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Buisson M, Faure PA, Lafon Desmurs B, Loiez C, Valentin B, Migaud H, Senneville E. Is there a cardiovascular risk associated with the use of fluoroquinolones for the treatment of osteoarticular infections? Analysis of a retrospective cohort of 817 patients from a surgical and infectious disease referral center (CRIOAC). Orthop Traumatol Surg Res 2025:104242. [PMID: 40216326 DOI: 10.1016/j.otsr.2025.104242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 04/05/2025] [Accepted: 04/07/2025] [Indexed: 04/14/2025]
Abstract
INTRODUCTION Bone joint infection is a rare but serious complication, the treatment of which most often requires intervention combined with prolonged high-dose antibiotic therapy. Fluoroquinolones are among the standard antibiotics for the treatment of these infections, particularly in combination with rifampicin for staphylococcal infections and as monotherapy for Gram-negative bacilli infections. However, recent studies, confirmed by several meta-analyses, have highlighted an increased cardiovascular risk such as aortic aneurysm and mitro-aortic regurgitation occurring early following fluoroquinolone use, leading to recommendations for caution from health agencies. These meta-analyses are often based on limited series with numerous indication biases (variable treatment durations) and low doses. We therefore conducted a single-center, single-prescriber, real-life study of a continuous series of osteo-articular infections. The objectives were to determine the rate of cardiovascular events (aortic aneurysm, mitro-aortic regurgitation) at 60 days, the mortality rate at 60 days, and at the final follow-up. HYPOTHESIS Our hypothesis was that despite long-term, high-dose treatments, there was no increased cardiovascular risk in patients treated for osteo-articular infections with fluoroquinolones. MATERIALS AND METHODS Between 2017 and 2019, 817 patients were treated at the CRIOAC (Referral Center for Complex Osteo-Articular Infections) Lille-Tourcoing (332/817 patients received treatment with fluoroquinolones). This retrospective cohort study assessed the onset or worsening of cardiovascular events (such as aortic aneurysms and mitro-aortic regurgitation) and death at 2 months using a propensity score. RESULTS After propensity score weighting, there was no significant difference in the risk of aortic aneurysm and mitro-aortic regurgitation at 60 days (Odds ratio (OR) 0.921 [0.317; 2.673], p = 0.879) or in the risk of death at 60 days (OR 1.252 [0.502; 3.118]; p = 0.630). There was also no significant difference in the risk of death at last follow-up after propensity score weighting (OR 1.011 [0.646; 1.582], p = 0.962). DISCUSSION The results of this study suggest that the use of fluoroquinolones in patients treated for osteoarticular infections does not pose a significant increased risk of aortic aneurysm, mitro-aortic regurgitation, or death within two months. We believe it is reasonable to continue prescribing fluoroquinolones for osteoarticular infections while maintaining surveillance for these events. LEVEL OF EVIDENCE III; case-control study with propensity score.
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Affiliation(s)
- Malo Buisson
- Université Lille-Hauts de France, Service Orthopédie, Centre Hospitalier Roger Salengro, rue Emile Laine, 59000 Lille, France; Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France.
| | - Philippe-Alexandre Faure
- Université Lille-Hauts de France, Service Orthopédie, Centre Hospitalier Roger Salengro, rue Emile Laine, 59000 Lille, France; Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France
| | - Barthelemy Lafon Desmurs
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing 155 rue du Président Coty, 59208 Tourcoing, France
| | - Caroline Loiez
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, Service de Microbiologie du CHU de Lille 2 avenue Oscar Lambrey, 59037 Lille, France
| | - Benjamin Valentin
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, Service de Pharmacie Clinique, Pharmacie, CHU de Lille, 59000 Lille, France
| | - Henri Migaud
- Université Lille-Hauts de France, Service Orthopédie, Centre Hospitalier Roger Salengro, rue Emile Laine, 59000 Lille, France; Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France
| | - Eric Senneville
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing 155 rue du Président Coty, 59208 Tourcoing, France
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Mitrani-Gold FS, Ju S, Drysdale M, Schultze A, Mu G, Logie J. Risk of collagen-related disorders and neurological events among patients with uncomplicated urinary tract infection following short treatment with fluoroquinolones: a cohort study. Antimicrob Agents Chemother 2024; 68:e0069024. [PMID: 39470200 PMCID: PMC11619313 DOI: 10.1128/aac.00690-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 09/18/2024] [Indexed: 10/30/2024] Open
Abstract
Studies of fluoroquinolone (FQ) safety across indications show increased collagen/neurological adverse event (AE) risk, yet patients still receive FQs for uncomplicated urinary tract infections (uUTIs). This retrospective, cohort study investigated the risk of collagen/neurological AEs of special interest (AESIs) with short-term FQ use versus standard-of-care antibiotics (trimethoprim-sulfamethoxazole [SXT], nitrofurantoin [NTF]) among female outpatients with uUTIs. This study was conducted between December 2009 and 2019 using Optum's de-identified Clinformatics Data Mart Database. Adjusted absolute risks were calculated for composite/collagen/neurological AESIs (Kaplan-Meier cumulative hazards, after applying stabilized inverse probability of treatment weighting [sIPTW]). Adjusted hazard ratios were generated (sIPTW Cox proportional hazard modeling). Overall, 954,777 patients were included: FQ (n = 386,537 [40.5%]); SXT (n = 237,120 [24.8%]); NTF (n = 314,585 [32.9%]). Adjusted absolute risk range for collagen/neurological AESIs was <1%-4.5%. The hazard (95% CI) of tendon rupture was 25% higher with FQ versus SXT (1.25 [1.00-1.57]; P = 0.0497). Patients receiving FQ had lower hazard of neurological (0.95 [0.93-0.97]; P < 0.0001), central nervous system (0.85 [0.80-0.89]; P < 0.0001), and peripheral nervous system (0.96 [0.93-0.98]; P = 0.0016) AESIs versus NTF. Following a short treatment duration, FQs were associated with increased risk of tendon rupture versus SXT and reduced risk (adjusted hazard ratios) of neurological AESI versus NTF. Individual patient risk and consequences for known uncommon, yet serious, AEs need to inform appropriate antibiotic choice in treating uUTIs. Patient profile, efficacy, microbiome impact, safety, and surveillance should inform antibiotic selection for uUTI management, in accordance with guidelines.
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Affiliation(s)
| | | | - Myriam Drysdale
- London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Anna Schultze
- London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - George Mu
- GSK, Collegeville, Pennsylvania, USA
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Wang LZ, Oehmichen B, Pariente B, Mohamedi N, Cheng C, Detriche G, Galloula A, Lilo Le Louet A, Messas E, Amar L, Goudot G, Mirault T. Fluoroquinolone Use Preceding Visceral Artery Dissection: A Case Series. Angiology 2024; 75:992-997. [PMID: 37855079 DOI: 10.1177/00033197231207945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2023]
Abstract
Fluoroquinolones (FQ), commonly prescribed antibiotics, may trigger aortic and carotid dissections. We report three successive cases of visceral artery dissection: one patient with celiac trunk dissection and two with dissection of the superior mesenteric artery. These events occurred up to 4 months after 7 to 14 days of FQ treatment (2 cases of ofloxacin, 1 of norfloxacin). There was no other apparent cause of dissection. These dissections were isolated, apart from a minimal aortic dissection separate from the visceral arterial dissection in one case. A case series cannot certify the relationship between dissection and FQ, but it can be hypothesized. The association between fluoroquinolone use and higher occurrence of aneurysm and dissection remains discussed in aortic syndrome. The potential link between FQ and visceral artery dissection is even less described but should be reported in the absence of previous cases in the literature. The pathophysiological theory is the induction of overexpression of some matrix metalloproteinases and a decrease of their inhibitors, provoking a dysregulation in collagen synthesis and degradation of the extracellular matrix.
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Affiliation(s)
- Louise Z Wang
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
| | - Boris Oehmichen
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
| | - Benjamin Pariente
- Hypertension Center, Georges Pompidou European Hospital, APHP, Paris, France
| | - Nassim Mohamedi
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
| | - Charles Cheng
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
| | - Grégoire Detriche
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
| | - Alexandre Galloula
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
| | - Agnès Lilo Le Louet
- Pharmacovigilance Center, Georges Pompidou European Hospital, APHP, Paris, France
| | - Emmanuel Messas
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
- Université Paris Cité, INSERM U970 PARCC, Paris, France
| | - Laurence Amar
- Hypertension Center, Georges Pompidou European Hospital, APHP, Paris, France
- Université Paris Cité, INSERM U970 PARCC, Paris, France
| | - Guillaume Goudot
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
- Université Paris Cité, INSERM U970 PARCC, Paris, France
| | - Tristan Mirault
- Vascular Medicine Department, Georges Pompidou European Hospital, APHP, Paris, France
- Université Paris Cité, INSERM U970 PARCC, Paris, France
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Yang M, Wang M, Zhou J, Wang T, Liu F, Li P, Li S, Zhang L, Liu Q. Establishment of metrological traceability for fluoroquinolones measurement in monitoring plan of quality and safety for agro-product in China. Microchem J 2022. [DOI: 10.1016/j.microc.2022.107315] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Nikol S, Nikol L. Update Aortenerkrankungen. AKTUELLE KARDIOLOGIE 2022. [DOI: 10.1055/a-1746-8079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungDie vorliegende Arbeit berichtet über die neuesten wissenschaftlichen Erkenntnisse im Zusammenhang mit Aortenaneurysmen und -dissektionen. Schwerpunkt hierbei sind die Pathophysiologie und
Genetik, der Einfluss von Fluorochinolonen auf Aortenaneurysmen und -dissektionen sowie Marker der Aortitis. Ferner werden die wichtigsten aktuellen Leitlinienempfehlungen aus den Jahren
2017 bis 2020 zusammengefasst – der Fokus liegt hierbei auf dem Screening, der Diagnostik, den Grenzwerten für die Therapieindikationen, der Art und den technischen Details der Behandlung
sowie Nachsorge von Aneurysmen der Aorta ascendens, des Aortenbogens, der Aorta descendens und abdominalis, Penetrating aortic Ulcers, bei genetisch bedingten Bindegewebserkrankungen mit
Aortenbeteiligungen, Aortitis und mykotischen Aneurysmen.
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Affiliation(s)
- Sigrid Nikol
- Klinische und Interventionelle Angiologie, Asklepios Kliniken Hamburg GmbH, Hamburg, Deutschland
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Pena RCF, Hofmann Bowman MA, Ahmad M, Pham J, Kline-Rogers E, Case MJ, Lee J, Eagle K. An assessment of the current medical management of thoracic aortic disease: A patient-centered scoping literature review. Semin Vasc Surg 2022; 35:16-34. [PMID: 35501038 DOI: 10.1053/j.semvascsurg.2022.02.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/11/2022] [Accepted: 02/11/2022] [Indexed: 11/11/2022]
Abstract
Thoracic aortic aneurysm and dissection are complex diagnoses that require management by multidisciplinary providers using a variety of medical therapies, surgical interventions, and lifestyle modifications. Pharmacological agents, such as β-blockers (atenolol) and angiotensin II type 1 receptor blockers (losartan), have been mainstay treatments for several years, and research from the past decade has continued to evaluate these and other medication classes to further improve patient morbidity and mortality. Combination β- and renin-aldosterone-angiotensin blockade, statins, metformin, antioxidants, and vitamins have been evaluated as therapeutics in both thoracic and abdominal aortic aneurysms, as well as the effects of various antibiotics (ie, fluoroquinolones and tetracyclines) and benefits of lifestyle modifications (eg, diet and exercise) and enhanced patient-centered care and treatment adherence. In addition, as our understanding of the genetic, biochemical, and pathophysiological mechanisms behind these diseases expands, so do potential targets for future therapeutic research (eg, interleukins, matrix metalloproteases, and mast cells). This review incorporates the major meta-analyses, systematic and generalized reviews, and clinical trials published from 2010 through 2021 that focus on these topics in thoracic aortic aneurysms (and abdominal aneurysms when thoracic literature is scarce). Several key ongoing clinical trials, case studies, and in vivo/in vitro studies are also mentioned. Furthermore, we discuss current gaps in the literature and the abundance of clinical evidence for some interventions in abdominal aneurysms with few thoracic correlates, thus indicating a need for investigation of these subjects in the latter.
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Affiliation(s)
- Robert C F Pena
- Department of Emergency Medicine, George Washington University Hospital, 2000 N Street NW, Apartment P3, Washington, DC 20036.
| | - Marion A Hofmann Bowman
- Department of Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI
| | - Myra Ahmad
- School of Medicine, University of Washington, Seattle, WA
| | - Julie Pham
- School of Medicine, University of Washington, Seattle, WA
| | | | | | - Jenney Lee
- School of Medicine, University of Washington, Seattle, WA
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Leonova MV. Collagen-associated side effects of fluoroquinolones: aneurysm and aortic dissection (systematic review). CONSILIUM MEDICUM 2022. [DOI: 10.26442/20751753.2022.1.201380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Well known for fluoroquinolones cause the development of collagen-associated side effects tendopathies with the risk of tendon rupture and retinal detachment, which is associated with the damaging effect and degradation of type I and type III collagen. The aorta is also rich in collagen type I and type III up to 8090%, which has the potential to play a role in the development of aortopathies in cases of fluoroquinolone use. Since 2015, the first publications of research results on the collagen-associated effect of fluoroquinolones on the development of aneurysm and aortic dissection, often called aortopathy, began to appear. A systematic review of observational studies and 5 meta-analyzes of the development of a novel side effect of fluoroquinolones is presented. An absolute incidence of this side effect of 1.1% and a twofold increased relative risk of developing aneurysm/aortic dissection (RR 2.042.23), aortic aneurysm (RR 1.742.83), and aortic dissection (RR 1.882.79). When analyzing age subgroups, an increase in the risk of aneurysm/aortic dissection was noted already from the age of 35 years and was more significant in elderly patients (over 65 years). Analisys of the course duration of fluoroquinolone use (314 days or 14 days) was carried out in two studies and showed an increase in the risk of aneurysm/aortic dissection with increasing duration of fluoroquinolone therapy (RR 1.72 versus RR 1.92). The risk of developing a fluoroquinolone-associated aortopathy was highest during the first 30 days after the course use of fluoroquinolones, with a slight decrease within 6090 days after the course. The signal was confirmed by the FDA pharmacovigilance system (USA) during the analysis of cases of aneurysm/aortic dissection against the background of fluoroquinolones use. International regulatory authorities (FDA and EMA) have announced official documents warning of an increased incidence of rare but serious cases of aortic dissection or ruptured aortic aneurysm with oral fluoroquinolones. Fluoroquinolones should not be given to patients at increased risk unless other treatment options are available. The increased risk category includes patients with a history of aortic or other blood vessel aneurysm, high blood pressure, and the elderly.
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Jun C, Fang B. Current progress of fluoroquinolones-increased risk of aortic aneurysm and dissection. BMC Cardiovasc Disord 2021; 21:470. [PMID: 34583637 PMCID: PMC8477541 DOI: 10.1186/s12872-021-02258-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 09/08/2021] [Indexed: 11/12/2022] Open
Abstract
Aortic aneurysm (AA) and aortic dissection (AD) are major life-threatening diseases around the world. AA is a localized or diffuse dilation of the aorta, while AD is the separation of the layers creating a false lumen within the aortic wall. Fluoroquinolones (FQ) remain one of the most important kind of antibiotics and have a wider clinical use and broad antibacterial spectrum. FQ were also reported to treat infected AA. The most common adverse events (AEs) of FQ are mild and reversible, like headaches, diarrhea and nausea. Due to FQ-related serious AEs, such as tendonitis and tendon rupture, chondrotoxicity, or retinal detachment, QT-prolongation and dysglycemia, the United States Food and Drug Administration (FDA) issued a black box warning for FQ for systemic use in 2016 and updated warnings for FQ several times since then. Of note, in December 2018, FDA issued several "black box warnings" against FQ with the latest safety announcement warning about an increased risk of ruptures in the aorta blood vessel in certain patients. Recently, many studies have indicated an association between FQ and an increase risk of AA and AD. However, the exact mechanism of FQ-induced AA/AD remains unclear. This review aims to highlight the latest research progress of the alarming association between FQ and AA/AD. Moreover, molecular mechanisms of FQ in increasing risk of AA and AD are explored. Hopefully, this review can provide novel insights into FQ-increased the risk of AA/AD and a starting place for stewardship interventions.
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Affiliation(s)
- Cui Jun
- Department of Cardiothoracic Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, Hubei, China
| | - Bian Fang
- Department of Pharmacy, Featured Preparations of Vitiligo Xiangyang Key Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, Hubei, China.
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Barberán J, Barberán LC, de la Cuerda A. [Safety in the selection of oral antibiotic treatment in community infections, beyond COVID-19]. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2021; 34:289-297. [PMID: 34319057 PMCID: PMC8329570 DOI: 10.37201/req/087.2021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Los antibióticos orales son uno de los fármacos más utilizados en la comunidad. Sus efectos adversos son generalmente poco frecuentes y leves, e incluyen toxicidad e interacciones medicamentosas. El mecanismo de producción es variado y no siempre bien conocido. El conocimiento de los efectos adversos con relevancia clínica puede permitir hacer un uso más juicioso de los antibióticos basados en el principio primero no hacer daño, primun non nocere. En esta revisión exploramos los principales efectos adversos de los antibióticos orales con énfasis en los β-lactámicos, macrólidos y fluoroquinolonas.
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Affiliation(s)
- J Barberán
- José Barberán, Servicio de Medicina Interna - Enfermedades infecciosas Hospital Universitario HM Montepríncipe. Universidad San Pablo CEU, Madrid, Spain.
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Vascular consequences of inflammation: a position statement from the ESH Working Group on Vascular Structure and Function and the ARTERY Society. J Hypertens 2021; 38:1682-1698. [PMID: 32649623 DOI: 10.1097/hjh.0000000000002508] [Citation(s) in RCA: 119] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
: Inflammation is a physiological response to aggression of pathogenic agents aimed at eliminating the aggressor agent and promoting healing. Excessive inflammation, however, may contribute to tissue damage and an alteration of arterial structure and function. Increased arterial stiffness is a well recognized cardiovascular risk factor independent of blood pressure levels and an intermediate endpoint for cardiovascular events. In the present review, we discuss immune-mediated mechanisms by which inflammation can influence arterial physiology and lead to vascular dysfunction such as atherosclerosis and arterial stiffening. We also show that acute inflammation predisposes the vasculature to arterial dysfunction and stiffening, and alteration of endothelial function and that chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis are accompanied by profound arterial dysfunction which is proportional to the severity of inflammation. Current findings suggest that treatment of inflammation by targeted drugs leads to regression of arterial dysfunction. There is hope that these treatments will improve outcomes for patients.
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The Association between the Risk of Aortic Aneurysm/Aortic Dissection and the Use of Fluroquinolones: A Systematic Review and Meta-Analysis. Antibiotics (Basel) 2021; 10:antibiotics10060697. [PMID: 34200836 PMCID: PMC8230555 DOI: 10.3390/antibiotics10060697] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 05/30/2021] [Accepted: 06/04/2021] [Indexed: 11/17/2022] Open
Abstract
This study aimed to investigate the association between the risk of aortic aneurysm (AA)/aortic dissection (AD) and the use of fluoroquinolones (FQs). PubMed, Embase, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Web of Science and Scopus were searched for relevant articles to 21st February 2021. Studies that compared the risk of AA/AD in patients who did and did not receive FQs or other comparators were included. The pooled results of nine studies with 11 study cohorts showed that the use of FQs increased the risk of AA/AD by 69% (pooled risk ratio (RR) = 1.69 (95% CI = 1.08, 2.64)). This significant association remained unchanged using leave-one-out sensitivity test analysis. Similar results were found for AA (pooled RR = 1.58 (1.21, 2.07)) but no significant association was observed for AD (pooled RR = 1.23 (0.93, 1.62)). Stratified by the comparators, the use of FQs was associated with a significantly higher risk of AA/AD compared to azithromycin (pooled RR = 2.31 (1.54, 3.47)) and amoxicillin (pooled RR = 1.57 (1.39, 1.78)). In contrast, FQ was not associated with a higher risk of AA/AD, when compared with amoxicillin/clavulanic acid or ampicillin/sulbactam (pooled RR = 1.18 (0.81, 1.73)), sulfamethoxazole–trimethoprim (pooled RR = 0.89 (0.65, 1.22)) and other antibiotics (pooled RR = 1.14 (0.90, 1.46)). In conclusion, FQs were associated with an increased risk of AA or AD, although the level of evidence was not robust. However, FQs did not exhibit a higher risk of AA or AD compared with other broad-spectrum antibiotics. Further studies are warranted to clarify the role of FQs in the development of AA or AD.
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Creamer TJ, Bramel EE, MacFarlane EG. Insights on the Pathogenesis of Aneurysm through the Study of Hereditary Aortopathies. Genes (Basel) 2021; 12:183. [PMID: 33514025 PMCID: PMC7912671 DOI: 10.3390/genes12020183] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 12/15/2022] Open
Abstract
Thoracic aortic aneurysms (TAA) are permanent and localized dilations of the aorta that predispose patients to a life-threatening risk of aortic dissection or rupture. The identification of pathogenic variants that cause hereditary forms of TAA has delineated fundamental molecular processes required to maintain aortic homeostasis. Vascular smooth muscle cells (VSMCs) elaborate and remodel the extracellular matrix (ECM) in response to mechanical and biochemical cues from their environment. Causal variants for hereditary forms of aneurysm compromise the function of gene products involved in the transmission or interpretation of these signals, initiating processes that eventually lead to degeneration and mechanical failure of the vessel. These include mutations that interfere with transduction of stimuli from the matrix to the actin-myosin cytoskeleton through integrins, and those that impair signaling pathways activated by transforming growth factor-β (TGF-β). In this review, we summarize the features of the healthy aortic wall, the major pathways involved in the modulation of VSMC phenotypes, and the basic molecular functions impaired by TAA-associated mutations. We also discuss how the heterogeneity and balance of adaptive and maladaptive responses to the initial genetic insult might contribute to disease.
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Affiliation(s)
- Tyler J. Creamer
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (T.J.C.); (E.E.B.)
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Emily E. Bramel
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (T.J.C.); (E.E.B.)
- Predoctoral Training in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Elena Gallo MacFarlane
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (T.J.C.); (E.E.B.)
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Davaapil H, Shetty DK, Sinha S. Aortic "Disease-in-a-Dish": Mechanistic Insights and Drug Development Using iPSC-Based Disease Modeling. Front Cell Dev Biol 2020; 8:550504. [PMID: 33195187 PMCID: PMC7655792 DOI: 10.3389/fcell.2020.550504] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 10/08/2020] [Indexed: 12/24/2022] Open
Abstract
Thoracic aortic diseases, whether sporadic or due to a genetic disorder such as Marfan syndrome, lack effective medical therapies, with limited translation of treatments that are highly successful in mouse models into the clinic. Patient-derived induced pluripotent stem cells (iPSCs) offer the opportunity to establish new human models of aortic diseases. Here we review the power and potential of these systems to identify cellular and molecular mechanisms underlying disease and discuss recent advances, such as gene editing, and smooth muscle cell embryonic lineage. In particular, we discuss the practical aspects of vascular smooth muscle cell derivation and characterization, and provide our personal insights into the challenges and limitations of this approach. Future applications, such as genotype-phenotype association, drug screening, and precision medicine are discussed. We propose that iPSC-derived aortic disease models could guide future clinical trials via “clinical-trials-in-a-dish”, thus paving the way for new and improved therapies for patients.
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Affiliation(s)
- Hongorzul Davaapil
- Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge, United Kingdom
| | - Deeti K Shetty
- Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge, United Kingdom
| | - Sanjay Sinha
- Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge, United Kingdom
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14
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Nikol S, Mathias K, Olinic DM, Blinc A, Espinola-Klein C. Aneurysms and dissections - What is new in the literature of 2019/2020 - a European Society of Vascular Medicine annual review. VASA 2020; 49:1-36. [PMID: 32856993 DOI: 10.1024/0301-1526/a000865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
More than 6,000 publications were found in PubMed concerning aneurysms and dissections, including those Epub ahead of print in 2019, printed in 2020. Among those publications 327 were selected and considered of particular interest.
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Affiliation(s)
- Sigrid Nikol
- Department of Angiology, ASKLEPIOS Klinik St. Georg, Hamburg, Germany.,University of Münster, Germany
| | - Klaus Mathias
- World Federation for Interventional Stroke Treatment (WIST), Hamburg, Germany
| | - Dan Mircea Olinic
- Medical Clinic No. 1, University of Medicine and Pharmacy and Interventional Cardiology Department, Emergency Hospital, Cluj-Napoca, Romania
| | - Aleš Blinc
- Department of Vascular Diseases, University Medical Centre Ljubljana, Slovenia.,Faculty of Medicine, University of Ljubljana, Slovenia
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15
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Abstract
Inherited thoracic aortopathies denote a group of congenital conditions that predispose to disease of the thoracic aorta. Aortic wall weakness and abnormal aortic hemodynamic profiles predispose these patients to dilatation of the thoracic aorta, which is generally silent but can precipitate aortic dissection or rupture with devastating and often fatal consequences. Current strategies to assess the future risk of aortic dissection or rupture are based primarily on monitoring aortic diameter. However, diameter alone is a poor predictor of risk, with many patients experiencing dissection or rupture below current intervention thresholds. Developing tools that improve the risk assessment of those with aortopathy is internationally regarded as a research priority. A robust understanding of the molecular pathways that lead to aortic wall weakness is required to identify biomarkers and therapeutic targets that could improve patient management. Here, we summarize the current understanding of the genetically determined mechanisms underlying inherited aortopathies and critically appraise the available blood biomarkers, imaging techniques, and therapeutic targets that have shown promise for improving the management of patients with these important and potentially fatal conditions.
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Affiliation(s)
- Alexander J. Fletcher
- University of Edinburgh Centre for Cardiovascular Science, Royal Infirmary of Edinburgh, United Kingdom (A.J.F., M.B.J.S., D.E.N., N.L.W.)
| | - Maaz B.J. Syed
- University of Edinburgh Centre for Cardiovascular Science, Royal Infirmary of Edinburgh, United Kingdom (A.J.F., M.B.J.S., D.E.N., N.L.W.)
| | - Timothy J. Aitman
- Centre for Genomics and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom (T.J.A.)
| | - David E. Newby
- University of Edinburgh Centre for Cardiovascular Science, Royal Infirmary of Edinburgh, United Kingdom (A.J.F., M.B.J.S., D.E.N., N.L.W.)
| | - Niki L. Walker
- University of Edinburgh Centre for Cardiovascular Science, Royal Infirmary of Edinburgh, United Kingdom (A.J.F., M.B.J.S., D.E.N., N.L.W.)
- Scottish Adult Congenital Heart Disease Service, Golden Jubilee National Hospital, Clydebank, Glasgow, United Kingdom (N.L.W.)
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16
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Gatti M, Bianchin M, Raschi E, De Ponti F. Assessing the association between fluoroquinolones and emerging adverse drug reactions raised by regulatory agencies: An umbrella review. Eur J Intern Med 2020; 75:60-70. [PMID: 31983604 DOI: 10.1016/j.ejim.2020.01.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 01/11/2020] [Accepted: 01/15/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Regulatory agencies warned against fluoroquinolones for the management of minor infections because of the risk of emerging adverse events (collagen-associated adverse events, neuropsychiatric toxicity and long-term disability). We aimed to assess quality and credibility of evidence as well as causality regarding these putative associations. METHODS MEDLINE, Scopus, Web of Science and PROSPERO were searched, from inception to August 2019, for systematic reviews with meta-analyses investigating emerging adverse events. Two investigators extracted data to grade quality (through validated AMSTAR-2 tool), rank credibility of the evidence (convincing, highly suggestive, suggestive, weak) through adapted criteria including E-value calculation, and assess causality (Hill's criteria). RESULTS Seven systematic reviews of observational studies providing 16 risk estimates [seven, five and four, respectively, for aortic aneurysm/dissection (AAD), retinal detachment (RD) and any tendon disorders (ATD)] met inclusion criteria. No systematic reviews with meta-analysis investigating the risk of neuropsychiatric toxicity or long-term disability were found. The associations between fluoroquinolones and AAD/ATD showed highly suggestive credibility and were supported by strong evidence of causality (double increased risk, especially within first 2 months of treatment). Conflicting data concerning the emergence of RD were retrieved, resulting in weak evidence of causality. Quality of the evidence ranged from high to low for AAD, from moderate to critically low for RD, and it was moderate for ATD. CONCLUSION Our analysis supports credible, plausible and highly suggestive associations with AAD (rare occurrence but strong causality) and ATD. Limitations of both umbrella reviews and observational evidence should be considered.
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Affiliation(s)
- Milo Gatti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy
| | - Matteo Bianchin
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy
| | - Emanuel Raschi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
| | - Fabrizio De Ponti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy
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Yang M, Liu F, Wang M, Zhou J, Zhang L, Wang T. Development of a whole liquid egg certified reference material for accurate measurement of enrofloxacin residue. Food Chem 2020; 309:125253. [DOI: 10.1016/j.foodchem.2019.125253] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 06/29/2019] [Accepted: 07/24/2019] [Indexed: 01/23/2023]
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18
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Relationship between fluoroquinolones and the risk of aortic diseases: a meta-analysis of observational studies. BMC Cardiovasc Disord 2020; 20:49. [PMID: 32013928 PMCID: PMC6998374 DOI: 10.1186/s12872-020-01354-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 01/21/2020] [Indexed: 12/12/2022] Open
Abstract
Background Our aim was to determine the relationship between the use of fluoroquinolones and the risk of aortic diseases. Methods PubMed, EMBASE and the Web of Science were searched from inception to July 6, 2019, to identify observational studies that evaluated the risk of aortic diseases associated in users of fluoroquinolones compared with nonusers or users of other antibiotics. The primary outcome was the first occurrence of aortic diseases. We used the GRADE approach to rate the strength of evidence. We used the inverse variance method random-effect model to estimate the odds ratios (ORs) with 95% CIs, and statistical heterogeneity was assessed by the I2 statistic. Results This meta-analysis enrolled 2,829,385 patients reported the relationship between fluoroquinolones and the risk of aortic diseases. Compared with nonusers or users of other antibiotics, users of fluoroquinolone had a significantly increased risk of aortic diseases (adjusted OR, 2.10; 95% CI, 1.65–2.68; P = .000, I2 = 16.4%). The quality of evidence was moderate, and the number needed to harm (NNH) for aortic diseases among patients was estimated to be 1301. Conclusions The fluoroquinolone use in patients significantly increases the risk of new-onset aortic diseases. Clinicians need to pay attention to these severe adverse events when considering fluoroquinolone use.
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Silva JT, San-Juan R, Fernández-Ruiz M, Aguado JM. Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation. World J Gastroenterol 2019; 25:3291-3298. [PMID: 31341356 PMCID: PMC6639553 DOI: 10.3748/wjg.v25.i26.3291] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 05/30/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023] Open
Abstract
Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.
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Affiliation(s)
- Jose Tiago Silva
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
| | - Rafael San-Juan
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Hospital “12 de Octubre” (imas12), School of Medicine, Universidad Complutense, Madrid 28041, Spain
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Meng L, Huang J, Jia Y, Huang H, Qiu F, Sun S. Assessing fluoroquinolone-associated aortic aneurysm and dissection: Data mining of the public version of the FDA adverse event reporting system. Int J Clin Pract 2019; 73:e13331. [PMID: 30809871 DOI: 10.1111/ijcp.13331] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 01/29/2019] [Accepted: 02/24/2019] [Indexed: 12/01/2022] Open
Abstract
AIMS A recent large epidemiological study found fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection. We aimed to examine fluoroquinolone (ciprofloxacin, levofloxacin and moxifloxacin) associated aortic aneurysm or dissection through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS Reports to the FAERS from 1 January 2004 to 31 December 2016 were analysed. Pharmacovigilance tools were used for quantitative detection of signals that is, drug-associated adverse events, including reporting odds ratio, proportional reporting ratio, information component given by a Bayesian confidence propagation neural network and empirical Bayes geometric mean. Sensitivity analyses that limited the data by gender and adverse event date also showed similar trends. RESULTS Based on 3721 adverse event reports, all three fluoroquinolones are associated with aortic aneurysm, and levofloxacin is associated with aortic dissection. The risk of aortic aneurysm is higher than the aortic dissection. Oral administration of fluoroquinolones is more likely to produce these adverse events. CONCLUSION The results obtained herein are consistent with clinical observations, suggesting the necessity for further clinical research on aortic aneurysm and dissection associated with fluoroquinolones.
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Affiliation(s)
- Long Meng
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jing Huang
- Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yuntao Jia
- Department of Pharmacy, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Huali Huang
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Feng Qiu
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shusen Sun
- Department of Pharmacy Practice, College of Pharmacy and Health Sciences, Western New England University, Springfield, Massachusetts
- Department of Pharmacy, Xiangya Hospital Central South University, Changsha, Hunan, China
- Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
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