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PubMed1993

Effect of immunization of pulmonary clearance of Moraxella catarrhalis in an animal model.

A murine model for pulmonary clearance of Moraxella catarrhalis was used to determine whether immunization could enhance clearance of this organism from the lungs. Animals actively immunized with outer membrane vesicles of M. catarrhalis cleared an endobronchial challenge with the homologous strain more quickly than did sham-immunized control animals. Western blot analysis of both this immune mouse serum and rabbit antiserum raised against outer membrane vesicles of M. catarrhalis indicated that antibodies were present to both outer membrane protein and lipooligosaccharide antigens. Passive immunization of mice with the immune rabbit serum resulted in enhanced pulmonary clearance of both homologous and heterologous strains of M. catarrhalis, indicating the involvement of serum antibody in this clearance process and the existence of conserved surface antigens in the two different M. catarrhalis strains. These results suggest that this model system may be useful for the identification of vaccine candidates among the surface antigens of M. catarrhalis.

Animals↗
PubMed1993

A mutation affecting expression of a major outer membrane protein of Moraxella catarrhalis alters serum resistance and survival in vivo.

A major outer membrane protein (CopB) of Moraxella catarrhalis is a target for antibodies that enhance clearance of this organism from the lungs of mice. A mini-Tn10kan transposon was inserted into the cloned copB gene from M. catarrhalis O35E, and an isogenic mutant unable to express the CopB protein was constructed by transforming this mutated gene into the wild-type strain. The mutant grew at the same rate as the wild-type parent strain in broth. Unlike the serum-resistant parent strain, this mutant was sensitive to killing by normal human serum, and its ability to survive and grow in the lungs of animals was impaired. Genetic restoration of CopB protein expression resulted in the simultaneous acquisition of wild-type levels of serum resistance and the ability to resist pulmonary clearance in vivo. Thus, the CopB protein of M. catarrhalis may be important in the interaction between this organism and the defense mechanisms of the respiratory tract.

Animals↗
PubMed1994

Epidemiology of Moraxella catarrhalis in children during the first 2 years of life: relationship to otitis media.

Nasopharyngeal colonization with Moraxella catarrhalis was evaluated in a large cohort of infants followed prospectively from birth to 2 years of age; 120 children were examined at 13 routine visits. Of these, 66% became colonized with M. catarrhalis by 1 year and 77.5% by 2 years. Nasopharyngeal colonization with M. catarrhalis increased from 27.0% during healthy visits to 62.7% during visits due to otitis media (P < .001). Otitis-prone children were colonized at 44.4% of all visits compared with 16.7% for children who did not have otitis media (P < .001). DNA from 112 strains of M. catarrhalis from 34 children were evaluated; 106 were successfully digested with restriction enzymes and demonstrated a great degree of heterogeneity. Children tended to acquire and eliminate a number of different strains. Intrafamilial spread of the same strain of M. catarrhalis was frequent. These data suggest that nasopharyngeal colonization with M. catarrhalis is common throughout infancy. A high rate of colonization is associated with an increased risk of otitis media.

Child, Preschool↗
PubMed1994

Use of serology to diagnose pneumonia caused by nonencapsulated Haemophilus influenzae and Moraxella catarrhalis.

Antibodies against nonencapsulated Haemophilus influenzae and Moraxella (Branhamella) catarrhalis were measured by ELISA in paired sera from 158 adult patients with pneumonia. A mixture of 10 clinical isolates of each species was used as antigen. Eleven patients (7%) showed significant increases in antibody to H. influenzae. In 3 of them, the organism was isolated from transtracheal aspirate and in another 7 from sputum, nasopharynx, or both. Six patients with nonencapsulated H. influenzae in transtracheal aspirate cultures did not show any antibody increase. Six patients had significant increases in antibody to M. catarrhalis. The organism was isolated in transtracheal aspirates from 1 of them and in sputum and nasopharynx (or both) from another 3. Two patients with M. catarrhalis in transtracheal aspirate cultures showed no antibody response. In conclusion, the serologic methods increased the possibility to diagnose infections caused by the two agents but had low sensitivity.

Adult↗
PubMed1994

A large, antigenically conserved protein on the surface of Moraxella catarrhalis is a target for protective antibodies.

A monoclonal antibody (MAb) to Moraxella catarrhalis O35E bound to a surface-exposed epitope of a proteinaceous antigen of this organism. The antigen, designated UspA, was present in every strain of the pathogen tested in a colony blot RIA. UspA had a molecular mass on SDS-PAGE that varied between 300 and 400 kDa, depending on the individual M. catarrhalis strain. Passive immunization of mice with the UspA-reactive Mab enhanced pulmonary clearance of M. catarrhalis. Use of this Mab to screen a M. catarrhalis genomic DNA library permitted identification of a recombinant bacteriophage expressing the M. catarrhalis UspA protein. The recombinant UspA protein was used in Western blot analysis with sera from patients with M. catarrhalis pneumonia. Convalescent-phase sera but not acute-phase sera from these patients contained antibodies to this M. catarrhalis surface protein, indicating that M. catarrhalis strains growing in vivo express this molecule.

Adult↗
PubMed1994

Experimental evidence for Moraxella-induced penicillin neutralization in pneumococcal pneumonia.

Resistance of microorganisms to antimicrobial agents is an increasing problem in the treatment of infectious diseases. In mixed infections, an interesting development can arise when one organism protects another from being killed by an antibiotic. Unfortunately, in the case of respiratory tract infections, experimental evidence of this development is poor. In this study, mice intranasally infected with a lethal number of pneumococci and treated with a curative dose of penicillin or amoxicillin died from pneumococcal pneumonia when they were coinoculated with beta-lactamase-producing Moraxella catarrhalis. beta-lactamase-negative M. catarrhalis did not show a similar indirect pathogenic effect. Treatment with a combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid was not affected by beta-lactamase-producing M. catarrhalis. These findings help explain antibiotic failure in respiratory tract infections, even though the causative microorganism is sensitive to the antibiotic in vitro.

Amoxicillin↗
PubMed1996

Moraxella catarrhalis in acute laryngitis: infection or colonization?

The complement phenotypes of Moraxella catarrhalis isolates obtained from adult patients with acute laryngitis were investigated using a microliter serum bactericidal assay and compared with those of other donor groups. Laryngitis isolates had a higher proportion (57%) of complement-resistant strains than did carrier strains from healthy 8- to 13-year-old schoolchildren (16%). The difference between these groups was statistically significant (chi2 [3 x 2 table] = 21.55; P < .001). The relatively frequent occurrence of the complement-resistant (virulence-associated) phenotype in adults with acute laryngitis supports the theory of an active role of M. catarrhalis in the pathogenesis of acute laryngitis.

Adolescent↗
PubMed1991

Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis isolated in the UK from sputa.

Four hundred and thirty-one Streptococcus pneumoniae, 1272 Haemophilus influenzae and 305 Moraxella (Branhamella) catarrhalis were isolated from sputa and identified in 28 UK laboratories during a ten week period in 1990. Disc diffusion susceptibility testing was performed in each centre using identical methods. Species-specific susceptibility breakpoints applied to data for six antimicrobial agents were determined from the distribution of isolates according to zone diameters of inhibition measured in participating laboratories and were correlated with minimum inhibitory concentration data obtained with 302 isolates sent to the coordinating centre. Inter-laboratory reproducibility was estimated by comparing peripheral and coordinating centre results for these 302 isolates and by distributing five reference strains to all laboratories for testing. Reduced susceptibility to ampicillin and amoxycillin-clavulanate was detected in less than 3% of S. pneumoniae, but 8.1% were resistant to tetracycline and 6.5% to erythromycin. Resistance to ampicillin due to production of beta-lactamase occurred in 9.4% of H. influenzae; another 5.2% were resistant to ampicillin and amoxycillin-clavulanate but were beta-lactamase-negative. 4.5% were resistant to tetracycline and most (86.6%) had MICs greater than or equal to 1 mg/L of erythromycin. Zone diameters around ampicillin discs were greater than or equal to 10 mm smaller than those around amoxycillin-clavulanate discs for 241 (79%) of M. catarrhalis. Although only 193/241 had been reported to be beta-lactamase positive by participating laboratories, data obtained at the coordinating centre confirmed that greater than or equal to 10 mm and less than or equal to 3 mm zone size differences correlated with beta-lactamase-positive and -negative isolates respectively. No M. catarrhalis were resistant to amoxycillin-clavulanate and less than 4% were resistant to either tetracycline or erythromycin. The prevalence of resistance to cefaclor was highest among H. influenzae (5.2%) and lowest among S. pneumoniae (0.9%). Only seven of 2008 isolates (two to three per species) were resistant to cefixime. The data suggest that the prevalence of resistance to ampicillin, tetracycline and erythromycin must be taken into consideration when treating respiratory infections.

Ampicillin Resistance↗
PubMed1992

Permeability of the outer membrane of Moraxella catarrhalis for beta-lactam antibiotics.

The susceptibility of ten clinical isolates and a standard reference strain, ATCC25238, of Moraxella catarrhalis to 22 beta-lactam antibiotics was examined and compared with that of Escherichia coli strain B. All the strains of M. catarrhalis tested, especially the non beta-lactamase-producing strain ATCC25238, were more susceptible to a rang of structurally unrelated beta-lactam antibiotics, including small Mr carbapenems, than E. coli B. The permeability of the M. catarrhalis outer membrane to beta-lactam antibiotics was examined by the swelling technique with proteoliposomes reconstituted from outer membranes. The diffusion rate of beta-lactams through the liposome membrane was inversely related to their Mr, a relationship which might be expected for entry by diffusion through a porin.

Anti-Bacterial Agents↗
PubMed1992

The antimicrobial susceptibility of Moraxella catarrhalis isolated in England and Scotland in 1991.

Between 1 January and 31 March 1991, 20 laboratories in England and Scotland sent a total of 413 consecutive clinical isolates of Moraxella catarrhalis to The London Hospital Medical College (LHMC). After confirmation of identity, the susceptibility of all isolates to 11 antimicrobial agents was determined. Of the 375 (90.8%) isolates which were found at LHMC to be beta-lactamase-positive, 174 produced zones of inhibition around 2 micrograms ampicillin disc which were greater than or equal to 20 mm in diameter and 252 were inhibited by less than or equal to 0.5 mg/L of ampicillin. However, 71 of these 375 had been reported to be ampicillin-susceptible by peripheral centres. While beta-lactamase had not been detected in 35 of these 71 isolates, the other 36 had been reported to be ampicillin-susceptible and beta-lactamase-positive. All 38 beta-lactamase-negative isolates produced zones greater than or equal to 30 mm in diameter and were inhibited by less than or equal to 0.06 mg/L of ampicillin. No M. catarrhalis isolate was found to be resistant to co-amoxiclav, tetracycline, chloramphenicol or cefaclor. Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition. Resistance to trimethoprim was uniform (MICs 2-128 mg/L). Two isolates showed intermediate susceptibility to cefixime (MIC 2 mg/L) but none was resistant to the new oral cephalosporin cefetamet or to the oral carbacephem loracarbef.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Susceptibility of Moraxella catarrhalis isolates to beta-lactam antibiotics in relation to beta-lactamase pattern.

Moraxella catarrhalis isolates (n = 413) were collected from 20 clinical laboratories in England and Scotland in 1991 and were examined for beta-lactamase production by isoelectric focusing. beta-Lactamases were found in 375 isolates of which, 349 (93.1%) had BRO-1 enzyme and 26 (6.9%) had BRO-2. Minor variation in electrofocusing pattern occurred within both enzyme types. Ampicillin MICs for BRO-1 producers were 25-fold higher than for non-producers, but those for BRO-2 producers were raised only four-fold. MICs of cefaclor, cefixime, loracarbef, co-amoxiclav and cefetamet generally were two- to four-fold higher for BRO-1 producers than for BRO-2 producers and enzyme non-producers. Similarly, the inhibition zones of discs containing cefaclor, cefixime, loracarbef or co-amoxiclav were smaller for BRO-1 producers than for non-producers. Amongst the compounds tested, cefetamet seemed the least affected by beta-lactamase production in both MIC and disc tests. Overall, these results indicate that BRO-1 enzyme predominates amongst M. catarrhalis isolates from the UK, as in other countries, and suggest that BRO-1 production gives slight protection against many of the newer oral beta-lactams as well as causing ampicillin resistance.

Anti-Bacterial Agents↗
PubMed1996

The clinical relevance of in-vitro resistance to penicillin, ampicillin, amoxycillin and alternative agents, for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

The documentation of antimicrobial resistance in respiratory pathogens, contained within the Alexander Project, does not necessarily translate into clinical resistance in the treatment of primary community-acquired pneumonia. There is, in particular, little evidence that penicillin resistance in pneumococci is clinically relevant for the treatment of pneumonia, and there is further evidence that the production of beta-lactamase by Haemophilus influenzae may not always be clinically relevant within this setting. beta-Lactamase producing H. influenzae and Moraxella catarrhalis should probably be treated with alternative agents when they cause exacerbations of chronic bronchitis. More studies are required to define the clinical breakpoints of macrolide and co-trimoxazole resistance in the treatment of pneumonia.

Amoxicillin↗
PubMed1996

Antibiotic susceptibility patterns of community-acquired respiratory isolates of Moraxella catarrhalis in western Europe and in the USA. The Alexander Project Collaborative Group.

Eight hundred and eighteen Moraxella catarrhalis strains, isolated in 1992 and 1993 at 15 centres in Western Europe and the USA were tested for beta-lactamase production and resistance to 15 antibiotics. The proportion of beta-lactamase producing strains in Europe rose significantly from 70% in 1992 to 82% in 1993, whilst in the USA the increase (85-92%) was not significant. Penicillin and amoxycillin resistance was more prevalent in the USA than in Europe. All penicillin-resistant strains isolated in the USA exhibited beta-lactamase activity, whilst 8% of beta-lactamase-negative strains isolated in Europe were also penicillin resistant. All but three isolates were sensitive to cefaclor, cefuroxime, cefixime and ceftriaxone, all but one were sensitive to ofloxacin and all were sensitive to ciprofloxacin and amoxycillin cluvulanate. Resistance to erythromycin was not encountered, although 19 strains had MICs > or = 0.5 mg/L. Of these, 15 came from European centres. Almost all strains were highly susceptible to clarithromycin, azithromycin, doxycycline and co-trimoxazole.

4-Quinolones↗
PubMed1997

Multicentre in-vitro evaluation of the susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to ciprofloxacin, clarithromycin, co-amoxiclav and sparfloxacin.

Seven laboratories, including a reference laboratory, tested the susceptibility of Moraxella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae strains to ciprofloxacin, clarithromycin, co-amoxiclav and sparfloxacin with the Etest. A total of 976 strains were collected. The results with ciprofloxacin and sparfloxacin were consistent for all laboratories, while those with clarithromycin and co-amoxiclav were not. The agreement between Etest MICs and broth microdilution was: ciprofloxacin and sparfloxacin, >95%; clarithromycin for all species, 71-85%; co-amoxiclav for H. influenzae, 31%. MIC90 values (broth dilution, mg/L) for M. catarrhalis, S. pneumoniae and H. influenzae were: sparfloxacin, 0.06, 0.5, 0.03; ciprofloxacin, 0.12, 2.0, 0.03; co-amoxiclav, 0.25, 0.25, 0.25; clarithromycin 0.25, 0.25 and 16.

Amoxicillin↗
PubMed1997

Increasing antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in Finland.

Respiratory and otitis isolates of 807 Streptococcus pneumoniae, 816 Haemophilus influenzae and 446 Moraxella catarrhalis were collected from 21 clinical microbiology laboratories for antimicrobial susceptibility testing in 1995. After a period of relative stability in 1981 and 1987-1990, beta-lactamase production increased in H. influenzae. Among middle ear isolates from children under 6 years, beta-lactamase production increased from 8% to 24% in H. influenzae and from 81% to 96% in M. catarrhalis since the survey in 1987-1990. 1.2% of S. pneumoniae were penicillin-resistant and 4.2% intermediately resistant; 5 years earlier among otitis isolates of children only 1.7% intermediate resistance was found. Ampicillin resistance was seen among 1.9% of non-beta-lactamase-producing strains of H. influenzae. Resistance to trimethoprim-sulphamethoxazole occurred in 9.4% of S. pneumoniae, 7.4% of H. influenzae and 0.7% of M. catarrhalis. Frequencies of azithromycin resistance were 3.0% in S. pneumoniae and 1.6% in H. influenzae, and those of tetracycline resistance were 6.7% in S. pneumoniae and 1.2% in H. influenzae.

Adolescent↗
PubMed1998

Sensitivity to sparfloxacin and other antibiotics, of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis strains isolated from adult patients with community-acquired lower respiratory tract infections: a European multicentre study. SPAR Study Group. Surveillance Programme of Antibiotic Resistance.

A survey of resistance to sparfloxacin was carried out in ten European countries, namely Slovakia, France, Germany, Great Britain, Hungary, the Republic of Ireland, Italy, The Netherlands, Portugal and Spain. Respiratory samples were collected from 4297 patients with lower respiratory tract infections and cultured for the presence of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Altogether 2101 strains were isolated and tested for their susceptibility to sparfloxacin, ciprofloxacin, erythromycin, tetracycline and penicillin G (S. pneumoniae) or amoxycillin (H. influenzae and M. catarrhalis). Each country tested strains using methods commonly used in that country, and with breakpoints selected based on those used in that country. Penicillin resistance in pneumococci was seen in those countries in which it had been reported previously, namely Spain, France and Hungary. Only four strains of pneumococci were resistant to sparfloxacin (MIC > or = 2 mg/L), while ciprofloxacin-resistant strains were isolated more frequently, particularly in the Republic of Ireland and Hungary. Almost all of the strains of H. influenzae tested were resistant to erythromycin, (MIC50 > or = 4 mg/L), but all strains were highly sensitive to sparfloxacin (MIC90 < or = 0.06 mg/L). The number of strains of H. influenzae producing beta-lactamase varied between countries, whereas most strains of M. catarrhalis produced beta-lactamase. In M. catarrhalis, erythromycin and tetracycline resistance was rare, but sensitivity to amoxycillin varied. Sparfloxacin was particularly active against H. influenzae and M. catarrhalis, and was the most active compound tested. Overall, the activity of sparfloxacin was greater than that of ciprofloxacin against all three pathogens, and resistance to it was rare.

Anti-Bacterial Agents↗
PubMed1999

In-vitro activity of levofloxacin, a new fluoroquinolone: evaluation against Haemophilus influenzae and Moraxella catarrhalis.

The in-vitro activity of levofloxacin was studied against 10 beta-lactamase-negative and 93 beta-lactamase-positive Moraxella catarrhalis isolates, and 65 beta-lactamase-negative and 35 beta-lactamase-positive Haemophilus influenzae isolates. The MICs of levofloxacin were determined by agar dilution on Mueller-Hinton agar (with the addition of 5% horse blood for M. catarrhalis) or on Haemophilus Test Medium for H. influenzae, and were compared with those of ofloxacin, ciprofloxacin and sparfloxacin, as well as pefloxacin and D-ofloxacin for M. catarrhalis. The fluoroquinolones showed similar activity against isolates of H. influenzae and M. catarrhalis, irrespective of beta-lactamase production. Levofloxacin (MIC50/90 0.06 mg/L) was 64 times more active against M. catarrhalis than D-ofloxacin (MIC50/90 4/8 mg/L) and twice as active as ofloxacin (MIC50/90 0.125 mg/L). Ciprofloxacin had an MIC50/90 of 0.03/0.06 mg/L and sparfloxacin showed an MIC50/90 of 0.015 mg/L against M. catarrhalis irrespective of the resistance phenotype of the isolates. Against H. influenzae, levofloxacin was twice as active as ofloxacin (MIC90 values 0.03 mg/L versus 0.06 mg/L), while the MIC90s of ciprofloxacin and sparfloxacin were both 0.015 mg/L. Our results therefore suggest that levofloxacin has potential for treating respiratory tract infections caused by H. influenzae and M. catarrhalis.

Anti-Infective Agents↗
PubMed1999

In-vitro activity of HMR 3647 against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and beta-haemolytic streptococci.

The in-vitro activity of HMR 3647 and seven comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, penicillin G, ciprofloxacin and levofloxacin) were tested against 207 Streptococcus pneumoniae and 200 beta-haemolytic streptococci. Ten comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, ampicillin, co-amoxiclav, cefuroxime, cefotaxime, ciprofloxacin and levofloxacin) were tested against 143 Haemophilus influenzae and 58 Moraxella catarrhalis. The MIC50 of HMR 3647 for S. pneumoniae was < or =0.008 mg/L, less than that for the macrolides or quinolones tested. Pneumococci with an erythromycin A MIC of 0.06 mg/L (n = 23) had an MIC50 of HMR 3647 < or =0.008 mg/L, whereas isolates with an erythromycin A MIC > or =1 mg/L (n = 34) had an MIC50 of HMR 3647 of 0.03 mg/L, a four-fold increase. In contrast, the difference in macrolide MIC50s for the two groups was > or =64-fold. The MIC50s foro beta-haemolytic streptococci, classified by Lancefield group, were in the range 0.015 to 0.06 mg/L for HMR 3647. H. influenzae were categorized into three groups according to cefuroxime MIC: <1 mg/L (n = 72); 2-4 mg/L (n = 29); and >4 mg/L (n = 42). The MIC50 of HMR 3647 increased two-fold with increasing cefuroxime MICs; beta-lactam MICs increased much more markedly. The MIC50 of HMR 3647 for M. catarrhalis was 0.03 mg/L. HMR 3647 has good activity against respiratory tract pathogens but in-vitro susceptibility is affected by erythromycin A susceptibility in S. pneumoniae and beta-haemolytic streptococci.

Anti-Bacterial Agents↗