A Reappraisal of Ciprofloxacin Use in Infants and Children

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS


Pediatr Pharm. 2018;24(8) 

In This Article

Ciprofloxacin Prescribing in Children

As a result of the risk for articular damage first identified with nalidixic acid, the precursor to the fluoroquinolones, the FDA has required manufacturers to include in their product labeling that these drugs are not a first choice for treatment of pediatric infections. Approved uses for ciprofloxacin in children are limited to the treatment of complicated urinary tract infections (UTIs) and pyelonephritis caused by E. coli not sensitive to other agents, prophylaxis or treatment of plague due to Yersinia pestis, and management of patients following inhalational anthrax exposure.[4]

Off-label prescribing of ciprofloxacin in children has been well documented. A recent study from Etminan and colleagues in The Pediatric Infectious Disease Journal evaluated oral fluoroquinolone prescribing in children in the United States between 2006 and 2015 using the PharMetrics Plus™ health claims database.[5] A total of 372,357 fluoroquinolone prescriptions were written for 2,754,431 children, with the frequency increasing each year until a peak in 2013. Ciprofloxacin was the most frequently used fluoroquinolone, accounting for 90% of the prescriptions. Nearly half of the prescriptions (48%) were written for children under 10 years of age and 22% were determined by the authors to have been inappropriate, based on guidelines for fluoroquinolone use published by the American Academy of Pediatrics in 2016.[6]

Another study of pediatric fluoroquinolone use was published by Meesters and colleagues in the February 2018 issue of BMC Infectious Diseases.[7] The authors analyzed the indications for systemic fluoroquinolone prescribing in children treated at two Belgian children's hospitals between 2010 and 2013. Of the 262 prescriptions evaluated, ciprofloxacin was used in all but nine. While the mean age of the patients being treated was 5.2 years (interquartile range 1.8–12.4 years), the majority of prescriptions were written for the 12 to 18-year-old group. Intravenous ciprofloxacin was used in 51% of the patients. Only 17% were for approved indications: 13 (5%) for refractory respiratory infections in children with cystic fibrosis and 31 (12%) for complicated UTIs or pyelonephritis. Most of the patients were given a fluoroquinolone as empiric treatment for central nervous system infections (representing 25% of prescriptions), respiratory tract infections or pneumonia (18%), or as prophylaxis in cancer patients with febrile neutropenia (18%). Thirty-five percent of the patients had positive bacterial cultures, with Pseudomonas aeruginosa being the most common organism identified.

Faghihi and colleagues found similar results in their 10-month observational study of children at the Children's Medical Center in Tehran.[8] From 14,511 hospital admissions, the authors identified 32 children who received oral or intravenous ciprofloxacin for at least 48 hours. The mean age of the patients was 8.9 + 3.9 years (range 2–18 years). Ciprofloxacin use was more common in younger children; 25 of the patients (78%) were less than 12 years of age. Twenty-five of the children (78%) were treated for an off-label indication. Of those, only 5 (15%) were considered justified by the authors, according to FDA and American Academy of Pediatrics guidelines or by evidence of infection with an organism resistant to standard therapy.

While these studies suggest that much of ciprofloxacin prescribing in children might be avoided, there are cases in which it remains an appropriate choice. Ciprofloxacin has been shown to be effective in the treatment of complicated pulmonary exacerbations in children with cystic fibrosis, management of refractory infections in immunosuppressed children receiving chemotherapy, and in the treatment of multidrug resistant sepsis.[9–11]

The first published account of using ciprofloxacin to treat multidrug-resistant neonatal sepsis was published in 1989.[10] Since that time, a number of case reports and case series describing its use in neonatal sepsis have appeared in print. In a 2011 systematic review, Kaguelidou and colleagues evaluated 32 papers, including 5 cohort studies and 27 single case reports or case series, confirming the earlier studies.[11] Ciprofloxacin was prescribed for sepsis caused by multidrug-resistant organisms or in the setting of a worsening clinical condition during first-line therapy. The rates of clinical response were estimated to be 64% and 91% in the two cohort studies and 83% in the cases and case series. The authors found no reports of serious adverse effects in these papers, although they acknowledge that the depth of evaluation and length of follow-up precluded making an assessment of the drug safety.