Risk of hepatotoxicity associated with fluoroquinolones: A national case–control safety study

Alshammari, Thamir M.; Larrat, E. Paul; Morrill, Haley J.; Caffrey, Aisling R.; Quilliam, Brian J.; LaPlante, Kerry L.

doi:10.2146/ajhp130165

Cited by 60 publications

(52 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The VA Healthcare System operates 151 medical centers and 827 community-based outpatient clinics throughout the US [19]. Inpatient and outpatient care is captured electronically in each VA healthcare facility through the electronic medical record system, which has been in place since 1999 [20].…”

Section: Methodsmentioning

confidence: 99%

Epidemiology of Pneumococcal Disease in a National Cohort of Older Adults

et al. 2014

Self Cite

View full text Add to dashboard Cite

IntroductionStreptococcus pneumoniae is a major cause of morbidity and mortality. We sought to describe the epidemiology of non-invasive and invasive pneumococcal disease in a national Veterans Affairs population within the United States.MethodsWe conducted a retrospective study in older patients (aged ≥50 years) with positive pneumococcal cultures from any site between 2002 and 2011. We described outpatient and inpatient pneumococcal disease incidence per 100,000 clinic visits/hospitalizations. Repeat cultures within a 30-day period were considered to represent the same episode. To describe the epidemiology of serious pneumococcal infections (bacteremia, meningitis, pneumonia), we assessed demographics, clinical characteristics, and risk factors for S. pneumoniae. Pneumonia was defined as a positive respiratory culture with a pneumonia diagnosis code. Bacteremia and meningitis were identified from positive cultures. Generalized linear mixed models were used to quantify changes over time.ResultsOver the study period, we identified 45,983 unique episodes of pneumococcal disease (defined by positive cultures). Incidence decreased significantly by 3.5% per year in outpatients and increased non-significantly by 0.2% per year in inpatients. In 2011, the outpatient and inpatient incidence was 2.6 and 328.1 infections per 100,000 clinic visits/hospitalizations, respectively. Among inpatients with serious infections, chronic disease risk factors for pneumococcal disease increased significantly each year, including respiratory disease (1.9% annually), diabetes (1.3%), and renal failure (1.0%). Overall, 30.2% of inpatients with serious infections had a pneumococcal immunization in the previous 5 years. Invasive disease (37.4% versus 34.9%, P = 0.004) and mortality (14.0% versus 12.7%, P = 0.045) were higher in non-vaccinated patients compared to vaccinated patients.ConclusionsIn our national study of older adults, the baseline health status of those with serious pneumococcal infections worsened over the study period. As the population ages and the chronic disease epidemic grows, the burden of pneumococcal disease is likely to increase thus highlighting the importance of pneumococcal vaccination.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-014-0025-y) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

Epidemiology of Pneumococcal Disease in a National Cohort of Older Adults

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…This report found that the chronic administration of ciprofloxacin could cause the up-regulation of CYP2E1 in mouse microsomes using Western blot analysis [33] . Recent clinical investigation has indicated a significant association between ciprofloxacin use and an increased risk of hepatotoxicity [34,35] . This hepatotoxicity has resulted from the induction of the drug metabolizing enzyme CYP2E1 by the administration of ciprofloxacin.…”

Section: Wwwnaturecom/aps Liu L Et Almentioning

confidence: 99%

Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats

et al. 2016

View full text Add to dashboard Cite

Aim: Caderofloxacin is a new fluoroquinolone that is under phase III clinical trials in China. Here we examined the effects of caderofloxacin on rat hepatic cytochrome P450 (CYP450) isoforms as well as the potential of caderofloxacin interacting with co-administered drugs. Methods: Male rats were treated with caderofloxacin (9 mg/kg, ig) once or twice daily for 14 consecutive days. The effects of caderofloxacin on CYP3A, 2D6, 2C19, 1A2, 2E1 and 2C9 were evaluated using a "cocktail" of 6 probes (midazolam, dextromethorphan, omeprazole, theophylline, chlorzoxazone and diclofenac) injected on d 0 (prior to caderofloxacin exposure) and d 15 (after caderofloxacin exposure). Hepatic microsomes from the caderofloxacin-treated rats were used to assess CYP2E1 activity and chlorzoxazone metabolism. The expression of CYP2E1 mRNA and protein in hepatic microsomes was analyzed with RT-PCR and Western blotting, respectively. Results: Fourteen-day administration of caderofloxacin significantly increased the activity of hepatic CYP2E1, leading to enhanced metabolism of chlorzoxazone. In vitro microsomal study confirmed that CYP2E1 was a major metabolic enzyme involved in chlorzoxazone metabolism, and the 14-d administration of caderofloxacin significantly increased the activity of CYP2E1 in hepatic microsomes, resulting in increased formation of 6-hydroxychlorzoxazone. Furthermore, the 14-d administration of caderofloxacin significantly increased the expression of CYP2E1 mRNA and protein in liver microsomes, which was consistent with the pharmacokinetic results. Conclusion: Fourteen-day administration of caderofloxacin can induce the expression and activity of hepatic CYP2E1 in rats. When caderofloxacin is administered, a potential drug-drug interaction mediated by CYP2E1 induction should be considered.

show abstract

“…The current focus of many clinical trials on serious adverse drug reactions may not adequately address treatment tolerance, which substantially affects treatment adherence and outcomes in programmatic settings. Thus, many adverse drug reactions, which are frequently dose-dependent and aggravated by co-morbidities (especially those with organ dysfunction and ageing 4,5 ), are often insufficiently evaluated in clinical trial settings but highly pertinent at both patient care and programme implementation levels when a very large patient population is involved. The need of clinical vigilance and diligent monitoring for all potential toxicities associated with high-dose moxifloxacin is imperative, especially for cardiotoxicity, which necessitates periodic electrocardiographic assessment throughout the treatment for all patients, with possibly 24-h Holter monitoring for selected cases to comprehensively detect potentially dangerous arrhythmia.…”

mentioning

confidence: 99%

Management of adverse reactions to high‐dose moxifloxacin used in multidrug‐resistant tuberculosis treatment programmes

Yew

Chang

2018

Respirology

View full text Add to dashboard Cite

Risk of hepatotoxicity associated with fluoroquinolones: A national case–control safety study

Abstract: The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.

Cited by 60 publications

References 51 publications

Epidemiology of Pneumococcal Disease in a National Cohort of Older Adults

Epidemiology of Pneumococcal Disease in a National Cohort of Older Adults

Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats

Management of adverse reactions to high‐dose moxifloxacin used in multidrug‐resistant tuberculosis treatment programmes

Contact Info

Product

Resources

About