Basim I. Asmar
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.
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.
The mode of transmission of the organism is presumed to be direct contact with contaminated respiratory tract secretions and/or droplet spread.
M catarrhalis is an aerobic gram-negative diplococcus that has a striking resemblance to meningococcus and gonococcus, except that it is unencapsulated.
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.
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.
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
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.
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.13 Presently, 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.
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.
Although bronchopulmonary infections caused by M catarrhalis have generally been noted in adults with chronic lung disease, pneumonia has also been reported in children. Lower respiratory tract infections due to M catarrhalisappear 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. 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.
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,21 conjunctivitis,22 pyogenic arthritis,23 peritonitis,24 preseptal cellulitis,25 bacteremia,26,27 and urinary tract infection.28 Meningitis caused by M catarrhalisoccasionally 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.
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. 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.
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 catarrhalisisolates 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.
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.
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.