A randomized comparative study of fleroxacin and ceftriaxone in enteric fever

464 Her& Hascoet, laboratory assistant; Miss Veronique Chenon and Mrs Sylvianne Teururai, nurses; and Mr I%ichart Regis, computer expert, Institut Malard e References Addiss, D G., Eberhard, M L., Lammie, I’ J., Bayard McNeeley, M., Lee, S H., McNeeley, D F & Spencer, H C (1993) Comparative efficacy of clearing-dose and single high-dose ivermectin and diethylcarbamazine against Wuchereria bancrofti microfilaraemia AmericanJournal of Tropical Medicine and Hygiene, 48,178-185 Cartel, J.-L., Spiegel, A., Nguyen, L., Genelle, B & Roux, J.F (1991) Double blind study on efficacy and safety of single doses of ivermectin and diethylcarbamazine for treatment of Polynesian Wuchererta bancrofti carriers Results at six months Tropical Medicine and Parasitology, 42,38-40 Cartel, J.-L., Nguyen, N L., Spiegel, A., Moulia-Pelat, J.-P., Plichart, R., Martin, I’ M V., Manuellan, A B & Lardeux, F (1992a) Wuchereria bancrofciinfection m human and mosquito populations of a Polynesian village ten years after interruption of mass chemoprophylaxis with diethylcarbamazine Transactions of the Royal Society of Tropical Medicine and Hy- giene,86,41@16 Cartel, J L., Nguyen, N L., Moulia-Pelat, J.-P., Plichart, R., Martin, I’ M V & Spiegel, A (1992b) Mass chemoprophylaxis of lymphatic filariasis with a single dose of ivermectin in a Polynesian community with a high Wucheretiabancrofti infection rate Transactionsof the Rcyal Sociey of Tropical Medicine and Hygiene, 86,537-540 Cartel, J.-L., Moulia-Pelat, J.-P., Glaziou, I’., Nguyen, L N., Chanteau, S & Roux, J.-F (1992~) Results of a safety trial on single dose treatments with 400 pgikg of ivermectin in bancroftian filariasis Tropical Medicine and Parasitology, 43, 263-266 Diallo, S., Aziz, M A., Ndir, O., Badiane, S., Bah, I B & Gaye, (1987) Dose-ranging study of ivermectin in treatment of filariasis due to Wuchereria bancrofti Lancet, i, 1030 Eberhard, M L., Hightower, A W., McNeeley, D F & Lammie, I’ J (1992) Long-term suppression of microfilaraemia following ivermectin treatment Transactions of the Royal So- TRANSACTIONS OF THE ROYAL SOCIETY OPTROPICAL MEDICINE study of in enteric Tran Tinh Hien, Nguyen Minh Duong, Huynh Duy Ha, Nguyen Thi Tuyet Hoa, To Song Diep, Le Thi Phi and Keith Arnold Centre for Tropical Diseases, Cho Quart Hospital, Typhoid Public Health, 24,80-86 Kumaraswami, V., Ottesen, E A., Vijayasekaran, V., Uma Devi, S., Swaminathan, M., Aziz, M A., Sarma, G R., Ragneathi Prabhakar & Tripathy, S I’ (1988) Ivermectin for treatment of Wuchereria bancrofti filariasis Efficacy and adverse reactions Journal of the American Medical Association, 259,31X)-3153 Moulia-Pelat, J I’., Glaziou, Ph., Nguyen, N L., Chanteau, S., Plichart, R., Beylier, I., Martin, I’ M V & Cartel, J.-L (1994) Ivermectin 400 ugikg: long-term suppression of microfilariae in Bancroftian filariasis Transactions of the Royal Society of Tropical Medicine and Hygiene, 88, 107-109 Ottesen, E A., Vijayasekaran, V., Kumaraswami, V., Perumal Pillai, S V., Sadanandam, M A., Frederick, B S., Prabhakar, R & Tripathy, S l’ (1990) A controlled trial of ivermectin and diethylcarbamazine in lymphatic lilariasis New EnglandJournal of Medicine, 322,1113-l 117 Perolat, I’., Guidi, C., Riviere, F & Roux, J (1986) Filariose de Bancroft en Polyntsie Francaise Situation epidtmiologique et perspectives apres 35 ans de lutte Bulletin de la Societe de Pathologie Ewotique, 79, 78-88 Richards, F O., jr, Eberhard, M L., Bryan, R T., McNeeley, D F., Lammie, I’ J., McNeeley, M B., Bernard, Y., Hightower, A W & Spencer?H C (1991) Comparison of high dose ivermectin and dtethylcarbamazine for activity against bancroftian lilariasis in Haiti AmericanJournal of Tropical Medicine and Hygiene, 44,3-10 Roux, J., Cartel, J.-L., Perolat, I’., Boutin, J I’., Sechan, Y., Lariviere, M & Aziz, M A (1989) Etude de l’ivermectine pour le traitement de la filariose lymphatique due & Wuchereria bancrofti var pacijica en I’olyntsie Francaise Bulletin de la Soci& de Pathologie Exotique, 82,72-81 Received August 1993; revised September accepted for publication September I993 1993; AND HYGIENE (1994) 88, 464-465 /Short A randomized comparative fleroxacin and ceftriaxone fever ciety of Tropical Medicine and Hygiene, 86,287-288 Kar, S K., l’atnaik, S., Mania, J & Kumaraswami, V (1993) Ivermectin in the treatment of bancroftian lilarial infection in Orissa, India Southeast AsianJournal of Tropical Medicine and Ho Chi Mirth City, Viet Nam or enteric fever is a common disease in Viet Nam In 1992in south Viet Nam there were 9179 clinical casesreported to the Pasteur Institute of Ho Chi Minh City and over 600 casesof enteric fever were clinically diagnosed at Cho Quan hospital, of whom 32% provided positive blood cultures Chloramphenicol-resistant typhoid was first described in Viet Nam from Cho Quan hospital in 1973(BUTLER et al., 1973), and from Nguyen Van Hoc hospital in 1975 (BROWN et al., 1975) In the mid 1970sthe prevalence of chloramphenicol resistance was 75% (BUTLER et al., 1977), but by the late 1980sit had dropped to 45% (Hoa, unpublished observation) In the early 1990sphysicians noticed (as they had in 1973) that patients with typhoid fever were not responding to chloramphenicol (proAddress for correspondence: Dr Tran Tinh Hien, Cho Quan Hospital, 190 Hen Ham Tu, Quan 5, Ho Chi Minh City, Viet Nam longed fever and persistence of signs and symptoms), and in addition they were not responding to ampicillin or to co-trimoxazole This indicated that there was an urgent need for new effective antibiotics for the treatment of typhoid fever The third generation cephalosporins have been reported to be very effective (ISLAM et al., 1988), especially ceftriaxone in a short treatment course of d (LASSERRE et al., 1991) The quinolones are also effective (ASPERILLA et al., 1990), in particular fleroxacin in a short treatment course of d (ARNOLD et al., 1993) An earlier quinolone, oxolinic acid, although effective in vitro against Salmonella typhi, had been found to be ineffective for typhoid fever at Cho Quan hospital at the time of the first appearanceof chloramphenicol resistance (SANFORD et al., 1976) Figure Percentages of enteric fever patientsstill febrile after treatment with ceftriaxone ( , 13 patients) and fleroxacin ( -, 16 patients) 465 Table Clinical and microbiological features of emetic fever patients and treatment results Fleroxacin Number Male/female ratio Age (years) Weight (kg) Duration of fever before trearmcnr (d) Leucocyte count ( x 10%)” No of blood isolates 5’ typhi s parat~phe’A ‘~jcrobiolo~i~ cure Clinical &e Fever c’learancetime (h) 16 1115 Ceftriaxone 24 (7; 17-43) 46 (8; 33-56) 15 1114 29 (15; 1672) 44 (5; 35-51) 15 (3; 9-21) 17 (9; 7-33) 5.81 (1.78; 3-5-S-S) 5.52 (1.92; 4-10.0) 14 13 16116;loO%) 16116(100%) 13114(93%)b 13115(87%) 160 (75; 78-306) 81 (40; 36-170) L “Means(standarddeviationsand rangesin parentheses) bOnepatient receiving one dose of ceftriaxone followed by dyspnoea and hypotensionwas excludedfrom rhe microbiologicalanalysisbut was included in the clinical evaluation ‘rz=13 for ceftriaxone Significant difference between the drugs (P-0.02); no other differencewas significant A study, approved by the hospital scientific and ethical committee, was carried out at Cho Quan Hospital in Ho Chi Minh City, Viet Nam, during 1992-1993 to compare a d course of fleroxacin (orally) with a d course of ceftriaxone (intravenously) because, although ceftriaxone is effective., an oral treatment is preferable Forty-six patients with a clinical diagnosis of typhoid fever (axillary temperature above 37.5”C over d, ‘toxic’ appearance and negative malaria blood film) were allocated at random to receive either fleroxacin 400 mg orally in a single dose daily for d or ceftriaxone g intravenously once a day for d, after their informed verbal consent had been obtained The temperature was measured every h, blood cultures and stool cultures were prepared before treatment was started and on day 7, with an additional blood culture on day Routine laboratory investigations for hepatic, renal and haematological assessmentwere done before and after treatment Patients were requested to return to the hospital for follow-up on days 14 and 2s after the end of treatment Thirty-one patients had enteric fever confirmed by positive blood culture before treatment (27 S typhi and S paratyphi A); their clinical and microbiological features and the results of treatment are shown in the Table All isolates were S.tv~hi exceut for S.z~~ratv&i A, in each treatment group Of the ‘s typhi, &I% w;e resistant to chloramphenicol, 46% to ampicillin, and 46% to cotrimoxazole (44% were resistance to all drugs); all were sensitive to fleroxacin and ceftriaxone bv disk diffusion The S paratyphi A isolates were sensitive to all drugs Of the 31 patients, 29 were evaluable for time to defervescence (axillary temperature