Assess Risk/Benefits Before Using Fluoroquinolones

Fluoroquinolones continue to play a role in pediatrics, but providers should continue to restrict their use to specific clinical situations and after a careful risk/benefit discussion with parents.

As in the 2006 American Academy of Pediatrics Clinical Report on use of systemic and topical fluoroquinolones, the use of parenteral fluoroquinolones is still endorsed for treatment of infections caused by multidrug-resistant pathogens and/or in situations where there is no other safe and effective parenteral agent. Oral fluoroquinolones also are considered for treatment of infections when the only other option is intravenous treatment with other classes of antibiotic agents.

The 2011 update to the AAP’s 2006 policy statement (Pediatrics 2011;128:e1034-45) reiterated this overall advice to restrict fluoroquinolone use in children, but added recent data on safety as well as information for newer agents such as levofloxacin, that were not discussed in the 2006 statement (Pediatrics 2006;118:1287-92).

Most of the current use of fluoroquinolones in children remains off label. The only Food and Drug Administration pediatric approvals are for the first-generation agent nalidixic acid for urinary tract infections (UTIs), ciprofloxacin for inhalational anthrax and complicated UTI and pyelonephritis, and the respiratory fluoroquinolone, levofloxacin, for inhalational anthrax. Moreover, only ciprofloxacin and levofloxacin are available in a suspension formulation.

Since publication of the previous AAP policy, the clinical value of fluoroquinolones for the treatment of UTIs caused by antibiotic-resistant uropathogens has been further documented. Moreover, the use of topical fluoroquinolone drops for external otitis/tympanostomy tube otorrhea – for which we have far less concern about toxicity – is now recommended as well.

When to Use Fluoroquinolons

A situation beyond UTI where an oral fluoroquinolone such as ciprofloxacin might be considered is in the setting of Pseudomonas aeruginosa osteomyelitis. Only 1.5% of nail puncture wounds are associated with subsequent infection (early infection is usually due to Streptococcus aureus) but when an only modestly painful infectious process at the site occurs beyond days 3-4 after the puncture, suspect P. aeruginosa. Such infections are usually initially treated with parenteral third- or fourth-generation cephalosporins with good pseudomonal coverage, i.e. ceftazidime or cefepime. But following good surgical debridement and when identification of the pathogen is available, outpatient treatment with oral ciprofloxacin is considered reasonable (assuming you have confirmed susceptibility).

A respiratory fluoroquinolone such as levofloxacin might be considered for treatment of nonmeningeal multidrug-resistant pneumococcal infection. We recently cared for a 5-month-old who presented with classic signs of mastoiditis with a large subperiosteal mastoid abscess. Serotype 19A Streptococcus pneumoniae was isolated from middle ear, the subperiosteal abscess, and mastoid bone. She responded well to surgical drainage and mastoidectomy with myringotomy tube placement and initial parenteral therapy with vancomycin (plus ceftriaxone), and was transitioned to oral levofloxacin.

Fluoroquinolone Safety in Children

We have more safety data now than we did in 2006, although still not enough to say with complete certainty that fluoroquinolones are without osteoarticular risk in children. Despite signals of cartilage damage seen in animal studies using very high or prolonged dosing, no published reports exist of physician-diagnosed cartilage damage in children in the United States, either from controlled clinical trials of fluoroquinolones or from unsolicited reporting to the FDA or drug manufacturers.

Two prospective, randomized studies on fluoroquinolone safety in children have been published since 2006. One study, involving 684 children aged 1-17 years, was performed at the request of the FDA by Bayer for ciprofloxacin in the treatment of complicated UTI and pyelonephritis. The other study, a 5-year safety assessment of 2,233 children who received levofloxacin treatment, was performed by Johnson & Johnson as part of their FDA-coordinated program of pediatric drug development. Some evidence of increased musculoskeletal complaints with fluoroquinolones was found in both studies, although neither data set strongly supported the occurrence of sustained injury to developing bones or joints in children with the two fluoroquinolones, compared with agents of other classes.

More safety data will become available in the future and will inform our decision making further, but I still don’t foresee widespread pediatric use. Fluoroquinolones are considered among the most broad-spectrum agents. In this era of increasing antimicrobial resistance, as we exercise responsible antimicrobial stewardship, the use of any broad spectrum agent needs to be carefully considered before use in every case. Fortunately at this time, the need to "go to" parenteral or oral fluoroquinolone therapy remains an uncommon occurrence for most pediatricians.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She and Dr. John Bradley were the cowriters of the statement, which comes from the Committee on Infectious Diseases of the AAP.

Fluoroquinolones continue to play a role in pediatrics, but providers should continue to restrict their use to specific clinical situations and after a careful risk/benefit discussion with parents.

As in the 2006 American Academy of Pediatrics Clinical Report on use of systemic and topical fluoroquinolones, the use of parenteral fluoroquinolones is still endorsed for treatment of infections caused by multidrug-resistant pathogens and/or in situations where there is no other safe and effective parenteral agent. Oral fluoroquinolones also are considered for treatment of infections when the only other option is intravenous treatment with other classes of antibiotic agents.

The 2011 update to the AAP’s 2006 policy statement (Pediatrics 2011;128:e1034-45) reiterated this overall advice to restrict fluoroquinolone use in children, but added recent data on safety as well as information for newer agents such as levofloxacin, that were not discussed in the 2006 statement (Pediatrics 2006;118:1287-92).

Most of the current use of fluoroquinolones in children remains off label. The only Food and Drug Administration pediatric approvals are for the first-generation agent nalidixic acid for urinary tract infections (UTIs), ciprofloxacin for inhalational anthrax and complicated UTI and pyelonephritis, and the respiratory fluoroquinolone, levofloxacin, for inhalational anthrax. Moreover, only ciprofloxacin and levofloxacin are available in a suspension formulation.

Since publication of the previous AAP policy, the clinical value of fluoroquinolones for the treatment of UTIs caused by antibiotic-resistant uropathogens has been further documented. Moreover, the use of topical fluoroquinolone drops for external otitis/tympanostomy tube otorrhea – for which we have far less concern about toxicity – is now recommended as well.

When to Use Fluoroquinolons

A situation beyond UTI where an oral fluoroquinolone such as ciprofloxacin might be considered is in the setting of Pseudomonas aeruginosa osteomyelitis. Only 1.5% of nail puncture wounds are associated with subsequent infection (early infection is usually due to Streptococcus aureus) but when an only modestly painful infectious process at the site occurs beyond days 3-4 after the puncture, suspect P. aeruginosa. Such infections are usually initially treated with parenteral third- or fourth-generation cephalosporins with good pseudomonal coverage, i.e. ceftazidime or cefepime. But following good surgical debridement and when identification of the pathogen is available, outpatient treatment with oral ciprofloxacin is considered reasonable (assuming you have confirmed susceptibility).

A respiratory fluoroquinolone such as levofloxacin might be considered for treatment of nonmeningeal multidrug-resistant pneumococcal infection. We recently cared for a 5-month-old who presented with classic signs of mastoiditis with a large subperiosteal mastoid abscess. Serotype 19A Streptococcus pneumoniae was isolated from middle ear, the subperiosteal abscess, and mastoid bone. She responded well to surgical drainage and mastoidectomy with myringotomy tube placement and initial parenteral therapy with vancomycin (plus ceftriaxone), and was transitioned to oral levofloxacin.

Fluoroquinolone Safety in Children

We have more safety data now than we did in 2006, although still not enough to say with complete certainty that fluoroquinolones are without osteoarticular risk in children. Despite signals of cartilage damage seen in animal studies using very high or prolonged dosing, no published reports exist of physician-diagnosed cartilage damage in children in the United States, either from controlled clinical trials of fluoroquinolones or from unsolicited reporting to the FDA or drug manufacturers.

Two prospective, randomized studies on fluoroquinolone safety in children have been published since 2006. One study, involving 684 children aged 1-17 years, was performed at the request of the FDA by Bayer for ciprofloxacin in the treatment of complicated UTI and pyelonephritis. The other study, a 5-year safety assessment of 2,233 children who received levofloxacin treatment, was performed by Johnson & Johnson as part of their FDA-coordinated program of pediatric drug development. Some evidence of increased musculoskeletal complaints with fluoroquinolones was found in both studies, although neither data set strongly supported the occurrence of sustained injury to developing bones or joints in children with the two fluoroquinolones, compared with agents of other classes.

More safety data will become available in the future and will inform our decision making further, but I still don’t foresee widespread pediatric use. Fluoroquinolones are considered among the most broad-spectrum agents. In this era of increasing antimicrobial resistance, as we exercise responsible antimicrobial stewardship, the use of any broad spectrum agent needs to be carefully considered before use in every case. Fortunately at this time, the need to "go to" parenteral or oral fluoroquinolone therapy remains an uncommon occurrence for most pediatricians.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She and Dr. John Bradley were the cowriters of the statement, which comes from the Committee on Infectious Diseases of the AAP.

Fluoroquinolones continue to play a role in pediatrics, but providers should continue to restrict their use to specific clinical situations and after a careful risk/benefit discussion with parents.

As in the 2006 American Academy of Pediatrics Clinical Report on use of systemic and topical fluoroquinolones, the use of parenteral fluoroquinolones is still endorsed for treatment of infections caused by multidrug-resistant pathogens and/or in situations where there is no other safe and effective parenteral agent. Oral fluoroquinolones also are considered for treatment of infections when the only other option is intravenous treatment with other classes of antibiotic agents.

The 2011 update to the AAP’s 2006 policy statement (Pediatrics 2011;128:e1034-45) reiterated this overall advice to restrict fluoroquinolone use in children, but added recent data on safety as well as information for newer agents such as levofloxacin, that were not discussed in the 2006 statement (Pediatrics 2006;118:1287-92).

Most of the current use of fluoroquinolones in children remains off label. The only Food and Drug Administration pediatric approvals are for the first-generation agent nalidixic acid for urinary tract infections (UTIs), ciprofloxacin for inhalational anthrax and complicated UTI and pyelonephritis, and the respiratory fluoroquinolone, levofloxacin, for inhalational anthrax. Moreover, only ciprofloxacin and levofloxacin are available in a suspension formulation.

Since publication of the previous AAP policy, the clinical value of fluoroquinolones for the treatment of UTIs caused by antibiotic-resistant uropathogens has been further documented. Moreover, the use of topical fluoroquinolone drops for external otitis/tympanostomy tube otorrhea – for which we have far less concern about toxicity – is now recommended as well.

When to Use Fluoroquinolons

A situation beyond UTI where an oral fluoroquinolone such as ciprofloxacin might be considered is in the setting of Pseudomonas aeruginosa osteomyelitis. Only 1.5% of nail puncture wounds are associated with subsequent infection (early infection is usually due to Streptococcus aureus) but when an only modestly painful infectious process at the site occurs beyond days 3-4 after the puncture, suspect P. aeruginosa. Such infections are usually initially treated with parenteral third- or fourth-generation cephalosporins with good pseudomonal coverage, i.e. ceftazidime or cefepime. But following good surgical debridement and when identification of the pathogen is available, outpatient treatment with oral ciprofloxacin is considered reasonable (assuming you have confirmed susceptibility).

A respiratory fluoroquinolone such as levofloxacin might be considered for treatment of nonmeningeal multidrug-resistant pneumococcal infection. We recently cared for a 5-month-old who presented with classic signs of mastoiditis with a large subperiosteal mastoid abscess. Serotype 19A Streptococcus pneumoniae was isolated from middle ear, the subperiosteal abscess, and mastoid bone. She responded well to surgical drainage and mastoidectomy with myringotomy tube placement and initial parenteral therapy with vancomycin (plus ceftriaxone), and was transitioned to oral levofloxacin.

Fluoroquinolone Safety in Children

We have more safety data now than we did in 2006, although still not enough to say with complete certainty that fluoroquinolones are without osteoarticular risk in children. Despite signals of cartilage damage seen in animal studies using very high or prolonged dosing, no published reports exist of physician-diagnosed cartilage damage in children in the United States, either from controlled clinical trials of fluoroquinolones or from unsolicited reporting to the FDA or drug manufacturers.

Two prospective, randomized studies on fluoroquinolone safety in children have been published since 2006. One study, involving 684 children aged 1-17 years, was performed at the request of the FDA by Bayer for ciprofloxacin in the treatment of complicated UTI and pyelonephritis. The other study, a 5-year safety assessment of 2,233 children who received levofloxacin treatment, was performed by Johnson & Johnson as part of their FDA-coordinated program of pediatric drug development. Some evidence of increased musculoskeletal complaints with fluoroquinolones was found in both studies, although neither data set strongly supported the occurrence of sustained injury to developing bones or joints in children with the two fluoroquinolones, compared with agents of other classes.

More safety data will become available in the future and will inform our decision making further, but I still don’t foresee widespread pediatric use. Fluoroquinolones are considered among the most broad-spectrum agents. In this era of increasing antimicrobial resistance, as we exercise responsible antimicrobial stewardship, the use of any broad spectrum agent needs to be carefully considered before use in every case. Fortunately at this time, the need to "go to" parenteral or oral fluoroquinolone therapy remains an uncommon occurrence for most pediatricians.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. She and Dr. John Bradley were the cowriters of the statement, which comes from the Committee on Infectious Diseases of the AAP.