Fluoroquinolones In Children Research Articles

Systematic review on the safety of the use of quinolones in the pediatric population

Background: The safety of fluoroquinolones in the pediatric population has been a matter of concern due to the potential for adverse effects such as growth cartilage toxicity. Despite their broad antimicrobial spectrum and efficacy, the prescription of fluoroquinolones in children and adolescents is limited by the risk of arthralgias and other side effects. This study aims to evaluate the safety of fluoroquinolones in pediatric patients and the impact of regulatory actions on their prescription. Material and methods: A systematic review of studies investigating the safety of fluoroquinolones in the pediatric population was conducted. Studies that met specific inclusion criteria were selected, and relevant information on the decrease in fluoroquinolone prescriptions and their adverse effects was extracted. Results: In the study on the safety and tolerability of quinolones in the pediatric population, 22% (199/904) of patients experienced adverse events following treatment with quinolones. Gastrointestinal disorders, such as nausea and diarrhea, were the most frequent, affecting 12% (108/904) of patients. This was followed by skin rashes and effects on the central nervous system, at 5% (45/904) and 3% (27/904) respectively. Moxifloxacin demonstrated good tolerability across all age cohorts, without significant joint or neuropathic adverse findings. Specific safety studies of moxifloxacin confirmed its safety, showing no significant differences in safety variables compared to other antibiotics. Conclusion: It is crucial to continue monitoring the safety of fluoroquinolones in the pediatric population to ensure an adequate balance between the benefits and risks of their use.

Exposure to antibiotics and precocious puberty in children: A school-based cross-sectional study in China

Foods and water can be contaminated with antibiotics in China, which may affect children's health, but evidence on antibiotic exposure with precocious puberty (PP) is limited. This study explored the association of antibiotic exposure with PP in a school-based setting. A cross-sectional study with multistage stratified cluster random sampling was conducted in Zhongshan City, Guangdong Province and Qufu City, Shandong Province in China from October 11 to December 5, 2019. A first-morning urine sample was collected to detect antibiotic exposure. We detected 33 of 45 types of antibiotics from eight categories in 928 primary school children aged 6–12 years using HPLS-MS/MS. Detection rate of antibiotics was stratified by sex, study site, and BMI. The Tanner stages were assessed by professional pediatricians from local hospitals. PP is defined as the onset of secondary characters before 8-year-old or menarche before 10-year-old for girls and before 9-year-old for boys. Multivariable logistic regression was performed to examine the association between antibiotic exposure and PP after adjusting potential confounders. The overall detection rate of antibiotics was 93.0% in 928 children. We found the detection rate of tetracyclines and fluoroquinolones in children with PP was significantly higher than that of children with normal puberty (41.4% vs 29.9%, 56.8% vs 50.6%, respectively, all p < 0.05). Both fluoroquinolones (odds ratio (OR): 1.835, 95% confidence interval (CI): 1.066–3.158) and tetracyclines (OR: 2.120, 95% CI: 1.175–3.825) were associated with increased OR of PP after adjusting sex, age, BMI, study site, and family income. Specifically, compared to the values less than the limits of detection, low concentration of ofloxacin from fluoroquinolones (OR: 2.056, 95% CI: 1.091–3.875) and high concentration of chlortetracycline (OR: 3.027, 95% CI: 1.126–8.140) and tetracycline from tetracyclines (OR: 2.756, 95% CI: 1.167–6.506) were associated with increased OR of PP. Exposure to antibiotics, especially fluoroquinolones and tetracyclines was positively associated with precocious puberty.

Outpatient Fluoroquinolone Use in Children, 2000-2018.

While fluoroquinolones are commonly used in adults, the use in children has been low. Since 2000, there were 3 US Food and Drug Administration (FDA) Boxed warnings regarding fluoroquinolones (2008, 2013, and 2016). Our objective was to describe the use of fluoroquinolones in children and assess the impact of 3 recent FDA warnings on fluoroquinolone use. From 2000 to 2018, we assessed claims for all outpatient prescription fills to measure the use of systemic fluoroquinolones and other broad-spectrum antibiotics in children less than 18 years old in the MarketScan Commercial Claims and Encounters database. We describe demographics, indication for antibiotic, and clinical characteristics. To assess the impact of FDA warnings on fill rates, we conducted an interrupted time-series analysis. The cohort included 34.6 million unique beneficiaries less than 18 years old with 441 062 fluoroquinolone fills (5.5 fills per 1000 person-years). The fluoroquinolone fill rate was highest among children > 11 years old. Urinary tract infection was the most common associated diagnosis (21.8%). Since 2008, the fluoroquinolone fill rate has declined. By the end of the study period in December 2018, in the (counterfactual) absence of the FDA warnings, fluoroquinolone fill rate would have been 7.5 (95% confidence interval [CI]: 5.2-9.7); however, the corresponding rate in observed data was 2.8 (95% CI: 1.7-3.9). Fluoroquinolone use was low compared with other common broad-spectrum antibiotics and declining trends over time were associated with FDA warnings, even though these warnings were not pediatric specific. Future work should assess the adverse events at issue in these warnings in children.

Pediatric fluoroquinolone prescription in South Korea before and after a regulatory intervention: A nationwide study, 2007-2015

ObjectiveTo investigate the impact of national implementation of age restriction on fluoroquinolone prescription in children and adolescents.MethodsData collected from the database of Health Insurance Review and Assessment Service in South Korea, a national health insurance system to analyze fluoroquinolone prescribing practice in children and adolescents younger than 18 years, between 2007 and 2015. The age restriction was implemented in December 2009. The annual prescription rate of FQ per 100,000 person-years was calculated and an autoregressive model was used to predict the prescription pattern if an intervention had not occurred.ResultsA total of 505,859 children received systemic fluoroquinolone during the study period—297,054 ciprofloxacin, and 208,805 levofloxacin. After implementation of the drug utilization review program, the annual prescription rate for ciprofloxacin declined by 97.5% (from 840 to 21 per 100,000 person-years, P < 0.001), and for levofloxacin by 96.4% (from 598 to 11 per 100,000 person-years, P < 0.001). The decline was more dramatic in the outpatient setting than in the inpatient setting for both drugs.ConclusionThe dramatic and sustained decline in prescription number and change in prescription pattern after the regulatory action suggests that the implementation under drug utilization review program was successful in controlling excessive and inappropriate use of fluoroquinolones in children, possibly guiding towards more judicious and selective prescription behavior.

The Use of Systemic and Topical Fluoroquinolones.

Appropriate prescribing practices for fluoroquinolones, as well as all antimicrobial agents, are essential as evolving resistance patterns are considered, additional treatment indications are identified, and the toxicity profile of fluoroquinolones in children has become better defined. Earlier recommendations for systemic therapy remain; expanded uses of fluoroquinolones for the treatment of certain infections are outlined in this report. Prescribing clinicians should be aware of specific adverse reactions associated with fluoroquinolones, and their use in children should continue to be limited to the treatment of infections for which no safe and effective alternative exists or in situations in which oral fluoroquinolone treatment represents a reasonable alternative to parenteral antimicrobial therapy.

The Risk of Musculoskeletal Adverse Events With Fluoroquinolones in Children: What Is the Verdict Now?

The Risk of Musculoskeletal Adverse Events With Fluoroquinolones in Children: What Is the Verdict Now?

Fluoroquinolones in children: update of the literature

The use of fluoroquinolones (FQ), antibiotics, which have excellent pharmacokinetic and pharmacodynamic characteristics and a broad spectrum of action, has increased dramatically in recent years, both in adults and children. Numerous safety and efficacy data are now available on FQ use in children, particularly regarding the treatment of complicated infections of the urinary tract, typhoid fever, pneumonia, acute external otitis, acute media otitis, meningoencephalitis, sepsis in neutropenic children and multidrug-resistant tuberculosis (MDR-TB), though sometimes studies have the limitations that they were conducted in selected populations, such as children with cystic fibrosis. Despite available safety data are encouraging, there is still an open debate on the toxicity of this class of antibiotics on weight-bearing joints in children. Not being able to exclude the possibility that, in rare cases, this event is likely to occur, their use in children should be limited to cases where the cost-benefit has been carefully examined, for example, in the case of sepsis or other severe infections from multi-resistant bacteria and not responsive to other classes of drugs. Furthermore, considering the increased use of FQ in children, it is possible that there is an increase in the incidence of infections from resistant germs (such as Escherichia coli, and pneumococci), as occurred in adults. In order to limit the diffusion of resistance, a judicious and appropriate use of this class of drugs is recommended.

Acute Bacterial Sinusitis in Children

On the basis of strong research evidence, the pathogenesis of sinusitis involves 3 key factors: sinusostia obstruction, ciliary dysfunction, and thickening of sinus secretions. On the basis of studies of the microbiology of otitis media, H influenzae is playing an increasingly important role in the etiology of sinusitis, exceeding that of S pneumoniae in some areas, and b-lactamase production by H influenzae is increasing in respiratory isolates in the United States. On the basis of some research evidence and consensus,the presentation of acute bacterial sinusitis conforms to 1 of 3 predicable patterns; persistent, severe, and worsening symptoms. On the basis of some research evidence and consensus,the diagnosis of sinusitis should be made by applying strict clinical criteria. This approach will select children with upper respiratory infection symptoms who are most likely to benefit from an antibiotic. On the basis of some research evidence and consensus,imaging is not indicated routinely in the diagnosis of sinusitis. Computed tomography or magnetic resonance imaging provides useful information when complications of sinusitis are suspected. On the basis of some research evidence and consensus,amoxicillin-clavulanate should be considered asa first-line agent for the treatment of sinusitis.

Systemic use of fluoroquinolone in children

Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.

Fluoroquinolones in Children With Fever and Neutropenia

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. 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. 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. 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.

The Use of Systemic and Topical Fluoroquinolones

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.

Efectos adversos musculoesqueléticos por el uso de fluoroquinolonas en niños: un metaanálisis

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. To evaluate by systematic review and meta-analysis the relation between fluoroquinolonas and musculoskeletal disorders in children. 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. 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). 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.

The use of fluoroquinolone in children

The fluoroquinolones are an important group of antibiotics widely used in the treatment of various infectious diseases in adults, as a result of an excellent spectrum of activity, good tissue penetration and convenient ways of administration. In recent decades, there has been extensive development, clinical investigation, licensure and use of fluoroquinolone antibiotics. However, the use of fluoroquinolones in children has been limited because of their potential to induce arthropathy in juvenile animals. Despite class label warnings against use in children, prescriptions for quinolone antibiotics to treat infections in children have become increasingly prevalent. The main use of fluoroquinolones in pediatrics should be, understandably, in serious life-threatening infections for which other antibiotics therapies are not effective or available. While most of the published studies failed to detect an increased rate of articular adverse effects in children treated with fluoroquinolones, an increase in the use of these compounds, particularly in community-acquired lower respiratory infections, could accelerate the emergence of multidrug-resistant (including fluoroquinolone) pneumococcal strains. This review will discus the main issues related to the use of fluoroquinolones in children, the major problems of resistance developing among these compounds, with special emphasis on the potential side effects and skilled use of these alternative potent drugs in pediatric infection.

Ciprofloxacin Treatment in Preterm Neonates in Bangladesh

Quinolone-induced arthropathic toxicity in weight-bearing joints observed in juvenile animals during preclinical testing has largely restricted the routine use of ciprofloxacin in the pediatric age group. As histopathologic, radiologic and magnetic resonance imaging monitoring evidence has gathered supporting the safety of fluoroquinolones in children, many pediatricians have started to prescribe quinolones to some patients on a compassionate basis. The objective of this study was to ascertain the safety of ciprofloxacin in preterm neonates <33 weeks gestational age treated at Dhaka Shishu (Children) Hospital in Bangladesh. Long-term follow up was done to monitor the growth and development of preterm infants who were administered intravenous ciprofloxacin in the neonatal period. Ciprofloxacin was used only as a life-saving therapy in cases of sepsis produced by bacterial agents resistant to other antibiotics. Another group of preterm neonates with septicemia who were not exposed to ciprofloxacin, but effectively treated with other antibiotics and followed up, were matched with cases for gender, gestational age and birth weight and included as a comparison group. Forty-eight patients in the ciprofloxacin group and 66 patients in the comparison group were followed up for a mean of 24.7 +/- 18.5 months and 21.6 +/- 18.8 months, respectively. No osteoarticular problems or joint deformities were observed in the ciprofloxacin group during treatment or follow up. No differences in growth and development between the groups were found. Ciprofloxacin is a safe therapeutic option for newborns with sepsis produced by multiply resistant organisms.

Guidelines for the use of fluoroquinolones in children have been released by the American Academy of Pediatrics (AAP) Committee on Infectious Diseases.

Guidelines for the use of fluoroquinolones in children have been released by the American Academy of Pediatrics (AAP) Committee on Infectious Diseases.

Guidelines for the use of fluoroquinolones in children have been released by the American Academy of Pediatrics (AAP) Committee on Infectious Diseases.

Guidelines for the use of fluoroquinolones in children have been released by the American Academy of Pediatrics (AAP) Committee on Infectious Diseases.

The use of fluoroquinolones in children: recent advances

Fluoroquinolones are an important group of antibiotics that are used widely in the treatment of various infectious diseases in adults as a result of their excellent spectrum of activity, significant tissue penetration and convenient routes of administration. Their use in children, however, has been limited until recently as a result of possible fluoroquinolone-induced joint toxicity. Nevertheless, this group of antibiotics is rapidly gaining consideration for use in children as new agents are emerging with a wide antimicrobial range of action and minimal toxicity, even in young children. This review presents the pharmacokinetics, clinical indications and possible toxicity of fluoroquinolones in children, as well as the newer agents and their safety profile in pediatrics.

Fluoroquinolones in children addressed in AAP policy

For the past two decades, the use of fluoroquinolones in children has been approached with caution and concern by pediatricians and the Food and Drug Administration (FDA). ![Figure][1] Dr. Bradley As more data on the safety and efficacy of this class of antimicrobials in children have

The Use of Systemic Fluoroquinolones

The only indications for which a fluoroquinolone (ie, ciprofloxacin) is licensed by the US Food and Drug Administration for use in patients younger than 18 years are complicated urinary tract infections, pyelonephritis, and postexposure treatment for inhalation anthrax. Nonetheless, approximately 520,000 prescriptions for fluoroquinolones were written in the United States for patients younger than 18 years in 2002; 13,800 were written for infants and children 2 to 6 years of age, and 2750 were written for infants younger than 2 years. Clinical trials of fluoroquinolones in pediatric patients with various diagnoses have been published and are reviewed. Fluoroquinolones cause arthrotoxicity in juvenile animals and have been associated with reversible musculoskeletal events in both children and adults. Other adverse events associated with fluoroquinolones include central nervous system disorders, photosensitivity, disorders of glucose homeostasis, prolongation of QT interval with rare cases of torsade de pointes (often lethal ventricular arrhythmia in patients with long QT syndrome), hepatic dysfunction, and rashes. The increased use of fluoroquinolones in adults has resulted in increased bacterial resistance to this class of antibacterial agents. This report provides specific guidelines for the systemic use of fluoroquinolones in children. Fluoroquinolone use should be restricted to situations in which there is no safe and effective alternative to treat an infection caused by multidrug-resistant bacteria or to provide oral therapy when parenteral therapy is not feasible and no other effective oral agent is available.

The use of fluoroquinolones in children

The fluoroquinolones are an important group of antibiotics widely used in the treatment of various infectious diseases in adults, as a result of an excellent spectrum of activity, good tissue penetration and convenient ways of administration. Their use in children is limited as a result of possible fluoroquinolone-induced joint/cartilage toxicity observed mainly in juvenile animal studies. Fluoroquinolones were successfully used in immunocompromised children and also in those suffering from multidrug-resistant Gram-negative infections (including neonatal infections and multidrug-resistant enteric infections caused by Salmonella and Shigella spp.). The fluoroquinolones were shown to be efficacious and well tolerated in the treatment of complicated cases of acute otitis media. The emergence of Streptococcus pneumoniae with reduced susceptibility to fluoroquinolones has been described worldwide. No arthropathy associated with fluoroquinolone use in children was evident. With the exception of cystic fibrosis and life-endangering infections, the use of fluoroquinolones in pediatrics should be limited to Gram-negative neonatal meningitis, Salmonella and Shigella spp. infections, chronic suppurative otitis media and some cases of complicated acute otitis media. Unskilled use of fluoroquinolones in children, particularly in community-acquired lower respiratory infections, could accelerate the emergence of pneumococcal resistance.