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1.
Molecules ; 29(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39274924

RESUMEN

In this report, a polytetrahydrofuran-coated polyester fabric phase sorptive extraction (FPSE) for the determination of doxycycline in human urine was described. The sol-gel polytetrahydrofuran sorbent proved to be superior against other sol-gel coated cellulose and polyester membranes tested. The effect of the extraction parameters including membrane surface area, sample pH and volume, salt concentration, extraction time, stirring rate, etc., on the extraction efficiency of the analyte was studied using the "one-factor-at-a-time" (OFAT) and Box-Behnken design approaches. The analytical method proposed was validated in compliance with FDA guidelines for bioanalytical procedures. The method was linear in the determination range of 100-5000 ng/mL with the determination coefficient of 0.9953. The limit of detection (LOD) and the lower limit of quantification for doxycycline was 17 and 100 ng/mL, respectively. The relative recoveries for intra-day and inter-day studies ranged from 98.5-112.2% and 89.6-96.8%, respectively. The relative standard deviation was lower than 14.7% in all cases, exhibiting good precision. The sol-gel polytetrahydrofuran-modified FPSE membranes were reusable for at least 30 times. The greenness of the developed method was evaluated using Sample Preparation Metric of Sustainability (SPMS) and Blue Applicability Grade Index (BAGI) metric tools. Finally, the analytical scheme was successfully employed for the quantitation of urinary doxycycline collected at various time points following the administration of doxycycline-containing tablets.


Asunto(s)
Doxiciclina , Furanos , Poliésteres , Humanos , Doxiciclina/orina , Doxiciclina/química , Poliésteres/química , Furanos/orina , Furanos/química , Límite de Detección , Extracción en Fase Sólida/métodos
2.
BMC Infect Dis ; 24(1): 929, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245722

RESUMEN

BACKGROUND: Brucellosis is a global public health concern and occurs mainly in young adults and the elderly, with children having a lower incidence, thus often leading to delayed treatment. This study aimed to describe the epidemiologic features and clinical characteristics of brucellosis in children. METHODS: In this retrospective study, the clinical data of five children diagnosed with brucellosis in Anhui Provincial Children's Hospital between January 1, 2021 and December 30, 2022 were analyzed. RESULTS: All five cases were from non-pastoral areas, among which three have a history of livestock exposure and originated from the countryside. All patients had medium-high grade fever, mostly accompanied by night sweats and malaise, and three had joint pains. Laboratory tests showed that their white blood cell count was normal or mildly raised, with lymphocytes as the predominant cell population. Four patients had anemia, four had aspartate aminotransferase and alanine aminotransferase abnormality, and two had elevated ferritin levels. All blood samples were positive for Brucella culture, one of which had positive bone marrow culture, and all had positive serology test results. All patients were treated with rifampicin, in combination with sulfamethoxazole or doxycycline for 6 weeks following diagnosis. Four children had a good prognosis, but one child had recurrent joint pain. CONCLUSIONS: The epidemiologic history of children from non-pastoral areas with brucellosis is often unclear; clinical manifestations and laboratory tests lack specificity; and they are easily delayed diagnosis. Clinicians should remain vigilant regarding the possibility of this disease in children with fever of unknown origin. The epidemiological history should be investigated in detail to improve the diagnostic ability of brucellosis. We recommend emphasizing serological testing. Children with brucellosis who receive timely diagnosis and standardized treatment can expect a favorable prognosis.


Asunto(s)
Antibacterianos , Brucelosis , Brucelosis/epidemiología , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Preescolar , Doxiciclina/uso terapéutico , China/epidemiología , Brucella/aislamiento & purificación , Rifampin/uso terapéutico , Sulfametoxazol/uso terapéutico , Fiebre/microbiología , Fiebre/etiología , Adolescente
3.
Virulence ; 15(1): 2399983, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39239906

RESUMEN

Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on Edwardsiella tarda ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of E. tarda to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in E. tarda, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying E. tarda resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.


Asunto(s)
Acetilcisteína , Antibacterianos , Doxiciclina , Farmacorresistencia Bacteriana , Edwardsiella tarda , Edwardsiella tarda/efectos de los fármacos , Edwardsiella tarda/genética , Doxiciclina/farmacología , Antibacterianos/farmacología , Acetilcisteína/farmacología , Especies Reactivas de Oxígeno/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Animales , Glutatión/metabolismo , Proteómica , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana
4.
BMJ Case Rep ; 17(9)2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256179

RESUMEN

In this case, a woman in her 80s presented to the emergency department with signs and symptoms of acute pancreatitis that began after starting a course of doxycycline. Common aetiologies of acute pancreatitis, including alcohol use, gallstones and hypertriglyceridaemia were ruled out. Less common aetiologies, including recent Endoscopic Retrograde Cholangiopancreatography (ERCP) procedure, hypercalcaemia, malignancy, infection and trauma, were also ruled out, making drug-induced acute pancreatitis the most likely aetiology. After consideration of her medication list, doxycycline was determined to be the offending medication. On discontinuation and treatment with fluids and analgesics, her condition slowly improved.This case illustrates a rare but severe complication of doxycycline use. Determining the aetiology of drug-induced acute pancreatitis is more difficult in older patients due to high rates of polypharmacy. Recognition of doxycycline as an aetiology of drug-induced pancreatitis may allow earlier recognition and intervention in cases of suspected pancreatitis without a clear common aetiology in older patients with polypharmacy.


Asunto(s)
Antibacterianos , Doxiciclina , Pancreatitis , Humanos , Doxiciclina/efectos adversos , Doxiciclina/uso terapéutico , Femenino , Pancreatitis/inducido químicamente , Antibacterianos/efectos adversos , Anciano de 80 o más Años , Enfermedad Aguda
5.
J Infect Dev Ctries ; 18(8): 1301-1307, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39288382

RESUMEN

INTRODUCTION: Leptospirosis and melioidosis are common in tropical and temperate climates and can be acquired by exposure to contaminated water and soil. However, concomitant leptospirosis and melioidosis infection is rarely described in the literature. We report a case of leptospirosis-melioidosis coinfection and systematically review the literature. CASE PRESENTATION: A 42-year-old male presented with fever associated with chills and rigor, dull aching pain in the right thigh, myalgia, progressive breathlessness, and dry cough for 10 days. At presentation, he was tachypneic and had tachycardia, and oxygen saturation was 46% in room air. Chest radiography and computed tomography scan showed interstitial involvement. Magnetic resonance imaging for thigh pain revealed right femur osteomyelitis. Leptospira serology was positive, and blood culture grew Burkholderia pseudomallei, confirming the diagnosis of melioidosis. Thus, a diagnosis of presumptive leptospirosis based on modified Faine's criteria and systemic melioidosis was made. He received doxycycline and intravenous meropenem and improved. RESULTS: We performed a systematic review to understand the spectrum of leptospirosis-melioidosis coinfection. We identified only nine cases of coinfection described in literature. Only one patient had septic arthritis, and our case is the only one presenting with osteomyelitis. Serology diagnosed leptospirosis, whereas melioidosis was confirmed by blood culture in most patients. The majority of coinfected patients developed some complications, and six died. CONCLUSIONS: Leptospirosis-melioidosis coinfection is rarely reported in the literature. Physicians should maintain a high index suspicion of leptospirosis-melioidosis coinfection in patients presenting with acute febrile illness following exposure to soil or freshwater, particularly in tropical and endemic regions.


Asunto(s)
Antibacterianos , Burkholderia pseudomallei , Coinfección , Leptospirosis , Melioidosis , Osteomielitis , Síndrome de Dificultad Respiratoria , Humanos , Melioidosis/complicaciones , Melioidosis/diagnóstico , Melioidosis/tratamiento farmacológico , Melioidosis/microbiología , Masculino , Adulto , Leptospirosis/complicaciones , Leptospirosis/diagnóstico , Osteomielitis/microbiología , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Coinfección/microbiología , Coinfección/diagnóstico , Antibacterianos/uso terapéutico , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/microbiología , Burkholderia pseudomallei/aislamiento & purificación , Doxiciclina/uso terapéutico , Meropenem/uso terapéutico , Meropenem/administración & dosificación
6.
BMC Nephrol ; 25(1): 291, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232673

RESUMEN

BACKGROUND: Membranoproliferative glomerulonephritis is a rare entity which can be a result from autoimmune diseases, caused by various medications and infections. CASE PRESENTATION: We herein present the case of a 62-year-old male patient who presented with fatigue and was found to have severe anemia, impaired renal function, and nephrotic syndrome. A renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) of the immune complex type with activation of the classical complement pathway. Further investigations led to the diagnosis of a chronic Coxiella burnetii-infection (Q fever), likely acquired during cycling trips in a region known for intensive sheep farming. Additionally, the patient was found to have a post endocarditic destructive bicuspid aortic valve caused by this pathogen. Treatment with hydroxychloroquine and doxycycline was administered for a duration of 24 months. The aortic valve was replaced successfully and the patient recovered completely. CONCLUSIONS: Early detection and targeted treatment of this life-threatening disease is crucial for complete recovery of the patient.


Asunto(s)
Endocarditis Bacteriana , Glomerulonefritis Membranoproliferativa , Fiebre Q , Humanos , Masculino , Fiebre Q/complicaciones , Fiebre Q/tratamiento farmacológico , Fiebre Q/diagnóstico , Glomerulonefritis Membranoproliferativa/etiología , Glomerulonefritis Membranoproliferativa/complicaciones , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Persona de Mediana Edad , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Enfermedad Crónica , Doxiciclina/uso terapéutico , Válvula Aórtica/patología , Válvula Aórtica/diagnóstico por imagen , Antibacterianos/uso terapéutico , Enfermedad de la Válvula Aórtica Bicúspide/complicaciones
7.
Front Cell Infect Microbiol ; 14: 1431141, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268484

RESUMEN

Introduction: Our work aims at establishing a proof-of-concept for a method that allows the early prediction of the bactericidal and bacteriostatic effects of antibiotics on bacteria using scanning electron microscopy (SEM) as compared to traditional culture-based methods. Methods: We tested these effects using Imipenem (bactericidal) and Doxycycline (bacteriostatic) with several strains of sensitive and resistant Escherichia coli. We developed a SEM-based predictive score based on three main criteria: Bacterial Density, Morphology/Ultrastructure, and Viability. We determined the results for each of these criteria using SEM micrographs taken with the TM4000Plus II-Tabletop-SEM (Hitachi, Japan) following an optimized, rapid, and automated acquisition and analysis protocol. We compared our method with the traditional culture colony counting gold standard method and classic definitions of the two effects. Results: Our method revealed total agreement with the CFU method and classic definition by visualizing the effect of the antibiotic at 60 minutes and 120 minutes using SEM. Discussion: This early prediction allows a rapid and early identification of the bactericidal and bacteriostatic effects as compared to culture that would take a minimum of 18 hours. This has several future applications in the development of SEM-automated assays coupled to machine learning models that identify the antibiotic effect and facilitate determination of bacterial susceptibility.


Asunto(s)
Antibacterianos , Doxiciclina , Escherichia coli , Imipenem , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana , Microscopía Electrónica de Rastreo , Antibacterianos/farmacología , Imipenem/farmacología , Doxiciclina/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/ultraestructura , Viabilidad Microbiana/efectos de los fármacos , Recuento de Colonia Microbiana
8.
BMC Ophthalmol ; 24(1): 385, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39218852

RESUMEN

BACKGROUND: Rickettsial disease has been commonly associated with retinitis, retinal vasculitis, and optic nerve involvement, but the development of retinal neovascularization has been very rarely reported. We herein describe a case of rickettsial retinitis complicated with the development of sea-fan retinal neovascularization documented with multimodal imaging, including fundus photography, SS-OCT, fluorescein angiography, and SS-OCT angiography. CASE PRESENTATION: A 26-year-old female with a history of fever one week earlier presented with sudden decreased vision in the left eye. Best-corrected visual acuity (BCVA) was 20/2000 and the patient was diagnosed with rickettsial retinitis along the superotemporal retinal vascular arcade associated with serous retinal detachment and retinal hard exudates. The indirect immunofluorescence test was positive for Rickettsia conorii, and the patient was treated with oral doxycycline (200 mg/day) and oral prednisone (0.75 mg/kg/day, with gradual tapering). Four weeks after presentation, the retinal infiltrate and associated serous retinal detachment had resolved, but retinal hard exudates had increased. A large sea-fan preretinal fibrovascular neovascularization became apparent along the superotemporal retinal vascular arcade, but there was no associated retinal ischemia on fluorescein angiography. The patient received an adjunctive single intravitreal injection of 1.25 bevacizumab. Sequential follow-up examinations showed shrinking of sea-fan retinal neovascularization, a complete resolution of retinal hard exudates, and the development of a self-limited vitreous hemorrhage. On last follow-up, 30 months after intravitreal bevacizumab injection, BCVA was 20/25. CONCLUSION: Patients with rickettsial retinitis may develop a sea-fan retinal neovascularization, with subsequent vitreous hemorrhage, putatively through inflammatory mechanisms. Multimodal imaging including OCT, fluorescein angiography, and OCT-angiography, is highly useful for accurate diagnosis and reliable monitoring of the evolution of retinitis, retinal neovascularization, and other retinal changes. The use of a combination therapy with oral doxycycline and corticosteroids and intravitreal anti-VEGF can improve outcomes.


Asunto(s)
Angiografía con Fluoresceína , Neovascularización Retiniana , Retinitis , Humanos , Femenino , Adulto , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/etiología , Retinitis/diagnóstico , Retinitis/microbiología , Retinitis/tratamiento farmacológico , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones por Rickettsia/diagnóstico , Infecciones por Rickettsia/complicaciones , Infecciones por Rickettsia/tratamiento farmacológico , Infecciones por Rickettsia/microbiología , Rickettsia conorii , Fondo de Ojo , Agudeza Visual , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Inyecciones Intravítreas , Doxiciclina/uso terapéutico , Bevacizumab/uso terapéutico
9.
J Infect ; 89(4): 106243, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142392

RESUMEN

OBJECTIVES: High rates of antibiotic prescription in residential aged care are likely to promote enteric carriage of antibiotic-resistant pathogens and increase the risk of antibiotic treatment failure. Despite their importance, relationships between antibiotic exposures and patterns of enteric resistance carriage in this population remain poorly understood. METHODS: We conducted a cross-sectional metagenomic cohort analysis of stool samples from residents of five long-term aged-care facilities in South Australia. Taxonomic composition was determined, and enteric carriage of antibiotic resistance genes (ARGs) was identified and quantified against the Comprehensive Antibiotic Resistance Database. Both the detection and abundance of stool taxa and ARGs were related to antibiotic exposures up to 12 months prior. Factors associated with the abundance of ARGs of high clinical concern were identified. RESULTS: Stool samples were provided by 164 participants (median age: 88 years, IQR 81-93; 72% female). Sixty-one percent (n = 100) of participants were prescribed antibiotics at least once in the prior 12 months (median prescriptions: 4, range: 1-52), most commonly a penicillin (n = 55, 33.5%), cephalosporin (n = 53, 32.3%), diaminopyrimidine (trimethoprim) (n = 36, 22%), or tetracycline (doxycycline) (n = 21, 12.8%). More than 1100 unique ARGs, conferring resistance to 38 antibiotic classes, were identified, including 20 ARGs of high clinical concern. Multivariate logistic regression showed doxycycline exposure to be the greatest risk factor for high ARG abundance (adjusted odds ratio [aOR]=14.8, q<0.001) and a significant contributor to inter-class selection, particularly for ARGs relating to penicillins (aOR=3.1, q=0.0004) and cephalosporins (aOR=3.4, q=0.003). High enteric ARG abundance was associated with the number of separate antibiotic exposures (aOR: 6.4, q<0.001), exposures within the prior 30 days (aOR: 4.6, q=0.008) and prior 30-100 days (aOR: 2.6, q=0.008), high duration of antibiotic exposure (aOR: 7.9, q<0.001), and exposure to 3 or more antibiotic classes (aOR: 7.4, q<0.001). Carriage of one or more ARGs of high clinical concern was identified in 99% of participants (n = 162, median: 3, IQR: 2-4), involving 11 ARGs conferring resistance to aminoglycosides, four to beta-lactams, one to glycopeptides, three to fluoroquinolones, and one to oxazolidinones. Carriage of ARGs of high clinical concern was positively associated with exposure to doxycycline (aminoglycoside, fluoroquinolone, and oxazolidinone ARGs) and trimethoprim (fluoroquinolone and beta-lactam ARGs). Analysis of doxycycline impact on microbiota composition suggested that observed resistome changes arose principally through direct ARG selection, rather than through the antibiotic depletion of sensitive bacterial populations. CONCLUSIONS: The gut microbiome of aged care residents is a major reservoir of antibiotic resistance. As a critical antibiotic in medical practice, a comprehensive understanding of the impact of doxycycline exposure on the gut resistome is paramount for informed antibiotic use, particularly in an evolving landscape of prophylactic applications. Near-universal asymptomatic carriage of clinically critical resistance determinants is highly concerning and reinforces the urgent need for improved management of antibiotic use in long-term aged care.


Asunto(s)
Antibacterianos , Doxiciclina , Heces , Humanos , Femenino , Masculino , Anciano de 80 o más Años , Doxiciclina/uso terapéutico , Doxiciclina/farmacología , Antibacterianos/farmacología , Estudios Transversales , Heces/microbiología , Farmacorresistencia Bacteriana/genética , Estudios de Cohortes , Australia del Sur/epidemiología , Anciano , Metagenómica , Portador Sano/microbiología , Portador Sano/epidemiología
11.
Praxis (Bern 1994) ; 113(6-7): 179-182, 2024 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-39166785

RESUMEN

INTRODUCTION: A hunter with a history of oncology, flu-like symptoms and ring-shaped erythema was treated with doxycycline in an outpatient setting on suspicion of a tick-borne disease. After obtaining a positive Francisella tularensis serology, antibiotic treatment was continued for a total of 21 days, followed by freedom of symptoms and falling CRP, but without prompt serological follow-up. In contrast to the previously described tularemia cases in Switzerland, the article shows less pronounced local finding without palpable lymphadenopathy.


Asunto(s)
Tularemia , Humanos , Masculino , Tularemia/diagnóstico , Tularemia/tratamiento farmacológico , Diagnóstico Diferencial , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Eritema/etiología , Gripe Humana/diagnóstico , Gripe Humana/complicaciones , Francisella tularensis/aislamiento & purificación , Persona de Mediana Edad , Suiza
12.
Biomacromolecules ; 25(9): 5968-5978, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39190052

RESUMEN

Effective drug delivery to bacterially infected mucosa remains a challenge due to the combined obstacles of the mucosal barrier, pH variations, and high concentrations of glutathione. However, polysaccharide-based responsive nanogels (NGs) can take advantage of these conditions to deliver specific antimicrobials. We explored the critical features of pH- and redox-responsive NGs to increase drug penetration, residence time, and efficacy in the infected mucosa. We prepared multifunctional NGs using hydroxypropyl cellulose as a template for the cross-linking of methacrylic acid with N,N'-bis(acryloyl)cystamine (BAC) or N,N'-methylenebis(acrylamide) (BIS). Studies of NG-mucin binding and the antibacterial efficacy of doxycycline-loaded NGs revealed the interplay between the response to pH and redox clues. Specifically, higher BAC composition increased mucus binding and controlled release in reductive conditions, while higher BIS composition yielded NGs with higher doxycycline-mediated antibacterial efficacy against Staphylococcus aureus. The findings reveal the potential of multiresponsive NGs in effective antimicrobial delivery in infected mucosa.


Asunto(s)
Nanogeles , Staphylococcus aureus , Staphylococcus aureus/efectos de los fármacos , Nanogeles/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Membrana Mucosa/metabolismo , Doxiciclina/farmacología , Doxiciclina/química , Doxiciclina/administración & dosificación , Doxiciclina/farmacocinética , Celulosa/química , Celulosa/análogos & derivados , Polietilenglicoles/química , Concentración de Iones de Hidrógeno , Portadores de Fármacos/química , Humanos
13.
PLoS Negl Trop Dis ; 18(8): e0012405, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39172763

RESUMEN

BACKGROUND: In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety. METHODS: For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331). RESULTS: Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence), Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline + Streptomycin (SUCRA values: 0.78). CONCLUSIONS: Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.


Asunto(s)
Antibacterianos , Brucelosis , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Brucelosis/tratamiento farmacológico , Humanos , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Adolescente , Niño , Estreptomicina/uso terapéutico , Rifampin/uso terapéutico , Quimioterapia Combinada
14.
Antimicrob Agents Chemother ; 68(9): e0059524, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39133023

RESUMEN

Bacillus anthracis, the causative agent of anthrax, is among the most likely bacterial pathogens to be used in a biological attack. Inhalation anthrax is a serious, life-threatening form of infection, and the mortality from acute inhaled anthrax can approach 100% if not treated early and aggressively. Food and Drug Administration-approved antibiotics indicated for post-exposure prophylaxis (PEP) or treatment of anthrax are limited. This study assessed the in vitro activity and in vivo efficacy of omadacycline and comparators against clinical isolates of B. anthracis, including a ciprofloxacin-resistant isolate. Minimum inhibitory concentrations (MICs) of omadacycline, ciprofloxacin, and doxycycline were determined against animal and human clinical isolates of B. anthracis, including the ciprofloxacin-resistant Ames strain BACr4-2. Mice were challenged with aerosolized BACr4-2 spores, and survival was monitored for 28 days post-challenge. Treatment was initiated 24 h after aerosol challenge and administered for 14 days. Omadacycline demonstrated in vitro activity against 53 B. anthracis isolates with an MIC range of ≤0.008-0.25 µg/mL, and an MIC50/MIC90 of 0.015/0.03 µg/mL. Consistent with this, omadacycline demonstrated in vivo efficacy in a PEP mouse model of inhalation anthrax caused by the Ames BACr4-2 ciprofloxacin-resistant B. anthracis isolate. Omadacycline treatment significantly increased survival compared with the vehicle control group and the ciprofloxacin treatment group. As antibiotic resistance rates continue to rise worldwide, omadacycline may offer an alternative PEP or treatment option against inhalation anthrax, including anthrax caused by antibiotic-resistant B. anthracis.


Asunto(s)
Carbunco , Antibacterianos , Bacillus anthracis , Ciprofloxacina , Pruebas de Sensibilidad Microbiana , Tetraciclinas , Ciprofloxacina/farmacología , Bacillus anthracis/efectos de los fármacos , Animales , Carbunco/tratamiento farmacológico , Carbunco/microbiología , Carbunco/mortalidad , Ratones , Antibacterianos/farmacología , Tetraciclinas/farmacología , Tetraciclinas/uso terapéutico , Femenino , Doxiciclina/farmacología , Farmacorresistencia Bacteriana , Humanos , Infecciones del Sistema Respiratorio
15.
Int J Mol Sci ; 25(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39201401

RESUMEN

Previous studies have demonstrated that when the cyclin D2 (CCND2), a cell-cycle regulatory protein, is overexpressed in human-induced pluripotent stem cells (hiPSCs), cardiomyocytes (CMs) differentiated from these CCND2-overexpressing hiPSCs can proliferate after transplantation into infarcted hearts, which significantly improves the cells' potency for myocardial regeneration. However, persistent CM proliferation could lead to tumor growth or the development of arrhythmogenic complications; thus, the goal of the current study was to generate a line of hiPSCs in which CCND2 overexpression could be tightly controlled. First, we transfected hiPSCs with vectors coding for a doxycycline-inducible Tet-On transactivator and S. pyogenes dCas9 fused to the VPR activation domain; then, the same hiPSCs were engineered to express guide RNAs targeting the CCND2 promotor. Thus, treatment with doxycycline (dox) activated dCas9-VPR expression, and the guide RNAs directed dCas9-VPR to the CCND2 promoter, which activated CCND2 expression. Subsequent experiments confirmed that CCND2 expression was dox-dependent in this newly engineered line of hiPSCs (doxCCND2-hiPSCs): CCND2 protein was abundantly expressed after 48 h of treatment with dox and declined to near baseline level ~96 h after dox treatment was discontinued.


Asunto(s)
Ciclina D2 , Doxiciclina , Células Madre Pluripotentes Inducidas , Regiones Promotoras Genéticas , Doxiciclina/farmacología , Ciclina D2/metabolismo , Ciclina D2/genética , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , ARN Guía de Sistemas CRISPR-Cas
16.
Lakartidningen ; 1212024 Aug 02.
Artículo en Sueco | MEDLINE | ID: mdl-39101261

RESUMEN

STI prophylaxis using doxycycline is discussed internationally for persons at high risk of STIs (Doxy-PEP). Doxy-PEP would probably have limited effect on gonorrhoea due to resistance to tetracyclines. Doxy-PEP may reduce the incidence of chlamydia and syphilis, but would not reduce the number of complicated infections. Further studies are needed on the effects of intermittent antibiotic use on the microbiome or antibiotic resistance in general.


Asunto(s)
Antibacterianos , Infecciones por Chlamydia , Doxiciclina , Gonorrea , Enfermedades de Transmisión Sexual , Humanos , Doxiciclina/administración & dosificación , Doxiciclina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Gonorrea/tratamiento farmacológico , Gonorrea/prevención & control , Enfermedades de Transmisión Sexual/prevención & control , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/tratamiento farmacológico , Sífilis/tratamiento farmacológico , Sífilis/prevención & control , Profilaxis Antibiótica , Farmacorresistencia Bacteriana
17.
BMC Infect Dis ; 24(1): 766, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090536

RESUMEN

BACKGROUND: Coxiella burnetii is a bacterium with extreme tenacity and contagiousness that is mainly transmitted by inhalation of contaminated aerosols. Nevertheless, a transmission by ticks is under discussion. We report a case of Q fever in an urban environment and far away from sheep breeding that caused a rare right-sided endocarditis. CASE PRESENTATION: A 55-year-old man who was in good health before the event developed a C. burnetii -endocarditis of the tricuspid valve. He had no contact with sheep and no recent travel in a rural or even endemic area. The infection originated in a strictly urban environment, and the patient's occupation as a cemetery gardener in Berlin, coupled with the close temporal and local exposure to wild boar, made a transmission by these animals a plausible hypothesis. The infection was confirmed by the German Reference Laboratory, and the patient recovered completely after treatment with doxycycline and hydrochlorquine. CONCLUSIONS: The specialities of this case report are the right-sided endocarditis and the transmission of C. burnetii in a metropolitan area without sheep contact. We think that this case should serve to increase awareness of the potential for Q fever infection even in non-rural areas.


Asunto(s)
Coxiella burnetii , Endocarditis Bacteriana , Fiebre Q , Válvula Tricúspide , Fiebre Q/transmisión , Fiebre Q/microbiología , Fiebre Q/diagnóstico , Fiebre Q/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Humanos , Válvula Tricúspide/microbiología , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/transmisión , Endocarditis Bacteriana/tratamiento farmacológico , Coxiella burnetii/aislamiento & purificación , Animales , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Ovinos
18.
Medicine (Baltimore) ; 103(32): e39268, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39121308

RESUMEN

RATIONALE: The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS. PATIENT CONCERNS: All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals. DIAGNOSES: The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS). INTERVENTIONS: Doxycycline treatment for 1 week. OUTCOMES: The patients' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal. LESSONS: By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.


Asunto(s)
Phlebovirus , Humanos , Masculino , Phlebovirus/aislamiento & purificación , Persona de Mediana Edad , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Síndrome de Trombocitopenia Febril Grave/epidemiología , China/epidemiología , Rickettsiosis Exantemáticas/diagnóstico , Rickettsiosis Exantemáticas/epidemiología , Femenino , Adulto , Doxiciclina/uso terapéutico , Enfermedades Endémicas , Errores Diagnósticos , Antibacterianos/uso terapéutico
19.
PLoS Negl Trop Dis ; 18(8): e0012313, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39102427

RESUMEN

Human granulocytotropic anaplasmosis (HGA) is a zoonotic tick-borne bacterial infection caused by Anaplasma phagocytophilum. While most cases are reported from North America, HGA has been recognized as an emerging disease in several regions of the world in recent decades. Most available data comes from case reports, case series and retrospective studies, while prospective studies and clinical trials are largely lacking. To obtain a clearer picture of the currently known epidemiologic distribution, clinical and paraclinical presentation, diagnostic aspects, complications, therapeutic aspects, and outcomes of HGA, we systematically reviewed the literature and analyzed and summarized the data. Cases of HGA are reported from all continents except from Antarctica. HGA primarily presents as an unspecific febrile illness (88.5% of the cases) often accompanied by thrombocytopenia (71.8% of the cases), abnormal liver injury tests (66.7% of the cases), and leukopenia (49.8% of the cases). Although we found complications reported in a total of 40.5% of the reviewed cases and severe and even life-threatening complications are not infrequent (e.g. acute renal failure 9.8%, multi organ failure 7.5%, ARDS 6.3%, a.o.), sequelae are rare (2.1% of the cases) and lethality is low (3.0% of the cases). Treatment with doxycycline shows a rapid response, with the fever subsiding in the majority of patients within one day of starting treatment. Unlike in human monocytotropic ehrlichiosis (HME), reports of opportunistic infections complicating HGA are rare. HGA during pregnancy does not appear to be associated with unfavorable outcomes. In addition, our analysis provides some evidence that HGA may differ in clinical aspects and laboratory characteristics in different regions of the world. Overall, the data analyzed indicates a non-negligible bias in reporting/publication, so a certain degree of caution is required when generalizing the data.


Asunto(s)
Anaplasma phagocytophilum , Humanos , Anaplasma phagocytophilum/aislamiento & purificación , Anaplasmosis/epidemiología , Anaplasmosis/tratamiento farmacológico , Anaplasmosis/microbiología , Antibacterianos/uso terapéutico , Femenino , Animales , Doxiciclina/uso terapéutico
20.
J Microbiol Methods ; 224: 107009, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39098402

RESUMEN

The present investigation aimed to quantitatively assess the level of parasitemia in dogs using qPCR.The dogs selected for this study were infected with the haemoprotozoan parasite Babesia gibsoni. In the study, dogs diagnosed with babesiosis were divided into two groups (n = 12) and subjected to distinct treatment strategies. The first group received clindamycin-metronidazole-doxycycline (CMD) therapy, while the second group was treated with a combination of buparvaquone-azithromycin (BPV-AZM). The level of parasitemia in the infected dogs was determined using an absolute quantification-based qPCR method. This assessment was conducted both prior to initiating the treatment and on the 10th day following the commencement of the treatment protocols. On the tenth day after the initiation of treatment, the CMD group exhibited a lower level of parasitemia in comparison to the BPV-AZM group. In the CMD treated groups, the mean parasitemia decreased from 4.9E + 06 to 3.4E + 06, indicating a reduction in parasitic load. Conversely, in the BPV-AZM treatment groups, the mean parasitemia increased from 1.62E + 06 to 2.87E + 06, suggesting an increase in parasitic load. On the 10th day, the CMD-treated group demonstrated a statistically significant decline in the level of parasitemia, with a P-value of ≤0.001. This indicates a strong and significant reduction in parasitic load following the CMD treatment. Therefore, the absolute quantification-based qPCR method could effectively assess the initial treatment response by measuring the level of parasitemia.


Asunto(s)
Babesia , Babesiosis , Clindamicina , Enfermedades de los Perros , Carga de Parásitos , Parasitemia , Reacción en Cadena en Tiempo Real de la Polimerasa , Animales , Perros , Enfermedades de los Perros/parasitología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Babesia/genética , Babesia/aislamiento & purificación , Parasitemia/parasitología , Parasitemia/veterinaria , Babesiosis/parasitología , Babesiosis/diagnóstico , Clindamicina/uso terapéutico , Carga de Parásitos/métodos , Doxiciclina/uso terapéutico , Azitromicina/uso terapéutico , Metronidazol/uso terapéutico , Antiprotozoarios/uso terapéutico , Naftoquinonas
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