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<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>28 July 2008<o:p></o:p></span></p>

<p class=3DMsoNormal><b style=3D'mso-bidi-font-weight:normal'><span
style=3D'mso-bidi-font-size:14.0pt;font-family:Arial'><o:p>&nbsp;</o:p></sp=
an></b></p>

<p class=3DMsoNormal><b style=3D'mso-bidi-font-weight:normal'><span
style=3D'mso-bidi-font-size:16.0pt;font-family:Arial;mso-bidi-font-family:"=
Times New Roman"'>Disease
due to F. tularensis &#8220;Fx1&#8221; Infection</span></b><span
style=3D'font-size:9.0pt;mso-bidi-font-size:16.0pt;font-family:Arial;mso-bi=
di-font-family:
"Times New Roman"'><o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:16.0=
pt;
font-family:Arial;mso-bidi-font-family:"Times New Roman"'><o:p>&nbsp;</o:p>=
</span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>The clinical history of a patient with a microbiological=
ly
atypical Francisella tularensis infection, termed &#8220;Fx1&#8221;, was
presented in a microbiology journal by co-authors from <st1:State w:st=3D"o=
n">Texas</st1:State>
and <st1:place w:st=3D"on"><st1:City w:st=3D"on">Umea</st1:City>, <st1:coun=
try-region
 w:st=3D"on">Sweden</st1:country-region></st1:place> over a decade ago.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>As part of a new series on this we=
bsite
of patients and clinical syndromes of past of particular interest, this
patient&#8217;s clinical course is summarized below.<o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>The patient was a 55 year-old man who lived in <st1:place
w:st=3D"on"><st1:City w:st=3D"on">Galveston</st1:City>, <st1:State w:st=3D"=
on">Texas</st1:State></st1:place>
on a beachfront cottage.<span style=3D'mso-spacerun:yes'>&nbsp; </span>He h=
ad
diabetes and had been on prednisone, 20mg each day for an unstated duration,
&#8220;for inflammatory nodular skin lesions of unknown etiology&#8221;. The
severity and treatment of his diabetes was also unstated. He was hospitaliz=
ed
in June 1991 with a three week history of weakness, shortness of breath on
exertion, chest pain, and restfulness.<span style=3D'mso-spacerun:yes'>&nbs=
p;
</span>He was found to have <span class=3DGramE>diffuse</span> wheezing in =
both
lungs and moderate enlargement of his liver and spleen. On his third day in=
 the
hospital he developed a high fever (39.8 C), headache, and an increased
peripheral white blood cell count. <o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>Work-up revealed two positive blood cultures obtained wi=
th
his fever that grew a Francisella species termed &#8220;Fx1&#8221;. An MRI
brain scan was interpreted as showing brain abscesses with a maximum size of
12mm.<span style=3D'mso-spacerun:yes'>&nbsp; </span>The initial spinal flui=
d exam
culture was not commented on, but there were 25 white blood cells (92% of w=
hich
were mononuclear cells), an elevated protein of 107 mg/dl and a glucose of
84mg/dl (without a peripheral blood glucose being reported and thus unable =
to
be interpreted as within normal limits or not). <o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>A chest X-ray after the fever appeared revealed &#8220;n=
ew
pleura-based infiltrates in the right lower lung&#8221;. No sputum was
produced. Extensive testing that included an echocardiogram, an EEG, and a
4-vessel cerebral angiogram was negative. The patient was treated with
&#8220;expanded-spectrum cephalosporins&#8221;. Subsequently, both his fever
and his right lower lung abnormality resolved.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>No information was provided on any
further brain imaging or longer-term clinical follow-up. His presumptive
diagnosis was bacteremia, pneumonia, and brain abscesses due to the
&#8220;Fx1&#8221; bacteria.<o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>Serologic testing for Francisella was negative when
performed two weeks after the positive blood culture. <span
style=3D'mso-spacerun:yes'>&nbsp;</span>The patient lived with a
&#8220;tick-infested dog&#8221;, but no results of testing for Fx1 infectio=
n of
the dog, the ticks, or any other potential environmental sources were
presented.<o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>The two positive blood cultures grew <span class=3DGramE=
>a
small, gram-negative coccoid bacteria</span> (&#8220;termed &#8220;Fx1&#822=
1;)
in the aerobic bottle after three days using the BACTEC blood culture syste=
m.
Importantly, the Vitek NHI panel suggested an (incorrect) identification of=
 the
Fx1 Francisella bacteria as Hemophilus Actinomycetemcomitans with a 99%
confidence level (see page 1998 under the &#8220;Growth and biochemical
results&#8221; section of this paper). . While this &#8220;Fx1&#8221; bacte=
rium
was susceptible in vitro to ceftriaxone, ciprofloxacin, imipenem and
chloramphenicol, it was resistant to penicillin, ampicillin, amoxicillin-cl=
avulanate,
aztreonam, cephalothin, and trimethoprim-sulfamethoxazole. <o:p></o:p></spa=
n></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>This patient is the only one published, to this
writer&#8217;s knowledge, with infection due to this Fx1 Francisella bacter=
ia
(in subsequent years further identified as Francisella tularensis novicida =
(or
&#8220;novicida-like&#8221;).<span style=3D'mso-spacerun:yes'>&nbsp; </span=
><o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>The importance of mis-identification of this bacteria as
Hemophilus Actinomycetemcomitans (with 99% confidence level by Vitek NHI
panel), should be emphasized in the event of an environmental contamination=
 with
Francisella &#8220;Fx1&#8221;. In such a situation, explicit public health =
and
medical recommendations must be made to perform surveillance and testing of=
 any
clinical specimens (e.g., blood, skin, sputum, pleural fluid, lung, spinal
fluid, or brain) from ill patients who could have been exposed to this cont=
aminated
environment who have Hemophilus Actinomycetemcomitans bacteria identified in
the clinical laboratory, given that the true identity of such bacteria could
well be an atypical Francisella tularensis species such as Fx1.<o:p></o:p><=
/span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>Daniel R. Lucey MD, MPH<o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>EROne Institutes, Department of Emergency Medicine<o:p><=
/o:p></span></p>

<p class=3DMsoNormal><st1:place w:st=3D"on"><st1:PlaceName w:st=3D"on"><span
  style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'>Was=
hington</span></st1:PlaceName><span
 style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'> <st=
1:PlaceType
 w:st=3D"on">Hospital</st1:PlaceType> <st1:PlaceType w:st=3D"on">Center</st=
1:PlaceType></span></st1:place><span
style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'><o:p>=
</o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>Adjunct Professor of Microbiology and Immunology<o:p></o=
:p></span></p>

<p class=3DMsoNormal><st1:place w:st=3D"on"><st1:PlaceName w:st=3D"on"><span
  style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'>Geo=
rgetown</span></st1:PlaceName><span
 style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'> <st=
1:PlaceType
 w:st=3D"on">University</st1:PlaceType> <st1:PlaceName w:st=3D"on">Medical<=
/st1:PlaceName>
 <st1:PlaceType w:st=3D"on">Center</st1:PlaceType></span></st1:place><span
style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'><o:p>=
</o:p></span></p>

<p class=3DMsoNormal><st1:place w:st=3D"on"><st1:City w:st=3D"on"><span
  style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'>Was=
hington</span></st1:City><span
 style=3D'font-size:9.0pt;mso-bidi-font-size:14.0pt;font-family:Arial'>, <s=
t1:State
 w:st=3D"on">D.C.</st1:State></span></st1:place><span style=3D'font-size:9.=
0pt;
mso-bidi-font-size:14.0pt;font-family:Arial'><o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'>Website for this posting: <a href=3D"http://www.bepast.o=
rg/">www.BePast.org</a><o:p></o:p></span></p>

<p class=3DMsoNormal><span class=3DGramE><span style=3D'font-size:9.0pt;mso=
-bidi-font-size:
14.0pt;font-family:Arial'>e-mail</span></span><span style=3D'font-size:9.0p=
t;
mso-bidi-font-size:14.0pt;font-family:Arial'>: DRL23@Georgetown.edu<o:p></o=
:p></span></p>

<p class=3DMsoNormal style=3D'tab-stops:135.0pt'><span style=3D'font-size:9=
.0pt;
mso-bidi-font-size:16.0pt;font-family:Arial;mso-bidi-font-family:"Times New=
 Roman"'><span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp; </span><o:p></o:p></span></p>

<p class=3DMsoNormal><span style=3D'font-size:9.0pt;mso-bidi-font-size:14.0=
pt;
font-family:Arial'><o:p>&nbsp;</o:p></span></p>

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