The best questions often stem from the inquisitive learner. As educators, we love—and are always humbled—by those moments when we get to say, “I don’t know.” For some of these questions, some may already know the answers. For others, some may never have thought to ask the question. For all, questions, comments, concerns, and critiques are encouraged. Welcome to the Kids Korner.

Question #1: What’s the deal with fluoroquinolones and bones/tendons in children?

Fluoroquinolones were spin-offs of antimalarial drugs and were approved for use in children in the 1960s. According to reviews by Burkhardt et al and Patel et al, quinolone-induced arthropathy changes have been seen in nearly all laboratory animals studied, particularly in weight-bearing joints and only in juvenile animals.^1,2 There are a number of case reports referenced by these authors that demonstrate that these joint changes can occur in children and adolescents. In these cases, joint complaints resolved with drug cessation. Also, the majority of these cases were cystic fibrosis patients who had received prolonged courses of fluoroquinolones.

In regard to pediatric findings, a study by Hampel et al retrospectively looked at 1,795 patients younger than 17 years of age and reported adverse events.³ The incidence of adverse events was 10.9 percent. While most adverse events were nausea, vomiting, and diarrhea, only 1.5 percent of the total population developed arthralgia. The median duration of ciprofloxacin treatment was 23 days. While this study was sponsored by Bayer—the maker of Cipro—these rates do appear to be consistent with other studies.²

In certain clinical scenarios, the use of a fluoroquinolone in a child may be necessary and appropriate, and the practitioner shouldn’t live in terror of destroying a child’s hopes of playing professional sports.

There are also prospective studies on this topic. A multicenter observational study by Chalumeau et al looked at potential adverse events between fluoroquinolone-exposed and control subjects (n=276 exposed; n=249 control).⁴ Patients were younger than 19 years of age, and the incidence of musculoskeletal adverse events was low (3.8 percent) but still higher than the incidence previously reported in adults (0.01 percent to 0.2 percent). All the bone/joint adverse events were transient. Another prospective study by Noel et al was a nonblinded, multicenter, randomized study of 2,523 children that looked at the association of levofloxacin with four different joint/bone complaints: tendinopathy, arthritis, arthralgia, and gait abnormality.⁵ Joint/bone complaints in weight-bearing joints were present in 2.9 percent of levofloxacin-exposed patients versus 1.6 percent of control patients. There were no abnormalities on computed tomography and magnetic resonance imaging scans of patients evaluated for these bone/joint complaints. All symptoms resolved with cessation of the drug.

Summary

Studies suggest a small—but statistically significant—increase in arthropathy/arthritis in children who take fluoroquinolones. It is predominately in weight-bearing joints but also transient. In certain clinical scenarios, the use of a fluoroquinolone in a child may be necessary and appropriate, and the practitioner shouldn’t live in terror of destroying a child’s hopes of playing professional sports.

Question #2: Is clindamycin a good option for outpatient treatment of chondritis/perichondritis of the ear in children?

This is a two-part question: 1) Does clindamycin penetrate the appropriate tissue (cartilage) adequately to potentially treat the disease? 2) Does it treat the appropriate bacteria?

Clindamycin does appropriately concentrate in bone, joints, and cartilage. Most studies demonstrating appropriate tissue penetration are animal studies. For example, an animal study by Eismont et al demonstrated adequate clindamycin concentrations in the nucleus pulposus of spinal intervertebral discs of rabbits.⁶

The most important question, though, is, does it treat the appropriate bacteria? The simple answer is no. There are a number of case reports on outbreaks of auricular chondritis/perichondritis that have occurred.^7–9 The majority of these cases have occurred in children and adolescents and have commonly involved Pseudomonas aeruginosa.¹⁰ A number of cases have required hospitalization with intravenous antibiotics. A common cause has been cartilaginous ear piercings at the mall. The bottom line is that practitioners need to cover for P. aeruginosa. What are our oral antibiotic options? Fluoroquinolones are a potential option, and these are discussed above.

As a side note, the culprit in most of these ear-piercing reports was contaminated cleaning solution used before the piercing was placed.

Summary

Clindamycin is not the appropriate antibiotic for outpatient treatment of chondritis/perichondritis of the ear. It does appropriately concentrate in cartilage but does not cover P. aeruginosa, the primary bacteria causing infection in cartilage of the ear. You need to give an oral antibiotic that covers Pseudomonas. That antibiotic is probably an oral fluoroquinolone.

Dr. Jones is assistant professor of pediatric emergency medicine at the University of Kentucky in Lexington.

Dr. Cantor is professor of emergency medicine and pediatrics, director of the pediatric emergency department, and medical director of the Central New York Poison Control Center at Upstate Medical University in Syracuse, New York.

References

1. Burkhardt JE, Walterspiel JN, Schaad UB. Quinolone arthropathy in animals versus children. Clin Infect Dis. 1997;25:1196-1204.
2. Patel K, Goldman JL. Safety concerns surrounding quinolone use in children. J Clin Pharmacol. 2016 Feb 10. [Epub ahead of print]
3. Hampel B, Hullmann R, Schmidt H. Ciprofloxacin in pediatrics: worldwide clinical experience based on compassionate use—safety report. Pediatr Infect Dis J. 1997;16:127-129.
4. Chalumeau M, Tonnelier S, D’Athis P, et al. Fluoroquinolone safety in pediatric patients: a prospective, multicenter, comparative cohort study in France. Pediatrics. 2003;111:e714-719.
5. Noel GJ, Bradley JS, Kauffman RE, et al. Comparative safety profile of levofloxacin in 2523 children with a focus on four specific musculoskeletal disorders. Pediatr Infect Dis J. 2007;26:879-891.
6. Eismont FJ, Wiesel SW, Brighton CT, et al. Antibiotic penetration into rabbit nucleus pulpous. Spine (Phila Pa 1976). 1987;12:254-256.
7. More DR, Seidel JS, Bryan PA. Ear-piercing techniques as a cause of auricular chondritis. Pediatr Emerg Care. 1999;15:189-192.
8. Keene WE, Markum AC, Samadpour M. Outbreak of Pseudomonas aeruginosa infections caused by commercial piercing of upper ear cartilage. JAMA. 2004;291:981-985.
9. Fisher CG, Kacica MA, Bennett NM. Risk factors for cartilage infections of the ear. Am J Prev Med. 2005;29:204-209.
10. Sosin M, Weissler JM, Pulcrano M, et al. Transcartilaginous ear piercing and infectious complications: a systematic review and critical analysis of outcomes. Laryngoscope. 2015;125:1827-1834.