Comparative activity of quinupristin/dalfopristin and RPR 106972 and the effect of medium on in-vitro test results. (1/118)

Quinupristin/dalfopristin and RPR 106972 were active in vitro against a wide range of aerobic Gram-positive organisms including Enterococcus faecium. However, most isolates of Enterococcus faecalis were resistant or of intermediate sensitivity. Against Staphylococcus aureus quinupristin/dalfopristin was more active but for all other species the range of activity of the two drugs was the same or RPR 106972 was more active. RPR 106972 was also more active against the respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis. Quinupristin/dalfopristin MICs for isolates of H. influenzae (1-8 mg/L) clustered around the breakpoint. There were differences in the quality of growth, but little difference in MICs or zone diameters was obtained on three different media: Mueller-Hinton (MHA), Iso-Sensitest (ISA), and Diagnostic Sensitivity Test (DST) agars. The addition of blood to the medium increased MICs 2- to 4-fold, with MHA showing the greatest increase, and reduced zone diameters around quinupristin/dalfopristin discs by 3-4 mm, with the greatest effect on ISA.  (+info)

Pathogenic neisseriae: complexity of pathogen-host cell interplay. (2/118)

Recent studies have provided insight into the function of important neisserial adhesins (pili and Opa) and their interaction with cellular receptors, including members of heparan sulfate proteoglycan, CD66, and integrin receptor families. These interactions not only allow colonization of the human mucosa but also stimulate cellular signaling cascades involving phosphatidylcholine-dependent phospholipase C, acidic sphingomyelinase and protein kinase C in epithelial cells, and Src-related kinases, Rac1, p21-activated kinase, and Jun N-terminal kinase in phagocytic cells. Activation of these pathways is essential for cellular entry and intracellular accommodation of the pathogens but also leads to early induction of cytokine release, thus priming the immune response. Detailed knowledge of the cellular signaling cascades that are activated by infection will aid us in applying both current and novel interfering drugs (in addition to classical antibiotic therapy) as therapy and prophylaxis for persistent or otherwise difficult-to-treat bacterial infections, including periodontal infections.  (+info)

Analysis of the immunological responses to transferrin and lactoferrin receptor proteins from Moraxella catarrhalis. (3/118)

Moraxella catarrhalis expresses surface receptor proteins that specifically bind host transferrin (Tf) and lactoferrin (Lf) in the first step of the iron acquisition pathway. Acute- and convalescent-phase antisera from a series of patients with M. catarrhalis pulmonary infections were tested against Tf and Lf receptor proteins purified from the corresponding isolates. After the purified proteins had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, we observed strong reactivity against Tf-binding protein B (TbpB; also called OMP1) and Lf-binding protein B (LbpB) but little or no reactivity against Tf-binding protein A (TbpA) or Lf-binding protein A (LbpA), using the convalescent-phase antisera. Considerable antigenic heterogeneity was observed when TbpBs and LbpBs isolated from different strains were tested with the convalescent-phase antisera. Comparison to the reactivity against electroblotted total cellular proteins revealed that the immune response against LbpB and TbpB constitutes a significant portion of the total detectable immune response to M. catarrhalis proteins. Preparations of affinity-isolated TbpA and LbpA reacted with convalescent-phase antisera in a solid-phase binding assay, but blocking with soluble TbpB, soluble LbpB, or extracts from an LbpA(-) mutant demonstrated that this reactivity was attributed to contaminants in the TbpA and LbpA preparations. These studies demonstrate the immunogenicity of M. catarrhalis TbpB and LbpB in humans and support their potential as vaccine candidates.  (+info)

Effect of carbon dioxide on testing of susceptibilities of respiratory tract pathogens to macrolide and azalide antimicrobial agents. (4/118)

The in vitro activities of erythromycin, azithromycin, and clarithromycin against 178 clinical isolates from the lower respiratory tract of patients with chronic obstructive pulmonary disease were determined by an agar dilution method. The plates were incubated in air alone or in 5% carbon dioxide. The MICs measured in air alone were lower for most isolates than those measured in 5% carbon dioxide, illustrating the "pH effect" of incubation in carbon dioxide. Testing of isolates in 5% carbon dioxide on pH-adjusted medium (pH 8.4) resulted in MICs of one or two doubling dilutions lower than those obtained on agar with a neutral pH. A bioassay of the three agents incubated in air and in 5% carbon dioxide resulted in a significant loss of activity of all three agents in the carbon dioxide-enriched atmosphere. However, this loss-of-activity effect was significantly reduced when the bioassay medium was adjusted to pH 8.4 prior to incubation in 5% carbon dioxide.  (+info)

Analysis of antigenic structure and human immune response to outer membrane protein CD of Moraxella catarrhalis. (5/118)

Moraxella catarrhalis is an important cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Outer membrane protein CD (OMP CD) is a 45-kDa protein which is a potential vaccine antigen to prevent infections caused by M. catarrhalis. Eight monoclonal antibodies were used to study the antigenic structure of the OMP CD molecule by assaying recombinant peptides corresponding to the sequence of the protein. This approach identified two surface-exposed epitopes, including one near the amino terminus (amino acids 25 to 44) and one in the central region of the molecule (amino acids 261 to 331). Assays with serum and sputum supernatants of adults with COPD revealed variable levels of antibodies to OMP CD among individuals. To determine which portions of the OMP CD molecule were recognized by human antibodies, three human serum samples were studied with six recombinant peptides which span the sequence of OMP CD. All three sera contained immunoglobulin G antibodies which recognized exclusively the peptide corresponding to amino acids 203 to 260 by immunoblot assay. Adsorption experiments with whole bacteria established that some of the human antibodies are directed at surface-exposed epitopes on OMP CD. We conclude that OMP CD is a highly conserved molecule which contains at least two separate epitopes which are exposed on the bacterial surface. While individual adults with COPD show variability in the immune response to OMP CD, a specific region of the OMP CD molecule (amino acids 203 to 260) is important as a target of the human immune response.  (+info)

DNA restriction patterns produced by pulsed-field gel electrophoresis in Moraxella catarrhalis isolated from different geographical areas. (6/118)

Pulsed field gel electrophoresis (PFGE) of the genomic DNA of Moraxella catarrhalis was done in 172 strains isolated from sputum of patients with respiratory infections in Nagasaki (130 strains), Europe (14 strains), Thailand (6 strains), Uganda (3 strains), Bangladesh (5 strains) and Kuwait (14 strains). Restriction endonuclease with SmaI generated 4-16 DNA fragments ranging from 1000 kb to 24.25 kb and was classified into 31 major groups. It was found that there were wide variations of DNA restriction patterns of strains isolated from the same and different geographical areas. DNA restriction patterns of strains isolated in Nagasaki during the last 12 years showed dynamic changes of the predominant strains in each time period. We conclude from this study that PFGE is a suitable method to document interstrain variation in M. catarrhalis.  (+info)

Survey of susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates to 26 antimicrobial agents: a prospective U.S. study. (7/118)

An antimicrobial susceptibility surveillance study of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates was performed during the winter of 1996-1997 in order to determine their susceptibilities to 5 fluoroquinolones and 21 other antimicrobial agents. Broth microdilution MICs were determined for 2, 752 isolates from 51 U.S. medical centers. Of the 1,276 S. pneumoniae isolates, 64% were susceptible, 17% were intermediate, and 19% were highly resistant to penicillin. On the basis of the MICs at which 90% of isolates are inhibited and modal MICs, the hierarchy of the five fluoroquinolones from most to least active was grepafloxacin > sparfloxacin > levofloxacin = ciprofloxacin > ofloxacin. For S. pneumoniae isolates for which penicillin MICs were elevated, the MICs of the cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole were also elevated, but the MICs of the fluoroquinolones, vancomycin, and rifampin were not. The prevalence of penicillin-susceptible pneumococci varied by U.S. Bureau of the Census region (range, 44% in the East South Central region to 75% in the Pacific region). In addition, S. pneumoniae isolates from blood were significantly more susceptible to penicillin than those from respiratory, ear, or eye specimens, and pneumococci from patients +info)

Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in the United States, 1997-1998. (8/118)

A national antimicrobial resistance surveillance study was conducted from December 1997 to May 1998 to determine the prevalence of antimicrobial resistance in 6620 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In this centralized study, which involved 163 institutions located in 43 states, we determined MICs for representatives of five antimicrobial classes: beta-lactams (penicillin, co-amoxiclav, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), co-trimoxazole, glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). In most S. pneumoniae isolates, all antimicrobials were to be found active, but amongst penicillin-resistant isolates (MICs > or = 2 mg/L), resistance to other beta-lactams, macrolides and co-trimoxazole was common. For vancomycin and levofloxacin, however, activity was not associated with penicillin resistance. The prevalence of penicillin-nonsusceptible (intermediate and resistant) pneumococci was highest in the South Atlantic (44%) and East South Central (43%) regions and lowest in the Mid-Atlantic (28%) and New England (28%) regions. Resistance to beta-lactams, macrolides and co-trimoxazole was more commonly found amongst respiratory isolates than blood isolates and in strains from patients < or = 12 years old than from older patients. beta-lactamase, which was detected in 33% of H. influenzae and 92% of M. catarrhalis strains, did not affect the activity of the beta-lactams under study other than ampicillin. Certain agents, such as vancomycin and the fluoroquinolones, remain highly active, and well-designed surveillance systems that monitor MIC distributions would be needed to detect a potential for reduced susceptibility. In addition, surveillance programmes should be designed to collect information about associated resistance as well as differences in prevalence associated with region, specimen source and patient age.  (+info)