rates of antibiotic prescription between the periods. Three pediatric primary care clinics and three emergency departments associated with Vanderbilt University Medical Center that served rural and suburban communities. All encounters with patients less than 18 years of age at participating sites. Intervention bundle included patient/caregiver educational materials, antibiotic use commitment posters, prescriber education through quarterly teaching sessions on common pediatric infections, communication skills training, app-based microlearning modules, access to local guidelines using the Firstline app, and quarterly audit and feedback with peer comparison on guideline-concordant antibiotic use. Among a total of 147,357 encounters (43,157 baseline, 100,200 intervention), overall percent of encounters with one or more antibiotics prescribed decreased from 12.4% to 11.9% ( = .01). Percent change varied by site and patient demographics. Overall guideline-concordant prescribing increased significantly for acute otitis media (77.7% baseline vs 85.7% intervention, < .001), streptococcal pharyngitis (73.8% baseline vs 81.7% intervention, < .001), and urinary tract infections (41.9% baseline vs 57.1% intervention < .001). Five-day antibiotic courses increased significantly (6.3% baseline vs 19.7% intervention, < .001). There was a significant decrease in rapid streptococcal testing (10.9% baseline vs 7.6% intervention, < .001). Tele-stewardship interventions were effective in outpatient pediatric primary care and emergency department settings, but effectiveness varied by site.