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Moraxella catarrhalis is a gram-negative aerobic
diplococcus that belongs to the Neisseraceae family.
It has been known as Micrococcus catarrhalis, Niesseria
catarrhalis, and Branhamella catarrhalis. It commonly
inhabits the upper respiratory tract. For many years, it was considered
a nonpathogenic member of the resident flora of the nasopharynx.
Over the past 25 to 30 years, it has been recognized as a genuine mucosal
pathogen and is now considered an important cause of otitis media
and sinusitis in healthy children and adults. It also causes lower
respiratory tract infections and exacerbation of bronchitis in adults
with chronic lung disease. Occasionally, it can cause a variety
of severe infections, including septicemia, pneumonia, and meningitis,
especially in the immunocompromised hosts.
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M catarrhalis is a normal inhabitant of the
upper respiratory tract. Nasopharyngeal colonization rate is highest
during infancy and early childhood and lowest in adulthood. Colonization
rates of as high as 36% to 50% in infants and
young children,1 and 1% to 3% in
adults,2 have been reported. In one study of a
large cohort of infants who were followed prospectively from birth
to 2 years of age, 66% became colonized with M
catarrhalis by 1 year and 77.5% by 2 years of
age. In the same group, nasopharyngeal colonization increased from
27% during healthy visits to 63% on visits associated
with otitis media.3 Other studies have shown that
colonization of children varies with the season and is more common
in fall and winter (46%) than in spring and summer (9%).4 Overall,
colonization was higher in children with upper respiratory tract
infection (36%) than in children without (18%),
and was more common in children ages 24 months (32%) than
in children older than 24 months (14%). Colonization with M
catarrhalis is reported to be more common in asthmatic
children than in normal children.
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Factors influencing colonization and elimination are not fully
understood, but adhesion to mucosal receptors and immune responses are
implicated in addition to bacterial colonization dynamics. In general,
potential pathogens are more likely to colonize the nasopharynx
of children prone to recurrent otitis media, where impaired local
immunity and repeated exposure to respiratory pathogens are additional
risk factors.5Colonization appears to be an ongoing
process with an elimination-colonization turnover of various strains.
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The mode of transmission of the organism is presumed to be direct
contact with contaminated respiratory tract secretions and/or
droplet spread.
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M catarrhalis is an aerobic gram-negative diplococcus
that has a striking resemblance to meningococcus and gonococcus,
except that it is unencapsulated. It grows well on blood and chocolate
agars, forming small, opaque, gray-white nonhemolytic colonies.
Recovery of the organism from the mixed flora of mucosal surfaces
can be enhanced by using selective culture media such as modified
Thayer-Martin or TV broth (Mueller-Hinton broth supplemented with
trimethoprim and vancomycin).
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After the nasopharynx is colonized, the organism appears to spread
contiguously from its respiratory colonizing position to the infection
site and cause mainly otitis media and sinusitis in children and
less often pneumonia in adults. There is no pathognomic feature
of M catarrhalis otitis media, sinusitis, or pneumonia. Colonization
of the tracheobronchial tree may lead to the development of bronchitis or
pneumonia in adults with underlying risk factors, such as smoking,
intercurrent viral infection, corticosteroid treatment, or immunosuppression.
++
In children, pneumonia may develop in those with intercurrent
viral infection, underlying lung disease, prematurity, or immunoglobulin
deficiency. Risk factors for development of bacterial tracheitis
and pneumonia in children in an intensive care setting include endotracheal
intubation and frequent suctioning.
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The predominant bacteria associated with otitis media in children
are Streptococcus pneumoniae, nontypeable Haemophilus
influenzae, and M catarrhalis. A cohort
of 306 infants were followed from birth through 12 months to determine
frequency and duration of nasopharyngeal colonization and risk of acute
otitis media (AOM) and otitis media with effusion (OME). M
catarrhalis was the most common bacterium isolated. Infants colonized
at 3 months of age or younger were at increased risk of AOM and
OME. Early colonization with M catarrhalis revealed
the greatest risk (relative risk [RR] = 1.24),
especially for OME (RR = 1.57). A strong relationship was
noted between the frequency of colonization and OM (r = 0.37, P <
0.001) for each pathogen.6
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Relatively little is known about the virulence traits of M
catarrhalis. A small number of studies on the interaction
between M catarrhalis receptors and human antigens
have been undertaken. In one study, the CD outer membrane protein
(OMP) of M catarrhalis specifically attached to
the mucin molecules from the nasopharynx and middle ear, but not to
mucin from the saliva and tracheobronchial mucin.7
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Such interaction represents the first step in the process of
bacterial colonization and infection. The CD OMP is considered a
potential vaccine candidate. The presence or absence of fimbriae
does not seem to influence the capacity of the bacterium to adhere.8M
catarrhalis also expresses both transferrin
and lactoferrin receptors on its surface. These proteins provide
the cell with the capacity to acquire iron by sequestering it from
the host carrier proteins.9 Those receptors are
virulence factors and immunogenic, and as such, are potential vaccine
candidates.10 Some M catarrhalis strains
produce a protein that confers resistance to complement. Complement-resistant strains
inhibit the terminal pathway of complement (ie, the formation of
the membrane attack complex of complement).11The endotoxin
of M catarrhalis, a lipopolysaccharide, may also
play a role in the disease process.
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Clinical Manifestations
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The most significant infections caused by M catarrhalis are
upper respiratory tract infections, including otitis media and sinusitis
in children and lower respiratory tract infections in adults.
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M catarrhalis is the third most common cause
of otitis media in children, following Streptococcus pneumoniae and
nontypable Haemophilus influenzae. Otitis media
is the most frequent infection caused by M catarrhalis in
children, and as such, causes significant morbidity and necessitates
the widespread use of antibiotics.3,12 Since 1980,
there has been an increase in the isolation of M catarrhalis from
middle ear exudates.13Presently, it accounts for
15% to 20% of pathogens recovered from middle
ear fluids of children with AOM; however, these isolation rates might
be an underestimation. In a study using PCR, M catarrhalis DNA
was detected in 46.4% of 97 middle ear specimens compared
to 54.6% for H influenzae DNA and 29.9% for S
pneumoniae DNA. The increase in the isolation rate of M
catarrhalis has been accompanied by the appearance of beta-lactamase–producing
strains, which now account for approximately 95% to 100% of
the isolates. The organism may occur as a single pathogen or in
combination with other organisms. Otitis media caused by M
catarrhalis cannot be distinguished clinically from otitis caused
by S pneumoniae or H influenzae. However,
the severity of otitis media symptoms appear to be lower for M
catarrhalis, and it is more likely to remit spontaneously
than is disease caused by S pneumoniae or H
influenzae.14
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Sinusitis is a very common infection in early childhood accounting
for about 5% to 10% of upper respiratory tract
infections.15 It is often underdiagnosed in children
because the symptoms are nonspecific. In acute sinusitis (when symptoms
are present for 10–30 days) and subacute sinusitis (30–120 days)
in children, S pneumoniae,H influenzae, and M
catarrhalis are the most frequently isolated pathogens. S
pneumoniae is found in 30% to 40% of
patients, whereas H influenzae and M catarrhalis each
account for about 20% of cases.15,16 The
clinical manifestations of sinusitis caused by M catarrhalis are
similar to those caused by S pneumoniae and H
influenzae.
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Although bronchopulmonary infections caused by M catarrhalis have
generally been noted in adults with chronic lung disease, pneumonia
has also been reported in children. However, establishing a microbiological
diagnosis of lower respiratory tract infection in children is notoriously
difficult. Lower respiratory tract infections due to M catarrhalis appear
to be relatively rare during childhood with most infections occurring
in children younger than 1 year.17 Expectorated
sputum and tracheal aspirates are more likely to yield a clinically
significant isolate than nasopharyngeal aspirates. Therefore, data
concerning the role of M catarrhalis in lower respiratory
tract infection are not conclusive. Because sputum samples are usually
not available in children, most documented pneumonia cases were
severe and occurred primarily in immunocompromised patients. In
one report, five premature infants younger than 6 months with preexisting
lung disease were diagnosed as having pneumonia following a 2- to
4-day prodrome of cough, tachypnea, and retractions. M catarrhalis was
recovered from bronchial aspirations. All patients required assisted
ventilation for marked hypoxia.18 Associated M
catarrhalis bacteremia has been reported in other patients
with pneumonia. In adults, M catarrhalis pneumonia
is more common in patients with chronic lung disease, AIDS, and
malignancy.
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Underlying conditions associated with increased predisposition
to M catarrhalis infections in children include
AIDS, leukemia, and immunoglobulin deficiencies. M catarrhalis has
also been reported as a cause of bacterial tracheitis,19,20 as
well as a variety of other infections including urethritis,21conjunctivitis,22 pyogenic
arthritis,23peritonitis,24 preseptal
cellulitis,25 bacteremia,26,27 and
urinary tract infection.28 Meningitis caused by M
catarrhalis occasionally results from hematogenous spread,29,30 or
as a complication of ventriculoperitoneal shunt infection.31 Endocarditis
is rare, and the few reported cases were associated with a high
mortality rate.32 Urethritis caused by M
catarrhalis can be mistaken for gonococcal urethritis.
Conjunctivitis caused by M catarrhalis in the newborn
can mimic ophthalmia neonatorum caused by Neisseria gonorrhoeae.
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Bacteremia caused by M catarrhalis is less well
understood and has been reported sporadically in a variety of clinical
settings, in both children and adults. The clinical severity of M catarrhalis bacteremia
has varied from self-limited febrile illness to lethal sepsis. Some
reviews indicate that a significant proportion of children with M
catarrhalis bacteremia had an underlying immune defect
(malignancy, AIDS, neutropenia, low IgG level) or a predisposing respiratory
factor (chronic lung disease, tracheostomy, mechanical ventilation).
However, some healthy, immunocompetent patients with no predisposing
factors have presented with M catarrhalis bacteremia.
In most such patients, the source of the infection was an upper
airway focus (otitis, sinusitis) or pneumonia.27 Children
with M catarrhalis bacteremia may present with
different clinical manifestations. Some children present with petechial
or purpuric rashes resembling infection caused by N meningitidis. Other
patients present with nonspecific symptoms and no focus of infection, similar
to patients with occult pneumococcal bacteremia.
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Before 1970, all strains of M catarrhalis were susceptible
to penicillin and ampicillin. However, β-lactamase-producing
strains progressively increased during the 1980s. Presently, almost
all M catarrhalis isolates are producers of β-lactamases
(prevalence over 90%) reducing susceptibility to penicillins
only. The β-lactamase inhibitors clavulanic acid
and sulbactam are active against the β-lactamase enzymes
produced by M catarrhalis.
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In vitro, M catarrhalis isolates are generally susceptible
to ampicillin/sulbactam and amoxicillin/clavulanic
acid; erythromycin; azithromycin; clarithromycin; trimethoprim-sulfamethoxazole; chloramphenicol;
tetracycline; aminoglycosides; fluoroquinolones (eg, ciprofloxacin);
and both second- and third-generation cephalosporins (cefuroxime,
cefaclor, cefprozil, cefpodoxime, cefixime, and loracarbef). Cefaclor
is less active than cefuroxime against M catarrhalis. Most β-lactamase-producing
strains respond to treatment with β-lactam/β-lactamase
inhibitor combination, as well as second- and third-generation cephalosporins.33 However,
antimicrobial treatment should be guided by in vitro susceptibility testing,
especially for invasive infections. M catarrhalis strains
are resistant to vancomycin, oxacillin, and clindamycin.
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The mode of transmission of the organism is by direct contact
with contaminated respiratory tract secretions and/or droplet
spread. Therefore, good hand-washing technique and sterilization
of instruments used in intubations and aspiration may reduce or
prevent nosocomial infections caused by M catarrhalis.
Cessation of smoking, as well as prevention of passive smoking,
may reduce M catarrhalis infections. Presently,
no vaccine is available for the prevention of M catarrhalis infections. Certain
protein components of the organism are considered potential vaccine
candidates; however, little or nothing is known about the optimal
routes for vaccine delivery or whether there is need for adjuvants.
One of the major challenges that still exists is to find mechanisms
that will effectively deliver protein antigens to mucosal surfaces.
Several strategies have been investigated and resulted in varying degrees
of success.34