Moraxella catarrhalis is a gram-negative, aerobic, oxidase-positive diplococcus that was first described in 1896. The organism has also been known as Micrococcus catarrhalis, Neisseria catarrhalis, and Branhamella catarrhalis; currently, it is considered to belong to the subgenus Branhamella of the genus Moraxella. For most of the 20th century, M catarrhalis was considered a saprophyte of the upper respiratory tract that was associated with no significant pathogenic consequences.
Various diagnostic studies and procedures may be warranted, depending on the site of the infection and underlying conditions. Confirmation of the diagnosis of M catarrhalis infection is based on culture. Any of a number of antimicrobial drugs may be used to treat M catarrhalis infection, depending on the need for use of oral or parenteral medication, the age of the patient, any underlying conditions present, the sensitivity of the organism, and the desired spectrum of coverage.
Studies have shown that M catarrhalis colonizes the upper respiratory tract in 28-100% of humans in the first year of life. In adults, the colonization rate is 1-10.4%. Colonization appears to be an ongoing process with an elimination-colonization turnover of various strains. Transmission is believed to be due to direct contact with contaminated secretions by droplets.
The endotoxin of M catarrhalis, a lipopolysaccharide similar to those found in Neisseria species, may play a role in the disease process. Some strains of M catarrhalis have pili or fimbriae, which may facilitate adherence to the respiratory epithelium. Some strains produce a protein that confers resistance to complement by interfering with the formation of the membrane attack complex. M catarrhalis also expresses specific proteins for iron uptake that act as receptors for transferrin and lactoferrin.
M catarrhalis has been shown to have increased cell adhesion and proinflammatory responses when cold shock (26°C for 3 hours) occurs. Physiologically, this may occur with prolonged exposure to cold air temperatures, resulting in coldlike symptoms.[1]
Humoral responses against M catarrhalis appear to be age-dependent, with the titer of immunoglobulin G (IgG) gradually increasing in children. Antibody responses to outer-membrane proteins have been obtained, predominantly in the IgG3 subclass.
Although the commensal status of M catarrhalis in the nasopharynx is still accepted, the organism is a common cause of otitis media and sinusitis and an occasional cause of laryngitis. M catarrhalis causes bronchitis and pneumonia in children and adults with underlying chronic lung disease and is occasionally a cause of bacteremia and meningitis, especially in immunocompromised persons. Bacteremia can be complicated by local infections, such as osteomyelitis or septic arthritis. M catarrhalis is also associated with nosocomial infections.
M catarrhalis is the third most common cause of otitis media and sinusitis in children (after Streptococcus pneumoniae and Haemophilus influenzae). M catarrhalis is estimated to be responsible for 3-4 million cases of otitis media annually, with an associated health care cost (direct and indirect) of $2 billion each year.
M catarrhalis infections may occur at any age. Although colonization is more common in children, only a small percentage of positive cultures findings have clinical significance in the pediatric population. In one study, 9% of cultures positive for M catarrhalis in children younger than 5 years and 33% of isolates from children aged 6-10 years were found to be clinically significant. However, all cultures positive for M catarrhalis had clinical importance in adults.
In one study involving adult patients, the male-to-female ratio was 1.6:1.
The prognosis of M catarrhalis infection is poor in hospitalized patients with underlying conditions, especially the following:
The most significant infections caused by M catarrhalis are upper respiratory tract infections (URTIs) such as otitis media and sinusitis in children and lower respiratory tract infections (LRTIs) in adults. Infections with M catarrhalis in adults are more common if underlying conditions are present, especially if the patient is elderly. In a study of 42 cases of pneumonia with M catarrhalis isolated as the single agent in sputum cultures, the mortality rate attributable to the underlying problems within 3 months of pneumonia was 45%.[2]
The history typically suggests the type of infection present (eg, upper respiratory tract infection [URTI], lower respiratory tract infection [LRTI], bacteremia, or endocarditis). Physical findings in M catarrhalis infections are similar to findings of infections with other organisms in the same location.
In 29% of common-cold episodes due to bacterial pathogens (including M catarrhalis), affected children continued to be symptomatic 10 days after the first appearance of symptoms.[3]
A clinical history of acute otitis media and otitis media with effusion with symptoms includes otalgia, fever, and hearing loss. Otitis media is a very common condition, especially in children. Approximately 70% of children experience at least 1 episode of otitis media during childhood. M catarrhalis has been isolated in 3-17.3% of middle ear exudates in children with otitis media.[4, 5]
In a patient with sinusitis, the clinical history commonly includes headache, pain in the maxillary or frontal area, fever, and cough. Young children present with persistent nasal discharge (lasting longer than 2 weeks) and cough, especially at night. M catarrhalis has been isolated in 22% of maxillary sinus aspirates in children as a single pathogen and in 72% of aspirates in combination with other organisms (eg, S pneumoniae or H influenzae).[6]
In adult patients who have a history of conditions such as chronic obstructive pulmonary disease (COPD), pneumoconiosis, asthma, malignancies, or immunosuppression and who show findings characteristic of bronchitis or pneumonia or exacerbations of their underlying condition, M catarrhalis infection is a possibility. M catarrhalis LRTI is also associated with smoking. M catarrhalis is isolated from sputum and transtracheal aspirate specimens at rates of 0.2-8.1%, accompanied by H influenzae and/or S pneumoniae in more than 30% of cases.[7, 8, 9, 10]
In children, LRTIs have been associated with a history of recent respiratory syncytial virus or cytomegalovirus infection or with more debilitating conditions, such as bronchopulmonary dysplasia, ventricular septal defect, leukemia, Arnold-Chiari syndrome, prematurity, or HIV infection.[11, 12]
Outbreaks of nosocomial infections with M catarrhalis have been reported, mostly involving pulmonary units or pediatric intensive care units (PICUs).
In 46% of patients with M catarrhalis bacteremia, no primary site of infection is found. Bacteremia is rare with M catarrhalis community-acquired pneumonia.[13] The following conditions have been found to predispose to M catarrhalis bacteremia:
M catarrhalis endocarditis has been described in patients with a history of valvular conditions or prostheses, as well as in patients who were previously healthy. It has also been described as a complication of balloon angioplasty.[14, 15] M catarrhalis has been identified as a pathogen in cleft palate repairs (resulting in a higher fistula rate).[16] Sporadic cases of other infections with M catarrhalis include the following:
Complications of M catarrhalis infection may include the following:
A complete blood count (CBC) should be obtained. An increased white blood cell (WBC) count with neutrophilia may be present.
Gram-negative diplococci are found on Gram staining of cultures. Strict adherence to the staining protocol is required. The accuracy of Gram staining for isolation of Neisseria or Moraxella species has been reported to agree perfectly with identification by culture.[19]
Confirmation of the diagnosis of M catarrhalis infection is based on isolation of the organism in culture. Cultures can be taken from middle ear effusion, the nasopharynx, sputum, sinus aspirates, transtracheal or transbronchial aspirates, blood, peritoneal fluid, wounds, or urine. Colonies are approximately 0.2 cm in diameter, opaque, and nonhemolytic after incubation on chocolate or blood agar for 48 hours. Characteristically, colonies can be pushed along the surface of the agar like a hockey puck.
With standard methods of identification, M catarrhalis can be differentiated from Neisseria species by not using sucrose, glucose, maltose, and lactose. Because Neisseria cinerea exhibits the same reaction pattern, the Superoxyl test must be added. For definitive identification, deoxyribonuclease (DNase) and nitrate reduction tests are performed; M catarrhalis produces DNase and reduces nitrate and nitrite levels.
Several rapid confirmatory tests are available to identify M catarrhalis, and they are all based on the ability of M catarrhalis to hydrolyze tributyrin. This provides immediate identification and separation from human Neisseria species, which do not hydrolyze tributyrin.
Serologic tests for infections with M catarrhalis are not widely used; cross-reactivity with Neisseria species in the detection of complement fixation antibodies by immunoelectrophoresis has been demonstrated. Serum antibodies to whole-cell proteins, to lipo-oligosaccharides, and to outer-membrane antigens have proved useful in the diagnosis of M catarrhalis infection. Other laboratory studies may be needed, depending on the site of infection and underlying conditions.
Imaging studies (eg, plain radiography or computed tomography [CT]) may be needed, depending on the site of infection.
Paranasal sinus radiography or CT scanning may be helpful. Chest radiography is often performed. If peritonitis is a possibility, abdominal radiography using a 3-way view is indicated.
Medical management of M catarrhalis infection depends on the infection site, age of the patient, underlying condition(s), and severity of the disease.
Consultation with an ear, nose, and throat specialist may be indicated in recurrent cases of otitis or sinusitis. Consultation with an infectious disease specialist is recommended for infections that do not respond to antibiotic treatment, infections in patients with underlying debilitating conditions, systemic infections with M catarrhalis, or infections in unusual locations.
Follow-up care with the patient’s primary care physician is highly recommended. Worsening symptoms warrant a return visit to the primary care physician.
Any of a number of antimicrobial drugs may be used to treat M catarrhalis infection, depending on the need for use of oral or parenteral medication, the age of the patient, any underlying conditions present, the sensitivity of the organism, and the desired spectrum of coverage.
Approximately 95% of M catarrhalis strains isolated in the United States produce beta-lactamase. Antibiotics such as penicillin, amoxicillin, and ampicillin are only effective against strains that do not produce beta-lactamase.
Amoxicillin-clavulanate, second- and third-generation oral cephalosporins, and trimethoprim-sulfamethoxazole (TMP-SMZ) are the most recommended agents. Alternatively, azithromycin or clarithromycin can be used. More than 90% of M catarrhalis strains have been shown to resist amoxicillin, and these rates vary by region.[20]
In one study, topical use of ciprofloxacin/dexamethasone for treatment of acute otitis media with otorrhea via tympanostomy tubes was found to have similar efficacy to that of topical use of ofloxacin in M catarrhalis infections.[21]
In another study, treatment with oral azithromycin 500 mg once daily for 3 days was found to be comparable with a 10-day regimen of oral clarithromycin 500 mg twice daily for the treatment of acute exacerbation of chronic bronchitis.[22]
Telithromycin, a ketolide derivative of erythromycin A, demonstrated good in vitro activity against M catarrhalis in a study of patients with acute exacerbations of chronic bronchitis.[23] However, severe liver disease associated with telithromycin use has been reported.[24] Note that telithromycin is not indicated for use in patients with myasthenia gravis.
Moxifloxacin, a quinolone, was found to be an effective treatment of M catarrhalis– associated community-acquired pneumonia in a dosage of 400 mg/day.[25]
Universal precautions, good hand-washing technique, and sterilization of instruments and tubes used in intubations, aspiration, or invasive procedures may reduce or prevent the nosocomial infections caused by M catarrhalis. Cessation of smoking and prevention of passive smoking may reduce M catarrhalis infections. Good general health habits (eg, proper rest, exercise, and diet) are helpful as well.
Research is under way to create a vaccine to prevent M catarrhalis infections.[26, 27] It is projected that 4.2 million episodes of otitis media would be prevented by a combined pneumococcal-nontypeable H influenzae–Moraxella vaccine.[28]
Various antimicrobial drugs may be used to treat Moraxella catarrhalis infection. Therapy should cover likely pathogens in the context of this clinical setting. Nearly all M catarrhalis strains produce beta-lactamase.
Clinical Context: Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It has the added advantage of exerting good anti-inflammatory activity by inhibiting migration of polymorphonuclear leukocytes (PMNs) Erythromycin is used for treatment of staphylococcal and streptococcal infections.
The recommended dosing schedule of erythromycin may result in gastrointestinal (GI) upset, warranting a switch to an alternative macrolide or to thrice-daily dosing. This agent covers most potential etiologic agents, including Mycoplasma species.
Although a 10-day treatment course seems to be standard, treating until the patient has been afebrile for 3-5 days seems a more rational approach. In children, age, weight, and severity of infection determine proper dosage. When twice-daily dosing is desired, half of the total daily dose may be taken every 12 hours. For more severe infections, double the dose.
Clinical Context: Azithromycin treats mild-to-moderate microbial infections.
Clinical Context: Clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Clinical Context: Cefaclor is a second-generation cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. Determine the proper dosage and route on the basis of the condition of the patient, severity of the infection, and susceptibility of the causative organism.
Clinical Context: Cefprozil binds to 1 or more of the penicillin-binding proteins (PBPs), thereby inhibiting cell-wall synthesis and resulting in bactericidal activity.
Clinical Context: Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of the first-generation cephalosporins while adding activity against Proteus mirabilis, H influenzae, Escherichia coli, Klebsiella pneumoniae, and M catarrhalis. The condition of the patient, severity of the infection, and susceptibility of the microorganism determine the proper dose.
Clinical Context: TMP-SMX inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Its antibacterial activity includes common urinary tract pathogens, except Pseudomonas aeruginosa.
Clinical Context: Cefotaxime is used for treatment of bloodstream infection and gynecologic infections caused by susceptible organisms. It arrests bacterial cell wall synthesis, thereby inhibiting bacterial growth. It is a third-generation cephalosporin with a gram-negative spectrum; it is less efficacious against gram-positive organisms.
Clinical Context: Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more PBPs.
Clinical Context: Ceftazidime is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftazidime arrests bacterial growth by binding to 1 or more PBPs. Its gram-negative spectrum includes M catarrhalis. Dosage depends on the severity of infection and the susceptibility of the organism.
Clinical Context: Ciprofloxacin is a fluoroquinolone with activity against most gram-negative organisms but no activity against anaerobes. It inhibits bacterial DNA synthesis and consequently growth.
Clinical Context: Levofloxacin is used for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Clinical Context: Moxifloxacin inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.
Amoxicillin-clavulanate, second- and third-generation oral cephalosporins, and trimethoprim-sulfamethoxazole (TMP-SMZ) are the most recommended agents. Alternatively, azithromycin or clarithromycin can be used. All other agents listed below are also effective.