Non-antibiotic Treatment Research Articles

An audit to evaluate the prescribing of antibiotics for acne against NICE guidelines in a digital setting

Abstract Introduction According to NICE guidelines, individuals with moderate to severe acne may be recommended a fixed combination of topical treatment along with either oral lymecycline or doxycycline for a 12-week regimen1. If improvement is observed in these patients, continuation of the oral antibiotic and non-antibiotic-topical treatment for an additional 12 weeks is advised. It's important to adhere to these guidelines and avoid prescribing monotherapy topical antibiotics, monotherapy oral antibiotics, or the combination of topical antibiotics with oral antibiotics2. This audit aims to verify our compliance with these guidelines and ensure the appropriate use of antibiotics in our prescribing within a digital setting where patients undergo photo assessment consultations. Aim The objective of this audit is to ascertain our adherence to the NICE acne guidelines regarding the duration of oral antibiotic therapy prescribed and the accurate prescribing of topical treatments in conjunction with the oral antibiotic1. The audit criteria entail ensuring that 100% of consultations result in prescriptions aligning with the following: oral antibiotic treatment not exceeding 6 months, a prescribed non-antibiotic topical treatment alongside oral antibiotics, and avoidance of prescribing a combination of topical antibiotics with oral antibiotics. Method A retrospective review was conducted on all consultations involving the prescribing of oral and topical antibiotics from 22.4.2023 to 18.4.2024. Each consultation was assessed for the quantity of oral antibiotics prescribed over a 12-month period and examined for the accompanying topical treatments. Additionally, checks were made to determine if the patient was currently taking any oral or topical antibiotics from other sources, ensuring that antibiotics were not overprescribed and that co-prescribing practices adhered to guidelines. Ethical approval was not required since this is a clinical audit. Results The data extraction identified 427 consultations in which patients were prescribed either oral antibiotics (361 cases) or topical antibiotics (Duac-66 cases). In 99% of the consultations, patients were not prescribed oral antibiotics for more than six months. The remaining 1% of patients had already been prescribed oral antibiotics from other sources. It is noted that additional queries should have been conducted to ascertain the duration of antibiotic use prescribed elsewhere. Furthermore, 99% of consultations adhered to the criteria of prescribing a non-antibiotic topical treatment alongside an oral antibiotic. The remaining 1% involved patients who were already using a topical antibiotic from another source, which should have been further investigated to ensure cessation upon initiation of the prescribed oral antibiotics. In all cases, patients were prescribed an appropriate topical treatment in conjunction with an oral antibiotic from our digital setting. Discussion This audit confirms high compliance with NICE guidelines for acne treatment within our digital consultation framework1. Specifically, 99% of consultations adhered to the duration regimen of oral antibiotics, ensuring prescriptions did not exceed six months. Additionally, the majority of cases, correctly included non-antibiotic topical treatments alongside oral antibiotics, minimising the risk of antibiotic resistance. However, slight differences were noted in cases where patients had existing prescriptions from other sources. These findings highlight the effectiveness of our prescribing practices and the importance of thorough patient medication history reviews.

Fe-based nanozyme with photothermal activity prepared from polymerization-induced self-assembly assays boosts the recovery of bacteria-infected wounds

Nowadays, the overuse of antibiotics has escalated bacterial infections into an increasingly severe global health threat. Developing non-antibiotic treatments has emerged as a promising strategy for treating bacterial infections. Notably, nanozyme-based composite materials have garnered growing interest. Therefore, the efficient preparation of nanozyme is important. Herein, we have presented an efficient method to prepare Fe-based nanozyme through polymerization-induced self-assembly assay to kill bacteria efficiently, which could significantly enhance the healing of infected wounds. Through polymerization-induced self-assembly assay, a large number of uniformly sized micelles, bearing imidazole groups, could be efficiently prepared. These nanoparticles subsequently chelate with Fe ions, followed by pyrolysis and etching processes, resulting in the production of uniformly small-sized nanozymes with high adsorption activity in the near-infrared region. The composite materials could effectively eradicate bacteria via a synergistic strategy of photothermal and catalytic therapies under infected microenvironments. In vivo animal models with full-thickness wounds showed that combination therapy not only eradicates 98 % of the bacteria but also significantly accelerates wound healing. This work underscores the utility of polymerization-induced self-assembly in the preparation of nanozymes and reveals promising applications of nanozymes in wound healing. Statement of significanceThis research introduces a functional nanozyme with photothermal activity, synthesized through polymerization-induced self-assembly, offering a promising non-antibiotic strategy to combat bacterial infections. This strategy enhances wound healing by combining photothermal and catalytic therapies, effectively eradicating drug-resistant bacteria while minimizing damage to healthy tissue. Our findings hold significant implications for the development of advanced antibacterial treatments and offer a robust assay to prepare nanozyme with small sizes. The prepared functional nanoparticles have a potential in wound healing, addressing a critical need in the face of rising antibiotic resistance.

Game-Changing Antibiotic Solutions for Chronic UTIs in Women

Urinary tract infections (UTIs) are prevalent in primary healthcare settings, with persistent recurrences posing significant challenges. These recurrences necessitate extended antibiotic use, adversely affecting patients' quality of life, mental health, and physical activity. The evolving defense mechanisms of bacteria against the host immune system and antibiotics complicate treatment. This article examines the pathomechanisms of recurrent UTIs, focusing on bacterial defense factors. Understanding these mechanisms is essential for developing innovative treatments, particularly non-antibiotic methods, to reduce antibiotic use and its associated side effects, thereby improving patients' overall well-being. The review synthesizes current knowledge on the pathomechanisms, diagnostics, and treatments for recurrent UTIs, emphasizing the impact on patients' mental and physical health. It highlights innovative, non-antibiotic treatment approaches.

Gaps in knowledge and recurrent urinary tract infections in women.

The focus of this review is to present recent literature and gaps in knowledge (GIKs) surrounding the current and future treatment and prevention of uncomplicated recurrent urinary tract infections (rUTIs) in women. Recurrent urinary tract infections are common, significantly reduce quality of life, and create a substantial economic burden to the healthcare system. They are disproportionately affecting the postmenopausal women. Antibiotics, which are used for the treatment and prophylaxis of uncomplicated rUTI, have become problematic, as there is a global rise in allergy and resistance to these agents and their use is associated with further antimicrobial resistance. Thus, in recent decades, several alternative, nonantibiotic approaches have been evaluated. There is a critical need for a concerted and standardized methodology for diagnosing, treating, and monitoring women with rUTIs. Additionally, novel nonantibiotic alternative treatment and preventive measures for UTIs are desperately required to address the global issue of antibiotic recalcitrance in all age groups, and specifically older women. Research efforts have sought to develop alternative and more effective techniques; many of which appear to be promising, but require additional evaluation and validation through clinical trials.

Urinary tract infections: pathogenesis, host susceptibility and emerging therapeutics.

Urinary tract infections (UTIs), which include any infection of the urethra, bladder or kidneys, account for an estimated 400 million infections and billions of dollars in health-care spending per year. The most common bacterium implicated in UTI is uropathogenic Escherichia coli, but diverse pathogens including Klebsiella, Enterococcus, Pseudomonas, Staphylococcus and even yeast such as Candida species can also cause UTIs. UTIs occur in both women and men and in both healthy and immunocompromised patients. However, certain patient factors predispose to disease: for example, female sex, history of prior UTI, or the presence of a urinary catheter or other urinary tract abnormality. The current clinical paradigm for the treatment of UTIs involves the use of antibiotics. Unfortunately, the efficacy of this approach is dwindling as the prevalence of antimicrobial resistance rises among UTI isolates, and the immense quantity of antibiotics prescribed annually for these infections contributes to the emergence of resistant pathogens. Therefore, there is an urgent need for new antibiotics and non-antibiotic treatment and prevention strategies. In this Review, we discuss how recent studies of bacterial pathogenesis, recurrence, persistence, host-pathogen interactions and host susceptibility factors have elucidated new and promising targets for the treatment and prevention of UTIs.

Unveiling the pathogenic and multidrug-resistant profiles of Vibrio alfacsensis: A potential identified threat in turbot (Scophthalmus maximus) aquaculture

Vibrio alfacsensis is traditionally seen as an environmental symbiont within its genus, with no detailedly documented pathogenicity in marine aquaculture to date. This study delves into the largely unexplored pathogenic potential and emerging antibiotic resistance of V. alfacsensis. The VA-1 strain, isolated from recirculating aquaculture system (RAS) effluent of cultured turbot (Scophthalmus maximus), underwent comprehensive analysis including biochemical identification, antibiotic susceptibility testing and reinfection trials. The results confirmed VA-1's pathogenicity and significant multiple antibiotic resistance. VA-1 could induce systemic infection in turbot, with symptoms like kidney enlargement, exhibiting virulence comparable to known Vibrio pathogens, with an LD50 around 2.36 × 106 CFU/fish. VA-1's remarkable resistance phenotype (14/22) suggested potential for genetic exchange and resistance factor acquisition in aquaculture environments. Phylogenetic analysis based on 16S rDNA sequences and whole-genome sequencing has firmly placed VA-1 within the V. alfacsensis clade, while genome-wide analysis highlights its similarity and diversity in relation to strains from across the globe. VA-1 contained numerous replicons, indicating the possibility for the spread of resistance and virulence genes. This study suggests V. alfacsensis may acquire and transfer pathogenic and resistant traits through horizontal gene transfer, a likelihood intensified by changing environmental and aquaculture conditions, highlighting the need for vigilant pathogen monitoring and new non-antibiotic treatments.

Programmed degradable core-shell nanoparticles eradicate mature biofilm via precise in-situ phototherapy

Combating bacterial biofilm poses a significant challenge because of the dense extracellular polymeric substance (EPS) barrier and inherent drug tolerance. Herein, the designed core-shell nanoparticles (DA3-NPs) that eradicate biofilm by precise in-situ phototherapy are reported. DA3-NPs are self-assembled using thermosensitive azo-polymers (AP3) to encapsulate GSH-degradable phototherapeutic polymers (DBP) via charge interaction. Notably, D-aminoalanine grafted onto the AP3 serves as a critical component, providing an electroneutral shell and bacterial peptidoglycan targeting ability to the DA3-NPs. Consequently, DA3-NPs effectively penetrate EPS up to a depth of 60 µm and precisely target the bacteria within the biofilms. Upon exposure to laser irradiation and the GSH microenvironment, DA3-NPs undergo sequential responses involving shell detachment and core disintegration. These processes facilitate point-to-point bacterial killing through the in-situ generations of ROS, carbon radicals and heat damage to the internal bacteria. Compared to non-targeted nanoparticles, DA3-NPs exhibit a 61-fold increase in biofilm removal efficiency. This study thus presents a precise in-situ phototherapy strategy for nonantibiotic treatment of biofilm infections.

Management of acute uncomplicated diverticulitis and adherence to current guidelines-a multicentre SNAPSHOT study.

To explore whether previous participation in clinical studies increases adherence to management guidelines in acute uncomplicated diverticulitis (AUD). This retrospective cohort study was designed to give a SNAPSHOT of the management of AUD at six hospitals, three of which had participated in the AVOD trial comparing antibiotic versus non-antibiotic treatment of AUD. Patients with AUD were included from March 2019 through June 2020 and followed for 90days. The primary outcome was treatment of AUD categorised by antibiotic treatment and inpatient or outpatient management compared between AVOD and non-AVOD hospitals. Descriptive statistics were compiled, and differences between hospitals were assessed with Pearson's chi-squared test. The cohort included 449 patients with AUD of which 63% were women and the median age was 63 (IQR: 52-73) years. Patient characteristics were comparable across the hospitals. Antibiotics were administered to 84 (19%) patients and 113 (25%) patients were managed as inpatients. Management varied significantly between AVOD and non-AVOD hospitals. The mean proportion of patients treated with antibiotics was 7% at AVOD hospitals compared to 38% at non-AVOD hospitals (p < 0.001). The mean proportion of in-hospital management was 18% at AVOD hospitals versus 38% at non-AVOD hospitals (p < 0.001). Most patients with AUD were managed according to current guidelines. However, the management varies between hospitals and previous participation in clinical studies may increase knowledge of and adherence to guidelines.

In situ deposition of nanobodies by an engineered commensal microbe promotes survival in a mouse model of enterohemorrhagic E. coli.

Engineered smart microbes that deliver therapeutic payloads are emerging as treatment modalities, particularly for diseases with links to the gastrointestinal tract. Enterohemorrhagic E coli (EHEC) is a causative agent of potentially lethal hemolytic uremic syndrome. Given concerns that antibiotic treatment increases EHEC production of Shiga toxin (Stx), which is responsible for systemic disease, novel remedies are needed. EHEC encodes a type III secretion system (T3SS) that injects Tir into enterocytes. Tir inserts into the host cell membrane, exposing an extracellular domain that subsequently binds intimin, one of its outer membrane proteins, triggering the formation of attaching and effacing (A/E) lesions that promote EHEC mucosal colonization. Citrobacter rodentium (Cr), a natural A/E mouse pathogen, similarly requires Tir and intimin for its pathogenesis. Mice infected with Cr(ΦStx2dact), a variant lysogenized with an EHEC-derived phage that produces Stx2dact, develop intestinal A/E lesions and toxin-dependent disease. Stx2a is more closely associated with human disease. By developing an efficient approach to seamlessly modify the C. rodentium genome, we generated Cr_Tir-MEHEC(ΦStx2a), a variant that expresses Stx2a and the EHEC extracellular Tir domain. We found that mouse pre-colonization with HS-PROT3EcT-TD4, a human commensal E. coli strain (E. coli HS) engineered to efficiently secrete- an anti-EHEC Tir nanobody, delayed bacterial colonization and improved survival after challenge with Cr_Tir-MEHEC(ΦStx2a). This study provides the first evidence to support the efficacy of engineered commensal E. coli to intestinally deliver therapeutic payloads that block essential enteric pathogen virulence determinants, a strategy that may serve as an antibiotic-independent antibacterial therapeutic modality.

Situations Predisposing Primary Care Patients to Use Antibiotics Without a Prescription in the United States

Background: Using antibiotics without medical guidance (non-prescription use) is a potential safety threat to individual and public health. Patients' situations can impact their intentions to use non-prescription antibiotics in the future (intended use). This survey (1) explores the dimensionality of 13 predefined situations to identify ‘summary factor,’ which include conceptually similar situations that influence patients’ intended use of non-prescription antibiotics, and (2) identifies the sociodemographic predictors associated with these summary factors. Methods: A cross-sectional survey was conducted from January 2020–June 2021 in the waiting rooms of six safety-net primary care clinics and two private emergency departments. We used principal component analysis as a data reduction technique and confirmed the factor structure of the situations (identifying three situational summary factors). Multivariate linear regression identified the sociodemographic predictors (e.g., age, gender, race, education, insurance, healthcare system, language preference, birth country, and health literacy) associated with each summary factor. Results: Of the 564 patients surveyed, the majority were female (72%), Hispanic or Latinx (47%), college-educated (44%), and received public health insurance (e.g., Medicaid or County Financial Assistance) (56%). The largest proportion of patients endorsed intended non-prescription antibiotic use for situations involving high doctor visit costs (29.8%), having leftover prescription antibiotics (50.4%), and experiencing symptom relief with prior use of antibiotics (47.5%) (Figure 1). We identified three situational summary factors: (1) perceived barriers to a doctor visit and receiving a prescription (Cronbach’s alpha [α]=0.96), (2) convenience and accessibility of non-prescription antibiotics (α=0.81), and (3) previous symptom relief with antibiotics (α=0.95). After controlling for gender, race, education, insurance, language preference, birth country, and health literacy, our multivariate regression results revealed that younger patients (P &lt; 0 .04) and patients attending the safety-net health system (P &lt; 0 .001) had more intended use of non-prescription antibiotics for all three summary factors (Figure 2). Conclusions: Our study revealed that younger patients and individuals receiving care from the safety-net clinics had an increased risk of intended non-prescription antibiotic use across all summary factors. Future stewardship interventions should consider the types of situations that drive patients' decisions to use antibiotics without a prescription. Interventions aimed at reducing barriers to healthcare (e.g., high costs and long waits associated with doctor appointments) and educating individuals on the risks associated with inappropriate antibiotic use while providing alternative (non-antibiotic) treatment options may reduce antibiotic use and antimicrobial resistance. Acknowledgments: This work is supported by grant number R01HS026901 from AHRQ and NRSA T-32 (6T32HC10031).Disclosure: Barbara Trautner: Stock: Abbvie--sold in December 2023; Abbott Laboratories--sold in December 2023; -Bristol Myers Squibb--sold in December 2023; Pfizer--sold in December 2023; Consultant--Phiogen—consultant. Contracted research through NIAID for STRIVE trial, currently testing Shionogi product; Contracted research--Peptilogics; Contracted research--Genentech

Cur@ZIF-8@BA nanomaterials with pH-responsive and photodynamic therapy properties promotes antimicrobial activity.

Antimicrobial photodynamic therapy (aPDT) has emerged as a highly promising strategy for non-antibiotic treatment of infections due to its unique advantages in efficient bactericidal action and reduction of drug resistance. The natural photosensitizing properties of curcumin (Cur) are widely acknowledged; however, its limited bioavailability has impeded its practical application. In this study, we developed a nanomaterial called Cur@ZIF-8@BA by encapsulating Cur within ZIF-8 and modifying the surface with boric acid (BA). The Cur@ZIF-8@BA exhibits pH-responsive properties and enhances bacterial binding, thereby effectively promoting photodynamic therapy. Moreover, its antibacterial activity against E. coli, Staphylococcus aureus and A. baumannii is significantly increased in the presence of light compared to a dark environment. The mechanism behind this may be that BA increases the affinity of Cur@ZIF-8@BA towards bacteria, and making released Zn2+ and BA from the nanomaterial increase bacterial cell membrane permeability. This facilitates efficient delivery of Cur into bacterial cells, resulting in generation of abundant reactive oxygen species (ROS) and subsequent bactericidal activity. In conclusion, our prepared Cur@ZIF-8@BA holds great promise as a photodynamically mediated antimicrobial strategy.

A review for non-antibiotic treatment of Helicobacter pylori: new insight.

Gastric ulcers and gastric cancer are brought on by the Helicobacter pylori bacteria, which colonizes under the stomach mucous membrane. Different medication regimens are used to remove it, but the illness returns and becomes more resistant, which lowers the treatment rates. Additionally, this bacterium now exhibits a skyrocketing level of multi-drug resistance, necessitating recurrent therapeutic treatments. The negative effects of synthetic medications in comparison to conventional therapies are another significant factor in favor of non-pharmacological therapy. The most significant side effects of popular anti-gastric ulcer medications include nausea, vomiting, and diarrhea. Stomach ulcers have previously been treated with herbal remedies and complementary treatments like probiotics. When probiotics are ingested, the host experiences several advantages that may be brought about by altering the bacterial flora in the digestive system. Additionally, stronger-acting chemical compounds and plant extracts can be employed to treat patients. In this article, we look at the substances and medications that are utilized in place of synthetic stomach ulcer-curing treatments.

Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis

Bacterial vaginosis (BV) is a common cause of vaginal infection. First-line treatments of BV are metronidazole and clindamycin. Due to the increase in antibiotic resistance, effective nonantibiotic treatments for BV are needed. To examine whether dequalinium chloride, a broad-spectrum antiseptic, is noninferior to oral metronidazole for the treatment of BV. This phase 4, multicenter, triple-blind, double-dummy, parallel, noninferiority randomized clinical trial was conducted from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Participants were premenopausal women 18 years or older with BV from 11 gynecologic practices and 1 hospital in Poland, Slovakia, and the Czech. Patients were randomized to treatment with dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg twice daily for 7 days). Double-dummy medication kits contained vaginal and oral tablets with placebo and active medication. The main outcome was the noninferiority margin (of 15 percentage points) in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment (visit 1). Noninferiority was met if the lower 95% CI for the difference in clinical cure rate was less than 15 percentage points at visit 1. A total of 147 women (mean [SD] age, 36.7 [9.0] years) were treated with dequalinium chloride (n = 72) or metronidazole (n = 75). The clinical cure rates at visit 1 were 64 of 69 (92.8%) for dequalinium chloride vs 69 of 74 (93.2%) for metronidazole in the intention-to-treat population, whereas in the per-protocol population, cure rates were 54 of 58 (93.1%) for dequalinium chloride vs 48 of 53 (90.6%) for metronidazole. The treatment differences of -0.5 percentage points (95% CI, -10.8 to 9.8 percentage points; P = .002) in the intention-to-treat population and 2.5 percentage points (95% CI, -9.4 to 14.4 percentage points; P = .001) in the per-protocol population confirmed the noninferiority of dequalinium chloride. The tolerability of dequalinium chloride was rated as very good by 30 of 50 patients (60.0%) but only by 21 of 54 (38.9%) for metronidazole. Three patients in the metronidazole group suspended treatment due to an adverse event. This randomized clinical trial showed that dequalinium chloride was not inferior to metronidazole for the treatment of BV. Dequalinium chloride had a similarly high cure rate but with better tolerability and fewer adverse events. With a similar efficacy to metronidazole and clindamycin, dequalinium chloride warrants consideration as first-line treatment for BV to help reduce antibiotic consumption. EudraCT: 2020-002489-15.

Natural Phytochemical and Visible Light at Different Wavelengths Show Synergistic Antibacterial Activity against Staphylococcus aureus.

As the risk of antibiotic-resistant bacteria increases, interest in non-antibiotic treatment is also increasing. Among the methods used in non-antibiotic therapy, natural antibiotics such as essential oils have disadvantages such as low efficiency. In the case of phototherapy, the light used for antibacterial activities has low penetration into the human body because of its short wavelength, making it of low medical utility. To solve this problem, this study aimed to determine conditions for enhancing the antibacterial activity of natural phytochemicals and visible light. Four natural phytochemical extracts that showed high antibacterial properties in previous studies were analyzed. Synergistic effects on antibacterial activity and cytotoxicity were determined when natural phytochemical extracts and visible light were simultaneously used. As a result, it was confirmed that the antibacterial activity increased by four times when Sanguisorba officinalis L. was irradiated with 465 nm for 10 min and 520 nm for 40 min, and Uncaria gambir Roxb. was irradiated with 465 nm for 10 min and 520 nm for 60 min compared to when Sanguisorba officinalis L. and Uncaria gambir Roxb. were used alone. The synergistic effect on antibacterial activity was independent of the absorption peak of the natural phytochemical extracts. In addition, in the case of natural phytochemical extracts with improved antibacterial activity, it was confirmed that the improvement of antibacterial activity was increased in inverse proportion to the light irradiation wavelength and in proportion to the light irradiation time. The antibacterial activity was enhanced regardless of antibiotic resistance. In the case of cytotoxicity, it was confirmed that there was no toxicity to A549 cells when treated with 465 nm, the shortest wavelength among the natural phytochemical extracts. These results show how to replace blue light, which has been underutilized due to its low transmittance and cytotoxicity. They also demonstrate the high medical potential of using natural phytochemical and visible light as a combination therapy.

What to do about recurrent urinary tract infections: A review of evidence behind emerging therapies.

Recurrent urinary tract infections (rUTIs) can be debilitating for patients and pose an increasing challenge in the primary care setting. An efficient approach enables timely access and effective carefor patients. Recent research and pharmaceutical developments have provided new avenues for treating this common condition. A narrative review was conducted to provide a targeted overview of contemporary management strategies in rUTIs to assist primary care physicians in managing patients with rUTIs efficiently and effectively. Recurrent urinary tract infections require investigation and risk factor identification. Appropriate patient education in the primary care setting, behavioural modifications and commencement of non-antibiotic treatment might reduce rUTI. Certain patients might require referral to a urologist for consideration of other treatment strategies and further investigation.

Qualitative study on shared decision making in cystitis management in general practice.

Cystitis is commonly treated with antibiotics, although non-antibiotic options could be considered for healthy non-pregnant women. Shared decision making (SDM) can be used in cystitis management to discuss the various treatment options but is not frequently applied in general practice. To identify barriers and facilitators for applying SDM in cystitis management in general practice. Qualitative explorative research in general practice with healthcare professionals (HCPs; GPs and GP assistants) and healthy non-pregnant women with a recent history of cystitis (patients). Individual semi-structured interviews were conducted between May and October 2022. We applied a combination of thematic and framework analysis. Ten GPs, seven GP assistants, and 15 patients were interviewed. We identified the following three main barriers and one key facilitator: (1) applying SDM is deemed inefficient; (2) HCPs assume that patients expect antibiotic treatment and some HCPs consider non-antibiotic treatment inferior; (3) patients are largely unaware of the various non-antibiotic treatment options for cystitis; and (4) HCPs recognise some benefits of applying SDM in cystitis management, including reduced antibiotic use and improved patient empowerment, and patients appreciate involvement in treatment decisions, but preferences for SDM vary. SDM is infrequently applied in cystitis treatment in general practice owing to the current focus on efficient cystitis management that omits patient contact, HCPs' perceptions, and patient unawareness. Nevertheless, both HCPs and patients recognise the long-term benefits of applying SDM in cystitis management. Our findings facilitate the development of tailored interventions to increase the application of SDM, which should be co-created with HCPs and patients, and fit into the current efficient cystitis management.

MANNosylation of Mesoporous Silica Nanoparticles Modifies TLR4 Localization and NF-κB Translocation in T24 Bladder Cancer Cells.

D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide(LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.

Comparison between intrauterine application of an antibiotic and an herbal product to treat clinical endometritis in dairy cattle – A randomized multicentre field study

Uterine diseases are main indications for antibiotic use in dairy cows. To test a non-antibiotic treatment option, we compared the effect of an intrauterine cephapirin (Metricure®; cefapirin benzathin 500 mg per dosis; CEPH) with an intrauterine applied herbal product (25 ml of EucaComp® PlantaVet containing alcoholic extracts of Calendula officinalis L., Mellissa officinalis L., Origanum majorana L. and Eucalyptus globulus Labill. (EUC)) on the clinical cure of endometritis.Examinations of 816 cows between 21 and 35 days after calving were performed and cases of clinical endometritis (n = 169) were included. Diagnosis based on a scoring system for vaginal discharge. Study animals were randomly assigned to one of two treatment groups and treated immediately. After excluding animals with incomplete datasets, 136 cows (EUC: n = 61; CEPH: n = 75) remained for the final analysis.In total, 64% (EUC: 61%, CEPH: 67%) of analysed endometritis cases were considered as clinically cured 14 ± 2 days after the first treatment, 15% stayed uncured after the application of a maximum of two consecutive treatments, leading to an overall clinical cure rate of 85% (EUC: 82%, CEPH: 88%). No statistically difference in clinical cure rates could be observed between both treatment groups nor 14 ± 2 days after the first treatment (p = 0.956) neither regarding the overall cure rate (p = 0.923).In conclusion, the clinical cure of dairy cows' endometritis after the intrauterine application of the herbal product was non-inferior to the intrauterine application of the antibiotic cephapirin. These results could contribute to reduce the antimicrobial use in the daily veterinary routine treatment of endometritis.

Construction of Ag/CdZnS QDs nanocomposite for enhanced visible light photoinactivation of Staphylococcus aureus

With increasing use of antibiotics, the development of antibiotic-resistant pathogens poses a serious threat to human health and the environment. Photocatalytic inactivation of these harmful pathogens is one of the novel and non-antibiotic treatments. The study fabricated Ag NPs decorated CdZnS QDs via a facile and biological co-precipitation method using L. camara plant extract as a green alternative to treat the toxic chemicals. The fabricated Ag/CdZnS QDs (NCs) were prepared for the efficient treatment of antibiotic-resistant pathogens as they raise a major global concern. The fabricated NCs were characterized with various characterization techniques to verify its physicochemical properties. The fabricated NCs have shown excellent photo-sterilization performance of 97 % against S. aureus. The excellent activity was attributed to the decoration of Ag NPs on CdZnS QDs as it helped in shortening band gap, improved visible light absorption ability, increased active sites, and boosted photogenerated electron/hole pairs stability. Radical trapping experiment and ESR analysis indicated the involvement of •OH and h+ in the photoinactivation of bacteria. The photo sterilization reaction of NCs was carried out under different environmental conditions, including light and dark conditions and different pH conditions. The experiment was carried out in sewage-treated water in order to test the real-time application, and the fabricated NCs achieved excellent 95.9 % photo-inactivation of S. aureus cells in sewage treated water and the Chemical Oxygen Demand (COD) of the system was increased after photo inactivation treatment. The fabricated NCs have also shown excellent reusable efficiency of 95% after six runs and the photostability and anti-corrosive nature of NCs were confirmed. The study provides an insight for the employment of photocatalysis for the sterilization of pathogens in real time aquatic environment across the globe.

Efficacy and clinical potential of phage therapy in treating methicillin-resistant Staphylococcus aureus (MRSA) infections: A review.

Staphylococcus aureus infections have already presented a substantial public health challenge, encompassing different clinical manifestations, ranging from bacteremia to sepsis and multi-organ failures. Among these infections, methicillin-resistant S. aureus (MRSA) is particularly alarming due to its well-documented resistance to multiple classes of antibiotics, contributing significantly to global mortality rates. Consequently, the urgent need for effective treatment options has prompted a growing interest in exploring phage therapy as a potential non-antibiotic treatment against MRSA infections. Phages represent a class of highly specific bacterial viruses known for their ability to infect certain bacterial strains. This review paper explores the clinical potential of phages as a treatment for MRSA infections due to their low toxicity and auto-dosing capabilities. The paper also discusses the synergistic effect of phage-antibiotic combination (PAC) and the promising results from in vitro and animal model studies, which could lead to extensive human clinical trials. However, clinicians need to establish and adhere tostandard protocols governing phage administration and implementation. Prominent clinical trials areneeded to develop and advance phage therapy as a non-antibiotic therapy intervention, meeting regulatory guidelines, logistical requirements, and ethical considerations, potentially revolutionizing the treatment of MRSA infections.