Auckland Healthcare Public Health Protection, Auckland, New Zealand
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Abstract |
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Introduction |
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Materials and methods |
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A per-oral pharyngeal specimen was obtained with a dry straight cotton-tipped swab. Each tonsillar bed and the posterior nasopharynx were swabbed, and the swab was plated directly on to modified ThayerMartin medium (Fort Richard Laboratories, Auckland, New Zealand) and placed into a candle jar for transport to the laboratory. Plates were incubated at 36°C in 5% CO2 and examined at 24, 36, 48 and 60 h. Colonies resembling Neisseria spp.underwent oxidase testing and, if oxidase-positive, Gram's stain. Three colonies of Gram-negative diplococci were subcultured on to individual sheep blood agar plates for identification and typing. Subculture plates were incubated for 1824 h at 36°C in 5% CO2. Neisseria spp. were further identified using a rapid carbohydrate degradation test (Neisseria Kwik; Microbiologics, St Cloud, MN, USA). Serogrouping was performed using N. meningitidis antisera A, B and C (Murex Diagnostics, Dartford, UK).
The sensitivity of isolates to ceftriaxone and rifampicin was determined using the Etest (AB Biodisk, Solna, Sweden). The medium used was MuellerHinton agar (Difco Laboratories, Detroit, MI, USA) supplemented with 5% sheep blood; incubation was for 18 h at 37°C with 5% CO2.
Participants were randomized to receive ceftriaxone or rifampicin. For those receiving rifampicin the first dose was observed. Rifampicin treatment consisted of four oral doses at 12 h intervals. Dosages were 5 mg/kg for children under 1 month old and 10 mg/kg for children of 1 month. Adults and children weighing >60 kg were given 600 mg per dose. Ceftriaxone dosages were 125 mg im (vastus lateralis muscle) for children <12 years and 250 mg for adults and children
12 years, with 2 mL of 1% lignocaine as diluent. For identified meningococcal carriers, a second swab was taken 6 days after the first to determine the efficacy of treatment. Efficacy was defined, for the purposes of this study, as the proportion of meningococcal carriers who were culture-negative at 6 days.
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Results |
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The efficacy of the two medications in eliminating all serogroups of N. meningitidis was similar (Table I): 95.1% (95% confidence interval (CI) 88.098.7%) for rifampicin and 97.0% (95% CI 91.599.4%) for ceftriaxone. Efficacy for serogroup B N. meningitidis was very similar: 97.6% (95% CI 87.499.9%) and 98.2% (95% CI 90.1100.0%), respectively. All seven isolates from therapeutic failures were sensitive to rifampicin and ceftriaxone with MICs of 0.0042 and <0.002 mg/L, respectively.
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Discussion |
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While this study did not specifically investigate the efficacy of ceftriaxone and rifampicin for serogroup C N. meningitidis, of 13 participants carrying this serogroup (eight given ceftriaxone and five rifampicin) there was one treatment failure in the rifampicin group. Based on this finding, and the fact that the ceftriaxone MIC range was the same (0.0040.008 mg/L) for serogroups B and C in New Zealand between 1996 and 1998, there would seem little point in further investigating efficacy for serogroup C N. meningitidis.
There were no secondary cases of meningococcal disease among participants in this study. It was, therefore, not possible to measure the effectiveness of ceftriaxone in terms of secondary case prevention.
The frequency of adverse events for rifampicin was higher than that found in other studies of 2 day courses.4,10 Both medications were used in children in their first month of life, without complication. While pain at the injection site is likely to be a barrier to its acceptability, ceftriaxone has a number of clear advantages over rifampicin, including full compliance and fewer contraindications because of potential drug interactions or pregnancy. In addition, the cost per course of ceftriaxone ($NZ11 including needle and syringe) was much lower than that of rifampicin ($NZ18). There was little difference in the time required to administer the two treatments. The time taken to enquire about contraindications and to counsel patients on the dosage regimen and adverse events for rifampicin was similar to that required for the administration of ceftriaxone.
There will be a range of issues to consider in deciding whether to give prophylactic ceftriaxone to close contacts of meningococcal disease cases. However, doubt concerning ceftriaxone's efficacy in eliminating nasopharyngeal carriage of serogroup B N. meningitidis should no longer be one of them.
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Acknowledgments |
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Notes |
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References |
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Received 30 March 1999; returned 7 September 1999; revised 15 October 1999; accepted 20 January 2000