Community-acquired Klebsiella pneumoniae systemic infection complicated
with rhombencephalitis
Delia-Maria Stanca a,b, Daniela Larisa Balab (corresponding author*), Mihaela Ruscãb, Andra Achim b Dafin Fior Mureșanua,b
a Iuliu Hațieganu of and Pharmacy , 43, 400012
b Cluj-Napoca County Emergency Hospital, Neurology
Department, Victor Babeș Street No. 43, 400012 Cluj-Napoca, Romania
*Corresponding author details:
-mailing address: , Neurology Department, Victor Babeș Street No. 43
400012
-email address:bala.daniella@yahoo.com
Key clinical message
CNS involvement in community-acquired Klebsiella pneumoniae infection is
rare and usually presents as abscess or meningitis, while, to our
knowledge, no cases of K. Pneumoniae infection complicated with
rhombencephalitis have been previously reported.
Abstract
Rhombencephalitis refers to inflammatory diseases of the
rhombencephalon. The encephalitic processes located to the
rhombencephalon are frequently associated with Listeria monocytogenes
and enterovirus infections. We report a case of community-acquired
Klebsiella Pneumoniae systemic infection with CNS involvement in an
adult patient without significant comorbidities.
Introduction
The term rhombencephalitis (RE) refers to inflammatory diseases
involving the hindbrain (brainstem and cerebellum).
It was described for the first time by two scientists, Edwin Bickerstaff
and Philip Cloake in 1951 (1,2) to designate
inflammatory affections of the rhombencephalon.
Rhombencephalitis has a wide range of etiologies, which can be divided
into infectious, autoimmune and paraneoplastic causes.
The most common infectious agent is Listeria monocytogenes, followed by
Enterovirus 71 and herpes viruses. The most common autoimmune cause is
Behcet’s disease and the most frequent paraneoplastic syndrome is caused
by small cell lung cancer. (3)
In Gram-negative CNS infections, a primary focus may be found in
neonates, traumatic or neurosurgical patients, but in adults without a
history of surgical operations the primary focus of the infection could
not be detected in up to 60% of cases. (4)
The most common presentations of Klebsiella pneumoniae (K.pneumoniae)
CNS infection in adult are meningitis and brain abscess, but cerebritis
and cerebral hemorrhage were also reported. (5)
Here, we report a case of K. pneumoniae septicemia associated with CNS
involvement in an immunocompentent patient, without neurosurgical or
trauma history.
Case presentation
We present a case of an immunocompetent 60 years old male patient
admitted to the Neurology Department with sudden onset of difficulty in
walking, poor balance, slurred speech and complaints of mild headache.
His past medical history included hypertension and a chronic right
sciatica, for which he received symptomatic treatment with NSAIDs and
paravertebral infiltration with steroids.
At the time of admission, he was apyrexial, alert and with no signs of
meningism. No facial asymmetry or palpeberal ptosis was noted. He had
bilateral gaze-evoked nystagmus, gait ataxia, bilateral cerebellar
dysmetria and dysarthria. Laboratory findings: minimal hepatic
cytolysis, inflammatory syndrome with leucocytosis (WBC= 22 x
109 cells/L, 90% neutrophils, erythrocyte
sedimentation rate= 40mm/h and C-reactive protein= 18mg/L).
An emergency brain CT angiography was performed and no acute lesions
were observed.
At first, an ischemic stroke in the vertebrobasilar region was suspected
and treatment with antiplatelet and statins was initiated.
Within a few hours of hospitalization, his condition worsened, he
presented several episodes of projectile vomiting and became less
responsive (somnolence alternating with agitation). Further on, his
neurological status deteriorated rapidly and he developed tetraplegia.
He became comatose (GCS=3 points), with non-reactive mydriatic pupils
and was immediately transferred to the intensive care unit (ICU).
Screening for MRSA, ESBL, VRE, and CRE was performed upon ICU admission,
with negative results.
Blood cultures were also taken within the first 24 hours of admission.
In the ICU department the patient became febrile, with marked
inflammatory syndrome. An encephalitic process was suspected and empiric
antibiotic therapy was initiated with Vancomycin, Ampicillin and
Meropenem, associated with Acyclovir.
He tested negative for HIV and syphilis.
Cerebrospinal fluid examination revealed a sanguinolent aspect of the
CSF, mild elevated leukocyte counts, elevated protein levels and normal
CSF/serum glucose ratio.
The patient was referred for an emergent brain MRI which showed
bilateral cerebellar lesions, hyperintense in T2/FLAIR, diffuse edema
involving bilateral cerebellum, medulla and pons, aspect suggestive for
encephalitis. Neither contrast enhanced lesion, nor leptomeningeal
enhancement were shown.
Chest radiograph was normal.
Cultures of CSF were positive for K. pneumoniae spp and it was detected
in blood and urine cultures as well, on the 5th day of admission. The
isolated strain was susceptible to the majority of antibiotics.
Therefore, a diagnosis of systemic infection with K. pneumoniae
complicated with rhombencephalitis was made.
The antibiotic treatment was adjusted according to the results of blood,
urine and CSF cultures.
A abdomino-pelvic CT scan was performed, to rule out neoplastic disease,
which could cause immune suppression. The examination revealed right
iliopsoas muscle abscess. An ultrasound guided drainage was performed
and the pus culture was also positive for K. pneumonie.
A second screening for multi-drug resistance bacteria was performed 9
days after ICU admission and Klebsiella CRE and ESBL was detected on
perianal and rectal swabs.
Outcome and follow-up
Despite intensive treatment, the patient’s condition did not improve and
he died on the 14th day of hospitalization.
Discussion
Our patient was a 60-year-old male with no previous hospital admissions
and no obvious risk factors for suppressed immune status, who developed
a systemic infection with CNS involvement, with an unusual pathogen.
Rhombencephalitis is usually caused by Listeria monocytogenes, followed
by herpes simplex virus (HSV) and Enterovirus-71, while to our
knowledge, no cases of K. Pneumoniae infection with CNS involvement
presenting as rhombencephalitis have been previously reported.
The differential diagnosis of rhombencephalitis should include multiple
sclerosis, Behcet’s disease, paraneoplastic syndrome and other
infectious diseases (Listeria monocytogenes, EBV, Mycoplasma etc).(6)
Listerial rhombencephalitis has a characteristic biphasic course: for
the first 2-4 days there are nonspecific symptoms, such as fever,
headache, nausea and vomiting, followed by progressive
asymmetrical cranial nerve palsies, cerebellar signs, hemiparesis and
impairment of consciousness. The onset of neurological deterioration is
usually abrupt. The syndrome progresses rapidly and sometimes has a
fatal outcome. (7)
In our case, the course of the syndrome was different, with mild
headache presenting as the first symptom, followed by cerebellar signs,
impairment of consciousness, quadriplegia and ultimately fever, with
rapid progression.
The diagnosis is usually achieved by MRI findings and confirmed by CSF
analysis in correlation with clinical manifestations.
Radiological findings reveal high signal intensities on T2-weighted ,
FLAIR and DWI (hypointese on ADC map) images in the brainstem and
cerebellum, with hypo- or isointense signal in T1. On Postgadolinium
T1-weighted series, there is variable enhancement, depending on the
etiology. MRI findings are not exclusive of any particular entity.(8)
CSF examination usually reveals moderate pleocytosis, normal/reduced
glucose concentration, elevated proteins. Positive CSF and blood
cultures are the most specific findings for diagnosis.
In this case, CT scan upon admission was unremarkable, which is possible
in the early course of the disease. When the clinical status of the
patient deteriorated, an MRI was performed, which evidenced lesions
characteristic for rhombencephalitis.
Community-acquired bacteremia is defined as a positive blood culture
taken on or within 48 hours of admission. (9) In our
case, the blood cultures were taken within 24 hours of admission.
Combining CSF, blood and urine cultures, with radiological and clinical
findings, we established the diagnosis of community-acquired K.
pneumoniae septicemia complicated with rhombencephalitis.
Klebsiella species are Gram-negative bacteria, found ubiquitously in
nature, including in plants, animals, and humans. It is the causative
agent of several types of infections in humans, including respiratory
tract infections, urinary tract infections (UTIs) and bloodstream
infections (BSI). (10)
K.pneumoniae strains can be divided into opportunistic, hypervirulent
and multidrug-resistant groups. Most frequently, opportunistic strains
cause hospital-acquired infection in patients with impaired host
defenses. (11)
Hypervirulent strains of K. Pneumoniae (Kp) affect healthy people in
community settings and can cause severe infections, such as pyogenic
liver abscess, endophthalmitis and meningitis. (12)
In recent years, new hypervirulent Kp strains have been associated with
life-threatening infections with distant metastasis and, despite the
presence of comorbidities in most patients, it is seen in younger,
healthy patients as well. (13,14)
Diabetes has been speculated as a significant risk factor of hvKP
infection. (15,16) It has been shown that infective
and proinflammatory properties of Klebisella are more virulent in the
alcoholic host. (17) Our patient had no history of
diabetes or alcohol abuse.
The frequency of Klebsiella as a CNS pathogen is increasing, with no
improvement in prognosis over a 15-year period despite the availability
of newer antibiotics. Particularly high mortality
with Klebsiella septicemia and CNS spread has been noted.(18)
K. pneumoniae is the second leading cause of (BSI) caused by
Gram-negative bacteria. (10,19)
BSI can be primary (no identifiable source) or, more often, secondary
infection through dissemination from a known source. The most common
sources of secondary BSI include the urinary tract, the gastrointestinal
tract, intravenous or urinary catheters and respiratory sites.(20)
K. pneumoniae psoas muscle abscess is a rare infection that has been
described in case reports and small institutional series, mostly from
Taiwan, where, since 1981, a distinctive syndrome of
community-acquired K. pneumoniae septicemia with liver abscess has been
reported. (21,22) Among those cases, 43 percent had
concurrent urinary infection. This syndrome is notable for high
mortality (10 to 40%), and some cases have been complicated by
meningitis or endophthalmitis. (23)
The psoas abscess is considered primary if the cause is hematogenous
seeding from a distant site by bacteremia or sepsis, and secondary if
there is a contiguous infectious source from vertebrae, pancreas,
kidney, ureter, appendix, bowel, or hip joint. (24)
The portal of entry of K. pneumoniae bacteremia is identified in only
32% of cases; it is usually urinary, digestive and hepato-biliary.
Other gateways - vascular, oral or lung, were rarely
found.(25)
In our case, it was difficult to establish the primary source of the
systemic infection.
The psoas major originates along the outer surfaces of the vertebral
bodies of T12 and L1-L3 and their associated intervertebral discs.
Taking into consideration the anatomy of the psoas muscle and the fact
that the patient received paravertebral infiltration in the lumbar
region for his sciatica, we can not rule out the hypothesis that the
psoas abscess was the primary source of infection.
Intramuscular injections can rarely result in serious infectious
complications such as abscesses which may progress to bacteriemia and
generalized sepsis.
Due to the proximity of iliopsoas abscess to the vertebrae, it is
possible that the adjacent structures could be infected via direct
invasion, causing epidural abscess, osteomyelitis or discitis. In this
case, the abdomino-pelvic CT scan did not evidence any of this. We can
not exclude that the lumbar sciatic was caused in the first place by an
infectious process in the lumbar region.
Another hypothesis is that the primary source of infection could be the
urinary tract infection, which could led to psoas abscess either by
contiguity or hematogenous spreading, with CNS involvement.
Management of rhombencephalitis includes treating the underlying cause
in addition to supportive management.
Carbapenems are typically the drug of choice to treat severe infections
caused by ESBL-producing bacteria.
Due to the selective pressure of treating ESBL infections with
carbapenems, resistance has emerged and K. pneumoniae is the most common
carbapenem-resistant Enterobacteriaceae (CRE).
Because Listeria and HSV are the most common treatable acute causes, it
is recommended to start empiric therapy with ampicillin and acyclovir
for all cases after CSF and blood samples have been obtained for
cultures and the polymerase chain reaction (PCR). Antibiotics can be
changed based upon MRI, culture results, PCR results.(26)
ICU-acquired infection is defined if the pathogen colonies are detected
on screening swabs samples 7 days after ICU admission, in previously
negative patients. (27) In our case,
community-acquired bacteriemia was associated with an ICU-acquired
infection (K.pneumoniae CRE and ESBL), leading to poor prognosis.
Given the aggressive course of the disease and the lack of response to
antibiotic treatment, we presume that a hypervirulent strain of K.
pneumoniae was involved in this case.
CNS infections represent a challenge for clinicians because of the poor
concentration achieved by antibiotics in the CSF. In particular, if the
isolated microorganism exhibits multiple resistances, the situation
becomes critical because of the relative difficulty of reaching the high
concentrations needed.
Despite advances in microbiology and imaging, rhombencephalitis can be a
diagnostic challenge due to the multitude of possible differential
diagnoses and the difficulty to determine etiology. Rapid diagnosis and
adequate treatment are important to reduce mortality and morbidity.(28) Overall mortality in rhombencephalitis is around
10-15%. (29)
A particularity of this case was the systemic infection with
K.pneumoniae and CNS involvement presenting as rhombencepahalitis in an
immunocompetent patient, without known comorbidities or risk factors
that could affect immunocompetence.
Another particularity of the case was the difficulty to establish the
primary source of K.pneumoniae systemic infection, which remained
unknown.
Conclusion
This case shows an unusual and severe CNS complication of a systemic
infection with K. pneumoniae - rhombencephalitis, which, to our
knowledge, has not been reported before.
It illustrates the difficulty of identifying the original site of
infection in the presence of several infected sites and bacteriemia.
It also shows the devastating course that community-acquired K.
Pneumoniae infection can have in an apparently immunocompetent patient,
without significant comorbidities.
Author contribution
Delia Maria Stanca: Consultant neurologist in charge of the patient.
Given approval of the final version of the paper.
Daniela Larisa Bala: Resident doctor, conception and design of the case
report.
Mihaela Ruscă: Resident doctor, drafting the work and revising it for
important intellectual content.
Andra Achim: Resident doctor, comparing the case report to the current
literature.
Dafin Fior Mureșanu: Coordinator of the team.
Acknowledgments
Many thanks to Ioana Robu, Iuliu Hațieganu University of Medicine and
Farmacy of Cluj, Romania, for the help in editing this manuscript.
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Figure 1: MRI axial fluid-attenuated inversion recovery (FLAIR) sequence
(A, B) and diffusion weighted image (DWI) sequence (C, D) showing
bilateral, asymmetric, hyperintensity in the cerebellum with extension
into the brainstem (A, C).