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BMJ Case Reports Jul 2024Coinfection of Pseudomonas and Aspergillus has not been previously reported in patients with chronic obstructive pulmonary disease (COPD). A middle-aged, thinly built...
Coinfection of Pseudomonas and Aspergillus has not been previously reported in patients with chronic obstructive pulmonary disease (COPD). A middle-aged, thinly built woman (Body Mass Index: 18.1 kg/m²) who smokes bidi (a type of tobacco) and has a history of exposure to open log fires for cooking, has been suffering from COPD for the last 4 years. She has been taking inhaled betamethasone and tiotropium. Additionally, she had uncontrolled diabetes for a few months. She presented with fever, productive cough, shortness of breath and chest pain for 5 days. She required non-invasive ventilation support for type-2 respiratory failure. Chest X-ray and CT confirmed pneumonia, cavities and abscesses in both lungs. Repeated sputum and bronchoalveolar lavage confirmed coinfections with and , respectively. Along with supportive therapy, she was treated with tablet levofloxacin and injection amikacin for 6 weeks based on culture sensitivity reports, and capsule itraconazole for 6 months. She recovered completely to her baseline COPD and diabetes status. This case study confirms that coinfections can occur in COPD and diabetes, highlighting the need for clinicians to be vigilant for the possibility of such symbiotic coinfections.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Female; Coinfection; Pseudomonas Infections; Middle Aged; Pseudomonas aeruginosa; Aspergillus fumigatus; Anti-Bacterial Agents; Diabetes Mellitus, Type 2; Pulmonary Aspergillosis; Antifungal Agents; Aspergillosis
PubMed: 38955386
DOI: 10.1136/bcr-2023-259285 -
BMJ Case Reports Jul 2024Lucio leprosy is a diffuse non-nodular form of lepromatous leprosy. Lucio phenomenon is a type of reactional state which occurs in untreated cases due to the bacillary...
Lucio leprosy is a diffuse non-nodular form of lepromatous leprosy. Lucio phenomenon is a type of reactional state which occurs in untreated cases due to the bacillary invasion of endothelial cells. We hereby describe a histopathologically confirmed case of Lucio leprosy with Lucio phenomenon. The patient presented with pleomorphic clinical features and started taking antileprosy treatment and systemic steroids. After few days of admission, she developed deep ulcers exposing the fascia. She also developed cardiogenic shock secondary to septicaemia. She was managed with inotropes and broad-spectrum antibiotics. The patient was given appropriate wound care and the ulcers healed within a period of 3 months and antileprosy drugs were continued. Our patient is a de novo case of Lucio leprosy with Lucio phenomenon and pleomorphic clinical features who developed near fatal septic shock. She was managed successfully. Despite the extensive disease manifestation, all the wounds healed completely.
Topics: Humans; Female; Leprosy, Lepromatous; Shock, Septic; Leprostatic Agents; Anti-Bacterial Agents; Shock, Cardiogenic; Middle Aged
PubMed: 38955383
DOI: 10.1136/bcr-2023-255477 -
PloS One 2024This study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) and the use of probiotics on the treatment of halitosis. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) and the use of probiotics on the treatment of halitosis.
METHODS
Fifty-two participants, aged from 18 to 25 years, exhaling sulfhydride (H2S) ≥ 112 ppb were selected. They were allocated into 4 groups (n = 13): Group 1: tongue scraper; Group 2: treated once with aPDT; Group 3: probiotic capsule containing Lactobacillus salivarius WB21 (6.7 x 108 CFU) and xylitol (280mg), 3 times a day after meals, for 14 days; Group 4: treated once with aPDT and with the probiotic capsule for 14 days. Halimetry with gas chromatography (clinical evaluation) and microbiological samples were collected from the dorsum of the tongue before and after aPDT, as well as after 7, 14, and 30 days. The clinical data failed to follow a normal distribution; therefore, comparisons were made using the Kruskal-Wallis test (independent measures) and Friedman ANOVA (dependent measures) followed by appropriate posthoc tests, when necessary. For the microbiological data, seeing as the data failed to follow a normal distribution, the Kruskal-Wallis rank sum test was performed with Dunn's post-test. The significance level was α = 0.05.
RESULTS
Clinical results (halimetry) showed an immediate significant reduction in halitosis with aPDT (p = 0.0008) and/or tongue scraper (p = 0.0006). Probiotics showed no difference in relation to the initial levels (p = 0.7530). No significant differences were found in the control appointments. The amount of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were not altered throughout the analysis (p = 0.1616, p = 0.2829 and p = 0.2882, respectively).
CONCLUSION
There was an immediate clinical reduction of halitosis with aPDT and tongue scraping, but there was no reduction in the number of bacteria throughout the study, or differences in the control times, both in the clinical and microbiological results. New clinical trials are necessary to better assess the tested therapies.
TRIAL REGISTRATION
Clinical Trials NCT03996044.
Topics: Humans; Halitosis; Probiotics; Adult; Photochemotherapy; Male; Female; Adolescent; Young Adult; Ligilactobacillus salivarius; Tongue; Anti-Infective Agents
PubMed: 38954692
DOI: 10.1371/journal.pone.0297351 -
PLoS Biology Jul 2024The prevalence of antibiotic-resistant pathogens has become a major threat to public health, requiring swift initiatives for discovering new strategies to control...
The prevalence of antibiotic-resistant pathogens has become a major threat to public health, requiring swift initiatives for discovering new strategies to control bacterial infections. Hence, antibiotic stewardship and rapid diagnostics, but also the development, and prudent use, of novel effective antimicrobial agents are paramount. Ideally, these agents should be less likely to select for resistance in pathogens than currently available conventional antimicrobials. The usage of antimicrobial peptides (AMPs), key components of the innate immune response, and combination therapies, have been proposed as strategies to diminish the emergence of resistance. Herein, we investigated whether newly developed random antimicrobial peptide mixtures (RPMs) can significantly reduce the risk of resistance evolution in vitro to that of single sequence AMPs, using the ESKAPE pathogen Pseudomonas aeruginosa (P. aeruginosa) as a model gram-negative bacterium. Infections of this pathogen are difficult to treat due the inherent resistance to many drug classes, enhanced by the capacity to form biofilms. P. aeruginosa was experimentally evolved in the presence of AMPs or RPMs, subsequentially assessing the extent of resistance evolution and cross-resistance/collateral sensitivity between treatments. Furthermore, the fitness costs of resistance on bacterial growth were studied and whole-genome sequencing used to investigate which mutations could be candidates for causing resistant phenotypes. Lastly, changes in the pharmacodynamics of the evolved bacterial strains were examined. Our findings suggest that using RPMs bears a much lower risk of resistance evolution compared to AMPs and mostly prevents cross-resistance development to other treatments, while maintaining (or even improving) drug sensitivity. This strengthens the case for using random cocktails of AMPs in favour of single AMPs, against which resistance evolved in vitro, providing an alternative to classic antibiotics worth pursuing.
Topics: Pseudomonas aeruginosa; Anti-Bacterial Agents; Antimicrobial Peptides; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Biofilms; Pseudomonas Infections
PubMed: 38954678
DOI: 10.1371/journal.pbio.3002692 -
JAMA Network Open Jul 2024
Topics: Humans; Anti-Bacterial Agents; beta-Lactams; Infusions, Intravenous; beta Lactam Antibiotics
PubMed: 38954420
DOI: 10.1001/jamanetworkopen.2024.18196 -
JAMA Network Open Jul 2024Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.
IMPORTANCE
Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.
OBJECTIVE
To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).
DESIGN, SETTING, AND PARTICIPANTS
This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.
EXPOSURES
EI-BL (ie, ≥3-hour infusion).
MAIN OUTCOMES AND MEASURES
EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).
RESULTS
Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.
Topics: Humans; Male; Female; Middle Aged; Gram-Negative Bacterial Infections; Anti-Bacterial Agents; beta-Lactams; Aged; Bacteremia; Infusions, Intravenous; Cohort Studies; United States; Adult; Retrospective Studies
PubMed: 38954416
DOI: 10.1001/jamanetworkopen.2024.18234 -
AAPS PharmSciTech Jul 2024Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating...
Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug's free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.
Topics: Diarylquinolines; Nanoparticles; Particle Size; Lipids; Chemistry, Pharmaceutical; Excipients; Drug Liberation; Antitubercular Agents; Drug Compounding; X-Ray Diffraction; Microscopy, Electron, Scanning; Drug Carriers; Administration, Oral; Liposomes
PubMed: 38954218
DOI: 10.1208/s12249-024-02873-z -
Environmental Geochemistry and Health Jul 2024Recently, the hazardous effects of antibiotic micropollutants on the environment and human health have become a major concern. To address this challenge,...
Recently, the hazardous effects of antibiotic micropollutants on the environment and human health have become a major concern. To address this challenge, semiconductor-based photocatalysis has emerged as a promising solution for environmental remediation. Our study has developed BiWO/g-CN (BWCN) photocatalyst with unique characteristics such as reactive surface sites, enhanced charge transfer efficiency, and accelerated separation of photogenerated electron-hole pairs. BWCN was utilized for the oxidation of tetracycline antibiotic (TCA) in different water sources. It displayed remarkable TCA removal efficiencies in the following order: surface water (99.8%) > sewage water (88.2%) > hospital water (80.7%). Further, reusability tests demonstrated sustained performance of BWCN after three cycles with removal efficiencies of 87.3, 71.2 and 65.9% in surface water, sewage, and hospital water, respectively. A proposed photocatalytic mechanism was delineated, focusing on the interaction between reactive radicals and TCA molecules. Besides, the transformation products generated during the photodegradation of TCA were determined, along with the discussion on the potential risk assessment of antibiotic pollutants. This study introduces an approach for utilizing BWCN photocatalyst, with promising applications in the treatment of TCA from various wastewater sources.
Topics: Water Pollutants, Chemical; Anti-Bacterial Agents; Oxidation-Reduction; Tetracycline; Catalysis; Wastewater; Bismuth; Graphite; Nitrogen Compounds; Tungsten Compounds; Photolysis; Water Purification; Sewage
PubMed: 38954124
DOI: 10.1007/s10653-024-02050-y -
Medical Microbiology and Immunology Jul 2024Streptococcus pneumoniae infection is a major public health concern with high morbidity and mortality rates. This study aimed to evaluate the serotype distribution,...
Serotype distribution, antibiotic resistance, multilocus sequence typing, and virulence factors of invasive and non-invasive Streptococcus pneumoniae in Northeast China from 2000 to 2021.
Streptococcus pneumoniae infection is a major public health concern with high morbidity and mortality rates. This study aimed to evaluate the serotype distribution, antimicrobial resistance changes, clonal composition, and virulence factors of S. pneumoniae isolates causing pneumococcal disease in northeast China from 2000 to 2021. A total of 1,454 S. pneumoniae isolates were included, with 568 invasive strains and 886 non-invasive strains. The patients from whom the S. pneumoniae were isolated ranged in age from 26 days to 95 years, with those ≤ 5 years old comprising the largest group (67.19%). 19 F, 19 A, 23 F, 14, and 6B were the most common serotypes, of which 19 A and 19 F were the main serotypes of invasive and non-invasive S. pneumoniae, respectively. CC271 was the most common multilocus sequence type. Serotype 14 had the lowest expression of cbpA, rrgA, and psrP genes, but expression levels of 19 A and 19 F genes were similar. All isolates were sensitive to ertapenem, moxifloxacin, linezolid, and vancomycin but highly resistant to macrolides, tetracyclines, and cotrimoxazole. Simultaneous resistance to erythromycin, clindamycin, tetracyclines, and trimethoprim/sulfamethoxazole was common pattern among multidrug-resistant isolates. Non-invasive S. pneumoniae had higher resistance to β-lactam antibiotics than invasive strains. 19 A and 19 F were the main strains of penicillin-resistant S. pneumoniae. The resistance rate of β-lactam antibiotics decreased from 2017 to 2021 compared to previous periods. Including PCV13 in the national immunization program can reduce the morbidity and mortality rates of pneumococcal disease effectively.
Topics: Streptococcus pneumoniae; Humans; Multilocus Sequence Typing; China; Virulence Factors; Pneumococcal Infections; Serogroup; Child, Preschool; Infant; Middle Aged; Adolescent; Anti-Bacterial Agents; Adult; Child; Aged; Young Adult; Aged, 80 and over; Infant, Newborn; Microbial Sensitivity Tests; Female; Male; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial
PubMed: 38954065
DOI: 10.1007/s00430-024-00797-w -
Archives of Microbiology Jul 2024Wild-type Lactococcus lactis strain LAC460 secretes prophage-encoded bacteriocin-like lysin LysL, which kills some Lactococcus strains, but has no lytic effect on the...
Wild-type Lactococcus lactis strain LAC460 secretes prophage-encoded bacteriocin-like lysin LysL, which kills some Lactococcus strains, but has no lytic effect on the producer. LysL carries two N-terminal enzymatic active domains (EAD), and an unknown C-terminus without homology to known domains. This study aimed to determine whether the C-terminus of LysL carries a cell wall binding domain (CBD) for target specificity of LysL. The C-terminal putative CBD region of LysL was fused with His-tagged green fluorescent protein (HGFPuv). The HGFPuv_CBDlysL gene fusion was ligated into the pASG-IBA4 vector, and introduced into Escherichia coli. The fusion protein was produced and purified with affinity chromatography. To analyse the binding of HGFPuv_CBDLysL to Lactococcus cells, the protein was mixed with LysL-sensitive and LysL-resistant strains, including the LysL-producer LAC460, and the fluorescence of the cells was analysed. As seen in fluorescence microscope, HGFPuv_CBDLysL decorated the cell surface of LysL-sensitive L. cremoris MG1614 with green fluorescence, whereas the resistant L. lactis strains LM0230 and LAC460 remained unfluorescent. The fluorescence plate reader confirmed the microscopy results detecting fluorescence only from four tested LysL-sensitive strains but not from 11 tested LysL-resistant strains. Specific binding of HGFPuv_CBDLysL onto the LysL-sensitive cells but not onto the LysL-resistant strains indicates that the C-terminus of LysL contains specific CBD. In conclusion, this report presents experimental evidence of the presence of a CBD in a lactococcal phage lysin. Moreover, the inability of HGFPuv_CBDLysL to bind to the LysL producer LAC460 may partly explain the host's resistance to its own prophage lysin.
Topics: Lactococcus lactis; Cell Wall; Bacteriocins; Escherichia coli; Green Fluorescent Proteins; Protein Domains; Recombinant Fusion Proteins; Protein Binding
PubMed: 38954047
DOI: 10.1007/s00203-024-04066-5