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PubMed2001

Antimicrobial susceptibilities of clinical isolates of Haemophilus influenzae and Moraxella catarrhalis collected during 1999-2000 from 13 countries.

OBJECTIVE: To determine antimicrobial activity against Haemophilus influenzae and Moraxella catarrhalis. METHODS: A central laboratory performed NCCLS susceptibility testing for all isolates and beta-lactamase and capsular serotype determinations for H. influenzae. RESULTS: A total of 2712 H. influenzae and 1079 M. catarrhalis were collected. H. influenzae susceptibilities were >90% for amoxicillin/clavulanate, cefaclor, loracarbef, cefprozil, cefuroxime, ciprofloxacin, azithromycin and clarithromycin and were <80% for trimethoprim/sulfamethoxazole and ampicillin. 19.3% were beta-lactamase positive. The most common serotype was type-b (5.6%); 86.1% were nontypeable. M. catarrhalis had MIC90 within therapeutic range for all antimicrobials except ampicillin. CONCLUSION: The conclusion of the study is that antimicrobials, except ampicillin and trimethoprim/sulfamethoxazole, remain good empiric choices against H. influenzae and M. catarrhalis.

Adolescent↗
PubMed2003

In vitro susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: a European multicenter study during 2000-2001.

OBJECTIVE: To assess the current (2001) activity of respiratory fluoroquinolones and comparator agents against respiratory pathogens isolated in European countries. METHODS: During 2000-2001, we prospectively collected 1995 isolates of Haemophilus influenzae, 1870 isolates of Streptococcus pneumoniae and 649 isolates of Moraxella catarrhalis from hospital laboratories in France, Germany, Greece, Italy, Spain and the UK. National Committee for Clinical Laboratory Standards (NCCLS)-approved broth microdilution antimicrobial susceptibility testing methods and interpretive criteria were used throughout. RESULTS: Of the S. pneumoniae isolates, 99.6% were susceptible to moxifloxacin, gatifloxacin and levofloxacin; the corresponding figure for H. influenzae was 100%. All M. catarrhalis isolates had moxifloxacin MICs </= 0.12 mg/L. For all three pathogens, fluoroquinolone susceptibility remained unchanged from the previous 1997-98 study. The incidence of penicillin non-susceptibility in the S. pneumoniae isolates tested remained similar to or higher than that recorded in previous studies: France, 165/291 (56.7%); Germany, 46/506 (9.1%); Greece, 20/55 (36.4%); Italy, 45/364 (12.4%); Spain, 146/268 (54.5%); and the UK, 26/386 (6.7%). Significant levels of resistance to oral compounds (cefuroxime, cefaclor, cefdinir, clarithromycin, azithromycin, tetracycline, and trimethoprim-sulfamethoxazole) were detected among S. pneumoniae isolates. beta-Lactamase production among H. influenzae isolates ranged from 6.2% to 33.1% per country, and ampicillin, clarithromycin or trimethoprim-sulfamethoxazole resistance were the most common phenotypes detected. beta-Lactamase production among M. catarrhalis isolates ranged from 94.1% to 100% per country. CONCLUSIONS: With the exception of a few localized reports, resistance to moxifloxacin and other new fluoroquinolones in common respiratory pathogens is a rare occurrence, despite significant resistance to other compound classes. Surveillance will play a key role in tracking changes in fluoroquinolone susceptibility in European countries.

Anti-Infective Agents↗
PubMed2003

Antimicrobial activity of LB10827, a new orally administered cephalosporin, tested against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.

A new orally administered cephalosporin, LB10827, was compared to 16 other antimicrobial agents tested against Streptococcus pneumoniae (520 strains), Haemophilus influenzae (302 strains) and Moraxella catarrhalis (188 strains) by reference broth microdilution methods. LB10827 (MIC90, 0.12 mg/L; highest MIC, 0.5 mg/L) was 8-16-fold more potent than cefdinir, cefpodoxime or cefuroxime when tested against S. pneumoniae. All Gram-negative strains were inhibited at </= 0.5 mg/L LB10827, which is an activity equal or superior to that of currently available and tested oral beta-lactams. LB10827 appears to be a promising agent worthy of continued investigations both in vitro and in vivo.

Administration, Oral↗
PubMed2002

Activity of oral beta-lactam antimicrobial agents versus respiratory tract isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the era of antibiotic resistance.

The management of outpatient respiratory tract infections with oral beta-lactam antimicrobial agents has been complicated by the emergence of beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis and isolates of Streptococcus pneumoniae that express varying levels of beta-lactam resistance because of altered penicillin-binding proteins. There is no question that all 3 of these important respiratory tract pathogens have changed conspicuously in the context of decreased activity of beta-lactam antimicrobial agents. The question arises, what does this change mean from a clinical perspective? In this review, the in vitro activity of various oral beta-lactam antimicrobial agents versus contemporary isolates of H influenzae, M catarrhalis, and S pneumoniae will be compared. The approach that is used in defining organisms as being susceptible or resistant to beta-lactam antimicrobial agents will be elucidated. Finally, an effort will be made to assess the ramifications of beta-lactam resistance for therapeutic efficacy in patients with respiratory tract infections caused by these 3 bacteria. We conclude that, notwithstanding diminished beta-lactam activity for many clinical isolates of H influenzae, M catarrhalis, and S pneumoniae, certain agents remain effective in treating outpatient respiratory tract infections.

Administration, Oral↗
PubMed1998

Reaction mechanism of fluoroacetate dehalogenase from Moraxella sp. B.

Fluoroacetate dehalogenase (EC 3.8.1.3) catalyzes the dehalogenation of fluoroacetate and other haloacetates. The amino acid sequence of fluoroacetate dehalogenase from Moraxella sp. B is similar to that of haloalkane dehalogenase (EC 3.8.1.5) from Xanthobacter autotrophicus GJ10 in the regions around Asp-105 and His-272, which correspond to the active site nucleophile Asp-124 and the base catalyst His-289 of the haloalkane dehalogenase, respectively (Krooshof, G. H., Kwant, E. M., Damborský, J., Koca, J., and Janssen, D. B. (1997) Biochemistry 36, 9571-9580). After multiple turnovers of the fluoroacetate dehalogenase reaction in H218O, the enzyme was digested with trypsin, and the molecular masses of the peptide fragments formed were measured by ion-spray mass spectrometry. Two 18O atoms were shown to be incorporated into the octapeptide, Phe-99-Arg-106. Tandem mass spectrometric analysis of this peptide revealed that Asp-105 was labeled with two 18O atoms. These results indicate that Asp-105 acts as a nucleophile to attack the alpha-carbon of the substrate, leading to the formation of an ester intermediate, which is subsequently hydrolyzed by the nucleophilic attack of a water molecule on the carbonyl carbon atom. A His-272 --> Asn mutant (H272N) showed no activity with either fluoroacetate or chloroacetate. However, ion-spray mass spectrometry revealed that the H272N mutant enzyme was covalently alkylated with the substrate. The reaction of the H272N mutant enzyme with [14C]chloroacetate also showed the incorporation of radioactivity into the enzyme. These results suggest that His-272 probably acts as a base catalyst for the hydrolysis of the covalent ester intermediate.

Acetates↗
PubMed2000

Polyp and fibrous adhesion formation in acute otitis media caused by non-typeable or type b Haemophilus influenzae or Moraxella catarrhalis.

Among a variety of other histopathologic changes, polyps and fibrous adhesions are readily formed in the middle ear mucosa during experimental acute otitis media (AOM) caused by Streptococcus pneumoniae. Quantitative studies on experimental AOM caused by other bacteria have shown that some of these histopathologic changes, such as adaptive bone modeling and increase in goblet cell density, differ according to the type of bacteria. This investigation surveys polyp and fibrous adhesion formation in experimental AOM caused by either non-typeable or type b Haemophilus influenzae, or Moraxella catarrhalis. Seventy-five rats were inoculated with 1 of these 3 bacteria (25 rats in each of 3 groups). Five rats from each group were sacrificed on days 4, 8, 16, 60 and 180 post-inoculation. The middle ear mucosae were dissected and histopathologic changes in whole-mount and section preparations were studied using light microscopy. Polyps were found in most ears and in the greatest numbers on the early days; fewer polyps were found on the later days, regardless of the type of bacteria. However, non-typeable and type b H. influenzae induced formation of significantly more polyps than M. catarrhalis. The polyps were primarily located in the epitympanum. Fibrous adhesions were primarily located in the hypotympanum and formed in almost all ears, on all days post-inoculation, regardless of the type of bacteria. Numbers increased to a peak on day 16 and then decreased. Non-typeable and type b H. influenzae induced formation of significantly more adhesions than M. catarrhalis, and the middle ears displayed a higher number of persisting adhesions in the animals inoculated with non-typeable H. influenzae. We conclude that polyps and adhesions are formed in experimental AOM regardless of bacterial type, confirming a pathogenesis based on inflammation. Both types of H. influenzae induce formation of greater numbers of polyps/adhesions than M. catarrhalis, and the non-typeable form causes more adhesive sequelae in the mucosa than the encapsulated type b.

Acute Disease↗
PubMed1998

Serum antibodies specific to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in children with otitis media with effusion.

We measured the levels of serum IgG antibodies to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in 168 children with otitis media with effusion (OME) who were followed prospectively, using ELISA. Serum IgG antibodies to CD, P6 and pneumococcal capsular polysaccharides were detected in all samples. The anti-pneumococcal polysaccharides antibody level was highest, followed by the anti-P6 antibody level and anti-CD antibody was lowest (median:interquartile ranges were 45.9:19.1-100 microg/ml, 15.6:9.70-23.2 microg/ml and 1.06:0.73-1.87 microg/ml, respectively). In children aged 0-6 years, there were positive correlations among the antibody levels (anti-CD vs anti-P6, r=0.325, p <0.001; anti-CD vs anti-polysaccharide, r=0.397, p <0.0001; anti-P6 vs anti-polysaccharide, r=0.175, p=0.057). However, no relationship was seen in children aged 7-15 years. Children were classified according to severity of OME during the 1-year follow-up. In children aged 0-6 years, the severity of OME correlated inversely with the levels of anti-CD antibody (r=-.23, p=0.012), of anti-P6 antibody (r=-0.292, p=0.0015), and of anti-pneumococcal polysaccharides antibody (r=-0.25, p=0.0064). However, no correlation was found between antibody levels and severity of OME in children aged 7-15 years. These data suggest that persistence and/or recurrence of OME may be due to an insufficient serum antibody response to middle ear pathogens in young children.

Adolescent↗
PubMed1998

Ribotyping of strains of Moraxella (Branhamella) catarrhalis cultured from the nasopharynx and middle ear of children with otitis media.

Moraxella (Branhaomella) catarrhalis is frequently present in the nasopharyngeal microflora of small children, especially during episodes of acute otitis media . By means of ribotyping (restriction endonuclease analysis of chromosomal DNA combined with rRNA probing), we studied the genetic heterogeneity of 78 cultures of M. catarrhalis obtained from different localities in the nasopharynx of nine young children with secretory otitis media. Using HindIII and PstI as endonucleases, five different ribotypes were recognized, representing at least five different genotypes of M. catarrhalis. The distribution of these types was found to be almost identical to the distribution among 16 M. catarrhalis strains cultured from middle ear exudates of 16 children with acute otitis media. Ribotype HAPA was found in two-thirds of all the cultures investigated, and 44% of the children harboured more than one ribotype in the nasopharynx at the same time. The vast majority of the nasopharyngeal M. catarrhalis cultures were beta-lactamase positive. One child had both a HAPA ribotype, beta-lactamase-negative strain in the nasopharyngeal secretions, and HAPA ribotype, beta-lactamase-positive strains at the entrance of the eustachian tube, the nasopharyngeal tonsils, the folds of the nasopharyngeal tonsils and the oropharynx. All except one of the M. catarrhalis strains cultured from middle ear exudates were beta-lactamase positive.

Child↗
PubMed1997

Selection of optimum laboratory tests for the identification of Moraxella catarrhalis.

We evaluated a variety of conventional and rapid tests and examined the erythromycin susceptibility of a collection of Moraxella catarrhalis and commensal neisseria strains in order to determine the optimum method for routine identification. One hundred and fifty three strains were tested by Gram stain, catalase, oxidase, carbohydrate degradation by two methods and the presence of esterases using indoxyl acetate, 4-methylumbelliferyl butyrate (MUB). Tween 80 and tributyrin as substrates. Erythromycin MICs and zone diameters around 1, 5 and 15 micrograms discs were determined by the NCCLS method for 151 of the strains. A combination of Gram stain, oxidase and either indoxyl acetate, spot MUB or tributyrin hydrolysis test proved to be reliable and potentially the most convenient for routine testing. MICs and zone diameters easily distinguished between the erythromycin-sensitive M. catarrhalis and the erythromycin-resistant commensal neisserias and would provide confirmation of identification if used for susceptibility testing.

Bacterial Typing Techniques↗
PubMed2000

Moraxella catarrhalis endocarditis: case report and review of the literature.

A case of bacterial endocarditis caused by Moraxella catarrhalis in an apparently immunocompetent Greek male is presented, which was diagnosed after a 2-month history of low-grade fever of unknown origin. The agent seems to be a rare pathogen, but due to the high mortality rate, it should always be considered in the differential diagnosis of relevant cases. Beta-lactamase production by many strains complicates the choice of antibiotic.

Adult↗
PubMed2001

Clinical "pneumococcal pneumonia" due to Moraxella osloensis: case report and a review.

A previously healthy 6-y-old girl presented with a disease very similar to pneumococcal pneumonia. However, Moraxella osloensis was isolated by lung tap. The patient responded well to a course of parenteral penicillin. This is probably the first documented case of community-acquired pneumonia associated with this agent. Clinical isolates of M. osloensis are rare and its pathogenesis has not been delineated; however, a literature review suggests that the organism is more common than is generally recognized.

Child↗
PubMed2004

Evaluation of restriction endonuclease analysis of BRO beta-lactamases in clinical and carrier isolates of Moraxella catarrhalis.

A rapid increase in the prevalance of beta-lactamase producing M. catarrhalis isolates has highlighted its pathogenic potential. In this study, we aimed to detect the BRO beta-lactamases of our clinical (n = 32) and carrier (n =32) strains of Moraxella catarrhalis and compare the relationship of the enzyme type in assesment of MIC results of the antibiotics tested. BRO beta-lactamases were differentiated by restriction endonuclease analysis. Antibiotic susceptibility was performed by the agar dilution method recommended by NCCLS (M7A5). The clinical isolates produced 96.9%, whereas the carrier strains produced 90.6% beta-lactamase positivity by the restriction enzyme analysis. BRO-1 was isolated as 90.6% (n =29) while the BRO-2 and non-beta-lactamase producers (NBLP) were isolated as 6.3% (n =2) and 3.1% (n =1) respectively among clinical isolates. The rate of BRO-1 in the carrier strains was 75.0% (n =24), BRO-2 was 15.6% (n =5) and NBLP was 9.4%, (n =3). The beta-lactamase production with nitrocefin test was 96.9% (31/32) in clinical isolates and 90.6% (29/32) in carrier strains. M. catarrhalis needs a continous monitoring of antibiotic susceptibility; in this era restriction endonuclease analysis could be useful to screen BRO beta-lactamase genes.

Adolescent↗
PubMed1998

Moraxella catarrhalis bacteraemia. A report on 3 cases and a review of the literature.

Over the last decade, an increase in invasive infections due to Moraxella catarrhalis has been reported. We have analysed 58 cases of bacteraemia due to M. catarrhalis reported in the literature and 3 cases found in Iceland, a total of 61 cases. Patients with bacteraemia could be divided into 3 groups on the basis of host factors. They were either immunocompromised, had underlying respiratory disorders. or were normal hosts. The clinical manifestation of M. catarrhalis bacteraemic infection ranged from a mild febrile illness to a fatal disease. The severity of the clinical picture did not reflect the patients' condition at the time of bacteraemia. The port of entry of the bacteraemia was frequently not elucidated in immunocompromised patients. Patients with a contributory respiratory tract disorder were more likely to develop bacteraemia as a result of a lower respiratory tract infection, whereas bacteraemia in a normal host was more frequently due to an upper respiratory tract infection. The overall prognosis of M. catarrhalis bacteraemia was good, the exception being when it caused endocarditis (5 cases), where mortality rates as high as 80% have been reported.

Anti-Bacterial Agents↗
PubMed1996

Neonatal meningitis due to Moraxella catarrhalis and review of the literature.

Moraxella catarrhalis has been reported with increasing frequency to be the aetiological agent of serious systemic infection in both children and adults. The first case of neonatal meningitis due to this organism is described herein. The fatal outcome and causes of failure of response to antimicrobial therapy are also discussed. A brief review of the literature describing the disease entities with which M. catarrhalis has been associated is presented.

Adult↗
PubMed1988

Purification, characterization, and pathogenicity of Moraxella bovis pili.

Pilins composed of the alpha or beta pilins of Moraxella bovis strain Epp63 were purified, subjected to chemical or enzymatic cleavage, and the resulting fragments sequenced by automated Edman degradation. alpha Pilin was found to be a 155-amino-acid polypeptide with a single intramolecular disulfide bridge. The beta pilin amino acid sequence substantiated the previously reported structure derived from the beta pilin gene DNA sequence, and indicated that the alpha and beta pilins of this strain are approximately 70% homologous. DNA hybridization studies of genomic DNA from the alpha- and beta-piliated variants of strain Epp63 indicated that the expression of the two pilin types was governed by an oscillating mechanism of chromosomal rearrangement. The alpha and beta pili were evaluated serologically and found to exhibit approximately 50% shared antigenicity, indicating that regions of conserved and heterologous sequence specify both type-specific and crossreacting epitopes. The pathogenicity of the alpha- and beta-piliated variants was studied by ocular inoculation of calves eyes; beta-piliated organisms were significantly more infectious than alpha-piliated organisms, indicating that beta pili confer, or are associated with, a relative advantage during the first stages of ocular infection. Preliminary analysis of other M. bovis strains suggests that each strain produces two types of pilin, and that this property may be characteristic of the species.

Amino Acid Sequence↗