The use of quinolones increases the risk of tendinopathies
the verdict
CONTESTED
contested - evenly split
refutedsupported
the weight of evidence
10 sources for · 2 against
Multiple studies and meta-analyses report a positive association between the use of quinolones and an increased risk of tendinopathies or tendon disorders, whereas other pediatric evaluations find no significant link or report such events as uncommon.
BACKGROUND Quinolone antibiotics are associated with increased risk of tendinopathy. Identifying at-risk individuals has important clinical implications. We examined whether age, sex, glucocorticoid use, obesity, diabetes, and renal failure/dialysis predispose individuals to the adverse effects of quinolones. METHODS Among 6.4 million patients in The Health Improvement Network (THIN) database, 28,907 cases of Achilles tendonitis and 7,685 cases of tendon rupture were identified in a case-crossover study. For each participant, we ascertained whether there was a prescription of a quinolone and comparison antibiotic within 30 days prior to diagnosis of tendon disorder (case period) as well as prescription of the same medications within 30 days one year prior to disease diagnosis (control period). RESULTS Use of quinolones was strongly associated with an increased risk of Achilles tendonitis (OR=4.3, 95% CI: 3.2–5.7) and tendon rupture (OR=2.0, 95% CI: 1.2–3.3). No association was found between the use of other antibiotics and either outcome. The association with Achilles tendonitis was stronger among participants who were older than 60 years (OR 8.3 vs. 1.6), non-obese (OR 7.7 vs. 2.4), and who used oral glucocorticoids (GC; OR 9.1 vs. 3.2) and nonsignificantly stronger in women (OR 5.0 vs. 3.6), diabetics (OR 7.0 vs. 4.1), and renal failure/dialysis (OR 20.0 vs. 3.9). The effect for tendon rupture was stronger in women, with borderline-significance in glucocorticoid users and non-obese. CONCLUSION Quinolone-associated tendinopathy is more pronounced among elderly, non-obese persons, and individuals with concurrent use of glucocorticoids.
<h4>Background</h4>Joint cartilage toxicity secondary to fluoroquinolone use has been observed in young animals. These early observations led to the contraindication of fluoroquinolones in children under 18 years. Nevertheless, quinolones may be the only option for oral treatment of infections caused by Pseudomonas aeruginosa.<h4>Objective</h4>To evaluate by systematic review and meta-analysis the relation between fluoroquinolonas and musculoskeletal disorders in children.<h4>Methods</h4>Data sources were Medline, Cochrane data base, and free-text search through Google and Yahoo. MESh terms were: quinolones and arthropathy-tendinopathy and children. Randomized clinical trials, cohorts and case-control studies with a primary outcome of arthropaty and/or tendinopathy were included. Each study was scored and classified for methodological key issues according to level of evidence. Data were extracted using a predetermined protocol.<h4>Results</h4>The search identified 277 studies of whom 8 were eligible for inclusion that included 23 166 patients. All except one failed to find a significant link between fluoroquinolones use and musculoskeletal disorders. The pooled odds ratio was 1.02 (CI 0.76-1.38).<h4>Conclusion</h4>Our meta-analysis does not support musculoskeletal disorders as a result of fluoroquinolones use in children under 18 years. Thus, in selected, appropriate, and mandatory cases fluoroquinolones should not be contraindicated in children.
Appropriate prescribing practices for fluoroquinolones are essential as evolving resistance patterns are considered, additional treatment indications are identified, and the toxicity profile of fluoroquinolones in children becomes better defined. Earlier recommendations for systemic therapy remain; expanded uses of fluoroquinolones for the treatment of certain infections are outlined in this report. Although fluoroquinolones are reasonably safe in children, clinicians should be aware of the specific adverse reactions. Use of fluoroquinolones in children should continue to be limited to treatment of infections for which no safe and effective alternative exists.
Antibacterial fluoroquinolones (FQs) are frequently used in treating infections. However, the value of FQs is debatable due to their association with severe adverse effects (AEs). The Food and Drug Administration (FDA) issued safety warnings concerning their side-effects in 2008, followed by the European Medicine Agency (EMA) and regulatory authorities from other countries. Severe AEs associated with some FQs have been reported, leading to their withdrawal from the market. New systemic FQs have been recently approved. The FDA and EMA approved delafloxacin. Additionally, lascufloxacin, levonadifloxacin, nemonoxacin, sitafloxacin, and zabofloxacin were approved in their origin countries. The relevant AEs of FQs and their mechanisms of occurrence have been approached. New systemic FQs present potent antibacterial activity against many resistant bacteria (including resistance to FQs). Generally, in clinical studies, the new FQs were well-tolerated with mild or moderate AEs. All the new FQs approved in the origin countries require more clinical studies to meet FDA or EMA requirements. Post-marketing surveillance will confirm or infirm the known safety profile of these new antibacterial drugs. The main AEs of the FQs class were addressed, highlighting the existing data for the recently approved ones. In addition, the general management of AEs when they occur and the rational use and caution of modern FQs were outlined.
Fluoroquinolones are highly effective antibiotics with many desirable pharmacokinetic and pharmacodynamic properties including high bioavailability, large volume of distribution, and a broad spectrum of antimicrobial activity. Despite their attractive profile as anti-infective agents, their use in children is limited, primarily due to safety concerns. In this review we highlight the pharmacological properties of fluoroquinolones and describe their current use in pediatrics. In addition, we provide a comprehensive assessment of the safety data associated with fluoroquinolone use in children. Although permanent or destructive arthropathy remains a significant concern, currently available data demonstrate that arthralgia and arthropathy are relatively uncommon in children and resolve following cessation of fluoroquinolone exposure without resulting in long-term sequelae. The concern for safety and risk of adverse events associated with pediatric fluoroquinolone use is likely driving the limited prescribing of this drug class in pediatrics. However, in adults, fluoroquinolones are the most commonly prescribed broad-spectrum antibiotics, resulting in the development of drug-resistant bacteria that can be challenging to treat effectively. The consequence of misuse and overuse of fluoroquinolones leading to drug resistance is a greater, but frequently overlooked, safety concern that applies to both children and adults and one that should be considered at the point of prescribing.
<h4>Background</h4>The results of animal experiments show that quinolone antibacterial drugs may permanently damage the soft tissues of the weight-bearing joints of young animals. Out of safety concerns, using quinolones in children has always been controversial.<h4>Objective</h4>The aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making.<h4>Data sources</h4>The MEDLINE (Ovid), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), International Pharmaceutical Abstracts (Ovid), CINAHL, CNKI, VIP, and WanFang Data databases were searched from inception to 8 September 2021.<h4>Study selection</h4>All types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies.<h4>Data extraction</h4>Data extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form.<h4>Results</h4>The overall incidence rate of adverse drug events (ADEs) in children using systemic quinolones was 5.39% and the most common ADEs were gastrointestinal reactions (incidence rate, 2.02%). Quinolone-induced musculoskeletal ADEs in children were uncommon (0.76%). Meta-analysis results showed that the risk of musculoskeletal ADEs in children using quinolones was higher than children in the control group (51 studies; rate ratio [RR] 2.03, 95% confidence interval [CI] 1.82-2.26; p < 0.001; I<sup>2</sup> = 18.6%; moderate-quality evidence). However, the subgroup analysis results showed that differences might only be observed in children who were followed up for 2 months to 1 year (2-6 months: RR 2.56, 95% CI 2.26-2.89; 7 months to 1 year: RR 1.35, 95% CI 0.98-1.86). Moreover, children (adolescents) aged between 13 and 18 years might be sensitive to the musculoskeletal toxicity of quinolones (RR 2.69, 95% CI 2.37-3.05; moderate-quality evidence) and the risk of levofloxacin-induced musculoskeletal ADEs might be higher (RR 1.33, 95% CI 1.00-1.77; low-quality evidence).<h4>Conclusions</h4>Although the existing evidence shows that quinolone-induced musculoskeletal ADEs seem to be only short-term and reversible, and no serious skeletal and muscular system damage cases have been reported in children, quinolones should be avoided unless necessary in children because the incidence rate of quinolone-related ADEs is not low and they are broad-spectrum antibiotics that will induce the emergence of resistant strains if used frequently.
Key Clinical MessageThe present case emphasizes the importance of adhering to strict indications when prescribing fluoroquinolones. Although rare, drug‐induced tendinopathy is not confined to fluoroquinolones. The patient's and physician's awareness should be increased to reduce fluoroquinolones‐associated morbidity, particularly in patients with previously described risk factors.
<h4>Background</h4>The escalating resistance of <i>Mycoplasma pneumoniae</i> to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although tetracyclines and quinolones have been proposed as alternative therapeutic options, concerns regarding age-specific safety issues and the lack of consensus in recommendations across various national guidelines prevail. Thus, the primary objective of this study is to ascertain the most efficacious interventions for second-line treatment of <i>M</i>. <i>pneumoniae</i> infection while considering the age-specific safety issues associated with these interventions.<h4>Methods</h4>In this systematic review and network meta-analysis we searched PubMed, Embase, CNKI, and WanFang Data, from inception up to November 11th, 2023. Studies of quinolones or tetracyclines for the treatment of people with <i>M. pneumoniae</i> infection were collected and screened by reading published reports, with any type of study included, and no individual patient-level data requested. A systematic review and direct meta-analysis compared the efficacy of tetracyclines and quinolones regarding time to defervescence (TTD) and the rates of fever disappearance within 24 h and 48 h of antibiotic administration, for managing <i>M</i>. <i>pneumoniae</i> infection. Bayesian network meta-analysis (NMA) was employed to indirectly assess the relative effectiveness of different interventions in people with <i>M</i>. <i>pneumoniae</i> infection and the safety profile of medication in paediatric patients. This study is registered with PROSPERO, CRD42023478383.<h4>Findings</h4>The systematic review and direct meta-analysis included a total of 4 articles involving 246 patients, while the NMA encompassed 85 articles involving a substantial cohort of 7095 patients. The NMA measured the effectiveness across all ages and included 7043 patients, with a mean age of 37.80 ± 3.91 years. Of the 85 included studies, 14 (16.5%) were at low risk of bias, 71 (83.5%) were at moderate risk, and no studies were rated as having a high risk of bias. In the direct meta-analysis, no statistically significant differences were found between tetracyclines and quinolones concerning TTD (mean difference: -0.40, 95% CI: -1.43 to 0.63; <i>I</i><sup><i>2</i></sup> = 0%), fever disappearance rate within 24 h of antibiotic administration (OR: 0.37, 95% CI: 0.08-1.79; <i>I</i><sup><i>2</i></sup> = 58%), and fever disappearance rate within 48 h of antibiotic administration (OR: 1.10, 95% CI: 0.30-3.98; <i>I</i><sup><i>2</i></sup> = 59%). However, the comprehensive NMA analysis of clinical response (in 70 studies; n = 6143 patients), shortening of TTD (in 52 studies; n = 4363 patients), shortening length of cough relief or disappearance (in 39 studies; n = 3235 patients), fever disappearance rate at 48 h (in four studies; n = 418 patients) revealed that minocycline exhibited the most favourable outcomes across these various parameters, and the analysis of fever disappearance rate at 24 h (in three studies; n = 145 patients) revealed that levofloxacin may be the most effective, as indicated by the rank probabilities and surface under the cumulative ranking area (SUCRA) value. Moxifloxacin ranked second in clinical response and in shortening the length of cough relief or disappearance, and third in shortening TTD. Notably, when evaluating the occurrence of adverse reactions in paediatric patients (in four studies; n = 239 children), levofloxacin was associated with the highest SUCRA value rankings for the rate of adverse events.<h4>Interpretation</h4>Our findings suggest that tetracyclines and quinolones may be equally effective. Based on the age of participants in the included studies, minocycline may be the most effective intervention for children over eight years of age when all preventive measures are considered, whereas moxifloxacin may benefit people under eight years of age. However, these re
<h4>Background</h4>There has been reluctance to use fluoroquinolones in children because of arthropathy in animal models; experience in pediatric fever and neutropenia (FN) has been limited. Our primary objective was to describe the effectiveness and safety of fluoroquinolones as empiric therapy for children with FN.<h4>Methods</h4>We conducted electronic searches of Ovid Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in which any type of fluoroquinolone was administered as empiric therapy for FN.<h4>Results</h4>Of the 7281 reviewed articles, 10 were included in the meta-analysis that encompassed 740 episodes of FN. All studies consisted of low-risk FN episodes. The risk of treatment failure was 17% among those given ciprofloxacin monotherapy (n = 5 studies), 17% among those given nonciprofloxacin fluoroquinolone monotherapy (n = 2 studies), and 24% among those given fluoroquinolone combination therapy (n = 3 studies; P = 0.80). There were no cases of infectious deaths reported. Rates of sepsis and adverse events were very low.<h4>Conclusion</h4>Experience with fluoroquinolones demonstrates excellent outcomes and short-term safety, although reported studies have been restricted to low-risk patients. Fluoroquinolones can be comfortably adopted for low-risk FN, although experience in high-risk FN is uncertain in pediatrics.
Introduction: Fluoroquinolone exposure is reportedly associated with a higher risk of tendon disorders, tendonitis, or tendon rupture. However, studies in East Asian populations have not confirmed these risks in patients with comorbidities or concomitant medication use. This cohort study was designed to investigate the associations among fluoroquinolone exposure, comorbidities, medication use, and tendon disorders in Taiwan. Materials and Methods: This population-based, nationwide, observational, cohort study used data from the National Health Insurance Research database in Taiwan, a nationwide claims database that covers more than 99% of the Taiwanese population. The study period was from January 2000 to December 2015, and the median follow-up time was 11.05 ± 10.91 years. Patients who were exposed to fluoroquinolones for more than three consecutive days were enrolled, and patients without fluoroquinolone exposure who were matched by age, sex, and index year were enrolled as controls. The associations of comorbidities and concomitant medication use with tendon disorder occurrence were analyzed using Cox regression models. Results: The incidence of tendon disorders were 6.61 and 3.34 per 105 person-years in patients with and without fluoroquinolone exposure, respectively (adjusted hazard ratio, 1.423; 95% confidence interval [1.02,1.87]; p = 0.021). Sensitivity analyses yielded similar results. Patients under 18 and over 60 years with fluoroquinolone exposure; those with chronic kidney disease, diabetes, rheumatologic disease, cardiac disease, lipid disorder, or obesity; and those who concomitantly used statins, aromatase inhibitors, or glucocorticoids, had a significantly higher risk of tendon disorders. Conclusion: The long-term risk of tendon disorders was higher in patients with fluoroquinolone exposure than in those without fluoroquinolone exposure. Clinicians should assess the benefits and risks of fluoroquinolone use in patients at high risk of tendon disorders who require fluoroquinolone administration.
Achilles tendinopathy is a common problem, but its exact aetiology remains unclear. To evaluate the association between potential clinical risk factors and Achilles tendinopathy. Systematic review. The databases Embase, MEDLINE Ovid, Web of Science, Cochrane Library and Google Scholar were searched up to February 2018. To answer our research question, cohort studies investigating risk factors for Achilles tendinopathy in humans were included. We restricted our search to potential clinical risk factors (imaging studies were excluded). We included 10 cohort studies, all with a high risk of bias, from 5111 publications identified. There is limited evidence for nine risk factors: (1) prior lower limb tendinopathy or fracture, (2) use of ofloxacin (quinolone) antibiotics, (3) an increased time between heart transplantation and initiation of quinolone treatment for infectious disease, (4) moderate alcohol use, (5) training during cold weather, (6) decreased isokinetic plantar flexor strength, (7) abnormal gait pattern with decreased forward progression of propulsion, (8) more lateral foot roll-over at the forefoot flat phase and (9) creatinine clearance of <60 mL/min in heart transplant patients. Twenty-six other putative risk factors were not associated with Achilles tendinopathy, including being overweight, static foot posture and physical activity level. From an ocean of studies with high levels of bias, we extracted nine clinical risk factors that may increase a person's risk of Achilles tendinopathy. Clinicians may consider ofloxacin use, alcohol consumption and a reduced plantar flexor strength as modifiable risk factors when treating patients with Achilles tendinopathy. CRD42017053258.
<h4>Background</h4>The use of fluoroquinolone antibiotics has been restricted in children because of their potential to cause adverse musculoskeletal events. This study was performed to systematically evaluate whether there is a difference between fluoroquinolone and non-fluoroquinolone antibiotics in terms of their associated risk of adverse musculoskeletal events in children.<h4>Methods</h4>Cochrane Library, Embase, and PubMed databases were used to retrieve studies related to fluoroquinolone and non-fluoroquinolone-induced musculoskeletal adverse events in children. A meta-analysis was performed using Stata 11.<h4>Results</h4>A total of 10 studies were included in the analysis. The combined results showed that there was no statistical difference between fluoroquinolone and non-fluoroquinolone groups in terms of musculoskeletal adverse events in children (risk ratio = 1.145, 95% confidence interval = 0.974 - 1.345, P = .101). Subgroup analysis was performed using a random-effects model. Here, the effects on the trovafloxacin and levofloxacin groups were significantly different from that of the control group. However, musculoskeletal adverse events due to either drug was not reported after long-term follow-up.<h4>Conclusions</h4>The results showed that fluoroquinolone and non-fluoroquinolone antibiotics were not different in terms of their ability to cause musculoskeletal adverse events in children. For this reason, fluoroquinolone antibiotics can be used in children as appropriate.<h4>Prospero registration number</h4>CRD42019133900.
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