RESUMO
OBJECTIVES: This study aimed to evaluate the biomechanical and histological effects of fluoroquinolones on surgically repaired tendon healing. MATERIALS AND METHODS: The Achilles tendons of 40 Wistar rats (mean weight: 213.5 g; range 201 to 242 g) were bilaterally surgically cut and repaired. The rats were randomly divided into four groups: the first and third groups were designated as control groups and did not receive drug therapy, whereas the second and fourth groups received 300 mg/kg ciprofloxacin for a week after the surgical procedure. The first and second groups had both tendons dissected at the end of the first week, while the third and fourth groups were dissected at the end of the third week. The left tendons were examined biomechanically, while the right tendons were examined histologically. RESULTS: Statistical analysis revealed that the mean maximum tensile forces of tendons in the first and second groups were 5.2±1.84 N (range, 2.9 to 8.5 N) and 11.1±2.65 N (range, 7.3 to 13.9 N), respectively, which was found to be statistically significant (p< 0.05). At the end of the third week, mean maximum tensile forces of the third and fourth groups were determined to be 20.7±5.0 N (range, 22.1 to 29.8 N) and 28.7±4.6 N (range, 22.1 to 36.8 N), respectively, which was also statistically significant (p< 0.05). Histologically, our results were compatible. CONCLUSION: This study demonstrated that ciprofloxacin did not exhibit the expected adverse effects on surgically repaired tendon healing in the early stages but likely contributed to healing in the short term by affecting the inflammatory phase.
Assuntos
Tendão do Calcâneo , Ciprofloxacina , Ratos Wistar , Traumatismos dos Tendões , Resistência à Tração , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/efeitos dos fármacos , Tendão do Calcâneo/patologia , Ratos , Ciprofloxacina/efeitos adversos , Ciprofloxacina/farmacologia , Resistência à Tração/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Traumatismos dos Tendões/tratamento farmacológico , Traumatismos dos Tendões/patologia , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Fenômenos Biomecânicos/efeitos dos fármacos , Masculino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/efeitos adversosRESUMO
BACKGROUND: Recently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR). METHODS: A retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals. RESULTS: Before exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48). CONCLUSIONS: The findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.
Assuntos
Insuficiência da Valva Aórtica , Estudos Cross-Over , Fluoroquinolonas , Insuficiência da Valva Mitral , Humanos , Fluoroquinolonas/efeitos adversos , Masculino , Insuficiência da Valva Mitral/induzido quimicamente , Insuficiência da Valva Mitral/epidemiologia , Feminino , Pessoa de Meia-Idade , Idoso , Insuficiência da Valva Aórtica/induzido quimicamente , Insuficiência da Valva Aórtica/epidemiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Adulto , Antibacterianos/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: The US Food and Drug Administration (FDA) issued a warning in December 2018 regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone (FQ) use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease and history of aneurysms. OBJECTIVE: To evaluate the impact of the safety warning on prescribing trends of FQs in the targeted population. METHODS: This cross-sectional study with an interrupted time series (ITS) analysis (January 2018-December 2019) used a 25% random sample of IQVIA PharMetrics® Plus for Academics health plan claims database. The impact of the warning on FQ utilisation was quantified among the targeted population and a non-targeted population. RESULTS: From 2018 to 2019, both study populations saw a decrease in the year-over-year percent change of FQ prescriptions per 100 000 beneficiaries (-11%, from 14 227 to 12 662, targeted; -15%, from 5227 to 4446, non-targeted) and proportion of FQ use versus other antibiotics (from 15.6% to 13.8%, targeted; from 9.4% to 8%, non-targeted). In the targeted population, the ITS analysis did not show a significant trend change, a change in level or postwarning trend in the monthly rate of FQ prescriptions per 1000 beneficiaries. A positive trend change was observed in the non-targeted population (0.07, <0.01-0.13), but there were no significant changes in level or post-warning trend. CONCLUSION: We did not find a change in FQ prescription rates after the warning. The utility of safety advisories as a primary tool for mitigating FQ use in high-risk populations should be revisited.
Assuntos
Antibacterianos , Aneurisma Aórtico , Dissecção Aórtica , Fluoroquinolonas , United States Food and Drug Administration , Humanos , Estados Unidos/epidemiologia , Estudos Transversais , Dissecção Aórtica/epidemiologia , United States Food and Drug Administration/estatística & dados numéricos , Aneurisma Aórtico/epidemiologia , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Análise de Séries Temporais Interrompida , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Padrões de Prática Médica/normas , Prescrições de Medicamentos/estatística & dados numéricos , AdultoRESUMO
Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.
Assuntos
Eletrocardiografia , Fluoroquinolonas , Moxifloxacina , Humanos , Adulto , Masculino , Eletrocardiografia/efeitos dos fármacos , Método Duplo-Cego , Feminino , Pessoa de Meia-Idade , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/farmacocinética , Moxifloxacina/efeitos adversos , Moxifloxacina/farmacocinética , Frequência Cardíaca/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Adulto Jovem , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Compostos Aza/efeitos adversos , Compostos Aza/farmacocinética , DesoxiadenosinasRESUMO
OBJECTIVE: Risk minimisation measures (RMM) are put in place to ensure safe and effective use of medicines. This study assessed whether RMM for five medicines are implemented in Dutch clinical guidelines. DESIGN: Descriptive study. METHOD: Dutch clinical guidelines where treatment with valproate, fluoroquinolones, methotrexate, metformin or fluorouracil was recommended were identified. In those guidelines that had been updated after publication of the RMM, we determined whether RMM-information was included in the guideline. RESULTS: Out of 50 identified guidelines recommending treatment with one of the five medicines, only 21 (42%) were revised after RMM-implementation. Of these 21 guidelines, 12 (n = 57%) included RMM-related information. CONCLUSION: Uptake of RMM information in Dutch clinical guidelines is limited and RMM-publication does not prompt guideline updates. This suggests that guidelines alone are not an optimal way to inform health care professionals of new safety warnings.
Assuntos
Guias de Prática Clínica como Assunto , Humanos , Países Baixos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Metotrexato/uso terapêutico , Metotrexato/efeitos adversos , Ácido Valproico/uso terapêutico , Ácido Valproico/efeitos adversos , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/efeitos adversos , Metformina/uso terapêutico , Metformina/efeitos adversos , Gestão de RiscosRESUMO
OBJECTIVES: Tetracyclines are the standard treatment for rickettsiosis, including Japanese spotted fever (JSF), a tick-borne rickettsiosis caused by Rickettsia japonica. While some specialists in Japan advocate combining fluoroquinolones with tetracyclines for treating JSF, the negative aspects of combination therapy have not been thoroughly evaluated. Whether fluoroquinolones should be combined with tetracyclines for JSF treatment is controversial. The study aimed to evaluate the disadvantages of fluoroquinolones combined with tetracyclines for JSF treatment. METHODS: This retrospective cohort study was conducted using a Japanese database comprising claims data from April 2008 to December 2020. The combination therapy group (tetracyclines and fluoroquinolones) was compared with the monotherapy group (tetracycline only) regarding mortality and the incidence of complications. RESULTS: A total of 797 patients were enrolled: 525 received combination therapy, and 272 received monotherapy. The adjusted odds ratio (OR) for mortality was 2.30 [95% confidence interval (CI): 0.28-18.77] in the combination therapy group with respect to the monotherapy group. According to the subgroup analysis, patients undergoing combination therapy with ciprofloxacin experienced higher mortality rates compared with those receiving monotherapy (adjusted ORâ=â25.98, 95% CIâ=â1.71-393.75). Additionally, 27.7% of the combination therapy group received NSAIDs concurrently with fluoroquinolones. The combination therapy with NSAIDs group was significantly more likely to experience convulsions than the monotherapy without NSAIDs group (adjusted OR: 5.44, 95% CI: 1.13-26.30). CONCLUSIONS: This study found no evidence that combination therapy improves mortality outcomes and instead uncovered its deleterious effects. These findings facilitate a fair assessment of combination therapy that includes consideration of its disadvantages.
Assuntos
Antibacterianos , Quimioterapia Combinada , Fluoroquinolonas , Tetraciclinas , Humanos , Estudos Retrospectivos , Feminino , Masculino , Japão , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Tetraciclinas/uso terapêutico , Tetraciclinas/administração & dosagem , Tetraciclinas/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Pessoa de Meia-Idade , Idoso , Adulto , Bases de Dados Factuais , Rickettsiose do Grupo da Febre Maculosa/tratamento farmacológico , Hospitais/estatística & dados numéricos , População do Leste AsiáticoRESUMO
Importance: Fluoroquinolone use has been associated with increased risk of uveitis and retinal detachment in noninterventional studies, but the findings have been conflicting and causality is unclear. Objective: To estimate the association of systemic fluoroquinolone use with acute uveitis or retinal detachment, using multiple analyses and multiple databases to increase the robustness of results. Design, Setting, and Participants: This cohort study used data from the Clinical Practice Research Datalink Aurum and GOLD UK primary care records databases, which were linked to hospital admissions data. Adults prescribed a fluoroquinolone or a comparator antibiotic, cephalosporin, between April 1997 and December 2019 were included. Adults with uveitis or retinal detachment were analyzed in a separate self-controlled case series. Data analysis was performed from May 2022 to May 2023. Exposures: Systemic fluoroquinolone or comparator antibiotic. Main Outcomes and Measures: The primary outcome was a diagnosis of acute uveitis or retinal detachment. Hazard ratios (HRs) were estimated in the cohort study for the association of fluoroquinolone prescription with either uveitis or retinal detachment, using stabilized inverse probability of treatment weighted Cox regression. Rate ratios (RRs) were estimated in the self-controlled case series, using conditional Poisson regression. Estimates were pooled across databases using fixed-effects meta-analysis. Results: In total, 3â¯001â¯256 individuals in Aurum (1â¯893â¯561 women [63.1%]; median [IQR] age, 51 [35-68] years) and 434â¯754 in GOLD (276â¯259 women [63.5%]; median [IQR] age, 53 [37-70] years) were included in the cohort study. For uveitis, the pooled adjusted HRs (aHRs) for use of fluoroquinolone vs cephalosporin were 0.91 (95% CI, 0.72-1.14) at first treatment episode and 1.07 (95% CI, 0.92-1.25) over all treatment episodes. For retinal detachment, the pooled aHRs were 1.37 (95% CI, 0.80-2.36) at first treatment episode and 1.18 (95% CI, 0.84-1.65) over all treatment episodes. In the self-controlled case series, for uveitis, the pooled adjusted RRs (aRRs) for fluoroquinolone use vs nonuse were 1.13 (95% CI, 0.97-1.31) for 1 to 29 days of exposure, 1.16 (95% CI, 1.00-1.34) for 30 to 59 days, and 0.98 (95% CI, 0.74-1.31) for 60 days for longer. For retinal detachment, pooled aRRs for fluoroquinolone use vs nonuse were 1.15 (95% CI, 0.86-1.54) for 1 to 29 days of exposure, 0.94 (95% CI, 0.69-1.30) for 30 to 59 days, and 1.03 (95% CI, 0.59-1.78) for 60 days or longer. Conclusions and Relevance: These findings do not support an association of systemic fluoroquinolone use with substantively increased risk of uveitis or retinal detachment. Although an association cannot be completely ruled out, these findings indicate that any absolute increase in risk would be small and, hence, of limited clinical importance.
Assuntos
Antibacterianos , Fluoroquinolonas , Descolamento Retiniano , Uveíte , Humanos , Fluoroquinolonas/efeitos adversos , Descolamento Retiniano/induzido quimicamente , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Antibacterianos/efeitos adversos , Adulto , Fatores de Risco , Idoso , Estudos Retrospectivos , Reino Unido/epidemiologia , Bases de Dados Factuais , IncidênciaRESUMO
AIM: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas. MATERIALS AND METHODS: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020). The study cohort included patients initiating either fluoroquinolones or amoxicillin while on sulphonylureas. Using an intent-to-treat exposure definition, we assessed the 30-day risk of severe hypoglycaemia (hospitalization with or death because of hypoglycaemia) associated with fluoroquinolones compared with amoxicillin. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycaemia after 1:5 matching on previous sulphonylurea use and propensity scores. Secondary analyses were stratified by demographics and glycated haemoglobin. RESULTS: Overall, 143 417 patients initiated fluoroquinolones (n = 13 123) or amoxicillin (n = 130 294) while on sulphonylureas. Compared with amoxicillin, fluoroquinolones were not associated with the risk of severe hypoglycaemia (HR, 1.17; 95% CI, 0.91-1.50). Fluoroquinolones were associated with an increased risk in patients <65 years (HR, 2.90; 95% CI, 1.41-5.97) but not in those ≥65 years (HR, 1.03; 95% CI, 0.79-1.35) in stratified analyses. There was no evidence of effect modification by sex or glycated haemoglobin. CONCLUSIONS: In patients using second-generation sulphonylureas, fluoroquinolones were not associated with an increased risk of severe hypoglycaemia compared with amoxicillin. An increased risk among younger adults is possible.
Assuntos
Diabetes Mellitus Tipo 2 , Fluoroquinolonas , Hipoglicemia , Hipoglicemiantes , Compostos de Sulfonilureia , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Compostos de Sulfonilureia/efeitos adversos , Feminino , Fluoroquinolonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Amoxicilina/efeitos adversos , Reino Unido/epidemiologia , Fatores de Risco , Adulto , Antibacterianos/efeitos adversosAssuntos
Tendão do Calcâneo , Antibacterianos , Fluoroquinolonas , Humanos , Tendão do Calcâneo/lesões , Ruptura/induzido quimicamente , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Traumatismos dos Tendões/induzido quimicamente , Administração Oral , Fatores de RiscoRESUMO
Overview of: Medicines and Healthcare products Regulatory Agency. Fluoroquinolone antibiotics: must now only be prescribed when other commonly recommended antibiotics are inappropriate. Drug Safety Update 2024;17:2.
Assuntos
Antibacterianos , Fluoroquinolonas , Fluoroquinolonas/efeitos adversos , Humanos , Antibacterianos/efeitos adversos , Estados UnidosRESUMO
BACKGROUND AND PURPOSE: A recent paradigm shift in proarrhythmic risk assessment suggests that the integration of clinical, non-clinical, and computational evidence can be used to reach a comprehensive understanding of the proarrhythmic potential of drug candidates. While current computational methodologies focus on predicting the incidence of proarrhythmic events after drug administration, the objective of this study is to predict concentration-response relationships of QTc as a clinical endpoint. EXPERIMENTAL APPROACH: Full heart computational models reproducing human cardiac populations were created to predict the concentration-response relationship of changes in the QT interval as recommended for clinical trials. The concentration-response relationship of the QT-interval prolongation obtained from the computational cardiac population was compared against the relationship from clinical trial data for a set of well-characterized compounds: moxifloxacin, dofetilide, verapamil, and ondansetron. KEY RESULTS: Computationally derived concentration-response relationships of QT interval changes for three of the four drugs had slopes within the confidence interval of clinical trials (dofetilide, moxifloxacin and verapamil) when compared to placebo-corrected concentration-ΔQT and concentration-ΔQT regressions. Moxifloxacin showed a higher intercept, outside the confidence interval of the clinical data, demonstrating that in this example, the standard linear regression does not appropriately capture the concentration-response results at very low concentrations. The concentrations corresponding to a mean QTc prolongation of 10 ms were consistently lower in the computational model than in clinical data. The critical concentration varied within an approximate ratio of 0.5 (moxifloxacin and ondansetron) and 1 times (dofetilide, verapamil) the critical concentration observed in human clinical trials. Notably, no other in silico methodology can approximate the human critical concentration values for a QT interval prolongation of 10 ms. CONCLUSION AND IMPLICATIONS: Computational concentration-response modelling of a virtual population of high-resolution, 3-dimensional cardiac models can provide comparable information to clinical data and could be used to complement pre-clinical and clinical safety packages. It provides access to an unlimited exposure range to support trial design and can improve the understanding of pre-clinical-clinical translation.
Assuntos
Fluoroquinolonas , Síndrome do QT Longo , Fenetilaminas , Sulfonamidas , Humanos , Relação Dose-Resposta a Droga , Eletrocardiografia , Fluoroquinolonas/efeitos adversos , Frequência Cardíaca , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/tratamento farmacológico , Moxifloxacina/uso terapêutico , Ondansetron/uso terapêutico , VerapamilRESUMO
PURPOSE: Consensus guidelines for hospitalized, non-severe community-acquired pneumonia (CAP) recommend empiric macrolide + ß-lactam or respiratory fluoroquinolone monotherapy in patients with no risk factors for resistant organisms. In patients with allergies or contraindications, doxycycline + ß-lactam is a recommended alternative. The purpose of this study was to compare differences in outcomes among guideline-recommended regimens in this population. METHODS: This retrospective, multicenter cohort study included patients ≥18 years of age with CAP who received respiratory fluoroquinolone monotherapy, empiric macrolide + ß-lactam, or doxycycline + ß-lactam. Major exclusion criteria included patients with immunocompromising conditions, requiring vasopressors or invasive mechanical ventilation within 48 hours of admission, and receiving less than 2 days of total antibiotic therapy. The primary outcome was in-hospital mortality. Secondary outcomes included clinical failure, 14- and 30-day hospital readmission, and hospital length of stay. Safety outcomes included incidence of new Clostridioides difficile infection and aortic aneurysm ruptures. FINDINGS: Of 4685 included patients, 1722 patients received empiric respiratory fluoroquinolone monotherapy, 159 received empiric doxycycline + ß-lactam, and 2804 received empiric macrolide + ß-lactam. Incidence of in-hospital mortality was not observed to be significantly different among empiric regimens (doxycycline + ß-lactam group: 1.9% vs macrolide + ß-lactam: 1.9% vs respiratory fluoroquinolone monotherapy: 1.5%, P = 0.588). No secondary outcomes were observed to differ significantly among groups. IMPLICATIONS: We observed no differences in clinical or safety outcomes among three guideline-recommended empiric CAP regimens. Empiric doxycycline + ß-lactam may be a safe empiric regimen for hospitalized CAP patients with non-severe CAP, although additional research is needed to corroborate these observations with larger samples.
Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Hospitalização , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Macrolídeos/uso terapêutico , Macrolídeos/efeitos adversos , beta-Lactamas/uso terapêutico , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversos , Mortalidade Hospitalar , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/efeitos adversos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Pneumonia Bacteriana/microbiologia , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Resultado do Tratamento , Estudos de Coortes , Tempo de InternaçãoRESUMO
The overuse of antibiotics in both humans and livestock has led to the antibiotic resistance phenomenon which is now considered one of the biggest problems in the modern world. Some antibiotics used to control or prevent infections in livestock poultry were registered a long time ago, and as a result, data on the possible side effects of their use, both for birds and humans, are incomplete and should be updated. An example of such an antibiotic is enrofloxacin which has been widely used in poultry since 1989. Data in recent years have begun to indicate that this antibiotic induces the process of apoptosis in diverse types of eukaryotic cells. Unfortunately, such studies have never been conducted on chicken models even though it is in poultry that this antibiotic is most commonly used. Therefore, the purpose of this work was to investigate whether enrofloxacin induces apoptosis in chicken cells of the UMNSAH/DF-1 line and to study the molecular mechanism of its action. The results of these experiments indicated that enrofloxacin induces apoptosis in chicken cells but not in human HEK-293 and PC3 cells. This induction was accompanied by changes in the morphology and size of mitochondria, the process of apoptosome formation and activation of executive caspases, which clearly indicates the role of the mitochondrial pathway in the induction of apoptosis by enrofloxacin. This study is the first to show the toxicity of enrofloxacin against chicken cells and to demonstrate the exact mechanism of its action. The results presented in this work show the need to monitor the concentration of antibiotic residues in poultry foods as well as to study their impact on public health to guarantee consumer safety and prevent the phenomenon of antibiotic resistance in bacteria.
Assuntos
Antibacterianos , Apoptose , Galinhas , Enrofloxacina , Fluoroquinolonas , Mitocôndrias , Enrofloxacina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Antibacterianos/toxicidade , Fluoroquinolonas/farmacologia , Fluoroquinolonas/toxicidade , Fluoroquinolonas/efeitos adversos , Aves Domésticas , Células HEK293 , Caspases/metabolismo , Linhagem CelularRESUMO
BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.