ArticlesRandomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis
Introduction
Fluoroquinolones are among the most commonly prescribed antimicrobial agents for adults.1 However, they cause arthropathy in juveniles of most animal species on which they have been tested,2 so they have been used sparingly in children. The quinolone agent nalidixic acid also causes arthropathy in juvenile animals,2 but that drug was approved for paediatric use before this toxic effect was known, and has not been associated with arthropathy in human beings.3, 4 Limited experience of fluoroquinolone use in children has shown that standard doses do not cause arthropathy.5 The fluoroquinolones are not available in liquid form, and their use in children has generally been restricted to those with chronic, potentially lethal disorders such as cystic fibrosis and malignant disorders,6, 7, 8 or with infections for which other antimicrobial treatments have not worked.9, 10
We assessed the efficacy of a suspension formulation of the fluoroquinolone agent ciprofloxacin to treat children with shigellosis. Although the fluoroquinolones are a mainstay of the treatment of enteric infections in adults,11, 12 studies of enteric infections in children have generally been small or poorly controlled.13, 14, 15 There is an increasing awareness of the need for systematic assessment of drugs in children, rather than extrapolation of the findings of studies in adults.16 Infections caused by shigella are a good choice of acute childhood infection on which to assess treatment with a fluoroquinolone,17 because they are potentially life-threatening,18 they are resistant to most available oral antimicrobial agents,19 and because the quinolone agent nalidixic acid was commonly used to treat them3 before shigella developed resistance to this drug.19
The study hypothesis was that ciprofloxacin would be equivalent to pivmecillinam in terms of efficacy and safety.
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Patients
Our randomised, double-blind controlled trial enrolled patients from the Dhaka Diarrhoea Treatment Centre at the International Centre for Diarrhoeal Disease Research, Bangladesh, between August, 1995, and March, 1997. We used the same study methods as in our previous studies.3, 11, 20, 21, 22 Eligible patients were children aged 2–15 years who had dysentery, defined as passage of grossly bloody-mucoid stools for 72 h or less, but who had not received any suitable antimicrobial therapy, which we
Results
143 children were enrolled in the study (figure 1). 13 patients (six in the ciprofloxacin group and seven in the pivmecillinam group) were excluded from the analysis of clinical efficacy because they were not eligible: 12 had no shigella isolate, and one had received a dose of nalidixic acid before study entry and was infected with a nalidixic-acid-susceptible strain of shigella. Ten children, five in each group, withdrew from the study before the assessment of clinical outcome on day 5 (two on
Discussion
For children moderately to severely ill with shigellosis, we have shown that ciprofloxacin suspension is clinically as effective, and bacteriologically more effective, than pivmecillinam tablets. Though the clinical success with ciprofloxacin was greater than that with pivmecillinam, the 15% difference was not statistically significant. This study was designed only to demonstrate clinical equivalence; a study with a larger sample size might have shown a significant difference in clinical
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