Association of the Japanese herbal kampo medicine kakkonto with antibiotic use and surgical drainage for noninfectious mastitis: A nationwide database study.

AIM: Kakkonto, a Japanese herbal kampo medicine, is empirically prescribed to improve milk stasis and ameliorate breast inflammation in patients with noninfectious mastitis. We investigated whether early use of kakkonto is associated with a reduction in antibiotic use and surgical drainage in patients with noninfectious mastitis. METHODS: We identified 34 074 patients with an initial diagnosis of noninfectious mastitis within 1 year of childbirth between April 2012 and December 2022 using the nationwide administrative JMDC Claims Database. Patients were divided into the kakkonto (n = 9593) and control (n = 9648) groups if they received and did not receive kakkonto on the day of the initial diagnosis of noninfectious mastitis, respectively. Antibiotic administration and surgical drainage within 30 days after the initial diagnosis of noninfectious mastitis in the two groups were compared using propensity score-stabilized inverse probability of treatment weighting analysis. RESULTS: The frequency of antibiotic administration within 30 days after the initial diagnosis of noninfectious mastitis was significantly lower in the kakkonto group than in the control group (10% vs. 12%; odds ratio, 0.88 [95% confidence interval, 0.80-0.96]). The frequency of antibiotic administration during 1-3 and 4-7 days after the initial diagnosis were also significantly lower in the kakkonto group than in the control group. The frequency of surgical drainage did not differ significantly between the two groups. CONCLUSIONS: Kakkonto was associated with reduced administration of antibiotics for noninfectious mastitis, making it a potential treatment option for relieving breast inflammation and promoting antimicrobial stewardship.

Anticancer, antioxidant, and antibacterial effects of nanoemulsion of Origanum majorana essential oil.

Background and Objectives: This study aimed to develop a natural nanoemulsion with antibacterial and anticancer properties. Materials and Methods: The chemical composition of the Origanum majorana essential oil was investigated using GC-MS analysis. Besides, the successful loading of the essential oil in the nanoemulsion was confirmed using ATR-FTIR analysis. Moreover, nanoemulsion's anticancer, antioxidant, and antibacterial activities were investigated. Results: Terpinen-4-o1 (46.90%) was identified as the major compound in the essential oil. The nanoemulsion with a 149 ± 5 nm droplet size and zeta potential of -11 ± 1 mV was prepared. The cytotoxic effect of the nanoemulsion against A-375 human melanoma cells (IC50 = 139 µg/mL) showed significantly more potency than A-549 human lung cancer cells (IC50 = 318 µg/mL). Interestingly, growth of Staphylococcus aureus (Gram-positive) and E. coli (Gram-negative) bacteria after treatment with 4800 µg/mL of nanoemulsion were obtained at 12 ± 2 and 6 ± 1%, respectively. However, the IC50 value of nanoemulsion against E. coli (580 µg/mL) was not significantly different (P > 0.05) from S. aureus (611 µg/mL). Conclusion: A straightforward preparation method, high stability, and multi-biological effects are the main advantages of the prepared nanoemulsion. Therefore it could be considered for further investigation in vivo studies or complementary medicine.

Phytomedicinal properties of Hygrophila schulli (Neeramulliya).

Hygrophila schulli which is known as "Neermulli'' in the vernacular is an herbaceous plant native to Sri Lanka. Ancient medicinal literature suggests the use of H. schulli whole plant or its parts for the treatment of different communicable and non-communicable diseases including diabetes mellitus and tuberculosis. Active constituents and secondary metabolites including alkaloids, tannins, steroids, proteins, flavonoids, and glycosides are identified to possess antimicrobial, antitumor, antioxidant, hepatoprotective, anthelmintic, nephroprotective, antidiabetic, anticataract, anti-inflammatory, anti-nociceptive, hematopoietic, diuretic, antiurolithiatic, antipyretic, neuroprotection, and anti-endotoxin activities. In this review, we reviewed clinical studies, patents, and analytical studies from the earliest found examples from 1886 to the end of 2021. We critically analyzed and attempt to summarize the information based on bioactivities and chemical composition of H. schulli plant extracts which will be of future use for researchers in this field.

Antibacterial effects of aqueous and alcoholic extracts of Zataria multiflora in comparison with chlorhexidine mouthwash on some pathogenic oral streptococci: An in vitro study.

Background: Increasing antibiotic resistance to pathogenic microorganisms (Streptococci) has led scientists around the world to turn to medicinal plants. In this study, the effects of aqueous and alcoholic extracts of Zataria multiflora on the in vitro growth of Streptococcus mutans and Streptococcus sanguis have been considered and compared with 0.2% chlorhexidine mouthwash. Materials and Methods: In this in vitro study, the inhibitory growth zone was accessed by the disc diffusion method after 48 h of incubation at 37 C. To find out the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of treatments, colony counts of cultured bacteria on nutrient agar have been considered at serial dilution at 1/2-1/1024 dilution rates. An independent t-test was used to compare the antibacterial effects of extracts while the level of significance of was considered to be 5% (P < 0.05). Results: The inhibitory growth zones of aqueous and alcoholic extracts on S. mutans were 26.8 mm and 35.8 mm, respectively, whereas growth zones for S. sanguis were considered as 25.8 mm and 33.2 mm, sequentially. Comparisons showed better effects of alcohol compared to aqueous extract (P > 0.05). The MIC and MBC assessments showed the same results (P > 0.05). In all comparisons, the effects of 0.2% chlorhexidine mouthwash were significantly better than both Z. multiflora aqueous and alcoholic extracts (P > 0.05). Conclusion: The different solvents may have contributed to the better effects of an alcoholic to aqueous extract of Z. multiflora on the growth of both bacteria. These two extracts could be used for early inhibition of the growth of the planktonic phase, as well as for better oral taste after chlorhexidine applications.

Small Molecular Fluorescent Probes: Application Progress of Specific Bacteria Detection and Antibacterial Phototherapy.

Bacterial infection is one of the leading causes of death worldwide and is easy to cause large-scale diseases. It is an urgent need to develop effective methods for the specific detection and treatment of bacterial infections. Recently, small molecular fluorescent probes, bridging the capability of imaging detection and sterilization, have attracted increasing attention. Fluorescence imaging assays have the benefit of being simple, specific, and fast, which is very advantageous in both in vitro and in vivo bacterial detection. Molecularly fluorophores for theranostics provide advantages of non-invasion, high specificity, and fewer side effects. In this review, we summarize the recent advances and design strategies of small molecular fluorescent probes for both targeted detection and treatment of bacteria. We hope that this review will provide guidance for the development of more effective fluorescent dyes in the future as well as encourage preclinical and clinical studies of phototherapy-mediated antimicrobial therapy.

Association between emergency department sepsis order set design and delay to second dose piperacillin-tazobactam administration.

BACKGROUND: Delay to first antibiotic dose in patients with sepsis has been associated with increased mortality. Second dose antibiotic delay has also been linked to worsened patient outcomes. Optimal methods to decrease second dose delay are currently unclear. The primary objective of this study was to evaluate the association between updating an emergency department (ED) sepsis order set design from one-time doses to scheduled antibiotic frequencies and delay to administration of second piperacillin-tazobactam dose. METHODS: This retrospective cohort study was conducted at eleven hospitals in a large, integrated health system and included adult patients treated in the ED with at least one dose of piperacillin-tazobactam ordered through an ED sepsis order set over a two year period. Patients were excluded if they received less than two doses of piperacillin-tazobactam. Midway through the study period, the enterprise-wide ED sepsis order set was updated to include scheduled antibiotic frequencies. Two patient cohorts receiving piperacillin-tazobactam were compared: those in the year before the order set update and those in the year post-update. The primary outcome was major delay, defined as an administration delay >25% of the recommended dosing interval, which was evaluated with multivariable logistic regression and interrupted time series analysis. RESULTS: 3219 patients were included: 1222 in the pre-update group and 1997 in the post-update group. The proportion of patients who experienced major second dose delay was significantly lower in the post-update group (32.7% vs 25.6%, p < 0.01; adjusted OR 0.64, 95% CI 0.52 to 0.78). No between-group difference was detected in the slope of monthly major delay frequency, but there was a significant level change (post-update change -10%, 95% CI -17.9% to -1.9%). CONCLUSIONS: Including scheduled antibiotic frequencies in ED sepsis order sets is a pragmatic mechanism to decrease delays in second antibiotic doses.

Ação antimicrobiana de extratos de gengibre (Zingiber officinale) e quilaia (Quillaja saponaria) isolados e associados sobre Pseudomonas aeruginosa resistente a antibióticos / Antimicrobial action of isolated and associated extracts of ginger (Zingiber officinale) and quilaia (Quillaja saponaria) on antibiotic-resistant Pseudomonas aeruginosa

Extratos de plantas têm demonstrado diversos efeitos positivos para a saúde, incluindo ação antimicrobiana, no entanto, o uso clínico da fitoterapia ainda é discreto, de modo que mais estudos sobre os efeitos benéficos do sinergismo farmacológico de extratos poderiam contribuir para sua aplicação terapêutica. O objetivo deste estudo foi avaliar os efeitos dos extratos glicólicos de gengibre (EG) e quilaia (EQ) isolados e em associação sobre 7 cepas clínicas de Pseudomonas aeruginosa e uma cepa padrão em forma planctônica e biofilmes monotípicos. Para a análise antimicrobiana sobre cultura planctônica foram feitos testes para determinação de Concentração Inibitória Mínima (CIM) e Concentração Microbicida Mínima (CMM) (CLSI, M07-A9) dos extratos isolados, além do Índice de Concentração Inibitória Fracionada (ICIF) e do Índice de Concentração Microbicida Fracionada (ICMF) para os extratos combinados. A análise estatística foi feita com método ANOVA e teste de Tukey para dados com distribuição normal e Kruskall-Wallis com Teste de Comparação Múltipla de Dunn para dados sem distribuição normal (significância de 5%). Para cepa padrão foram determinadas CIM igual a 3,12 mg/mL e CMM igual a 6,25 mg/mL para ambos os extratos. Para cepas clínicas as CIM do EG foram 3,12 ou 6,25 mg/mL e de EQ 1,56 ou 3,12 mg/mL, enquanto os valores de CMM foram de 6,25 mg/mL para EG e de 1,56, 3,12 ou 6,25 mg/mL para EQ. Os resultados de ICIF indicaram 15 associações sinérgicas e 4 associações aditivas dos extratos contra a cepa padrão e, dentre cepas clínicas, foram obtidos 15 resultados aditivos. A partir dos resultados de ICMF foram identificadas 6 associações sinérgicas e 1 associação aditiva contra a cepa padrão, além de 8 associações com efeito aditivo contra cepas clínicas. A partir dos resultados de testes em culturas planctônicas foi avaliada a ação antibiofilme sobre as cepas em que foram observadas reduções de viabilidade de 36,7 e 34% para o EG (50 e 25 mg/mL) e 51,3 e 51,4% para EQ (25 e 12,5 mg/mL) contra cepa padrão. As reduções em cepas clínicas variaram de 43 a 73% com EG e de 36 a 79% para EQ. As associações dos extratos promoveram reduções de viabilidade de 8 a 35% contra 5 das 7 cepas clínicas. Conclui-se que os extratos glicólicos de gengibre e quilaia apresentam ação antimicrobiana de forma isolada e combinados com efeito aditivo sobre a forma planctônica de cepas clínicas resistentes de P. aeruginosa. De forma isolada, os extratos apresentaram importante ação preventiva na formação dos biofilmes dessas cepas, podendo ser considerados potenciais fitoterápicos com aplicações terapêuticas para o combate das infecções por P. aeruginosa. (AU)

Plant extracts have demonstrated several positive health effects, including antimicrobial action, however, the clinical use of phytotherapy is still discreet, so that more studies on the beneficial effects of pharmacological synergism of extracts could contribute to its therapeutic application. The aim of this study was to evaluate the effects of glycolic extracts of ginger (EG) and quilaia (EQ) alone and in combination on 7 clinical strains of Pseudomonas aeruginosa and a standard strain in planktonic form and monotypic biofilms. For the antimicrobial analysis on planktonic culture, tests were performed to determine the Minimum Inhibitory Concentration (MIC) and Minimum Microbicidal Concentration (MMC) (CLSI, M07-A9) of the isolated extracts, in addition to the Fractional Inhibitory Concentration Index (FICI) and the Fractionated Microbicidal Concentration Index (FICM) for the combined extracts. Statistical analysis was performed using the ANOVA method and Tukey's test for data with normal distribution and Kruskall-Wallis with Dunn's Multiple Comparison Test for data without normal distribution (5% significance). For the standard strain, MIC were determined equal to 3.12 mg/mL and MMC equal to 6.25 mg/mL for both extracts. For clinical strains the MIC of EG were 3.12 or 6.25 mg/mL and 1.56 or 3.12 mg/mL of EQ, while the MMC values were 6.25 mg/mL for EG and 1.56, 3.12 or 6.25 mg/ml for EQ. The FICI results indicated 15 synergistic and 4 additive associations of the extracts against the standard strain and, among clinical strains, 15 additive results were obtained. From the FICM results, 6 synergistic and 1 additive association against the standard strain were identified, in addition to 8 associations with additive effect against clinical strains. Based on the results of tests on planktonic cultures, the antibiofilm action were evaluated on the strains in which viability reductions of 36 and 34% were observed for EG (50 and 25 mg/mL) and 51% were observed for EQ (25 and 12, 5 mg/mL) against the standard strain. Reductions in clinical strains ranged from 43 to 73% with EG and from 36 to 79% for EQ. Associations of extracts promoted viability reductions of 8 to 35% against 5 out of 7 clinical strains. It is concluded that the glycolic extracts of ginger and quilaia have antimicrobial action in isolation and combined with additive effect on the planktonic form of resistant clinical strains of P. aeruginosa. Isolated, the extracts showed an important preventive action in the formation of biofilms of these strains and may be considered potential herbal medicines with therapeutic applications to combat P. aeruginosa infections. (AU)

Effects of breast milk intake ratio during hospitalization on antibiotic therapy duration in preterm infants less than 34 gestational weeks: a multicenter retrospective cohort study / 中华围产医学杂志

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d<DOT≤15.0 d), Q 3 (15.0 d<DOT≤27.0 d) and Q 4 (DOT>27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%<breast milk intake ratio≤50%), medium-ratio breastfeeding group (50%<breast milk intake ratio≤75%) and high-ratio breastfeeding group (breast milk intake ratio>75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Look-Back and Look-Forward Durations and the Apparent Appropriateness of Ambulatory Antibiotic Prescribing.

Ambulatory antibiotic stewards, researchers, and performance measurement programs choose different durations to associate diagnoses with antibiotic prescriptions. We assessed how the apparent appropriateness of antibiotic prescribing changes when using different look-back and look-forward periods. Examining durations of 0 days (same-day), -3 days, -7 days, -30 days, ±3 days, ±7 days, and ±30 days, we classified all ambulatory antibiotic prescriptions in the electronic health record of an integrated health care system from 2016 to 2019 (714,057 prescriptions to 348,739 patients by 2391 clinicians) as chronic, appropriate, potentially appropriate, inappropriate, or not associated with any diagnosis. Overall, 16% percent of all prescriptions were classified as chronic infection related. Using only same-day diagnoses, appropriate, potentially appropriate, inappropriate, and not-associated antibiotics, accounted for 14%, 36%, 22%, and 11% of prescriptions, respectively. As the duration of association increased, the proportion of appropriate antibiotics stayed the same (range, 14% to 18%), potentially appropriate antibiotics increased (e.g., 43% for -30 days), inappropriate stayed the same (range, 22% to 24%), and not-associated antibiotics decreased (e.g., 2% for -30 days). Using the longest look-back-and-forward duration (±30 days), appropriate, potentially appropriate, inappropriate, and not-associated antibiotics, accounted for 18%, 44%, 20%, and 2% of prescriptions, respectively. Ambulatory programs and studies focused on appropriate or inappropriate antibiotic prescribing can reasonably use a short duration of association between an antibiotic prescription and diagnosis codes. Programs and studies focused on potentially appropriate antibiotic prescribing might consider examining longer durations.

Antimicrobial resistance of microorganisms present in periodontal diseases: A systematic review and meta-analysis.

Objective: The aim of this study was to estimate the antimicrobial resistance in microorganisms present in periodontal diseases. Methods: A systematic review was conducted according to the PRISMA statement. The MEDLINE (PubMed/Ovid), EMBASE, BVS, CINAHL, and Web of Science databases were searched from January 2011 to December 2021 for observational studies which evaluated the antimicrobial resistance in periodontal diseases in permanent dentition. Studies that allowed the antimicrobial consumption until the time of sample collection, studies that used laboratory acquired strains, studies that only characterized the microbial strain present, assessment of cellular morphological changes, sequencing system validation, and time series were excluded. Six reviewers, working in pairs and independently, selected titles, abstracts, and full texts extracting data from all studies that met the eligibility criteria: characteristics of patients, diagnosis of infection, microbial species assessed, antimicrobial assessed, identification of resistance genes, and virulence factors. "The Joanna Briggs Institute" critical appraisal for case series was adapted to assess the risk of bias in the included studies. Results: Twenty-four studies (N = 2.039 patients) were included. Prevotella and Porphyromonas species were the most cited microorganisms in the included studies, and the virulence factors were related to Staphylococcus aureus. The antimicrobial reported with the highest frequency of resistance in the included studies was ampicillin (39.5%) and ciprofloxacin showed the lowest frequency of resistance (3.4%). The most cited genes were related to macrolides. The quality of the included studies was considered critically low. Conclusion: No evidence was found regarding the profile of antimicrobial resistance in periodontal diseases, requiring further research that should focus on regional population studies to address this issue in the era of increasing antimicrobial resistance. Clinical relevance: The knowledge about the present microorganism in periodontal diseases and their respective antimicrobial resistance profiles should guide dentists in prescribing complementary therapy for these infections. Systematic review registration: [http://dx.doi.org/10.1097/MD.0000000000013158], identifier [CRD42018077810].

Anti-Inflammatory and Anti-Bacterial Potential of Mulberry Leaf Extract on Oral Microorganisms.

Mulberry leaves extract (Morus alba extracts; MAE) is known to have therapeutic potentials for numerous human diseases, including diabetes, neurological disorders, cardiovascular diseases, and cancers. However, there has not been sufficient research proving therapeutic effects on oral disease and its related oral risk factors. Thus, we investigated whether MAE has any anti-inflammatory and anti-bacterial effects on risk factors causing oral infectious diseases. To examine the anti-inflammatory response and bacterial inhibition of MAE, we measured intracellular reactive oxygen species (ROS) generation, production of pro-inflammatory cytokines, and the bacterial growth rate. Our study showed that MAE has anti-inflammatory activities, which inhibit the ROS generation and suppressed the production of pro-inflammatory cytokines (TNF-α and IL-6) in human monocyte THP-1 cells by stimulating lipopolysaccharide (LPS) and/or F. nucleatum, which are the virulent factors in periodontal diseases. Furthermore, MAE inhibited the bacterial growth on oral microorganisms (F. nucleatum and S. mutans) infected THP-1 cells. These findings suggested that MAE could be a potential natural source for therapeutic drugs in oral infectious disease.

Antibiotic therapy of chronic bacterial prostatitis is more effective considering antibiotic susceptibility of all pathogens isolated.

PURPOSE: Because of the insufficient efficacy of the current treatment of chronic bacterial prostatitis (CBP), it is justified to search for a more effective antibiotic therapy (ABT). MATERIALS AND METHODS: This single-centre prospective observational comparative study was conducted in 2012 to 2019 (patients: 60 men with CBP; age: 20-45 y). The clinical examination was performed on admission and at 1, 3, 6, or 12 months. All patients underwent the Meares-Stamey test to obtain expressed prostatic secretion (EPS) and/or post-massage urine (PMU) samples for extended bacteriological examination. The patients were randomly divided into 2 treatment groups (30/30 patients): group I, fluoroquinolones (FQs); group II, a combination of FQs with cephalosporins/macrolides with a treatment duration of 1 month. RESULTS: Patients of both groups had severe symptomatic CBP with an average duration of 4 years. Twenty-three microorganisms (15 aerobes, 9 anaerobes) were identified in PMU. At 3 months follow-up, a positive clinical effect was noted in both groups, which was significant (p<0.05) only in group II concerning NIH-CPSI questionnaire, leukocyturia, prostate volume, maximum urine flow, and decreased pathospermia. At 6 months follow-up, in group II the frequency of Escherichia coli and Enterococcus spp. decreased significantly. In group I aerobes changed only insignificantly from the initial level, but anaerobes increased significantly. In group II the titers of both, aerobes and anaerobes, were significantly lower (p<0.05) at 6 months follow-up as compared to initial values. CONCLUSIONS: ABT targeting all taxa in EPS/PMU is a more effective alternative to standard therapeutic regimens for CBP.

Changing Patterns of Causative Pathogens over Time and Efficacy of Empirical Antibiotic Therapies in Acute Cholangitis with Bacteremia.

Background/Aims: To select appropriate empirical antibiotics, updates on the changes in pathogens are essential. We aimed to investigate the changes in pathogens and their antibiotic susceptibility in acute cholangitis (AC) with bacteremia over a period of 15 years. Furthermore, the efficacy of empirical antibiotic therapies and the risk factors predicting antibiotic-resistant pathogens (ARPs) were analyzed. Methods: A total of 568 patients with AC and bacteremia who were admitted to Daegu Catholic University Medical Center from January 2006 to December 2020 were included. Their medical records were retrospectively reviewed. In addition, the data were grouped and analyzed at 3-year intervals under the criteria of Tokyo Guideline 2018. Results: During the study period, 596 pathogens were isolated from blood cultures of 568 patients. The three most common pathogens were Escherichia coli (50.5%), Klebsiella species (24.5%), and Enterococcus species (8.1%). The proportion of vancomycin-resistant Enterococci (VRE) has increased since the mid-2010 (0.0% to 4.3%, p=0.007). There was emergence of carbapenem-resistant Enterobacteriaceae (CRE) in 2018 to 2020, albeit not statistically significant (1.3%, p=0.096). Risk factors predicting ARP were healthcare-associated infection, history of previous biliary intervention, and the severity of AC. For patients with these aforementioned risk factors, imipenem was the most effective antibiotic and piperacillin-tazobactam was also effective but to a lesser degree (susceptibility rates of 92.1% and 75.0%, respectively). Conclusions: The proportion of VRE has increased and CRE has emerged in AC. In addition, healthcare-associated infection, history of previous biliary intervention, and the severity of AC were independent risk factors predicting ARP. For patients with these risk factors, the administration of imipenem or piperacillin-tazobactam should be considered.

Bixa orellana L. (Achiote, Annatto) as an antimicrobial agent: A scoping review of its efficiency and technological prospecting.

ETHNOPHARMACOLOGICAL RELEVANCE: Bixa orellana L. is reported to have numerous applications in traditional medicine and pharmacological properties such as wound healing, analgesic, hemostatic, and antioxidant activities. Recently, the literature has shown scientific interest of its antimicrobial properties aiming the development of cost-effective phytotherapeutic agents. However, no literature are available in witch the antimicrobial and technological prospecting are summarized. AIM OF STUDY: This study aimed to systematically review articles and patents related to the antimicrobial activity of B. orellana. METHODS: The review followed the guidelines proposed by The Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers performed a literature search up to November 2021 in eight databases: Medline (PubMed), Scopus, Scifinder, Web of Science, Cochrane, Embase, Scielo, and Biblioteca Virtual em Saúde. The following databases for the patent search were analyzed: United States Patent and Trademark Office (USPTO), Google Patents, National Institute of Industrial Property (INPI), World Intellectual Property Organization (WIPO), and Espacenet (European Patent Office, EPO). The grey literature was searched using the ProQuest Dissertations and Periódicos Capes Theses database. The methodological quality and risk of bias in the included studies were carried out using Review Manager (RevMan) 5.3.5. RESULTS: After analyzing the 47 studies and five patents fulfilled all the criteria and were included in the present investigation. The evidence suggests that this herbal medicine is effective against several fungi, Gram-positive and Gram-negative bacteria, being more effective to Gram-negative bacteria. Regarding the risk of bias and methodological quality analysis, most studies a high risk of bias related to random sequence generation and allocation concealment. CONCLUSION: Up to now, the evidence in the literature suggests that the use of B. orellana preparations for antimicrobial preparations has some effectiveness. However, further research is needed using standard B. orellana preparations to determine their effectiveness as antimicrobial agents and expanding their application at an industrial level, in addition in vivo studies are needed for this confirmation.

Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis.

BACKGROUND: The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, preclinical evidence for its utility in other disease indications has yet to be provided. Here we studied the therapeutic potential of EBL-1003 in the treatment of complicated urinary tract infection and acute pyelonephritis (cUTI/AP). METHODS: A combination of data-base mining, antimicrobial susceptibility testing, time-kill experiments, and four murine infection models was used in a comprehensive assessment of the microbiological coverage and efficacy of EBL-1003 against Gram-negative uropathogens. The pharmacokinetics and renal toxicology of EBL-1003 in rats was studied to assess the therapeutic window of EBL-1003 in the treatment of cUTI/AP. FINDINGS: EBL-1003 demonstrated broad-spectrum activity and rapid multi-log CFU reduction against a phenotypic variety of bacterial uropathogens including aminoglycoside-resistant clinical isolates. The basicity of amines in the apramycin molecule suggested a higher increase in positive charge at urinary pH when compared to gentamicin or amikacin, resulting in sustained drug uptake and bactericidal activity, and consequently in potent efficacy in mouse infection models. Renal pharmacokinetics, biomarkers for toxicity, and kidney histopathology in adult rats all indicated a significantly lower nephrotoxicity of EBL-1003 than of gentamicin. INTERPRETATION: This study provides preclinical proof-of-concept for the efficacy of EBL-1003 in cUTI/AP. Similar efficacy but lower nephrotoxicity of EBL-1003 in comparison to gentamicin may thus translate into a higher safety margin and a wider therapeutic window in the treatment of cUTI/API. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Efecto antibacteriano del aceite esencial de Minthostachys mollis (Griseb) L. frente a Streptococcus mutans y Lactobacillus acidophilus / Antibacterial effect of Minthostachys mollis(Griseb) L.essential oil against Streptococcus mutansand Lactobacillus acidophilus

Introducción: El uso de los aceites esenciales de plantas medicinales ha demostrado poseer propiedades antibacterianas frente a diversas especies bacterianas. Objetivo: Identificar la composición química del aceite esencial de Minthostachys mollis (Griseb) L. y determinar su actividad antibacteriana frente a Streptococcus mutans y Lactobacillus acidophilus. Métodos: Se realizó un estudio experimental in vitro. Se empleó el software EpiInfoTM para el cálculo de las repeticiones. Se obtuvo aceite esencial de M. mollis proveniente de la región altoandina del Perú. La composición química fue analizada por cromatografía de gases acoplada a espectrometría de masas. La actividad antibacteriana se evaluó por medio del método de difusión en disco, además, se identificó la concentración mínima inhibitoria y la concentración mínima bactericida. Resultados: Los principales constituyentes del aceite esencial fueron mentona (32,9 por ciento) y eucaliptol (28,06 por ciento). El aceite esencial fue efectivo para inhibir el crecimiento de S. mutans y L. acidophilus, con halos de inhibición de 19,040 ± 0,883 mm y 18,008 ± 0,861 mm. La clorhexidina al 0,12 por ciento fue más efectiva que el aceite esencial para inhibir el crecimiento de L. acidophilus (p < 0,05). Una concentración de 1,6 por ciento (v/v) del aceite esencial fue inhibitoria y bactericida frente a S. mutans; para L. acidophilus una concentración de 3,2 por ciento (v/v) fue inhibitoria. Conclusiones: Los principales constituyentes del aceite esencial de M. mollis fueron mentona y eucaliptol y demostró ser efectivo para inhibir el crecimiento de S. mutans y L. acidophilus(AU)

Introduction: The use of essential oils from medicinal plants has been shown to possess antibacterial properties against various bacterial species. Objective: To identify the chemical composition of the essential oil of Minthostachys mollis (Griseb) L. and determine its antibacterial activity against Streptococcus mutans and Lactobacillus acidophilus. Methods: An experimental study was performed in vitro. EpiInfoTM software was used to calculate the repetitions. Essential oil of M. mollis was obtained from the high Andean region of Peru. The chemical composition was analyzed by gas chromatography coupled to mass spectrometry; antibacterial activity was evaluated by means of the disk diffusion method, in addition the minimum inhibitory concentration and the minimum bactericidal concentration were identified. Results: The main constituents of the essential oil were menthone (32.9 percent) and eucalyptol (28.06 percent). The essential oil was effective in inhibiting the growth of S. mutans and L. acidophilus, with inhibition halos of 19.040 ± 0.883 mm and 18.008 ± 0.861 mm. Chlorhexidine 0.12 percent was more effective than essential oil in inhibiting the growth of L. acidophilus (p < 0.05). A concentration of 1.6 percent (v/v) of the essential oil was inhibitory and bactericidal against S. mutans; for L. acidophilus a concentration of 3.2 percent (v/v) was inhibitory. Conclusions: The main constituents of the essential oil of M. mollis were menthone and eucalyptol and it was shown to be effective in inhibiting the growth of S. mutans and L. acidophilus(AU)

A Randomized Clinical Trial of Standard versus Expanded Cultures to Diagnose Urinary Tract Infections in Women.

PURPOSE: We compared urinary tract infection (UTI) symptom resolution rates at 7-10 days in symptomatic women randomized to treatment based on standard urine culture (SUC) versus expanded quantitative urine culture (EQUC) results. MATERIALS AND METHODS: Women ≥18 years old who responded "yes" to "do you feel you have a UTI?" agreed to urethral catheterization and followup. Symptoms were assessed using the validated UTI Symptom Assessment (UTISA) questionnaire. Culture method was randomized 2:1 (SUC:EQUC); antibiotics were prescribed to women with positive cultures. The primary outcome, UTI symptom resolution, was determined 7-10 days following enrollment on all participants regardless of treatment. RESULTS: Demographic data were similar between groups. Of the SUC and EQUC groups 63% and 74% had positive cultures (p=0.10), respectively. Of participants with positive cultures 97% received antibiotics. Primary outcome data were provided by 215 of 225 participants (SUC 143 [95%], EQUC 72 [97%]). At the primary outcome assessment, 64% and 69% in the SUC and EQUC groups, respectively, reported UTI symptom resolution (p=0.46); UTISA scores improved from baseline in the EQUC arm compared to the SUC arm (p=0.04). In the subset of women predominated by non-Escherichia coli (76), there was a trend toward more symptom resolution in the EQUC arm (21%, p=0.08). CONCLUSIONS: Symptom resolution was similar for the overall population (E. coli and non-E. coli) of women treated for UTI symptoms based on SUC or EQUC. Although the sample size limits conclusions regarding the utility of EQUC in women with non-E. coli uropathogens, the detected trend indicates that this understudied clinical subset warrants further study.

Knowledge and behavior of consumers towards the non-prescription purchase of antibiotics: An insight from a qualitative study from New Delhi, India.

BACKGROUND: In Low-and Middle-Income Countries, including India, consumers often purchase antibiotics over-the-counter (OTC) from retail pharmacies. This practice leads to the inappropriate use of antibiotics in the community which is an important driver for the development of antimicrobial resistance. A better understanding of consumers' views towards this grave public health concern is critical to developing evidence-based intervention programs for awareness among the general population. OBJECTIVE: To explore knowledge, practice and, behavior of consumers towards antibiotics, antibiotic use, antimicrobial resistance, purchasing behavior of consumers for antibiotics, and to gain insight which will help in developing evidence-based policy interventions. METHODS: 72 in-depth consumer interviews were conducted in all 11 districts of the National Capital Territory of Delhi. The qualitative data were analyzed using thematic analysis. RESULTS: Our study found that retail pharmacies were the first point of consultation for common ailments for patients/consumers once home remedies failed; they were largely unaware of the threat of antimicrobial resistance. Consumers' knowledge of antibiotic use and about antimicrobial resistance was low, they used old prescriptions, and bought antibiotics OTC to save time and money. Despite the presence of regulations constituted to regulate the sale of antibiotics by the Government and the implementation of national campaigns, the practice of self-medication and behaviors such as OTC purchase, non-adherence to prescribed antibiotics was prevalent. Consumers perceive that antibiotics provide quick relief and accelerate the curing process and retail pharmacy shops try to protect their retail business interests by honoring old prescriptions and self-medication for antibiotics. CONCLUSIONS: The lack of awareness and insufficient knowledge about what antibiotics are and issues such as antimicrobial resistance or antibiotic resistance resulted in misuse of antibiotics by consumers. Limited access to public healthcare and affordability of private healthcare are factors that contribute towards the self-medication/OTC purchase of antibiotics. The regular misuse of antibiotics through irrational use reinforces the need for strong enactment of strategies like continuous community awareness campaigns. Mitigation efforts should focus upon educating consumers continuously and sustainably for the understanding of antibiotic misuse, antimicrobial resistance, and promote better compliance with regulations.

Are propolis extracts potential pharmacological agents in human oral health? - A scoping review and technology prospecting.

ETHNOPHARMACOLOGICAL RELEVANCE: The antimicrobial potential of propolis - a honey bee product - was correlated with its traditional use as a natural medicine, mainly known for antimicrobial and antioxidant properties. Moreover, research on natural products in dentistry has increased in recent years in the search for products with greater therapeutic activity, lower toxicity, better biocompatibility, and more affordable cost to the population. OBJECTIVE: Considering that the beneficial effect of propolis is acknowledged for several oral conditions, this study aimed to synthesize the research and technological forecasts of existing evidence on the use of propolis extract as a potential antimicrobial agent in dentistry. METHODS: Studies were identified through an investigation in the PubMed, Web of Science, Scopus, and Scielo electronic databases. Additionally, the following patent databases were screened: Google Patents, WIPO, INPI, Espacenet, and Questel Orbit. The data were tabulated and analyzed using Microsoft Office Excel 2013 and Questel Orbit. RESULTS: A total of 174 scientific articles and 276 patents fulfilled all the criteria and were included in the investigation. The highest number of patents (n = 144) was produced by China. Additionally, the most prevalent studies were performed on an experimental basis (72%), followed by clinical studies (n = 27) and review articles (n = 21). The effect of using propolis has been extensively observed in oral care products, periodontics, pathology, and cariology, among other dental specialties. CONCLUSION: It was possible to identify the current scientific and technological scenario of the application of propolis in dentistry, with the number of patents increasing in recent years. However, all studies related to the use of propolis in dentistry have shown a potentially safe antimicrobial agent in an extensive field of application.

Plant Natural Products as Antimicrobials for Control of Streptomyces scabies: A Causative Agent of the Common Scab Disease.

The common scab disease caused by Streptomyces scabies, a soil-dwelling Gram-positive bacterium, is an economically important disease of potatoes and other tuber crops. The lack of effective treatments against this disease accounts for large economic losses globally. Plant extracts were screened to find several that effectively inhibited Streptomyces scabies growth in culture. Seven tinctures showed the greatest inhibition of S. scabies growth by reducing pathogen growth in culture by 75% or more. These extracts were myrrh, garlic, cayenne, barberry, frankincense, wild indigo root, and lavender. Myrrh extract from Commiphora myrrha, a resin made from tree sap, showed strong antibacterial activity by reducing the growth of S. scabies to 13% of the control. Additionally, a flavonoid library was screened to identify several compounds that were effective to control the pathogen growth. The flavonoids that showed the greatest inhibition of Streptomyces scabies growth were sophoraflavanone G, jaceosidin, baicalein, and quercetin. Minimum inhibitory concentrations for the effective flavonoids were calculated to be 6.8 ± 0.4 µM, 100.0 ± 2.1 µM, 202.9 ± 5.3 µM, and 285.2 ± 6.8 µM, respectively. The mean lethal doses for these flavonoids against Streptomyces scabies were 2.0 ± 0.1 µM, 22.6 ± 0.5 µM, 52.9 ± 1.3 µM, and 37.8 ± 1.0 µM, respectively. A live/dead assay showed complete cell death in the presence of sophoraflavanone G indicative of a bactericidal mechanism for flavonoid action on Streptomyces scabies. Scanning electron and transmission electron microscopy imaging showed damaged cell membrane morphologies when Streptomyces scabies was exposed to these flavonoids. Mycelia appeared as flat and deflated structures with contents seen as spewing from branching hyphae with numerous holes and tears in the membrane structure indicative of cell death. Sophoraflavanone G showed the greatest potency and potential as a natural antibiotic from the library of tested flavonoids. These results suggest that these plant compounds act on the pathogen through a bactericidal mechanism involving cell membrane destabilization and disruption leading to cell death.