An Introduction to childhood Kingella Kingae infections

An Introduction to
childhood Kingella
Kingae infections
Prof. Dr. Saad S Al Ani
Prof. of Pediatrics
Senior Pediatric consultant
Saad’s Kids Clinic
anahbaghdad@gmail.com

Introduction
Kingella kingae: A type of bacteria
that has emerged from obscurity to
become known as an important cause
of invasive infections in young
children
25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani
2

Kingella kingae
•Fastidious
•Facultative anaerobic
•β-hemolytic
•Appears as pairs or short chains of
gram-negative coccobacilli with
tapered ends
•Member of the Neisseriaceae family
3
https://www.researchgate.net/publication/233671839_Kingella_kingae_A_Pediatric_Pathogen_of_Increasing_Importance

K. kingae is a recognized
commensal in the oropharynx of
young children particularly in
ages 6 to 48 months
4
El Houmami N, Minodier P, Dubourg G, et al. An outbreak
of Kingella kingae infections associated with hand, foot and mouth
disease/herpangina virus outbreak in Marseille, France,
2013. Pediatr Infect Dis J. 2015;34(3):246–250

The clinical presentation of disease
due to Kingella kingae is often
subtle so that making the diagnosis
requires a high index of suspicion.
5

Species of Kingella
There are four species of Kingella:
• K. kingae, the most common, is
part of the bacterial flora
• K. indologenes, K. denitrificans
both causing endocarditis
• K. oralis found in dental plaque
6
https://en.wikipedia.org/wiki/Kingella_kingae

Routine laboratory tests may be normal
because the organism is difficult to
culture
7
https://en.wikipedia.org/wiki/Kingella_kingae

Epidemiology
• Asymptomatically carried in the
posterior pharynx
• Colonization:
Usually starts after age 6 months
Reaches a prevalence of 10%
between 12 and 24 months
Decreases in older children
8

Proposed pathogenesis of K. kingae infections
9
https://go.gale.com

Associated infections
K. kingae invasive infections have
been associated with:
• Hand-foot-mouth disease
• Herpes simplex virus causing
stomatitis
• Varicella zoster virus
• Human rhinovirus
10
El Houmami N, Mirand A, Dubourg G, et al. Hand, foot and mouth disease and
Kingella kingae infections. Pediatr Infect Dis J. 2015;34(5):547–548

Prerequisite for invasive disease
which is commonly triggered by
viral infections
11
El Houmami N, Minodier P, Dubourg G, et al. An outbreak
of Kingella kingae infections associated with hand, foot and mouth
disease/herpangina virus outbreak in Marseille, France,
2013. Pediatr Infect Dis J. 2015;34(3):246–250

Transmission
• By close contact between young
children
• A recent reported increase in :
Oropharyngeal carriage rates
Outbreaks of invasive disease
involving the skeletal system in
day-care centers
12

Epidemiology (Cont.)
Pharyngeal colonization plays a
crucial role in the transmission of
the organism through intimate
contact between siblings and
playmates
13

• Daycare attendance increases the risk
for colonization and transmission
• Clusters of invasive infection have
been reported in childcare facilities
14

Invasive K. kingae disease is most
frequently diagnosed in otherwise
healthy children between ages 6
months and 3 yr,
15

Pathogenesis
K. kingae
by pili &
nonpilus adhesin
adherence of the organism to the
pharyngeal epithelium
16

Pathogenesis (Cont.)
17
Gram-stain of a positive blood-culture vial from a child with K kingae bacteremia, which shows typical pairs and
short chains of Gram-negative coccobacilli (gray arrows). RBCs indicates red blood cells.
https://pediatrics.aappublications.org

Pathogenesis (Cont.)
K. kingae secretes a potent
Repeats-in-Toxin (RTX) toxin
that exhibits deleterious activity to:
– Respiratory epithelial cells
– Macrophages
– Synoviocytes
18

Play a role in:
– Disrupting the respiratory
mucosa
– Promoting survival of the
bacterium in the bloodstream
– Facilitating invasion of skeletal
system tissues
19

20
ResearchGate

The frequent presentation of
K. kingae disease
21
Upper respiratory
infection
Herpetic stomatitis
Hand-foot-and-
mouth disease
Buccal aphthous ulcer
suggesting that viral-induced damage to the
colonized mucosal surface facilitates invasion
of the bloodstream

Clinical presentation
• Septic arthritis is the most common
invasive K. kingae infection in
children
• followed by:
Bacteremia
Osteomyelitis
Endocarditis
22

Clinical presentation (Cont.)
K. Kingae is the most frequent etiology
of skeletal system infections in
children 6 months to 3 yr old in at
least some countries
23

• Invasive K. kingae infections is
frequently mild (With the exception
of patients with endocarditis)
-body temperature <38°C
- normal CRP Level
- normal WBC count
Are common
24

K. kingae infections requiring
a high index of clinical
suspicion
25

Septic Arthritis
• K. kingae –driven arthritis especially
affects the large, weight-bearing
joints
• involvement of:
-Small metacarpophalangeal
-Sternoclavicular
-Tarsal joints
Is not unusual
26

Septic Arthritis
27
My Health Alberta - Alberta.ca

Septic Arthritis ( Cont.)
• Is an acute presentation
• Involvement of the hip joint
resembles toxic synovitis
• should be always suspected in
children <4 yr old presenting with
hip pain or a limp
28

Synovial fluid :
• <50,000 WBCs/µL in almost 25%
of the patients,
• The Gram stain is positive in only a
small percentage of cases
29

30
Digital Commons @ Otterbein - Otterbein University

Osteomyelitis
K. kingae osteomyelitis usually
involves the long bones of the
extremities
31

Osteomyelitis (Cont.)
32
Journal of Clinical Microbiology - American Society for Microbiolo
Knee X-ray analyses
(anteroposterior [a] and lateral
views) demonstrate a round lytic
lesion (arrow) circled by a well-
defined sclerotic margin (dotted
arrow), located in the inferior
metaphysis of the femur,
adjacent to the physis (arrow).
The lateral view also shows a
unilamellar inferoanterior
periosteal reaction (arrowhead).

The calcaneus, talus, sternum,
and clavicle are also frequently
affected
(They are rarely infected by other
bacterial pathogens)
33

• Insidious
• Diagnosed after ≥1 week in
70% of patients.
34

• MRI shows mild bone and soft
tissue changes
• Involvement of the epiphyseal
cartilage appears to be
specifically associated with K.
kingae
35

MRI of acute osteomyelitis
in long bones of children
36
https://www.sciencedirect.com/science/article/pii/S1877056816300998

Chronic osteomyelitis and
functional orthopedic disabilities
are unusual
37

Spondylodiscitis
K. kingae is the 2nd most common
bacterium isolated in children <4
yr old with spondylodiscitis
38

Spondylodiscitis (Cont.)
• Usually Involves the lumbar
intervertebral spaces
• Less frequency:
- thoracolumbar
- thoracic
- lumbosacral
-cervical disks
39
https://www.spineuniverse.com/anatomy/lumbar-spine

presentation
Limping Refusal to sit or walk
Lumbar pain Neurologic symptoms
Back stiffness Abdominal complaints
40

MRI studies
demonstrate
narrowing of the
intervertebral
space
41
https://www.researchgate.net/publication/6731419_Kingella_kingae_spondylodiscitis_in_a_child

• Respond well to appropriate
antibiotic treatment
• recover without complications
42

Occult Bacteremia
Usually : mild to moderate fever,
symptoms suggestive of a viral
upper respiratory infection
43

Occult Bacteremia (Cont.)
-Mean CRP level of 2.2 mg/dL
-Mean WBC count of 12,700/µL.
•Children with K. kingae
bacteremia respond favorably to
a short course of antibiotics
44

Endocarditis
•The disease may affect native
as well as prosthetic valves
•Typically, the left side of the
heart is involved, usually the
mitral valve
45

Endocarditis(Cont.)
•Predisposing factors include :
-cardiac malformations or
-rheumatic valvular disease
•Some patients have previously
normal hearts
46

Endocarditis(Cont.)
Fever and acute-phase reactants
are elevated more in patients with
endocarditis than in those with
uncomplicated bacteremia
47

Echo of an infant with
K. kingae endocarditis
48
Yackov Berkun,et al.Kingella
kingae endocarditis and sepsis in
an infan. European Journal of
Pediatrics volume 163, pages687–
688(2004)

Because of the potential
severity of K. kingae
endocarditis, routine
echocardiographic
evaluation of children
with isolated bacteremia
is indicated
49

Despite the exquisite
susceptibility of K. kingae
to antibiotics,
complications are common
50

Endocarditis: Complications
Cardiac failure
Septic shock
Cerebrovascular accident (stroke)
Other life-threatening
complications
are common
• Mortality rate is high ( >10% )
51

Diagnosis
• Isolation of the bacterium
• Positive nucleic acid amplification
test (NAAT); polymerase chain
reaction PCR)
from a normally sterile site such as
blood, synovial fluid, or bone tissue
52

Diagnosis (Cont.)
K. kingae grows on routine
bacteriologic media BUT its
recovery from exudates is
frequently unsuccessful
53
https://alchetron.com/Kingella-kingae

Diagnosis (Cont.)
Testing bone and joint specimens
by NAAT that targets specific K.
kingae genes results in a 4-fold
improvement in the detection of
the organism
54

Treatment
K. kingae is usually highly susceptible
to penicillin and cephalosporins but
exhibits decreased susceptibility to
oxacillin
55

Treatment (Cont.)
First-line therapy for skeletal
infections in young children :
IV 2nd or 3rd generation
cephalosporin , pending culture
results
56

First-line therapy (Cont.)
For skeletal infections in young
children :
IV 2nd or 3rd generation
cephalosporin , pending culture
results
57

Resistant of K. kingae
To
• Glycopeptide antibiotics (always)
• Clindamycin (majority )
58

Skeletal infections caused by
community-associated methicillin-
resistant S. aureus are common, So
vancomycin or clindamycin are
initially administered
59

Guide switching to oral
antibiotics
1. Favorable clinical response
2. Decreasing CRP levels to
≤20 µg/mL
60

Antibiotic Treatment
duration
Antibiotic treatment for K. kingae
has ranged from:
2-3 wks for arthritis
3-6 wks for osteomyelitis
3-12 wks for spondylodiscitis
61

Most patients respond promptly to
conservative treatment with
appropriate antibiotics and do not
require invasive surgical procedures
62

Antibiotic Treatment K.
kingae
63

Bacteremia without
focal infection
• Initially :an IV β-lactam antibiotic
• Subsequently: an oral drug once the
clinical condition has improved.
• In most cases:
duration of therapy is 1-2 wks
64

Endocarditis
Usually treated with an IV β-
lactam antibiotic alone or in
combination with an
aminoglycoside for 4-7 wks
65

Endocarditis (Cont.)
Early surgical intervention is
necessary for life-threatening
complications unresponsive to
medical therapy
66

Prevention
The risk of asymptomatic
pharyngeal carriers for
developing an invasive K.
kingae infection is low
67

Prevention (Cont.)
If cases occur , SO prophylactic
antibiotic therapy to eradicate
colonization in contacts and
prevent further cases of disease
is indicated .
68

Prophylactic antibiotic
therapy
Either rifampin alone, 10 mg/kg or
20 mg/kg twice daily for 2 days,
Or
rifampin with amoxicillin (80
mg/kg/day) for 2 days or 4 days
69

70
123FreeVectors

References
• https://www.researchgate.net/publication/233671839_Kingella_kingae_A_Pediatric_Pathogen_of_Increasing_Impo
rtance
• El Houmami N, Minodier P, Dubourg G, et al. An outbreak of Kingella kingae infections associated with hand, foot
and mouth disease/herpangina virus outbreak in Marseille, France, 2013. Pediatr Infect Dis J. 2015;34(3):246–250
• https://en.wikipedia.org/wiki/Kingella_kingae
• https://go.gale.com
• El Houmami N, Mirand A, Dubourg G, et al. Hand, foot and mouth disease and Kingella kingae infections. Pediatr
Infect Dis J. 2015;34(5):547–548
• https://pediatrics.aappublications.org
• https://www.sciencedirect.com/science/article/pii/S1877056816300998
• https://www.spineuniverse.com/anatomy/lumbar-spine
• https://www.researchgate.net/publication/6731419_Kingella_kingae_spondylodiscitis_in_a_child
• Yackov Berkun,et al.Kingella kingae endocarditis and sepsis in an infan. European Journal of
Pediatrics volume 163, pages687–688(2004)
• Yagupsky P, Dubnov-Raz G, Gené A, Ephros M, Israeli-Spanish Kingella kingae Research Group. Differentiating
Kingella kingae septic arthritis of the hip from transient synovitis in young children. J Pediatr . 2014;165:985–989.
• https://alchetron.com/Kingella-kingae
• Dubnov-Raz G, Ephros M, Garty BZ, et al. Invasive pediatric Kingella kingae infections: a nationwide collaborative
study. Pediatr Infect Dis J. 2010;29(7):639–643
• Yagupsky P. Kingella kingae: carriage, transmission, and disease. Clin Microbiol Rev. 2015;28(1):54–79
• http://drugline.org/medic/term/kingella-kingae
• https://www.researchgate.net/publication/233671839_Kingella_kingae_A_Pediatric_Pathogen_of_Increasing_Impo
rtance
71

An Introduction to childhood Kingella Kingae infections

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