Moraxella Catarrhalis Strains Research Articles

Morphostructural Damage and the Inhibition of Bacterial Adhesiveness of Staphylococcus aureus and Moraxella catarrhalis Induced by Moxifloxacin

The aim of this study was to investigate the ability of moxifloxacin to interfere with the mechanism of bacterial adhesion and disrupt the morphological and structural integrity of bacteria. Three Staphylococcus aureus and three Moraxella catarrhalis strains were grown in the presence of 1/2-1/128 minimum inhibitory concentration (MIC) serial dilutions and incubated with human epithelial cells. A significant decrease in adhesion was observed from 1/2 MIC to 1/64 MIC for S. aureus, and from 1/2 MIC to 1/16 MIC for M. catarrhalis.The use of atomic force microscopy, a new technique capable of revealing surface structures in three-dimensional detail and at very high resolution, showed the rapid onset and time course of the sequence of disruptive morphostructural events following the incubation of both S. aureus and M. catarrhalis with sub-MICs of moxifloxacin. Our findings suggest that less than conventional MIC moxifloxacin concentrations may be effective in reducing bacterial adhesiveness and structural integrity on which the maintenance of bacterial activity depends.

Current status of bacterial resistance in the otolaryngology field: results from the Second Nationwide Survey in Japan.

The study reported here was a nationwide assessment of otitis media (466 patients with acute suppurative otitis media and 476 with chronic suppurative otitis media), sinusitis (447 with acute sinusitis and 426 with chronic sinusitis), acute tonsillitis (724 patients), and peritonsillar abscess (141 patients) performed between November 1998 and March 1999. Eighty university hospitals, 79 affiliated hospitals, and 103 general practitioners participated. Methicillin-resistant Staphylococcus aureus(MRSA) comprised 15.6% of the 786 isolated strains of S. aureus. MRSA was frequently detected in patients with suppurative otitis media, but was uncommon in those with acute tonsillitis or peritonsillar abscess, and it was more common in those who had already been treated than in those who had not, with a significant difference between the groups. Vancomycin (VCM) showed the highest antimicrobial activity against MRSA and no VCM resistance was detected. Penicillin-sensitive Streptococcus pneumoniae(PSSP), penicillin-intermediate-resistant S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) accounted for 49.6%, 28.5%, and 21.9% of the 228 isolated strains of S. pneumoniae, respectively. PISP and PRSP were frequently detected in children aged 5 years or younger. beta-Lactamase was produced by 96 of the 100 strains (96%) of Moraxella (Branhamella) catarrhalis. The 281 strains of Haemophilus influenzae isolated consisted of 199 beta-lactamase-negative, ampicillin-sensitive (BLNASe) strains (70.8%), 65 beta-lactamase-negative ampicillin-resistant (BLNAR) strains (23.1%), and 17 beta-lactamase-producing strains (6.0%). BLNAR strains were frequently detected in pretreated patients. Of these 281 strains of H. influenzae, 214 had nontypable capsules. In conclusion, the major bacterial species showed resistance to beta-lactams, indicating that care should be taken when selecting an appropriate antimicrobial agent.

Activity of nine oral agents against gram-positive and gram-negative bacteria encountered in community-acquired infections: Use of pharmacokinetic/pharmacodynamic breakpoints in the comparative assessment of beta-lactam and macrolide antimicrobial agents

Background: The application of pharmacokinetic (PK) and pharmacodynamic (PD) data in conjunction with minimum inhibitory concentrations (MICs) of antibacterial agents has been shown to allow for improved selection and appropriate dosing of antimicrobial agents for specific infections, increasing the likelihood of bacteriologic cure and, through this, reducing the risk for the development of resistant organisms. Objectives: This study was undertaken to provide data on current levels of resistance among common community-acquired bacterial species to 7 betalactam antimicrobial agents (including the combination product amoxicillin/clavulanate), azithromycin, and clarithromycin, determined through application of the PK/PD breakpoints based on time-above-MIC for the beta-lactams and the nonazalide macrolide clarithromycin, and on 24-hour serum area under the curve divided by MIC for the azalide macrolide azithromycin. Methods: The antimicrobial products tested were amoxicillin/clavylanate, cefpodoxime, cefdinir, cefditoren, cefprozil, cefuroxime, cefixime, azithromycin, and clarithromycin. The bacterial species comprised 70 penicillin-susceptible, 68 penicillin-intermediate, and 69 penicillin-resistant strains of Streptococcus pneumoniae; 46 beta-lactamase-positive and 54 beta-lactamase-negative strains of Haemophilus influenzae; 49 strains of Moraxella catarrhalis; and 100 methicillin-sensitive strains of Staphylococcus aureus (MSSA). Strains were isolated from clinical specimens obtained from outpatient-acquired infections in 1 clinical center in the Northeast and 1 in the north-central area of the United States within the past 2 years. National Committee for Clinical Laboratory Standards microdilution MIC methodology was used. PK/PD breakpoints were obtained from previously published studies and were based on blood values. Results: Amoxicillin/clavulanate was the product to which the greatest percentage of susceptible, intermediate, and resistant strains of pneumococci were sensitive at the PK/PD breakpoint, followed by cefditoren, cefpodoxime, cefuroxime, cefdinir, and cefprozil. None of the cephalosporins were active against penicillin-resistant pneumococci. Cefditoren and cefpodozime were the agents to which the greatest percentage of beta-lactamase-positive and beta-lactamase-negative strains of H influenzae were sensitive, followed by amoxicillin/clavulanate, cefdinir, and cefuroxime. Cefprozil was inactive against H influenzae. All of the beta-lactam products were active against M catarrhalis. All but cefpodoxime, cefditoren, and cefixime were active against MSSA. Conclusions: In this study, based on PK/PD breakpoints, amoxicillin/clavulanate had the best overall activity of the 9 antimicrobial products tested. Cefpodoxime and cefditoren were active against ⩾90% of strains of penicillin-susceptible and penicillin-intermediate pneumococci, H influenzae, and M catarrhalis. The macrolides azithromycin and clarithromycin were active against penicillin-susceptible and penicillin-intermediate pneumococci and M catarrhalis; they were inactive against H influenzae and penicillin-resistant pneumococci.

Activity of oral β-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 β-lactam antimicrobial agents has been complicated by the emergence of β-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis and isolates of Streptococcus pneumoniae that express varying levels of β-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 β-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 β-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 β-lactam antimicrobial agents will be elucidated. Finally, an effort will be made to assess the ramifications of β-lactam resistance for therapeutic efficacy in patients with respiratory tract infections caused by these 3 bacteria. We conclude that, notwithstanding diminished β-lactam activity for many clinical isolates of H influenzae, M catarrhalis, and S pneumoniae, certain agents remain effective in treating outpatient respiratory tract infections. (Otolaryngol Head Neck Surg 2002;127:S17-S23.)

Antimicrobial Action of Nitens® Mouthwash (Cetyltrimethylammonium Naproxenate) on Multiple Isolates of Pharyngeal Microbes: A Controlled Study against Chlorhexidine, Benzydamine, Hexetidine, Amoxicillin, Amoxicillin-Clavulanate, Clarithromycin, and Cefaclor

Background: Acute oropharyngeal and respiratory tract infections are due to a wide spectrum of microorganisms. The aim of this study was to compare and evaluate the in vitro activity of four antiseptics (cetyltrimethylammonium naproxenate, chlorhexidine, benzydamine, hexetidine) to four antibiotics (amoxicillin, amoxicillin-clavulanate, clarithromycin, cefaclor) on strains of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae. Methods: Susceptibility tests were performed on 90, aerobic and anaerobic, bacterial strains, isolated from nasopharyngeal swabs and sputum. Minimum inhibitory concentrations (by microdilution) and minimum bactericidal concentrations were determined and compared. Results: Our selected panel of bacteria was highly susceptible to the antiseptics, particularly to chlorhexidine and naproxenate, even more so than two of the most frequently used antibiotics. Data were statistically significant (p < 0.005). Conclusions: In view of their bactericidal and anti-inflammatory properties, these antiseptics may be effective in controlling the transitory colonization of the oral cavity by microbes that cause or worsen disease in patients with mild infections.

Oral antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates from Japanese children

The minimum inhibitory concentrations (MICs) of 11 oral antibiotics were measured for 140 Streptococcus pneumoniae, 115 Haemophilus influenzae, and 46 Moraxella catarrhalis strains isolated from Japanese children. The antibiotics selected included a range of commonly prescribed agents together with a selection of new cefems and a penem. Cefditoren was most active against the highly penicillin resistant S. pneumoniae, β-lactamase-producing H. influenzae and β-lactamase-negative ampicillin-resistant H. influenzae. However, amoxycillin retained good activity against the penicillin-susceptible or -intermediately resistant S. pneumoniae (88.6%) and most of ampicillin-susceptible or -intermediately resistant H. influenzae (87.9%). We thus consider that amoxycillin remains a useful initial choice for the treatment of paediatric respiratory infections in Japan.

Diagnosis and management of acute otitis media in the urgent care setting

The prevalence of otitis media is increasing, which affects health care resource utilization across all segments, including the urgent care setting. One of the greatest challenges in the management of acute otitis media (AOM) is the effective treatment of cases caused by pathogens that are resistant to commonly used antibiotics. Whereas the production of β-lactamases among strains of Haemophilus influenzae and Moraxella catarrhalis is an important consideration for antimicrobial therapy, the high prevalence of resistance to penicillin and other classes of antibiotics among strains of Streptococcus pneumoniae represents a greater clinical concern. The Centers for Disease Control and Prevention (CDC) recently convened the Drug Resistant S. pneumoniae Therapeutic Working Group to develop evidence-based recommendations for the treatment of AOM in an era of prevalent resistance. The recommendations from this group included amoxicillin as the preferred first-line drug because of the demonstrated activity against penicillin-intermediate and -resistant strains of S. pneumoniae, using higher dosages of up to 90 mg/kg per day in certain settings. For patients in whom initial treatment is unsuccessful after 3 days, the recommended agents included high-dose amoxicillin-clavulanate (for activity against β-lactamase-producing pathogens), clindamycin, cefuroxime axetil, or 1 to 3 doses of intramuscular ceftriaxone. The principles set forth in these guidelines can assist the therapeutic decisionmaking process for practitioners in the urgent care setting. [McCracken GH Jr. Diagnosis and management of acute otitis media in the urgent care setting. Ann Emerg Med. April 2002;39:413-421.]

A new intra-NALT route elicits mucosal and systemic immunity against Moraxella catarrhalis in a mouse challenge model

Mucosally administered antigens are often poorly immunogenic due to the difficulty of transporting antigens through the mucosal epithelium. We investigated a new route of intranasal-associated lymphoid tissue (intra-NALT) administration of antigens to circumvent the antigen transportation barrier. A comparative study was carried out on mice administered with killed whole cells of Moraxella catarrhalis strain 25238 plus cholera toxin (CT) by intra-NALT injection and nasal inoculation. Both routes induced significant elevations of several isotype antibodies against strain 25238 in saliva, lung lavage, and serum as measured by an enzyme-linked immunosorbent assay (ELISA). Most of these antibodies were paralleled by the numbers of their corresponding antibody forming cells in mucosal or systemic lymphoid tissues. However, intra-NALT injection elicited higher levels of immunoglobulin (Ig) A and IgG in saliva, IgA and IgG in lung lavage, and IgG and IgM in sera than nasal inoculation ( P≤0.05). In addition, both routes generated significant reductions of bacteria in lungs following an aerosol challenge with strain 25238 in a mouse model of pulmonary clearance. Once again, intra-NALT route showed better bacterial clearance in mouse lungs than nasal inoculation ( P<0.01). These results demonstrate that intra-NALT administration of antigens is a convenient and effective route for mucosal immunization that elicits improved mucosal and systemic immunity. This new route can be used as a model to study mucosal antigens or vaccine candidates for antigen activation and interaction with the NALT that is one of major inductive sites for common mucosal immune system.

Susceptibility to moxifloxacin and other antimicrobial agents of major pathogens responsible for community acquired respiratory tract infection in Poland

The in vitro activity of moxifloxacin was compared with that of other antimicrobial agents against 470 bacterial strains isolated from patients with respiratory tract infection. Bacteria studied included 110 penicillin susceptible and 110 penicillin non-susceptible Streptococcus pneumoniae, 50 strains of S. pyogenes, 120 strains of Haemophilus influenzae and 80 strains of Moraxella catarrhalis. Moxifloxacin was the most active of the antimicrobials tested.

Is antimicrobial resistance also subject to globalization?

In recent years one of the more alarming aspects of clinical microbiology has been the dramatic increase in the incidence of resistance to antibacterial agents among pathogens causing nosocomial as well as community-acquired infections. There are profound geographic differences in the incidence of resistance among pathogens of the respiratory tract, only some of which can be explained by the local use of antibiotics. A high percentage of Moraxella catarrhalis strains produce beta-lactamase and are thus resistant to many beta-lactam antibiotics. In contrast, beta-lactamase production among strains of Haemophilus influenzae rarely reaches more than 30% around the world. Methicillin-resistance in Staphylococcus aureus is a common and increasing problem in hospitals but its extent varies both locally and nationally. Resistance is usually associated with the local spread of resistant strains. High standards of hygiene in hospitals can prevent the spread of such strains but once established they can be difficult to eradicate. Although Streptococcus pyogenes remains highly susceptible to penicillins, even after many decades of their use, resistance to macrolides has occurred. This resistance can rise and fall. Although the increase of macrolide resistance in S. pyogenes can often be associated with an increase in the use of these drugs, this is not always so. In some cases it has been shown to be caused by the spread of one or more resistant clones. Eradication of these clones can reduce the level of resistance markedly. Resistance to both macrolides and penicillins among strains of Streptococcus pneumoniae is seen world-wide but is highly variable from country to country. Local habits of drug usage may play a part. In Italy, for example, there is preference for the use of parenteral third-generation cephalosporins for some severe infections and there is a corresponding low level of penicillin-resistance among pneumococci.

Analysis of the expression of the putatively virulence-associated neisserial protein RmpM (class 4) in commensal Neisseria and Moraxella catarrhalis strains

The RmpM protein has been reported to be present only in pathogenic Neisseria species. In the present study we demonstrate that this protein is also present at least in N. lactamica and N. sicca strains. The N. lactamica protein reacts with a RmpM-specific monoclonal antibody (185,H-8), having a molecular mass (∼31 kDa) slightly lower than that of the meningococcal RmpM, and mouse antibodies from sera against outer membrane vesicles from both N. lactamica and N. sicca strains cross-react with the meningococcal RmpM. PCR and hybridization experiments with a complete rmpM probe agree with the immunodetection experiments. Our results strongly suggest that the meningococcal RmpM should not be considered a virulence marker, and the presence of this protein in the commensal species agrees with its role as a structural protein, proposed for the RmpM, which should be considerably conserved in the Neisseria species.

Analysis of the expression of the putatively virulence-associated neisserial protein RmpM (class 4) in commensal Neisseria and Moraxella catarrhalis strains.

The RmpM protein has been reported to be present only in pathogenic Neisseria species. In the present study we demonstrate that this protein is also present at least in N. lactamica and N. sicca strains. The N. lactamica protein reacts with a RmpM-specific monoclonal antibody (185,H-8), having a molecular mass ( approximately 31 kDa) slightly lower than that of the meningococcal RmpM, and mouse antibodies from sera against outer membrane vesicles from both N. lactamica and N. sicca strains cross-react with the meningococcal RmpM. PCR and hybridization experiments with a complete rmpM probe agree with the immunodetection experiments. Our results strongly suggest that the meningococcal RmpM should not be considered a virulence marker, and the presence of this protein in the commensal species agrees with its role as a structural protein, proposed for the RmpM, which should be considerably conserved in the Neisseria species.

Antibiotic susceptibilities among recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis from fifteen countries.

Between July 1998 and July 1999, 3,060 Haemophilus influenzae and 1,486 Moraxella catarrhalis strains were isolated in 31 centers in 15 countries in order to determine their antimicrobial susceptibilities and the presence of beta-lactamase production in Haemophilus influenzae. Overall 17.1% of the Haemophilus influenzae isolates were beta-lactamase positive, while more than 95% were susceptible to amoxicillin/clavulanate, cefaclor, loracarbef, cefuroxime, azithromycin and ciprofloxacin. Eleven (0.3%) isolates were beta-lactamase positive and ampicillin resistant and 7 (0.2%) isolates were ciprofloxacin resistant. The minimum inhibitory concentrations for 90% of the isolates tested were lowest for ciprofloxacin (0.03) and highest for cefprozil (8) against Moraxella catarrhalis.

Bacterial Resistence in the New Millennium: Its impact on antibiotic selection for respiratory tract infections

The targets of antibiotic intervention in respiratory tract infections continue to change. For example, the minimum inhibitory concentrations (MICs) of beta-lactams for Streptococcus pneumoniae have increased up to 100-fold in recent years. Because the mechanism of resistance in this respiratory tract pathogen is an alteration in penicillin-binding proteins, the higher the MIC of penicillin, the higher the MICs of all beta-lactams. Macrolide resistance in S pneumoniae is highly prevalent in many countries and correlates with penicillin resistance. Because the mechanisms of resistance to tetracyclines, chloramphenicol, and macrolides share the same transposon, resistance to multiple antibiotics in S pneumoniae is common. Although the prevalence of resistance to fluoroquinolones in S pneumoniae is low, it may well increase once these agents are widely prescribed for pediatric patients. The prevalence of ss-lactamase-producing strains of Haemophilus influenzae is stable even though it differs among individual countries. However, beta-lactam activity against H influenzae varies considerably worldwide. The efficacy of macrolide activity against H influenzae is questionable, and resistance to the fluoroquinolones is rare. Virtually all strains of Moraxella catarrhalis produce beta-lactamase. Most oral antibiotics, including the macrolides, are more active against M catarrhalis than H influenzae. Clearly, reassessment of current prescribing practices is critical if antibiotic efficacy is to be preserved and the risk for selection of resistance minimized in the new millennium.

Genetic diversity among strains of Moraxella catarrhalis cultured from the nasopharynx of young and healthy Brazilian, Angolan and Dutch children.

The present study describes the carriage patterns and genetic variability of Moraxella catarrhalis strains isolated from children living in different countries. Moraxella catarrhalis is genetically heterogeneous, but little is known about its geographic distribution and phenotypic and genetic diversity in warm-climate countries. A collection of 99 isolates from 30 Brazilian, 19 Angolan and 50 Dutch healthy children, all less than 5 years of age, was investigated for phenotypic and genotypic relatedness. The isolates from the three countries were similar where biochemical reactivity was concerned: 89 strains were beta-lactamase-producing and 87 were complement-resistant as determined by phenotype. There was no geographical difference in the prevalence of beta-lactamase-producing isolates, but the carriage rate of complement-resistant strains was significantly higher in Dutch than in Angolan children (P=0.004). Complement resistance of 66 randomly selected strains was genetically confirmed in a Southern hybridization assay by a novel DNA probe that is specific for complement-resistant strains and that demonstrated a sensitivity of 97% and a specificity of 100%. PCR amplification based on the probe sequence had a sensitivity of 98% and a specificity of 57% when compared to the outcome of a conventional culture spot test. PCR restriction fragment length polymorphism analysis of the MU 46 locus and pulsed-field gel electrophoresis of SpeI DNA macrorestriction fragments revealed genetic heterogeneity of strains from within and between the three countries, and no geographical clustering could be established. In conclusion, similar phenotypic characteristics but genotypic heterogeneity was found among Moraxella catarrhalis strains colonizing children in three different continents.

Epidemiological survey of bacterial resistance in upper respiratory tract infections in Italy

The vast majority of infections in the upper airways are caused by four bacterial species;, in Italy as elsewhere, antibiotics resistant strains are emerging. Enzymatic resistance to β-lactams in Haemophilus influenzae is becoming more important and affects 15% of isolates. On the other hand less than 0.3% of H. influenzae strains are fluoroquinolone-resistant. The number of β-lactamase-producing Moraxella catarrhalis strains in Italy has been thought to be lower than in other countries, but recent studies suggest 90% of strains are positive, a figure similar to figures reported in the international literature. The most recent data estimate high-level resistance to penicillin in pneumococci to be around 5%, but varies greatly in different geographical areas and with the different origins of the isolates. In spite of the low incidence of penicillin-resistant strains, the most recent figures for macrolide-resistance in Streptococcus pneumoniae range from 26.4 to 31.7%. More than 3 years after the dramatic increase in erythromycin-resistant Streptococcus pyogenes, the resistance levels in Italy are still among the highest in the world. Unlike the experience in other countries, resistance is often related not to the active efflux of antibiotic from the bacterial cell but to ribosomal methylation, thus affecting not only 14- and 15-membered macrolides, but also 16-membered compounds and lincosamides.

Enhancement of clearance of bacteria from murine lungs by immunization with detoxified lipooligosaccharide from Moraxella catarrhalis conjugated to proteins.

Moraxella catarrhalis strain 25238 detoxified lipooligosaccharide (dLOS)-protein conjugates induced a significant rise of bactericidal anti-LOS antibodies in animals. This study reports the effect of active or passive immunization with the conjugates or their antiserum on pulmonary clearance of M. catarrhalis in an aerosol challenge mouse model. Mice were injected subcutaneously with dLOS-tetanus toxoid (dLOS-TT), dLOS-high-molecular-weight proteins (dLOS-HMP) from nontypeable Haemophilus influenzae (NTHi), or nonconjugated materials in Ribi adjuvant and then challenged with M. catarrhalis strain 25238 or O35E or NTHi strain 12. Immunization with dLOS-TT or dLOS-HMP generated a significant rise of serum anti-LOS immunoglobulin G and 68% and 35 to 41% reductions of bacteria in lungs compared with the control (P<0.01) following challenge with homologous strain 25238 and heterologous strain O35E, respectively. Serum anti-LOS antibody levels correlated with its bactericidal titers against M. catarrhalis and bacterial CFU in lungs. Additionally, immunization with dLOS-HMP generated a 54% reduction of NTHi strain 12 compared with the control (P<0.01). Passive immunization with a rabbit antiserum against dLOS-TT conferred a significant reduction of strain 25238 CFU in lungs in a dose- and time-dependent pattern compared with preimmune serum-treated mice. Kinetic examination of lung tissue sections demonstrated that antiserum-treated mice initiated and offset inflammatory responses more rapidly than preimmune serum-treated mice. These data indicate that LOS antibodies (whether active or passive) play a major role in the enhancement of pulmonary clearance of different test strains of M. catarrhalis in mice. In addition, dLOS-HMP is a potential candidate for a bivalent vaccine against M. catarrhalis and NTHi infections.

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important β-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 β-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC 90 in μg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06–0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC 90, 0.5 μg/ml) was 4- to 128-fold more active than comparison β-lactams against the pneumoococci and was the most potent β-lactam (including penicillin) versus β-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T 1/2 of 1.5–2 h and C max values of 2.8 and 4.6 μg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 μg/ml for 4 to 6 hours (33–50% of dosing interval). Consequently, a susceptible MIC of ≤ 1 μg/ml or ≤ 2 μg/ml was proposed with zone diameter correlates of ≥ 18 and ≥ 15 mm (5-μg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at ≤ 0.5 μg/ml. Expanded clinical investigations seem warranted.

Analysis of Moraxella catarrhalis by DNA typing: evidence for a distinct subpopulation associated with virulence traits.

Two DNA typing methods, probe-generated restriction fragment length polymorphism analysis and single-adapter amplified fragment length polymorphism analysis, were used to study the genetic relationships among 90 Moraxella catarrhalis strains. Both methods were found to be highly concordant, generating a dendrogram with 2 main branches. The division of the M. catarrhalis population into 2 subspecies was supported by analysis of the 16S rRNA sequences. Both beta-lactamase-positive and beta-lactamase-negative strains were found in all main branches, suggesting horizontal transfer of the beta-lactamase gene. In contrast, 2 virulence traits, complement resistance and adherence to epithelial cells, were strongly associated with 1 of the 2 subspecies. The branch depth suggested that complement-resistant adherent strains diverged from a common ancestor more recently than did complement-sensitive nonadherent strains. These findings suggest the existence of subpopulations of M. catarrhalis that differ in virulence, and they may have implications for vaccine development.

Structural Analysis of Plasmid pLQ510 from Moraxella catarrhalis E22

The complete nucleotide sequence of plasmid pLQ510 from Moraxella catarrhalis strain E22 has been determined. This plasmid contained 12,082 bp with 38% GC content. Five open reading frames that encoded predicted proteins with homology to plasmid-encoded proteins from other bacteria were identified. A putative origin of replication that contained an AT-rich region followed by four direct repeats and an inverted repeat was identified.