Henkilökohtaisestikin asia on tärkeä ( Olen käyttänyt ciprofloxacin ja norfloxacin- lääkekuureja vuosien varrella ja olen näihin asti pitänyt niitä erinomaisina antibiootteina, myös itselleni, koska en siedä penisilliiniä tai laajakirjoisia penisilliinejä, erytromysiiniäkään tuskin).
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Items: 13
1. FQ, LEVOFLOXACIN
Sommet A, Bénévent J, Rousseau V, Chebane L, Douros A, Montastruc JL, Montastruc F.
J Gen Intern Med. 2018 Dec 18. doi: 10.1007/s11606-018-4774-2. [Epub ahead of print] No abstract available.
aortic aneurysms; aortic dissection; fluoroquinolones; levofloxacin
- PMID:30565153
- DOI:10.1007/s11606-018-4774-2
2. FQ
Frankel WC, Trautner BW, Spiegelman A, Grigoryan L, LeMaire SA.
Antimicrob Agents Chemother. 2019 Jan 29;63(2). pii: e01712-18. doi: 10.1128/AAC.01712-18. Print 2019 Feb.
3. FQ
Noman AT, Qazi AH, Alqasrawi M, Ayinde H, Tleyjeh IM, Lindower P, Bin Abdulhak AA.
Int J Cardiol. 2019 Jan 1;274:299-302. doi: 10.1016/j.ijcard.2018.09.067. Epub 2018 Sep 21.
Our findings indicate that current fluoroquinolone use was significantly associated with increased risk of aortic aneurysm and dissection. Health care providers need to be aware of this serious association and use fluoroquinolones judiciously in order to minimize the risk of the serious sequela of aortopathy.
4. FQ
DeLaney MC.
Br J Hosp Med (Lond). 2018 Oct 2;79(10):552-555. doi: 10.12968/hmed.2018.79.10.552.
Fluoroquinolones
are a widely used class of antibiotic that are effective in treating a
wide variety of pathogens. Despite their popularity there is increasing
concern regarding the potential complications associated with these
agents. Patients who take a fluoroquinolone have an increased risk of
developing tendinopathy, peripheral neuropathy, and aortic aneurysm or dissection. Providers should consider the risk of these potential complications before using these medications. PMID:30290736 DOI: 10.12968/hmed.2018.79.10.552
5. FQ
Singh S, Nautiyal A.
J Am Coll Cardiol. 2018 Sep 18;72(12):1379-1381. doi: 10.1016/j.jacc.2018.07.018. No abstract available.
6. FQ
Lee CC, Lee MG, Hsieh R, Porta L, Lee WC, Lee SH, Chang SS.
J Am Coll Cardiol. 2018 Sep 18;72(12):1369-1378. doi: 10.1016/j.jacc.2018.06.067.
Previous studies raised safety concerns on the association between fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and dissection (AA/AD). OBJECTIVES: This study sought to evaluate this association via a case-crossover analysis in a large national administrative database. METHODS: A
case-crossover design was used to compare the distributions of
fluoroquinolone exposure for the same patient across a 60-day period
before the AA/AD event (hazard period) and 1 randomly selected 60-day
period (referent period) between 60 to 180 days before the AA/AD events.
In the sensitivity analysis, the authors repeated the main analysis
using a 1:5 ratio of hazard period to referent period, to adjust for the
effect of time-variant confounders. A disease-risk score-matched time
control analysis was performed to investigate the potential time-trend
bias. The risks were calculated by a conditional logistic regression
model. RESULTS:
A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95% CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure. CONCLUSIONS: Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.
A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95% CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure. CONCLUSIONS: Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. KEYWORDS:
aortic and arterial diseases; aortic aneurysm; aortic dissection; fluoroquinolones
7. FQ, CIPROFLOXACIN
LeMaire SA, Zhang L, Luo W, Ren P, Azares AR, Wang Y, Zhang C, Coselli JS, Shen YH.
JAMA Surg. 2018 Sep 1;153(9):e181804. doi: 10.1001/jamasurg.2018.1804. Epub 2018 Sep 19.
Fluoroquinolones
are among the most commonly prescribed antibiotics. Recent clinical
studies indicated an association between fluoroquinolone use and
increased risk of aortic aneurysm and dissection
(AAD). This alarming association has raised concern, especially in
patients with AAD with risk of rupture and in individuals at risk for
developing AAD. Objective:
To examine the effect of ciprofloxacin on AAD development in mice. Design, Setting, and Participants: In a mouse model of moderate, sporadic AAD, 4-week-old male and female C57BL/6J mice were challenged with a high-fat diet and low-dose angiotensin infusion (1000 ng/min/kg). Control unchallenged mice were fed a normal diet and infused with saline. After randomization, challenged and unchallenged mice received ciprofloxacin (100 mg/kg/d) or vehicle through daily gavage during angiotensin or saline infusion. Aortic aneurysm and dissection development and aortic destruction were compared between mice. The direct effects of ciprofloxacin on aortic smooth muscle cells were examined in cultured cells. Results: No notable aortic destruction was observed in unchallenged mice that received ciprofloxacin alone. Aortic challenge induced moderate aortic destruction with development of AAD in 17 of 38 mice (45%) and severe AAD in 9 (24%) but no rupture or death. However, challenged mice that received ciprofloxacin had severe aortic destruction and a significantly increased incidence of AAD (38 of 48 [79%]; P = .001; χ2 = 10.9), severe AAD (32 of 48 [67%]; P < .001; χ2 = 15.7), and rupture and premature death (7 of 48 [15%]; P = .01; χ2 = 6.0). The increased AAD incidence was observed in different aortic segments and was similar between male and female mice. Compared with aortic tissues from challenged control mice, those from challenged mice that received ciprofloxacin showed decreased expression of lysyl oxidase, an enzyme that is critical in the assembly and stabilization of elastic fibers and collagen. These aortas also showed increased matrix metalloproteinase (MMPs) levels and activity, elastic fiber fragmentation, and aortic cell injury. In cultured smooth muscle cells, ciprofloxacin treatment significantly reduced lysyl oxidase expression and activity, increased matrix metalloproteinase expression and activity, suppressed cell proliferation, and induced cell death. Furthermore, ciprofloxacin-a DNA topoisomerase inhibitor-caused nuclear and mitochondrial DNA damage and the release of DNA into the cytosol, subsequently inducing mitochondrial dysfunction, reactive oxygen species production, and activation of the cytosolic DNA sensor STING, which we further showed was involved in the suppression of lysyl oxidase expression and induction of matrix metalloproteinase expression. Conclusions and Relevance:
Ciprofloxacin increases susceptibility to aortic dissection and rupture in a mouse model of moderate, sporadic AAD. Ciprofloxacin should be used with caution in patients with aortic dilatation, as well as in those at high risk for AAD.
To examine the effect of ciprofloxacin on AAD development in mice. Design, Setting, and Participants: In a mouse model of moderate, sporadic AAD, 4-week-old male and female C57BL/6J mice were challenged with a high-fat diet and low-dose angiotensin infusion (1000 ng/min/kg). Control unchallenged mice were fed a normal diet and infused with saline. After randomization, challenged and unchallenged mice received ciprofloxacin (100 mg/kg/d) or vehicle through daily gavage during angiotensin or saline infusion. Aortic aneurysm and dissection development and aortic destruction were compared between mice. The direct effects of ciprofloxacin on aortic smooth muscle cells were examined in cultured cells. Results: No notable aortic destruction was observed in unchallenged mice that received ciprofloxacin alone. Aortic challenge induced moderate aortic destruction with development of AAD in 17 of 38 mice (45%) and severe AAD in 9 (24%) but no rupture or death. However, challenged mice that received ciprofloxacin had severe aortic destruction and a significantly increased incidence of AAD (38 of 48 [79%]; P = .001; χ2 = 10.9), severe AAD (32 of 48 [67%]; P < .001; χ2 = 15.7), and rupture and premature death (7 of 48 [15%]; P = .01; χ2 = 6.0). The increased AAD incidence was observed in different aortic segments and was similar between male and female mice. Compared with aortic tissues from challenged control mice, those from challenged mice that received ciprofloxacin showed decreased expression of lysyl oxidase, an enzyme that is critical in the assembly and stabilization of elastic fibers and collagen. These aortas also showed increased matrix metalloproteinase (MMPs) levels and activity, elastic fiber fragmentation, and aortic cell injury. In cultured smooth muscle cells, ciprofloxacin treatment significantly reduced lysyl oxidase expression and activity, increased matrix metalloproteinase expression and activity, suppressed cell proliferation, and induced cell death. Furthermore, ciprofloxacin-a DNA topoisomerase inhibitor-caused nuclear and mitochondrial DNA damage and the release of DNA into the cytosol, subsequently inducing mitochondrial dysfunction, reactive oxygen species production, and activation of the cytosolic DNA sensor STING, which we further showed was involved in the suppression of lysyl oxidase expression and induction of matrix metalloproteinase expression. Conclusions and Relevance:
Ciprofloxacin increases susceptibility to aortic dissection and rupture in a mouse model of moderate, sporadic AAD. Ciprofloxacin should be used with caution in patients with aortic dilatation, as well as in those at high risk for AAD.
8.
Harris PC, Torres VE.
In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2002 Jan 10 [updated 2018 Jul 19].
2002 Jan 10 [updated 2018 Jul 19].
9. FQ
Demetrious JS.
Chiropr Man Therap. 2018 Jul 9;26:22. doi: 10.1186/s12998-018-0193-z. eCollection 2018.
10. FQ
Pasternak B, Inghammar M, Svanström H.
BMJ. 2018 Mar 8;360:k678. doi: 10.1136/bmj.k678. Abstract OBJECTIVE:
To investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection. DESIGN:
Nationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection. SETTING:
Sweden, July 2006 to December 2013. PARTICIPANTS:
360 088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360 088). MAIN OUTCOME MEASURES:
Cox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment. RESULTS:
Nationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection. SETTING:
Sweden, July 2006 to December 2013. PARTICIPANTS:
360 088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360 088). MAIN OUTCOME MEASURES:
Cox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment. RESULTS:
Within the 60 day risk period, the rate of aortic aneurysm or dissection
was 1.2 cases per 1000 person years among fluoroquinolone users and 0.7
cases per 1000 person years among amoxicillin users. Fluoroquinolone
use was associated with an increased risk of aortic aneurysm or dissection
(hazard ratio 1.66 (95% confidence interval 1.12 to 2.46)), with an
estimated absolute difference of 82 (95% confidence interval 15 to 181)
cases of aortic aneurysm or dissection
by 60 days per 1 million treatment episodes. In a secondary analysis,
the hazard ratio for the association with fluoroquinolone use was 1.90
(1.22 to 2.96) for aortic aneurysm and 0.93 (0.38 to 2.29) for aortic dissection. CONCLUSIONS: In a propensity score matched cohort, fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection. This association appeared to be largely driven by aortic aneurysm. Published
by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions. Comment in
- Fluoroquinolones and the aorta. [BMJ. 2018]
Juurlink DN1. Comment on
- PMID:
- 29519782
- DOI:
- 10.1136/bmj.k988
11. FQ
Aortic Dissection and Aortic Aneurysms Associated with Fluoroquinolones: A Systematic Review and Meta-Analysis. Singh S, Nautiyal A.
Am J Med. 2017 Dec;130(12):1449-1457.e9. doi: 10.1016/j.amjmed.2017.06.029. Epub 2017 Jul 21. Review. Abstract BACKGROUND: Our objective was to evaluate the association between fluoroquinolone use and aortic dissection or aortic aneurysm in a systematic review and meta-analysis. METHODS: We
searched Medline, Embase, and Scopus from inception to February 15,
2017. We selected controlled studies for inclusion if they reported data
on aortic dissection and aortic aneurysm associated with fluoroquinolones
exposure versus no exposure. Data were extracted by 2 independent
reviewers, with disagreements resolved through further discussion. We
assessed the quality of studies using the Newcastle-Ottawa Scale for
observational studies and the strength of evidence using the Grading of
Recommendations Assessment, Development, and Evaluation approach. The
odds ratios (ORs) from observational studies were pooled using the
fixed-effect inverse variance method, and statistical heterogeneity was
assessed using the I2 statistic. RESULTS: After a review of 714 citations, we included 2 observational studies in the meta-analysis. Current use of fluoroquinolones was associated with a statistically significantly increased risk of aortic dissection (OR, 2.79; 95% confidence interval [CI], 2.31-3.37; I2 = 0%) and aortic aneurysm (OR, 2.25; 95% CI, 2.03-2.49; I2 = 0%)
in a fixed-effects meta-analysis. The unadjusted OR estimates and
sensitivity analysis using a random-effects model showed similar
results. We rated the strength of evidence to be of moderate quality.
The number needed to treat to harm for aortic aneurysm for elderly patients aged more than 65 years who were current users of fluoroquinolones was estimated to be 618 (95% CI, 518-749). CONCLUSIONS: Evidence from a small number of studies suggests that exposure to fluoroquinolones is consistently associated with a small but significantly increased risk of aortic dissection and aortic aneurysm. Copyright © 2017 Elsevier Inc. All rights reserved. KEYWORDS: Aortic aneurysm; Aortic dissection; Fluoroquinolones; Meta-analysis; Systematic review
12. FQ
[No authors listed]
Prescrire Int. 2016 Jul;25(173):184. No abstract available.
13.
Lee CC, Lee MT, Chen YS, Lee SH, Chen YS, Chen SC, Chang SC.
JAMA Intern Med. 2015 Nov;175(11):1839-47. doi: 10.1001/jamainternmed.2015.5389. Abstract IMPORTANCE:
Fluoroquinolones
have been associated with collagen degradation, raising safety concerns
related to more serious collagen disorders with use of these
antibiotics, including aortic aneurysm and dissection. OBJECTIVE:
To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection. DESIGN, SETTING, AND PARTICIPANTS:
We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan's National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex. EXPOSURES: Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection. MAIN OUTCOMES AND MEASURES:
Risk of developing aortic aneurysm or dissection. RESULTS:
A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score-adjusted RR, 2.15; 95% CI, 0.97-4.60). CONCLUSIONS AND RELEVANCE: Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.
To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection. DESIGN, SETTING, AND PARTICIPANTS:
We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan's National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex. EXPOSURES: Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection. MAIN OUTCOMES AND MEASURES:
Risk of developing aortic aneurysm or dissection. RESULTS:
A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score-adjusted RR, 2.15; 95% CI, 0.97-4.60). CONCLUSIONS AND RELEVANCE: Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.
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