UNASSIGNED: To investigate receipt of antibiotics among patients with neuroborreliosis after initial antibiotic treatment, likely attributable to posttreatment symptoms.
UNASSIGNED: We performed a nationwide, matched, population-based cohort study in Denmark (2009-2021). We included all Danish patients with neuroborreliosis, i.e. a positive Borrelia burgdorferi intrathecal antibody index test and a cerebrospinal fluid leukocyte count ≥10 × 106/l, and initially treated with doxycycline. To form a comparison cohort, we randomly extracted individuals from the general population matched 1:10 to patients with neuroborreliosis on date of birth and sex. The main outcome was receipt of doxycycline, and the secondary outcome was receipt of phenoxymethylpenicillin. We calculated short-term (<1 year) and long-term (≥1 year) hazard ratios (HR) with 95% confidence intervals (95%CI).
UNASSIGNED: We included 463 patients with neuroborreliosis and 2,315 comparison cohort members. Compared with the comparison cohort members, patients with neuroborreliosis initially treated with doxycycline had increased receipt of additional doxycycline within 1 year (HR: 38.6, 95%CI: 17.5-85.0) and ≥1 years (HR: 3.5, 95%CI: 1.9-6.3). Compared with comparison cohort members, patients with neuroborreliosis had no increased receipt of phenoxymethylpenicillin (<1 year HR 1.0, 95%CI: 0.7-1.3; ≥1 years HR 1.2, 95%CI: 0.9-1.5).
UNASSIGNED: After initial antibiotic treatment, patients with neuroborreliosis have increased receipt of doxycycline particularly within one year after initial antibiotic therapy but also subsequently. The lack of increased receipt of phenoxymethylpenicillin suggests that the receipt of doxycycline was not merely due to differences in healthcare-seeking behaviour, increased risk of early Lyme borreliosis due to exposure, or differences in antibacterial usage in general.

UNASSIGNED: Over the past decade, the pharmacy sector\'s policy, academic and professional spheres have increasingly drawn attention to the opportunities to better leverage the untapped potential of the community pharmacy sector in contributing to global efforts to reduce antimicrobial resistance (AMR). While efforts are in train, progress is slow.
UNASSIGNED: To draw insights from global experts in the field to identify a broad range of potential future policy directions to support community pharmacists\' involvement in antimicrobial stewardship (AMS).
UNASSIGNED: A modified Delphi technique, comprising two survey rounds to build consensus amongst global community pharmacy sector stakeholders and opinion leaders. In Round 1, participants rated their level of agreement with 28 statements across the three domains of policy design, implementation design, and monitoring and evaluation. Participants were also invited to contribute feedback in Round 1, which was reflected as new statements (n = 10) in Round 2. In Round 2, participants were asked to re-assess Round 1 statements in view of the group consensus and to rate the new statements.
UNASSIGNED: 289 participants were invited to participate. 48/289 (17% response rate) completed Round 1, and 25/42 (60% response rate) completed Round 2. Consensus (defined as >70% agreement) was achieved for 79% (n = 30) of the statements across the three domains.
UNASSIGNED: Pharmacy sector experts agreed that acknowledging community pharmacists in AMS national action plans is an important component, signalling a recognition of the sector\'s contribution to whole-of-nation AMS efforts. Implementation components that achieved consensus reflect the profession\'s evolution to a professional service driven model, particularly in complementary AMS initiatives including infection prevention and control measures. Context-specific adjustments to support implementing these AMS measures will be required, in addition to striking the appropriate balance to support the pace of increased community pharmacists\'involvement in AMS with building whole-of-profession buy-in.

BACKGROUND: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing).
METHODS: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed.
CONCLUSIONS: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship.
BACKGROUND: ISRCTN11633399. Registered 24/06/2022.

OBJECTIVE: Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA.
METHODS: This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity.
RESULTS: There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events.
CONCLUSIONS: Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.

Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of culture-proven EOS in The Netherlands. In this retrospective study from 2019 to 2021, data were collected from 15 Dutch hospitals, comprising 13 regional hospitals equipped with Level I-II facilities and 2 academic hospitals equipped with Level IV facilities. Data included birth rates, number of neonates started on antibiotics for suspected EOS, number of neonates that continued treatment beyond 48 h and number of neonates with culture-proven EOS. Additionally, blood culture results were documented. Data were analysed both collectively and separately for regional and academic hospitals. A total of 103,492 live-born neonates were included. In 4755 neonates (4.6%, 95% CI 4.5-4.7), antibiotic therapy was started for suspected EOS, and in 2399 neonates (2.3%, 95% CI 2.2-2.4), antibiotic treatment was continued beyond 48 h. Incidence of culture-proven EOS was 1.1 cases per 1000 live births (0.11%, 95% CI 0.09-0.14). Overall, for each culture-proven EOS case, 40.6 neonates were started on antibiotics and in 21.7 neonates therapy was continued. Large variations in treatment rates were observed across all hospitals, with the number of neonates initiated and continued on antibiotics per culture-proven EOS case varying from 4 to 90 and from 4 to 56, respectively. The high number of antibiotic prescriptions compared to the EOS incidence and wide variety in clinical practice among hospitals in The Netherlands underscore both the need and potential for a novel approach to the management of neonates with suspected EOS.

BACKGROUND: Antimicrobial resistance (AMR) is an important global public health concern in adults and children. Laryngotracheobronchitis (croup) is a common acute respiratory infection (ARI) among children, most often caused by a virus, and should not be treated with antibiotics. Reducing the usage of unnecessary antibiotics in ARI using an antimicrobial stewardship program (ASP) is an effective measure against AMR in children. This study investigates the antibiotic prescription pattern in pediatric patients with laryngotracheobronchitis in Korea. Our results will be useful to improve the ASP.
METHODS: The data were obtained from the government agency Health Insurance Review and Assessment Service. We analyzed outpatient prescriptions issued to children ≤ 5 years of age with a first-listed diagnosis code for laryngotracheobronchitis, i.e., International Classification of Disease, 10th Revision, code J050 (croup), J040 (laryngitis), or J041 (tracheitis), during 2017-2020. For each prescription, demographic information and information about medical facilities visited (type of hospital, specialty of physician, location of hospital) were extracted. The overall antibiotic prescription rate was subsequently estimated, and multivariable analysis was conducted to determine the associated factors of antibiotic prescription. Prescribed antibiotics were described and classified into extended-spectrum penicillins, cephalosporin, and macrolides.
RESULTS: Of 2,358,194 prescriptions reviewed, 829,172 (35.2%) contained antibiotics. In the multivariable analysis, management in a hospital was the strongest factor associated with antibiotic prescription (adjusted odds ratio [aOR], 22.33; 95% confidence interval [CI], 20.87-23.89; P < 0.001), followed by management in a clinic (aOR, 12.66; 95% CI, 11.83-13.54; P < 0.001) and management in a general hospital (aOR, 8.96; 95% CI, 8.37-9.59; P < 0.001). Antibiotic prescription was also significantly associated with patients who were ≤ 2 years of age, managed by a pediatric specialist, and treated at a hospital located in a non-metropolitan region. Overall, extended-spectrum penicillins were the most frequently prescribed (18.6%) antibiotics, followed by cephalosporins (9.4%) and macrolides (8.5%).
CONCLUSIONS: The results of our study suggest that ASPs need to focus on physicians in hospitals, clinics, general hospitals, and pediatric specialties. Providing education programs to these groups to increase awareness of AMR and appropriate antibiotics use could be effective ASP policy and may help to reduce unnecessary prescriptions of antibiotics for laryngotracheobronchitis among pediatric patients and therefore potentially AMR in children in Korea.

BACKGROUND: This study aimed to present real-life data on the use, efficacy, and safety of administering antibiotic therapy through portable elastomeric pumps (pEP) in the outpatient setting.
METHODS: This retrospective observational cohort study was conducted from January 2020 to May 2023 in a large academic hospital in Rome, Italy. All patients receiving antibiotic therapy via pEP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary outcome was the treatment response. Secondary endpoints were adverse events attributable to the drug administered, the vascular catheter, or the infection itself.
RESULTS: Of the 490 patients referred to our outpatient parenteral antibiotic therapy (OPAT) unit, 94 (19.2%) received antibiotic therapy via pEP and were included in the final analysis. The most frequently treated infections were those involving bone and prosthetics, including spondylodiscitis (n=27; 28.8%). Most infections were due to Pseudomonas aeruginosa (n=55; 48.3%). Cefepime (n=32; 34.0%), piperacillin/tazobactam (n=29; 30.9%), ceftolozane/tazobactam (n=7; 7.5%), and oxacillin (n=7; 7.5%) were the most frequently administered antibiotics. The infection cure rate reached 88.3% (n=83). 12 patients (12.8%) reported adverse events, of which half (6.4%) were drug-related and half (6.4%) were line-related.
CONCLUSIONS: OPAT through portable elastomeric infusion pumps proved to be safe and effective. It also contributed to the reduction of healthcare costs, fully respecting the principles of personalized medicine. This strategy has emerged as a promising tool for antibiotic stewardship and infection control.

BACKGROUND: The digitalization of information systems allows automatic measurement of antimicrobial consumption (AMC), helping address antibiotic resistance from inappropriate drug use without compromising patient safety.
OBJECTIVE: Describe and characterize a new automated AMC surveillance service for intensive care units (ICUs), with data stratified by referral clinic and linked with individual patient risk factors, disease severity, and mortality.
METHODS: An automated service collecting data from the electronic medical record was developed, implemented, and validated in a healthcare region in northern Sweden. We performed an observational study from January 1, 2018, to December 31, 2021, encompassing general ICU care for all ≥18-years-olds in a catchment population of 270000 in secondary care and 900000 in tertiary care. We used descriptive analyses to associate ICU population characteristics with AMC outcomes over time, including days of therapy (DOT), length of therapy, defined daily doses, and mortality.
RESULTS: There were 5608 admissions among 5190 patients with a median age of 65 (IQR 48-75) years, 41.2% females. The 30-day mortality was 18.3%. Total AMC was 1177 DOTs in secondary and 1261 DOTs per 1000 patient days and tertiary care. AMC varied significantly among referral clinics, with the highest total among 810 general surgery admissions in tertiary care at 1486 DOTs per 1000 patient days. Case-mix effects on the AMC were apparent during COVID-19 waves highlighting the need to account for case-mix. Patients exposed to more than three antimicrobial drug classes (N = 242) had a 30-day mortality rate of 40.6%, with significant variability in their expected rates based on admission scores.
CONCLUSIONS: We introduce a new service and instructions for automating local ICU-AMC data collection. The versatile long-term ICU-AMC metrics presented, covering patient factors, referral clinics and mortality outcomes, are expected to be beneficial in refining antimicrobial drug use.

UNASSIGNED: Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance.
UNASSIGNED: The objective of this qualitative study was to explore general practitioners\' (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs.
UNASSIGNED: GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs\' experiences and behaviours were recorded and analysed using an interpretive phenomenological approach.
UNASSIGNED: From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: \'male cystitis does not exist\'. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be \'potent\' antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system.
UNASSIGNED: GPs\' experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs\' antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed.KEY MESSAGESDefining a male urinary tract infection represents a diagnostic challenge for GPs.A diagnosis based on clinical evidence alone is insufficient and complementary tests are required.A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.

BACKGROUND: Antimicrobial stewardship programs are a critical tool for addressing the rising threat of antimicrobial resistance.
OBJECTIVE: To determine changes in patterns of antimicrobial use in Queensland public hospitals following introduction of the National Safety and Quality Health Service antimicrobial stewardship standard.
METHODS: A retrospective pre/post intervention study was conducted across Queensland public hospitals at the ecological level using Queensland Health\'s MedTRx database. An interrupted time series analysis was performed using linear regression models to determine rates of antimicrobial use by quarterly aggregated defined daily dose per 1000 patient days, for groups of hospitals stratified by peer group classification. Pre-defined time periods for antimicrobial stewardship program implementation in response to the introduction of the standard were analysed.
RESULTS: In the post intervention period, there was a decrease in overall use of systemic antimicrobials, glycopeptides, carbapenems and fluoroquinolones in principal referral and public acute group A hospitals. A decrease in overall use was also observed for smaller regional and remote public acute group C and D hospitals, however, increases in glycopeptide and fluoroquinolone use were observed. Third generation cephalosporin use was unchanged for all hospital peer groups. The proportion of overall use that was accounted for by narrow spectrum penicillin was low for all facilities, with modest improvements in the post intervention period observed in principal referral facilities only.
CONCLUSIONS: These findings add to current knowledge on the effectiveness of legislative quality standards on antimicrobial stewardship at the macro level and highlight gaps to target for future programs.