TITLE: Antibiotics for the Treatment of Tularemia: Clinical-Effectiveness, Cost- Effectiveness, and Guidelines

Transcription

1 TITLE: Antibiotics for the Treatment of Tularemia: Clinical-Effectiveness, Cost- Effectiveness, and Guidelines DATE: 28 July 2009 RESEARCH QUESTIONS: 1. What is the clinical-effectiveness of antibiotics for the treatment of tularemia? 2. What is the cost-effectiveness of antibiotics for the treatment of tularemia? 3. What are the guidelines for choice of antibiotics, dosage of antibiotics, and duration of antibiotics for the treatment of tularemia? METHODS: A limited literature search was conducted on key health technology assessment resources, including PubMed, the Cochrane Library (Issue 3, 2009, University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, international health technology agencies, and a focused Internet search. The search was limited to English language articles published between 2004 and July, Filters were applied to limit the retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, controlled clinical trials, observational studies, economic studies, and guidelines. Internet links were provided, where available. The summary of findings was prepared from the abstracts of the relevant information. Please note that data contained in abstracts may not always be an accurate reflection of the data contained within the full article. Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in which a third party owns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a web site, redistributed by or stored on an electronic system without the prior written permission of CADTH or applicable copyright owner. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.

2 RESULTS: HTIS reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessment reports, systematic reviews, and meta-analyses are presented first. These are followed by randomized controlled trials, controlled clinical trials, observational studies, economic evaluations, and evidence-based guidelines. OVERALL SUMMARY OF FINDINGS: Four relevant guidelines were identified pertaining to the choice, dosage, and duration of antibiotic treatment of tularemia. 1-4 No relevant information pertaining to the clinical- or costeffectiveness of antibiotics for the treatment of tularemia was identified. For choice of antibiotic, streptomycin 1-4 was recommended by all four, and both gentamicin 1,3,4 and ciprofloxacin 1-3 were each recommended as good treatment options by three of the identified guidelines. Doxyxycline 2,3 was recommended by two guidelines, and other aminoglycosides, 2 as well as quinolone 4 were recommended as treatment options in one guideline each. The World Health Organization (WHO) recommended that for severe cases of tularemia that require hospitalization, parenteral administration of an aminoglycoside (e.g., gentamicin or streptomycin) should be the first-line treatment for both children and adults. 3 Ciprofloxaxcin and doxyxycline are recommended in less severe cases or in the case of mass casualties. With the exception of the Health Protection Agency, who recommended gentamicin for women, 1 the other guidelines 2,4 did not recommend a specific antibiotic as a first-line therapy option. Three guidelines outlined separate drug and dose options for children and for adults. 1-3 The same three guidelines 1-3 provided guidance on duration of antibiotic treatment for tularemia and found that, in general, antibiotics should be taken for one to two weeks. 1-3 For dosing information, see Table 1 and for more complete information regarding dosage, duration, and choice of antibiotic treatment refer to the full guidelines. Links to the full guidelines are provided in the reference list. Antibiotics for the Treatment of Tularemia 2

3 Detailed information has been summarized in Table 1. Table 1: Summary of recommendations for antibiotic treatment of tularemia Guideline Patient population Drug Dose Duration HPA Centre for Infections 1 Finnish Medical Society 2 WHO 3 Gentamicin (first choice in pregnancy) 5 mg/kg IM or IV once Adults Ciprofloxacin 400 mg IV twice (change to oral 500 mg twice when appropriate) Children Adults Children Adults Gentamicin Streptomycin Ciprofloxacin 2.5 mg/kg IM or IV three times 15 mg/kg IM twice (not to exceed 2 g per day 15 mg/kg PO twice (maximum 500 mg, not to exceed 1 g per day)* 14 days 14 days 10 days 10 days 10 days Ciprofloxacin 500 mg twice NA Doxyxycline 100 mg twice days Streptomycin NA 1-2 weeks Aminoglycocides NA 1-2 weeks Ciprofloxacin mg/kg NA twice (maximum adult dose not to be exceeded even if dose calculation based on body weight is indicated) Gentamicin (option for 2.5 mg/kg twice NA (should be individualized for Streptomycin 1 g IM twice 10 days (or more, depending on clinical response) Antibiotics for the Treatment of Tularemia 3

4 BICHAT 4 Children NA Ciprofloxacin (option for mg twice IV or PO days (should be individualized for At least 15 days Doxycycline 100 mg twice PO Gentamicin 5 6 mg/kg At least 10 days divided into 2 or 3 doses Streptomycin 15 mg/kg twice At least 10 days (up to 2 g) Ciprofloxacin 15 mg/kg twice At least 10 days (up to 1 g) Streptomycin NA NA Gentamicin NA NA Quinolone NA NA (considered an alternative treatment) BICHAT=Taskforce on Bioterrorism; g=gram; HPA=Health protection agency; IM=intramuscular; IV=intravenous; kg=kilogram; mg=milligram; NA=not available in the abstract; PO=oral; WHO=World Health Organization *See full guideline for full dosing information on ciprofloxacin for children. Antibiotics for the Treatment of Tularemia 4

5 REFERENCES SUMMARIZED: Health technology assessments Systematic reviews and meta-analyses Randomized controlled trials Controlled clinical trials Observational studies Economic evaluations Guidelines and recommendations 1. Health Protection Agency(UK). Tularemia guidelines for action in the event of a deliberate release. In. London: HPA Centre for Infections; Version Available : (accessed 2009 Jul 27) See section 2.2 Treatment 2. National Guideline Clearinghouse. Tularaemia. In: Guideline.gov [database online]. Rockville(MD): NGC; NGC: Available: (accessed 2009 Jul 27) 3. World Health Organization. WHO guidelines on tularaemia: In: WHO guidelines [database online]. Geneva(CH): WHO Press; Available: (accessed 2009 Jul 27). See section 5 Treatment 4. Bossi P, Tegnell A, Baka A, Van LF, Hendriks J, Werner A, et al. Bichat guidelines for the clinical management of tularaemia and bioterrorism-related tularaemia. Euro Surveill 2004;9(12):E9-10. PubMed: PM PREPARED BY: Kristen Moulton, BA, Research Assistant Ray Banks, AB, MA, MLS, Information Specialist Health Technology Inquiry Service htis@cadth.ca Tel: Antibiotics for the Treatment of Tularemia 5

6 APPENDIX FURTHER INFORMATION: Review articles 5. Center for Infectious Disease Research & Policy. Tularemia: current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis. Minneapolis: University of Minnesota; Available: (accessed 2009 Jul 23). See section on Treatment Additional references 6. Baddour LM, Zheng ZJ, Labarthe DR, O'Connor S. ACCF/AHA/CDC conference report on emerging infectious diseases and biological terrorism threats. Task Force I: direct cardiovascular implications of emerging infectious diseases and biological terrorism threats. Circulation 2007;115(12): Available: (accessed 2009 Jul 23). PubMed: PM MacIntyre CR, Seccull A, Lane JM, Plant A. Development of a risk-priority score for category A bioterrorism agents as an aid for public health policy. Mil Med 2006;171(7): PubMed: PM Antibiotics for the Treatment of Tularemia 6