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Background Antibiograms are stewardship tools that provide antimicrobial resistance data for regional bacterial isolates to guide treatment of infections. Objectives To develop regional antibiograms of urinary Escherichia coli isolates from cats and dogs. Animals Escherichia coli isolates cultured from feline (N = 143) and canine (640) urine from 2013 to 2017, from Kansas State University (N = 335) and private practice (N = 448) patients in the Midwestern United States. Methods Retrospective review of urine culture and susceptibility results. Antibiograms were created for 10 commonly used antimicrobial agents using Clinical and Laboratory Standards Institutes guidelines. Results No isolates from cats were susceptible to amoxicillin‐clavulanate (susceptibility [S] ≤ 0.25/0.12) or amoxicillin (S ≤ 0.25); isolates from dogs had low susceptibility to amoxicillin 53% (S ≤ 8). Conversely, isolates from dogs had high susceptibility to amoxicillin‐clavulanate 92% (S ≤ 8/4), despite equal 90th percentile minimum inhibitory concentrations (8 μg/mL) for feline and canine populations. Resistance to other antimicrobials was uncommon (≤7% for isolates from cats, ≤14% for isolates from dogs). Conclusions and Clinical Importance The disparity in susceptibility for amoxicillin and amoxicillin‐clavulanate between isolates from cats and dogs likely reflects higher breakpoints for urinary tract infections (UTIs) in dogs. Urine concentration data for these antimicrobials in cats might support a UTI‐specific breakpoint for cats and increase potential therapeutic options for managing UTIs in cats with first‐line antimicrobials. Decreased susceptibility among isolates from dogs to amoxicillin (53%) compared to amoxicillin‐clavulanate (92%) might support amoxicillin‐clavulanate as a better empirical choice for UTIs in dogs in this geographical region.

Treatment for the eradication of Helicobacter pylori infection, a leading cause of peptic ulcer disease and an important risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma, is indicated whenever infection is identified. However, treatment success rates with current guideline-recommended proton-pump inhibitor (PPI)-based regimens remain suboptimal, with one potential factor associated with treatment failure being inadequate acid suppression. Vonoprazan (Voquezna ® ) is a first-in-class potassium-competitive acid blocker with the potential to provide potent and sustained acid suppression. Following clinical trials conducted mainly in Asia (supported by post-marketing experience from Asia) and the phase III PHALCON-HP trial conducted in the USA and Europe, vonoprazan is now approved in the USA for use in combination with amoxicillin (dual therapy) or amoxicillin and clarithromycin (triple therapy) for the treatment of H. pylori infection in adults. The vonoprazan-based dual and triple therapy regimens were generally well tolerated in PHALCON-HP. In addition, vonoprazan has advantages including a rapid onset of action and no food effect, making vonoprazan-based dual and triple therapy regimens valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection. Plain Language Summary Infection with the bacterium Helicobacter pylori is a leading cause of peptic ulcer disease and has been identified as an important risk factor for gastric cancer. Current recommended treatments for H. pylori infection generally involve a combination of antibiotics together with an acid suppressant, such as a proton-pump inhibitor (PPI). However, treatment success rates with current guideline-recommended PPI-based regimens remain suboptimal. Vonoprazan (Voquezna ® ), from a new class of drugs known as potassium-competitive acid blockers, has the potential to provide potent and sustained acid suppression. Based on the findings of a pivotal trial (PHALCON-HP) conducted in the USA and Europe, vonoprazan is now approved in the USA for the treatment of H. pylori infection in adults when used in combination with amoxicillin, or amoxicillin and clarithromycin. Alongside the demonstrated efficacy and tolerability of the vonoprazan-based regimens, vonoprazan has a rapid onset of action and can be taken with or without food. Thus, vonoprazan-based dual and triple therapy regimens present valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment. The potential recovery of the human gut microbiota after an antibiotic treatment, and its effects on our health, are poorly understood. Here, the authors use a mouse model mimicking paediatric antibiotic use to shed new light into these processes.

Staphylococcal infections are often hard to treat due to increasing resistance, especially to β-lactams. Previous studies described the synergy between common antibiotics and isoflavonoids; however, little is yet known about the combinatory effects of antibiotics with products of human isoflavone metabolism. In this study, demethyltexasin (DT), a human body metabolite of soybean isoflavones, was evaluated for its possible antistaphylococcal combinatory effect with amoxicillin and oxacillin. For comparison, common therapeutically used combination of amoxicillin/clavulanic acid was tested. DT showed strong synergistic interactions against most of Staphylococcus aureus strains when combined with amoxicillin (sum of fractional inhibitory concentrations [ΣFIC] 0.257–0.461) and oxacillin (ΣFIC 0.109–0.484). When oxacillin was combined with DT, resistance to this antibiotic was overcome in many cases. Moreover, antibiotic/DT combinations were effective mainly against methicillin-resistant S. aureus (MRSA); however, the commonly used drug amoxicillin/clavulanic acid was effective only against sensitive strains. Our results indicated DT as a compound able to act synergistically with β-lactams. In addition, some combinations are effective against MRSA and decrease staphylococcal resistance. To the best of our knowledge this is the first report of the antimicrobial synergistic effects of isoflavone human body metabolite with common antibiotics. DT seems to be a possible candidate for further research focused on antistaphylococcal drug development, especially against antibiotic-resistant strains.

The increasing rates of antibiotic resistance in Helicobacter pylori ( H. pylori ) are a major concern of the decreasing eradication rate. Large-scale and long-period studies on antimicrobial susceptibility of H. pylori in children are limited. This study aimed to describe the temporal changes of antibiotic resistance among children in southeast China. Gastric biopsies obtained from children were cultured for H. pylori from 2015 to 2020. Susceptibility to clarithromycin (CLA), amoxicillin (AML), metronidazole (MTZ), furazolidone (FZD), tetracycline (TET) and levofloxacin (LEV) was tested. Data from 2012 to 2014 reported previously were obtained for comparing the change in temporal trends of antibiotic resistance. A total of 1638 (52.7%) H. pylori strains were isolated from 3111 children recruited. The resistance rates to CLA, MTZ and LEV were 32.8%, 81.7% and 22.8%, respectively. There were 52.9% strains resistant to single resistance, 28.7% to double resistance, and 9.0% to triple resistance. The total resistance rate and resistance rates to CLA, MTZ, LEV, CLA + LEV and CLA + MTZ + LEV increased annually in a linear manner. All resistant patterns except single resistance increased obviously from 2015 to 2017 and 2018 to 2020 compared to that from 2012 to 2014. Double resistance to CLA + MTZ increased significantly with age. The resistance rate to CLA and triple resistance to CLA, MTZ and LEV increased in children with prior H. pylori treatment than that from children without prior treatment. The antibiotic resistance rates of H. pylori were high in a large pediatric population in southeast China from 2015 to 2020. Individual treatment based on susceptibility test is imperative and optimal regimens should be chosen in H. pylori eradication therapy.

This study explores the potential of Carboxymethy Cellulose/Amoxicillin/Nano-Hydroxyapatite suspensions (CMC/AMX/nHA) for the treatment of dentin hypersensitivity, particularly in the context of periodontitis treatment. The CMC/AMX/nHA suspension was compared with the commonly used clinical desensitizing agent Bifluorid12 and the broad-spectrum antibiotic Minocycline Hydrochloride. Microscopic observation and antimicrobial experiments were conducted to quantitatively and qualitatively assess the ability of CMC/AMX/nHA to seal dentinal tubules and its antimicrobial properties. Additionally, a resin bonding experiment was performed to evaluate the effect of CMC/AMX/nHA on dentin bonding. The research results indicate that CMC/AMX/nHA demonstrates good biocompatibility, with excellent drug delivery capabilities, bacterial growth inhibition, and no interference with subsequent repair treatments during desensitization therapy. These findings suggest that CMC/AMX/nHA has high translational potential and may be effectively applied in clinical oral medicine.

Lyme borreliosis is a tick-borne disease that predominantly occurs in temperate regions of the northern hemisphere and is primarily caused by the bacterium Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia. Infection usually begins with an expanding skin lesion, known as erythema migrans (referred to as stage 1), which, if untreated, can be followed by early disseminated infection, particularly neurological abnormalities (stage 2), and by late infection, especially arthritis in North America or acrodermatitis chronica atrophicans in Europe (stage 3). However, the disease can present with any of these manifestations. During infection, the bacteria migrate through the host tissues, adhere to certain cells and can evade immune clearance. Yet, these organisms are eventually killed by both innate and adaptive immune responses and most inflammatory manifestations of the infection resolve. Except for patients with erythema migrans, Lyme borreliosis is diagnosed based on a characteristic clinical constellation of signs and symptoms with serological confirmation of infection. All manifestations of the infection can usually be treated with appropriate antibiotic regimens, but the disease can be followed by post-infectious sequelae in some patients. Prevention of Lyme borreliosis primarily involves the avoidance of tick bites by personal protective measures. Lyme borreliosis is a tick-borne disease that is caused by the bacteria Borrelia burgdorferi , Borrelia afzelii and Borrelia garinii . This Primer by Steere and colleagues discusses the epidemiology, mechanisms and management of Lyme borreliosis in North America and Europe.

Mycobacterium abscessus ( ) infections are a growing menace to the health of many patients, especially those suffering from structural lung disease and cystic fibrosis. With multidrug resistance a common feature and a growing understanding of peptidoglycan synthesis in , it is advantageous to identify potent β-lactam and β-lactamase inhibitor combinations that can effectively disrupt cell wall synthesis. To improve existing therapeutic regimens to address serious infections, we evaluated the ability of durlobactam (DUR), a novel diazobicyclooctane β-lactamase inhibitor to restore susceptibilities in combination with β-lactams and provide a biochemical rationale for the activity of this compound. In cell-based assays, susceptibility of subsp. isolates to amoxicillin (AMOX), imipenem (IMI), and cefuroxime (CXM) was significantly enhanced with the addition of DUR. The triple drug combinations of CXM-DUR-AMOX and IMI-DUR-AMOX were most potent, with MIC ranges of ≤0.06 to 1 μg/mL and an MIC /MIC of ≤0.06/0.25 μg/mL, respectively. We propose a model by which this enhancement may occur, DUR potently inhibited the β-lactamase Bla with a relative Michaelis constant ( ) of 4 × 10 ± 0.8 × 10 μM and acylation rate ( / ) of 1 × 10 M s . Timed mass spectrometry captured stable formation of carbamoyl-enzyme complexes between DUR and Ldt and d,d-carboxypeptidase, potentially contributing to the intrinsic activity of DUR. Molecular modeling showed unique and favorable interactions of DUR as a Bla inhibitor. Similarly, modeling showed how DUR might form stable Michaelis-Menten complexes with Ldt and d,d-carboxypeptidase. The ability of DUR combined with amoxicillin or cefuroxime and imipenem to inactivate multiple targets such as d,d-carboxypeptidase and Ldt supports new therapeutic approaches using β-lactams in eradicating . Durlobactam (DUR) is a potent inhibitor of Bla and provides protection of amoxicillin and imipenem against hydrolysis. DUR has intrinsic activity and forms stable acyl-enzyme complexes with Ldt and Ldt . The ability of DUR to protect amoxicillin and imipenem against Bla and its intrinsic activity along with the dual β-lactam target redundancy can explain the rationale behind the potent activity of this combination.

Infected wounds are a major threat among diabetic patients. Technological advancements are currently increasing the number of new adjunctive therapies that may be potent agents for speeding recovery, lowering the amputation rate and limiting infection recurrences. A novel formula with promising antibacterial activity, namely sericin/propolis/Amoxicillin nanoparticles, was assessed as a potent treatment of infected wounds in normal and diabetic rats. Skin wound healing efficiency was assessed through wound healing scorings, bacterial load assessment and histological examinations. It was revealed that upon using sericin/propolis/Amoxicillin nanoparticles, complete wound healing was successfully achieved after 10 and 15 days postinjury for nondiabetic and diabetic rats, respectively. However, the bacterial load in the induced infected wounds was extremely low (0–10 CFU/mL) after 15 days post-treatment. The histological studies revealed that the dermis was more organized with new matrix deposition, and mature collagen fibers were observed among the treated animal groups. The present study is the first preclinical study which reported the importance of silk sericin in the form of nano-sericin/propolis loaded with Amoxicillin as an effective treatment against bacterial wound infections.

Ampicillin (AMP) and amoxicillin (AMX) are widely used penicillin antibiotics. After administration to humans and animals, they are largely excreted in unchanged or metabolized forms, leading to their release into wastewater. In surface waters, their concentrations usually reach the ng∙L−1 range and rarely exceed µg∙L−1, although in India AMX levels above mg∙L−1 were detected in hospital effluents. The limited efficiency of wastewater treatment plants allows these compounds to enter aquatic and terrestrial environments, where they affect various organisms. The aim of this study was to assess the effects of AMP, AMX, and their mixture on wheat, one of the most extensively cultivated cereals. Determinations were carried out using standardized methodologies. The results showed that antibiotics induce oxidative stress in plants, with symptoms observed only at concentrations of 1000 mg∙kg−1 of soil DW. At this level, changes included altered antioxidant enzyme activity (APX, SOD, POD, and CAT), increased proline and H2O2 content, and reduced MDA levels. By contrast, antibiotics had minimal influence on glutathione and ascorbate and caused only slight changes in photosynthetic pigments and chlorophyll fluorescence.