Vol. 11. No. 5



Treatment of Tularemia with Ciprofloxacin O. Scheell., R. Reiersen 2, T. Hoel 3

A case of tularemia which occurred after close contact with a cat is presented. After unsuccessful amoxicillin treatment, a two-week course of doxycycline was given whereupon the patient responded well. However, the patient relapsed shortly after and was then given ciprofloxacin for two weeks. The patient then recovered completely. Clinical trials are needed in order to establish whether a quinolone could be the drug of choice for treatment of tularemia.

Tularemia in Norway, as elsewhere in Europe, is caused by Francisella tularensis biovar B (palaearctica). Although not lethal, tularemia caused by biovar B has a protracted course, leavIng the patient disabled for months if not treated COrrectly. According to standard reference books (1, 2), streptomycin is still the drug of choice. However, in Norway, as in many other European COUntries, streptomycin is no longer a registered drug. Evaluation of newer antibiotics in the treatment of Francisetla tularensis infections is incomplete, and the literature is therefore of limited help only on the question of which drug to use. We report on a patient successfully treated with oral ciprofloxacin.

cycline was administered again for three weeks. A blood sample taken nearly four weeks after the injury showed an agglutinating antibody titre for Francisella tularensis of 1/1000. The patient's condition improved again under doxycycline, but three days after completion of treatment the patient suffered another relapse with fever and deep axillary pain. Blood cultures performed at this stage were negative. Upon physical examination the patient presented with an enlarged, painful axillary lymph node, but was otherwise symptomless and had no fever. With the exception of a stationary antibody titre of 1/1000, laboratory parameters were normal. A two-week course of oral ciprofloxacin (750 mg twice daily) was initiated. After this the patient recovered completely, and no sign of relapse was seen at a follow-up examination two months later. During these events the cat showed no obvious signs of disease. However, testing of a serum sample from the animal revealed an antibody titre for Francisella tularensis of 1/500.

Discussion. Although the source of infection in

Case Report. A 37-year-old previously healthy Veterinary surgeon cut his forefinger while hysterectomising a cat. Three days later a small ulcer appeared, followed a few days later by a SWollen axillary lymph node, fever, malaise and Chills. Suspecting the cat as the source of infection, the patient treated himself with oral doxycycline for 3 to 4 days after which time he consuited a physician, Doxycycline was then replaced with amoxicillin. After ten days on amoxiciUin the patient presented with relapsing fever and malaise following transient improvement. Doxy-

this patient was rather unusual, the case history was typical for ulceroglandular tularemia. It is important to diagnose tularemia correctly since Francisella tularensis is resistant to most beta-lactam antibiotics, including all penicillins. In the absence of a four-fold titre rise, a single antibody titre of >-.1/160 is considered diagnostic of past or current infection (1). This titre level is usually reached in the third to fourth week of infection. In the present case the symptoms described together with the antibody titre of 1/1000 suggested current tularemia. Blood cultures were not performed until eight weeks after onset of disease, which is unfortunate as blood culturing enhances the possibility of early diagnosis of tularemia (35). When tularemia is suspected, the choice of antibiotics for treatment has previously been limited. Gentamicin has been proposed as an alternative to streptomycin (3, 6). However, in Europe only biovar B of Francisella tularensis occurs, as opposed to the sometimes lethal biovar A which occurs in the USA, home of both the highly virulent biovar A (tularensis) and the less virulent biovar B.

Norwegian Defence Microbiological Laboratory, Geit2myrsveien75, 0462 Oslo, Norway. Department of Medicine,Rogaland Central Hospital, Ar3~auer Hansens vei 20, 4011 Stavanger, Norway. , .. uepartment of Bacteriology,National Institute of Put~tle Health, Geitmyrsveien75S0462 Oslo, Norway.

Our patients are thus often treated as outpatients rendering intravenous drug therapy impractical. Oral chloramphenicol has been given, and an oral tetracycline is the usual choice for therapy, but clinical relapse occurs unless these drugs are administered for extended periods (6, 7). In the


present case relapse was seen after three weeks on doxycycline. Two groups of investigators have reported good results using intravenous erythromycin (8, 9), but they did not study oral administration of this antibiotic. Unlike American isolates, E u r o p e a n isolates have been found to be highly resistant to erythromycin (10). However, due to a difference in the procedures used for susceptibility testing it is possible that resistance is not recognized in vitro in American biovar B isolates (11). The fact that our patient was successfully treated with ciprofloxacin may be explained by the high intracellular concentrations attained by quinolones, a prerequisite for therapeutic efficacy in this case as Francisella tularensis is an intracellular parasite. However, despite good in vitro activity against another intracellular parasite, Brucella melitensis, ciprofloxacin was unsuccessful in the treatment of brucellosis in a clinical trial (12). Recently, five Finnish patients with tularemia were reported to respond well to treatment with either ciprofloxacin or norfloxacin (13). Despite these initial successes further clinical experience is n e e d e d in order to establish whether a quinolone is the drug of choice for treatment of tularemia.

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

9. Harrell RE, Simmons HF: Pleuropulmonary tularemia: successful treatment with erythromycin. Southern Medical Journal 1990, 83: 1363-1364. 10. Olsu~ev NG, Meshcheryakova IS: Infraspecific taxonomy of tularemia agent Francisella tularensis McCoy et Chapin. Journal of Hygiene, Epidemiology, Microbiology and Immunology 1982, 26: 291-299. 11. Baker CN, Hollis DG, ThornsberryC: Antimierobial susceptibility testing of Francisella tularensis with a modified Mueller-Hinton broth. Journal of Clinical Microbiology 1985, 22: 212-215. 12. Lang R, Raz R, Sacks T, Shapiro M: Failure of prolonged treatment with ciprofloxacin in acute infections due to Brucella melitensis. Journal of Antimicrobial Chemotherapy 1990, 26: 841-846. 13. Syrjiil~iH, Schildt R, Riisiiinen S: In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacin and ciprofloxacin. European Journal of Clinical Microbiology and Infectious Diseases 1991, 10: 68-70.

Evaluation of a Latex Test for Rapid Detection of Pneumococcal Antigens in Sputum S. W e l l s t o o d

References 1. Boyce JM: Francisella tularensis (tularemia). In: Mandell GL, Douglas RG, Bennett JE (ed): Principles and practice of infectious diseases. Churchill Livingstone, New York, 1990, p. 1742-1746. 2. Hornick RB: Tularemia. In: Hoeprich PD, Jordan MC (ed): Infectious diseases. Lippincott, Philadelphia, 1989, p. 1289-1295. 3. Provenza JM, Klotz SA, Penn RL: Isolation of Francisella tularensis from blood. Journal of Clinical Microbiology 1986, 24: 453-455. 4. Tiirnvik A, Henning C, Falsen E, Sandstrlim G: Isolation of Francisella tularensis biovar palaearctica from human blood. European Journal of Clinical Microbiology and Infectious Diseases 1989, 8: 146-150. 5. Hoel T, Scheei O, Nordahl SHG, Sandvik 1':. Water and airborne Francisella tularensis biovar palaearctica isolated from human blood. Infection 1991, 19: 348-350. 6. Evans ME, Gregory DW, Schaffner W, McGee ZA: Tularemia: a 30-year experience with 88 cases. Medicine 1985, 64: 251-269. 7. Overholt EL, Tigrett WD, Kadull PJ, Ward MK, Charkes ND, Rene RM, Salzman TE, Stephens M: An analysis of laboratory acquired tularemia. Treatment with broad spectrum antibiotics. American Journal of Medicine 1961, 30: 785-806. 8. Westerman EL, McDonald J: Tularemia pneumonia mimicking Legionnaires' disease: isolation of organisms on CYE agar and successful treatment with erythromyein. Southern Medical Journal 1983, 76: 1169-1170.

A latex agglutination test (Directigen) for detection of pneumococcal capsular polysaccharide antigens in sputum was evaluated in comparison to culture and Gram stain using 121 sputum specimens. The sensitivity, specificity and rate of agreement of the latex test compared to culture were 90 %, 79 % and 8 1 % , respectively. The results suggest that the latex test may be useful for detecting pneumococcal antigen in sputum.

Streptococcus p n e u m o n i a e is responsible for the majority of cases of community-acquired pneumonia. Several authors have demonstrated that the detection of pneumococcal capsular polysaccharide antigen (PCPA) in sputum correlated well with the presence of pneumococcal infection and was more specific than culture or G r a m stain (1-3). Several antigen detection methods have been applied to sputum specimens (4-8) with varying sensitivity and specificity.

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Treatment of tularemia with ciprofloxacin.

A case of tularemia which occurred after close contact with a cat is presented. After unsuccessful amoxicillin treatment, a two-week course of doxycyc...
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