Non-antibiotic Treatment Research Articles

Environmental Bovine Mastitis Pathogens: Prevalence, Antimicrobial Susceptibility, and Sensitivity to Thymus vulgaris L., Thymus serpyllum L., and Origanum vulgare L. Essential Oils.

Mastitis is considered to be one of the most important diseases of dairy cows in terms of health, production, and economy. Being the most common cause of antibiotic consumption in dairy cows, treatment of this disease is one of the biggest challenges in the veterinary profession as an increasing number of pathogens develop resistance to antibiotics used in the treatment. Therefore, new alternative approaches for limiting the use of antibiotics in livestock are required. For this reason, our study aimed to investigate prevalence of environmental mastitis associated bacterial strains, as well as the sensitivity of isolated strains to different antibiotics. Additionally, the therapeutic potential of three essential oils (EOs) was tested against bovine Serratia spp. and Proteus spp. mastitis pathogens, based on their chemical composition, as well as antibacterial potential. The study was carried out on 81 milk samples collected from dairy cows with mastitis. In order to determine prevalence of S. marcescens and P. mirabilis, microbiological isolation and identification were performed. Antimicrobial susceptibility testing was performed by disk diffusion method and the microdilution method was used to determine the antibacterial activity of selected EOs. In the oregano EO, a total of 23 compounds were detected, with carvacrol as a dominant component (78.94%). A total of 26 components were present in the EO of common thyme, where thymol was the most abundant compound (46.37%). Thymol also dominated (55.11%) the wild thyme EO. All tested EOs displayed antibacterial activity against all strains to different extents, while wild and common thyme EOs were the most effective. It could be concluded that the tested EOs represent promising therapeutic candidates for effective non-antibiotic treatment of mastitis.

Effect of bovine lactoferrin on recurrent urinary tract infections: in vitro and in vivo evidences.

Uropathogenic Escherichia coli (UPEC) strains are the primary cause of urinary tract infections (UTIs). UPEC strains are able to invade, multiply and persisting in host cells. Therefore, UPEC strains are associated to recurrent UTIs requiring long-term antibiotic therapy. However, this therapy is suboptimal due to the increase of multidrug-resistant UPEC. The use of non-antibiotic treatments for managing UTIs is required. Among these, bovine lactoferrin (bLf), a multifunctional cationic glycoprotein, could be a promising tool because inhibits the entry into the host cells of several intracellular bacteria. Here, we demonstrate that 100μg/ml bLf hinders the invasion of 2.0 ± 0.5 × 104CFU/ml E. coli CFT073, prototype of UPEC, infecting 2.0 ± 0.5 × 105 cells/ml urinary bladder T24 epithelial cells. The highest protection (100%) is due to the bLf binding with host surface components even if an additional binding to bacterial surface components cannot be excluded. Of note, in the absence of bLf, UPEC survives and multiplies, while bLf significantly decreases bacterial intracellular survival. After these encouraging results, an observational survey on thirty-three patients affected by recurrent cystitis was performed. The treatment consisted in the oral administration of bLf alone or in combination with antibiotics and/or probiotics. After the observation period, a marked reduction of cystitis episodes was observed (p < 0.001) in all patients compared to the episodes occurred during the 6months preceding the bLf-treatment. Twenty-nine patients did not report cystitis episodes (87.9%) whereas the remaining four (12.1%) experienced only one episode, indicating that bLf could be a worthwhile and safe treatment in counteracting recurrent cystitis.

An In-silico Study Showing Potentials of Selected Anthocyanin Derivatives against Uropathogenic E. coli Adhesin Protein

Urinary tract infections (UTI) caused primarily by uropathogenic Escherichia coli (UPEC) are indeed an extremely contagious disease that affects people all over the world. FimH is a major virulence component in UTI pathogenesis, and inhibiting FimH function can be an efficient means to disarm UPEC bacteria, as well as a crucial target in the development of non-antibiotic mediated UTI treatment options. The goal of this study was to identify anthocyanins in plant parts and assess&#x0D; their pharmacological characteristics. A computational methodology was used to predict the pharmacological characteristics of such substances. Compounds with pharmacophores comparable to those of known fimH inhibitors were chosen. Following that, additional research was carried out to assess their drug similarity, inhibitory potential, and IC50 values. Thus, the present study reports few novel fimH inhibitors derived from the selected plant’s phytochemicals, and is significant owing to their therapeutic implication as a non-antibiotic mediated therapy for UTI.

Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT.

Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex®; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women. Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. Eight UK NHS secondary care sites. A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (p-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) (p = 0.06). All other secondary outcomes and adverse events were similar in both arms. This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

Neutrophil NOX2 is Required to Control Experimental Urinary Tract Infection

Abstract Urinary tract infections (UTIs) affect 150 million people worldwide. Uropathogenic Escherichia coli (UPEC) is the primary pathogen causing over 80% of UTIs. Systemic antibiotic treatment is the only available therapy for UTIs. Thus, novel non-antibiotic treatments for UTI are necessary. The NADPH oxidase complex 2 (NOX2) has an essential role in the antimicrobial response against many bacterial and fungal infections, but its role during UTIs remains unknown. Objective To study the role of NOX2 in bacterial killing during experimental UTI. Methods Female wild-type (WT) C57BL/6 mice, NOX2 knockout (KO) mice, and WT mice treated with a NOX2 inhibitor were transurethrally infected with UPEC (CFT073 strain). NOX2 protein expression was analyzed by Western blotting. Cellular sources of NOX2 were identified by immunofluorescence. Neutrophils were isolated from murine bone marrow. Human neutrophils were purified from peripheral blood of healthy donors. Purified neutrophils were infected with UPEC in vitro. UPEC burden was assessed by enumerating colony forming units (CFU). Reactive oxygen species (ROS) production was quantified using the Amplex™ Red kit. Results NOX2 KO mice, or mice treated with NOX2 inhibitor, were more susceptible to experimental UTI compared to WT mice. Immunofluorescence microscopy localized NOX2 primarily in infiltrating neutrophils. Neutrophils from NOX2 KO mice exhibited impaired extracellular ROS production and increased intracellular bacteria compared to WT controls, after challenged with UPEC in vitro. Similar effects occurred in human and murine neutrophils following chemical inhibition of NOX2 in vitro. Conclusion Neutrophil NOX2 serves a critical antimicrobial role during experimental UTI. Supported by grant from NIH (K01 DK128379-01)

An all-in-one CO gas therapy-based hydrogel dressing with sustained insulin release, anti-oxidative stress, antibacterial, and anti-inflammatory capabilities for infected diabetic wounds

To effectively treat diabetic wounds, the development of versatile medical dressings that can long-term regulate blood glucose and highly effective anti-oxidative stress, antibacterial and anti-inflammatory are critical. Here, an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) was developed via the dynamic Schiff base reaction between the amino groups on quaternized chitosan (QCS) and the aldehyde groups on benzaldehyde-terminated F108 (F108-CHO) micelles. CORM-401 (an oxidant-sensitive CO-releasing molecules) was encapsulated in the hydrophobic core of F108-CHO micelles and insulin was loaded in the three-dimensional network structure of ICOQF. The dynamic Schiff base bonds not only endowed ICOQF with good tissue adhesion, injectability and self-healing, but also gave it sustained and controllable insulin release ability. In addition, ICOQF could quickly generate CO in inflamed wound tissue by consuming reactive oxygen species. The generated CO could effectively anti-oxidative stress by activating the expression of heme oxygenase; antibacterial by inducing the rupture of bacterial cell membranes and mitochondrial dysfunction and inhibiting the synthesis of adenosine triphosphate; and anti-inflammatory by inhibiting the proliferation of activated macrophages and promoting the polarization of the M1 phenotype to the M2 phenotype. Due to these outstanding properties, ICOQF significantly promoted the healing of STZ-induced MRSA-infected diabetic wounds accompanied by good biocompatibility. This study clearly shows that ICOQF is a versatile hydrogel dressing with great application potential for the management of diabetic wounds. Statement of significanceThe development of some versatile hydrogel dressings that can not only provide a prolonged and controlled insulin release property but also utilize a non-antibiotic treatment modality for highly effective antibacterial, anti-inflammatory, and anti-oxidative stress effects is vital for the successful treatment of diabetic wounds. Herein, we developed an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) with sustained and controllable insulin release abilities. Moreover, ICOQF could not only quickly release CO in the inflamed wound tissue by consumption of reactive oxygen species but also utilize the generated CO to highly effectively anti-oxidative stress, antibacterial, and anti-inflammatory. ICOQF therapy substantially promoted the healing of STZ-induced MRSA-infected diabetic wounds. Overall, this work provides a multifunctional hydrogel dressing for the management of diabetic wounds.

Non-antibiotic treatment of acute urinary tract infection in primary care: a qualitative study.

BackgroundThe views of women with acute, uncomplicated urinary tract infection (auUTI) on the acceptability of non-antibiotic treatment options are poorly understood.AimTo establish women’s thoughts on and experience of non-antibiotic treatment for auUTIs.Design and settingQualitative interview study with primary care patients in Oxfordshire, UK, embedded within the Cranberry for Urinary Tract Infection (CUTI) feasibility trial.MethodOne-to-one, semi-structured interviews were conducted between August 2019 and January 2020 with some CUTI trial participants and some patients who were not part of the CUTI trial who had experienced at least one urinary tract infection (UTI) in the preceding 12 months in Oxfordshire, UK. Interviews were analysed using thematic analysis.ResultsIn total, 26 interviews were conducted and analysed. Women expected to receive an immediate antibiotic for their UTI but were aware of the potential harms of this approach. They were keen to find a non-antibiotic, ‘natural’ alternative that could effectively manage their symptoms. In certain situations (early illness, milder illness, and with no important upcoming engagements), women indicated they would be prepared to postpone antibiotic treatment by up to 3 days, especially if offered an interim non-antibiotic option with perceived therapeutic potential.ConclusionMany women with auUTIs are open to trying non-antibiotic treatments first in certain situations. There is scope for more dialogue between primary care clinicians and patients with auUTI around delaying antibiotic treatment and using non-antibiotic options initially, which could reduce antibiotic consumption for this common infection.

Astodrimer sodium and bacterial vaginosis: a mini review

Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age, and is associated with a substantial burden on women’s physical, emotional, sexual and social lives, as well as being linked to a number of gynaecological and obstetrical complications and adverse pregnancy outcomes. Antibiotics, such as metronidazole or clindamycin, are recommended as first-line treatment for BV, but may be associated with antibiotic resistance, high rates of recurrence and poor patient treatment satisfaction. Astodrimer sodium gel is a novel, non-antibiotic treatment for BV that is not systemically absorbed. It prevents pathogenic bacteria from adhering to the vaginal wall, and disrupts and inhibits the formation of pathogenic bacterial biofilms. Clinical cure rates of 50–57% were observed in patients with BV treated with astodrimer sodium compared with 17–21% treated with placebo (p < 0.001) in Phase 3 trials. In a separate Phase 3 trial, recurrence of BV occurred in 44% of patients treated with astodrimer sodium compared with 54% of patients who received placebo (p = 0.015). Astodrimer sodium is well tolerated, with vulvovaginal candidosis being the only treatment-related adverse event reported to occur more often than with placebo. The availability of astodrimer sodium, a well-tolerated, convenient, non-antibiotic treatment for BV, represents significant progress in the treatment of this burdensome condition.

Management of acute uncomplicated diverticulitis without antibiotics: compliance and outcomes -a retrospective cohort study

MethodsRecent randomized control trials (RCTs) have confirmed that antibiotics in acute uncomplicated diverticulitis (AUD) neither accelerate recovery nor prevent complications or recurrences.A retrospective cohort study was conducted, including all consecutive AUD patients hospitalized 2015- 2018 at Helsingborg Hospital (HH) and Skåne University Hospital (SUS), Sweden. HH had implemented a non-antibiotic treatment protocol in 2014 while SUS had not. Main outcomes were proportion of patients treated with antibiotics, complications, recurrences, and adherence to routinely colon evaluation.ResultsA total of 583 AUD patients were enrolled, 388 at SUS and 195 at HH. The diagnosis was CT-verified in 320 (83%) vs. 186 (95%) patients respectively (p < 0.001). Forty-three (11%) and 94 (48%) of patients respectively did not receive antibiotics during hospitalization (p < 0.001). CRP was higher in the antibiotic group compared to the non-antibiotic group, both at admission and peak (90 mg/L vs 65 mg/L; p = 0.016) and (138 mg/L and 97 mg/L; p < 0.001). There were no significant differences in recurrences (22.0% vs. 22.6%; p = 0.87) and complications (2.5% vs. 2.9%; p = 0.77) between the antibiotic/non-antibiotic groups.ConclusionThe structured treatment protocol led to reduced antibiotic use and a higher standard of care in terms of CT-verification. Clinicians’ compliance to the treatment protocol and best clinical practice was poor and warrants further studies.

A Review Paper on Acne

Among the most common skin problems is eczema concerns between teenagers is acne. This disease affects every sebaceous glands unit. Acne is created by impassable pilosebaceous units proionobacterium acnes is also detected. Acne sensitivity is examined in order to determine the optimal treatment option. Acne medication is necessary to avoid damage and adverse affective effects must commence as early as practicable. It should be tailored to each patient's specific needs, keeping in mind the kind of acne, its intensity, the patient's ability to use the treatment, and his or her mental state. Topical therapies are the most widely used handling treatment mild-acne. Strong acne is treated with oral anti-biotics. Following that, anti-biotic opposition can be condensed by utilising non-antibiotic interesting treatments. Iso-tretinoin is a drug that is being used to treat acute acne and can lead to long-term resolution. If medical experts gave more knowledge and attention, acne treatment may be considerably improved.

Engineered Liposomes Protect Immortalized Immune Cells from Cytolysins Secreted by Group A and Group G Streptococci.

The increasing antibiotic resistance of bacterial pathogens fosters the development of alternative, non-antibiotic treatments. Antivirulence therapy, which is neither bacteriostatic nor bactericidal, acts by depriving bacterial pathogens of their virulence factors. To establish a successful infection, many bacterial pathogens secrete exotoxins/cytolysins that perforate the host cell plasma membrane. Recently developed liposomal nanotraps, mimicking the outer layer of the targeted cell membranes, serve as decoys for exotoxins, thus diverting them from attacking host cells. In this study, we develop a liposomal nanotrap formulation that is capable of protecting immortalized immune cells from the whole palette of cytolysins secreted by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis—important human pathogens that can cause life-threatening bacteremia. We show that the mixture of cholesterol-containing liposomes with liposomes composed exclusively of phospholipids is protective against the combined action of all streptococcal exotoxins. Our findings pave the way for further development of liposomal antivirulence therapy in order to provide more efficient treatment of bacterial infections, including those caused by antibiotic resistant pathogens.

Synergistic Effects of Phage-Antibiotic Combinations against Citrobacter amalonaticus.

Non-antibiotic alternative treatments to combat the increasing number of infections caused by multidrug resistant bacteria are urgently needed. In recent years, bacteriophages have reemerged to potentially replace or complement the role of antibiotics, as bacterial viruses have the ability to inactivate pathogens. This study aimed to evaluate the synergy of phage-antibiotic combinations. A Citrobacter amalonaticus isolate was used in this study together with the phage MRM57. Eight different antibiotics with different mechanisms of action were used in combination with the phage to study the impact of the combination treatment on the minimal inhibitory concentrations. We found that antibiotic concentration dependent synergism exists, albeit at different extents, with very low numbers of phages. This demonstrates the use of phages as an adjuvant with a sublethal concentration of antibiotics as an effective therapeutic strategy.

Use of a Smartphone Medication Reminder Application to Support Emerging Adult Adherence to Non-Antibiotic Treatment for Viral Upper Respiratory Tract Infection.

Objective:This research study is a test of the efficacy of a smartphone-installed medication reminder application to support provider-recommended treatment plans for young adult patients who were seen for upper respiratory tract infections (URTIs) and were not prescribed an antibiotic.Methods:Two hundred seventy-five patients seen at a university student health center for URTI symptoms were randomly assigned to the medication reminder app intervention or a control group and then surveyed both 1 and 14 days after their medical visits with questions about the treatment plan, their satisfaction with medical care, and the electronic support tools.Results:Compared to the control condition, patients using the reminder app reported more adherence to provider-recommended treatment plans. Patients with lower social support availability benefited more from being provided with these tools.Conclusion:These findings suggest that medication reminder apps have utility for increasing patient adherence to non-antibiotic URTI treatment plans, particularly among patients who lack high-quality informational and tangible social support.Innovation:This study demonstrates innovation in use of the medication reminder app to promote antibiotic stewardship with young adult patients in primary care.

Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT.

Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur. The objective is to assess whether or not intravaginal lactic acid gel is clinically effective and cost-effective for treating recurrent bacterial vaginosis compared with oral metronidazole (Flagyl, Sanofi). This was an open-label, multicentre, parallel-arm, randomised (1 : 1) controlled trial. This took place in one general practice and 19 sexual health centres in the UK. Women aged ≥ 16 years with bacterial vaginosis symptoms and one or more episode(s) within the past 2 years took part. The interventions were 5 ml of intravaginal lactic acid gel taken once daily for 7 days (intervention) or 400-mg oral metronidazole tablets taken twice daily for 7 days (control). The primary outcome was the resolution of bacterial vaginosis symptoms 14 days after randomisation. The secondary outcomes were time to first recurrence of symptoms; number of recurrences and treatment courses over 6 months; microbiological resolution on microscopy of vaginal smears at week 2; time to resolution of symptoms; tolerability, adherence and acceptability of the treatment; prevalence of concurrent sexually transmitted infections; quality of life; and cost-effectiveness. Recruitment stopped prior to reaching the target of 1900 participants on recommendation from the Data Monitoring Committee and Trial Steering Committee after a planned review of the results indicated that the research question had been answered. Overall, 518 participants were randomised and primary outcome data were available for 409 participants (79%; 204 in the metronidazole arm, 205 in the lactic acid gel arm). Participant-reported symptom resolution at week 2 was higher with metronidazole (143/204; 70%) than with lactic acid gel (97/205; 47%) (adjusted risk difference -23.2%, 95% confidence interval -32.3% to -14.0%). Recurrence in 6 months in a subset of participants who had initial resolution and were available for follow-up was similar across arms (metronidazole arm: 51/72, 71%; lactic acid gel arm: 32/46, 70%). A higher incidence of some side effects was reported with metronidazole than with lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). At week 2, the average cost per participant with resolved symptoms was £86.94 (metronidazole), compared with £147.00 (lactic acid gel). Some participants preferred using lactic acid gel even if they perceived it to be less effective than metronidazole. Loss to follow-up for collection of the primary outcome data was 21% and was similar in both arms. There is a risk of bias owing to missing outcome data at 3 and 6 months post treatment. A higher initial response was seen with metronidazole than with lactic acid gel, but subsequent treatment failure was common with both. Lactic acid gel was less cost-effective than metronidazole. In general, women disliked taking repeated courses of metronidazole and preferred lactic acid gel, even when they were aware that it was less likely to provide symptom resolution. In the absence of effective curative therapy, further evaluation of non-antibiotic treatments to control the symptoms of recurrent bacterial vaginosis is required to improve quality of life for these patients. Further microbiological analysis of vaginal samples would be useful to identify additional factors affecting response to treatment. Current Controlled Trials ISRCTN14161293. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 2. See the NIHR Journals Library website for further project information.

New therapies for nontuberculous mycobacterial lung infection.

Although nontuberculous mycobacterial pulmonary disease is increasing in incidence, outcomes remain less than optimal highlighting the unmet need for developing novel therapies. Several new antibiotic formulations, novel antibiotics, and novel nonantibiotic treatments have recently demonstrated positive results in treating nontuberculous mycobacterial pulmonary disease. Promising novel therapies are currently under investigation fueling much needed interest and enthusiasm in the nontuberculous mycobacterial pulmonary disease space and will hopefully lead to improved understanding and outcomes in this complex disease.

Rational development and evaluation of novel formulations for urinary health

ObjectiveUrinary tract infections (UTI) among women form a substantial part of medical practice and both patients and medical professionals have an interest in non-antibiotic treatments and preventative measures. This research provides preliminary data on a multi-functional composition, DAPAD, which explored several biologic activities of relevance to UTI. Study DesignThis formulation included D-mannose, citric acid, three prebiotic compounds, and extracts of dandelion and astragalus. Studies performed employed 4 bacterial strains that have relevance to UTI including E. coli, Proteus mirabilis, Streptococcus agalactiae and Enterococcus faecalis. ResultsKey findings from in vitro studies included: DAPAD at full- and half-strength inhibited growth of all UTI bacteria. Evidence for D-mannose agglutination of E. coli was demonstrated. D-mannose also showed unexpected effects on bacterial membrane integrity with vital staining and modest growth restriction. We did not demonstrate growth inhibition by dandelion or astragalus extracts but the latter showed diminished cytokine elaboration by bladder epithelial cells. ConclusionDAPAD is a multifunctional composition that may warrant further development as a UTI treatment or preventive if supported by clinical evaluation.

Non-antibiotic treatment of interdigital hyperplasia secondary infected with digital dermatitis treponemes in dairy cows

Since the spread of classical digital dermatitis (DD) lesions within the cattle population, frequency of infections of interdigital hyperplasia (IH) lesions with DD-associated Treponema spp. (IH+DD) increased. The aim of the present case series is to describe an alternative treatment technique to surgical lesion removal or local treatment of HI+DD lesions with antibiotics. In this report, the effect of repeated local administration of salicylic acid paste, protected by a water repellent bandage was described and assessed for the treatment of four dairy cows with IH+DD lesions. Milker's fat Eutra was applied to the unaffected skin adjacent to the lesion to protect healthy skin from the keratolytic properties of salicylic acid paste. Treatment was repeated at weekly intervals in all four cases until the IH+DD lesions had completely clinically healed. Two cows additionally showed classical DD lesions between the heels. Clinical healing was defined as remission of IH and complete healing of the DD lesions located on IH lesions and between the heels. Complete healing was evident at three weeks of treatment in all four cases. Weekly repeated topical application of salicylic acid paste under bandage may be recommended as an alternative to surgical or antibiotic treatment of IH+DD lesions.

What Does Patient-Centered Communication Look Like?: Linguistic Markers of Provider Compassionate Care and Shared Decision-Making and Their Impacts on Patient Outcomes

ABSTRACT Patient-centered communication promotes positive patient outcomes. This study examines the linguistic markers of two key dimensions of patient-centered communication (i.e., provider compassionate care and shared decision-making) and their mediating effects on patient perceived quality of and affective responses to the provider’s treatment recommendations. Transcripts (N = 343) of provider talk from provider-patient interactions in medical visits for upper respiratory infection symptoms where patients were not prescribed with antibiotics were analyzed with the Linguistic Inquiry and Word Count (LIWC) dictionary. Results showed that providers’ use of affiliation words positively predicted patients’ perceptions of their providers’ compassionate care. Providers’ use of insight words negatively predicted patients’ perceptions of provider shared decision-making. Meanwhile, providers’ use of first-person singular pronouns, causation and differentiation words, and clout words were positively related to perceived provider shared decision-making. Patient perceived compassionate care and shared decision-making further increased patients’ positive affect toward and perceived quality of non-antibiotic treatment recommendations. These perceptions also reduced their negative affect toward the recommendations. Implications of the findings are discussed with regard to patient-centered communication in relation to the promotion of antibiotic stewardship.

M-score and wound healing assessment of 2 nonantibiotic topical gel treatments of active digital dermatitis lesions in dairy cattle

This open-label, randomized clinical trial with positive control compared the treatment of active digital dermatitis (DD) lesions (stages M1, M2, and M4.1) on dairy cattle hind feet with an enzyme alginogel or a copper and zinc chelate gel (coppergel). Upon recruitment (d 0), active DD lesions were cleaned, photographed, treated, and bandaged. This procedure was repeated on d 3 and d 7, with treatment and bandaging discontinued for those lesions that had transitioned to the M0, M3, or M4 stage on d 7. Day 10 was considered the end of the treatment trial, and all recruited feet were cleaned and photographed. Treatment effect of the 2 products was assessed not only using the M-score but also using general wound healing progress criteria. Improvement of M-score was defined as transition to M0, M3, or M4 stages, or to lesions with a smaller ulcerative area (e.g., M2 stage to M1 stage). Lesions with improved wound healing had at least one of the following criteria when compared with the previous observation: decreased defect size, healthier granulation tissue color (pink-red instead of purple-grayish), more regular aspect of granulation tissue surface, wound contraction, or epithelization starting from the surrounding skin. Both primary outcomes were assessed using a multivariable logistic regression analysis. Lesions treated with the enzyme alginogel had a decreased adjusted odds ratio for M-score improvement (aOR: 0.04; 95% confidence interval: 0.01-0.11). Lesions treated with the coppergel mostly transitioned to chronic lesions, whereas lesions treated with the enzyme alginogel mostly remained active lesions. The wound healing progress of almost 70% of the lesions treated with coppergel could not be scored, for the greater part due to the presence of crust materials. With these unscorable lesions classified as "improved," there was no treatment effect on wound healing progress (aOR: 0.99; 95% confidence interval: 0.34-3.05), whereas with unscorable lesions classified as "not improved," the enzyme alginogel outperformed the coppergel with regard to wound healing progress (aOR: 2.48; 95% confidence interval: 1.07-5.79). None of the products used in our study achieved high cure rates (transition to the M0 stage) for active DD lesions. Low cure rates of topical treatment of DD, together with the important role of chronic lesions in the epidemiology of DD, indicate that future research should investigate how to achieve successful wound management of DD lesions, thereby mitigating pain associated with the lesions and reducing both transmission and prevalence of DD within herds.

Prescribing of long-term antibiotics to adolescents in primary care: a retrospective cohort study.

BackgroundAntibiotic overuse is linked to increased risk of antimicrobial resistance. Long-term antibiotics are commonly used for treating acne and prophylaxis of urinary tract infection. Their contribution to the overall burden of antibiotic use is relatively unknown.AimTo describe the volume of commonly prescribed long-term (≥28 days) antibiotic prescriptions in adolescents and young adults, trends over time, and comparisons with acute prescriptions.Design and settingA retrospective cohort study using UK electronic primary care records.MethodPatients born between 1979 and 1996 and with data in the Care and Health Information Analytics database were included. The main outcome measures were antibiotic prescription rates per 1000 person-years and antibiotic prescription days per person-year between the ages of 11 and 21.ResultsIn total, 320 722 participants received 710 803 antibiotic prescriptions between the ages of 11 and 21 years from 1998 to 2017. Of these 710 803 prescriptions, 191 443 (26.93%) were for long-term antibiotics (≥28 days and ≤6 months in duration). Long-term antibiotics accounted for more than two-thirds (72.48%) of total antibiotic exposure (days per person-year). Total long-term antibiotic prescribing peaked in 2013 at just under 6 days per person-year and declined to around 4 days in 2017.ConclusionAmong adolescents and young adults, exposure to long-term antibiotics (primarily lymecycline used for acne) was much greater than for acute antibiotics and is likely to make an important contribution to antimicrobial resistance. Urgent action is needed to reduce unnecessary exposure to long-term antibiotics in this group. Increasing the use of, and adherence to, effective non-antibiotic treatments for acne is key to achieving this.