The Other Siblings: Respiratory Infections Caused by Moraxella catarrhalis and Haemophilus influenzae Larry Lutwick, MD, and Laila Fernandes, MD Corresponding author Moraxella catarrhalis Larry Lutwick, MD Infectious Diseases (IIIE), VA Medical Center, 800 Poly Place, Bacteriology Brooklyn, NY 11219, USA. M. catarrhalis is a Gram negative, aerobic diplococcus E-mail: [email protected] that was initially described by Anton Ghon and Rich- Current Infectious Disease Reports 2006, 8:215–221 ard Pfeiffer as Micrococcus catarrhalis at the end of the Current Science Inc. ISSN 1523-3847 19th century. For most of the first century of its rec- Copyright © 2006 by Current Science Inc. ognition, M. catarrhalis is considered to be a human mucosal commensal organism based on its common finding as an inhabitant of the oropharynx of healthy Respiratory infections remain substantial causes of mor- adults. During a significant amount of this time, based bidity and mortality globally. In this paper, two substantial on phenotypic characteristics as well as microbiologic players in bacterial-associated respiratory disease are colony appearances, the diplococcus was referred to assessed as to their respective roles in children and adults as Neisseria catarrhalis. Of note, in 1963, N. catarrhalis and in the developed and developing world. Moraxella was found to contain two distinct species, catarrhalis catarrhalis, although initially thought to be a nonpathogen, and cinerea [1]. continues to emerge as a cause of upper respiratory Reclassification of the genus of this microorganism disease in children and pneumonia in adults. No vaccine occurred in 1970 when significant phylogenetic dispari- is currently available to prevent M. catarrhalis infection. ties between N. catarrhalis and the generally considered Haemophilus influenzae type b, originally thought to be the “true” Neisseria species (such the meningococcus and cause of influenza, has now been limited epidemiologically gonococcus) were elucidated. These findings resulted in in the developed world due to an effective immunization the movement of the organism into the newly created but it continues to be a major player in the developing genus of Branhamella [2]. This genus was to honor Sara world. Nonencapsulated strains of H. influenzae still Branham whose pioneering work on N. meningitidis and remain as significant causes of respiratory infections in influenza virus helped introduce the importance of the the developing world especially in exacerbation of chronic bacteriology into public health. obstructive lung disease. Finally, and in brief, the spectrum Fourteen years later, the taxonomy of this organism of Brazilian purpuric fever due to a specific biotype of (neé Micrococcus) changed once more with its reassign- H. influenzae is discussed. ment into the genus Moraxella [3] based on DNA-DNA hybridization, rRNA-DNA hybridization, and 16S ribosomal DNA sequence and cell wall fatty acid com- Introduction parisons. This genus therefore contained the diplococcus Certainly Streptococcus pneumoniae is recognized as the “big M. catarrhalis and other moraxellae such as osloensis that brother” of respiratory infections, especially pneumonia. is bacillary in shape. Many other pyogenic bacteria like the pneumococcus, In blood agar, the organism produces nonhemolytic, however, are primary respiratory pathogens. This paper round, opaque, grayish-white colonies that remain intact addresses two of the other major bacterial causes of respi- when pushed across the surface of the agar [4••]. On Gram ratory infections throughout the world after Streptococcus stain, M. catarrhalis appears as a standard Neisseria organ- pneumoniae, Moraxella catarrhalis and Haemophilus influenzae, ism does, as a Gram negative diplococcus with adjacent the other siblings in the respiratory infection family. flattened sides. In addition to being oxidase positive, the 216 Pleuropulmonary and Bronchial Infections organism is generally DNase, nitrate and nitrite reduction, nary respiratory involvement with this organism has been and tributyrin hydrolysis positive [4••]. described. Not only cases of sinusitis and otitis media have been described in children [4••], but also the diplococcus Carriage has been linked to cases of laryngitis and tracheobronchitis, An inverse relationship between age and healthy carriage the latter often associated with an exacerbation of chronic rate is found with this organism. Up to 75% of children obstructive pulmonary disease (COPD). can be colonized with M. catarrhalis [4••] whereas the An association of laryngitis in the adult with Morax- carriage rate in healthy adults is generally regarded to ella has been made by Hol et al. [14] in the Netherlands. be 1% to 5% [4••,5••]. Carriage rates of the organism The group had previous observed that the organism appear to be higher during the fall and winter months. could be isolated from more than 50% of 40 cases of lar- Murphy [5••] states that colonization rates appear to be yngitis and none of 40 controls but it was not clear if the higher in adults with chronic respiratory diseases. This organism had a pathogenic role in the disease. The find- asymptomatic carriage appears to be a dynamic one with ing that the laryngitis isolates had a higher proportion individuals eliminating one strain and then acquiring a (57%) of complement-resistant strains than did carrier genetically distinct strain later. strains from healthy 8- to 13-year-old school children (16%) with a P < 0.001 the finding of complement-resis- Respiratory disease in childhood tant (virulence-associated) phenotype in adults with As has been recognized to be the case with meningococcal acute laryngitis supports the theory of an active role of disease, pediatric longitudinal studies have revealed M. catarrhalis in the pathogenesis of acute laryngitis. that newly acquired nasopharyngeal colonization with Just as the pneumococcus and H. influenzae (especially a strain of M. catarrhalis precedes the development of nontypeable strains) have been associated with acute exac- infection due to this strain [6]. Systemic infections such erbations of COPD with increasing amount and purulence as meningitis and/or bacteremia do occur (especially in of respiratory secretions, M. catarrhalis is now linked as the immunoincompetent individual [7] but are rare. In well. Murphy [5••] presents a number of lines of evidence cases of bacteremia as many as 50% of them may develop to link this organism to COPD exacerbations: a rash which can resemble that in meningococcemia [8]. Most cases of M. catarrhalis infection in children are 1. Some patients with exacerbations of COPD will represented by upper respiratory infections such as otitis have Gram stains of the expectorated sputum media, bacterial sinusitis, and bronchitis/tracheitis. revealing the predominant organism being a Gram Bacteriologically, Moraxella accounts for about 20% negative kidney bean-shaped diplococcus with of acute or subacute sinus infections in children with significant growth of the organism upon culture. Haemophilus influenzae also causing 20% and Streptococcus 2. Pure cultures of the organism have been pneumoniae 40% [9]. Similar numbers have been generated obtained in some cases of exacerbation in secre- for pediatric otitis media [10]. Verduin et al. [4••] suggest tions obtained through transtracheal aspiration that the incidence of M. catarrhalis causing these infec- to avoid the contamination of oral flora. tions may well be higher as it is not easily isolated from 3. Improvement of symptoms may occur only when, relatively low redox potential (anaerobic) environments. since most M. catarrhalis strains produce a beta- Studies have been published that suggest that the severity lactamase, antimicrobial treatment is modified to of symptoms and the bacterial load in the middle ear fluid a drug resistant to bacterial beta-lactamase. are lower for Moraxella infections as compared with the 4.. Antibodies may develop to the homologous strain other common bacterial causes of otitis media [11]. of the organism that was isolated during the event. Bacterial pneumonia due to this organism has been felt to be relatively uncommon with most of them Pneumonia due to this organism certainly appears occurring in pediatric patients younger than 1 year of to be more common in the elderly than in the pediat- age [12]. The co-morbidity of bronchopulmonary dys- ric cohort. One study from Belgium done prospectively plasia appears to be a predisposing problem in pediatric regarding community-acquired pneumonia in the elderly M. catarrhalis pneumonia [13]. Although uncommon reported that 8% of pneumonias in those older than 60 in most studies, good documentation of the diagnosis years of age were caused by this diplococcus [15]. The has been made by the isolation of the organism in pure same group reported that the asymptomatic carriage rate culture from tracheal aspirates as well as finding the appeared to increase in those older than 60 years of age organism in blood culture. to about 25% from 5% in those adults younger than 60 years of age. Most of the older individuals who develop Respiratory disease in adults M. catarrhalis pneumonia have, as many with other Although occasional extrarespiratory infections with bacterial pneumonias, significant co-morbidities [16,17]. M. catarrhalis occur in the adult including endocarditis, most These cofactors include COPD, congestive heart failure, and infections are related to the respiratory system. Nonpulmo- diabetes mellitus. In the