BACKGROUND: The optimal duration of therapy of aminoglycosides in combination regimens is expected to be different to monotherapy regimens; and shorter durations could help minimize toxicity without compromising efficacy. The aim of this review was to assess the evidence for the optimal duration of aminoglycosides in beta-lactam/aminoglycoside combinations used for the treatment of Gram-negative bacterial infections.
METHODS: PubMed, Cochrane, Embase, Scopus, Web of Science, and CINHAL databases were searched. Covidence software was used for article screening and management. Studies were included if they clearly reported the duration of therapy of aminoglycosides in beta-lactam/aminoglycoside combinations used against Gram-negative bacteria. The protocol is registered with PROSPERO (CRD42023392709).
RESULTS: A total of 45 beta-lactam/aminoglycoside combination courses from 32 articles were evaluated. The duration of therapy of aminoglycosides in combinations regimens ranged from 1 to 14 days, varying with the type of infection treated. In half (51.1%; (23/45) of the combinations, aminoglycosides were administered for a duration ranging from 6 to 9 days. In 26.7% (12/45) of the combinations, the duration of aminoglycoside therapy was ≤ 5 days. In the remaining 22.2% (10/45) of these combinations, the aminoglycosides were administered for a duration of ≥ 10 days. Aminoglycosides were administered for a longer duration of 7-14 days in 12 (75%) of the 16 combination courses that induced toxicity.
CONCLUSIONS: Long duration of aminoglycoside use is associated with increased risk of toxicity. However, there is a lack of evidence on defining an optimal duration of aminoglycoside therapy in beta-lactam/aminoglycoside combination regimens that ensures clinical efficacy-outcomes whilst minimizing toxicity-outcomes.

Primary care antimicrobial stewardship programs have limited success in reducing antibiotic use, prompting the search for new strategies. Convincing general practitioners to resist antibiotic prescription amid uncertainty or patient demands usually poses a significant challenge. Despite common practice, standard durations for common infections lack support from clinical studies. Contrary to common belief, extending antibiotic treatment beyond the resolution of symptoms does not seem to prevent or reduce antimicrobial resistance. Shortening the duration of antibiotic therapy has shown to be effective in mitigating the spread of resistance, particularly in cases of pneumonia. Recent hospital randomised trials suggest that ending antibiotic courses by day three for most lower respiratory tract infections is effective and safe. While community studies are scarce, it is likely that these shorter, tailored courses to meet patients\' needs would also be effective and safe in primary care. Therefore, primary care studies should investigate the outcomes of advising patients to discontinue antibiotic treatment upon symptom resolution. Implementing patient-centred, customised treatment durations, rather than fixed courses, is crucial for meeting individual patient needs.

BACKGROUND: Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children two years and older with AOM, most receive long (10-day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system.
METHODS: Electronic medical record (EMR) data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a diagnosis of AOM from 2019-2022 were included. The primary outcome was the percent of 5-day prescriptions. Secondary outcomes included the proportion of 7-day prescriptions, 10-day prescriptions, prescriptions for non-first line antibiotics, cases associated with treatment failure, AOM recurrence, and adverse drug events.
RESULTS: Among 73,198 AOM encounters for children 2 years and older, 61,612 (84%) encounters resulted in an antibiotic prescription. Most prescriptions were for 10 days (45,689; 75%), 20% were for 7 days (12,060), and only 5% were for 5 days (3,144). Treatment failure, AOM recurrence, adverse drug events, hospitalizations, and office, emergency department or urgent care visits for AOM within 30 days after the index visit were rare.
CONCLUSIONS: Despite national guidelines that recommend shorter durations for children with uncomplicated AOM, 75% of our cohort received 10-day durations. Shortening durations of therapy for AOM could reduce antibiotic exposure and should be a priority of pediatric antibiotic stewardship programs.

Community-acquired pneumonia (CAP) is a common infectious syndrome in Australia and a leading global cause of morbidity and mortality. It drives a significant amount of antimicrobial prescribing in Australia. Accurate assessment and stratification of CAP severity is important. However, adequate evaluation is challenging and controversy remains about the optimal method. Streptococcus pneumoniae is the most commonly identified bacterial pathogen causing CAP. As such, oral amoxicillin monotherapy is the mainstay of empirical therapy for low-severity CAP. The need to start empirical therapy for pathogens such as Mycoplasma pneumoniae and Legionella species in low-severity CAP remains controversial; evaluating the causative pathogen on clinical grounds alone is difficult. Oral antibiotics recommended for CAP (e.g. amoxicillin, doxycycline) have excellent bioavailability and may be used instead of intravenous therapy in some hospitalised patients. A duration of 5 days of antibiotic therapy is recommended in clinical practice guidelines for patients with uncomplicated CAP who meet stability criteria at follow-up.

OBJECTIVE: In patients with de novo heart failure with reduced ejection fraction (HFrEF), improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy. However, improvement may not be completed within 90 days.
METHODS: Patients with HFrEF and LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator between 2017 and 2022 from 68 sites were enrolled, starting with a registry phase for 3 months and followed by a study phase up to 1 year. The primary endpoints were LVEF improvement > 35% between Days 90 and 180 following guideline-recommended medical therapy initiation and the percentage of target dose reached at Days 90 and 180.
RESULTS: A total of 598 patients with de novo HFrEF [59 years (interquartile range 51-68), 27% female] entered the study phase. During the first 180 days, a significant increase in dosage of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was observed (P < .001). At Day 90, 46% [95% confidence interval (CI) 41%-50%] of study phase patients had LVEF improvement > 35%; 46% (95% CI 40%-52%) of those with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68% (95% CI 63%-72%). In 392 patients followed for 360 days, improvement > 35% was observed in 77% (95% CI 72%-81%) of the patients. Until Day 90, sustained ventricular tachyarrhythmias were observed in 24 wearable cardioverter-defibrillator carriers (1.8%). After 90 days, no sustained ventricular tachyarrhythmia occurred in wearable cardioverter-defibrillator carriers.
CONCLUSIONS: Continuous optimization of guideline-recommended medical therapy for at least 180 days in HFrEF is associated with additional LVEF improvement > 35%, allowing for better decision-making regarding preventive implantable cardioverter-defibrillator therapy.

OBJECTIVE: Urinary tract infection (UTI) is the most common bacterial infection in infants. Current practice guidelines suggest a treatment duration of 7 to 14 days. Suboptimal therapy may increase the risk for recurrent UTIs leading to renal scarring and possibly chronic kidney disease. The primary objective is to evaluate the duration of therapy for UTIs and its association with the incidence of recurrent UTIs in a neonatal intensive care unit (NICU). The secondary objectives are to identify the risk factors and the most common organisms for recurrent UTIs.
METHODS: Patients were identified via the diagnosis codes for UTIs and were included if admitted to the NICU and if they received antibiotics prior to hospital discharge. Patients were divided into 2 groups: antibiotic treatment for 7 days or fewer and antibiotic treatment for greater than 7 days.
RESULTS: Eighty-six infants were included in the study. Twenty-six patients received antibiotics for 7 days or fewer, and 60 for more than 7 days. In the study, the median birth weight was 977 g and the median gestational age was 27.6 weeks. There was no significant difference in the rate of recurrent UTIs between the 2 groups (p = 0.66). However, in the subgroup analysis, the incidence was higher for patients receiving antibiotic therapy for fewer than 7 days versus 7 days (p = 0.03).
CONCLUSIONS: There was no difference in recurrence of UTI between treatment groups (≤7 days versus >7 days), and recurrence was seen in a higher percentage of patients with a urinary tract anomaly.

BACKGROUND: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications.
OBJECTIVE: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature.
METHODS: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool.
RESULTS: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 - 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 - 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 - 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 - 0.11, p < 0.001).
CONCLUSIONS: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up.

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BACKGROUND: The appropriate duration of antimicrobial therapy for febrile urinary tract infection (fUTI) in children has not been established. This study examined the optimal duration of treatment for fUTI in children.
METHODS: We created a protocol that used fever duration to determine the duration of antibiotic administration. Transvenous antibiotics were administered until 3 days after resolution of fever, followed by oral antibiotics for 1 week. Diagnosis of fUTI was based on a fever of 37.5°C or higher and a quantitative culture of catheterized urine yielded a bacteria count of ≥5 × 104. Acute focal bacterial nephritis (AFBN) and pyelonephritis (PN) were diagnosed on the basis of contrast-enhanced computed tomography (eCT) findings. We retrospectively reviewed treatment outcomes.
RESULTS: Of the 78 patients treated according to our protocol, data from 58 were analyzed-49 children (30 boys) had PN and nine (three boys) had AFBN. Blood test results showed that patients with AFBN had significantly higher white blood cell counts and C-reactive protein levels than did those with PN; however, urinary findings and causative bacteria did not differ between groups. Time to resolution of fever and duration of intravenous antibiotic administration were significantly longer in patients with AFBN than in those with PN. However, average duration of AFBN treatment was 14.2 days, which was shorter than the previously reported administration period of 3 weeks. No recurrence was observed in AFBN patients.
CONCLUSIONS: A protocol that used fever duration to determine the duration of antimicrobial treatment was useful. Invasive examinations, such as eCT, were not required.