Fluoroquinolone antibiotics in children with multidrug resistant typhoid

Abstract

SIR—Fluoroquinolone antibiotics are considered to be contraindicated in children because of their potential for arthropathogenicity. In immature experimental animals, principally beagle dogs, this class of compounds damages cartilaginous end-plates of long bones. There is no evidence that a similar process occurs in people, but caution has dictated that alternative drugs should be used in children. But for some infections there are no alternatives. In children with cystic fibrosis infected with multidrug resistant Pseudomonas aeruginosa long courses of high-dose fluoroquinolones have been used successfully without complications. Fluoroquinolones have been used in children with drug-resistant shigellosis for which nalidixic acid, a less effective and equally arthropathogenic quinolone, is considered the treatment of choice. There is growing acceptance amongst paediatricians that these antibiotics can be used in other life-threatening infections. Strains of Salmonella typhi, which are resistant to ampicillin, co-trimoxazole, and chloramphenicol, have become increasingly prevalent. Fortunately, these multidrugresistant strains retain sensitivity to third-generation cephalosporins and fluoroquinolone antibiotics. But Salmonella typhi in-vivo often does not behave as expected from standard in-vitro sensitivity tests. Despite similar invitro minimum inhibitory concentrations, third-generation cephalosporins have proved consistently inferior to fluoroquinolone antibiotics in-vivo. Patients receiving thirdgeneration cephalosporins often remain ill for more than 1 week whereas the average time to fever clearance with fluoroquinolones is 4 days. Fluoroquinolones are highly effective in children with multidrug-resistant typhoid or other systemic salmonelloses, and there have been no reported serious adverse effects. In Vietnam, where multidrugresistant typhoid has spread rapidly over the past 3 years, the fluoroquinolones remain over 95% effective with carrier rates less than 5%, whereas parenteral and oral third-generation cephalosporins have failure rates above 20%. However, the principal advantage of the fluoroquinolones in uncomplicated typhoid is their remarkable efficacy with treatment courses as short as 2 or 3 days. Cure rates with ofloxacin given for 3 days (15 mg/kg daily) in two recent studies were 100% (n=118) and 96% (n=50). Fluoroquinolone resistance is still rare. These short-course treatments are a far cry from the traditional 2–3 week regimens with high-dose chloramphenicol or co-trimoxazole. The fluoroquinolones have also proved safe in children in Vietnam. In over 500 prospectively studied children there was no evidence of acute bone or joint adverse effects, and in 300 children who received between 3 and 10 days’ treatment and were followed for 2 years there were no adverse effects on growth. We recommend fluoroquinolones for children with typhoid fever and other systemic salmonelloses in areas where multidrug resistance is common. They are as safe and more effective than alternative treatments.