Dynamic Expressions of Liver Tissue Apoptosis-related Genes of Vibrio Vulnificus Sepsis Rats and the Effects of Antibacterial Agents

Dynamic changes in mRNA expressions of liver tissue apoptosis-promoting genes Fas and Bax and apoptosis-inhibiting gene Bcl-2 of vibrio vulnificus sepsis rats were detected and the effects of antibacterial agents were examined. The rat model with Vibrio vulnificus sepsis （VV group） was established and some of the Vibrio vulnificus sepsis rats were treated with antibacterial agents （AA group）. The mRNA expressions of Fas, Bax and Bcl-2 were measured by reverse transcription polymerase chain reaction （RT-PCR）. As compared with normal control group （NC group）, the ex- pressions of Fas and Bax mRNA in liver tissue at all different time points in VV group were increased significantly （P〈0.05）, and the highest levels of Fas and Bax mRNA expressions were 6 and 12 h after the infection, respectively. At the same time, the expression of Bcl-2 mRNA in liver tissue at all different time points in VV group were decreased significantly （P〈0.05）, and the lowest level of Bcl-2 mRNA expression appeared 2 h after the infection. The mRNA expressions of Bcl-2 in liver tissue 9 and 12 h after the infection in AA group were increased significantly （P〈0.05） compared with NC group, while the expressions of Fas and Bax mRNA were not significantly different from those of NC group. Compared with VV group, the expression of Fas mRNA in AA group was decreased （P〈0.05） and Bax rnRNA was decreased significantly 12 and 16 h after the infection （P〈0.05）, while the expressions of Bcl-2 mRNA were increased significantly 9, 12 and 16 h after the infection （P〈0.05）. It is concluded that the mRNA expressions of liver tissue apoptosis-promoting genes Fas and Bax were increased remarkably in vibrio vulnificus sepsis rats, whereas the expression of apoptosis-inhibiting gene Bcl-2 mRNA was decreased obviously in sepsis rats in early stage. The treatment with cefoperazone sodium and levofloxacin lactate could inhibit the expression of Fas mRNA and Bax mRNA and enhance the expression ofBcl-2 rnRNA at the same time.

From Environmental Toxicants to Antibacterial Agents:BPA Analogues Selectively Inhibit the Growth of Gram-Positive Bacteria by Disturbing Biosynthesis of the Cell Wall

Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous studies.However,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and health.Given the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug resistance.In this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 cells.The developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial substances.Collectively,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.

Cow dung-derived biochars engineered as antibacterial agents for bacterial decontamination

Disposal of the pollutants arising from farming cattle and other livestock threatens the environment and public safety in diverse ways.Herein,we report on the synthesis of engineered biochars using cow dung as raw material,and investigating these biochars as antibacterial agents for water decontamination.By coating the biochars with N-halamine polymer and loading them with active chlorine (i.e.,Cl+),we were able to regulate them on demand by tuning the polymer coating and bleaching conditions.The obtained N-halamine-modified biochars were found to be extremely potent against Escherichia coli and Staphylococcus aureus.We also investigated the possibility of using these N-halamine-modified biochars for bacterial decontamination in real-world applications.Our findings indicated that a homemade filter column packed with N-halamine-modified biochars removed pathogenic bacteria from mining sewage,dairy sewage,domestic sewage,and artificial seawater.This proposed strategy could indicate a new way for utilizing livestock pollutants to create on-demand decontaminants.

Prediction Model of Antibacterial Activities for Inorganic Antibacterial Agents Based on Artificial Neural Networks

Quantitatively evaluation of antibacterial activities of inorganic antibacterial agents is an urgent problem to be solved. Using experimental data by an orthogonal design, a prediction model of the relation between conditions of preparing inorganic antibacterial agents and their antibacterial activities has been developed. This is accomplished by introducing BP artificial neural networks in the study of inorganic antibacterial agents. It provides a theoretical support for the development and research on inorganic antibacterial agents. Key words inorganic antibacterial agent - antibacterial activity - neural networks - nanometer material

Magnetic polyacrylonitrile/ZIF-8/Fe_(3)O_(4) nanocomposite bead as an efficient iodine adsorbent and antibacterial agent

The efficient adsorption of radioactive iodine(^(129)I and^(131)I)as nuclear waste is of great importance.Polymer nanocomposites consist of metal-organic frameworks(MOFs)developing for various pollutions sorption and separation have attracted much attention.This study reports the fabrication of magnetic polyacrylonitrile(PAN)/zeolitic imidazolate frameworks(ZIF-8)nanocomposites,PAN/ZIF-8(x%)/Fe_(3)O_(4),x=30 and 50,as iodine capture adsorbents.The PAN/ZIF-8(x%)/Fe_(3)O_(4)nanocomposite beads were fabricated via the phase inversion method,and their potential for iodine capture and separation in solution and vapor was investigated through UV-vis and weighing methods,respectively.Also,antibacterial activity of the as-prepared beads was assessed against E.coil and S.aureus.The as-fabricated compounds were studied by various techniques such as Fourier-transform infrared,X-ray diffraction,scanning electron microscope,energy-dispersive X-ray spectroscopy mapping,transmission electron microscope,N_(2)adsorption isotherm,and vibrating sample magnetometer.The iodine capture results showed that the efficiency of nanocomposites is remarkably higher than the pure PAN beads.Additionally,the asprepared nanocomposite adsorbents displayed higher capture capacities for iodine vapor(1524-4345mg·g^(-1))than iodine solution(187-295 mg·g^(-1)).The as-obtained magnetic nanocomposites can be successfully separated from polluted media by simple filtration or an external magnet,regenerated through washing with ethanol,and reused.Fast capturing,high sorption capacity,rapid separation,and good reusability make the PAN/ZIF-8(x%)/Fe_(3)O_(4)nanocomposites highly effective adsorbents for the separation of iodine from wastewater.Additionally,PAN/ZIF-8(50%)/Fe_(3)O_(4)bead can be considered as a potential new antibacterial agent for water and wastewater treatment.

Antibacterial Dental Resin Composites: A Narrative Review

Lack of antibacterial properties in resin-based composites (RBCs) is one of the flaws that cause the failure of filling clinically. Several agents have been incorporated to endow RBCs with antibacterial properties. In this review, we summarize the recent antibacterial agents between 2015 and 2020 using keywords of antibacterial or antimicrobial dental resin composites by PubMed databases. The most effective strategies are concerned with polymerizable monomers (50%), followed by filler particles (39%) and leachable agents (11%). A recent modification of the antibacterial agent is either by combining two agents from the same category or mixing agents from different categories in one. More than two methods were used in one study to assess antibacterial efficacy. The most common method was biofilm colony-forming units (CFUs) counting method (40%), followed by live/dead bacteria staining assay of biofilms (25%), metabolic activity assay of biofilms using MTT assay (16%), lactic acid production assay of biofilms (8%), agar diffusion test (8%), and other methods (3%) such as minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC).

药品集中带量采购对抗菌药物使用的影响分析:以阿莫西林为例

目的分析抗菌药物集中带量采购(以下简称“集采”)后使用变化,为完善我国带量采购政策和促进合理用药提供参考。方法采用描述性统计分析和间断时间序列分析方法,将第二批和第三批药品集采政策落地时间设为政策干预点,分析2019年1月—2021年12月全国医药企业阿莫西林销售量和销售金额在集采前后的变化情况。结果阿莫西林胶囊剂和颗粒剂在集采后销售量大幅上升,非中选的胶囊剂和颗粒剂销售量也有所上升,但涨幅低于市场整体增长率。非集采剂型中的阿莫西林片剂和混悬剂销售量和销售金额均出现降低,口服剂型中选能有效降低同为口服剂型的其他非集采品规销售量,阿莫西林注射剂销售量和销售金额在集采后短期内明显增长,通过模型预测阿莫西林注射剂长期的销售量和销售金额呈下降趋势。结论药品带量采购能够实现药价降低且达成以量换价的目标,中选药品使用量显著增长,但需要关注同通用名下非集采剂型的使用量情况,减少不同剂型间替代使用的情况;应该进一步扩大抗菌药物集采范围,将更多临床具体替代关系的药物纳入采购范畴,加强对临床抗菌药物的使用监测,保障临床抗菌药物合理使用。

Precise phase adjustment and antibacterial property of copper sulfide particles in confined mesoporous silica nanoreactor

Bacteria-caused wound infection greatly threatens human health,thus developing an efficient and safe antibacterial agent without drug resistance is still a great challenge.Herein,a confined vulcanization strategy is proposed to construct copper sulfides-loaded dual-mesoporous silica nanospheres(Cux-Sy@DMSNs)with various crystal phases for reactive oxygen species(ROS)-mediated and photothermal antibacterial application.With the pore confinement of DMSNs,the crystal phases of copper sulfides including CuS,Cu_(9)S_(5)and Cui.96S can be easily controlled by changing the vulcanization temperature.The relationships between the crystal phases and photothermal properties as well as peroxidase-like activity of copper sulfides were systematically investigated.Results show that the obtained CuS@DMSNs exhibited higher photothermal ability with remarkable photothermal conversion efficiency of 36.86%in the second near-infrared region(NIR-II)and better peroxidase-like activity,compared to those of Cu_(9)S_(5)@DMSNs and Cu_(1.96)S@DMSNs.As a result,the in vitro experiments showed the good antibacterial effect against both gram-negative E.coli and gram-positive S.aureus under 1064 nm laser irradiation and the presence of H_(2)O_(2).Besides,the CCK-8 assay indicated that CuS@p-DMSNs have minimal cytotoxicity against normal human umbilical vein endothelial cells at the ranged concentrations.Therefore,the resultant CuS@p-DMSNs could act as a promising antibacterial agent for deep wound bacterial infection treatment.

Effects of Multiple Cleaning and Disinfection Interventions on Infectious Diseases in Children: A Group Randomized Trial in China

Objective To assess the effectiveness of multiple cleaning and disinfection interventions in the homes and kindergartens, in reducing gastrointestinal and respiratory illnesses of children. Methods From October 2010 to September 2011, we performed a prospective, controlled study in China. 408 children under 5 years old were recruited and group randomized into intervention and control groups. Families and kindergartens in the intervention group were provided with antibacterial products for hand hygiene and surface cleaning or disinfection for one year. Each child＇s illness symptoms and sick leave were recorded every day. Results A total of 393 children completed the study, with similar baseline demographics in each of the 2 groups. Except for abdominal pain, the odds of symptoms （fever, cough and expectoration, runny nose and nasal congestion, diarrhea）, illness （acute respiratory illness and gastrointestinal illness）, and sick leave per person each month were significantly reduced by interventions. The rates of fever, diarrhea, acute respiratory illness, gastrointestinal illness and sick leave per person per year were significantly decreased as well. Conclusion Not only the acute respiratory children were significantly reduced by multiple and gastrointestinal illness but the sick leave rate in interventions.

Preliminary pharmacological evaluation of Alocasia indica Schott tuber

To elucidate potential antioxidant, antidiarrheal, cytotoxic, and antibacterial activities of the ethanol extract of A/ocasia indica Schott tuber in different experimental models established in vitro and in vivo. METHODS： In vitro antioxidant activity was evaluated by 2, 2-diphenyl-l-picrylhydrazyl （DPPH） radical-scavenging assay. Phenolic content was estimated by using Folin-Ciocalteu＇s reagent while reducing ability was measured by ferric reducing power assay./n vivo antidiarrheal studies were carried out in mice, and the activity was evaluated in castor oil and magnesium sulfate- induced diarrhea. Disk diffusion assay was utilized to determine antibacterial activity against a number of pathogenic bacterial strains. Acute toxicity test was carried out to measure the safe doses for the extract. RESULTS： In DPPH radical-scavenging assay, the extract exhibited strong radical-scavenging activity with the 50% inhibitory concentration value of 42.66 IJg/mL. Total phenolic content was found to be 542.26 mg gallic acid equivalent per 100 g of dried tuber extract, whereas flavonoid content was found to be 4.30 mg quercetin equivalent/g of dried tuber extract. In reducing power assay, the extract showed strong reducing power in a concentration-dependent manner. The extract significantly （P 〈 0.01） enhanced the latent period and decreased defecation in both castor oil- and magnesium sulfate-induced diarrhea. The extract also lessened gastrointestinal motility in mice. Potential antibacterial activity was exhibited by the extract against all the tested bacterial strains in disk diffusion assay. The 50% lethal concentration against brine shrimp nauplii was 81.09 μg/mL. CONCLUSION： The results demonstrated that the ethanol extract of A. inc/ica has potential antioxidant, antidiarrheal, cytotoxic, and antibacterial activity.

Spinal Epidural Abscess in Patients with Sepsis Who Experienced Significant Improvements after Complete Paralysis: Two Case Reports

Spinal epidural abscess (SEA) is a rare condition, and a delay in its diagnosis causes paralysis. In this study, we report two rare cases of delayed diagnosis of SEA whose conditions improved after a state of complete paralysis. The first case was a 71-year-old diabetic man who received a corticosteroid injection for shoulder pain that caused intensified pain. Thereafter, the patient developed paralysis of both legs in stage IV according to Heusner staging. Subsequently, he was diagnosed with multiple abscesses and sepsis. He was in a poor state of health. Therefore, we treated his epidural abscess conservatively. After a month, his muscle strength had improved to Heusner stage III-A, and he was transferred to another hospital. The second case was a 64-year-old diabetic man who received an epidural corticosteroid injection for lower back pain. However, the pain intensified and was admitted to the hospital for pyelonephritis. He developed paralysis in both of his arms and legs presenting as a Heusner stage IV, caused by a cervical epidural abscess. A laminoplasty was performed and paralysis was improved. However, the patient subsequently developed a left subcortical hemorrhage. He underwent surgery. However, his right hemiplegia persisted, and on Day 21, he was transferred back to the previous hospital with a Heusner III-A. We could improve the patients’ paralysis by cooperating closely with infectious disease specialists and spine surgeons, taking intensive care, applying antibacterial agents appropriately, and operating quickly.

Formation of α,α'-Bis(substituted benzylidene)cycloalkanones from Masked Aldehydes Promoted by Samarium(III) Triiodide

Diacetates 1 and N-[(1-benzotriazol-l-yl)alkyl]amides 2, both masked forms of aldehydes, could undergo deprotection and condensation with cycloalkanones in a one-pot procedure promoted by samarium(III) iodide (SmI3) to afford α,α'-bis(substituted benzylidene) cycloalkanones in good yields.

King cobra peptide OH-CATH30 as a potential candidate drug through clinic drug-resistant isolates

Cationic antimicrobial peptides （AMPs） are considered as important candidate therapeutic agents, which exert potent microbicidal properties against bacteria, fungi and some viruses. Based on our previous findings king cobra cathelicidin （OH-CATH） is a 34-amino acid peptide that exerts strong antibacterial and weak hemolytic activity. The aim of this research is to evaluate the efficacy of both OH-CATH30 and its analog D-OH-CATH30 against clinical isolates comparing with routinely utilized antibiotics in vitro. In this study, 584 clinical isolates were tested （spanning 2013-2016） and the efficacy of the candidate peptides and antibiotics were determined by a broth microdilution method according to the CLSI guidelines. Among the 584 clinical isolates, 85% were susceptible to OH-CATH30 and its analogs. Both L- and D-OH-CATH30 showed higher efficacy against （toward） Gram-positive bacteria and stronger antibacterial activity against nearly all Gram-negative bacteria tested compare with antibiotics. The highest bactericidal activity was detected against Acinetobacter spp., including multi-drug-resistant Acinetobacter baumannfi （MRAB） and methicillin-resistant Staphylococcus aureus （MRSA）. The overall efficacy of OH-CATH30 and its analogs was higher than that of the 9 routinely used antibiotics. OH-CATH30 is a promising candidate drug for the treatment of a wide variety of bacterial infections which are resistant to many routinely used antimicrobial agents.

Current perspectives of nanoparticles in medical and dental biomaterials

Nanotechnology is gaining tremendous impetus due to its capability of modulating metals into their nanosize, which drastically changes the chemical, physical and optical properties of metals. Nanoparticles have been intro- duced as materials with good potential to be extensively used in biological and medical applications. Nanoparticles are clusters of atoms in the size range of 1-100 nm. Inorganic nanoparticles and their nano-composites are applied as good antibacterial agents. Due to the outbreak of infectious diseases caused by different pathogenic bacteria and the development of antibiotic resistance, pharmaceutical companies and researchers are searching for new antibacterial agents. The metallic nanoparticles are the most promising as they show good antibacterial properties due to their large surface area to volume ratios, which draw growing interest from researchers due to increasing microbial resistance against metal ions, antibiotics and the development of resistant strains. Metallic nanoparticles can be used as effective growth inhibitors in various microorganisms and thereby are applicable to diverse medical devices. Nanotechnology discloses the use of elemental nanoparticles as active antibacterial ingredient for dental materials. In dentistry, both restorative materials and oral bacteria are believed to be responsible for restoration failure. Secondary caries is found to be the main reason to restoration failure. Secondary caries is primarily caused by invasion of plaque bacteria （acid-producing bacteria） such as Streptococcus mutans and lactobacilli in the presence of fermentable carbohydrates. To make long-lasting restorations, antibacterial materials should be made. The potential of nanoparticles to control the formation of biofilms within the oral cavity is also coming under in- creasing scrutiny. Possible uses of nanoparticles as topically applied agents within dental materials and the appli- cation of nanoparticles in the control of oral infections are also reviewed.

Primer containing dimethylaminododecyl methacrylate kills bacteria impregnated in human dentin blocks

Antibacterial dimethylaminododecyl methacrylate （DMADDM） was recently synthesized. The objectives of this study were to： （1） investigate antibacterial activity of DMADDM-containing primer on Streptococcus mutans impregnated into dentin blocks for the first time, and （2） compare the antibacterial efficacy of DMADDM with a previous quaternary ammonium dimethacrylate （QADM）. Scotchbond Multi-Purpose （SBMP） bonding agent was used. DMADDM and QADM were mixed into SBMP primer. Six primers were tested： SBMP control primer P, P＋2.5% DMADDM, P＋5% DMADDM, P＋7.5% DMADDM, P＋10% DMADDM, and P＋10% QADM. S. mutans were impregnated into human dentin blocks, and each primer was applied to dentin to test its ability to kill bacteria in dentinal tubules. Bacteria in dentin were collected via a sonication method, and the colony-forming units （CFU） and inhibition zones were measured. The bacterial inhibition zone of P＋10% DMADDM was 10 times that of control primer （P〈0.05）. CFU in dentin with P＋10% DMADDM was reduced by three orders of magnitude, compared with control. DMADDM had a much stronger antibacterial effect than QADM, and antibacterial efficacy increased with increasing DMADDM concentration. Dentin shear bond strengths were similar among all groups （P〉0.1）. In conclusion, antibacterial DMADDM-containing primer was validated to kill bacteria inside dentin blocks, possessing a much stronger antibacterial potency than the previous QADM. DMADDM-containing bonding agent was effective in eradicating bacteria in dentin, and its efficacy was directly proportional to DMADDM mass fraction. Therefore, DMADDM may be promisine for use in bonding agents as well as in other restorative and oreventive materials to inhibit bacteria.

Contact Mechanism of the Ag-doped Trimolybdate Nanowire as An Antimicrobial Agent

Antibacterial Ag-agents are intensively applied as broad spectrum, high-stability, high-efficiency and high-safety inorganic antibacterial agents. We have developed a new kind of antibacterial Ag-agent, namely Ag_2-x(NH_4)xMo_3O_(10) ·3H_2O nanowires(NWs). Carrying Ag atoms in the lattice and Ag-rich nanoparticles on the surface, the Ag-doped NWs show strong antibacterial effects for a variety of bacteria including E.coli, Staphylococcus aureus, Candida albicans and Aspergil lus niger. By performing systematic comparison experiments, we have proven that the main antibacterial effects are neither resulted from the tiny amount of Ag+ions released from the Ag-doped NWs in aqueous solutions, nor resulted from Ag-rich nanoparticles of fragments of the NWs when they are slowly dissolved in the Martin broth. Instead, the effects are mainly resulted from a contact mechanism, under which, the Ag-doped NWs need to be physically in contact with the bacteria to be eliminated. This is a novel phenomenon observed in the interactions between nanomaterials and live cells, which is worthy of further investigation at the molecular scale. As the Ag-doped NWs are not dissolved in pure water or weak acids, one may find practical antibacterial applications in textile industry and food storage industry for these unique nanomaterials.

Pharmacological evaluation of Musa seminifera Lour. fruit

OBJECTIVE： To study potential antioxidant, analgesic, antidiarrheal, and antibacterial activities of the ethanol extract of Musa seminifera Lour. fruit in different established in vivo and in vitro experimental models. METHODS： In vitro antioxidant activity was studied in 2,2-diphenyl-1-picrylhydrazyl （DPPH） radical-scavenging assay. Phenolic content was determined using Folin-Ciocalteu＇s reagent. Reducing ability was evaluated by ferric reducing power assay. Peripherally and centrally acting analgesic activity was studied in three different in vivo models, namely, acetic acid-induced writhing, hot-plate test, and tail-flick test in Swiss albino mice. In vivo antidiarrheal activity was evaluated in castor oil- and magnesium sulfate-induced diarrhea in mice. Gastrointestinal motility test was also carried out in mice. All studies in mice were undertaken at the doses of 250 and 500 mg/kg body weight. Antibacterial activity was assessed by disk diffusion assay against some Gram-positive and Gram-negative bacterial strains. Acute toxicity test was conducted to assess the safe doses of the extract. RESULTS： The extract showed 50% inhibitory concentration value of 12.65 μg/mL in DPPH radical- scavenging assay. Phenolic content was found to be 589.83 mg gallic acid equivalent per 100 g of dried fruits extract. Reducing power was in a concentration-dependent manner, and strongly comparable with the standard ascorbic acid. The extract demonstrated significant inhibition of writhing in acetic acid-induced writhing test at both dose levels （P〈0.01）. The extract also raised pain threshold in both hot-plate and tail-flick test in a dose-dependent manner, and the results were statistically significant （P〈0.01）. The extract significantly （P〈0.01） increased latent period, and decreased defecation in both castor oil- and magnesium sulfate-induced diarrhea. The extract also decreased gastrointestinal motility in mice. In disk diffusion assay, the extract showed potential antibacterial activity against all the tested bacterial strains. CONCLUSION： The results suggest that the ethanol extract of M. seminifera fruit has potential antioxidant, analgesic, antidiarrheal, and antibacterial activities.

Comparative efficacy and optimal duration of first-line antibiotic regimens for acute otitis media in children and adolescents:a systematic review and network meta-analysis of 89 randomized clinicaltrials

Introduction Antibiotic use for acute otitis media(AOM)is one of the major sources of antimicrobial resistance.However,the effective minimal antibiotic duration for AOM remains unclear.Moreover,guidelines often recommend broad ranges(5-10 days)of antibiotic use,yet the clinical impact of such a wide window has not been assessed.Methods We systematically searched PubMed/MEDLINE,Embase,Scopus,Web of Science,and Cochrane Library from database inception to 6 October 2021.Network meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children(PROSPERO CRD42020196107).Results For amoxicillin and amoxicillin-clavulanate,7-day regimens were noninferior to 10-day regimens in clinical responses[amoxicillin:risk ratio(RR)0.919(95%CI 0.820-1.031),amoxicillin-clavulanate:RR 1.108(0.957-1.282)],except for≤2 years.For the third-generation cephalosporins,7-day and 10-day regimens had similar clinical responses compared to placebo[7-day:RR 1.420(1.190-1.694),10-day:RR 1.238(1.125-1.362)compared to placebo].However,5-day regimens of amoxicillin-clavulanate and third-generation cephalosporins were inferior to 10-day regimens.Compared to amoxicillin,a shorter treatment duration was tolerable with amoxicillin-clavulanate.Conclusions Our findings indicated that 1O days of antibiotic use may be unnecessarily long,while the treatment duration should be longer than 5 days.Otherwise,5-day regimens would be sufficient for a modest treatment goal.Our findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM,and a narrower antibiotic duration window should be re-established.