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Tularemia

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Tularemia

Admission Criteria/Initial Stabilization

Based on clinical improvement and the ability to tolerate oral antibiotics and adhere to treatment/follow-up recommendations ‚

As tolerated, high-calorie, easily digestible ‚

For patient information, see the CDC Web site/FAQ and Key Facts on Tularemia: ‚

11 Centers for Disease Control and Prevention. Reported tularemia cases " ”United States, 2004-2013. http://www.cdc.gov/tularemia/statistics/state.html. Accessed 2015.22 Adams ‚ DA, Gallagher ‚ KM, Jajosky ‚ RA, et al. Summary of notifiable diseases " ”United States, 2011. MMWR Morb Mortal Wkly Rep. 2013;60(53):1 " “117.33 Snowden ‚ J, Stovall ‚ S. Tularemia: retrospective review of 10 years ' experience in Arkansas. Clin Pediatr (Phila). 2011;50(1):64 " “68.44 Hofinger ‚ DM, Cardona ‚ L, Mertz ‚ GJ, et al. Tularemic meningitis in the United States. Arch Neurol. 2009;66(4):523 " “527.55 T ƒ ¤rnvik ‚ A, Chu ‚ MC. New approaches to diagnosis and therapy of tularemia. Ann N Y Acad Sci. 2007;1105:378 " “404.66 Maurin ‚ M, Castan ‚ B, Roch ‚ N, et al. Real-time PCR for diagnosis of oculoglandular tularemia. Emerg Infect Dis. 2010;16(1):152 " “153.77 Splettstoesser ‚ W, Guglielmo-Viret ‚ V, Seibold ‚ E, et al. Evaluation of an immunochromatographic test for rapid and reliable serodiagnosis of human tularemia and detection of Francisella tularensis-specific antibodies in sera from different mammalian species. J Clin Microbiol. 2010;48(5):1629 " “1634.88 Weber ‚ IB, Turabelidze ‚ G, Patrick ‚ S, et al. Clinical recognition and management of tularemia in Missouri: a retrospective records review of 121 cases. Clin Infect Dis. 2012;55(10):1283 " “1290.

Use aminoglycosides and quinolones with caution.

GENERAL MEASURES

  • Contact and respiratory droplet isolation; negative air pressure room not necessary
  • Handle secretions carefully.
  • Hydration, fever control, antibiotics, wet saline dressings for skin lesions
  • Recovery requires intact cell-mediated immunity.
  • Bacterium is readily killed by heat (56 ‚ °C for 10 minutes)

MEDICATION

  • Aminoglycosides (gentamicin or streptomycin) are the antimicrobials of choice:Gentamicin: 5 mg/kg/day divided BID " “TIDRoutine serum level monitoring for aminoglycosidesStreptomycin (classic drug of choice but may not be available): 15 to 20 mg/kg/day IM divided BID for 7 to 14 days, not to exceed 2 g/dayRarely usedPotential vestibular or nephrotoxicityConcern over drug-resistant strains in biologic warfareTularemic meningitis: CSF aminoglycoside levels vary so treat with an aminoglycoside plus chloramphenicol or doxycycline for 14 to 21 days, following clinical findings, fever as guide (4)[C],(8)[A].
  • For mild/moderate diseaseDoxycycline 100 mg BID for 14 daysCiprofloxacin 500 to 750 mg BID for 14 days
  • Doxycycline and ciprofloxacin are considered drugs of choice in mass-casualty situations (biowarfare). Prophylaxis after an aerosol exposure is effective if administered within 24 hours:Ciprofloxacin: 500 mg PO BID for 10 days; not approved, usually not recommended in pediatricsDoxycycline (Doryx, Vibra-Tabs, Vibramycin): 100 mg PO BID for 14 to 21 days; if ≥8 years
  • Ž ²-Lactams (e.g., penicillin derivatives), most cephalosporins, clotrimazole, and many macrolides are ineffective or have resistance.
  • Gentamicin: 5 mg/kg/day divided BID " “TID
  • Routine serum level monitoring for aminoglycosides
  • Streptomycin (classic drug of choice but may not be available): 15 to 20 mg/kg/day IM divided BID for 7 to 14 days, not to exceed 2 g/dayRarely usedPotential vestibular or nephrotoxicityConcern over drug-resistant strains in biologic warfare
  • Tularemic meningitis: CSF aminoglycoside levels vary so treat with an aminoglycoside plus chloramphenicol or doxycycline for 14 to 21 days, following clinical findings, fever as guide (4)[C],(8)[A].
  • Rarely used
  • Potential vestibular or nephrotoxicity
  • Concern over drug-resistant strains in biologic warfare
  • Doxycycline 100 mg BID for 14 days
  • Ciprofloxacin 500 to 750 mg BID for 14 days
  • Ciprofloxacin: 500 mg PO BID for 10 days; not approved, usually not recommended in pediatrics
  • Doxycycline (Doryx, Vibra-Tabs, Vibramycin): 100 mg PO BID for 14 to 21 days; if ≥8 years
  • Chloramphenicol: may be difficult to obtain
  • Tetracycline: higher relapse rate
  • Fluoroquinolones (ciprofloxacin) are gaining wider acceptance, show high cure rates/low side effects, and may be used as alternative therapy against F. tularensis type B only.

ISSUES FOR REFERRAL

  • Infectious disease consult
  • Notify public health authorities.

INPATIENT CONSIDERATIONS

  • Depends on severity
  • Hospitalize if fever with shortness of breath, concern for septicemia, or need for surgery

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Monitor hearing during long-term therapy with aminoglycosides.
  • Monitor renal function during long-term therapy with aminoglycosides or quinolones.

DIET

PATIENT EDUCATION

  • http://www.bt.cdc.gov/agent/tularemia
  • http://emergency.cdc.gov/agent/tularemia/facts.asp

PROGNOSIS

  • Complete cure if treated early; immunity is lifelong.
  • Mortality: <2% if treated; higher in typhoidal disease

COMPLICATIONS

  • Lung abscess, adult respiratory distress syndrome (ARDS)
  • Hepatic dysfunction, rhabdomyolysis, renal failure
  • Osteomyelitis, meningitis, endocarditis, mediastinitis, pericarditis, peritonitis, conjunctivitis
  • Drug-induced side effects (e.g., diarrhea, renal failure)

REFERENCES

ADDITIONAL READING

  • Ata ‚ N, K „ ±l „ ± ƒ § ‚ S, ƒ –vet ‚ G, et al. Tularemia during pregnancy. Infection. 2013;41(4):753 " “756.
  • Centers for Disease Control and Prevention. Tularemia " ”United States, 2001 " “2010. MMWR Morb Mortal Wkly Rep. 2013;62(47):963 " “966.
  • Dennis ‚ DT, Inglesby ‚ TV, Henderson ‚ DA, et al. Tularemia as a biological weapon: medical and public health management. JAMA. 2001;285(21):2763 " “2773.
  • Kosker ‚ M, Celik ‚ T, Yuksel ‚ D. Treatment of tularemia during pregnancy. J Infect Dev Ctries. 2015;9(1):118 " “119.
  • L ƒ µhmus ‚ M, Janse ‚ I, van de Goot ‚ F, et al. Rodents as potential couriers for bioterrorism agents. Biosecur Bioterror. 2013;11(Suppl 1):S247 " “S257.
  • Steinr ƒ ¼cken ‚ J, Graber ‚ P. Oropharyngeal tularemia. CMAJ. 2014;186(1):E62.

CODES

ICD10

  • A21.9 Tularemia, unspecified
  • A21.0 Ulceroglandular tularemia
  • A21.1 Oculoglandular tularemia
  • A21.8 Other forms of tularemia
  • A21.3 Gastrointestinal tularemia
  • A21.2 Pulmonary tularemia
  • A21.7 Generalized tularemia

ICD9

  • 021.9 Unspecified tularemia
  • 021.0 Ulceroglandular tularemia
  • 021.3 Oculoglandular tularemia
  • 021.8 Other specified tularemia
  • 021.1 Enteric tularemia
  • 021.2 Pulmonary tularemia

SNOMED

  • Tularemia (disorder)
  • Ulceroglandular tularemia (disorder)
  • Oculoglandular tularemia (disorder)
  • Oropharyngeal tularemia
  • Glandular tularemia (disorder)
  • Pulmonary tularemia
  • Enteric tularemia

CLINICAL PEARLS

  • A high index of suspicion is required to make the diagnosis of tularemia. Consider biologic terrorism based on epidemiologic presentation. If bioterrorism is suspected, contact appropriate authorities and coordinate rapid diagnostic testing through the Laboratory Response Network 1-866-576-5227.
  • Treat suspected or confirmed cases.
  • Aminoglycosides are treatment of choice.
  • Serologic and special ELISA studies (and PCR/real-time PCR studies where available) are recommended for diagnosis. A CDC 24-hour/7-day-a-week toll-free hotline is available at 800-232-4636 to answer clinical questions.