Final Diagnosis -- Legionella micdadei prosthetic valve endocarditis with a septic emboli to the brain

FINAL DIAGNOSIS   Legionella micdadei prosthetic valve endocarditis with a septic emboli to the brain.

When the diagnosis became known, we re-examined the original brain abscess using the Gram and Warthin-Starry silver stain (Figure 3A and 3B).

DISCUSSION

Legionella micdadei

L. micdadei, initially named as Pittsburgh pneumonia agent and later as L. pittsburgensis, was first described as a gram-negative, weakly acid-fast bacillus distinct from L. pneumophilia in 1979 by Pasculle et al. in acute purulent pneumonia cases from two renal-transplant patients (1). Later same year, Myerowitz et al. reported eight more cases and presented Pittsburgh pneumonia agent as a newly recognized cause of life-threatening bacterial pneumonia in immunocompromised patients. Recent institution of daily high-dose corticosteriod therapy was the most consistent feature associated with the disease in all patients (2). Serologic studies with an indirect fluorescent-antibody technic was proposed as a sensitive test for the diagnosis of the disease. It was found that the organism resembled L. pneumophila and other Legionella-like organisms in growth requirements and composition of fatty acids; but differed in genetic relatedness, antigenic composition, and colonial morphology and had distinctive characteristics that would allow it to be identified as a different species ( Legionella pittsburgensis) (3). L. micdadei does not produce beta-lactamase and grows best on buffered charcoal yeast extract (BCYE) agar without added cephalosporins (4).

Legionella spp. and endocarditis

Legionella spp. cause nosocomial pneumonia and, rarely, disease of extrapulmonary sites. Prosthetic valve endocarditis (PVE) accounts for 7-25% of cases of infective endocarditis in developed countries. Legionella is in the differential diagnosis of "culture negative endocarditis" (5, 6). Twelve cases of PVE due to Legionella spp. have now been documented, including two cases of Legionella micdadei PVE; one diagnosed serologically and another culture-proven (5, 6). All were cured; 10 underwent valve replacement (5). The source of the Legionella in these cases could not be identified with certainty.

Between 1982 and 1988, 7 patients at Stanford University was shown to have PVE caused by L. pneumophilia or L. dumoffii (7). Examination of legionella isolates by means of molecular techniques demonstrated that the Stanford L. pneumophilia isolates were genotypically identical to isolates from the hospital drinking water. L dumoffii isolates from patients with endocarditis were derived from a single strain unique to this medical center. The authors concluded that legionella infection was nosocomially acquired in the perioperative period (7). All patients with endocarditis had a chronic course (3 to 19 months after surgery) of fever, night sweats, weight loss, and anemia, but no embolic events or immune-complex deposition disease (7). Anemia was reported as a frequent feature, and its severity appeared to be correlated with the duration of the infection. Leukocyte counts were normal, but thrombocytopenia was observed.

Legionella endocarditis should be suspected in febrile patients with prosthetic valves and negative blood cultures. Since most of reported cases are nosocomial in origin, Legionella endocarditis is likely to occur in small outbreaks. Diagnostic delays vary from 3 to 19 months after surgery.

Treatment

The new macrolide antibiotics, such as clarithromycin and azithromycin, show more effective in-vitro activity and a better intracellular and tissue penetration than erythromycin, as do the quinolones, especially levofloxacin (8).

Our patient was started on an intravenous 6 week levofloxacin treatment.

SUMMARY

Legionella spp. are recognized causes of blood culture-negative prosthetic valve endocarditis, especially in immunosuppressed patients and nosocomial infections. The diagnosis can be confirmed by culture on enriched media or by PCR performed on excised valvular material. The prognosis is generally favorable, although valve replacement is often necessary for cure.

We are unaware of a source in this case. The patient was not diagnosed with pneumonia at any point and there were no outbreaks reported during the time of her hospitalization. It is possible that the disease was due to community acquired L. micdadei considering the long time intervals between her operations.

REFERENCES

1. Pasculle AW, Myerowitz RL, Rinaldo CR Jr.New bacterial agent of pneumonia isolated from renal-transplant recipients. Lancet. 1979 Jul 14;2(8133):58-61.
2. Myerowitz RL, Pasculle AW, Dowling JN, Pazin GJ Sr, Puerzer M, Yee RB, Rinaldo CR Jr, Hakala TR. Opportunistic lung infection due to "Pittsburgh Pneumonia Agent". N Engl J Med. 1979 Nov 1; 301 (18): 953-8.
3. Pasculle AW, Feeley JC, Gibson RJ, Cordes LG, Myerowitz RL, Patton CM, Gorman GW, Carmack CL, Ezzell JW, Dowling JN. Pittsburgh pneumonia agent: direct isolation from human lung tissue. J Infect Dis. 1980 Jun;141(6):727-32.
4. Pasculle AW, Dowling JN, Weyant RS, Sniffen JM, Cordes LG, Gorman GM, Feeley JC.Susceptibility of Pittsburgh pneumonia agent (Legionella micdadei) and other newly recognized members of the genus Legionella to nineteen antimicrobial agents. Antimicrob Agents Chemother. 1981 Dec;20(6):793-9)
5. Patel MC, Levi MH, Mahadevi P, Nana M, Merav AD, Robbins N. L. micdadei PVE successfully treated with levofloxacin/valve replacement: case report and review of literature. Journal of Infection (2005) 51, 265-268.
6. Park D, Pugliese A, Cunha BA. Legionella micdadei prosthetic valve endocarditis. Infection. 1994 May-Jun; 22(3):213-5.
7. Tompkins LS, Roessler BJ, Redd SC, Markowitz LE, Cohen ML. N Engl J Med 1988; 318; 530-535.
8. Bartram J, Chartier Y, Lee JV,Pond K, Surman-Lee S. Legionella and the prevention of Legionellosis. 2007. WHO. p.16.

Contributed by Isil Yildiz, MD and A. William Pasculle, Sc.D.