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Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21â¯758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87â¯025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.
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Antibacterianos , Erupciones por Medicamentos , Macrólidos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Administración Oral , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Estudios de Casos y Controles , Cefalosporinas/efectos adversos , Cefalosporinas/administración & dosificación , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Hospitalización/estadística & datos numéricos , Macrólidos/administración & dosificación , Macrólidos/efectos adversos , Nitrofurantoína/administración & dosificación , Nitrofurantoína/efectos adversos , Ontario/epidemiología , Penicilinas/administración & dosificación , Penicilinas/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Medición de Riesgo/estadística & datos numéricosRESUMEN
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.
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Tendón Calcáneo , Ciprofloxacina , Ratas Wistar , Traumatismos de los Tendones , Resistencia a la Tracción , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Tendón Calcáneo/cirugía , Tendón Calcáneo/lesiones , Tendón Calcáneo/efectos de los fármacos , Tendón Calcáneo/patología , Ratas , Ciprofloxacina/efectos adversos , Ciprofloxacina/farmacología , Resistencia a la Tracción/efectos de los fármacos , Traumatismos de los Tendones/cirugía , Traumatismos de los Tendones/tratamiento farmacológico , Traumatismos de los Tendones/patología , Antibacterianos/farmacología , Antibacterianos/efectos adversos , Fenómenos Biomecánicos/efectos de los fármacos , Masculino , Fluoroquinolonas/farmacología , Fluoroquinolonas/efectos adversosAsunto(s)
Antibacterianos , Humanos , Antibacterianos/efectos adversos , Fluoroquinolonas/efectos adversos , Polineuropatías/inducido químicamente , Masculino , Enfermedades Desmielinizantes/inducido químicamente , Femenino , Persona de Mediana Edad , Anciano , Conducción Nerviosa/efectos de los fármacosRESUMEN
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.
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Electrocardiografía , Fluoroquinolonas , Moxifloxacino , Humanos , Adulto , Masculino , Electrocardiografía/efectos de los fármacos , Método Doble Ciego , Femenino , Persona de Mediana Edad , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/farmacocinética , Moxifloxacino/efectos adversos , Moxifloxacino/farmacocinética , Frecuencia Cardíaca/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Adulto Joven , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Compuestos Aza/efectos adversos , Compuestos Aza/farmacocinética , DesoxiadenosinasRESUMEN
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.
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Insuficiencia de la Válvula Aórtica , Estudios Cruzados , Fluoroquinolonas , Insuficiencia de la Válvula Mitral , Humanos , Fluoroquinolonas/efectos adversos , Masculino , Insuficiencia de la Válvula Mitral/inducido químicamente , Insuficiencia de la Válvula Mitral/epidemiología , Femenino , Persona de Mediana Edad , Anciano , Insuficiencia de la Válvula Aórtica/inducido químicamente , Insuficiencia de la Válvula Aórtica/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología , Adulto , Antibacterianos/efectos adversos , Factores de RiesgoRESUMEN
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.
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Antibacterianos , Aneurisma de la Aorta , Disección Aórtica , Fluoroquinolonas , United States Food and Drug Administration , Humanos , Estados Unidos/epidemiología , Estudios Transversales , Disección Aórtica/epidemiología , United States Food and Drug Administration/estadística & datos numéricos , Aneurisma de la Aorta/epidemiología , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/uso terapéutico , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Análisis de Series de Tiempo Interrumpido , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Pautas de la Práctica en Medicina/normas , Prescripciones de Medicamentos/estadística & datos numéricos , AdultoRESUMEN
Given the paucity of safety data on fluoroquinolone antibiotics in pregnancy, a prospective observational cohort study was conducted in pregnant women who sought help and advice on drug use at two teratology information institutes in Japan. The primary endpoint of the study was the incidence of major congenital anomalies. The study population included pregnant women exposed to (i) fluoroquinolones (fluoroquinolone group), (ii) ß-lactams (infectious control group), or (iii) other agents considered to be nonteratogenic in humans (nonteratogenic control group) during the first trimester. The frequency of major congenital anomalies was compared across groups using a logistic regression model that adjusted for maternal age, smoking status, drinking status, facility consulted, and time of consultation. The fluoroquinolone group consisted of 411 women who had 383 children born alive. The infectious control and nonteratogenic control groups consisted of 1416 and 1482 women who had 1322 and 1401 children born alive, respectively. The incidence of major congenital anomalies was 1.5%, 2.0%, and 1.6% in the fluoroquinolone group, infectious control, and nonteratogenic control groups, respectively. Logistic regression showed that fluoroquinolone exposure is not a significant risk factor for major congenital anomalies. In conclusion, first-trimester exposure to fluoroquinolone antibiotics was not associated with increased maternal or fetal risks.
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Anomalías Inducidas por Medicamentos , Antibacterianos , Fluoroquinolonas , Resultado del Embarazo , Primer Trimestre del Embarazo , Humanos , Femenino , Embarazo , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/uso terapéutico , Japón/epidemiología , Adulto , Resultado del Embarazo/epidemiología , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Estudios Prospectivos , Incidencia , Factores de Riesgo , Bases de Datos Factuales , Exposición Materna/efectos adversos , Pueblos del Este de AsiaRESUMEN
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.
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Antibacterianos , Quimioterapia Combinada , Fluoroquinolonas , Tetraciclinas , Humanos , Estudios Retrospectivos , Femenino , Masculino , Japón , Fluoroquinolonas/uso terapéutico , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Tetraciclinas/uso terapéutico , Tetraciclinas/administración & dosificación , Tetraciclinas/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Persona de Mediana Edad , Anciano , Adulto , Bases de Datos Factuales , Rickettsiosis Exantemáticas/tratamiento farmacológico , Hospitales/estadística & datos numéricos , Pueblos del Este de AsiaRESUMEN
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.
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Guías de Práctica Clínica como Asunto , Humanos , Países Bajos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Metotrexato/uso terapéutico , Metotrexato/efectos adversos , Ácido Valproico/uso terapéutico , Ácido Valproico/efectos adversos , Fluoroquinolonas/uso terapéutico , Fluoroquinolonas/efectos adversos , Metformina/uso terapéutico , Metformina/efectos adversos , Gestión de RiesgosRESUMEN
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.
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Diabetes Mellitus Tipo 2 , Fluoroquinolonas , Hipoglucemia , Hipoglucemiantes , Compuestos de Sulfonilurea , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Compuestos de Sulfonilurea/efectos adversos , Femenino , Fluoroquinolonas/efectos adversos , Masculino , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Hipoglucemiantes/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Amoxicilina/efectos adversos , Reino Unido/epidemiología , Factores de Riesgo , Adulto , Antibacterianos/efectos adversosRESUMEN
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.
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Antibacterianos , Fluoroquinolonas , Desprendimiento de Retina , Uveítis , Humanos , Fluoroquinolonas/efectos adversos , Desprendimiento de Retina/inducido químicamente , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Uveítis/inducido químicamente , Uveítis/tratamiento farmacológico , Uveítis/diagnóstico , Antibacterianos/efectos adversos , Adulto , Factores de Riesgo , Anciano , Estudios Retrospectivos , Reino Unido/epidemiología , Bases de Datos Factuales , IncidenciaRESUMEN
Fluoroquinolones (FQs) are one of the most commonly prescribed classes of antibiotics. Although they were initially well tolerated in randomized clinical trials, subsequent epidemiological studies have reported an increased risk of threatening, severe, long-lasting, disabling and irreversible adverse effects (AEs), related to neurotoxicity and collagen degradation, such as tendonitis, Achilles tendon rupture, aortic aneurysm, and retinal detachment. This article reviews the main potentially threatening AEs, the alarms issued by regulatory agencies and therapeutic alternatives. (AU)
Las fluoroquinolonas son una de las clases de antibióticos más prescritas. Aunque inicialmente fueron bien toleradas en ensayos clínicos aleatorizados, estudios epidemiológicos posteriores han informado de un mayor riesgo de efectos adversos efectos adversos amenazantes, graves, duraderos, incapacitantes e irreversibles, relacionados con la neurotoxicidad y la degradación del colágeno, como tendinitis, rotura del tendón de Aquiles, aneurisma aórtico y desprendimiento de retina. Este artículo repasa los principales efectos adversos potencialmente amenazadores, las alarmas emitidas por las agencias reguladoras y las alternativas terapéuticas. (AU)
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Humanos , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/farmacología , Desprendimiento de Retina , Aneurisma de la Aorta , Antibacterianos , Estudios EpidemiológicosAsunto(s)
Tendón Calcáneo , Antibacterianos , Fluoroquinolonas , Humanos , Tendón Calcáneo/lesiones , Rotura/inducido químicamente , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Traumatismos de los Tendones/inducido químicamente , Administración Oral , Factores de RiesgoRESUMEN
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.
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Antibacterianos , Fluoroquinolonas , Fluoroquinolonas/efectos adversos , Humanos , Antibacterianos/efectos adversos , Estados UnidosRESUMEN
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.
Asunto(s)
Fluoroquinolonas , Síndrome de QT Prolongado , Fenetilaminas , Sulfonamidas , Humanos , Relación Dosis-Respuesta a Droga , Electrocardiografía , Fluoroquinolonas/efectos adversos , Frecuencia Cardíaca , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/tratamiento farmacológico , Moxifloxacino/uso terapéutico , Ondansetrón/uso terapéutico , VerapamiloRESUMEN
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.