Tetracycline in the treatment of cholera caused by Vibrio cholerae O1 resistant to the drug in vitro.

Sir, Tetracycline, the most commonly-used antibiotic in cholera, reduces stool volume, duration of diarrhoea, and duration of excretion of Vibrio cholerae to about half that seen in patients treated without antibiotics (1). After oral administration, concentrations of tetracycline become relatively high in the intestinal lumen because of partial unabsorption and hepatobiliary excretion (2). It was our clinical impression that conventional dose of tetracycline given orally results in sufficiently high intestinal luminal concentration that much exceeds the minimum inhibitory concentration (MIC), so it might be effective in cholera caused by V. cholerae O1 resistant to the drug in vitro. If so, this phenomenon would replicate the experience with tetracycline-resistant Shigella infection in which tetracycline was thought to be efficacious (3). Pickering et al. treated symptomatic shigellosis patients successfully with a single oral dose of 2.5 g of tetracycline hydrochloride even in tetracycline-resistant strains of Shigella flexneri and S. sonnei (3). Now-a-days, emergence of strains of V. cholerae O1 resistant to tetracycline is a global problem (4-6). So, we conducted a pilot study to explore efficacy of tetracycline in the treatment of cholera caused by V. cholerae O1 resistant to tetracycline in vitro. This study was carried out at the Dhaka hospital of ICDDR,B: Centre for Health and Population Research during June 1995-December 1996. Both male and female adult patients, aged 18-60 years, with history of watery diarrhoea for [less than or equal to] 24 hours were considered suitable for inclusion in the study, provided females were not pregnant and patients had no other obvious infection or complicating medical illness at the time of entry into the study. No patient who had received any prior antimicrobial therapy for the current episode of diarrhoea was enrolled. Before enrollment, stool samples collected from the selected patients were examined by dark-field microscopy and the results confirmed the provisional clinical diagnosis of cholera. The enrolled patients were severely dehydrated except a few who had moderate dehydration, and rehydration was done within three hours by intravenous polyelectrolyte solution ( in mmol/L: [Na.sup.+] 133, [K.sup.+] 13, [Cl.sup.-] 98, and acetate 48). They were observed for four hours, during which time hydration was maintained with oral rehydration salts solution (rice-based ORS) or intravenous fluid. After the observation period, each patient was given 500 mg of tetracycline six hourly orally for three days. After initial rehydration, the patients were given normal meals except those containing milk and milk products to avoid chelation of tetracycline. On enrollment, fresh stool sample was taken from each patient for culture (inoculated into tellurite taurocholate gelatin agar, Mackonkey and Shigella-Salmonella agar) and sensitivity test. The patients whose stool cultures revealed only V. cholerae O1 remained in the study. Microbiological study of stool for V. cholerae was done daily until discharge. Drug susceptibility test was done by the disc-diffusion method (Kirby-Bauer) for tetracycline, erythromycin, and ciprofloxacin. For V. cholerae O1 resistant to tetracycline, the zone diameter of the disc was considered