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Microbiology Spectrum Jul 2024A total of 334 isolates were recovered from 6,223 pet rectal samples collected at 50 pet clinics, 42 pet shops, 7 residential areas, and 4 plazas. Forty serovars were...
A total of 334 isolates were recovered from 6,223 pet rectal samples collected at 50 pet clinics, 42 pet shops, 7 residential areas, and 4 plazas. Forty serovars were identified that included all strains except for one isolate that did not cluster via self-agglutination, with Typhimurium monophasic variant, Kentucky, Enteritidis, Pomona, and Give being the predominant serovars. Fifty-one sequence types were identified among the isolates, and ST198, ST11, ST19, ST451, ST34, and ST155 were the most common. The top four dominant antimicrobials to which isolates were resistant were sulfisoxazole, ampicillin, doxycycline, and tetracycline, and 217 isolates exhibited multidrug resistance. The prevalence of β-lactamase genes in isolates was 59.6%, and among these isolates, 185 harbored , followed by (66) and (10). Moreover, six PMQR genes, namely, including (4.8%), (4.2%), (0.9%), (18.9%), (16.5%), and (1.5%), were detected. QRDR mutations (76.6%) were very common in isolates, with the most frequent mutation in (T57S) (47.3%). Furthermore, we detected six tetracycline resistance genes in 176 isolates, namely, (A) (39.5%), (B) (8.1%), (M) (7.7%), (D) (5.4%), (J) (3.3%), and (C) (1.8%), and three sulfonamide resistance genes in 303 isolates, namely, (84.4%), (31.1%), and (4.2%). Finally, we found 86 isolates simultaneously harboring four types of resistance genes that cotransferred 2-7 resistance genes to recipient bacteria. The frequent occurrence of antimicrobial resistance, particularly in dogs and cats, suggests that antibiotic misuse may be driving multidrug-resistant among pets.IMPORTANCEPet-associated human salmonellosis has been reported for many years, and antimicrobial resistance in pet-associated has become a serious public health problem and has attracted increasing attention. There are no reports of from pets and their antimicrobial resistance in Chongqing, China. In this study, we investigated the prevalence, serovar diversity, sequence types, and antimicrobial resistance of strains isolated from pet fecal samples in Chongqing. In addition, β-lactamase, QRDR, PMQR, tetracycline and sulfonamide resistance genes, and mutations in QRDRs in isolates were examined. Our findings demonstrated the diversity of serovars and sequence types of isolates. The isolates were widely resistant to antimicrobials, notably with a high proportion of multidrug-resistant strains, which highlights the potential direct or indirect transmission of multidrug-resistant from pets to humans. Furthermore, resistance genes were widely prevalent in the isolates, and most of the resistance genes were spread horizontally between strains.
Topics: China; Animals; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Salmonella; Pets; Microbial Sensitivity Tests; Salmonella Infections, Animal; Serogroup; Genotype; beta-Lactamases; Phenotype; Bacterial Proteins
PubMed: 38757951
DOI: 10.1128/spectrum.03542-23 -
Experimental and Therapeutic Medicine Jun 2024Central nervous system (CNS) tuberculosis mainly manifests as tuberculous meningitis and intracranial tuberculosis; intramedullary tuberculosis is uncommon. Scrub typhus...
Central nervous system (CNS) tuberculosis mainly manifests as tuberculous meningitis and intracranial tuberculosis; intramedullary tuberculosis is uncommon. Scrub typhus is an acute naturally occurring infectious disease caused by . CNS tuberculoma following typhus is rare. The present study described a 60-year-old man with high fever, muscle soreness, yellowish skin and sclera and hepatosplenomegaly. At first, the patient was diagnosed with scrub typhus, after treatment with doxycycline he recovered completely. However, half a month after discharge, the patient experienced headache, night sweats and anorexia. Tuberculosis-specific enzyme-linked immunospot assay showed positive Mycobacterium tuberculosis antibody in cerebrospinal fluid (CSF). Metagenomic next-generation sequencing detected the presence of in CSF. Magnetic resonance imaging of the brain and spinal cord showed multiple rings enhancing lesions in the cerebral hemispheres, cerebellum, brainstem and spinal cords. After the diagnosis of CNS tuberculoma, the patient was started on conventional anti-tuberculosis therapy resulting in a good prognosis.
PubMed: 38756901
DOI: 10.3892/etm.2024.12548 -
Frontiers in Veterinary Science 2024Antimicrobial resistance (AMR) is commonly associated with the inappropriate use of antibiotics during meat-rabbit production, posing unpredictable risks to rabbit...
Antimicrobial resistance (AMR) is commonly associated with the inappropriate use of antibiotics during meat-rabbit production, posing unpredictable risks to rabbit welfare and public health. However, there is limited research on the epidemiological dynamics of antibiotic resistance among bacteria indicators derived from local healthy meat-rabbits. To bridge the knowledge gap between antibiotic use and AMR distribution, a total of 75 () and 210 spp. strains were successfully recovered from fecal samples of healthy meat-rabbits. The results revealed that diverse AMR phenotypes against seven commonly used antimicrobials, including ampicillin (AMP), amoxicillin-clavulanic acid (A/C), doxycycline (DOX), enrofloxacin (ENR), florfenicol (FFC), gentamicin (GEN), and polymycin B (PMB), were observed among most strains of and spp. in two rabbit farms, although the distribution pattern of antibiotic resistance between young and adult rabbits was similar. Among them, 66 strains showed resistance against 6 antimicrobials except for PMB. However, 164 spp. strains only exhibited acquired resistance against DOX and GEN. Notably, the DOX-based AMR phenotypes for and spp. strains were predominant, indicating the existing environmental stress conferred by DOX exposure. The MICs tests suggested elevated level of antibiotic resistance for resistant bacteria. Unexpectedly, all GEN-resistant spp. strains resistant high-level gentamicin (HLGR). By comparison, the and were highly detected among 35 multi-resistant strains, and genes widely spread among the 40 double-resistant spp. strains. Nevertheless, the presence of ARGs were not concordant with the resistant phenotypes for a portion of resistant bacteria. In conclusion, the distribution of AMR and ARGs are prevalent in healthy meat-rabbits, and the therapeutic antimicrobials use in farming practice may promote the antibiotic resistance transmission among indicator bacteria. Therefore, periodic surveillance of antibiotic resistance in geographic locations and supervisory measures for rational antibiotic use are imperative strategies for combating the rising threats posed by antibiotic resistance, as well as maintaining rabbit welfare and public health.
PubMed: 38756516
DOI: 10.3389/fvets.2024.1369655 -
The Lancet. Global Health Jul 2024Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment.
METHODS
In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913.
FINDINGS
Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups.
INTERPRETATION
Nodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections.
FUNDING
Medical Research Council (UK).
TRANSLATION
For the Luo translation of the abstract see Supplementary Materials section.
Topics: Humans; Child; Adolescent; Female; Male; Doxycycline; Nodding Syndrome; Double-Blind Method; Uganda; Treatment Outcome; Anti-Bacterial Agents; Onchocerca volvulus
PubMed: 38754459
DOI: 10.1016/S2214-109X(24)00102-5 -
The Lancet. Global Health Jul 2024
Topics: Humans; Doxycycline; Anti-Bacterial Agents; Nodding Syndrome
PubMed: 38754458
DOI: 10.1016/S2214-109X(24)00182-7 -
PloS One 2024Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a...
BACKGROUND
Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a pathological characteristics of CRS. Activation of fibroblasts in the nasal mucosal stroma, differentiation and collagen deposition, and subepithelial fibrosis have been associated with CRS.
OBJECTIVES
We aimed to assess the inhibitory effects of doxycycline and deoxycholic acid-polyethyleneimine conjugate (DA3-Doxy) on myofibroblast differentiation and extracellular matrix (ECM) production in nasal fibroblasts stimulated with TGF-β1.
METHODS
To enhance efficacy, we prepared DA3-Doxy using a conjugate of low-molecular-weight polyethyleneimine (PEI) (MW 1800) and deoxycholic acid (DA) and Doxy. The synthesis of the DA3-Doxy polymer was confirmed using nuclear magnetic resonance, and the critical micelle concentration required for cationic micelle formation through self-assembly was determined. Subsequently, the Doxy loading efficiency of DA3 was assessed. The cytotoxicity of Doxy, DA3, PEI, and DA-Doxy in nasal fibroblasts was evaluated using the WST-1 assay. The anti-tissue remodeling and anti-inflammatory effects of DA3-Doxy and DA3 were examined using real-time polymerase chain reaction (Real-time PCR), immunocytochemistry, western blot, and Sircol assay.
RESULTS
Both DA3 and DA3-Doxy exhibited cytotoxicity at 10 μg/ml in nasal fibroblasts. Doxy partially inhibited α-smooth muscle actin, collagen types I and III, and fibronectin. However, DA3-Doxy significantly inhibited α-SMA, collagen types I and III, and fibronectin at 5 μg/ml. DA3-Doxy also modulated TGF-β1-induced changes in the expression of MMP 1, 2, and 9. Nonetheless, TGF-β1-induced expression of MMP3 was further increased by DA3-Doxy. The expression of TIMP 1 and 2 was partially reduced with 5 μg/ml DA3-Doxy.
CONCLUSIONS
Although initially developed for the delivery of genetic materials or drugs, DA3 exhibits inhibitory effects on myofibroblast differentiation and ECM production. Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs.
Topics: Humans; Polyethyleneimine; Deoxycholic Acid; Fibroblasts; Cell Differentiation; Doxycycline; Extracellular Matrix; Transforming Growth Factor beta1; Myofibroblasts; Nasal Mucosa; Actins
PubMed: 38753593
DOI: 10.1371/journal.pone.0285655 -
Drug Target Insights 2024Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market.... (Review)
Review
Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields-cardiovascular, cancer, and diabetes-and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.
PubMed: 38751378
DOI: 10.33393/dti.2024.3019 -
BMC Chemistry May 2024Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to...
Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to brucellosis treatment, enhancing the efficacy of doxycycline and rifampicin through the use of poly (lactic-co-glycolic) acid coupled with cadmium-telluride quantum dots (Dox-Rif-PLGA@CdTe). The double emulsion solvent evaporation method was employed to prepare Dox-Rif-PLGA@CdTe. The study scrutinized the physicochemical attributes of these nanoparticles. The impact of antibiotic-loaded nanoparticles on Brucella melitensis was evaluated through well diffusion, minimum inhibitory concentration (MIC), and cell culture. The chemical analysis results demonstrated a possibility of chemical reactions occurring among the constituents of nanoparticles. Assessments using the well diffusion and MIC methods indicated that the impact of free drugs and nanoparticles on bacteria was equivalent. However, the drug-loaded nanoparticles significantly decreased the colony-forming units (CFUs) within the cell lines compared to free drugs. In conclusion, the synthesis of nanoparticles adhered to environmentally friendly practices and demonstrated safety. The sustained drug release over 100 h facilitated drug accumulation at the bacterial site, resulting in a heightened therapeutic effect on B. melitensis and improved outcomes in brucellosis treatment. The application of these synthesized nanodrugs exhibited promising therapeutic potential.
PubMed: 38750589
DOI: 10.1186/s13065-024-01200-8 -
Alternative Therapies in Health and... May 2024Ureaplasma spp. comprise a group of mycoplasmas containing two human-associated species, namely, Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA). The...
OBJECTIVE
Ureaplasma spp. comprise a group of mycoplasmas containing two human-associated species, namely, Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA). The characterization of Ureaplasma species as pathogens contributing to male infertility remains a subject of considerable controversy. While numerous authors have proposed a relationship between UUR and changes in fertility, there is limited evidence supporting the involvement of UPA in this context. There has been an increased focus on Ureaplasma spp. and its potential role in the development of male infertility, especially over the past few years. The review aims to clarify the relationship between Ureaplasma species and male infertility.
METHODS
Firstly, we introduce a background of the appropriate biology including growth characteristics, the divided biovars, and the transmission pathways. Secondly, we examine the studies that support a causal role for Ureaplasma spp. in the development of infertility in the last 30 years. Finally, the diagnosed method, antimicrobial susceptibility, and potential therapeutic considerations are evaluated.
RESULTS
UPA and UUR can impair semen motility. The species of Ureaplasma spp., the sexual history of the patient, the number of sexual partners, the load of Ureaplasma, and antimicrobial resistance are expected to constitute key risk factors in the development of male infertility. In terms of treatment, Doxycycline remains the drug of first choice for ureaplasmal infections.
CONCLUSION
Ureaplasma spp. are not simply "innocent bystanders" in infertility and may indeed be an "underestimated enemy of human reproduction". Ureaplasma spp. can be considered an etiological agent in unexplained infertility and a useful marker.
PubMed: 38743894
DOI: No ID Found -
Turkish Journal of Pharmaceutical... May 2024The present study focused on the formulation of mucoadhesive bilayer composite films for the treatment of periodontitis and evaluation of their physicochemical...
OBJECTIVES
The present study focused on the formulation of mucoadhesive bilayer composite films for the treatment of periodontitis and evaluation of their physicochemical properties.
MATERIALS AND METHODS
The solvent casting technique was used to prepare films. The primary layer (D) was prepared with flaxseed and hydroxypropyl methylcellulose composite to sustain the release of doxycycline hyclate. The second layer (S) comprised sodium alginate and polyvinyl alcohol composite for faster release of clove oil. Both layers were combined to generate the bilayer film (B). All formulations were characterized further to obtain an optimized formulation.
RESULTS
Attenuated total reflection-Fourier transform infrared radiation results showed intactness of drug and clove oil in the presence of excipients. The pH of the films was compatible with the periodontal cavity and the thickness was suitable for inserting into the cavity. The immediate release layer showed faster disintegration and swelling. The content of clove oil was above 80%. The rate of swelling of the primary layer was slow and drug content complied with the United States Pharmacopoeia. Scanning electron microscope analysis revealed intact, non-porous and smooth films. Films exhibited better mechanical strength and bioadhesiveness. Clove oil was released from the immediate release layer within 10 min, and doxycycline hyclate release was retarded to a minimum of up to 8 h in the primary layer as well as the bilayer. Formulation also had a significant effect on both and .
CONCLUSION
In the current study, bilayers were successfully prepared and characterized. The optimized formulation can be effectively used for the treatment of periodontitis.
PubMed: 38742834
DOI: 10.4274/tjps.galenos.2023.15945