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Clinical Laboratory Jun 2024Non-tuberculous mycobacterial pulmonary infections (NTM-PD) are becoming increasingly common in clinical practice, and early detection and accurate determination of the...
BACKGROUND
Non-tuberculous mycobacterial pulmonary infections (NTM-PD) are becoming increasingly common in clinical practice, and early detection and accurate determination of the infecting pathogen is crucial for subsequent treatment. We report a case of NTM-PD in a healthy middle-aged female with Mycobacterium tuberculosis complex group (MAC) infection confirmed by mNGS examination.
METHODS
Appropriate laboratory tests, chest CT scan, bronchoscopic alveolar lavage fluid (BALF) examination, and macrogenomic next-generation sequencing (mNGS) were performed to establish the diagnosis.
RESULTS
Chest CT showed multiple inflammatory lesions in the right middle lobe, and BALF sent for mNGS finally confirmed the diagnosis of MAC infection. After symptomatic treatment with azithromycin combined with ethambutol and rifampicin, the patient improved and was discharged from the hospital.
CONCLUSIONS
In patients with pulmonary infections, pathogens should be clarified early to determine the diagnosis. mNGS of BALF samples have high specificity in detecting pathogens of infectious diseases, especially complex mixed infectious disease pathogens.
Topics: Humans; Female; Mycobacterium avium-intracellulare Infection; Mycobacterium avium Complex; Bronchoalveolar Lavage Fluid; Middle Aged; Tomography, X-Ray Computed; High-Throughput Nucleotide Sequencing; Pneumonia; Azithromycin; Rifampin
PubMed: 38868891
DOI: 10.7754/Clin.Lab.2024.240108 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2024Aim: To investigate the effectiveness of rifaximin and probiotics for the correction of intestinal permeability in patients with metabolic-associated fatty liver disease... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of rifaximin and probiotics for the correction of intestinal permeability in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus.
OBJECTIVE
Aim: To investigate the effectiveness of rifaximin and probiotics for the correction of intestinal permeability in patients with metabolic-associated fatty liver disease (MAFLD) in combination with type 2 diabetes mellitus.
PATIENTS AND METHODS
Materials and Methods: The prospective interventional randomized investigation included 68 patients with MAFLD in combination with type 2 diabetes, who were examined and divided into the 2 groups of treatment.
RESULTS
Results: The serum levels of interleukin (IL) - 6, IL-10 and zonulin, indicators of liver functional activity, liver attenuation coefficient between treatment group vs. control group after 2 weeks, 1 month, 3 and 6 months of therapy were significant differed. The serum levels of IL-6 and zonulin significantly decreasing and increasing of IL-10 in the treatment group after 2 weeks, 1, 3 and 6 months of combined therapy. When comparing of stool short-chain fatty acids concentration between treatment group vs. control group after 2 weeks, 1 month, 3 and 6 months of therapy the levels of acetic, butyric and propionic acids significantly differences and increase in their levels were established.
CONCLUSION
Conclusions: The results of the study in dynamics during 6 months show that the additional appointment of rifaximin, multispecies probiotic and prebiotic to metformin in patients with MAFLD and type 2 diabetes led to the elimination of subclinical inflammation, modulation of the permeability of the intestinal barrier and lowering increased intestinal permeability, as well as to the lower serum activity of liver aminotransferases and decrease the stage of steatosis.
Topics: Humans; Rifaximin; Diabetes Mellitus, Type 2; Probiotics; Male; Female; Middle Aged; Prospective Studies; Permeability; Non-alcoholic Fatty Liver Disease; Haptoglobins; Rifamycins; Treatment Outcome; Adult; Interleukin-6; Intestinal Mucosa; Protein Precursors; Intestinal Barrier Function
PubMed: 38865630
DOI: 10.36740/WLek202404118 -
Microbiology Spectrum Jun 2024Since 1999, doxycycline and hydroxychloroquine have been the recommended treatment for chronic Q fever, a life-threatening disease caused by the bacterial pathogen, ....
UNLABELLED
Since 1999, doxycycline and hydroxychloroquine have been the recommended treatment for chronic Q fever, a life-threatening disease caused by the bacterial pathogen, . Despite the duration of its use, the treatment is not ideal due to the lengthy treatment time, high mortality rate, resistant strains, and the potential for contraindicated usage. A literature search was conducted to identify studies that screened large panels of drugs against to identify novel targets with potential efficacy against . Twelve candidate antimicrobials approved for use in humans by the US Food and Drug Administration were selected and minimum inhibitory concentrations (MICs) were determined against the low virulence strain Nine Mile phase II. Rifabutin and rifaximin were the best performing antibiotics tested with MICs of ≤0.01 µg mL. Further screening of these top candidates was conducted alongside two drugs from the same class, rifampin, well-characterized and rifapentine, not previously reported against . These were screened against virulent strains of representing three clinically relevant genotypes. Rifapentine was the most effective in the human monocytic leukemia cell line, THP-1, with a MIC ≤0.01 µg mL. In the human kidney epithelial cell line, A-498, efficacy of rifapentine, rifampin, and rifabutin varied across strains with MICs between ≤0.001 and 0.01 µg mL. Rifampin, rifabutin, and rifapentine were all bactericidal against ; however, rifabutin and rifapentine demonstrated impressive bactericidal activity as low as 0.1 µg mL and should be further explored as alternative Q fever treatments given their efficacy .
IMPORTANCE
This work will help inform investigators and physicians about potential alternative antimicrobial therapies targeting the causative agent of Q fever, . Chronic Q fever is difficult to treat, and alternative antimicrobials are needed. This manuscript explores the efficacy of rifamycin antibiotics against virulent strains of representing three clinically relevant genotypes . Importantly, this study determines the susceptibility of to rifapentine, which has not been previously reported. Evaluation of the bactericidal activity of the rifamycins reveals that rifabutin and rifapentine are bactericidal at low concentrations, which is unusual for antibiotics against .
PubMed: 38864598
DOI: 10.1128/spectrum.01034-24 -
Cureus May 2024We present a 45-year-old African American male with a medical history of advanced-stage HIV/AIDS (CD4 count: 1 cell/μL) and poor adherence to highly active...
We present a 45-year-old African American male with a medical history of advanced-stage HIV/AIDS (CD4 count: 1 cell/μL) and poor adherence to highly active antiretroviral therapy (HAART), who presented with symptoms of diarrhea, weakness, and respiratory distress. Upon admission, duodenal and colonic biopsies revealed a diffuse histiocytic infiltrate consistent with complex (MAC), and a cecal biopsy was positive for Kaposi sarcoma (KS). Further workup showed consolidation and a right pleural effusion on chest X-ray, suggesting a pneumonia infection. The patient's hypoglycemic state and lung consolidation raised concerns for sepsis, despite negative blood cultures for the first 24 hours. The patient was initiated on HAART and treated with azithromycin, rifabutin, and ethambutol for disseminated MAC. Despite the aggressive immunotherapy, the patient's condition did not improve, and he eventually expired. This case uniquely highlights the wide range of opportunistic infections and malignancies that can present in individuals with advanced-stage HIV/AIDS, underscoring the importance of early recognition and treatment. This susceptible demographic warrants further research due to the non-solidified prognosis of individuals with severe immunodeficiency.
PubMed: 38864070
DOI: 10.7759/cureus.60129 -
Trends of Mycobacterium tuberculosis and rifampicin resistance at the Ho Teaching Hospital in Ghana.PloS One 2024Tuberculosis remains a major public health threat worldwide, causing significant morbidity and mortality, particularly in low- and middle-income countries. In recent...
BACKGROUND
Tuberculosis remains a major public health threat worldwide, causing significant morbidity and mortality, particularly in low- and middle-income countries. In recent years, efforts to combat tuberculosis have focused on strengthening healthcare systems and increasing access to diagnostics and treatment services. There is scarcity of data on the prevalence of Mycobacterium tuberculosis and rifampicin-resistant tuberculosis in the Volta region of Ghana. Therefore, the aim of this study was to determine the trends of Mycobacterium tuberculosis and rifampicin resistance in a major teaching hospital in Ghana spanning a six-year period.
METHODOLOGY
A retrospective cross-sectional hospital study was conducted at Ho Teaching Hospital, Ho, Ghana. Study data included archived results on tuberculosis testing using GeneXpert from 2016-2021. Archived data on tuberculosis testing were collected and entered using Microsoft Excel 2019. IBM SPSS (v26) was used for a statistical analysis of the prevalence of tuberculosis. P-value <0.05 was considered statistically significant.
RESULTS
The study included 5128 presumptive tuberculosis cases from 2016 to 2021, of which 552 were positive, revealing an overall prevalence of 10.76%. Males exhibited a significantly higher prevalence of tuberculosis (14.20%) compared to females (7.48%), with a male-to-female ratio of 2:1. The burden of tuberculosis varied significantly between age groups, with those aged 30-45 years and 46-60 years facing twice the risk compared to those under 15 years (p<0.001). Rainy seasons correlated with heightened tuberculosis occurrences (12.12%) compared to dry seasons (8.84%) (p = 0.008). Rifampicin-resistant tuberculosis was prevalent at 3.45%, slightly higher in women, particularly in the 45-59 age group (5.97%). In particular, tuberculosis prevalence exhibited fluctuations, peaking in 2016 (17.1%) and 2020 (11.5%), with a trough in 2019 (4.6%).
CONCLUSION
The overall prevalence of laboratory confirmed tuberculosis was 10.76%, and resistance to rifampicin, 3.45%, indicating high infection and possible treatment failure. Considering its infectious nature, this calls for concerted efforts to curb the spread of the infection.
Topics: Humans; Ghana; Rifampin; Female; Male; Mycobacterium tuberculosis; Adult; Middle Aged; Hospitals, Teaching; Adolescent; Young Adult; Retrospective Studies; Cross-Sectional Studies; Tuberculosis, Multidrug-Resistant; Prevalence; Aged; Child; Child, Preschool; Infant; Drug Resistance, Bacterial; Antitubercular Agents
PubMed: 38857257
DOI: 10.1371/journal.pone.0305161 -
Bioorganic Chemistry Aug 2024The notable characteristics of recently emerged Antibody-Drug Conjugates (ADCs) encompass the targeting of Human Epidermal growth factor Receptor 2 (HER2) through...
The notable characteristics of recently emerged Antibody-Drug Conjugates (ADCs) encompass the targeting of Human Epidermal growth factor Receptor 2 (HER2) through monoclonal antibodies (mAbs) and a high ratio of drug to antibody (DAR). The achievements of Kadcyla® (T-DM1) and Enhertu® (T-Dxd) have demonstrated that HER2-targeting antibodies, such as trastuzumab, have shown to be competitive in terms of efficacy and price for development. Furthermore, with the arrival of T-Dxd and Trodelvy®, high-DAR (7-8) ADCs, which differ from the moderate DAR (3-4) ADCs that were formerly regarded as conventional, are being acknowledged for their worth. Following this trend of drug development, we endeavored to develop a high-DAR ADC using a straightforward approach involving the utilization of DM1, a highly potent substance, in combination with the widely recognized trastuzumab. To achieve a high DAR, DM1 was conjugated to reduced cysteine through the simple design and synthesis of various dimaleimide linkers with differing lengths. Using LC and MS analysis, we have demonstrated that our synthesis methodology is uncomplicated and efficacious, yielding trastuzumab-based ADCs that exhibit a remarkable degree of uniformity. These ADCs have been experimentally substantiated to exert an inhibitory effect on cancer cells in vitro, thus affirming their value as noteworthy additions to the realm of ADCs.
Topics: Humans; Immunoconjugates; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Trastuzumab; Molecular Structure; Cell Proliferation; Drug Screening Assays, Antitumor; Maleimides; Dose-Response Relationship, Drug; Antineoplastic Agents; Structure-Activity Relationship; Maytansine; Cell Line, Tumor; Antineoplastic Agents, Immunological
PubMed: 38850783
DOI: 10.1016/j.bioorg.2024.107504 -
Archives of Dermatological Research Jun 2024Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains... (Review)
Review
Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains uncertain due to limited systematic evidence. Our objective was to analyze antistreptococcal therapies' effectiveness in improving psoriasis. We conducted a systematic review following PRISMA guidelines, evaluating antistreptococcal treatment efficacy in psoriasis patients from PubMed, Scopus, and Embase databases until August 14, 2022. Eligible studies included psoriasis patients undergoing antistreptococcal therapy, regardless of demographics or psoriasis type. 50 studies (1778 patients) were analyzed, with penicillins/aminopenicillins as the most studied antibiotics (21 studies), showing mixed outcomes, some reporting significant improvement in guttate psoriasis, while others showed no significant difference. Rifampin demonstrated positive results in most of ten studies, and macrolides showed varying effectiveness in two studies. Tonsillectomy in 14 studies (409 patients) mainly focusing on guttate and chronic plaque psoriasis showed positive outcomes, indicating improved symptoms and quality of life. Limitations include heterogeneous studies, sampling bias, and quality of evidence. This systematic review reveals limited and varied evidence for systemic antibiotic therapy efficacy in psoriasis treatment, while tonsillectomy emerges as a potentially beneficial antistreptococcal option, urging further well-designed, controlled studies with larger sample sizes and standardized protocols for better comparisons.
Topics: Humans; Psoriasis; Anti-Bacterial Agents; Streptococcal Infections; Treatment Outcome; Quality of Life; Penicillins; Rifampin
PubMed: 38850287
DOI: 10.1007/s00403-024-03051-8 -
Scientific Reports Jun 2024Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture...
Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management.
Topics: Humans; Male; Female; Artificial Intelligence; Middle Aged; Tuberculosis, Pulmonary; Retrospective Studies; Treatment Outcome; Aged; Sputum; Adult; Mycobacterium tuberculosis; Rifampin; Republic of Korea; Tomography, X-Ray Computed; Antitubercular Agents; Radiography, Thoracic
PubMed: 38849439
DOI: 10.1038/s41598-024-63885-0 -
Journal of the Canadian Association of... Jun 2024Updated 2016 consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC)...
BACKGROUND
Updated 2016 consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days.
OBJECTIVES
This was a retrospective cohort study to describe and compare the efficacy of anti- treatment regimens over the periods 2007-2015 and 2016-2021 as well as antibiotic resistance.
METHODS
A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients.
RESULTS
-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016-2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) ( < 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7-26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016-2021 and sequential therapy in 2007-2015 (83% [66/80]) ( = 0.535, RD 4%, 95% CI -8.5-16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016-2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007-2015 to 2016-2021 (28% [13/46] to 61% [35/57], < 0.05, RD 33%, 95% CI 11.6-54.4%).
CONCLUSIONS
Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50-57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.
PubMed: 38841147
DOI: 10.1093/jcag/gwad051 -
Analytica Chimica Acta Jul 2024The widespread use and abuse of antibiotics has resulted in the pollution of water sources with antibiotic residues, posing a threat to human health, the environment,...
BACKGROUND
The widespread use and abuse of antibiotics has resulted in the pollution of water sources with antibiotic residues, posing a threat to human health, the environment, and the economy. Therefore, a highly sensitive and selective method is required for their detection in water samples. Herein, advanced ultrasensitive electrochemical sensor platform was developed by integrating gold-silver alloy nanocoral clusters (Au-Ag-ANCCs) with functionalized multi-walled carbon nanotube-carbon paste electrode (f-MWCNT-CPE) and choline chloride (ChCl) nanocomposites for simultaneously determining the residues of antimicrobial drugs, rifampicin (RAMP) and norfloxacin (NFX), in water samples.
RESULTS
The developed sensor (Au-Ag-ANCCs/f-MWCNTs-CPE/ChCl) was extensively characterized using several analytical (UV-Vis, FT-IR, XRD, SEM, and EDX) and electrochemical (EIS, CV, and SWV) techniques. It exhibited outstanding performance in a wide linear range, from 14 pM to 115 μM for RAMP, and from 0.9 nM to 200 μM for NFX, with a limit of detection (LOD, 3σ/m, S/N = 3, n = 5) and a limit of quantification (LOQ, 10σ/m, S/N = 3, n = 5) values of 2.7 pM and 8.85 pM for RAMP, and 0.14 nM and 0.47 nM for NFX, respectively. The sensor also exhibited exceptional reproducibility, stability, and resistance to interference.
SIGNIFICANCE
The developed sensor was effectively utilized to determine RAMP and NFX residues in hospital wastewater, river, and tap water samples, yielding recoveries within the range of 96.8-103 % and relative standard deviations below 5 %. Generally, the proposed sensor demonstrated remarkable performance in detecting the target analytes, making it an ideal tool and the first of its kind for addressing global antibiotic residue pollutants in water sources.
Topics: Norfloxacin; Water Pollutants, Chemical; Electrochemical Techniques; Rifampin; Electrodes; Limit of Detection; Anti-Bacterial Agents; Nanotubes, Carbon
PubMed: 38834274
DOI: 10.1016/j.aca.2024.342746