HACEK Organisms

Susan S. Huang, M.D.

ID conference
March 2001
The Origin of HACEK
Isolation of fastidious gram-negative organisms have been noted for decades. In 1979, Ellner et al,
1
described a group of fastidious organisms which shared the features of slow growth, a preference for
carbon dioxide for solid medium culture, and a tendency to granular growth in broth. Originally, these
organisms were designated the HB group. Subsequently, HB-1 was later named Eikenella corrodens, HB-2
became Haemophilus aphrophilus, and both HB-3 and HB-4 were classified as Actinomyces
actinomycetemcomitans.
In 1982, Geraci and Wilson
2
reviewed the cases of endocarditis due to gram negative organisms seen at the
Mayo Clinic from 1958-79. They compared the outcomes between several groups of organisms including
one comprised of fastidious, antibiotic-sensitive, and usually capnophilic, coccobacillary organisms:
Haemophilus sp., A. actinomycetemcomitans, C. hominis, E. corrodens, and K. kingii (labeled the
HACEK group).
Haemophilus aphrophilus: 1940
Epidemiology
Haemophilus species are well known to be cultured from oral flora with a prevalence of 30-45%. A few
studies have evaluated H. aphrophilus in particular. Kraut et al.
3
cultured it from gingival scrapings and
interdental material of 16/45 (36%) healthy adult volunteers whose dental health was not determined.
Nevertheless, when isolated, it comprised <1% of the total aerobic flora. Of note, upon repeat sampling, 7
months later, an additional 7 subjects had positive cultures for H. aphrophilus. Brown
4
evaluated 4,247
respiratory specimens including oropharynx, nasopharynx, sputum, BAL, and pleural fluid. He found that
43% of specimens included one species of Haemophilus with H. aphrophilus being isolated in 1.5% of
samples. (Of note, E. corrodens 1.9%, A. actinomycetemcomitans 1.7%.)
Microbiology
5

6
H. aphrophilus is a small gram negative coccobacillus that grows best in enriched CO
2
environments. At
the time it was named, it was common knowledge that the gas bubbles, or froth (aphros), from wine
fermentation was due to carbon dioxide. Hence, it received the name Aphrophilus, meaning foam-
loving. Interestingly, it has been shown that H. aphrophilus will grow in moist atmospheres in the
absence of CO
2
, but that it grows best at 35 C, 5-10% CO
2
with moist air. It forms non-hemolytic smooth,
moist, dome-shaped, opaque colonies on chocolate and blood agar. In 24 hours, a slight greening of the
agar is often seen and in repeated subculture, some strains acquire the morphology of a long bacillus with a
bent axis.
There were several initial reports of strains of H. aphrophilus that did not require X factor. This
observation led some to advocate for its removal from the Haemophilus heme-loving grouping. In 1976,
Kilian definitively demonstrated X-factor independence, but, despite this, the species has remained in the
Haemophilus genus due to the preponderance of similar chemical characteristics.
Clinical Manifestations
In 1940, Khairat
7
first described H. aphrophilus as the causative agent in a fatal case of endocarditis.
Eighteen years later, a second case of H. aphrophilus was described by Toshach and Bain,
8
also a case of
fatal endocarditis. By the mid 80s, there were 132 reported cases: 55% endocarditis, 15% brain abscesses,
with the remainder comprised of sinusitis, meningitis, pneumonitis, bacteremia, and empyema.
To avoid publication bias and obtain a more accurate distribution of the infections caused by H.
aphrophilus, Bieger et al.
5
reviewed all isolates from the Mayo Clinic between 1971-76. Of the 42 isolates,
only 9 were found in isolation (7 bacteremias, 1 lung abscess, and 1 sinus drainage).
Sources Predisposing Conditions .
26% wound infections 43% Trauma or surgery (including dental)
24% abscess (neck, periodontal, brain) 26% Malignancy
12% endocarditis 1% Congenital Heart Disease
12% bacteremia in absence of endocarditis <1% Rheumatic Heart Disease
Although one must be wary of referral bias, this suggests that the most common infections seen with H.
aphrophilus are wounds and abscesses, not endocarditis as the published literature might suggest.
Similarly, rheumatic heart disease and congenital heart disease may be less of a predisposing factor than
suggested by historical cases where 22% had a history of RHD and 17% were reported to have congenital
heart lesions.
In this study, the most common risk factor was trauma or surgery. Unfortunately, they did not differentiate
this further to help us determine what proportion of this was related to traumatic injury involving oral
secretions or dental infections. Bacteremia in the absence of endocarditis most commonly occurred in
patients with malignancy undergoing chemotherapy, presumably due to loss of oral mucosal integrity from
mucositis. It was in this setting that H. aphrophilus was often cultured in isolation, although in previous
reports, it has been cultured in isolation from multiple sites.
9
Notably, in 50% of bacteremic cases, no
endocarditis was found.
Brain Abscess and Congenital Heart Disease
Fischbein et al.
10
studied the relationship between Haemophilus aphrophilus brain abscess and congenital
heart disease at Bostons Childrens Hospital. From 1960-73, 26 children presented with brain abscesses.
Among these, the most common organism isolated was alpha-hemolytic streptococci, followed by H.
aphrophilus. Three of the abscesses growing H. aphrophilus had congenital heart disease (2 with Tetralogy
of Fallot and 1 with tricuspid atresia). Unfortunately, the total number due to H. aphrophilus was not
given.
Several reasons have been proposed to explain why Haemophilus aphrophilus has a predilection to form
brain abscesses in persons with cyanotic congenital heart lesions.
1) Cyanosis from R-to-L shunting causes a predisposition to brain ischemia, infarct and
encephalomalacia via hypoxia
2) Cyanosis produces polycythemia and sludging, also resulting in ischemia, infarct and
encephalomalacia
3) Bacteremic events bypass the usual pulmonary filter and allow bacteria to have direct
access to the brain
4) Encephalomalacia and infarcted areas of the brain allow trapped bacteria to fester without
adequate clearance
5) Further hypoxia set up by other organisms, provides conditions of low O
2
tension that
favor the growth of capnophilic organisms such as H. aphrophilus.
Most would agree that H. aphrophilus appears to be an opportunist in that it causes disease in the presence
of predisposing conditions/tissue damage.
Canine Transmission?
In 1969, Fager
11
first described a patient with a brain abscess due to H. aphrophilus. Interestingly, this
patient was noted to have a few small popular erythematous neck lesions and gave a history of a having a
pet poodle who habitually licked him on the neck. The poodles saliva was cultured and found to have H.
aphrophilus.
In 1964, Isom et al.
12
described a similar case of isolated H. aphrophilus brain abscess in an 11 year-old
girl, also finding H. aphrophilus upon culturing the saliva of the patients pet dog. Fischbein et al. also
reported cases in the setting of canine contact, but did not pursue cultures of the dogs saliva.
In 1986, Abla et al.
13
reported a 58yo man who presented with R upper extremity numbness, weakness and
a focal seizure. He was found to have a L parietal abscess which grew H. aphrophilus in isolation. He
owned 4 poodles which often licked his neck and hands. Because of this report and the preceding
descriptions of canine carriage, all four poodles were screened by salivary cultures. One poodle was found
to carry H. aphrophilus. No other predisposing risk factors were found the patient was edentulous (but
had dentures), his TTE was negative, and all 6 of his family members had negative interdental cultures for
H. aphrophilus. His poodle was treated with amoxicillin 250mg po TID x 3 weeks and was subsequently
found to be culture negative.
Susceptibility
Unlike E. corrodens where disk diffusion was considered the gold standard method of determining
susceptibilities, microbiologists
6

14
have shown that disc diffusion is unreliable in H. aphrophilus when
compared to MIC testing.
Overall, studies
9
have consistently shown the following susceptibilities for H. aphrophilus:
Resistant to vancomycin, clindamycin, and oxacillin.
Susceptible to chloramphenicol, gentamicin, streptomycin
Variably susceptible to penicillin, ampicillin, cephalothin, erythromycin, tetracycline
One study which tested 40 clinical strains by broth microdilution showed variable susceptibility to
penicillin at 48% and 20% susceptibility to ampicillin. To date, no one has reported attempting to
characterize or confirm beta-lactamase production in H. aphrophilus despite the suggestion that one exists.
Haemophilus paraphrophilus
Epidemiology
Also recognized in 5-25% of human orophayngeal flora.
1

15
Microbiology
Initially described by Zinneman et al.
16
in 1968 as a novel capnophilic Haemophilus which was factor-V
dependent. It is a gram-negative coccobacillus notable for the fact that it can be easily misidentified.
17

18
Confusion has arisen between H. paraphrophilus and:
1) H. aphrophilus, from which it is morphologically indistinguishable. Nevertheless, it
can be distinguished from the latter by its requirement for V factor. Both
aphrophilus and paraphrophilus belong to a cluster of Haemophilus species that
does not require heme despite its nomenclature.
2) H. parainfluenzae, with which it shares its non-hemolytic morphology and
dependence on V, but not X, factor. Fermentation of lactose can distinguish H.
paraphrophilus from the latter.
3) E. corrodens, because both can produce pitting of agar, although this is classically
described with Eikenella corrodens. Biochemical testing will distinguish between
the two.
Clinical Manifestations
Zinnemans initial description of the species involved 24 clinical isolates from the oropharynx (4),
maxilla (1), brain (3 abscesses), respiratory tract (1), paronychia (4), gastrointestinal tract (3),
vagina (6), and urine (2). Chadwick et al.
17
described 34 strains from the UK sent to the National
Collection of Type Cultures (NCTC, London) for speciation which involved multiple sources
including brain abscesses (8), antral/duodenal/appendix abscesses (8), blood (3), eye or face
wound (4), and dog bite (1). They also reported a case of H. paraphrophilus sacroilitis.
Nevertheless, not unlike the other HACEK organisms, the most commonly associated infection
with H. paraphrophilus is endocarditis. A review of 12 cases
19
suggested that H. paraphrophilus
endocarditis occurred most commonly in young adults and involved the mitral valve in the setting
of mitral valve prolapse. It was also noted to frequently give rise to major embolic events,
including a case of multiple brain abscesses.
Actinobacillus actinomycetemcomitans 1912
In 1912, Klinger
1
isolated Actinobacillus actinomycetemcomitans from 5 of 12 cutaneous lesions involving
Actinomyces. He named it A. actinomycetemcomitans because he believed it was unable to cause infection
except in conjunction with Actinomyces israelii. Shortly thereafter, Holm et al.
9
reported its occurrence in
30% of infections involving Actinomyces. Initially, it was believed that the organisms could only cause
disease in combination with anaerobic Actinomyces. However, the reports of 32 well-documented cases of
Actinobacillus by King and Tatum
20
in 1962 provided conclusive evidence that A. actinomycetemcomitans
would produce infection on its own. A series of 23 cases of endocarditis were reviewed in 1966 by Page et
al,
9
and in 1973, the first case of brain abscess due to A. actinomycetemcomitans was described.
21
It is found in the upper respiratory flora of 17% of normal subjects. It causes protracted and insidious
diseases including endocarditis, particularly in those with abnormal valves. Similar to C. hominis, cerebral
emboli and CHF typically occur late, after antibiotics have been initiated.
This organism causes a variety of infections
22
, most commonly endocarditis, soft tissue abscesses, and
periodontal infection. In fact, it is highly associated with dental disease, being found in 50% of adults with
periodontitis and 97% of those with juvenile periodontal disease. In a series of 57 cases of endocarditis due
to A. actinomycetemcomitans, poor dentition (46%) and abnormal cardiac valves (60%) were found to be
predisposing factors. Artificial valves (25%) were found in 25% of cases, followed by congenital heart
disease ( 22%), rheumatic heart disease (12%), and pacemakers (4%). Notably, only 44% presented with
fever >38 C, and only 58% reported prior fevers, even though most reported other constitutional symptoms.
Less commonly, A. actinomycetemcomitans can cause brain abscesses, thyroid abscesses, parotitis,
endophthalmitis, pneumonia/empyema, pericarditis, osteomyelitis, and UTIs.
A. actinomycetemcomitans is a small coccoid to coccobacillary gram-negative rod that, in contrast to H.
aphrophilus, has a definite requirement of CO
2
for growth. After 24 hours, growth on agar results in
punctate, domed, translucent colonies which can show a characteristic four to six pointed star-like
projections. The star grows into the agar and remains after the colonies are scraped off.
A. actinomycetemcomitans strains are markedly sensitive to tetracycline, streptomycin, and
chloramphenicol, with variable sensitivity to ampicillin (35%) and penicillin (60%).
9
Thus, it is surprising
that classical therapy involved penicillin or ampicillin +/- an aminoglycoside. Limited experience suggests
that first and second generation cephalosporins may be used to treat endocarditis due to Actinobacillus.
However, in vitro data suggests that 3
rd
generation cephalosporins would be more efficacious. Rifampin
has been shown to be synergistic in vitro with penicillin or ceftriaxone in 30% of strain, but in vivo data is
limited. Patients with periodontal disease are often treated with 14d of prophylactic tetracycline before
major dental manipulation. Resistance to penicillin seems to be independent of penicillinase production.
Eikenella corrodens: 1948
Eikenella corrodens is a facultative anaerobic gram-negative rod that is part of the endogenous flora of
mucosal surfaces, particularly the mouth, where it is a common component of dental plaque and can be
found in 30
23
-40% of healthy gums. It is also found within the upper respiratory tract, lower GI tract, and
female genital tract.
24
Although Eikenella can be part of the normal oral, respiratory, and GI flora, it is seldom a pathogen. In a
series of 159 transtracheal aspirate samples sent for anaerobic culture from 1974-77 (Wadsworth VA
Hospital, Los Angeles), only 16 cultured Eikenella, and only 7 of these were associated with active
infection.
25
Of 140,000 cultures (all sites) reported from Boston City Hospital,
26
only 72 were E.
corrodens, and only 1 of the 72 was cultured in isolation. Nevertheless, Eikenella has been reported as the
causal agent in multiple infections.
History
In 1948, Henriksen reported isolating 3 strains of a novel gram-negative anaerobe from patients with
endometritis, pulmonary abscess, and peri-anal abcess. He noted that this microbe indented the growth
medium, and therefore named it corroding bacillus.
In 1958, Eiken described 21 strains of gram-negative obligate and facultative anaerobes which caused
pitting of the agar plate. He named them Bacteroides corrodens. Most of these strains were from oral
infections; one was from a brain abscess.
In 1972 J ackson and Goodman separated out the obligate from the facultative anaerobes described by
Eiken. They redefined the characteristics and classified the strict anaerobes as Bacteroides corrodens,
later to be re-named Bacteroides ureolyticus. The facultative anaerobes were named Eikenella corrodens.
Clinical Disease
Initial reports of Eikenella corrodens occurred in patients with severe underlying illnesses, often describing
wound infections around tracheostomy sites. The lack of reports of infection in healthy persons and the
fact that Eikenella was largely found in mixed infections led many to believe that Eikenella was not
pathogenic in isolation. In fact, attempts to directly inoculate Eikenella into subcutaneous tissues of animal
failed to produce abscesses unless streptococcal strains were simultaneously inoculated.
23

27
However, in 1979, DeMello and Leonard
28
described cases of E. corrodens in previously healthy
individuals lacking comorbidities. He described four young adults who had sustained trauma to their lip or
jaw followed by infection with Eikenella corrodens. In all four cases, despite antibiotics, the infection was
not cleared until surgical debridement occurred. These infections were notable for resistance to
Clindamycin, an antibiotic often used for head and neck infections. It was also described as an organism
that was reminiscent of anaerobic infections, although not anaerobic itself. Wounds were described as
producing a particularly foul smell, but small amounts of pus.
It was felt that Eikenella was somewhat of an opportunistic pathogen relying upon either:
1) Impaired vasculature from tissue necrosis, or
2) Presence of other organisms to invade traumatized tissues and use
available oxygen in tissues so the O2 tension drops
Types of Infections
1) Human bite wounds
a. Clenched fist injuries
b. 21 cases of hand infections early 80s
2) Skin popping wounds
23

29
a. From saliva: IVDU licking needles/site
3) Head and neck infections
30
a. Soft tissue infections
b. Osteomyelitis
c. Orbital cellulitis
d. Acne carbuncles
4) Respiratory tract infections
25

27
a. Aspiration pneumonia
b. Necrotizing pneumonia
c. Empyema
5) Other
a. Brain abscess
b. Subdural empyema
c. Visceral abscesses
d. Thrombophlebitis
e. Bacteremia
Drug abuse
Brooks et al.
23
found that abusers of methylphenidate were developing Eikenella corrodens skin abscesses.
Methylphenidate (Ritalin) was used by heroin addicts on methadone maintenance since it is not detected on
urine toxicology screens. The tablets were crushed, dissolved in water, and injected intravenously or
subcutaneous (skin popping). Typically, addicts would put their mouths on injection sites and/or lick their
needles.
CNS Infections
Cheng et al.
31
reviewed all reported cases (19) of Eikenella brain infections through 1983.
Cases Sources .
Brain abscesses (11) Sinusitis (7)
Subdural abscesses (5) Otitis Media (4)
Epidural abscess (1) Dental infections (3)
Meningitis cases (2) Pneumonia (1)
Not stated (3)
5 cases (temporal abscess, occipital abscess, meningitis (2), subdural abscess (2))
demonstrated Eikenella corrodens in pure culture.
7 cases were found in mixed infections with a variety of streptococci
All cases of epidural or subdural empyemas were associated with underlying sinusitis.
Nevertheless, among brain abscesses, it is uncommon to isolate E. corrodens. In a review of all
cerebral abscesses from 1985-88 at the National University of Malaysia,
32
only 1 of 75 cases cultured E.
corrodens. That case involved a mixed infection in a child with cyanotic heart disease. The distribution of
cases seen in that hospital included 65% under the age of 20, and 13% which had sterile cultures.
Predisposing conditions included chronic OM (23%), meningitis (13%), cyanotic congenital heart disease
(12%), and chronic sinusitis (3%). Streptococcus milleri was found in 17 of 75 cases. Seven were linked
to cyanotic congenital heart disease. Eleven of 17 were isolated in pure culture.
Among the organisms found in mixed infections with E. corrodens, streptococcal species are the
most common co-infecting agent (both alpha and beta hemolytic), followed by staph aureus, then
haemophilus and enterobacteriaceae species.
23
Meningitis
The 2 meningitis cases
33
showed poly predominant leukocytosis (WBC 4,000 and 21,750) with elevated
protein and low to normal glucose. However, the cases were reported in 1973 and 1974 and cannot exclude
by present-day radiology the presence of an initial parameningeal process i.e. intracerebral abscess with
ventricular rupture.
Flossing
The vast majority of CNS infections due to Eikenella are associated with dental, aural, or sinus infections.
However, Burdick et al.
34
report a case of a 38yo man in excellent health who presented with a left parietal
brain abscess with the only risk factor elucidated was avid flossing for 5-8 minutes twice daily until he
achieved 5 bleeding points.
Foreign Bodies
Among the less common sources of brain abscess include pulmonary infections which allow bacteria to
penetrate the tracheobronchial mucosal barrier, bypass the pulmonary filter, and gain access to the CNS.
Eikenella corrodens has been reported in two cases of brain abscess in children due to foreign bodies in the
pulmonary tree.
35
One 2 year-old child presented with fever, irritability and severe retro-orbital pain and
was found to have two brain abscesses in the absence of endocarditis. Cultures grew Staphylococcus
aureus, alpha hemolytic streptococcus and E. corrodens. CXR showed a metallic needle in the left lower
lobe which, on endoscopy, was noted to be embedded in the mucosa.
A second 2 year old child with fever and perihilar infiltrates developed progressive neurologic decline.
MRI showed a R temporal brain abscess with cultures growing E. corrodens and alpha hemolytic
streptococcus. He had had a cough for the past 3 months which had initially presented as a pneumonia.
Immunodeficiency screens, sweat test, and echocardiogram were normal. Bronchoscopy revealed 2
sunflower seeds that were partially embedded into the wall of the R main bronchus. Removal and longterm
antibiotics resulted in complete resolution.
Microbiology
Gram negative, straight slender rod, pleomorphic or coccobacillary
Capnophilic facultative anaerobe (CO2 is a strong stimulant for growth)
Grows slowly on blood or chocolate, >2 days to see pinpoint colonies
Best isolated on blood agar plates with clindamycin
Colonies are small, gray, non-hemolytic
50% will cause pitting of the agar
Odor of musty chlorine bleach
Grows poorly on MacConkey
Oxidase-positive, Catalase-negative
Susceptibility
23

25

36

37
Disk diffusion inaccurate and MICs problematic since grows in clumps so that uniform suspensions are
difficult to achieve. Favored approach =agar dilution. MICs were uniformly 1-2 dilutions lower than agar
dilution susceptibilities. MBC and MICs were close (1 dilution) or equivalent (60%).
In general:
Susceptible: PCN, amp, ureidopenicillins,fluoroquinolones, 2
nd
/3
rd
generation cephalosporins
Variably Susceptible: Gent, erythromycin, 1
st
generation cephalosporins, tetracycline
Resistant: Clindamycin, Metronidazole, and Oxacillin
Careful since difficult to grow, thus may be suggestive of anaerobic infection. However, unresponsive to
metronidazole or clindamycin.
Beta-Lactamases:
Plasmids bearing beta-lactamases have been isolated from many mouth flora, including Eikenella
corrodens. Kinder et al.
38
reviewed penicillin resistance among subgingival flora in 42 individuals and
found that beta-lactamase producing species were found in 2/3 of all hosts and represented about 1% of
total culturable flora. The majority of resistant species included Bacteroides, Veillonella, Eikenella,
Haemophilus, and Capnocytophaga.
Rotger et al.
39
characterized a plasmid bearing beta-lactamase in Eikenella corrodens in 1986, following
increasing reports of penicillin resistance in gingival flora. This enzyme was a plasmid-encoded, TEM-like
beta lactamase with the plasmid also coding for streptomycin and sulfonamide resistance. Lacroix et al.
40
reported a constitutive chromosomal beta-lactamase that is preferentially a penicillinase, and strongly
inhibited by clavulanate or sulbactam. It only weakly hydrolyzes cefotaxime, aztreonam, and imipenem.
Treatment Options
Classically, treated with penicillin or ampicillin (+aminoglycoside for endocarditis). Now, in
light of beta-lactamase production, favor ureidopenicillins or 3
rd
generation cephalosporins until beta-
lactamase production determined. Fluoroquinolones have good activity in vitro. Drainage of abscesses
remains the critical intervention.
Cardiobacterium hominis 1964
Cardiobacterium hominis was initially reported in the NEJ M as a Pasteurella-like organism in 1962.
41
It
was subsequently characterized and named by Slotnick
42
in a 1964 paper titled: Further characterization of
an unclassified group of bacteria causing endocarditis in men: Cardiobacterium hominis. Both Slotnick
and others noted that this organism seemed to selectively cause endocarditis, and more specifically,
endocarditis in humans.
C. hominis is present
43
in 68% of upper respiratory flora in normal hosts regardless of age. In addition, it
is found in 70% of stool isolates and rarely (1%) in vaginal or cervical smears. It appears to be of
extremely low virulence, and is not pathogenic for mice, guinea pigs, rabbits or pigeons despite
intravenous, intraperitoneal, or subcutaneous injections (10
8
organisms).
C. hominis has only been described in bloodstream infections, either due to endocarditis or unknown
sources in neutropenia or sepsis. By 1983, only 34 cases
44
of C. hominis infections had been reported.
75% of cases of endocarditis had known structural cardiac abnormalities, and 13% had prosthetic valves.
In one series of endocarditis due to C. hominis, 86% had fever, but 55% never exceeded 101F. Strikingly,
it presents as a chronic infection with a mean duration to diagnosis of over 5 months. This is significantly
longer than the interval (54 days) noted for diagnosis of endocarditis due to other HACEK organisms.
Embolic events occurred in 44%, with a propensity to progress to emboli or CHF despite appropriate
antibiotics. False +RPRs are common. Blood cultures become negative immediately after the institution
of therapy, although fevers may persist for several weeks.
It is a pleomorthic gram-negative organism often found in pairs, short chains, or formations of teardrops,
rosettes, or clusters. Ends of these rods are often enlarged and may retain gram-positive stain. It is a
capnophilic facultative anaerobe which can grow in aerobic conditions with high humidity. Colonies are
punctate, gray, moist, round, raised, and non-hemolytic.
It is sensitive to penicillin, streptomycin, tetracycline and chloramphenicol. The uniform susceptibility to
penicillin distinguishes it from H. aphrophilus and A. actinomycetemcomitans.
Kingella Kingae - 1968
The bacterium
45
later known as Kingella kingae was first described by Elizabeth O. King at the CDC. It
was initially described with other Moraxella-like organisms as Moraxella new species 1. In 1968, it was
isolated and characterized as Moraxella kingii in honor of Elizabeth King. In 1974, the name was modified
to reflect the female gender of the founding scientist: Moraxella kingae. Finally, in 1976, the organism was
assigned to the genus Kingella, and acquired the name Kingella kingae.
Kingella kingae was originally found in 1.1% of pharyngeal cultures, but likely has a higher prevalence due
to difficulties with culture in the 1960s. More recently, it has been isolated in 33% of tonsilar cultures in
children attending day-care.
46
K. kingae is a coccoid to medium sized rectilinear rod found in pairs and short chains. It is gram-negative,
but has a tendency to resist decolorization. There are two main colony types. One is small, convex,
translucent and beta-hemolytic. A second is the corroding variant with a raised central papilla and a
granular surface, also beta-hemolytic. K. kingae is an aerobe that grows optimally at 33-37 C.
Pathogenically, K. kingae behaves like Neisseria meningitides which initially colonizes the nasopharynx
and then subsequently can lead to bacteremia and widely disseminated infection of heart valves, skin,
bones, and joints. By 1997, only 10 cases of endocarditis in children and 10 cases in adults had been
reported. It can infect both normal and abnormal valves, and is associated with frequent complications of
endocarditis (embolisms, CHF), although this may represent publication bias. Insidious septic arthritis is a
common manifestation, particularly in children with normal joints. The knee is the most common joint
infected. Complete recovery without sequela is expected. Transient bacteremia, paraspinal abscesses,
diskitis, cellulitis, and meningitis are rarely reported.
In children, 70% of disease involves the skeletal system, predominantly septic arthritis. In a study of
diseases due to Kingella Kingae in children from southern Israel, Yagupsky and Dagan found that 45% of
affected children were 13-24 months old, with an attack rate of 27 cases/100,000 children under 24 months.
Almost 90% of all children with invasive K. kingae infections have been under the age of 5.
Therapeutic recommendations are anecdotal due to the small number of cases due to this organisms.
Classically, treatment involves penicillin or ampicillin with or without an aminoglycoside. However, K.
kingae is quite susceptible to most agents, including beta-lactam antibiotics, aminoglycosides,
ciprofloxacin, tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol. There is, however,
substantial resistance to clindamycin (38.6%),
47
and, in 1993, Sordillo et al. reported a beta-lactamase strain
causing sepsis.
48
References

1
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2
Geraci J E, Wilson WR. Endocarditis due to gram-negative bacteria. Mayo Clin Proc 1982; 57: 145-8.
3
Kraut MS, Attebery HR, Finegold SM, Sutter VL. Detection of Haemophilus aphrophilus in the human
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4
Brown WJ . Incidence of Haemophilus spp. and similar organisms in the adult respiratory tract. Abstracts
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5
Bieger RC, Brewer NS, Washington J A. Haemophilus aphrophilus: a microbiologic and clinical review
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7
Khairat O. Endocarditis due to a new species of Haemophilus. J Pathol Bacteriol 1940; 50:497-505.
8
Toschach S, Bain GO. Acquired acortic sinus aneurysm caused by Hemophilus aphrophilus. Am J Clin
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9
Page MI, King EO. Infection due to Actinobacillus actinomycetemcomitans and Haemophilus
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10
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