Version May 2024
INTRODUCTION — Moraxella catarrhalis is a gram-negative diplococcus that commonly colonizes the upper respiratory tract. It is a leading cause of otitis media in children, acute exacerbations of chronic obstructive pulmonary disease (COPD), and acute bacterial rhinosinusitis.
The epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of infections caused by M. catarrhalis are discussed here.
Acute otitis media, COPD, and acute rhinosinusitis are discussed separately:
●(See "Acute otitis media in children: Epidemiology, microbiology, and complications".)
●(See "Acute otitis media in children: Clinical manifestations and diagnosis".)
●(See "Acute otitis media in children: Treatment".)
●(See "Acute otitis media in adults".)
●(See "Management of infection in exacerbations of chronic obstructive pulmonary disease".)
●(See "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis".)
●(See "Acute bacterial rhinosinusitis in children: Microbiology and management".)
●(See "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis".)
●(See "Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment".)
●(See "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease".)
EPIDEMIOLOGY
Prevalence and incidence
Colonization — Colonization with M. catarrhalis is a predisposing factor for infection, and its prevalence is highly dependent on age [1-8]. In infants, nasopharyngeal colonization with M. catarrhalis is common, with reported prevalence ranging from 30 to 100 percent [1-5,9]. By adulthood, prevalence declines to approximately 1 to 5 percent. Among adults with chronic obstructive pulmonary disease (COPD), the prevalence is higher, but precise rates have not been measured [6]. Across age groups, colonization appears to be episodic, with different M. catarrhalis strains colonizing the upper respiratory tract over time [6,10].
Infection — M. catarrhalis is among the top three causes of otitis media in children, acute exacerbations of COPD, and acute bacterial rhinosinusitis.
●Approximately 10 to 20 percent of acute otitis media cases in children are caused by M. catarrhalis, with the highest rates observed in children <24 months old [7,8,11,12]. M. catarrhalis is also being increasingly recognized as a cause of recurrent and chronic otitis media in children [13-16].
●Similarly, approximately 10 to 20 percent of acute COPD exacerbations are caused by M. catarrhalis [6,17].
●The great majority of cases of acute rhinosinusitis are viral [18]. Acute bacterial infections account for only 0.5 to 2 percent of cases. Of those, M. catarrhalis accounts for approximately 5 to 15 percent of cases [19,20].
M. catarrhalis is an infrequent cause of other infections, such as community-acquired pneumonia and bacteremia [21,22]. Other invasive infections are rare [22-25]. (See 'Pneumonia and invasive infections' below.)
Effect of pneumococcal vaccination — Rates of colonization and infection with M. catarrhalis are rising due to the widespread use of pneumococcal vaccinations, which alter the respiratory tract microbiome. With vaccine use, colonization with vaccine serotypes of Streptococcus pneumoniae generally declines, while colonization with other microorganisms such as M. catarrhalis, Haemophilus influenzae, and nonvaccine S. pneumoniae serotypes rises [5,16,26-33]. Similar changes have been observed in the prevalence of pathogens that cause otitis media and acute rhinosinusitis [15,19,34-40]. Further changes are expected as newer vaccines are developed and vaccination rates grow.
Transmission — M. catarrhalis is transmitted from person to person, likely via respiratory droplets and fomites [41]. Clusters of cases have been reported in hospital settings [41-44], daycare centers [45], and among family members [46,47].
MICROBIOLOGY — M. catarrhalis is an aerobic, nonmotile gram-negative diplococcus. The organism is an exclusively human pathogen with an ecologic niche in the upper respiratory tract. The organism belongs to the Moraxellaceae family and Moraxella genus [48]. Multiple strain types exist within the species, and virulence factors and pathogenic potential vary among strains [10]. Other species within the Moraxella genus are rarely pathogenic in humans, although some colonize the upper respiratory tract and, less often, the skin and urogenital tract [49-52].
PATHOGENESIS — The pathogenesis of M. catarrhalis infections involves complex interactions among viral pathogens, bacterial copathogens, and the host immune response.
For most infections, the initial step in pathogenesis is adherence to and colonization of mucosal surfaces. M. catarrhalis expresses a dozen or more adhesins, each with different binding specificities for host structures [10,12,53-55]. Following adherence, bacteria invade the respiratory mucosa. Primary cellular targets include the epithelial cells lining the respiratory mucosa, antigen-presenting cells, neutrophils, and lymphocytes [10,56,57]. Adherence and invasion trigger an excessive proinflammatory immune response, which in turn damages host tissues and promotes spread of the infection [10,58-61]. The proinflammatory response also leads to the hyperproduction of mucus along the respiratory tract. Certain virulence factors have immune-evasive functions such as inactivation of the complement system [10,62-66] and inhibition of toll-like receptor 2 signaling. As bacteria aggregate, biofilms can form, which reduce the host's ability to clear the organism and promote resistance to antibiotic therapy [10,67-69]. Phase variable expression of methyltransferases mediates the regulation of expression of multiple genes that are important in virulence [70,71]. In acute otitis media, adherence to the mucosal surface is not sufficient to cause disease [72,73]. A cofactor, such as a viral infection, is likely needed to precipitate migration to the middle ear via the Eustachian tube [74,75]. M. catarrhalis is often isolated with S. pneumoniae and H. influenzae in respiratory tract cultures [75-79] and may facilitate polymicrobial infection by sheltering these organisms from complement-mediated immune destruction, promoting biofilm formation, and releasing beta-lactamase into the local environment [80-86]. Similar factors may be involved in the pathogenesis of acute bacterial rhinosinusitis, which is frequently preceded by viral infections and can be polymicrobial. (See "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Pathogenesis' and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis", section on 'Pathophysiology and microbiology' and "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Pathogenesis'.)
While copathogens likely play a role in the pathogenesis of acute exacerbations of COPD, the acquisition of new M. catarrhalis strains appears to be the critical factor [87,88]. The mucosal surface of the lower respiratory tract in patients with COPD is generally damaged, remodeled, and fibrotic, which facilitate adherence and colonization. The acquisition of a new strain of M. catarrhalis provokes airway inflammation [58,89,90], which can result in clinical exacerbations [6,87]. With clearance of the new strain, antibodies are produced and protective immunity against the same strain develops but not against other strains [6,91-93]. (See "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease", section on 'Etiology'.)
CLINICAL MANIFESTATIONS — The most common clinical manifestations of M. catarrhalis infections are acute otitis media (AOM), acute exacerbations of chronic obstructive pulmonary disease (COPD), and acute rhinosinusitis.
Acute otitis media — Signs and symptoms of AOM due to M. catarrhalis do not differ substantially from otitis media caused by other pathogens and commonly include fever, ear pain, and a bulging tympanic membrane. However, M. catarrhalis is generally considered to be less virulent than other common otopathogens such as S. pneumoniae and H. influenzae. In a large cohort study evaluating children <5 years old with AOM, complications such as tympanic membrane perforation and mastoiditis occurred less frequently with M. catarrhalis than with S. pneumoniae or H. influenzae.
AOM caused by M. catarrhalis most often occurs in younger children, especially those under two years old [78], and is rare in adults. AOM is often preceded by a viral upper respiratory tract infection. Most cases of AOM due to M. catarrhalis occur in late fall to early spring [11]. The seasonal nature of infection correlates with the incidence of respiratory viral infections, which are probable cofactors in AOM pathogenesis. (See 'Pathogenesis' above.)
The clinical features of acute otitis media in children are discussed in detail separately.
Acute exacerbations of COPD — The clinical features of acute exacerbations of chronic obstructive pulmonary disease (COPD) caused by M. catarrhalis are similar to those of exacerbations caused by other bacteria. Common symptoms include increased cough, sputum production, sputum purulence (change in color), and dyspnea when compared with baseline. (See "Chronic obstructive pulmonary disease: Diagnosis and staging", section on 'Clinical Presentation'.)
Persons with COPD are commonly colonized with M. catarrhalis [6,17]. New strains are acquired and cleared from the sputum routinely. In about 50 percent of cases, acquisition of a new strain leads to clinical exacerbation [6,17,87]. Exacerbations caused by M. catarrhalis occur throughout the year, but more cases occur in late fall to early spring [17].
Acute bacterial rhinosinusitis — Signs and symptoms of acute bacterial sinusitis caused by M. catarrhalis are similar to those caused by other bacteria and include fever, nasal obstruction, purulent nasal discharge, facial pain, and headache. There is no clinical feature that helps distinguish acute rhinosinusitis caused by M. catarrhalis from acute rhinosinusitis caused by other bacteria. (See "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Clinical features' and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis".)
Pneumonia and invasive infections — M. catarrhalis is an infrequent cause of other infections. Community-acquired pneumonia due to M. catarrhalis occurs most frequently in older adults, persons with cardiopulmonary disease or diabetes mellitus, and/or immunocompromised persons [21,94-96].
Invasive infections caused by M. catarrhalis are rare [22-25]. A 2007 review of the literature reported only 75 cases of invasive infection; these included bacteremia, endocarditis, pneumonia, periorbital cellulitis, neonatal meningitis, and septic arthritis [22]. Seventy-two of the 75 patients (96 percent) had bacteremia. Invasive infections have been reported across age groups and in both immunocompromised and immunocompetent patients [22,97]. Although no clear risk factors for invasive infection have been identified, a small case-control study detected an increased rate of bacteremia in children with transnasal devices such as nasogastric tubes [98].
DIAGNOSIS
Clinical diagnosis — Characteristic clinical features usually are sufficient for diagnosis of the most common clinical syndromes caused by M. catarrhalis:
●Acute otitis media is typically diagnosed by visualization of a bulging tympanic membrane on pneumatic otoscopy [99]. Symptoms that support the diagnosis include ear pain and fever. (See "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Clinical diagnosis'.)
●Acute exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by an increase in baseline dyspnea, cough, and sputum production. The presence of purulent sputum raises the likelihood of a bacterial cause. (See "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease".)
●Acute rhinosinusitis is characterized by fever, nasal obstruction, nasal discharge, facial pain, and headache. The presence of prolonged symptoms or symptoms that improve but then worsen (double worsening) raise the likelihood of a bacterial cause. (See "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis" and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis".)
For most patients, pursuing a microbiologic diagnosis usually is unnecessary because testing can be invasive (eg, tympanocentesis for otitis media), treatment is empiric, and results generally do not change management.
Microbiologic diagnosis — Microbiologic testing is generally reserved for patients with acute or recurrent otitis media or acute bacterial rhinosinusitis who have failed empiric antibiotic therapy, patients with severe COPD exacerbations, or patients who may otherwise benefit from directed antibiotic therapy. One randomized trial showed that antibiotic treatment had minimal benefit for children without nasopharyngeal bacterial pathogens by culture, including M. catarrhalis [100]. Nasopharyngeal cultures may be a strategy to reduce unnecessary antibiotic use in this setting.
Microbiologic diagnosis is made by Gram stain and culture of the organism from the affected site. On Gram stain, M. catarrhalis appears as a gram-negative diplococcus that is morphologically similar to Neisseria species (picture 1). Because Neisseria spp are a normal part of the upper respiratory tract flora, some microbiology laboratories do not proceed to culture when organisms that look like Neisseria spp are identified. In such cases, a specific request to culture the organism may be needed.
In culture, the organism grows as round, opaque colonies on blood and chocolate agar, which typically turn pink after 48 hours. The "hockey puck sign" (the ability of colonies to slide across agar without disruption) is a characteristic feature of M. catarrhalis. In most laboratories, antibiotic susceptibility testing is not routinely performed but can be requested when there is a need for precise targeted antibiotic therapy.
The abundance of M. catarrhalis detected on Gram stain or culture may also have diagnostic value (eg, heavy growth on sputum culture in a patient with an acute COPD exacerbation suggests M. catarrhalis infection rather than colonization).
Molecular assays for the detection of M. catarrhalis, such as polymerase chain reaction, are in development but not yet commercially available [101-103].
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of M. catarrhalis infection varies with the site of involvement but generally includes other pathogens that commonly colonize or infect the upper respiratory tract such as S. pneumoniae, H. influenzae, and respiratory viruses. There are no characteristic clinical features that help distinguish infection caused by M. catarrhalis from infection caused by other pathogens.
TREATMENT — Most cases of acute otitis media, acute chronic obstructive pulmonary disease (COPD) exacerbations, and acute bacterial rhinosinusitis are treated empirically. (See "Acute otitis media in children: Treatment", section on 'Initial antibiotic therapy' and "Acute otitis media in adults", section on 'Treatment of acute otitis media' and "Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment" and "Acute bacterial rhinosinusitis in children: Microbiology and management", section on 'Empiric antibiotics'.)
When directed therapy is needed, the selection of an agent depends on the clinical syndrome, the severity of infection, the susceptibility pattern of the organism (if known), and patient drug intolerances and comorbidities. M. catarrhalis is generally susceptible to the following antibiotics or antibiotic classes [39,49,104]:
●Trimethoprim-sulfamethoxazole
●Cephalosporins
●Macrolides
●Tetracyclines
●Fluoroquinolones
Selecting among these agents based on individual patient characteristics is a reasonable approach to treatment. However, it should be noted that resistance to macrolides and tetracyclines has been reported in Asia. Although M. catarrhalis is also routinely susceptible to piperacillin, ticarcillin, and aminoglycosides, most M. catarrhalis infections do not require intravenous antibiotics [49].
Nearly all strains of M. catarrhalis produce beta-lactamase and are resistant to penicillin, ampicillin, and amoxicillin [105-108]. M. catarrhalis is also resistant to clindamycin and vancomycin [49]. These agents should not be used for treatment.
PREVENTION — No vaccines are commercially available. However, several candidate vaccines are in development [13,53,109-112].
SUMMARY AND RECOMMENDATIONS
●Microbiology and epidemiology – Moraxella catarrhalis is a gram-negative diplococcus that commonly colonizes and infects the respiratory tract. Rates of infection with M. catarrhalis are rising due to the widespread use of pneumococcal vaccinations, which alter the respiratory tract microbiome. (See 'Epidemiology' above and 'Introduction' above.)
●Clinical manifestations – The most common clinical manifestations of M. catarrhalis infections are acute otitis media in children, acute exacerbations of chronic obstructive pulmonary disease (COPD) in adults, and acute rhinosinusitis. Less common manifestations include pneumonia and bacteremia. Other invasive infections are rare. (See 'Clinical manifestations' above.)
●Seasonality – There are no characteristic clinical features that distinguish infections caused by M. catarrhalis from other bacterial pathogens, although M. catarrhalis tends to be more common in late fall to early spring compared with other times of the year. (See 'Clinical manifestations' above and 'Differential diagnosis' above.)
●Diagnosis
•The most common infections caused by M. catarrhalis are diagnosed clinically. Microbiologic diagnosis can be made by culture but is not routinely performed because testing can be invasive (eg, tympanocentesis for otitis media); treatment is empiric, and results usually do not change management. (See 'Clinical diagnosis' above.)
•Pursuing a microbiologic diagnosis is generally reserved for patients with acute or recurrent otitis media or acute bacterial rhinosinusitis who have failed empiric antibiotic therapy, patients with severe COPD exacerbations, or patients who may otherwise benefit from directed antibiotic therapy. (See 'Microbiologic diagnosis' above.)
●Antibiotic treatment
•Antibiotic treatment for most cases of acute otitis media, acute COPD exacerbations, and acute bacterial rhinosinusitis is empiric. (See 'Treatment' above.)
•When directed therapy for M. catarrhalis is needed, the selection of an agent depends on the site and severity of infection, the susceptibility pattern of the organism, and patient drug intolerances and comorbidities. (See 'Treatment' above.)
-M. catarrhalis is generally susceptible to amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, extended-spectrum cephalosporins, macrolides, tetracyclines, and fluoroquinolones, although resistance to macrolides and tetracyclines has been reported in Asia.
-Most M. catarrhalis strains are resistant to penicillin, amoxicillin, ampicillin, vancomycin, and clindamycin.
●Prevention – No vaccines targeting M. catarrhalis are commercially available. However, several candidate vaccines are in development. (See 'Prevention' above.)
ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.
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