Chalumeau et al. The most commonly affected systems were the gastrointestinal followed by musculoskeletal arthralgias of large joints or myalgias but no tendinopathy , skin, and central nervous systems. Adverse musculoskeletal events occurred more frequently in the FQ group than in the controls 3. Although adverse events did occur more frequently with FQ treatment, all cases were transient, and no severe or persistent musculoskeletal injuries were observed at follow-up.
A large, prospective safety study conducted by Bayer compared 1 intravenous ceftazidime with intravenous ciprofloxacin, permitting oral step-down therapy, and 2 oral ciprofloxacin with oral cefixime or trimethoprim-sulfamethoxazole for the treatment of complicated urinary tract infections in children aged years 18 , One of the primary objectives of the study was to evaluate musculoskeletal safety with ciprofloxacin therapy.
At 6 weeks follow-up, the arthropathy rate was 9. In a systematic review of ciprofloxacin safety in 16, children from studies, musculoskeletal adverse events occurred in pediatric patients estimated risk, 1. Patient age at occurrence of arthropathy ranged from 7 months to 17 years median age, 10 years.
Musculoskeletal events were reversible through conservative management, which included cessation of antibiotics. Kaguelidou et al. The study population for this review included ciprofloxacin-treated patients and controls from 5 cohort studies, as well as ciprofloxacin-treated neonates from 27 case reports or series.
Ciprofloxacin was used in neonates as a salvage therapy for sepsis caused by multidrug-resistant pathogens or for clinical exacerbation after first-line antibiotic therapy. No serious adverse events were observed.
Analysis of the short-term and long-term effects of ciprofloxacin on cartilage and growth indicated no significant differences between ciprofloxacin and control groups with respect to these factors. Using multiple-regression modeling and adjusting for weight and gestational age at birth, 2 of the studies showed no significant relationship between ciprofloxacin use and the cartilage size of the right knee, as measured by ultrasound 27 , and no height differences at 12 months corrected age Noel et al.
Spontaneous reports of 1 or more musculoskeletal adverse events arthritis, arthralgias, tendinopathy, or gait abnormality were higher in levofloxacin-treated children than in those treated with non-FQ antibiotics at both 2-month 2. However, long-term outcomes of children with musculoskeletal adverse events during the 5-year safety study were slightly higher in the control group 2. Of note, current studies are investigating moxifloxacin safety in the pediatric population 30 , Despite the limited indications for the use of FQs in the pediatric population and concerns for adverse events, approximately , FQ prescriptions were written for patients younger than 18 years in the United States US in An estimated 13, of those prescriptions were for children years of age, and 2, were written for those 2 years and younger Although there have been no systemic data on FQ use in children in Korea, 1 study, which analyzed the antibiotic prescription patterns of pediatricians and ENT ear, nose, and throat physicians, reported that the proportion of quinolones prescribed was 3.
These data should be interpreted with caution, as they were collected from prescription sheets in 7 community pharmacies within Ulsan City, Korea More data are clearly needed to assess FQ use in Korean children.
Currently, FQs that are approved by the U. Food and Drug Administration FDA for use in children include ciprofloxacin for the treatment of inhalation anthrax, complicated urinary tract infections, and pyelonephritis along with levofloxacin for inhalational anthrax 15 , Ciprofloxacin is the only FQ approved by the European Medicines Agency for use in the following pediatric conditions: bronchopulmonary infections in cystic fibrosis caused by Pseudomonas aeruginosa , complicated urinary tract infections, pyelonephritis, and inhalation anthrax both for postexposure prophylaxis and curative treatment Ciprofloxacin and levofloxacin are available as oral suspensions in many countries.
An oral suspension of ciprofloxacin is available in the US, Canada, and 15 European countries 34 , but systemic FQ use is not approved in Korea for any indication in children younger than 18 years. Additionally, oral suspensions are not available in Korea. The World Health Organization WHO has provided guidelines for the management of common illnesses in hospitals with limited resources. In the 18th WHO Expert Committee meeting for "The Selection and Use of Essential Medicines," the committee concluded that the effectiveness and safety of FQs in the treatment of life-threatening bacterial infections, such as resistant tuberculosis, dysentery, and cholera, in children have been sufficiently established In , the American Academy of Pediatrics AAP published a policy statement summarizing the assessment of risks and benefits of FQs in pediatric patients According to the AAP, situations in which FQs may be useful include multidrug-resistant infections for which there is no safe and effective alternative, and when parenteral therapy is not feasible and no other effective oral agent is available.
As data on the musculoskeletal safety of FQs in the pediatric population accumulate, more guidelines recommend FQ use in children.
In the clinical practice guidelines for community-acquired pneumonia CAP in infants and children by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America IDSA 37 , levofloxacin was recommended in certain situations as an alternative treatment option for Streptococcus pneumoniae , Haemophilus influenzae typeable [A-F] or nontypeable , Mycoplasma pneumoniae , Chlamydia trachomatis , and Chlamydia pneumoniae.
Levofloxacin is preferred in oral therapy step-down therapy or mild infection for CAP caused by penicillin-resistant S. Moxifloxacin is recommended as an alternative oral agent for CAP caused by M. In addition, levofloxacin is now recommended in children as a treatment option for acute bacterial rhinosinusitis according to the IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults 38 : with a history of type I hypersensitivity to penicillin, as a second-line agent for children with risk for antibiotic resistance, failed initial therapy, or severe infection requiring hospitalization.
Updated WHO guideline from for drug-resistant tuberculosis recommended that second-line antituberculosis regimens should include a later-generation FQ such as levofloxacin, moxifloxacin, or gatifloxacin Although concerns about potential musculoskeletal adverse effects in young children treated with FQs remain, many previous studies have repeatedly shown no significant increase in musculoskeletal complications in these children.
In a review article, Schaad 40 commented that the triad of feared arthrotoxicity, potential explosion in bacterial resistance, and enormous requirements regarding adequate study and postmarketing control would make it unlikely that FQs will ever be recommended for treating common infections in children. However, clinicians today are facing more situations when the use of FQs should be considered in treating pediatric patients who have not responded to standard therapy and those who are infected with multidrug-resistant pathogens, including tuberculosis.
In addition, in areas with restricted medical resources, FQs may be the only option for the treatment of serious infections, especially when parenteral drug administration is not available. In conclusion, FQs should not be used in pediatric patients for routine infections when other safe and effective antimicrobials are available. However, FQs should be considered in life-threatening and difficult-to-treat infections when alternative agents cannot be used.
No potential conflict of interest relevant to this article was reported. National Center for Biotechnology Information , U. Journal List Korean J Pediatr v. Korean J Pediatr. Published online May Find articles by Soo-Han Choi. Find articles by Eun Young Kim. Find articles by Yae-Jean Kim. Author information Article notes Copyright and License information Disclaimer.
Corresponding author. Received Dec 18; Accepted Mar This article has been cited by other articles in PMC. Quincy, Massachusetts. Casa Grande, Arizona. Waterford, Connecticut. Pediatrics, General.
Outpatient Pediatrician. Peabody, Massachusetts. Maternal-Fetal Medicine. New York City, New York. Vascular Neurologist- Hartford Hospital - 2. Hartford, Connecticut. Controversy: The routine use of tetracyclines in children aged less than 8 years is not recommended because of a long-standing association of these agents with permanent tooth discoloration.
Tetracyclines, which bind to cations, can result in the formation of tetracycline—calcium complexes that irreversibly deposit in developing bones and teeth. Tetracycline-induced photosensitivity, another adverse event in the pediatric population, usually manifests as a light-sensitive rash similar to an exaggerated sunburn.
This occurs because of the extensive absorption of ultraviolet light by the tetracyclines. While phototoxicity can be a significant concern, the permanent nature of tooth discoloration underscores the importance of avoiding the use of these agents in young children whenever possible.
However, when tetracycline use is imperative, limited evidence suggests that minimizing the total dose and length of exposure and using a tetracycline with decreased calcium binding may reduce the risk of tooth discoloration.
Potential Benefits: In certain difficult-to-treat infections with limited alternative therapies, tetracycline may be efficacious and relatively safe in children aged less than 8 years. Another indication for the use of tetracyclines and fluoroquinolones in children is the treatment of Bacillus anthracis infection or exposure. The American Academy of Pediatrics AAP recommendations on fluoroquinolones limit their use to three major circumstances: 1 FDA-approved indications; 2 multidrug-resistant pathogens with no safe or effective alternative; and 3 oral fluoroquinolone sensitivity when all other options are IV only see dosing recommendations, TABLE 2.
The AAP recommends the use of tetracyclines in infections where the benefits outweigh the risks of adverse events. These include rickettsial infections such as RMSF or ehrlichiosis, and other infections such as cholera and anthrax. In children, the pharmacokinetic and pharmacodynamic processes of many drugs, especially antibiotics, may be different compared with those in adults.
Because of the ongoing safety concerns surrounding the use of fluoroquinolones and tetracyclines in children, these agents should continue to be limited to treatment of FDA-approved indications or for infections for which no safe and effective alternative exists.
Developmental pharmacology—drug disposition, action and therapy in infants and children. N Engl J Med. Routledge PA. Pharmacokinetics in children.
J Antimicrob Chemother. Drug metabolism and disposition in children. Fundam Clin Pharmacol. The use of systemic fluoroquinolones. The use of systemic and topical fluoroquinolones. Ciprofloxacin safety in paediatrics: a systematic review.
Arch Dis Child. Comparative safety profile of levofloxacin in children with a focus on four specific musculoskeletal disorders. Pediatr Infect Dis J. Relationship between fluoroquinolone use and changes in susceptibility to fluoroquinolones of selected pathogens in 10 United States teaching hospitals, Clin Infect Dis. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae : a case-control study.
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