Torsades de pointe probably related to sparfloxacin

350

Letters

4. Taylor DN, Pitarangsi C, Echeverria P, Dinega BM: Campylobacter enteritis during doxycycline prophylaxis for malaria in Thailand. Lancet 1988, ii: 578-579. 5. DuPont HL, Ericsson C: Prevention and treatment of traveller's diarrhoea. New England Journal of Medicine 1993, 328: 1821-1827. 6. Kuschner RA, Trofa AF, Thomas RJ, Hoge CW, Pitarangsi C, Amato S, Olafson RP, Echeverria P, Sadoff JC, Taylor DN: Use of azithromycin for the treatment of CampyIobacter enteritis in travellers to Thailand, an area where ciprofloxacin resistance is prevalent. Clinical Infectious Diseases 1995, 21: 536-541. 7. Sjogren E, Kaijser B, Werner M: Antimicrobial susceptibilities of Campylobacter jejuni and Campylobacter coil isolated in Sweden: a 10-year follow-up report. Antimicrobial Agents and Chemotherapy 1992, 36: 2847-2849. 8. Hirschl AM, Wolf D, Berger J, Rotter ML: In vitro suscep~ tibility of Campylobacter jejuni and Campylobacter coli isolated in Austria to erythromycin and ciprofloxacin. Zentratbtatt for Bakteriologie 1990, 272: 443-447. 9. Rautelin H, Renkonen OV, Kosunen TU: Emergence of fluoroquinolone resistance in Campylobacterjejuni and Campylobacter coli in subjects from Finland. Antimicrobial Agents and Chemotherapy 1991, 35: 2065-2069. 10. Gomez-Garces JL, Cogollo R, Alos Jl: Susceptibilities of fluoroquinolone-resistantstrains of Campylobacterjejuni to 11 oral antimicrobial agents. Antimicrobial Agents and Chemotherapy 1995, 39: 542-544. 11. Tee W, Mijch A, Wright E, Yung A: Emergence of multidrug resistance in Campylobacterjejuni. Clinical Infectious Diseases 1995, 21: 634-638.

Torsades de Pointe Probably Related to Sparfloxacin We describe the first case of torsades de pointe probably related to treatment with sparfloxacin, a new, long half-life extended-spectrum quinolone active against Streptococcus pneumoniae. A 47-year-old woman was hospitalized for a suppurative otitis media and mastoiditis. Haemophilus influenzae and Streptococcus pneumoniae were recovered from purulent otorrhea. She suffered from a previous moderate unsubstitute anterior pituitary insufficiency. The first routine electrocardiogram showed ST segment depression and T-wave inversion in leads V2 through V4. QT and QTc intervals were 0.34 and 0.46 s, respectively. Because of allergy to betalactam antibiotics, treatment with oral sparfloxacin (400 mg the first day and 200 mg on subsequent days) associated with intravenous rifampin (1500 mg daily) was initiated. On the sixth day, she felt dizzy and lost consciousness; this was associated with torsades de pointe on the cardioscope followed by cardiac ar-

Eur. J. Clin. Microbiol. Infect. Dis.

rest requiring cardiopulmonary resuscitation. The electrocardiogram showed QT and QTc intervals of 0,35 and 0.60 s, respectively. A 24-hour continuous electrocardiography confirmed numerous episodes of torsades de pointe and a four-minute ventricular tachycardia. Torsades de pointe occurred after episodes of sino-auricular block. Laboratory studies showed the following: potassium, 4 mmol/1; calcium, 2.1 mmol/l; and magnesium and red cell magnesium content, 0.8 and 2 mmol/1 respectively. Renal function (creatinine clearance 87 ml/min) and hepatic function (bilirubin 12 ixmol/1, factor V 68%) were normal. Echocardiography was normal. Trough serum level of sparfloxacin was 2.5 txg/m122 hours after the last 200 mg dose of sparfloxacin. Sparfloxacin was discontinued, and the QTc returned to baseline within one week (0.46 s). Another 48-hour continuous electrocardiography was normal, showing no ventricular ectopy, sino-auricular block, or torsades de pointe. After another normal echocardiography and normal treadmill exercise test, the staff cardiologists concluded that the patient suffered from a mild idiopathic long QT syndrome. Torsades de pointe refers to ventricular tachycardia characterized by polymorphic QRS complexes that change in amplitude and cycle length, giving the appearance of oscillations around the baseline. This rhythm is by definition associated with QT prolongation. The latter may result from electrolyte disturbances (particularly hypokaliemia and hypomagnesemia) or the use of a variety of antiarhythmic drugs (especially quinidine), phenothiazines, and tricyclic antidepressants. A median increase of 2.8% QT interval has been reported in 2200 phase III healthy volunteers treated with sparfloxacin, so far without any arrhythmic complication (1). The increase of QT interval seemed to be proportional to the increase of plasmatic sparfioxacin concentration. In this case, the trough level was much higher than would be expected from pharmacokinetics studies in healthy volunteers (C min = 0.5 + 0.14 txg/ml) (1), despite normal renal and hepatic functions, Sparfloxacin administration was carefully monitored by trained intensive care nurses and overdosage seems unlikely. Rifampin has not previously been implicated in such reaction, and a role for it here seems unlikely. That the reaction was a result of sparfloxacin is highly probable on the basis of time lapse after administration, sympto-

Vol. 15, 1996

matology, and return to baseline status after sparfloxacin treatment was discontinued (2). We believe that sparfloxacin should be used cautiously in patients with pre-existing QT prolongation and that patients should be screened for QT prolongation before being given this drug.

H. Dupont, J.F. Timsit*, B. Souweine, B. Gachot, M. Wolff, B. Regnier Clinique de R6animationdes MaladiesInfecfieuses,Centre Hospitalier Universitaire Bichat Claude/Bernard, 46 Rue Henri Huchard,75018Paris, France.

References 1. Medan J: Dictionnaire Vidal. Vidal, Paris, 1995, p. 1650. 2. Begaud B, Evreux JC, Jouglard J, Lagier G: Imputabilit des effets inattendus ou toxiques des m4dicaments: actualisation de la m4thode fran(~aise. Th4rapie 1985, 40: 111-118.

Antimicrobial Susceptibility of Escherichia coli O157 and Other Enterohaemorrhagic Escherichia coli Isolated in Italy Infection with verocytotoxin-producing strains of Escherichia coli (VTEC) is associated with a wide range of illnesses in humans, the clinical manifestations of which include mild diarrhoea, haemorrhagic colitis, haemolytic uraemic syndrome, and thrombotic thrombocytopenic purpura (1). Although strains of VTEC may belong to many serotypes, the majority of severe human infections is caused by strains of serogroups O157 and, to a lesser extent, 026 and Ol11, which have also been termed enterohaemorrhagic Escherichia coli, or EHEC (1). There is no specific treatment for EHEC infection. The diarrhoeal phase of the disease is self-limiting, and the efficacy of early antibiotic therapy in preventing the progression to haemolytic uraemic syndrome is still unclear (2, 3). The conducting of clinical trials to clarify this matter could be complicated by the emergence of antibiotic resistance among EHEC strains causing human disease. Even though Escherichia coli O157 is widely considered sensitive to multiple classes of antibiotics

Letters

351

(1), strains showing multiple resistance to streptomycin, tetracycline, and sulphisoxazole have been described in the USA (4, 5). No data are available on the antimicrobial susceptibility of non-O157 EHEC clinical isolates. In the present study 29 strains of E H E C isolated in Italy from severely diseased humans and from cattle, the main natural reservoir of these organisms (1), were tested for susceptibility to antimicrobial agents in common clinical use as well as to other drugs to which Escherichia coli O157 has previously been resistant. Twenty-two of the strains were isolated from patients with bloody diarrhoea, haemolytic uraemic syndrome, or both between 1988 and 1994 (6, 7). All strains were from epidemiologically unrelated cases representing different episodes of infection. Ten strains belonged to serotype O157:H7, one to O157:H-, six to O l 1 1 : H - , four to O26:Hll, and one to O26:H-. Two isolates, one of serotype O26:Hll and one of O l 1 1 : H - , were from calves with diarrhoea. Five strains, four O157:H7 and one O26:Hll, were isolated from healthy calves at a slaughterhouse. Serotyping was done by standard techniques and confirmed by the World Health Organization International Reference Centre for Escherichia and Klebsiella in Copenhagen, Denmark. The type of verocytotoxin (VT) produced was identified by cytotoxicity assays with Vero cells, using neutralizing antisera specific to VT1 and the VT2 group (6). The disk diffusion method (8) was used to test isolates for susceptibility to the following antibiotics: ampicillin, ceftazidime, ceftriaxone, cephalothin, chloramphenicol, ciprofloxacin, gentamicin, streptomycin, sulphisoxazole, tetracycline, and trimethoprim-sulphamethoxazole. Escherichia coil ATCC 25922 was used as control. Conjugation experiments for R-plasmid transfer from EHEC strains to Escherichia coli K12 were performed as described by Anderson and Threlfall (9). All of the EHEC isolates were susceptible to ceftazidime, ceftriaxone, and ciprofloxacin. Twelve of the 15 O157 strains (9 from humans and 3 from cattle) were susceptible to all antimicrobial agents tested, while all but two of the non-O157 isolates were resistant to one or more agents. Table 1 shows the antibiotic resistance patterns of the isolates by serotype, source, and type of verocytotoxin produced. One of the three resistant O157 strains, isolated from bovine stools, showed the same resistance