OBJECTIVE: To assess trends in antibiotic use across a large cohort of extremely low birth-weight (<1000 g; ELBW) infants admitted to academic and community neonatal intensive care units (NICUs) across the USA over a 13-year period.
METHODS: Repeated cross-sectional cohort study.
METHODS: Premier Health Database, a comprehensive administrative database of inpatient encounters from academic and community hospitals across the US.
METHODS: ELBW inborn infants admitted to NICUs from 1 January 2009 to 31 December 2021.
METHODS: N/A MAIN OUTCOME MEASURES: Absolute and relative changes in (1) proportion of ELBW infants with antibiotic exposure and (2) days of therapy (DOT) per 1000 patient days, over time. Average annual differences were estimated using generalised linear regression with 95% CI. Disposition trends were also measured.
RESULTS: Among 36 701 infants admitted to 402 NICUs, the proportion exposed to antibiotics was essentially unchanged (89.9% in 2009 to 89.3% in 2021; absolute reduction of -0.6%); generalised linear regression estimated an annual absolute difference of -0.3% (95% CI (-0.6%) to (-0.07%); p=0.01). DOT per 1000 patient days decreased from 337 in 2009 to 210 in 2021, a 37.8% relative difference and annual relative difference of -4.3% ((-5.2%) to (-3.5%); p<0.001). Mortality was unchanged during the study period.
CONCLUSIONS: We found a substantial reduction in antibiotic DOT despite no substantive change in the proportion of infants exposed to antibiotics. This suggests the success of stewardship efforts aimed at antibiotic duration and highlight the need for improved approaches to identifying ELBW infants at highest risk of infection.

Assessment is an essential component for all educational programs and must check competence acquirement while foster and promote learning. Progress Test (PT) is well recognized to assess cognitive knowledge, clinical reasoning and decision making in the clinical context, offering important information about the individual performance and program quality. It is widely used in Brazilian and international medical schools; however, it still has little role in assessing medical residents in Brazil. We present the experience of a PT pilot implementation in an Infectious Diseases residency program over two years. The first, second and third-year residents did four serial exams with 40 multiple choice questions (item)/each. Preceptors were trained on best practices on item writing. All the items were reviewed by a panel of experts and, after approval, included in the item bank. All participants answered a survey on their perceptions about the experience. The final score was higher for the third-year residents in all exam applications. The level of satisfaction was high among the participants, who mentioned the learning opportunity with the exam and the feedback. PT can improve residents\' assessment along the training period and residents\' performance should guide review and improvement of the programs.

OBJECTIVE: To determine the added diagnostic value of dipsticks for urinary tract infections (UTI) in acutely hospitalised individuals.
METHODS: Prospective population-based cohort study.
METHODS: North Denmark.
METHODS: All adults (≥18 years) examined with dipsticks at emergency departments in North Denmark Region from September 20 through 23 October 2021.
METHODS: UTI was defined as ≥1 symptom of new-onset frequency, dysuria or suprapubic tenderness combined with a positive urine culture. Positive dipsticks were defined as any reaction for leucocyte esterase and/or nitrite.
RESULTS: Dipsticks were used in 1052/2495 (42%) of acutely hospitalised patients with a median age of 73 years (IQR 57-82) and 540 (51%) were female. Overall, 89/1052 (8%) fulfilled the UTI criteria and urine cultures were done in 607/1052 (58%) patients. Among patients examined with both dipstick and urine culture, sensitivity and specificity for UTI were 87% (95% CI 78% to 93%) and 45% (95% CI 41% to 50%). Positive and negative predictive values were 21% (95% CI 17% to 26%) and 95% (95% CI 92% to 98%), whereas positive and negative likelihood ratios were 1.58 (95% CI 1.41 to 1.77) and 0.30 (95% CI 0.18 to 0.51). Pretest probabilities of UTI ranged from 29% to 60% in participants with specific UTI symptoms with corresponding post-test probabilities of 35-69% if dipsticks were positive and 12-27% if dipsticks were negative. Results remained comparable if final clinical diagnosis was used as outcome among all patients examined with dipsticks. Modified Poisson regression yielded an adjusted relative risk of 4.41 (95% CI 2.40 to 8.11) for empirical antibiotics for UTI in participants without specific UTI symptoms and a positive dipstick.
CONCLUSIONS: Dipsticks yielded limited clinical decision support compared with a symptom-driven approach in this study and were independently associated with excess antibiotics for UTI.

OBJECTIVE: To compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines.
METHODS: An open-label, phase IV randomised study conducted across six UK sites.
METHODS: Neonatal units, postnatal wards, community recruitment following discharge.
METHODS: 129 preterm infants born at a gestation of <35 weeks (64 in group 1 (2+1), 65 in group 2 (3+1)) were included in the analysis. Analysis was completed for postprimary samples from 125 participants (59 in group 1, 66 in group 2) and for postbooster samples from 118 participants (59 in both groups).
METHODS: Infants randomised to 4CMenB according to a 2+1 or a 3+1 schedule, alongside routine vaccines.
METHODS: Serum bactericidal antibody (SBA) assays performed at 5, 12 and 13 months of age: geometric mean titres (GMTs) and proportions of infants achieving titres ≥4 compared between groups.
RESULTS: There were no significant differences in SBA GMTs between infants receiving a 2+1 compared with a 3+1 schedule following primary or booster vaccination, but a significantly higher proportion of infants had an SBA titre ≥4 against strain NZ98/254 (porin A) at 1 month after primary vaccination using a 3+1 compared with a 2+1 schedule (3+1: 87% (95% CI 76 to 94%), 2+1: 70% (95% CI 56 to 81%), p=0.03).At 12 weeks of age those in the 3+1 group, who received a dose of 4CMenB, had significantly more episodes of fever >38.0°C than those in the 2+1 group who did not (group 2+1: 2% (n=1); 3+1: 14% (n=9); p=0.02).
CONCLUSIONS: Both schedules were immunogenic in preterm infants, although a lower response against strain NZ98/254 was seen in the 2+1 schedule; ongoing disease surveillance is important in understanding the clinical significance of this difference.
BACKGROUND: NCT03125616.

OBJECTIVE: To analyse the performance of the urine Gram stain for predicting a positive urine culture (UC) in young infants with fever without source (FWS) and pyuria.
METHODS: Observational study; secondary analysis of a prospective registry-based cohort study.
METHODS: Paediatric emergency department; tertiary teaching hospital.
METHODS: Infants ≤90 days old with FWS, pyuria and urine Gram stain requested seen between 2010 and 2022.
METHODS: Performance of the Gram stain, defined as positive if any bacteria were seen, for predicting urinary tract infection (UTI: UC by urethral catheterisation growing >10 000 CFU/mL of a single bacterial pathogen).
RESULTS: Among 367 febrile infants with pyuria, 281 (76.6%) had a positive Gram stain and 306 (83.3%) had a positive UC (277; 90.5% Escherichia coli).Rates of positive UC in patients with positive and negative Gram stains were 97.2% and 38.4%, respectively (p<0.01), showing a sensitivity of 89.2% (95% CI: 85.2% to 92.2%) and a specificity of 86.9% (95% CI: 76.2% to 93.2%). Sensitivity was lower for diagnosing UTIs caused by bacteria other than E. coli (69.0% vs 91.3% for UTIs caused by E. coli; p<0.01).Two (2.1%) of the 86 infants with negative Gram stains were diagnosed with bacteraemia unrelated to a UTI (Streptococcus pneumoniae and Staphylococcus aureus).
CONCLUSIONS: Around a third of infants with pyuria and a negative Gram stain will eventually be diagnosed with a UTI. These patients have a higher rate of UTIs caused by bacteria other than E. coli. Bacterial infections other than UTIs should also be considered in such cases.

BACKGROUND: In Catalonia, infants under 6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyse nirsevimab\'s effectiveness across primary and hospital care outcomes.
METHODS: Retrospective cohort study from 1 October 2023 to 31 January 2024, including all infants born between April and September 2023. We established two cohorts based on nirsevimab administration (immunised and non-immunised). We followed individuals until the earliest moment of an outcome-RSV infection, primary care attended bronchiolitis and pneumonia, hospital emergency visits due to bronchiolitis, hospital admission or intensive care unit (ICU) admission due to RSV bronchiolitis-death or the end of the study. We used the Kaplan-Meier estimator and fitted Cox regression models using a calendar time scale to estimate HRs and their 95% CIs.
RESULTS: Among 26 525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0.124 (95% CI: 0.086 to 0.179) and an adjusted HR for ICU admission of 0.099 (95% CI: 0.041 to 0.237). Additionally, the adjusted HRs observed for emergency visits were 0.446 (95% CI: 0.385 to 0.516) and 0.393 (95% CI: 0.203 to 0.758) for viral pneumonia, 0.519 (95% CI: 0.467 to 0.576) for bronchiolitis attended in primary care and 0.311 (95% CI: 0.200 to 0.483) for RSV infection.
CONCLUSIONS: We demonstrated nirsevimab\'s effectiveness with reductions of 87.6% and 90.1% in hospital and ICU admissions, respectively. These findings offer crucial guidance for public health authorities in implementing RSV immunisation campaigns.

UNASSIGNED: To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions.
UNASSIGNED: Retrospective cohort study in England using OpenSAFELY-TPP.
UNASSIGNED: Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England.
UNASSIGNED: Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023.
UNASSIGNED: Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18).
UNASSIGNED: The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic.
UNASSIGNED: Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups.

OBJECTIVE: To evaluate the implementation of an antimicrobial stewardship programme-led inpatient beta-lactam allergy de-labelling programme using a direct oral provocation test (OPT).
METHODS: One-year quality improvement study using a before-after design.
METHODS: Free-standing tertiary care paediatric hospital.
METHODS: Patients with a reported beta-lactam allergy admitted to the paediatric medicine inpatient unit.
METHODS: Following standardised assessment and risk stratification of reported symptoms, patients with a low-risk history were offered an OPT. Beta-lactam allergy labels were removed if a reported history was considered non-allergic or after successful OPT.
METHODS: Removal of inappropriate beta-lactam allergy labels.
RESULTS: 80 patients with 85 reported beta-lactam allergies were assessed. Median age was 8.1 years (IQR 4.8-12.9) and 34 (42%) were female. The majority (n=55, 69%) had an underlying medical condition. Amoxicillin was the most reported allergy (n=25, 29%). Reported reactions were primarily dermatological (n=65, 77%). Half of participants (n=40) were ineligible for OPT, with equal proportions due to clinical reasons or the nature of the reported reaction. Of the 40 eligible patients, 28 patients (70%) were de-labelled either by history alone (n=10) or OPT (n=18). All OPTs were successful. De-labelling allowed five additional patients (11% of those receiving antibiotics) to receive the preferred beta-lactam. Including patients who were subsequently assessed in the allergy clinic, almost half of all evaluated patients were de-labelled (n=37, 46%).
CONCLUSIONS: An antimicrobial stewardship programme-led programme using a direct OPT was feasible and safe for expanding beta-lactam allergy de-labelling to paediatric patients admitted to the paediatric medicine inpatient unit.

Background In 2018, the World Health Organisation (WHO) released interim guidelines, advising a change of regimens to dolutegravir-based first- and second-line antiretroviral therapy (ART), based on which, in 2021, the National Aids Control Organisation (NACO) updated its guidelines to include the tenofovir + lamivudine + dolutegravir (TLD) regimen as a first line of therapy for all people living with HIV (PLHIV) and second- and third-line regimens to dolutegravir-based regimens. Considering this change of regimen, the adverse drug reaction (ADR) profiling and longitudinal prescription pattern of antiretroviral and concomitant medications in adult patients at the ART centre of a tertiary care hospital were assessed in this study. Methods Ninety-seven PLHIV out of all the patients who attended the ART centre from September 2021 to July 2022 were enrolled and followed up for six months. The ADRs that occurred during this period were collected along with details of prescription patterns and analyzed by descriptive statistics. Causality assessment for ADR was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Results Seventy-eight percent (n=76 out of 97) of patients experienced at least one ADR, and 128 ADRs were seen in 97 patients. The most common ADRs were increased alkaline phosphatase (39.0%, n=128), dyslipidaemia (12.5%, n=128), and nephrotoxicity (10.1%, n=128). The drug most suspected of causing ADRs was dolutegravir (27.5%, n=342). The most common therapeutic regimen was TLD (71.2%, n=97). The most prescribed drug was lamivudine (30.6%, n=1183). The most prescribed concomitant medication was cotrimoxazole (15%, n=312). Conclusions Dolutegravir-based regimens have been implemented for PLHIV in a phased-out manner from previous non-dolutegravir-based ART regimens, which is in line with the recent NACO guidelines. However, it has also led to an increase in dolutegravir-associated ADRs like increased alkaline phosphatase, dyslipidaemia, and nephrotoxicity. Continuous monitoring of prescriptions and ADRs can add to our knowledge regarding their use and ADRs.

OBJECTIVE: To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections.
METHODS: Multi-centre observational cohort study using data from 2009 to 2018 clinical records.
METHODS: Canadian children\'s hospitals (7) and community hospitals (3).
METHODS: Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections.
METHODS: Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation.
METHODS: Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates.
RESULTS: Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018.
CONCLUSIONS: Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes.