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1.
Trials ; 23(1): 427, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597993

RESUMO

BACKGROUND: Inappropriate antibiotic use can cause harm and promote antimicrobial resistance, which has been declared a major health challenge by the World Health Organization. In Australian residential aged care facilities (RACFs), the most common indications for antibiotic prescribing are for infections of the urinary tract, respiratory tract and skin and soft tissue. Studies indicate that a high proportion of these prescriptions are non-compliant with best prescribing guidelines. To date, a variety of interventions have been reported to address inappropriate prescribing and overuse of antibiotics but with mixed outcomes. This study aims to identify the impact of a set of sustainable, multimodal interventions in residential aged care targeting three common infection types. METHODS: This protocol details a 20-month stepped-wedge cluster-randomised trial conducted across 18 RACFs (as 18 clusters). A multimodal multi-disciplinary set of interventions, the 'AMS ENGAGEMENT bundle', will be tailored to meet the identified needs of participating RACFs. The key elements of the intervention bundle include education for nurses and general practitioners, telehealth support and formation of an antimicrobial stewardship team in each facility. Prior to the randomised sequential introduction of the intervention, each site will act as its own control in relation to usual care processes for antibiotic use and stewardship. The primary outcome for this study will be antibiotic consumption measured using defined daily doses (DDDs). Cluster-level rates will be calculated using total occupied bed numbers within each RACF during the observation period as the denominator. Results will be expressed as rates per 1000 occupied bed days. An economic analysis will be conducted to compare the costs associated with the intervention to that of usual care. A comprehensive process evaluation will be conducted using the REAIM Framework, to enable learnings from the trial to inform sustainable improvements in this field. DISCUSSION: A structured AMS model of care, incorporating targeted interventions to optimise antimicrobial use in the RACF setting, is urgently needed and will be delivered by our trial. The trial will aim to empower clinicians, residents and families by providing a robust AMS programme to improve antibiotic-related health outcomes. TRIAL REGISTRATION: US National Library of Medicine Clinical Trials.gov ( NCT04705259 ). Prospectively registered in 12th of January 2021.


Assuntos
Anti-Infecciosos , Gestão de Antimicrobianos , Idoso , Antibacterianos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Gestão de Antimicrobianos/métodos , Austrália , Humanos , Prescrição Inadequada/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
N Engl J Med ; 386(18): 1721-1731, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35353979

RESUMO

BACKGROUND: The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear. METHODS: We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 µg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization. RESULTS: A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events. CONCLUSIONS: Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).


Assuntos
Anti-Infecciosos , COVID-19 , Ivermectina , Adulto , Assistência Ambulatorial , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Teorema de Bayes , COVID-19/tratamento farmacológico , Método Duplo-Cego , Hospitalização , Humanos , Ivermectina/efeitos adversos , Ivermectina/uso terapêutico , SARS-CoV-2 , Resultado do Tratamento
4.
J Nanobiotechnology ; 20(1): 151, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35307031

RESUMO

BACKGROUND: The absence of an effective treatment and vaccine in HIV-1 pandemic place preventive strategies such as safety and effective microbicide development as a central therapeutic approach to control HIV-1 pandemic nowadays. RESULTS: Studies of cytotoxicity, immune population status, inflammation or tissue damage and mainly prophylactic inhibition of HIV-1 infection in vaginal human explants demonstrate the biosafety and effectivity of G2-S16 dendrimer. Human explants treated with G2-S16 dendrimer or treated and HIV-1 infected do not presented signs of irritation, inflammation, immune activation or T cell populations deregulation. CONCLUSIONS: Herein we conclude that G2-S16 dendrimer has demonstrated sufficient efficacy, biosafety, effectivity and behavior in the closest to the real-life condition model represented by the human healthy donor vaginal tissue explants, to raise G2-S16 dendrimer as a promising candidate to clinical trials to develop an effective microbicide against HIV-1 infection.


Assuntos
Anti-Infecciosos , Dendrímeros , Anti-Infecciosos/efeitos adversos , Dendrímeros/efeitos adversos , Feminino , HIV-1 , Humanos , Vagina
5.
Int J Clin Pharm ; 44(2): 557-563, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35157228

RESUMO

Background In the Netherlands, home treatment with intravenous antimicrobial therapy is a relatively new concept. Although several studies have shown that outpatient parenteral antimicrobial therapy (OPAT) can be administered safely, people receiving antimicrobials at home remain at risk for adverse events, including readmission. Aim The aim of our retrospective study was to identify risk factors for readmission in patients discharged with OPAT. Method Patients who were at least 18 years or older, discharged with OPAT between January 2016-December 2018 were included. Variables that were collected consisted of baseline demographics, complications, readmission within 30 days and treatment failure. Multivariate logistic regression analysis was performed to identify risk factors for readmission. Results A total of 247 patients were included; the most common reason for OPAT was bone and joint infections (17%). Penicillin (37%), cephalosporin (26%) and vancomycin/aminoglycoside (15%) were the most commonly prescribed antimicrobials. Among patients receiving medication subject to therapeutic drug monitoring (i.e. aminoglycosides or vancomycin), 51% (19/37) received weekly therapeutic drug monitoring. Receiving aminoglycosides or vancomycin (adjusted OR 2.05; 95% CI 1.30-3.25, p < 0.05) and infection of prosthetic material (adjusted OR 2.92, 95% CI 1.11-7.65, p < 0.05) were independent risk factors associated with readmission. Conclusion Although patients receiving medication subject to therapeutic drug monitoring are at higher risk of readmission, only half of the patients discharged with aminoglycosides or vancomycin were monitored according to IDSA guidelines. A specialized team in charge of monitoring patients with OPAT is more likely to increase the rate of monitoring to prevent readmissions and complications.


Assuntos
Anti-Infecciosos , Readmissão do Paciente , Assistência Ambulatorial/métodos , Aminoglicosídeos , Antibacterianos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Humanos , Infusões Parenterais , Pacientes Ambulatoriais , Estudos Retrospectivos , Fatores de Risco , Vancomicina/efeitos adversos
6.
Oxid Med Cell Longev ; 2022: 6025900, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154569

RESUMO

The use of phytochemicals is gaining interest for the treatment of metabolic syndromes over the synthetic formulation of drugs. Senna is evolving as one of the important plants which have been vastly studied for its beneficial effects. Various parts of Senna species including the root, stem, leaves, and flower are found rich in numerous phytochemicals. In vitro, in vivo, and clinical experiments established that extracts from Senna plants have diverse beneficial effects by acting as a strong antioxidant and antimicrobial agent. In this review, Senna genus is comprehensively discussed in terms of its botanical characteristics, traditional use, geographic presence, and phytochemical profile. The bioactive compound richness contributes to the biological activity of Senna plant extracts. The review emphasizes on the in vivo and in vitro antioxidant and anti-infectious properties of the Senna plant. Preclinical studies confirmed the beneficial effects of the Senna plant extracts and its bioactive components in regard to the health-promoting activities. The safety, side effects, and therapeutic limitations of the Senna plant are also discussed in this review. Additional research is necessary to utilize the phenolic compounds towards its use as an alternative to pharmacological treatments and even as an ingredient in functional foods.


Assuntos
Anti-Infecciosos/efeitos adversos , Antioxidantes/efeitos adversos , Compostos Fitoquímicos/efeitos adversos , Extratos Vegetais/efeitos adversos , Plantas Medicinais/química , Senna (Planta)/química , Animais , Etnofarmacologia/métodos , Humanos , Medicina Tradicional/efeitos adversos , Fitoterapia/efeitos adversos , Componentes Aéreos da Planta/química , Raízes de Plantas/química
7.
Neurogastroenterol Motil ; 34(2): e14277, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34662472

RESUMO

BACKGROUND: This study investigated the antidiarrheal potential of the aqueous extract (AECR) and hydroalcoholic extract of Campomanesia reitziana leaves (HECR), its ethyl acetate (EAF) and dichloromethane fractions (DCMF), and myricitrin isolated from EAF. METHODS: The total phenols and flavonoids were measured, followed by chromatography and myricitrin isolation. The 2,2-diphenyl-1-picryl-hydrazyl scavenger activity, the cytotoxicity, and the effects on LPS-induced nitrite production in intestinal epithelial cells (IEC-6) were quantified. The effect of HECR, EAF, DCMF, and AECR on intestinal motility (IT), gastric emptying (GE), and castor oil-induced diarrhea in mice was determined, as well as its antimicrobial activity. KEY RESULTS: The administration of AECR 10% (10 ml/kg, p.o), but not HECR (300 mg/kg), reduced the GE and IT by 52 and 51%. The EAF and DCMF at 300 mg/kg also reduced IT but did not change GE. Moreover, AECR and EAF, but not DCMF, inhibited the castor oil-induced diarrhea and naloxone or metoclopramide pretreatment did not change these effects. Myricitrin did not change IT and the evacuation index of mice. Finally, the dry residue of AECR inhibited bacterial growth and EAF showed bacteriostatic activity against S. aureus, E. coli, and S. typhimurium and antifungal for C. albicans. However, none of the preparations alter the viability of Giardia spp. trophozoites. CONCLUSIONS: The AECR and EAF can be effective to treat diarrhea acting through opioid- or dopaminergic type 2 receptor-independent mechanisms and by its antimicrobial actions.


Assuntos
Anti-Infecciosos , Óleo de Rícino , Analgésicos Opioides/efeitos adversos , Animais , Anti-Infecciosos/efeitos adversos , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Óleo de Rícino/toxicidade , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Escherichia coli , Motilidade Gastrointestinal , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Staphylococcus aureus
8.
Eur J Med Genet ; 65(1): 104388, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34768013

RESUMO

Cockayne syndrome (CS) is a rare autosomal recessive genetic disorder characterized by growth failure and progressive multisystem dysfunction caused by deficient nucleotide excision repair. Whereas metronidazole (MTZ) hepatotoxicity is quite rare in the general population, cases of severe hepatic reaction to MTZ have been reported in CS patients. We report here the case of a 21-year-old CS patient who presented with jaundice following one week of treatment with MTZ combined with spiramycin for dental care. This case is the first one documented with a liver biopsy. Histopathological analysis revealed portal and lobular inflammation with predominance of neutrophils, ballooning degeneration and severe cholestasis without bile duct damage. The outcome was marked by regression of jaundice over 6 weeks. Analysis of this case highlights the probable responsibility of MTZ and adds support to the recommendation to strictly avoid the prescription of this drug in CS patients.


Assuntos
Anti-Infecciosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Síndrome de Cockayne , Metronidazol/efeitos adversos , Adulto , Doença Hepática Induzida por Substâncias e Drogas/patologia , Síndrome de Cockayne/patologia , Humanos , Icterícia/induzido quimicamente , Icterícia/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Adulto Jovem
9.
J Patient Saf ; 18(1): e217-e224, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569099

RESUMO

OBJECTIVES: Sulfonylureas, the second most common oral diabetes treatment, have interactions with antimicrobials that substantially increase the risk of hypoglycemia. The objectives of this study are to quantify the concurrent use of sulfonylureas and interacting antimicrobial in U.S. ambulatory care and to examine whether interacting antimicrobials are used for an appropriate indication. METHODS: We analyzed the 2006-2016 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual probability samples of visits to U.S. office-based physicians. We determined nationally representative estimates of visits for adults with concurrent use of sulfonylureas and 7 antimicrobials with established interactions. We examined whether visit diagnoses included appropriate indications for antibiotics according to national guidelines. RESULTS: There were 2.5 million visits per year (95% confidence interval [CI] 2.2-2.9) in which sulfonylureas were used with systemic antimicrobials, of which 1 million (95% CI, 0.8-1.2) or 38.0% (95% CI, 32.3%-44.0%) were interacting antimicrobials. Sulfonylurea users had similar odds of interacting antimicrobial use as patients using diabetes medications without antimicrobial interactions (adjusted odds ratio, 1.07; 95% CI, 0.82-1.40). The most common interacting antimicrobials used with sulfonylureas were fluoroquinolones, accounting for 59.9% (95% CI, 50.7%-68.2%) of antimicrobials, and sulfamethoxazole-trimethoprim, accounting for 21.1% (95% CI, 14.8%-29.2%). There was no appropriate antibiotic indication in 69.7% (95% CI, 55.2%-81.1) of visits with interacting antibiotic use. CONCLUSIONS: Sulfonylureas and antimicrobials with potentially hazardous interactions are frequently used together. To reduce resultant hypoglycemic events, there is a need for interventions to increase physician awareness and promote antibiotic stewardship.


Assuntos
Anti-Infecciosos , Hipoglicemia , Adulto , Anti-Infecciosos/efeitos adversos , Interações Medicamentosas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Compostos de Sulfonilureia/efeitos adversos , Estados Unidos
10.
Biomed Res Int ; 2021: 1401945, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917680

RESUMO

OBJECTIVE: Mangifera indica Linn, Bridelia ferruginea Benth, and Alstonia boonei De Wild are three plants commonly used in the traditional treatment of urinary tract infections in Benin. This study sets out to assess the cytotoxic and teratogenic effects of extracts of these plants on Artemia salina larvae and hen embryos. METHODS AND RESULTS: The aqueous and ethanolic extracts were obtained by maceration of the powders in solvents. Larval cytotoxicity was performed on Artemia salina larvae. The teratogenic effect of these plants was evaluated on chick embryos at 100 mg/kg and 300 mg/kg. The extracts were injected on the 7th and 14th days of incubation. The quality of the hatched chicks was evaluated by the Tona score followed by the hematological and the biochemical parameter assays. The extracts did not show cytotoxicity on the larvae. The eggs treated with plant extracts at 300 mg/kg significantly lowered the hatchability rate, except for the Mangifera indica Linn. The chicks obtained were all at the very good quality. Then, no significant variation was observed between hematological parameters except white blood cells. For the biochemical parameters, only ASAT showed some significant variations for a few extracts. It would be important to assess the genotoxicity of the plant extracts to determine more broader toxicity. These data justify the use of these medicinal plants in traditional Beninese medicine and constitute in fact a source of production of anti-infectious drugs.


Assuntos
Larva/efeitos dos fármacos , Medicina Tradicional/efeitos adversos , Plantas Medicinais/efeitos adversos , Plantas Medicinais/química , Teratogênese/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacologia , Benin , Embrião de Galinha , Galinhas , Leucócitos/efeitos dos fármacos , Mangifera/química , Testes de Mutagenicidade/métodos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia
12.
Front Immunol ; 12: 748019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691059

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for patients with hematological malignancies. Acute Graft versus host diseases (GVHD) is a major immune mediated side effect of allo-HCT that can affect the central nervous system (CNS) in addition to post-allo-HCT vascular events, drug toxicity or infections. Here we summarize and discuss recent preclinical data on the CNS as a target of acute GVHD and the known mechanisms contributing to neurotoxicity with a focus on microglia and T cells. We also discuss open questions in the field and place the findings made in mouse models in a clinical context. While in mice the neurological deficits can be assessed in a controlled fashion, in patients the etiology of the CNS damage is difficult to attribute to acute GVHD versus infections, vascular events, and drug-induced toxicity. Ultimately, we discuss novel therapies for GVHD of the CNS. Our understanding of the biological mechanisms that lead to neurotoxicity after allo-HCT increased over the last decade. This review provides insights into CNS manifestations of GVHD versus other etiologies of CNS damage in mice and patients.


Assuntos
Doenças do Sistema Nervoso Central/etiologia , Infecções do Sistema Nervoso Central/imunologia , Sistema Nervoso Central/efeitos dos fármacos , Transtornos Cerebrovasculares/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Aloenxertos/imunologia , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/imunologia , Infecções do Sistema Nervoso Central/tratamento farmacológico , Transtornos Cerebrovasculares/imunologia , Modelos Animais de Doenças , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Camundongos , Primatas , Linfócitos T/imunologia , Linfócitos T/transplante
14.
Respir Res ; 22(1): 243, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526011

RESUMO

BACKGROUND: The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. METHODS: We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). RESULTS: Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI - 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI - 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). CONCLUSIONS: In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.


Assuntos
Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Quimioterapia Combinada/efeitos adversos , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/diagnóstico , Gastroenteropatias/mortalidade , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Mortalidade/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
15.
Int J Biol Macromol ; 191: 405-413, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34547316

RESUMO

This study aimed to develop polysaccharide-based emulsions incorporated with lavender essential oil and their application on cellulosic support for patches obtaining. The lavender essential oil has been added to emulsions as an active compound mainly due to its antimicrobial properties. In this study, emulsions were used to deliver active ingredients (lavender essential oil). The chemical composition of essential oil was analyzed using gas chromatography-mass spectrometry (GC/MS). A total of seven emulsions (RiACL) were evaluated by determining rheological parameters and microbiological analysis. One of the emulsions (R7ACL) was applied to cellulosic support to obtain non-irritating textiles with controlled release of the active compound and moisturizing effects. Obtained cellulosic support was analyzed in terms of active compound controlled release, toxicity and antimicrobial testing, and skin analysis in healthy volunteers. It was found that the cellulosic supports treated with O/W emulsions are non-irritating, have softness and moisturizing effects, and can be used safely in topical applications for patches obtaining.


Assuntos
Celulose/química , Lavandula/química , Óleos Voláteis/química , Pele/efeitos dos fármacos , Adolescente , Adulto , Idoso , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Emulsões/efeitos adversos , Emulsões/química , Emulsões/farmacologia , Humanos , Pessoa de Meia-Idade , Staphylococcus aureus/efeitos dos fármacos , Têxteis/normas
16.
BMC Urol ; 21(1): 133, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535099

RESUMO

BACKGROUND: Drug-induced urolithiasis falls into two categories: drug-induced and metabolically-induced. Certain antimicrobials are associated with each; sulfonamides are associated with drug- or metabolite-containing calculi when taken in large doses over a long period of time. Trimethoprim-sulfamethoxazole, a member of the sulfonamide family, is a rare cause of drug-induced calculi. Cases of sulfonamide urolithiasis occurring in patients with known stone disease have rarely been reported. CASE PRESENTATION: We report a case of a patient with a brief history of recurrent calcium oxalate nephrolithiasis requiring 2 ureteroscopic procedures whose existing 6 mm lower pole renal stone more than quadrupled in size to form a 4 cm renal staghorn after 4 months of high-dose treatment for Nocardia pneumonia with trimethoprim-sulfamethoxazole. After ureteroscopy with laser lithotripsy and basketing of fragments, the stone was found to be predominantly composed of N4-acetyl-sulfamethoxazole, a metabolite of sulfamethoxazole. CONCLUSION: Stones composed of sulfamethoxazole or its metabolites are rare but have known associated risk factors that should be considered when prescribing this antibiotic. This case report illustrates additional risk factors for consideration, including pre-existing urinary calculi that may serve as a nidus for sulfamethoxazole deposition, and reviews treatment and prevention methods.


Assuntos
Anti-Infecciosos/efeitos adversos , Cálculos Renais/induzido quimicamente , Sulfametoxazol/efeitos adversos , Anti-Infecciosos/análise , Feminino , Humanos , Cálculos Renais/química , Pessoa de Meia-Idade , Sulfametoxazol/análise
18.
BMC Pharmacol Toxicol ; 22(1): 47, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462002

RESUMO

BACKGROUND: Acute kidney injury (AKI) is associated with significant increases in short- and long-term morbidity and mortality. Drug-induced AKI is a major concern in the present healthcare system. Our spontaneous reporting system (SRS) analysis assessed links between AKI, along with patients' age, as healthcare-associated risks and administered anti-infectives. We also generated anti-infective-related AKI-onset profiles. METHOD: We calculated reporting odds ratios (RORs) for reports of anti-infective-related AKI (per Medical Dictionary for Regulatory Activities) in the Japanese Adverse Drug Event Report database and evaluated the effect of anti-infective combination therapy. The background factors of cases with anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were matched using propensity score. We evaluated time-to-onset data and hazard types using the Weibull parameter. RESULTS: Among 534,688 reports (submission period: April 2004-June 2018), there were 21,727 AKI events. The reported number of AKI associated with glycopeptide antibacterials, fluoroquinolones, third-generation cephalosporins, triazole derivatives, and carbapenems were 596, 494, 341, 315, and 313, respectively. Crude RORs of anti-infective-related AKI increased among older patients and were higher in anti-infective combination therapies [anti-infectives, ≥ 2; ROR, 1.94 (1.80-2.09)] than in monotherapies [ROR, 1.29 (1.22-1.36)]. After propensity score matching, the adjusted RORs of anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were 0.67 (0.58-0.77) and 1.49 (1.29-1.71), respectively. Moreover, 48.1% of AKI occurred within 5 days (median, 5.0 days) of anti-infective therapy initiation. CONCLUSION: RORs derived from our new SRS analysis indicate potential AKI risks and number of administered anti-infectives.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Anti-Infecciosos/efeitos adversos , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Farmacovigilância , Adulto Jovem
19.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445180

RESUMO

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC-MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.


Assuntos
Anti-Infecciosos/efeitos adversos , Dapsona/efeitos adversos , Endometriose/induzido quimicamente , Glycyrrhiza , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Adulto , Antioxidantes/uso terapêutico , Endometriose/prevenção & controle , Eritrócitos/efeitos dos fármacos , Feminino , Glycyrrhiza/química , Humanos , Estresse Oxidativo/efeitos dos fármacos , Adulto Jovem
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