Tularemic Pneumonia -- Tennessee

In October and December 1982, three cases of primary tularemic pneumonia were reported to the Tennessee State Department of Public Health. None of the patients manifested ulceroglandular disease; all three recovered.

Case 1: On October 26, a 48-year-old insulin-controlled diabetic male resident of Mississippi was admitted to a Memphis hospital with sepsis and acute rhabdomyolysis. He had a temperature of 40.6 C (105 F), a markedly elevated white blood cell (WBC) count with many young cells, a right lower-lobe pneumonia, and myoglobinuria with a creatine phosphokinase (CPK) of 1049. He was begun on cefamandole; when his condition deteriorated on the second day, tobramycin was added. Tularemia was suspected on the third day, and his wife indicated he had skinned rabbits 2 days before admission. Although admission blood cultures were eventually found positive for Francisella tularensis by the state laboratory, initial confirmation of the diagnosis was provided by a convalescent-phase F. tularensis titer of 5400 at 2 weeks. The patient has since fully recovered.

Case 2: On December 24, a 37-year-old male resident of Mississippi was admitted to a Memphis hospital with pneumonia and sepsis. Therapy was begun with penicillin; tobramycin and erythromycin were added, and nafcillin was given briefly. On December 27, the patient suffered a respiratory arrest and has since required mechanical ventilation. Significant complications included prolonged hypotension treated with vasopressors, anuric renal failure requiring dialysis, and coma.

Although subsequent information indicated the patient hunted daily, a correct diagnosis was not established until January 17, when the state laboratory identified F. tularensis in blood taken on December 25; no growth was detected in the broth until January 3. By the end of January, the patient remained intubated, stuporous without spontaneous muscle movement below the neck, and anuric, and suffered Escherichia coli sepsis, suspected Candida sepsis, and gangrene of the feet. However, he slowly recovered and was discharged in his fourth hospital month.

Case 3: On December 31, a 50-year-old previously healthy male was admitted to a Nashville hospital with a 2-week history of fever, chills, and productive cough. On admission, he had bilateral pneumonia with a WBC count of 28,400, and therapy was begun with ampicillin. His condition worsened; he experienced respiratory failure requiring mechanical ventilation and acute renal failure requiring dialysis. Tularemia was considered in the differential diagnosis; the patient's wife indicated he had skinned a rabbit 1 week before onset of symptoms. Gentamicin was begun on January 2. Although admission blood cultures and the lung biopsy were subsequently reported positive for F. tularensis by the state laboratory, the diagnosis was initially confirmed by a 4-fold rise in F. tularensis slide test agglutination titers from 80 to 320 between the third and eleventh hospital days. The agglutination titer subsequently rose to 16,000 on January 18. The patient eventually recovered normal renal and respiratory function and was discharged. Reported by J Fowler, MD, R Taylor, MD, Memphis City Hospital, M Gelfand, MD, W Bounds, MD, Methodist Hospital, Memphis, A Savage, MD, T Brown, MD, H Wilson, MD, Veterans Administration Medical Center, Nashville, RH Hutchenson, Jr, MD, State Epidemiologist, Tennessee State Dept of Public Health; Div of Field Svcs, Epidemiology Program Office, Div of Bacterial Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Pneumonia due to hematogenous dissemination occurs in 10%-15% of ulceroglandular tularemia cases and 30%-80% of typhoid cases, but primary tularemic pneumonia is believed rare (1). A history of tick exposure or hunting may be a useful diagnostic clue but is frequently absent (1,2). Chest x-ray findings are variable and nonspecific (3).

In general, tularemia cases tend to be more severe in North America than in other parts of the world, possibly because type A strains of F. tularensis are present in North America but not elsewhere (4). Type A strains are associated with rabbits and tick vectors and are biochemically characterized by their ability to ferment glycerol and possession of the enzyme citrulline ureidase (5-7). Type B strains are also found in North America but are an uncommon cause of human illness (4,8). The isolates from the Tennessee patients fermented glycerol and were probably type A strains.

Bacteremia probably occurs frequently in tularemia, but direct isolates from blood are rarely reported. In the current cases, the blood culture methodology was similar at all three hospitals and was based on use of a Bactec* instrument to detect microbial growth. The blood was inoculated into enriched tryptic soy broth (TSB) for aerobic culture, a prereduced enriched TSB for anaerobic culture and, at one hospital, a resin bottle for antimicrobial inactivation. Neither the aerobic nor the resin-bottle medium contained cystine or cysteine, which probably accounts for the slow growth rate subsequently observed The anaerobic medium contained cysteine, but F. tularensis is an aerobe. A low growth index (

30 40) was observed only in the aerobic cultures after 7-9 days incubation. Gram stains of the broth were negative at two hospitals and considered positive at the third only because F. tularensis had already been isolated from a lung biopsy on the patient. Acridine-orange stain of the broth was positive at one hospital (9). Subculture of aerobic, anaerobic, and resin-bottle cultures to supplemented chocolate agar resulted in visible growth at 72 hours. Supplements used in the chocolate agar were cystine only, VX* only, and IsoVitaleX* and cystine. Commercial biochemical system tests did not prove useful in isolate identification at the hospital laboratories.

Controlled studies of antimicrobial therapy for tularemia have not been done for some years. Streptomycin is commonly accepted as the drug of choice, and recommended alternative drugs, albeit frequently associated with clinical relapse, are tetracycline or chloramphenicol (1). None of these drugs was used in the current cases. Studies at CDC found that the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBS) for isolates from all three patients were 1 ug or less for both gentamicin and tobramycin. Gentamicin has been previously reported effective for tularemia (10, 11). The MIC and MBC for the other drugs used in treating the patients indicate probable lack of efficacy.

References

1. Boyce JM. Francisella tularensis (tularemia). In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practice of infectious diseases. New York: Wiley 1979:1784-8.

2. Teutsch SM, Martone WJ, Brink EW, et al. Pneumonic tularemia on patients indicate probable lack of efficacy. References

3. Boyce JM. Francisella tularensis (tularemia). In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practice of infectious diseases. New York: Wiley 1979:1784-8.

4. Teutsch SM, Martone WJ, Brink EW, et al. Pneumonic tularemia on Martha's Vineyard. N Engl J Med 1979;301:826-8.

5. Miller RP, Bates JH. Pleuropulmonary tularemia: a review of 29 patients. Am Rev Respir Dis 1969;99:31-41.

6. Jellison WL. Tularemia in North America, 1930-1974. Missoula, Montana: University of Montana, 1974.

7. Olsufyev NG, Emelyanova OS. Further studies of strains of tularemic bacteria of the old and new world. J Hyg Epidemiol Microbiol Immunol 1962;6:193-205.

8. Hornick RB, Eigelsbach HT. Tularemia epidemic--Vermont, 1968. N Engl J Med 1969;281:1310. Letter.

9. Marchette NJ, Nicholes PS. Virulence and citrulline ureidase activity of Pasteurella tularensis. J Bacteriol 1961;82:26-32.

10. Jellison WL, Owen CR, Bell JF, Kohls GM. Tularemia and animal populations: ecology and epizootiology. Wildlife Disease 1961;17:1-22.

11. Burdash NM, Manos JP, Bannister ER, Welborn AL. Acridine orange staining and radiometric detection of microorganisms in blood cultures. J Clin Microbiol 1983;17:463-5.

12. Alford RH, John JT, Bryant RE. Tularemia treated successfully with gentamicin. Am Rev Respir Dis 1972;106:265-8.

13. Mason WL, Eigelsbach HT, Little SF, Bates JH. Treatment of tularemia, including pulmonary tularemia, with gentamicin. Am Rev Respir Dis 1980;121:39-45.

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