Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O75191 (H. influenzae)
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We conducted a large, multicenter, randomized, open-label study throughout France comparing the efficacy and safety of cefixime suspension (8 mg/kg/day, b.i.d., for 10 days) versus amoxicillin-clavulanate suspension (80 mg/kg/day, t.i.d., for 10 days) in 510 children (ages 6 to 36 months) with acute otitis media. The most frequent microorganisms colonizing the nasopharynx at the start of treatment were Streptococcus pneumoniae (51.5%), Haemophilus influenzae (45%) and Moraxella catarrhalis (30.2%). Rates of beta-lactamase positivity were 32.1% and 95.3% for H. influenzae and M. catarrhalis, respectively. Decreased susceptibility of S. pneumoniae to penicillin was found in 39.7% of isolates. Clinical efficacy was 87.8% (223/254) for cefixime and 87.0% (215/247) for amoxicillin-clavulanate. At the 5-week follow-up visit, relapse had occurred in 15.7% (31/197) of cefixime-treated patients and in 15.6% (32/205) of those treated with amoxicillin-clavulanate. We conclude that these two regimens are equally effective in acute otitis media in children.
Infection 1995
PMID:Acute otitis media in children: a study of nasopharyngeal carriage of potential pathogens and therapeutic efficacy of cefixime and amoxicillin-clavulanate. 853 37

Prevention of nontypeable Haemophilus influenzae otitis media by vaccination is an important health care goal. Proteins important in bacterial adherence deserve consideration as potential vaccine candidates. Two colleagues and I previously identified a family of immunogenic high-molecular-weight proteins important in adherence of nontypeable H. influenzae to human epithelial cells (J.W. St. Geme III, S. Falkow, and S.J. Barenkamp, Proc. Natl. Acad. Sci. USA, 90:2875-2879, 1993). In the work described here, I determined whether immunization with two such adherence proteins, HMW1 and HMW2, purified from prototype nontypeable Haemophilus strain 12, would modify the course of experimental otitis media caused by the homologous strain. Chinchillas received three monthly subcutaneous injections with 40 microgram of an HMW1/HMW2 protein mixture in Freud's adjuvant. One month after the last injection, animals were challenged by intrabullar inoculation with 300 CFU of nontypeable H. influenzae 12. Infection developed in five of five control animals versus 5 of 10 immunized animals (P = 0.08, Fisher exact, one-tailed). Among infected animals, bacterial counts in middle ear fluid specimens 7 days postchallenge were significantly greater in control animals than in immunized animals (P = 0.014, Mann-Whitney U test). Serum antibody titers following immunization were comparable in uninfected and infected animals. However, infection in immunized animals was uniformly associated with the appearance of bacteria downregulated in expression of the high-molecular-weight proteins, suggesting bacterial selection in response to immunologic pressure. Although protection following immunization was incomplete, these data suggest that the high-molecular-weight adhesion proteins are potentially important protective antigens which might represent one component of a multicomponent nontypeable Haemophilus vaccine.
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PMID:Immunization with high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae modifies experimental otitis media in chinchillas. 860 86

In an evaluator-blind, parallel-group, multicenter study, the efficacy and tolerability of ceftibuten 400 mg capsules once daily were compared with clarithromycin 500 mg twice daily for 7-14 days in the treatment of 309 patients with acute exacerbation of chronic bronchitis (AECB). Clinical (n = 262) and microbiological (n = 71) assessments were conducted before treatment, during days 4-6 of treatment, and at 0-6 and 7-21 days after treatment. Clinical efficacy success rates (cure/improvement) at the end of treatment (0-6 days) were 91.0% for ceftibuten and 93.0% for clarithromycin. In the intent-to-treat population, the overall clinical assessment showed a success rate of 77.6% (121/156) in the ceftibuten group and 78.4% (120/153) in the clarithromycin group (95% confidence interval, -10.8 to +9.0%). One patient in each of the ceftibuten and clarithromycin groups had a microbiological relapse and became a treatment failure. The overall success rate was 84.3% for ceftibuten and 86.7% for clarithromycin (C.I. -11.7%, +6.9). Overall eradication of the target pathogens (Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae) was 84.8% for ceftibuten and 89.5% for clarithromycin. Eradication rates for ceftibuten at 0-6 days post treatment were 95.2% (H. influenzae), 87.5% (M. catarrhalis), and 100% (S. pneumoniae), compared with 85.7%, 100% and 100%, respectively, for clarithromycin. Significantly fewer patients in the ceftibuten group experienced treatment-related adverse events than in the clarithromycin group (5.3 vs 21.9%; p < 0.001). This difference was due to a large number of patients in the clarithromycin group reporting taste perversion (12.6%) or gastrointestinal adverse events (9.9%). Given its tolerability and efficacy profiles, and the advantage of once-daily administration, ceftibuten provides a rational alternative for the treatment of AECB.
Infection
PMID:Randomized comparison of once-daily ceftibuten and twice-daily clarithromycin in the treatment of acute exacerbation of chronic bronchitis. 950 88

Thirty-eight clinical isolates of Haemophilus influenzae and ten clinical isolates of Streptococcus pneumoniae were examined for IgA1 protease production. A suspension of surface material of each individual strain was incubated with human secretory IgA; IgA1 cleavage products were detected by SDS-PAGE and immunoblotting. The high incidence of IgA1 protease-positive strains (68.4% of the examined H. influenzae and 100% of the examined S. pneumoniae strains) confirms that IgA1 protease activity is a frequent characteristic of these two species. Yet the presence of this enzyme is, if at all, only a minor decisive factor for the induction of symptomatic infections of the upper respiratory tract by IgA1 protease-positive bacteria.
Infection
PMID:IgA1 protease production by bacteria colonizing the upper respiratory tract. 956 83

The case of a patient with systemic lupus erythematosus presenting with severe leg cellulitis caused by Hemophilus influenzae non-B biotype III is reported. Skin infections caused by H. influenzae in general, and of the extremities in particular, seem to be rare in adults. This is the first reported case of cellulitis caused by H. influenzae biotype III. The infection was treated successfully with antibiotics. This case highlights the importance of blood cultures and prompt antimicrobial treatment in febrile adults with cellulitis, especially immunocompromised patients.
Infection
PMID:Hemophilus influenzae biotype III cellulitis in an adult. 1002 7

In an ongoing prospective study, IL-1 concentrations were measured in 78 children (aged 3-36 months) with acute otitis media receiving antibiotics. Middle ear fluid IL-1 concentrations were determined using ELISA kits. Ninety-eight middle ear fluid samples were obtained by tympanocentesis at enrollment (day 1) and 43 samples were collected on days 4-5. Ninety-two pathogens were isolated in 77/98 samples obtained on day 1: 55 Haemophilus influenzae, 34 Streptococcus pneumoniae, 2 Moraxella catarrhalis and 1 Streptococcus pyogenes. Among 37 paired samples initially culture-positive, eradication of the pathogen was achieved on day 4-5 in 20 while pathogens were still present in 17. On day 1, IL-1 was detected in 61/77 (79%) culture-positive samples vs 9/21 (43%) culture-negative ones (P = 0.003). The mean +/- SD middle ear fluid concentration of IL-1 on day 1 was significantly higher in culture-positive (316 +/- 508 pg/ml) than in culture-negative samples (111 +/- 245 pg/ml) (P = 0.01). When paired samples were evaluated, IL-1 decreased on days 4-5 in 13/20 (65%) ears where bacterial eradication was achieved, but also in 11/19 (58%) with persistent or new infection. The mean IL-1 concentrations decreased on days 4-5 in the 20 samples from ears where bacterial eradication was achieved (330 +/- 460 vs 118 +/- 294 pg/ml, P = 0.1) but also in the 17 samples where it was not (465 +/- 660 vs 232 +/- 289 pg/ml, P = 0.02). No significant differences were found between day 1 and days 4-5 in the mean IL-1 concentrations measured in patients with H. influenzae vs S. pneumoniae or concomitant H. influenzae and S. pneumoniae. It was concluded that: 1) IL-1 was detected in the middle ear fluid of most patients with acute otitis media; 2) significantly higher IL-1 concentrations were found in patients with culture-positive than in those with culture-negative acute otits media; 3) IL-1 concentrations decreased on days 4-5 of antibiotic therapy, whether the pathogen was eradicated or not.
Infection
PMID:Dynamics of interleukin-1 production in middle ear fluid during acute otitis media treated with antibiotics. 1037 27

There is an overwhelming consensus on the fact that Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis represent the prevailing bacterial pathogens of community-acquired lower respiratory tract infections. Their specific incidence as causative agents of the more common syndromes is known to vary even profoundly depending on geographic location, and the same holds true for the rates of resistance to antimicrobial drugs. Europe does not escape the threat posed by the present pandemic spread of penicillin resistance in S. pneumoniae although, as expected, countries like Spain and France are greatly affected, while others including Germany, Italy, The Netherlands and the Scandinavian region are comparatively spared. In several sites multiple resistance has been described in S. pneumoniae and the most affected drugs include penicillin, the macrolides, co-trimoxazole and tetracycline. In H. influenzae synthesis of beta-lactamases the main trait of resistance is expressed. Lack of susceptibility to beta-lactams dictated by a different mechanism remains extremely rare. Considerable variations in the incidence of this characteristic are apparent when European countries are considered. France and Spain are again widely affected, while Germany, The Netherlands and Italy display rates of beta-lactamase-positive H. influenzae of about 10%. M. catarrhalis must be considered generally resistant to non-protected aminopenicillins since over 90% of these organisms produce beta-lactamases.
Infection 1999
PMID:Epidemiology of resistance to antimicrobial drugs in the major respiratory pathogens circulating in Europe. 1088 19

Bony tissues are integral parts of the function of the middle ear and the protection of adjacent vital structures. To explore the reaction of middle ear bone to acute otitis media, rats were challenged with Streptococcus pneumoniae and Haemophilus influenzae. Local changes were monitored for up to 1 month. After reverse transcription, competitive polymerase chain reaction was used to determine the expression levels of two molecular markers of bone formation, osteocalcin and procollagen I, and the two cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, in the bone. Middle ear bone responded rapidly to bacterial challenge, and the reaction depended upon the causative agent. On day 1, IL-6 and TNF-alpha transcripts were detected in the bone from all middle ears. After a short period of decreased expression of osteocalcin, during which the otitis diagnosis could not be made clinically, the levels of bone formation markers increased dramatically. The maximum levels of these markers were reached on days 6 and 14 for animals challenged with H. influenzae and pneumococci, respectively. Infections induced by pneumococci had a longer duration, and after the initial phase the production of osteocalcin and procollagen transcript were significantly higher in the pneumococcus-infected animals. The results indicate that even in an uncomplicated infection, the bone of the bulla reacts to an acute otitis media with a short period of inhibited osteoblast activity followed by a longer period of new bone formation.
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PMID:Expression of molecular markers for bone formation increases during experimental acute otitis media. 1127 36

Sickle cell anaemia (SCA) predisposes a child to infections for various reasons, including increased bone marrow turnover, poor perfusion and functional asplenia leading to decreased opsonisation of polysaccharide encapsulated organisms. Bacteria and viruses that most frequently cause serious infections in children with sickle cell disease are Streptococcus pneumoniae, Haemophilus influenzae type b, Salmonella spp., Escherichia coli, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, parvovirus B19 and hepatitis A, B and C viruses. Penicillin prophylaxis has decreased the incidence of infection-related morbidity and mortality significantly in children with SCA. Children <3 years of age are administered oral penicillin 125mg twice daily, and the dose is increased to 250mg twice daily for the >3 to 5 year age group. Adherence to the penicillin prophylactic regimen is recommended for children with SCA who are >5 years of age. For children with SCA who have recurrent invasive pneumococcal infections, an effort is made to keep the child on penicillin prophylaxis indefinitely. The administration of various childhood vaccines has also made an appreciable impact on the overall morbidity and mortality associated with infection in children with SCA. The administration of the heptavalent conjugate pneumococcal vaccine (PCV7) has provided control of invasive pneumococcal infections, and the prophylactic use of the H. influenzae type b conjugate vaccine has reduced the incidence of septicaemia and meningitis caused by this organism. Other vaccines used prophylactically in children with SCA include hepatitis A and B, and vaccines against influenza and varicella viruses. The immediate administration of intravenous antibacterials, after appropriate blood and urine cultures, is of great importance in the treatment of the febrile child with SCA. Ceftriaxone and cefotaxime have been recommended for the treatment of septic episodes in SCA associated with S. pneumoniae, Haemophilus and Salmonella spp. Infection with Yersinia enterocolitica may be treated with cefotaxime or an aminoglycoside. The prevalence of Helicobacter pylori infection in SCA is unknown. Effective therapies include metronidazole, tetracycline or amoxicillin. Parvovirus infections require supportive care and specific antiviral therapy is not indicated. The judicious use of antimicrobials is encouraged in view of the worldwide emergence of multidrug-resistant strains. The long term sequelae associated with infections in children with SCA can be decreased with the implementation of immunisation programmes and effective and prompt treatment with appropriate antibacterials.
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PMID:Prevention and management of infection in children with sickle cell anaemia. 1173 65

Polysaccharide(PS)-encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis are among the most prevalent bacterial pathogens of humans. Infections caused by these organisms are both common (otitis media, sinusitis) and severe (meningitis, bacteremia). Antibodies directed against the capsular PS of encapsulated bacteria prevent infection by promoting opsonophagocytic killing. Most bacterial PS, however, are type II T-cell-independent (TI-2) antigens that are poorly immunogenic in young children at highest risk of developing disease. Conjugation of bacterial PS to a protein carrier converts the immune response to a T-cell-dependent (TD) form and significantly improves the immunogenicity of PS, especially in infants. H. influenzae type b (Hib) is a major cause of invasive infection in non-immune children. The medical importance of this pathogen and the availability of both TI-2 and TD Hib PS vaccine formulations have made the human anti-Hib-PS immune response an excellent model for the study of the biology of these B cell responses.
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PMID:Antibody repertoires in infants and adults: effects of T-independent and T-dependent immunizations. 1182 16


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