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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular basis of central nervous system invasiveness by Haemophilus influenzae has been studied by using genetically defined mutants and in vivo and in vitro model systems. Capsular polysaccharide and lipopolysaccharide are important microbial determinants of the ability of H. influenzae to traverse the nasopharynx and localize in the cerebrospinal fluid and meninges after bacteremia. The genes for type b capsule confer greater invasive potential than do those for other capsular polysaccharides, although the molecular basis for this is not understood. Mutants have also indicated the role of lipopolysaccharide in enhancing the efficiency of bacterial translocation from the nose to the blood and in facilitating intravascular survival. Organisms that localize successfully in the blood and central nervous system are the progeny of a small fraction of the original challenge inoculum, often a single bacterium.
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PMID:Molecular basis of invasive Haemophilus influenzae type b disease. 158 86

Phagocytosis may be important in clearing Haemophilus influenzae from the bloodstream. To define the effect of type b capsule on phagocytosis, binding and ingestion by macrophages was measured for 5 isogenic sets of capsule-sufficient strains (clinical isolates and type b transformants of capsule-deficient mutants) and capsule-deficient mutants (strains lacking a 9-kb EcoRI fragment of chromosomal DNA associated with type b capsule expression). Capsule-sufficient strains were not bound in the absence of serum, whereas capsule-deficient strains were bound and ingested (1.8-5.1 organisms/macrophage; 59%-97% ingested). In the presence of nonimmune serum, capsule-sufficient strains were largely bound but not ingested (4.7-7.2 organisms/macrophage; 7%-21% ingested), whereas capsule-deficient strains were nearly all ingested (6.2-10.5 organisms/macrophage; 93%-97% ingested). Strains resisting ingestion caused persistent bacteremia 24 h after intravenous challenge in mice and were more likely than readily ingested strains to cause persistent bacteremia or death in infant rats. Thus, type b capsule inhibits ingestion by macrophages; resistance to ingestion may be an important virulence determinant of type b organisms.
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PMID:Type b capsule inhibits ingestion of Haemophilus influenzae by murine macrophages: studies with isogenic encapsulated and unencapsulated strains. 160 93

The immunological basis for protection against Brazilian purpuric fever (BPF), a fulminant infection of young children associated with bacteremia with Haemophilus influenzae biogroup aegyptius, is unknown. Candidate antigens to which protective antibodies may be directed include cell surface proteins and lipooligosaccharide (LOS). We studied the activity of antisera to LOS purified from a BPF H. influenzae biogroup aegyptius isolate. Anti-LOS antisera contained anti-LOS antibody by enzyme immunoassay and immunoblot and no detectable anti-outer membrane protein antibodies by immunoblot. Anti-LOS antisera had minimal bactericidal activity and were not protective against the homologous strain in an infant rat model of bacteremia. Antiserum to whole bacterial cells had a titer of anti-LOS antibody similar to that of anti-LOS antisera and was bactericidal and protective. Removal of anti-LOS antibodies from anti-whole cell antiserum by affinity chromatography did not result in a loss of bactericidal activity. Serum from a normal adult contained anti-LOS antibodies and had bactericidal activity. However, anti-LOS antibodies purified from this serum did not have detectable bactericidal activity. These studies suggest that anti-LOS antibodies produced in rats are not bactericidal and do not contribute to protection against experimental bacteremia with BPF strains of H. influenzae biogroup aegyptius.
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PMID:Antibodies to lipooligosaccharide of a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius lack bactericidal and protective activity. 163 9

Chemical mutagenesis techniques and genetic transformation methods were used to construct isogenic mutants of Haemophilus influenzae type b (Hib) defective in the ability to synthesize lipooligosaccharide (LOS). A mutant (17B) which expressed a LOS molecule with an altered oligosaccharide was less virulent than the wild-type parent strain, as determined by measurement of the ability of these strains to produce bacteremia in infant rats after intranasal challenge. Further mutagenesis of this mutant strain yielded two new mutants with different LOS phenotypes. Mutant 7A was slightly sensitive to the bactericidal activity present in normal infant rat serum and was even less virulent than its immediate parent strain (17B) in the intranasal challenge model. However, both mutants 17B and 7A could produce bacteremia and meningitis when introduced into infant rats by the intraperitoneal route. The other LOS mutant (14A) derived from mutant 17B exhibited a level of virulence equivalent to that of the original wild-type strain. Genetic transformation of wild-type chromosomal DNA into the essentially avirulent mutant 7A and selection of transformants on the basis of their LOS antigenic characteristics resulted in the sequential restoration of full virulence to this mutant. These findings suggest that LOS is involved on at least two different levels in the ability of Hib to produce invasive disease in the infant rat model. Changes in LOS phenotype can independently affect the ability of Hib to produce bacteremia after intranasal challenge and the sensitivity of Hib to killing by normal infant rat serum. These results reinforce the significance of Hib LOS in the expression of virulence by this pathogen.
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PMID:Effect of mutations in lipooligosaccharide biosynthesis genes on virulence of Haemophilus influenzae type b. 169 25

Modulation of the host's inflammatory response in bacterial meningitis may be beneficial. In this study, the effects of dexamethasone and HWA-138, an analog of pentoxifylline, on CSF cultures and cochlear inflammation in an infant rat model of Haemophilus influenzae type b were studied. Five-day-old infant rats were inoculated once intraperitoneally with 1 x 10(4) to 10 x 10(4) CFU of H. influenzae type b (strain 1406). Twenty-four hours later, infant rats were treated intraperitoneally with one dose of ampicillin (0.1 mg/g of body weight), cefotaxime (0.05 mg/g), or cefuroxime (0.05 mg/g) alone or in combination with one dose of dexamethasone (0.00015 mg/g) or HWA-138 (0.005 mg/g). Twenty-four hours after treatment with cefuroxime plus dexamethasone, animals had a significantly (P less than or equal to 0.04) greater incidence of bacteremia and meningitis (eight of nine animals) than that in animals of the other treatment groups. Overall, dexamethasone was associated with less inflammation (P less than 0.04) of the cochlear nerve compared with that from antibiotic treatment alone. In this model, when suboptimal antimicrobial therapy is administered, anti-inflammatory agents may be beneficial with respect to reducing cochlear inflammation. However, dexamethasone and cefuroxime lead to a higher rate of positive blood and cerebral spinal fluid cultures than cefuroxime alone.
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PMID:Effect of dexamethasone or HWA-138 in combination with antibiotics in experimental Haemophilus influenzae type b infection. 175 17

We questioned whether strains of ampicillin-resistant, non-beta-lactamase-producing (AmpR NBLP) Haemophilus influenzae with lower affinity penicillin-binding proteins (PBPs) might have altered virulence. The virulence of resistant transformant strains and the susceptible recipient was compared using infant rats. Following intraperitoneal inoculation, there was a significantly lower mortality rate and incidence and magnitude of bacteremia with two of three transformants compared to the recipient strain. Reduced virulence was not associated with greater bactericidal activity of serum or human neutrophils or faster clearance of the transformant following intravenous injection. Heated rat or human plasma supported exponential growth of the recipient, but not the transformant, suggesting deficient in vivo multiplication. We conclude that H. influenzae with altered PBPs are less virulent in an infant rat model which may be related to differences in in vivo growth.
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PMID:Virulence of non-beta-lactamase-mediated ampicillin-resistant Haemophilus influenzae. 176 51

Haemophilus influenzae type b (HIB) is a well-recognized cause of serious infection in infants and toddlers. However, little information exists regarding HIB infections in older children. This report describes serious HIB infections in 23 children (eight immunocompromised; 15 immunocompetent) older than 59 months of age. Data were collected over an 11-year period. The mean age of the children was 7.6 years (range, 5-15 years), and 14 were male. While three of the eight immunocompromised children had HIB pneumonia, none of the immunocompetent group had this diagnosis. Eleven of the 15 immunocompetent children had epiglottitis or meningitis. HIB bacteremia without focal infection occurred in four children, two immunocompromised and two immunocompetent. This study supports the recommendation of empiric HIB antibiotic therapy for children up to 12 years of age who have serious infections. Antibiotics effective against HIB should be included in the presumptive antibiotic therapy of seriously ill immunocompromised children, regardless of age.
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PMID:Haemophilus influenzae type b bacteremia in older children. 178 18

Cefdinir, a so-called third-generation oral cephalosporin was tested in vitro against over 700 pathogens from patients with bacteremia. Cefdinir was very active against the Enterobacteriaceae with a 50% minimum inhibitory concentration (MIC50) value range of less than or equal to 0.03-8 micrograms/ml. The enteric species having the highest MIC90S (greater than or equal to 16 micrograms/ml) were Citrobacter freundii, and the enterobacters, Morganella morganii, Proteus vulgaris, and Serratia marcescens. Cefdinir was generally two- to fourfold less active than cefixime, but markedly more potent with a wider spectrum compared with older oral cephalosporins, cefaclor or cefuroxime. In contrast to cefixime, cefdinir inhibited Staphylococcus aureus (MIC90, 1 micrograms/ml) and other staphylococci. Pneumococci, beta-hemolytic streptococci, Haemophilus influenzae, Moraxella catarrhalis, and pathogenic Neisseria spp. (MIC90S, 0.12-0.5 micrograms/ml) were cefdinir susceptible, but Pseudomonas aeruginosa, oxacillin-resistant staphylococci and Bacteroides fragilis gr. strains were resistant. Cefdinir was generally bactericidal with a minimal inoculum effect at 10(6) colony-forming units per spot. Cefdinir beta-lactamase hydrolysis by some recently described extended broad spectrum beta-lactamases was suspected. Cefdinir exhibited a wide, balanced spectrum for an oral cephalosporin indicating possible clinical use against susceptible pathogens in respiratory tract, urinary tract, genital and cutaneous infections.
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PMID:In vitro activity evaluations of cefdinir (FK482, CI-983, and PD134393). A novel orally administered cephalosporin. 179 57

Haemophilus influenzae infections of the genitourinary tract are rare. A case of a life-threatening Haemophilus influenzae bacteremia associated with a septic abortion is presented. Sexual transmission of bacteria after orogenital contact is proposed as a possible source of this uncommon infection.
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PMID:A life-threatening sexually transmitted Haemophilus influenzae in septic abortion: a case report. 185 17

The rapid quantitation of bacteria in blood was achieved by using a novel assay method for gram-negative bacterial lipopolysaccharide (endotoxin, LPS). The assay involves the capture of specific LPS onto microtiter plates by means of monoclonal antibodies directed against the oligosaccharide region of the LPS, followed by detection of the bound LPS by a chromogenic Limulus amebocyte lysate (LAL) system. This immunolimulus (IML) assay combines the specificity of monoclonal antibodies with the sensitivity of the LAL system to achieve the first specific, sensitive quantitation of bioactive endotoxin in plasma. In the animal model tested, Haemophilus influenzae type b (Hib) bacteremia in infant rats, there was a strong correlation between IML results and the concentration of Hib colony-forming units in blood samples (r = .845, P less than .001). Using antibodies with appropriate specificities, this approach should be useful for rapid detection of a wide range of gram-negative bacteria and endotoxins in blood.
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PMID:Detection of experimental Haemophilus influenzae type b bacteremia and endotoxemia by means of an immunolimulus assay. 185 84


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