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Infectious bovine keratoconjunctivitis: isolation of Moraxella bovis from two groups of young beef cattle in fly control field trials during 1981.

The rate of infection with Moraxella bovis was determined for two herds of calves during the course of a year. High infection rates with the haemolytic variant were found in the herds while they were housed during their first winter but this infection rate fell steadily after turnout. A rise in infections with the non-haemolytic variant was observed during this time. The animals remained free from clinical infectious bovine keratoconjunctivitis during the summer, unlike similar groups of animals in previous years. Immunity, weather and flies are considered for their possible relevance to this observation.

Animals↗

Evidence for the existence of endotoxic activity in three strains of Moraxella.

The phenol extraction technique was used to obtain material with endotoxic activityfrom three strains of Moraxella. This material was subjected to partial purification. Biological activity was determined by inoculation of the extracts into the skinof rabbits, and noting the resultant skin reactions. Although containing some cellular contaminants such as nucleic acid from the extraction procedure, the endotin preparations showed biological activity in the microgram range. Killed but unextracted cellsalso elicited skil reactions when injected intradermally into the rabbit. A partial analysis of the biochemical components of the endotoxin revealed that these three strains contain endotoxin whose composition is similar in several respects to that of the endotoxins of the neisseriae and some of the enteric bacteria.

Animals↗

Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-kappaB activation and histone deacetylase activity reduction.

Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease (COPD) and may also contribute to the pathogenesis of COPD. Little is known about M. catarrhalis-bronchial epithelium interaction. We investigated activation of M. catarrhalis infected bronchial epithelial cells and characterized the signal transduction pathways. Moreover, we tested the hypothesis that the M. catarrhalis-induced cytokine expression is regulated by acetylation of histone residues and controlled by histone deacetylase activity (HDAC). We demonstrated that M. catarrhalis induced a strong time- and dose-dependent inflammatory response in the bronchial epithelial cell line (BEAS-2B), characterized by the release of IL-8 and GM-CSF. For this cytokine liberation activation of the ERK and p38 mitogen-activated protein (MAP) kinases and transcription factor NF-kappaB was required. Furthermore, M. catarrhalis-infected bronchial epithelial cells showed an enhanced acetylation of histone H3 and H4 globally and at the promoter of the il8 gene. Preventing histone deacetylation by the histone deacetylase inhibitor trichostatin A augmented the M. catarrhalis-induced IL-8 response. After exposure to M. catarrhalis, we found a decrease in global histone deacetylase expression and activity. Our findings suggest that M. catarrhalis-induced activation of il8 gene transcription was caused by interference with epigenetic mechanisms regulating il8 gene accessibility. Our findings provide insight into important molecular and cellular mechanisms of M. catarrhalis-induced activation of human bronchial epithelium.

Bronchi↗

Studies on haemagglutination and serum resistance status of strains of Moraxella catarrhalis isolated from the elderly.

A total of 40 strains of Moraxella catarrhalis, isolated from the sputum of elderly persons with respiratory tract infections and from nasopharyngeal swabs from healthy elderly, were examined for haemagglutination of human red blood cells and resistance to bactericidal activity in normal human serum (NHS). 15 of 20 strains isolated from the infected elderly and 3 of 20 strains isolated from the healthy elderly showed haemagglutinating properties (p < 0.001). Similarly, 13 of 20 strains from the infected group and 2 of 20 strains from the healthy group were found to be resistant to the bactericidal activity of NHS (p < 0.001). Strains of M. catarrhalis which were associated with respiratory tract infections in the elderly, in contrast to strains colonizing the healthy elderly, were found to be predominantly haemagglutinating for human red blood cells and resistant to complement killing in NHS.

Adult↗

Killing rate and growth rate comparison for newer beta-lactamase-stable oral beta-lactams against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

A new method of data presentation that takes into account the relationship between growth and killing rate was used to evaluate the comparative in vitro bactericidal activity of cefpodoxime, cefuroxime, cefixime and an amoxicillin/clavulanic acid combination against Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis. For each strain, the viable count decrease (log CFU/ml) after 6 h of exposure to different antibiotic concentrations was plotted against the viable count increase in the control culture, over the same time. Higher killing rates than those predicted by growth rates were defined as a positive balance; lower rates than those predicted by growth rates were defined as a negative balance. The activity of the 4 drugs against S. pneumoniae and M. catarrhalis was characterized by a positive balance. Conversely, the 3 cephalosporins showed a negative balance for H. influenzae.

Anti-Bacterial Agents↗

Antibacterial activity of cefixime against Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae in the presence of Moraxella (Branhamella) catarrhalis.

We measured the sizes of the inhibition zones of oral beta-lactam antibiotics for Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae in the presence of beta-lactamase-producing-Moraxella (Branhamella) catarrhalis by the agar double-layer method. The sizes of the zones of amoxicillin for S. pneumoniae alone were the largest, followed in a descending order by those of cefixime and cefaclor. In the presence of 10(7) CFU/ml of M.(B.) catarrhalis, however, significant reduction of the sizes of the zones was seen with amoxicillin and cefaclor; inhibition with cefixime was nearly unchanged. Similar results were observed in those for S. pyogenes. These variable findings were attributed to the difference in stability of these drugs to the beta-lactamase produced by M.(B.) catarrhalis. When the susceptibility of H. influenzae in the presence of 10(8) CFU/ml of M.(B.) catarrhalis to cefixime, cefoteram, cefpodoxime, cefotiam and cefuroxime was examined, the sizes of the inhibition zones of all the drugs were reduced by the presence of 10(8) CFU/ml of M.(B.) catarrhalis, but those of cefixime were the largest of all the drugs tested. Our agar double-layer method is simple and useful for evaluating the influence of beta-lactamase-producing organism, as M.(B.) catarrhalis, on the disk susceptibility of other pathogens to antibiotics.

Cefixime↗

In vitro activity of a new broad-spectrum, beta-lactamase-stable oral cephalosporin, cefixime, in comparison with other drugs, against Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pneumoniae.

Cefixime, a new orally absorbed iminomethoxyaminothiazolyl cephalosporin, was tested against some microorganisms involved in upper and lower respiratory tract infections such as Haemophilus (influenzae and parainfluenzae), Moraxella catarrhalis and Streptococcus pneumoniae, isolated in the period from November 1990 to April 1991. Its activity was compared to nine other antimicrobial agents: erythromycin, trimethoprim-sulfamethoxazole, ampicillin, amoxicillin-clavulanate, cefaclor, ceftazidime, ceftriaxone, cefotaxime and ofloxacin. Cefixime inhibits 90% of S. pneumoniae, H. influenzae and H. parainfluenzae, both beta-lactamase producers (BLP) or not (NBLP) at concentrations of less than 0.25 mg/l. It inhibits 90% of M. catarrhalis (BLP and NBLP) at concentrations of less than 1 mg/l. In general, cefixime has a superior in vitro activity with respect to cefaclor and the other cephalosporins as well as erythromycin and amoxicillin (the last one in BLP strains). In the evaluation of the antibacterial activity of beta-lactam against Haemophilus and M. catarrhalis, the authors observed different indications in the guidelines for ampicillin. Cefixime is not destroyed by the plasmid-mediated beta-lactamase produced by Haemophilus sp. and M. catarrhalis (TEM and ROB in Haemophilus strains and BRO in M. catarrhalis). In view of its excellent in vitro activity against the commonly encountered respiratory tract pathogens, cefixime is indicated in the therapy of these infections.

Administration, Oral↗

Characterization of BRO enzymes and beta-lactamase transfer of Moraxella (Branhamella) catarrhalis isolated in Japan.

Of the 68 strains of beta-lactamase-producing Moraxella (Branhamella) catarrhalis isolated in Japan that were studied, 62 (91%) produced the BRO-1-type beta-lactamase and 6 (9%) produced the BRO-2 type. There were no strains containing the BRO-3-type beta-lactamase. We compared the susceptibility of BRO-1- and BRO-2-producing strains to various oral beta-lactam antibiotics. We found that the BRO-1-producing strains were less susceptible than the BRO-2-producing strains. Although the BRO-1 and BRO-2 types showed a similar hydrolysis pattern, the specific activity of BRO-1 was 3-fold that of BRO-2. We examined the transfer of the BRO-1 and BRO-2 genes to non-beta-lactamase-producing M. catarrhalis No. 4020 and found that of the 13 donor strains producing BRO-1, 11 (85%) were able to transfer the gene for BRO-1 production by conjugation. Of the 6 donor strains producing BRO-2, 2 (33%) were able to transfer the gene for BRO-2 production by conjugation. For 3 of the 13 (23%) BRO-1-producing strains and 1 of the 6 (17%) BRO-2-producing strains, about 13 Mdalton of plasmids were detected. These plasmid-containing strains were used as donors, and in beta-lactamase-producing transconjugants the same size of plasmids was detected. However, when the total DNA is extracted from strains with the ability to transfer by conjugation, the transformation of the beta-lactamase-producing gene can occur regardless of the presence or absence of plasmids. Furthermore, even if purified plasmids are transformed, beta-lactamase-producing transformants are not obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Conjugation, Genetic↗

Antibiotic resistance patterns of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: a prospective study in Murcia, Spain, 1983-1992.

We prospectively determined the role of commonly used antibiotics in the emergence of antimicrobial resistance among the predominant pathogens associated with the respiratory tract. Clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from otic exudates, exudates obtained by puncture of the paranasal sinuses, sputum samples or blood cultures obtained from hospital inpatients with symptoms of significant upper or lower respiratory tract infection were analyzed. Between 1983 and 1992 a statistically significant increase in strains of S. pneumoniae and H. influenzae resistant to ampicillin, erythromycin and co-trimoxazole was detected. A significant increase in strains of M. catarrhalis resistant to ampicillin was also found. The increase in the consumption of aminopenicillins, co-trimoxazole and macrolides was associated with an increase in strains of S. pneumoniae, H. influenzae and M. catarrhalis resistant to these agents.

Ampicillin Resistance↗

Susceptibility of Moraxella catarrhalis to 21 antimicrobial drugs: validity of current NCCLS criteria for the interpretation of agar disk diffusion antibiograms.

Ninety-four clinical isolates of Moraxella catarrhalis were examined for susceptibility to 21 antimicrobial drugs; 67 isolates (= 71.3%) produced beta-lactamase(s). In terms of antibiotic resistance, the number of isolates resistant to penicillin G, ampicillin, and cotrimoxazole were 56, 32, and 1, respectively. The number of isolates with intermediate susceptibility to penicillin G, ampicillin, ciprofloxacin, ofloxacin, cotrimoxazole, and fosfomycin were 11, 34, 1, 2, 2, and 47, respectively. All 94 isolates proved susceptible to ampicillin + 10 micrograms/ml of sulbactam, amoxicillin + 4 micrograms/ml of clavulanic acid, cefuroxime, cefotaxime, cefepime, cefepime, cefixime, imipenem, meropenem, chloramphenicol, doxycycline, tetracycline, fusidic acid, erythromycin, clarithromycin, and rifampin, as based on currently valid NCCLS criteria, where applicable. There were no very major or major discrepancies between agar dilution and agar disk diffusion test results. There were only a few minor discrepancies between test results, specifically: penicillin G (category IV = 4, category VI = 1); ampicillin (category IV = 4, category V = 1, category VI = 7), amoxicillin + clavulanic acid (category III = 11), cotrimoxazole (category IV = 1, category V = 1, category VI = 1), ciprofloxacin (category V = 1), and ofloxacin (category VI = 2). The sole exception was fosfomycin, with a total of 25 minor discrepancies encountered (category III = 14, category V = 9, category VI = 2). Wilkins-Chalgren agar compared favorably with Mueller-Hinton agar following examination with 11 selected antimicrobial drugs against 31 representative isolates of M. catarrhalis.

Anti-Bacterial Agents↗

Moraxella catarrhalis in chronic obstructive pulmonary disease: burden of disease and immune response.

RATIONALE: Moraxella catarrhalis is frequently present in the sputum of adults with chronic obstructive pulmonary disease (COPD). Little is known about the role of M. catarrhalis in this common disease. OBJECTIVE: To elucidate the burden of disease, the dynamics of carriage, and immune responses to M. catarrhalis in COPD. METHODS: Prospective cohort study of 104 adults with COPD in an outpatient clinic at the Buffalo Veterans Affairs Medical Center. MEASUREMENTS: Clinical information, sputum cultures, molecular typing of isolates, and immunoassays to measure antibodies to M. catarrhalis. MAIN RESULTS: Over 81 months, 104 patients made 3,009 clinic visits, 560 during exacerbations. Molecular typing identified 120 episodes of acquisition and clearance of M. catarrhalis in 50 patients; 57 (47.5%) of the acquisitions were associated with clinical exacerbations. No instances of simultaneous acquisition of a new strain of another pathogen were observed. The duration of carriage of M. catarrhalis was shorter with exacerbations compared with asymptomatic colonization (median, 31.0 vs. 40.4 days; p = 0.01). Reacquisition of the same strain was rare. The intensity of the serum IgG response was greater after exacerbations than asymptomatic colonization (p = 0.009). Asymptomatic colonization was associated with a greater frequency of a sputum IgA response than exacerbation (p = 0.009). CONCLUSIONS: M. catarrhalis likely causes approximately 10% of exacerbations of COPD, accounting for approximately 2 to 4 million episodes annually. The organism is cleared efficiently after a short duration of carriage. Patients develop strain-specific protection after clearance of M. catarrhalis from the respiratory tract.

Aged↗

Moraxella catarrhalis--infected alveolar epithelium induced monocyte recruitment and oxidative burst.

The recruitment of monocytes appears to be a crucial factor for inflammatory lung disease. Alveolar epithelial cells contribute to monocyte influx into the lung, but their impact on monocyte inflammatory capacity is not entirely clear. We thus analyzed the modulation of monocyte oxidative burst by A549 and isolated human alveolar epithelial cells. Epithelial infection with Moraxella catarrhalis induced monocyte adhesion, transepithelial migration, and superoxide generation, whereas stimulation with lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1beta, or interferon-gamma induced adhesion or transmigration, but failed to initiate monocyte burst. The effect of microbial challenge was mimicked by phorbol myristate acetate and inhibited by the protein kinase C inhibitor bisindoylmaleimide. Furthermore, evidence for a role of platelet-activating factor-signaling in monocytes is presented. Monocyte burst was neither induced by supernatant nor affected by fixation of A549 cells, excluding the contribution of epithelium-derived soluble factors but emphasizing the mandatory role of intercellular contact. The employment of blocking antibodies, however, denied a role for the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, or CD11b/CD18 and CD49d/CD29. In essence, infection of alveolar epithelial cells with M. catarrhalis might amplify the inflammatory capacity of invading monocytes eliciting their superoxide production. The epithelial response to this microbial challenge thus clearly differed from that to proinflammatory cytokines.

Carcinogens↗

Interference of nontypeable Haemophilus influenzae and Moraxella catarrhalis by Streptococcus oralis in adenoid organ culture: a possible strategy for the treatment of the otitis-prone child.

The role of viridans group streptococci (Streptococcus oralis) in the prevention of colonization with nontypeable Haemophilus influenzae and Moraxella catarrhalis was investigated in an adenoid organ culture system. The adenoids from 100 patients who were undergoing adenoidectomy for either hypertrophy or recurrent otitis media were used. Streptococcus oralis Parker uniformly inhibited colonization with nontypeable H. influenzae or M. catarrhalis over a 24-hour period of incubation in adenoid organ culture. Streptococcus oralis Booth, a noninhibitory strain, did not significantly reduce colonization with nontypeable H. influenzae and M. catarrhalis. The results indicate that some strains of S. oralis may inhibit colonization with potential pathogens in the nasopharynx. It is therefore possible that colonization with inhibitory strains of viridans streptococci may be used in the nasopharynx as a relatively safe and inexpensive approach to prevention of recurrent otitis media in some children.

Adenoids↗

Immune response to Moraxella catarrhalis in children with otitis media: opsonophagocytosis with antigen-coated latex beads.

Opsonic antibody activity against Moraxella catarrhalis was determined in sera from children with otitis media. The antibody was determined with a new assay utilizing outer membrane antigen-coated latex beads. Antigen-coated beads opsonized in heat-inactivated pooled human serum phagocytosed 47.5 +/- 36.1 beads per 100 neutrophils compared to 15.6 +/- 10.2 beads per 100 neutrophils opsonized in hypogammaglobulinemic serum (p < .025). Antigen-coated beads opsonized in homologous sera from 11 children with M. catarrhalis otitis media demonstrated increased opsonic activity in convalescent sera (34.6 +/- 27.1) compared to acute sera (15.5 +/- 6.7; p < .05). These data suggest that infection with M catarrhalis is associated with the development of opsonic antibody.

Antigens, Bacterial↗

Experimental otitis media with Moraxella (Branhamella) catarrhalis.

Two hundred fifty gerbils and 7 chinchillas were utilized in 11 experiments to determine the effect of inoculating viable and heat-killed suspensions of Moraxella (Branhamella) catarrhalis into the middle ear cavity. Development of otitis media was observed by otoscopy and histopathology. Gerbils were found to be susceptible to 2 x 10(4) viable M catarrhalis cells. Depending on the number of cells inoculated, the resulting untreated inflammation was a very mild to moderately severe, self-limiting disease with no permanent sequelae except in animals inoculated with high [10(6) to 10(7)] numbers of bacteria. Viable bacteria could not be isolated from the middle ears 24 hours after inflammation was induced. Heat-killed cells produced less severe acute inflammation with no permanent sequelae. We conclude 1) gerbils and chinchillas are susceptible to a self-limited inflammation caused by M catarrhalis, 2) no infection occurs, since viable bacteria cannot be recovered from middle ear aspirates, and 3) viable cells produce more severe inflammation than heat-killed cells.

Animals↗

Moraxella (Branhamella) catarrhalis bacteremia in children. A report of two patients and review of the literature.

We report two cases of Moraxella catarrhalis (M. catarrhalis) bacteremia in apparently healthy children. One patient had bilateral otitis media and the other had pharyngitis and sinusitis; both patients had uncomplicated clinical courses. A literature review revealed 22 reported cases of M. catarrhalis bacteremia in children, 14 (63%) of which occurred in patients who had no identified underlying condition. Eight (36%) cases were seen in children who were immunocompromised. Nine (40%) patients presented with either purpura, petechia, or a maculopapular rash. M. catarrhalis is well known as a respiratory pathogen, but it has not been recognized as a common cause of unsuspected bacteremia in children.

Anti-Bacterial Agents↗

Pathogenesis of corneal lesions caused by Moraxella bovis in gnotobiotic calves.

Moraxella bovis was instilled into the conjunctival sac of gnotobiotic calves and corneas were sampled serially after infection. Lesions developed in seven of eight infected calves, but were absent in a noninfected control calf. Histologically, M. bovis was first seen in foci of swollen epithelium and within basal epithelial cells adjacent to ulcers. Corneal ulcers were severe in later stages of infection; fibrin deposits, neutrophils, and bacteria were present in the stromas. Examination of early lesions by scanning electron microscopy showed M. bovis in pits on the surfaces of dark epithelial cells, enmeshed in degenerate epithelial cells and within erosions and an ulcer; in later samples, bacteria were rare. Ultrastructurally, M. bovis was seen in surface pits in superficial epithelial cell processes and within swollen epithelial cells. In stroma, M. bovis was frequently seen among collagen fibrils, within neutrophil phagosomes, and associated with cellular debris. This study demonstrates that a virulent strain of M. bovis can invade bovine corneal epithelial cells and can cause keratitis in the absence of injurious ultraviolet irradiation or other known predisposing environmental factors.

Animals↗

Conjunctival lesions caused by Moraxella bovis in gnotobiotic calves.

Hemolytic Moraxella bovis was instilled into the conjunctival sac of gnotobiotic calves, and conjunctivae were sampled serially after infection. Bilateral lesions developed in seven of eight infected calves. Histologically, M. bovis was first seen within swollen epithelial cells near the lid margins and occasionally within superficial epithelium in other areas. Conjunctival erosions and ulcers were seen in later stages. Scanning electron microscopy showed M. bovis in pits on surfaces of epithelial cells and in erosions on palpebral conjunctivae; lesions were prominent near lid margins. By transmission electron microscopy, M. bovis was seen within swollen epithelial cells near lid margins; many epithelial cells had undergone cytolysis. This study demonstrates that virulent M. bovis can invade bovine conjunctival epithelial cells and cause conjunctivitis in the absence of injurious ultraviolet irradiation or other predisposing environmental factors.

Animals↗