Kingella Kingae An Emerging Pathogen in Young Pediatrics 2011

STATE-OF-THE-ART REVIEW ARTICLES
Kingella kingae: An Emerging Pathogen in Young

Children
AUTHORS: Pablo Yagupsky, MD,a Eric Porsch, MA,b and
Joseph W. St Geme, III, MDb
abstract
Kingella kingae is being recognized increasingly as a common etiology

of pediatric osteoarticular infections, bacteremia, and endocarditis,
which reects improved culture methods and use of nucleic acid
amplication techniques in clinical microbiology laboratories. K kingae colonizes the posterior pharynx of young children and is transmitted from child to child through close personal contact. Day care
attendance increases the risk for colonization and transmission, and
clusters of K kingae infections among day care center attendees have
been reported. Key virulence factors in K kingae include type IV pili and
a potent RTX toxin. In previously healthy children, 95% of K kingae
infections are diagnosed between the ages of 6 and 48 months. Among
children with underlying medical conditions, K kingae disease may
occur at older ages as well. The clinical presentation of K kingae disease is often subtle and may be associated with normal levels of acutephase reactants, which underscores the importance of a high index of
suspicion. K kingae is usually susceptible to -lactam antibiotics, and
infections typically respond well to medical treatment, with the exception of cases of endocarditis. Pediatrics 2011;127:557565
Clinical Microbiology, Soroka University Medical Center,

Ben-Gurion University of the Negev, Beer-Sheva, Israel; and
bDepartments of Pediatrics and Molecular Genetics and
Microbiology, Duke University Medical Center, Childrens Health
Center, Durham, North Carolina
KEY WORDS
Kingella kingae, children, pathogenesis, carriage, invasive
disease, daycare centers
ABBREVIATIONS
PCRpolymerase chain reaction
DCCday care center
www.pediatrics.org/cgi/doi/10.1542/peds.2010-1867
doi:10.1542/peds.2010-1867
Accepted for publication Nov 17, 2010
Address correspondence to Pablo Yagupsky, MD, Clinical
Microbiology Laboratory, Soroka University Medical Center,
Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel.
E-mail: yagupsky@bgu.ac.il
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2011 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no nancial relationships relevant to this article to disclose.
PEDIATRICS Volume 127, Number 3, March 2011
Downloaded from pediatrics.aappublications.org at Health Internetwork on June 10, 2015
557
Over the past 2 decades there has been

a growing interest in the role of Kingella kingae as an invasive pediatric
pathogen. Increasing use of improved
culture methods1 4 and polymerasechain-reaction (PCR)-based assays57
has demonstrated that K kingae is a
common etiology of bacteremia and
osteoarticular infections in children
younger than 4 years.8,9 In this review
we summarize current knowledge of
the microbiology, epidemiology, transmission, pathogenesis, clinical presentation, diagnosis, and treatment of K
kingae infections in children.
MICROBIOLOGY
K kingae is a facultative anaerobic,
-hemolytic, Gram-negative organism
that appears as pairs or short chains
of plump bacilli with tapered ends (Fig
1) and that tends to resist decolorization, which sometimes results in its
misidentication as Gram-positive.10
It is oxidase-positive, yields negative
catalase, urease, and indole reactions,
produces acid from glucose and maltose but not from other sugars,10,11 and
can be readily identied by commercial systems such as API NH or VITEK 2
(bioMrieux, Marcy-lEtoile, France).
K kingae grows on routine sheep blood
agar and chocolate agar, produces
RBCs
RBC
FIGURE 1
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.
558
YAGUPSKY et al
marked impressions on the agar surface, and fails to grow on MacConkey

or Krigler agar.10 A CO2-enriched atmosphere enhances growth, but only a
small fraction of strains are truly
capnophilic.11
CARRIAGE AND TRANSMISSION OF

K kingae
Asymptomatic colonization of the upper respiratory tract is a common
strategy among a number of bacterial
pathogens that survive and spread in
the human population; examples include Streptococcus pneumoniae and
Neisseria meningitidis. Results of
recent studies using a selective
vancomycin-containing medium to inhibit growth of resident Gram-positive
bacteria have shown that K kingae is a
member of the normal commensal
ora of the posterior pharynx and is
almost never found in nasopharyngeal
cultures.1113 Children usually rst acquire K kingae after the age of 6
months. The colonization rate increases to 9% to 12% between the ages
of 12 to 24 months and then gradually
declines in older children and adults,
which suggests an age-related immune response that eradicates the organism from the pharynx in older
people.12,14
To investigate the dissemination of K
kingae in the community and the potential clinical signicance of upper respiratory tract colonization, the relatedness of pharyngeal isolates from a
large cohort of young healthy carriers
was studied by pulsed-eld gel electrophoresis and compared with historical
isolates recovered over a 15-year period.13 Geographic clustering of isolates
that exhibited indistinguishable genotyping proles was found in households and neighborhoods, which indicates child-to-child spread of K kingae
between siblings and playmates. Some
isolates were identical to K kingae
strains recovered in the past from car-
riers and patients with invasive disease, which demonstrates long-term

persistence and potential virulence of
some of the colonizing strains.13
It is interesting to note that a recent
report described 3 patients with invasive K kingae infections who had genotypically identical isolates recovered
from the pharynx and the bloodstream, which supports the idea that
upper respiratory colonization represents the rst step in the pathogenesis
of invasive disease.15
EPIDEMIOLOGY OF INVASIVE
K kingae DISEASE
K kingae disease is diagnosed most
commonly in young children (Fig 2). In
a recent Israeli multicenter study, 296
of 312 (95%) children with invasive K
kingae disease in whom the patients
age was known were younger than 4
years (calculated annual incidence: 9.4
in 100 000 in children aged 0 4 years).
Only 4 (1%) patients were younger
than 6 months.16 The male-to-female
ratio among cases was 1.3.16 Among
321 patients, 169 (53%) had osteoarticular infections, including 140 cases
of septic arthritis, 19 cases of osteomyelitis, 7 cases of osteomyelitis and
arthritis of the adjacent joint, and 3
cases of tenosynovitis.16 Among the remaining patients, 140 were diagnosed
with bacteremia without a focus, 4 had
bacteremia associated with a lower
respiratory tract infection, and 8 had
endocarditis. Meningitis,17 ocular infections,18 peritonitis,19 and pericarditis20 are rare manifestations of K kingae disease that have been described
in other reports but were absent from
this series.
Children younger than 4 years who develop K kingae disease are generally
otherwise healthy.4,11,16 In contrast,
older children and adults with K kingae
disease often have underlying chronic
disease, immunosuppressing condi-
50
50
children with disease and from asymptomatic carriers attending the same
classrooms were genotypically identical, which indicates that infections
were caused by virulent strains that
had spread extensively within the facilities. Isolates of K kingae from control
DCCs had distinct genotypic patterns,
which indicates that each DCC facility
may be considered an autonomous epidemiologic unit.22,23
40
36
30
22
20
10
10
3
3035
mo
3641
mo
05
mo
611
mo
1217
mo
1823
mo
2429
mo
IMMUNITY TO K kingae
1
4247
mo
1
66 mo
1
21
y
Age
FIGURE 2
Age distribution of 128 patients with invasive K kingae infections diagnosed in southern Israel in
19872010. The 2 oldest patients (aged 66 months and 21 years) presented with endocarditis and had
predisposing factors (Williams syndrome with supravalvular aortic stenosis and systemic lupus
erythematosus, respectively).
tions, malignancy, or cardiac valve

pathology.4,11,16
In Israel, invasive K kingae disease occurs throughout the year; it is most
common during November and December and least common between February and April.4,11,16 In a large prospective study in which pharyngeal
carriage of K kingae was determined
in February through May and October
through December, the prevalence
was comparable for the 2 periods,
which suggests that the seasonal distribution of invasive K kingae disease
cannot be readily explained by the epidemiology of pharyngeal carriage.14
DAY CARE CENTER ATTENDANCE

AND K kingae MORBIDITY
The results of several studies have indicated that day care center (DCC) attendance is associated with an increased risk of K kingae colonization
and transmission. In a longitudinal
surveillance study performed over an
11-month period, 35 of 48 (73%) children who were attending a DCC had at
least 1 pharyngeal culture test positive
for K kingae, and an average of 28% of
the children harbored K kingae in the

pharynx at any given time.12 Molecular
typing of isolates by using immunoblotting, ribotyping, and pulsed-eld
gel electrophoresis revealed genotypic similarities and person-toperson transmission among DCC attendees.21 One strain accounted for
46% of all isolates, and a second strain
accounted for another 28% of the isolates, which suggests that some
strains are particularly efcient mucosal colonizers.22 The same strain was
often present continuously or intermittently for weeks or months in a given
child and was then replaced by a new
strain, which indicates that carriage is
a dynamic process with relatively frequent turnover of colonizing organisms, similar to observations made
with other respiratory pathogens.21
Recently, clusters of invasive K kingae
disease were detected in DCCs in the
United States and Israel.2224 Affected
children presented with osteomyelitis,
septic arthritis, endocarditis, or spondylodiscitis. Investigation of these outbreaks revealed that isolates from
In a longitudinal study, titers of immunoglobulin G (IgG) antibodies against

K kingae outer-membrane proteins
were high at 2 months of age, reached
a nadir at the age of 6 to 7 months,
remained low until the age of 18
months, and increased at the age of 24
months.25 Serum IgA levels against
K kingae outer-membrane proteins
were lowest at 2 months of age and
slowly increased during the period between 4 and 7 months of age. Further
increases in IgG and IgA antibodies
were observed in children older than
24 months.25 The low attack rate of disease, absence of pharyngeal carriage,
and high levels of IgG but no IgA antibodies detected in the rst 6 months of
life suggest that immunity to colonization and disease in early infancy is
probably conferred by maternal antibodies. The high prevalence of K kingae in the pharynx and the high incidence of invasive infections among
6- to 24-month old children coincide
with the age at which antibody levels
are lowest. Increasing antibody levels
among older children presumably reect cumulative experience with K kingae or with cross-reacting antigens of
other organisms, which results in a decline in the carriage rate and burden
of clinical disease.25 Because of the relative rarity of invasive disease, asymptomatic pharyngeal colonization is
likely to be an immunizing event. However, exposed epitopes are polymorphic, and the immune response elic-
559
ited by carriage seems to be

incomplete and strain-specic and
does not prevent colonization by an antigenically different strain.26
PATHOGENESIS OF DISEASE
The pathogenesis of disease caused by
K kingae is believed to begin with colonization of the posterior pharynx. The
process of colonization likely involves
adherence to respiratory epithelial
cells, which is mediated in vitro at
least in part by type IV pili that are composed primarily of a major pilin subunit called PilA1.27,28 The PilA1 protein
shares homology with the major pilin
subunit in type IV pili expressed by
other bacterial pathogens, including
Pseudomonas aeruginosa PilA, N meningitidis PilE, and Neisseria gonorrhoeae PilE. In addition, K kingae pili
contain 2 minor pilus-associated proteins referred to as PilC1 and PilC2,
which seem to play complementary
roles and inuence the efciency of adherence to respiratory epithelial cells.
Examination of a series of clinical isolates of K kingae revealed that the majority of pharyngeal isolates are piliated and express abundant pili.27
After colonization of the posterior
pharynx, K kingae must breach the epithelium to enter the bloodstream. Patients with invasive K kingae disease
frequently present with symptoms of a
viral respiratory infection, evidence of
herpetic gingivostomatitis, or concomitant buccal aphthous ulcers, which
suggests that viral-induced damage to
the respiratory mucosa facilitates
K kingae invasion of the bloodstream.8,11,29 Beyond the role of viral
coinfection, K kingae produces a potent extracellular toxin that belongs to
the RTX family of toxins and is capable
of lysing epithelial, synovial, and macrophage cells.30 This toxin may facilitate disruption of the respiratory epithelium, perhaps with an enhanced
effect in the setting of viral coinfection.
560
YAGUPSKY et al
Once in the bloodstream, K kingae

must be able to evade a variety of host
defense mechanisms. Most bacterial
pathogens that produce bacteremic
disease in children produce an extracellular polysaccharide capsule that
facilitates resistance to serum-killing
activity and opsonophagocytosis. Examples include S pneumoniae, N meningitidis, Haemophilus inuenzae type
b, Streptococcus agalactiae, and Escherichia coli. Analysis of the genome of
K kingae strain 269-492 reveals open
reading frames with homology to the
ctrABCD operon involved in polysaccharide export and encapsulation in
N meningitidis (unpublished data),
which raises the possibility that K kingae elaborates a polysaccharide capsule as a mechanism to promote intravascular survival and dissemination to
distant sites.
In patients in whom K kingae is able to
persist in the bloodstream, the organism may produce uncomplicated bacteremia or instead disseminate to
joints, bones, or the endocardium. Recent analysis of a large collection of K
kingae clinical isolates revealed that
strains recovered from the blood of
patients with uncomplicated bacteremia were generally piliated but typically expressed relatively few pili. In
contrast, strains recovered from joint
uid, bone aspirates, or the blood of
patients with endocarditis were generally nonpiliated.27 It is possible that
low-density piliation facilitates a tropism for joints, bones, and the endocardium and potentiates an inammatory response, which then selects
against piliated organisms.27 Consistent with this possibility, pili promote
efcient adherence to cultured synovial cells.28 Similar to type IV pili expressed by other pathogens, K kingae
pili are regulated by a transcription factor called 54 and by a
2-component sensor/regulator system
referred to as PilS/PilR.31 Mutations in
the PilS sensor result in reduced density of pili, similar to the relative decrease in density of pili in isolates
recovered from the bloodstream compared with the posterior pharynx.31 In
contrast, mutations in the PilR response regulator result in elimination
of piliation, similar to the absence of
pili in isolates from joints and bones.31
At this point, it is unclear what environmental factors inuence 54, PilS, and
PilR activity and control the density of K
kingae piliation.
CLINICAL PRESENTATION OF
K kingae INFECTIONS
Most patients with invasive K kingae
disease have moderate fever, but
some are afebrile.4,11,16 Constitutional
symptoms are typically lacking except
in patients with endocarditis.4,11,16
Peripheral white blood cell count,
C-reactive protein level, and erythrocytesedimentation rate are generally
mildly to moderately elevated but may
be normal.4,11,16
Skeletal System Infections
K kingae septic arthritis generally involves large joints such as the knee,
hip, ankle, or shoulder.11,16 In addition,
the small metacarpophalangeal, sternoclavicular, and tarsal joints are
overrepresented in K kingae disease
compared with septic arthritis because of other pathogens.11,16,32 In a recent study by Dubnov-Raz et al,16 the
mean white blood cell count in synovial
uid in patients with K kingae septic
arthritis was 130 000/L (range:
5000 to 300 000/L), and the
differential contained 90% to 96%
neutrophils.
Although K kingae osteomyelitis usually affects the long bones, involvement of the calcaneus, talus, sternum,
or clavicle may occur.11,16 Patients with
K kingae osteomyelitis have a signicantly more prolonged duration of
symptoms before admission com-
pared with children with septic arthritis (9.2 9.4 vs 3.2 3.0 days, respectively).16 Despite the diagnostic delay,
chronic osteomyelitis and orthopedic
sequelae seem to be uncommon.11,33,34
Nowadays, K kingae is responsible for
more than one-quarter of all cases
of hematogenous spondylodiscitis in
children younger than 4 years.3538 This
disease usually involves the lumbar
discs, and patients present with limping, low-back pain, refusal to sit or
walk, or neurologic symptoms. Radiograph or MRI studies reveal narrowing
of the intervertebral space. Patients
with K kingae spondylodiscitis respond well to appropriate antibiotic
treatment and recover without longterm complications.36,37
Although bone and joint infections are
not considered self-limited diseases,
transient involvement of the skeletal
system during an episode of K kingae
bacteremia may occur.32,39,40 Children
in this circumstance present with
limping or refusal to walk or bear
weight but without objective signs of
osteomyelitis or septic arthritis. In the
few published cases, by the time blood
cultures became positive, the fever
and skeletal complaints had resolved
without antimicrobial therapy, which
suggests an abortive clinical course.
Despite the favorable experience of
withholding therapy for some children
with possible skeletal system involvement from whom K kingae is isolated,
caution is recommended, and adequate antibiotics should probably be
administered to all patients from
whom the organism is recovered from
a normally sterile body uid.
Bacteremia
K kingae bacteremia without evidence
of endocarditis has been observed primarily in children.4,8,11,16,41,42 The duration of symptoms before diagnosis
ranges from 1 to 7 days, and the mean
maximal fever is 39.0C.4 In the study
by Dubnov-Raz et al,4 laboratory values

in children with K kingae bacteremia
included a mean peripheral blood leukocyte count of 12 700/L (range:
7120 47 040/L), a mean C-reactive
protein level of 2.2 mg/dL (range: 0.6
13.4 mg/dL), and a mean erythrocytesedimentation rate of 50 mm/hour
(range: 14 115 mm/hour). Patients
with K kingae bacteremia without
endocarditis respond favorably to a
short course of antibiotics.8,11
has been recommended by some

authors.47
Endocarditis
DIAGNOSIS
K kingae is included in the HACEK

(Haemophilus species, Actinobacillus
actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens,
and Kingella species) group of organisms that is collectively responsible
for up to 5% of cases of bacterial endocarditis. In contrast to other K kingae
infections, endocarditis has been diagnosed primarily in older children and
adults.11 In approximately one-half of
patients the infection affects a native
valve. A predisposing cardiac malformation or rheumatic heart disease is
commonly observed, but some patients have previously normal heart
valves.11,24,43 46 Typically, the left side of
the heart is involved, usually the mitral
valve. In general, fever and acutephase reactants are more elevated in
patients with endocarditis compared
with those with uncomplicated bacteremia; however, no particular cutoff
value accurately distinguishes between the 2 conditions.16 Despite the
remarkable susceptibility of K kingae
to antibiotics, cardiac failure, septic
shock, mycotic aneurisms, pulmonary
infarctions, meningitis, cerebrovascular accidents, and other lifethreatening complications are common, and the overall mortality rate is
16%.11,24,43 45 Because of the potential
severity of K kingae endocarditis, routine echocardiographic evaluation of
all people from whom the organism is
isolated from a normally sterile site
Lower Respiratory Tract Infections

K kingae has been isolated from the
blood or pleural uid of previously
healthy and immunocompromised
adult and pediatric patients with
epiglottitis, laryngotracheobronchitis,
pneumonia, or pyothorax,11 which suggests that the organism may cause
lower respiratory tract infections.
Culture Detection of K kingae

The recovery of K kingae from purulent
specimens seeded onto solid culture
media is suboptimal and results in a
lack of growth in many instances.1,11
The yield of cultures can be signicantly improved by inoculating clinical
specimens into aerobic blood-culture
vials from a variety of automated
blood-culture systems such as BACTEC
(Becton Dickinson, Cockeysville, MD),
BacT/Alert (Organon Teknika Corporation, Durham, NC), and Hemoline DUO
(bioMrieux, Paris, France).11 When
positive blood-culture vials are subcultured onto routine solid media, K kingae grows readily, which suggests
that exudates exert an inhibitory effect
on the bacterium and that dilution of
purulent material in a large volume of
broth may decrease the concentration
of inhibitory factors, which improves
the recovery of this fastidious organism.1 In studies conducted in Israel and
France in which blood-culture vials
were consistently used for culturing
synovial uid aspirates, K kingae was
isolated in almost half of the young
children with culture-proven septic arthritis, which indicates that this
method should be routinely used to improve the bacteriologic diagnosis.3,9
PCR Detection of K kingae
Because of the risk for long-term orthopedic sequelae after bone and joint
561
TABLE 1 Performance of Culture and PCR-Based Methods for Detecting K kingae in Children With Skeletal System Infections
Reference (Year)
Culture
Method
Positive K kingae
Culture, n/N (%)
PCR
Method
Conventional PCR Primers
RT-PCR Primers
Positive PCR/
Total, n/N (%)
Sthelin et al52 (1998)

Moumile et al53 (2003)
Verdier et al5 (2005)
Rosey et al54 (2007)
Chometon et al6 (2007)
Luegmair et al55 (2008)
Fuursted et al35 (2008)
Ilharreborde et al7 (2009)
Cherkaoui et al51 (2009)
Ceroni et al50 (2010)
Total
C
BCV SM
BCV SM
BCV SM
BCV SM
BCV
C
BCV SM
SM
SM
0/1
13/18
9/24
6/21
17/39
2/4
0/1
7/31
0/2
0/23
54/164 (32.9)
C
C
C
C RT
C RT
C RT
C
RT
C RT
RT
Universal
27F 1492R
91E 13BS
27F 244
91E 13BS
91E 13BS
Universal
BAK11w BAK2 BAK533r
1/1
18/18
24/24
20/21
39/39
4/4
1/1
31/31
2/2
23/23
163/164 (99.4)
27F 244
Ki K2 (cpn60 gene)
Ki K2 (cpn60 gene)
Kingprobe (cpn60 gene)

rtxA rtxB25
rtxA rtxB25
C indicates conventional PCR; BCV, blood-culture vial; SM, solid media; RT, real-time.
infections, prompt bacteriologic conrmation of the diagnosis and early

initiation of appropriate antimicrobial
therapy are critical. However, results
of cultures of bone aspirates and synovial uid are often negative. Furthermore, even if a bacterium is isolated,
complete identication and antibiotic
susceptibility testing require 2 to 3 additional days.48
In recent years, the use of conventional
and real-time PCR has enabled identication of the etiology of septic arthritis
and osteomyelitis within 24 hours.32,48
This approach involves extracting DNA
from clinical samples, incubation of
the DNA with broad-range oligonucleotide primers that anneal to constant
regions of the 16S ribosomal RNA gene,
and amplication of the intervening sequence, which varies according to bacterial species.48 The resulting amplication products are either
sequenced and compared with sequences in the GenBank database or
hybridized with organism-specic
probes. In addition, PCR assays that
amplify K kingaespecic targets
such as cpn60 or the RTX toxin genes
were developed and have been associated with high reliability.6,7,4951
Studies published over the previous
decade have shown that PCR enhances detection of K kingae in bone
and joint samples compared with
routine cultures and blood-culture
562
YAGUPSKY et al
vials, as summarized in Table 1.

These studies clearly showed that recovery of K kingae by culture remains unsatisfactory, even when
samples are inoculated into bloodculture vials. PCR-based assays substantially improve detection of the
organism, which shows that K kingae
is the leading etiology of septic arthritis and osteomyelitis in children
aged 6 to 48 months and is responsible for a large fraction of culturenegative infections in this age
group.
Treatment of Invasive Infections
Antibiotic Susceptibility
Because of the lack of specic guidelines for the treatment of K kingae infections, patients have been treated
with a variety of antibiotics according
to protocols developed for infections
caused by traditional pathogens. Because of the benign course followed by
most invasive K kingae infections, it is
possible that short antibiotic courses
are adequate for patients with bacteremia or osteoarthritis. However, at
this stage, the lack of controlled studies precludes formulation of evidencebased recommendations on the preferable antibiotic and the optimal
length of therapy for K kingae disease.
K kingae is almost always highly susceptible to penicillins and cephalosporins, although -lactamase production has been reported in rare
isolates.5658 With few exceptions, K
kingae is also susceptible to aminoglycosides, macrolides, trimethoprimsulfamethoxazole, tetracyclines, chloramphenicol, and uoroquinolones. The
organism exhibits decreased susceptibility to oxacillin (minimum inhibitory
concentration range: 0.2596 g/mL;
minimum inhibitory concentration required to inhibit the growth of 50% of
organisms: 2 g/mL) and is fully resistant to trimethoprim and glycopeptide
antibiotics.11,58 Nearly 40% of isolates
are resistant to clindamycin.58
The empirical drug therapy for skeletal infections in children usually consists of intravenous administration
of oxacillin/nafcillin or a secondor third-generation cephalosporin
while pending culture results.11 In areas in which community-associated
methicillin-resistant Staphylococcus
aureus is prevalent, a combination of a
-lactam antibiotic and vancomycin is
recommended.59 The initial antibiotic
regimen is frequently changed to ampicillin or cefuroxime once K kingae is
identied and -lactamase production
is excluded. Clinical response and a variety of acute-phase reactants are
used to guide switching to oral antibiotics and dening duration of therapy.
TREATMENT
Antibiotic treatment has generally varied from 2 to 3 weeks for K kingae arthritis, from 3 to 6 weeks for K kingae
osteomyelitis, and from 3 to 12 weeks
for K kingae spondylodiscitis.11 Although some children with septic arthritis have been managed with repeat
joint aspirations and lavage,40 most patients with skeletal system involvement respond promptly to conservative treatment with appropriate
antibiotics and do not require invasive
surgical procedures.11
Children with K kingae bacteremia are
generally treated initially with an intravenous -lactam antibiotic and are
subsequently switched to an oral
-lactam once the clinical condition
has improved. In most cases, the total
duration of therapy ranges from 1 to 2
weeks.8,11
Patients with K kingae endocarditis
are usually treated with an intravenous -lactam antibiotic alone or in
combination with an aminoglycoside
for 4 to 7 weeks. Early surgical
intervention is necessary for lifethreatening complications that are unresponsive to medical therapy.11,43 46
Eradication of Carriage
In the 3 reported outbreaks of K kingae
disease among DCC attendees, antibiotics were administered to contacts in an attempt to prevent further cases; either rifampin 20 mg/kg
twice daily for 2 days23 or a combination of rifampin 20 mg/kg twice daily

for 2 days and amoxicillin 80 mg/kg
per day for either 2 days24 or 4 days22
was used. K kingae was eradicated
from the pharynx in 67% to 80% of
colonized children in 2 of the outbreaks.22,23 In the third outbreak, the
pretreatment colonization rate was
low, which precluded assessment of
the chemoprophylaxis effect.24 Although experience has been limited,
it seems prudent to consider administration of short antibiotic courses
to contacts aged 6 to 48 months
when clusters of disease are detected in DCC settings.
FUTURE DIRECTIONS
For most of the 4 decades since the
rst description of K kingae, the organism was considered a rare cause of
human disease. However, since the
early 1990s there have been an increasing number of reports of K kingae disease, which indicates that this
pathogen is a common cause of bacteremia, septic arthritis, and osteomyelitis in young children. Most of the existing case series are derived from
European and Israeli sources, and
there have been limited reports from
the United States. When considering
this discrepancy, it is notable that detection of this fastidious organism
strongly depends on the microbiologic
methodology used. In Israel and
France, the blood-culture vial method

has been widely adopted for culturing
joint aspirates,3,16 whereas this practice seems to be less common in the
United States. A surveillance conducted in 20012002 by the Infectious
Diseases Society of America Emerging
Infections Network identied lack of
consultation with a pediatric infectious diseases specialist and unwillingness of bacteriology laboratories to
process blood-culture vials seeded
with synovial uid as barriers to the
use of this approach.60 In addition, because only half of the children with K
kingae bacteremia have a body temperature of 39.0C, and one-third
have a leukocyte count of 15 000
white blood cells per mL, the current
US guidelines for managing young febrile children with no apparent focus,
which rely on the height of fever and
white blood cell count for obtaining
blood cultures, may not be sufciently
sensitive to detect this condition in
children.16,61 Furthermore, specic PCR
assays have revolutionized the diagnosis of K kingae in recent years but are
not in broad use in US hospitals, which
hampers detection of the organism. Increasing use of novel microbiologic
methods and familiarity of clinical microbiology laboratories with the identication of K kingae will expand our
current knowledge of this intriguing
pediatric pathogen.
REFERENCES
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FLIGHT PATTERNS: Last week I spent a lot of time building a fairly complex ight
itinerary between Burlington, San Diego, Addis Ababa, Ethiopia and Kampala,
Uganda. Remarkably, over the space of 48 hours, the price uctuated by hundreds of dollars, and even over the course of a few minutes, some ights
became unavailable or cost a few dollars more. As reported in The Wall Street
Journal (January 27, 2011: Life & Culture), nding cheap airfare is all about
timing. Travel experts report that Tuesdays and Wednesdays are the best days
to buy tickets. Airline ticket discounts are typically announced on Monday
nights. Airlines in the same market may match prices on Tuesday. By the end of
the week, the promotion may have expired or all seats taken. Conversely, when
airlines want to raise ticket prices, they do so on Thursday evenings and wait to
see if their competitors match the price. If not, the fares can be rolled back the
following Monday. Computers track ticket sales and can add seats at a price
point if sales are slow or remove them if sales are brisk. Monitoring fare tends
to be more brisk on the weekdays. The airline and travel consolidators all report
far more tickets are sold midweek than on weekends. This pattern may be
remnant of the days when business travelers booked through travel agents who
tended to work Monday through Friday. With more and more people booking
directly online, and many Americans on social media outlets such as Twitter and
Facebook, some carriers are breaking the pattern and experimenting with
tweeting very short duration sales. According to the article, while purchase
dates clearly can impact the cost of a ticket, the departure date selected has
greater impact. Tuesday, Wednesday, and Saturday departures tend to be less
expensive than Monday, Friday, or Sunday ights. As for me, I was quite happy
that a non-stop ight from San Diego to Washington, DC suddenly became available and with my exible schedule, I could depart Kampala on a Tuesday saving
almost $400.
Noted by WVR, MD
565
Kingella kingae: An Emerging Pathogen in Young Children

Pablo Yagupsky, Eric Porsch and Joseph W. St Geme III
Pediatrics 2011;127;557; originally published online February 14, 2011;
DOI: 10.1542/peds.2010-1867
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2011 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Kingella kingae: An Emerging Pathogen in Young Children

Pablo Yagupsky, Eric Porsch and Joseph W. St Geme III
Pediatrics 2011;127;557; originally published online February 14, 2011;
DOI: 10.1542/peds.2010-1867
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/127/3/557.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2011 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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