In this study, we assess healthcare providers\' adherence to therapeutic drug monitoring (TDM) guidelines for gentamicin in neonates. Conducted at the Maternity and Children\'s Hospital in Makkah, Saudi Arabia, from July 2020 to July 2022, it retrospectively analyzed the compliance of healthcare workers in managing neonates treated with gentamicin. Covering 410 neonates, primarily diagnosed with respiratory distress (56%) and sepsis (32%), the study revealed that while a majority of trough and peak levels conformed to guidelines, substantial deviations were noted in cases of respiratory distress. This underlines the necessity for targeted TDM strategies, particularly in managing respiratory distress in neonates, to ensure optimal treatment efficacy and safety. The findings urge stringent compliance with TDM guidelines, emphasizing personalized approaches in neonatal gentamicin therapy for improved healthcare outcomes.

Although aminoglycosides are frequently prescribed to neonates and children, the ability to reach effective and safe target concentrations with the currently used dosing regimens remains unclear. This study aims to evaluate the target attainment of the currently used dosing regimens for gentamicin in neonates and children. We conducted a retrospective single-center cohort study in neonates and children receiving gentamicin between January 2019 and July 2022, in the Beatrix Children\'s Hospital. The first gentamicin concentration used for therapeutic drug monitoring was collected for each patient, in conjunction with information on dosing and clinical status. Target trough concentrations were ≤1 mg/L for neonates and ≤0.5 mg/L for children. Target peak concentrations were 8-12 mg/L for neonates and 15-20 mg/L for children. In total, 658 patients were included (335 neonates and 323 children). Trough concentrations were outside the target range in 46.2% and 9.9% of neonates and children, respectively. Peak concentrations were outside the target range in 46.0% and 68.7% of neonates and children, respectively. In children, higher creatinine concentrations were associated with higher gentamicin trough concentrations. This study corroborates earlier observational studies showing that, with a standard dose, drug concentration targets were met in only approximately 50% of the cases. Our findings show that additional parameters are needed to improve target attainment.

BACKGROUND: Infective endocarditis (IE) is still a severe disease with elevated morbidity and mortality. Nevertheless, the last European guidelines (GL) date back to 2015, and a recent survey described a diffuse suboptimal adherence to their recommendations. Here, we described a real-life scenario about adherence to IE treatment GL.
METHODS: This was a retrospective, multicentric, case-control study. All the cases of IE admitted to our wards from 2016 to 2020 were enrolled. Patients were divided into two groups, according to the non-adherence (group A, cases) or adherence (group B, controls) to 2015 ESC guidelines. Only targeted treatments were considered. Groups were compared for demographic, clinical, microbiological, and laboratory data and outcome. As a post hoc analysis, we analysed the characteristics of deviations from the guidelines and how these deviations affected mortality.
RESULTS: A total of 246 patients were enrolled, with 128 (52%) in group A and 118 (48%) in group B. Groups were homogeneous except for aetiologies: staphylococcal and blood-culture-negative IE were more frequent in group A, while streptococcal and enterococcal IE were more frequent in group B (p < 0.001). In-hospital mortality was comparable in the two groups. The most frequent causes of deviations from the guidelines were use of daptomycin, in addition to standard treatments and the missing administration of rifampin or gentamycin.
CONCLUSIONS: Adherence to 2015 ESC guidelines was limited but it did not affect mortality.

Objective:Intratympanic（IT） drug delivery receives attention due to its effectivity in treatment for Menière\'s disease（MD）. Due to the release of the consensuses and new evidence on IT drug delivery for MD have been published, the review with a view to supplementing the details of IT treatment of MD is indispensable. Methods:The literatures on IT injection for MD treatment over the last two decades are retrieved, International consensus（ICON） on treatment of Menière\'s disease（2018）, Clinical Practice Guideline（2020） and European Position statement on Diagnosis and Treatment of Menière\'s disease（2018） are taken into account for reference, and follow advice from experts from Europe, USA and China. Results:Experts agree on the following: ①The effectiveness of IT methylprednisolone（ITM） on vertigo control seems to be somewhat better than that of IT dexamethasone（ITD）, and ITM can restore hearing in some cases. ②Due to the ototoxicity of aminoglycosides, the application of intratympanic gentamicin（ITG） in MD patients with good hearing is conservative. However, some studies suggest that ITG with low doses has no significant effect on hearing, which needs to be further proved by clinical studies with high levels of evidence. ③Currently, generally accepted treatment endpoint of ITG is no vertigo attack in a 12-month period or a vestibular loss in objective tests in the affected ear. Conclusion:More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD.
目的：鼓室内（intratympanic，IT）注射药物治疗梅尼埃病（MD）因其疗效显著而备受关注。由于IT注射药物治疗MD的共识和新证据的发布，对IT注射药物治疗MD进行细节上的补充具有重要意义。 方法：检索近二十年来有关IT注射药物治疗MD的文献，参考《梅尼埃病治疗国际共识（ICON）》（2018年），《美国梅尼埃病临床实践指南》（2020年）和《梅尼埃病诊断治疗的欧洲立场声明》（2018），并遵循来自欧洲、美国和中国的专家意见。 结果：专家一致认为：①鼓室内注射甲泼尼龙（ITM）对眩晕控制的疗效优于鼓室内注射地塞米松（ITD），ITM有恢复MD患者听力的可能性。②由于氨基糖甙类药物的耳毒性，鼓室内注射庆大霉素（ITG）在听力良好MD患者中的应用持谨慎态度。但也有研究表明，小剂量ITG对听力没有显著影响，还需要高水平证据的临床研究进一步证明。③目前普遍接受的ITG治疗终点是在12个月内无眩晕发作或受累耳客观检查提示前庭功能丧失。 结论：对IT注射药物治疗MD的药物类型、疗效和治疗终点还需要更多高证据水平的研究进行评价。.

OBJECTIVE: Intratympanic (IT) drug delivery receives attention due to its effectivity in treatment for Menière\'s disease (MD). Due to the release of the consensuses and new evidence on IT drug delivery for MD have been published, the review with a view to supplementing the details of IT treatment of MD is indispensable.
METHODS: The literatures on IT injection for MD treatment over the last two decades are retrieved, International consensus (ICON) on treatment of Menière\'s disease (2018), Clinical Practice Guideline (2020) and European Position statement on Diagnosis and Treatment of Meniere\'s Disease (2018) are taken into account for reference, and follow advice from experts from Europe, USA and China.
RESULTS: Experts agree on the following: (1) The effectiveness of IT methylprednisolone (ITM) on vertigo control seems to be somewhat better than that of IT dexamethasone (ITD), and ITM can restore hearing in some cases. (2) Due to the ototoxicity of aminoglycosides, the application of intratympanic gentamicin (ITG) in MD patients with good hearing is conservative. However, some studies suggest that ITG with low doses has no significant effect on hearing, which needs to be further proved by clinical studies with high levels of evidence. (3) Currently, generally accepted treatment endpoint of ITG is no vertigo attack in a 12-month period or a vestibular loss in objective tests in the affected ear.
CONCLUSIONS: More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD.

Ménière\'s disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many, and approaches typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies.
The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

Ménière\'s disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid (endolymph) volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Conventional imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many and typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies.
The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

The National Institute for Health and Care Excellence published guidelines for managing early-onset neonatal infections in 2012. It recommended provision for reporting blood cultures (BCs) with growth detected or not detected at 36 h. To determine if this was followed, a telephone survey was conducted amongst lead biomedical scientists based at microbiology laboratories (N = 209) in the UK. Overall, 202/209 responded and 139/202 had on-site facilities for BCs. BC results with growth detected or not detected at 36 h were available out-of-hours in 36/139 (26.6%) and 66/139 (47.5%) neonatal units, respectively. Early discontinuation of antibiotics should lead to improved antibiotic stewardship.

International guidelines are available to help physicians prescribe appropriate antibiotic regimens to patients with infective endocarditis (IE). However some topics of these guidelines are controversial. We conducted an international survey to assess physicians\' adherence to these guidelines, focusing on these controversial items. An invitation to participate to a 15-question online survey was sent in 2012-2013 to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members, scientific societies and corresponding authors of publications on IE mentioned in PubMed from 1990 to 2012, inclusive. Eight hundred thirty-seven physicians participated in the survey, and 625 (74.7%) completed it over the first question. The results showed great heterogeneity of practices. Claiming to follow guidelines was marginally associated with more guideline-based strategies. Gentamicin use depended on causative pathogens (p <0.001) and physician specialty (p 0.02). Eighty-six per cent of the physicians favoured vancomycin alone or in combination with gentamicin or rifampicin as a first-line treatment for left-sided native valve methicillin-resistant Staphylococcus aureus IE, 31% considered switching to oral therapy as a therapeutic option and 33% used the ampicillin and ceftriaxone combination for enterococcal IE as a first-line therapy. Physician specialty significantly affected the choice of a therapeutic strategy, while practicing in a university hospital or the number of years of practice had virtually no impact. Our survey, the largest on IE treatment, underscores important heterogeneity in practices for treatment of IE. Nonetheless, physicians who do not follow guidelines can have rational strategies that are based on the literature. These results could inform the revision of future guidelines and identify unmet needs for future studies.

BACKGROUND: Gentamicin is an aminoglycoside antibiotic that is highly effective in treating Gram-negative infections, but inappropriate use leads to toxicity. In 2010, the Australian Therapeutic Guidelines (Antibiotic) were revised to recommend the use of computerised methods to individualise dosing of gentamicin and optimise therapy, rather than traditional nomogram approaches.
OBJECTIVE: To determine whether gentamicin prescribing was compliant with the Australian Therapeutic Guidelines, version 14 (2010) in a setting where computerised dose recommendation resources and computerised decision support were available, and to determine why the resources were effective or ineffective in achieving compliance to guidelines.
METHODS: During phase 1, a retrospective audit of gentamicin prescribing from 1 January 2012 to 31 December 2012 (n = 826) at a 320-bed teaching hospital in Sydney was undertaken. In phase 2, 12 doctors from specialties with high-volume prescribing of gentamicin were interviewed.
RESULTS: Intravenous gentamicin was used in 545 cases, 81% of which were for short-term therapy (≤48 h). Doctors feared inducing toxicity in patients, but limited the dose rather than altering the dosing interval according to renal function. Of the \'continued\' dosing cases, 55% went unmonitored and the computerised dose recommendation service was rarely used. Doctors were unaware of its availability despite electronic alerts accompanying prescriptions of gentamicin.
CONCLUSIONS: In comparison with the national guidelines, there was significant under-dosing and monitoring practices were haphazard. Computerised electronic alerts were ineffective in informing users. To improve prescribing practices, we recommend exploring alternative computerised decision support approaches (e.g. pre-written orders) and more pervasive and persuasive implementation strategies.