Ionic Liquid-Based Silane for SiO2 Nanoparticles: A Versatile Coupling Agent for Dental Resins.

The current longevity of dental resins intraorally is limited by susceptibility to acidic attacks from bacterial metabolic byproducts and vulnerability to enzymatic or hydrolytic degradation. Here, we demonstrate synthesizing an ionic liquid-based antibiofilm silane effective against Streptococcus mutans, a major caries pathogen. Furthermore, we incorporate this silane into dental resins, creating antibiofilm- and degradation-resistant materials applicable across resin types. FTIR, UV-vis, and NMR spectroscopy confirmed the synthesis of the expected ionic liquid-based silane. The characterization of SiO2 after the silanization indicated the presence of the silane and how it interacted with the oxide. All groups achieved a degree of conversion similar to that found for commercial resin composites immediately and after two months of storage in water. The minimum of 2.5 wt % of silane led to lower softening in solvent than the control group (GCTRL) (p < 0.05). While the flexural strength indicated a lower value from 1 wt % of silane compared to GCTRL (p < 0.05), the ultimate tensile strength did not indicate differences among groups (p > 0.05). There was no difference within groups between the immediate and long-term tests of flexural strength (p > 0.05) or ultimate tensile strength (p > 0.05). The addition of at least 5 wt % of silane reduced the viability of S. mutans compared to GCTRL (p < 0.05). The fluorescence microscopy analysis suggested that the higher the silane concentration, the higher the amount of bacteria with membrane defects. There was no difference among groups in the cytotoxicity test (p > 0.05). Therefore, the developed dental resins displayed biocompatibility, proper degree of conversion, improved resistance against softening in solvent, and stability after 6 months of storage in water. This material could be further developed to produce polymeric antimicrobial layers for different surfaces, supporting various potential avenues in developing novel biomaterials with enhanced therapeutic characteristics using ionic liquid-based materials.

Cefiderocol for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model.

Background: To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. Methods: The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol. Results: Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years. Conclusion: This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS. Limitations: Given existing evidence, the estimates of the value of cefiderocol are highly uncertain. Future work: Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value. Study registration: No registration of this study was undertaken. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.

This project tested new methods for estimating the value to the NHS of an antimicrobial, cefiderocol, so its manufacturer could be paid fairly even if very little drug is used in order to reduce the risk of bacteria becoming resistant to the product. Clinicians said that the greatest benefit of cefiderocol is when used for complicated urinary tract infections and pneumonia acquired within hospitals caused by two types of bacteria (called Enterobacterales and Pseudomonas aeruginosa), with a resistance mechanism called metallo-beta-lactamase. Because there were no relevant clinical trial data, we estimated how effective cefiderocol and alternative treatments were by doing a systematic literature review of studies that grew bacteria from infections in the laboratory and tested the drugs on them. We linked this to data estimating the long-term health and survival of patients. Some evidence was obtained by asking clinicians detailed questions about what they thought the effects would be based on their experience and the available evidence. We included the side effects of the alternative treatments, some of which can cause kidney damage. We estimated how many infections there would be in the UK, whether they would increase over time and how resistance to treatments may change over time. Clinicians told us that they would also use cefiderocol to treat intra-abdominal and bloodstream infections, and some infections caused by another bacteria called Stenotrophomonas. We estimated how many of these infections there would be, and assumed the same health benefits as for other types of infections. The total value to the NHS was calculated using these estimates. We also considered whether we had missed any additional elements of value. We estimated that the value to the NHS was £18­71 million over 20 years. This reflects the maximum the NHS could pay for use of cefiderocol if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using this antimicrobial. However, these estimates are uncertain due to limitations with the evidence used to produce them and assumptions that had to be made.

The inhibitory effects of carvacrol, nystatin, and their combination on oral candidiasis isolates.

BACKGROUND: Candida, a common oral microbiota, can cause opportunistic fungal infections. With rising Candida infections and limited effective antifungals, new treatments are needed. This study investigates carvacrol essential oil's effect on oral candidiasis, alone and with nystatin, compared to nystatin alone. MATERIALS AND METHODS: In this study, oral samples were collected from dental clinic patients, especially denture users. The presence of Candida was confirmed and cultured from these samples. Candidiasis was detected by observing Candida colonies. Drug sensitivity was tested on 100 positive samples. The minimum concentration of inhibition and lethality of each isolate was evaluated using nystatin and carvacrol. The results were compared using two-way analysis of variance. Finally, the minimum inhibitory concentration (MIC) of nystatin and carvacrol was calculated individually and in combination. RESULTS: The present study found that Candida albicans and non-albicans species were equally prevalent. Carvacrol showed significant biological activity against all Candida species, with an average MTT of 50.01%. The average MIC value of carvacrol was 24.96 µg/ml, indicating its potential to inhibit Candida growth. The mean Minimum Fungicidal Concentration (MFC) value of carvacrol was 23.48 µg/ml, suggesting its effectiveness in killing the fungi. CONCLUSION: The study's findings reveal that the MIC of carvacrol was significantly lower than that of nystatin and the combination of nystatin and carvacrol. This suggests that carvacrol holds potential as an effective herbal remedy for candidiasis.

Perfil da microbiota e padrões de resistência aos antimicrobianos em uroculturas de pacientes transplantados renais / Profile of the microbiot and anti-microbain resistance patterns in urocultures of reneal transplant patients

Objetivo: analisar o perfil de micro-organismos presentes e resistência destes aos antimicrobianos em uroculturas de pacientes transplantados renais no período de 2021-2022. Métodos: trata-se de um estudo transversal com análise quantitativa dos dados de uroculturas positivas de pacientes transplantados renais, acompanhados no Hospital Geral de Fortaleza entre janeiro de 2021 a dezembro de 2022. Foi empregado um instrumento de pesquisa elaborado, contendo variáveis classificatórias, e os dados foram obtidos por meio de registros das uroculturas existentes no sistema de prontuário eletrônico utilizado pelo hospital. Resultados: das 534 uroculturas solicitadas, 36,7% apresentaram resultado positivo, sendo 60,4% de mulheres com idades entre 20 e 59 anos. A maioria dos casos foram desenvolvidos por pacientes que receberam acompanhamento ambulatorial (56,2%). Os micro-organismos isolados foram, predominantemente, enterobactérias (81,34%), com prevalência de E.coli (69,30%). Os perfis de sensibilidade antimicrobiana variaram, com a resistência da E.coli a antibióticos como ampicilina, ácido nalidíxico, norfloxacino e ciprofloxacino. Conclusões: essas descobertas fornecem informações importantes sobre métodos clínicos específicos, métodos preventivos e melhorias na qualidade de vida dos transplantados renais.

Objective: to analyze the profile of microorganisms present and their resistance to antimicrobials in urocultures of renal transplant patients in 2021-2022. Methods: it is a cross-sectional study with quantitative data analysis from positive urocultures of renal transplant patients accompanied at the General Hospital of Fortaleza between January 2021 and December 2022. An elaborate research instrument containing classification variables was employed, and the data were obtained through records of the urocultures existing in the electronic checkbook system used by the hospital. Results: of the 534 urocultures requested, 36.7% showed a positive result, of which 60.4% were women aged between 20 and 59. Most cases were developed by patients who received outpatient follow-up (56.2%). The isolated microorganisms were predominantly enterobacteria (81.34%), with the prevalence of E.coli (69.30%). Antimicrobial sensitivity profiles varied, with E.coli resistance to antibiotics such as ampicillin, nalidixic acid, norfloxacin, and ciprofloxacin. Conclusion: these findings provide important information about specific clinical methods, preventive methods, and improvements in the quality of life of renal transplant patients.

Anti-Candida activity and in vitro toxicity screening of antifungals complexed with ß-cyclodextrin.

The emergence of resistant fungal species and the toxicity of currently available antifungal drugs are relevant issues that require special consideration. Cyclodextrins inclusion complexes could optimize the antimicrobial activity of such drugs and create a controlled release system with few side effects. This study aimed to assess the in vitro toxicity and antifungal effectiveness of nystatin (Nys) and chlorhexidine (Chx) complexed or not with ß-cyclodextrin (ßCD). First, a drug toxicity screening was performed through the Artemia salina bioassay. Then, the minimum inhibitory concentrations (MICs) against Candida albicans were determined with the broth microdilution test. After MICs determination, the cytotoxicity of the drugs was evaluated through the methyl-thiazolyl-tetrazolium (MTT) and neutral red (NR) assays and through cell morphology analysis. The PROBIT analysis was used to determine the median lethal concentration (LC50), and the cell viability values were submitted to one-way analysis of variance(ANOVA)/Tukey (α = 0.05). Overall, the ßCD-complexed antifungals were less toxic against A. salina than their raw forms, suggesting that inclusion complexes can reduce the toxicity of drugs. The MICs obtained were as follows: Nys 0.5 mg/L; Nys:ßCD 4 mg/L; Chx 4 mg/L; and Chx:ßCD 8 mg/L. Chx showed significant cytotoxicity (MTT: 12.9 ± 9.6%; NR: 10.6 ± 12.5%) and promoted important morphological changes. Cells exposed to the other drugs showed viability above 70% with no cellular damage. These results suggest that antifungals complexed with ßCD might be a biocompatible option for the treatment of Candida-related infections.

The effect of TiO2 nanoparticles on bacterial growth: the effect of particle size and their structure - a systematic review.

One of the widely used microbiological methods to determine the toxicity of chemicals, catalysts, and other types of materials is the minimum inhibitory concentration (MIC) test. The present study aims to investigate the influence of composition of composite materials based on TiO2 and their particle size as well as bacterial type and shape based on the MIC values reported in the literature. The results show that among the 36 articles selected, most of the studies used Escherichia coli (E. coli) (26) and Staphylococcus aureus (S. aureus) (19) bacteria to determine MIC values. This study revealed that the MIC in values below 70 µg ml-1 for S. aureus was lower than that for E. coli bacteria (below 200 µg ml-1). Importantly, MIC value decreased from 60.6 to 7.66 µg ml-1 with decrease in the size of nanoparticles. It follows from the increased surface area for smaller-sized particles, thus increased interaction with bacteria during MIC test.

Candidemia in Adult Patients in the ICU: A Reappraisal of Susceptibility Testing and Antifungal Therapy.

OBJECTIVE: To provide updates on the epidemiology and recommendations for management of candidemia in patients with critical illness. DATA SOURCES: A literature search using the PubMed database (inception to March 2023) was conducted using the search terms "invasive candidiasis," "candidemia," "critically ill," "azoles," "echinocandin," "antifungal agents," "rapid diagnostics," "antifungal susceptibility testing," "therapeutic drug monitoring," "antifungal dosing," "persistent candidemia," and "Candida biofilm." STUDY SELECTION/DATA EXTRACTION: Clinical data were limited to those published in the English language. Ongoing trials were identified through ClinicalTrials.gov. DATA SYNTHESIS: A total of 109 articles were reviewed including 25 pharmacokinetic/pharmacodynamic studies and 30 studies including patient data, 13 of which were randomized controlled clinical trials. The remaining 54 articles included fungal surveillance data, in vitro studies, review articles, and survey data. The current 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Management of Candidiasis provides recommendations for selecting empiric and definitive antifungal therapies for candidemia, but data are limited regarding optimized dosing strategies in critically ill patients with dynamic pharmacokinetic changes or persistent candidemia complicated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Outcomes due to candidemia remain poor despite improved diagnostic platforms, antifungal susceptibility testing, and antifungal therapy selection for candidemia in critically ill patients. Earlier detection and identification of the species causing candidemia combined with recognition of patient-specific factors leading to dosing discrepancies are crucial to improving outcomes in critically ill patients with candidemia. CONCLUSIONS: Treatment of candidemia in critically ill patients must account for the incidence of non-albicans Candida species and trends in antifungal resistance as well as overcome the complex pathophysiologic changes to avoid suboptimal antifungal exposure.

Antimicrobial resistance patterns and empiric antibiotic selections for patients admitted from post-acute care facilities.

PURPOSE: To characterize the susceptibilities of positive bacterial cultures and the appropriateness of empiric antimicrobial regimens for patients admitted from post-acute care facilities (PACFs). METHODS: This was a retrospective quality improvement study. The study included patients admitted from a PACF to one of 2 tertiary care teaching hospitals within the University of Pennsylvania Health System, located in Philadelphia, PA, from August 2020 to December 2021. Patients were included if they had at least one positive culture within 72 hours of admission. RESULTS: A total of 167 patients and 230 isolates from the study period were evaluated. The majority of positive cultures were from a urinary source (114 of 230, 49.6%). Nineteen patients (11.4%) had a history of multidrug-resistant organisms. The most common empiric antibiotics used were vancomycin (61.7%) and cefepime (59.3%). Sixty-one patients (36.5%) received inappropriate empiric therapy based on the culture results. When comparing our hospitals' general antibiogram to that of only PACF patients, Escherichia coli and Klebsiella pneumoniae had at least a 20% difference in susceptibility to levofloxacin, ceftriaxone, and cefepime. Extended-spectrum ß-lactamase resistance was also higher in the PACF cohort (odds ratio, 2.09; 95% confidence interval, 1.4-3.1). CONCLUSION: Clinically significant differences in antimicrobial susceptibility were found among patients admitted from PACFs compared to our health system's general antibiogram. The increased resistance rates identified in this study support the need for hospitals to evaluate this at-risk patient population, which may drive changes to empiric antibiotic prescribing practices.

Prevalence and antimicrobial resistance profile of pathogens isolated from patients with urine tract infections admitted to a university hospital in a medium-sized Brazilian city

ABSTRACT This study aimed to determine the antibiotic profile of microorganisms isolated from urine samples of patients with community urine tract infections (UTI) admitted to the University Hospital of the Federal University of Sao Carlos to support an appropriate local empirical treatment. A retrospective cross-sectional study was conducted from October 2018 to October 2020. Data from 1,528 positive urine cultures for bacterial pathogens and antibiograms were tabulated. Bacterial species prevalence and their resistance profile were analyzed and compared by sex and age. For Gram-negative fermenting bacteria, resistance rates were compared between patients with previous hospitalization and the total of infections caused by this group. For comparisons, the Chi-square test was performed, using Fisher's exact test when necessary (BioEstat program, adopting p ≤ 0.05). A multivariate analysis was applied to assess the effect of the studied variables in predicting multidrug resistance. Infections were more prevalent in women and older adults. Gram-negative bacteria represented 90.44% of total cultures. In both sexes, E. coli prevalence was significantly higher in adults compared with older adults (p < 0.0001). For several antibiotics, resistance rates were higher in the older adults compared with other ages and in patients with Gram-negative fermenting infections and previous hospitalization compared with the total of infections by this group of bacteria. The closer to the hospitalization, the higher the number of antibiotics with superior resistance rates. Resistance rates for aminoglycosides, carbapenems, ceftazidime, nitrofurantoin, piperacillin+tazobactam, and fosfomycin were less than 20%, considered adequate for empirical treatment. Only hospitalization in the previous 90 days was statistically significant in predicting infections by multidrug-resistant bacteria.

[Comparison of Epsilometer test and agar dilution method in detecting the sensitivity of Helicobacter pylori to metronidazole].

OBJECTIVE: Agar dilution method (ADM) was used as the golden standard to evaluate the consistency of Epsilometer test (E-test) in detecting the sensitivity of Helicobacter pylori (H. pylori) to metronidazole. METHODS: From August 2018 to July 2020, patients with H. pylori infection treated for the first time in Peking University Third Hospital for gastroscopy due to dyspepsia were included in this study. Gastric mucosas were taken from the patients with H. pylori infection. H. pylori culture was performed. Both the ADM and E-test were applied to the antibiotic susceptibility of H. pylori to metro-nidazole, and the consistency and correlation between the two methods were validated. RESULTS: In the study, 105 clinical isolates of H. pylori were successfully cultured, and the minimum inhibitory concentration ≥ 8 mg/L was defined as drug resistance. Both ADM and the E-test showed high resistance rates to metronidazole, 64.8% and 62.9%, respectively. Among them, 66 drug-resistant strains were detected by ADM and E-test, and 37 were sensitive strains, so the consistency rate was 98.1%. Two strains were evaluated as drug resistance by ADM, but sensitive by the E-test, with a very major error rate of 1.9%. There was zero strain sensitive according to ADM but assessed as resistant by the E-test, so the major error rate was 0%. Taking ADM as the gold standard, the sensitivity of E-test in the detection of metronidazole susceptibility was 97.1% (95%CI: 0.888-0.995), and the specificity was 100% (95%CI: 0.883-1.000). Cohen's kappa analysis showed substantial agreement, and kappa coefficient was 0.959 (95%CI: 0.902-1.016, P < 0.001). Spearmans correlation analysis confirmed this correlation was significant (r=0.807, P < 0.001). The consistency evaluation of Bland-Altman method indicated that it was good, and there was no measured value outside the consistency interval. In this study, cost analysis, including materials and labor, showed a 32.2% higher cost per analyte for ADM as compared with the E-test (356.6 yuan vs. 269.8 yuan). CONCLUSION: The susceptibility test of H. pylori to metronidazole by E-test presents better agreement with ADM. Because it is less expensive, less labor intensive, and more rapid, it is an easy and reliable method for H. pylori susceptibility testing.

Applications of Lab on a Chip in Antimicrobial Susceptibility of Staphylococcus aureus: A Systematic Review.

Background and Objectives: Staphylococcus aureus is a prevalent bacterium capable of inducing various infections, including skin and soft tissue infections, bloodstream infections, pneumonia, and surgical site infections. The emergence of antimicrobial resistance in S. aureus, particularly methicillin-resistant S. aureus, has raised substantial concerns within global healthcare settings. Prior to antibiotic prescription, the ideal approach is antimicrobial susceptibility testing (AST); however, this is frequently perceived as excessively complex and time-intensive. Lab-on-a-chip (LOC) technology holds promise in addressing these challenges and advancing fundamental microbiological research while also aiding in the development of therapeutic strategies. This systematic review aims to evaluate the potential utility of LOC for AST of S. aureus. Materials and Methods: This study adhered to the PRISMA guidelines. Various databases, including SCOPUS, PubMed/MEDLINE, SCIELO, and LILACS, in addition to gray literature sources, were employed in the review process. Results: Sixteen studies were included in this systematic review. All these studies detailed the effectiveness, rapidity, and predictability of LOC systems for assessing S. aureus susceptibility to various antibiotics. When comparing the LOC approach to traditional manual methods, it was evident that LOC requires a minimal quantity of reagents. Furthermore, most studies reported that the entire LOC procedure took 10 min to 7 h, with results being equally accurate as those obtained through traditional AST protocols. Conclusions: The potential application of LOC for AST of S. aureus is emphasized by its ability to provide rapid access to minimum inhibitory concentration data, which can substantially aid in selecting the most suitable antibiotics and dosages for treating challenging infections caused by this microorganism. Moreover, the rapid AST facilitated by LOC holds promise for enhancing the appropriateness and efficacy of therapy in clinical settings.

In vitro sensitivity of Malassezia furfur isolates from HIV-positive and negative patients to antifungal agents / Sensibilidad in vitro a antifúngicos de aislamientos de Malassezia furfur de pacientes positivos y negativos para HIV

INTRODUCTION: Malassezia is a lipophilic and lipid-dependent yeast genus belonging to the skin microbiota of humans and other animals. However, due to dysbiosis processes or other factors in the host, this yeast can cause different pathologies, ranging from skin diseases, such as seborrheic dermatitis, to fungemia. Isolation of Malassezia furfur has been reported in HIV-positive patients with or without skin lesions. Due to its opportunistic nature and its variable resistance to antifungal compounds, it is relevant to know the Malassezia sensitivity profiles. OBJECTIVE: To determine the sensitivity to different antifungal agents, of clinical isolates of M. furfur obtained from HIV-positive or negative patients, with or without seborrheic dermatitis. MATERIALS AND METHODS: Assessment of isolates sensitivity to itraconazole, voriconazole, fluconazole, and amphotericin B was performed by two techniques: (1) Broth microdilution using Clinical and Laboratory Standards Institute (CLSI) protocol M27-A3 with modifications; and (2) agar tests using Etest®. RESULTS: Isolates obtained from HIV patients showed an increase in the minimum inhibitory concentration of fluconazole, voriconazole, and amphotericin B, compared with those of non-HIV patients. Itraconazole was the antifungal with the lowest minimum inhibitory concentration (MIC) in most isolates. CONCLUSION: We observed differences in the sensitivity profiles of M. furfur isolates according to the context of the patient. High MIC of antifungals like fluconazole, commonly used for treating pathologies caused by Malassezia, were identified.

Introducción: Malassezia es un género de levaduras lipofílicas que dependen de los lípidos y hacen parte de la microbiota de la piel de humanos y otros animales. No obstante, debido a procesos de disbiosis u otros factores en el huésped, esta levadura puede llegar a causar diferentes enfermedades: desde cutáneas (como dermatitis seborreica) hasta fungemias. Se han reportado aislamientos de Malassezia furfur en pacientes positivos para HIV, con lesiones cutáneas o sin ellas. Por su carácter oportunista y sensibilidad variable a los compuestos antifúngicos, es relevante conocer los perfiles de sensibilidad. Objetivo: Determinar la sensibilidad a diferentes antifúngicos de aislamientos clínicos de M. furfur obtenidos de pacientes positivos o negativos para HIV, con dermatitis seborreica o sin ella. Materiales y métodos: La sensibilidad de los aislamientos a itraconazol, voriconazol, fluconazol y anfotericina B, se determinó mediante dos técnicas: microdilución en caldo según el protocolo M27-A3 del Clinical & Laboratory Standards Institute (CLSI), con modificaciones, y pruebas en agar mediante Etest®. Resultados: Los aislamientos obtenidos de pacientes con HIV mostraron aumento de la concentración inhibitoria mínima a fluconazol, voriconazol y anfotericina B, en comparación con los de pacientes sin HIV. Por otro lado, al evaluar la mayoría de los aislamientos, el itraconazol fue el antifúngico con la menor concentración inhibitoria mínima. Conclusión: Se evidencian diferencias en los perfiles de sensibilidad de los aislamientos de M. furfur, según el contexto del paciente, y elevadas concentraciones inhibitorias mínimas de antifúngicos como el fluconazol, usados comúnmente para el tratamiento de las enfermedades causadas por Malassezia spp.

In vitro sensitivity of Malassezia furfur isolates from HIV-positive and negative patients to antifungal agents / Sensibilidad in vitro a antifúngicos de aislamientos de Malassezia furfur de pacientes positivos y negativos para HIV

Introduction. Malassezia is a lipophilic and lipid-dependent yeast genus belonging to the skin microbiota of humans and other animals. However, due to dysbiosis processes or other factors in the host, this yeast can cause different pathologies, ranging from skin diseases, such as seborrheic dermatitis, to fungemia. Isolation of Malassezia furfur has been reported in HIV-positive patients with or without skin lesions. Due to its opportunistic nature and its variable resistance to antifungal compounds, it is relevant to know the Malassezia sensitivity profiles. Objective. To determine the sensitivity to different antifungal agents, of clinical isolates of M. furfur obtained from HIV-positive or negative patients, with or without seborrheic dermatitis. Materials and methods. Assessment of isolates sensitivity to itraconazole, voriconazole, fluconazole, and amphotericin B was performed by two techniques: (1) Broth microdilution using Clinical and Laboratory Standards Institute (CLSI) protocol M27-A3 with modifications; and (2) agar tests using Etest®. Results. Isolates obtained from HIV patients showed an increase in the minimum inhibitory concentration of fluconazole, voriconazole, and amphotericin B, compared with those of non-HIV patients. Itraconazole was the antifungal with the lowest minimum inhibitory concentration (MIC) in most isolates. Conclusion. We observed differences in the sensitivity profiles of M. furfur isolates according to the context of the patient. High MIC of antifungals like fluconazole, commonly used for treating pathologies caused by Malassezia, were identified.

Introducción. Malassezia es un género de levaduras lipofílicas que dependen de los lípidos y hacen parte de la microbiota de la piel de humanos y otros animales. No obstante, debido a procesos de disbiosis u otros factores en el huésped, esta levadura puede llegar a causar diferentes enfermedades: desde cutáneas (como dermatitis seborreica) hasta fungemias. Se han reportado aislamientos de Malassezia furfur en pacientes positivos para HIV, con lesiones cutáneas o sin ellas. Por su carácter oportunista y sensibilidad variable a los compuestos antifúngicos, es relevante conocer los perfiles de sensibilidad. Objetivo. Determinar la sensibilidad a diferentes antifúngicos de aislamientos clínicos de M. furfur obtenidos de pacientes positivos o negativos para HIV, con dermatitis seborreica o sin ella. Materiales y métodos. La sensibilidad de los aislamientos a itraconazol, voriconazol, fluconazol y anfotericina B, se determinó mediante dos técnicas: microdilución en caldo según el protocolo M27-A3 del Clinical & Laboratory Standards Institute (CLSI), con modificaciones, y pruebas en agar mediante Etest®. Resultados. Los aislamientos obtenidos de pacientes con HIV mostraron aumento de la concentración inhibitoria mínima a fluconazol, voriconazol y anfotericina B, en comparación con los de pacientes sin HIV. Por otro lado, al evaluar la mayoría de los aislamientos, el itraconazol fue el antifúngico con la menor concentración inhibitoria mínima. Conclusión. Se evidencian diferencias en los perfiles de sensibilidad de los aislamientos de M. furfur, según el contexto del paciente, y elevadas concentraciones inhibitorias mínimas de antifúngicos como el fluconazol, usados comúnmente para el tratamiento de las enfermedades causadas por Malassezia spp.

Septic arthritis of the temporomandibular joint managed with arthroscopy: a case report.

Septic arthritis of the temporomandibular joint (SATMJ) is an uncommon bacterial or fungal infection of the joint space. A 68-year-old man with underlying diabetes mellitus and a history of liver transplant, who was on immunosuppressants, presented to the oral and maxillofacial surgery department of the authors´ institution in Portugal. His main symptoms were arthralgia in the right temporomandibular joint, malocclusion, pre-auricular swelling and erythema. After clinical, laboratory, and imaging evaluations, diagnoses of chronic suppurative otitis media and SATMJ were made. The patient was managed with arthroscopy of the right temporomandibular joint, which allowed joint fluid collection for microbiological examination, lavage, and biopsy. The biopsy sample was positive for Pseudomonas aeruginosa. After surgery, targeted intravenous antibiotic treatment (amikacin) was given for 30 days. No recurrence of any complaints was reported after 12 months of follow-up.

Susceptibility-guided sequential strategy versus empirical therapy for Helicobacter pylori infection: study protocol for a randomised controlled trial.

BACKGROUND: New treatment strategies are required against infections caused by Helicobacter pylori, which grows increasingly resistant to antibiotics. Polymerase chain reaction-based methods for antibiotic susceptibility testing are available for detecting H. pylori-specific mutations that confer resistance to clarithromycin and levofloxacin. Several meta-analyses have compared eradication rates for susceptibility-guided versus empirical therapy for H. pylori treatment; however, all have significant limitations and high heterogeneity, and the results are contradictory. The main objective of this trial is to assess whether a sequential strategy based on molecular susceptibility testing-guided therapy for H. pylori has a better eradication rate than empirical therapy. METHODS: This trial is designed as a prospective, randomised, open-label, active-controlled and single-centre study. Men and women who are H. pylori-positive, naïve to treatment, and aged 18-65 years will be recruited. A total of 500 participants will be randomised to receive either empirical therapy or a susceptibility-guided sequential strategy. Bismuth quadruple therapy will be the empirical first-line therapy, and in case of failure, high-dose dual (proton-pump inhibitor + amoxicillin) treatment will be the rescue therapy. For the susceptibility-guided sequential strategy, regimen selection will be based on H. pylori susceptibility to clarithromycin (first-line) and levofloxacin (rescue). A first-line treatment of clarithromycin triple therapy will be selected for clarithromycin-sensitive strains. For clarithromycin resistance, a high-dose dual therapy will be selected. During the rescue treatment, a levofloxacin quadruple regimen will be selected for levofloxacin-sensitive strains, and a furazolidone quadruple regimen will be selected for others. The primary outcome is the first-line eradication rate in both groups, and the overall (including first and rescue therapies) H. pylori eradication rate in both groups is one of the secondary outcomes. The eradication rates of H. pylori will be analysed by intention-to-treat analysis, modified intention-to-treat analysis, and per-protocol analysis. DISCUSSION: This randomised controlled trial will provide objective and valid evidence about the value of polymerase chain reaction-based molecular methods for antibiotic susceptibility testing in guiding H. pylori eradication. TRIAL REGISTRATION: Clinicaltrials.gov NCT05549115. Released on 18 September 2022. First posted on 22 September 2022. Enrolment of the first participant on 20 September 2022. The study is retrospectively registered.

Infecciones causadas por Staphylococcus aureus de la Comunidad. Estudio de sensibilidad y tendencias en población pediátrica. Años 2015 a 2020

Introducción: Staphylococcus aureus (SA) puede ocasionar cuadros infecciosos severos y muerte. La emergencia de cepas resistentes a meticilina constituye un desafío terapéutico. Objetivos: determinar el perfil de resistencia antimicrobiana de: Staphylococcus aureus adquirido en la comunidad (SA-CA), obtenidos de muestras biológicas de niños, entre 2015 a 2020. Material y Método: estudio descriptivo, observacional y retrospectivo. Las muestras para cultivos se extrajeron al ingreso hospitalario del paciente. Para determinación de resistencia y sensibilidad se utilizó normas de CSLI. Resultados: 244 aislamientos de SA-CA. Masculinos 99 (59%), menores de un año: 42 (25%), de 2 a 5 años: 34 (20%), de 6 a 11 años: 50 (30%) y entre 12 a 15 años: 42 (25%). De los aislados, 72% fueron SAMR (121/168) y 28% SAMS (47/168). Se observó un incremento de tasas anuales de aislamientos SAMR en infecciones de la comunidad desde el 2015 al 2020. Los aislamientos se originaron en piel y partes blandas 53,2 %; sangre 37,4%, orina 3,5%, LCR 2,4%, liquido articular 1,7%, abscesos profundos 1,2% y liquido pleural 0,6%. La prevalencia de SAMR-CA fue de 60,5 en el 2015, 59,6 %, 61,5%, 72,2 %, 67,3% y 75,5 % en los años sucesivos. No se aisló ninguna cepa resistente a la vancomicina. El 10,1% de las cepas estudiadas presentó resistencia inducida a la clindamicina. Conclusión: El SAMR se ha establecido como patógeno de la comunidad. La resistencia inducida por clindamicina fue del 10,1%. Un tercio de las infecciones fueron causadas por SAMS. Las prevalencias de SAMS muestran tendencia a la disminución.

Introduction: Staphylococcus aureus (SA) can cause severe infectious conditions and death. The emergence of methicillin-resistant strains constitutes a therapeutic challenge. Objectives: to determine the antimicrobial resistance profile of: Staphylococcus aureus acquired in the community (SA-CA), obtained from biological samples of children, between 2015 and 2020. Material and Method: descriptive, observational and retrospective study. The samples for cultures were extracted upon hospital admission of the patient. To determine resistance and sensitivity, CSLI standards were used. Results: 244 isolates of SA-CA. Males 99 (59%), under one-year-old: 42 (25%), from 2 to 5 years old: 34 (20%), from 6 to 11 years old: 50 (30%) and between 12 and 15 years old: 42 (25%). Of the isolates, 72% were SAMR (121/168) and 28% SAMS (47/168). An increase in annual rates of MRSA isolates in community infections was observed from 2015 to 2020. The isolates originated in skin and soft parts 53.2 %; blood 37.4%, urine 3.5%, CSF 2.4%, joint fluid 1.7%, deep abscesses 1.2% and pleural fluid 0.6%. The prevalence of MRSA-CA was 60.5 in 2015, 59.6%, 61.5%, 72.2%, 67.3%, and 75.5% in subsequent years. No vancomycin resistant strain was isolated. 10.1% of the strains studied presented induced resistance to clindamycin. Conclusion: MRSA has been established as a community pathogen. The resistance induced by clindamycin was 10.1%. One third of the infections was caused by SAMS. The prevalence of SAMS shows a downward trend.

Clinical characteristics and drug resistance profile of patients with endobronchial tuberculosis in South Korea: single-center experience.

BACKGROUND: Tuberculosis (TB) is a major infectious disease worldwide; there has been a significant increase in the number of elderly patients with TB, largely contributing to TB-related mortality. Although endobronchial tuberculosis (EBTB) is a unique form of pulmonary TB, available data on the clinical characteristics and drug susceptibility (DST) patterns of patients with EBTB are scarce. METHODS: We evaluated the clinical characteristics of patients with EBTB in South Korea and the culture-based DST patterns of EBTB. Further, the DST patterns were compared between elderly (≥65 years) and young (<65 years) patients. We retrospectively reviewed data of patients with EBTB who had the results of DST and were diagnosed between January 2013 and December 2019 at a tertiary referral hospital in South Korea. Phenotypic DST of 15 first-line and second-line anti-TB drugs was performed using Mycobacterium tuberculosis isolates prior to treatment. RESULTS: Of the 230 patients with EBTB, 69% were in elderly patients (≥65 years). Any-resistance occurred in 24 patients (10.4%), while multi-drug resistance (MDR) and extensive drug resistance (XDR) were observed in six patients (2.6%). Compared to that of the elderly treatment-naïve patients, previously treated elderly patients had a significantly higher proportion of resistance to rifampin (14.3% vs. 2.2%; P=0.031), ethambutol (9.5% vs. 0.7%; P=0.046), and pyrazinamide (9.5% vs. 0.7%; P=0.046). Further, MDR/XDR was observed more frequently in the previously treated elderly patients than that in the treatment-naïve elderly patients (14.3% vs. 1.4%; P=0.017). A relatively small number of drug-resistant cases (5.6%) were observed in young patients. CONCLUSIONS: Elderly EBTB patients with previous Anti-tuberculous medications had a significantly higher proportion of drug-resistant TB. These patients should be carefully assessed using DST analysis before treatment.

High levels of antimicrobial resistance in Escherichia coli and Salmonella from poultry in Ecuador.

Objective: To describe antimicrobial resistance profiles of Escherichia coli and Salmonella spp. isolated from chicken carcasses and the antimicrobials commonly used in animals in Ecuador and provide information on antimicrobial resistance patterns for implementing evidence-based corrective measures. Methods: Meat samples were collected from chicken carcasses in 199 slaughterhouses across Ecuador as part of a national pilot study for monitoring antimicrobial resistance in agricultural sources in 2019. Samples were tested for E. coli and Salmonella spp. Sensitivity to 10 critically important and three highly important antimicrobials (from a human health perspective) was assessed. The country report submitted to the World Organization for Animal Health was accessed to extract the quantity of antimicrobials produced or imported for use in animals. Results: Of 383 samples, E. coli was isolated from 148 (39%) and Salmonella spp. from 20 (5%) samples. Ninety percent of the isolates were resistant to at least one critically important antimicrobial. Resistance was highest to erythromycin (E. coli 76%; Salmonella spp. 85%) and tetracycline (E. coli 71%; Salmonella spp. 90%). Critically or highly important antimicrobials (colistin, tetracycline, trimethoprim/sulfamethoxazole) formed the bulk (87%) of antimicrobials used in animals as per the World Organization for Animal Health report. Conclusions: High prevalence of antimicrobial resistance in poultry in Ecuador calls for the development of guidelines and regulations on the use of antimicrobials and for engagement with livestock producers. The existing surveillance system needs to be strengthened to improve the monitoring of antimicrobial use and evolving resistance patterns.

Development of multiplex real-time PCR for detection of clarithromycin resistance genes for the Mycobacterium abscessus group.

Introduction. The M. abscessus molecular identification and its drug-resistance profile are important to choose the correct therapy.Aim. This work developed a multiplex real-time PCR (mqPCR) for detection of clarithromycin resistance genes for the Mycobacterium abscessus group.Methodology. Isolates received by Adolfo Lutz Institute from 2010 to 2012, identified by PCR restriction enzyme analysis of a fragment of the hsp65 gene (PRA-hsp65) as M. abscessus type 1 (n=135) and 2 (n=71) were used. Drug susceptibility test (DST) for CLA were performed with reading on days 3 and 14. Subespecies identification by hsp65 and rpoB genes sequencing and erm(41) and rrl genes for mutation detection and primer design were performed. erm(41) gene deletion was detected by conventional PCR. Primers and probes were designed for five detections: erm(41) gene full size and with deletion; erm(41) gene T28 and C28; rrl gene A2058.Results. In total, 191/206 (92.7 %) isolates were concordant by all methods and 13/206 (6.3 %) were concordant only between molecular methods. Two isolates (1.0 %) were discordant by mqPCR compared to rrl gene sequencing. The mqPCR obtained 204/206 (99.0 %) isolates in agreement with the gold standard, with sensitivity and specificity of 98 and 100 %, respectively, considering the gold standard method and 92 and 93 % regarding DST.Conclusion. The mqPCR developed by us proved to be an easy-to-apply tool, minimizing time, errors and contamination.