Comparative efficacy of ampicillin and trimethoprim-sulfamethoxazole in otitis media.
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Seventy-nine children with acute otitis media were the subjects in a study designed to compare the effectiveness of ampicillin and trimethoprim-sulfamethoxazole in this infection. They received either of these two agents according to a double-blind randomized procedure that also took the child's weight into account. No significant difference was found in the clinical outcome between the two treatment regimens. Undesirable side effects from TMP-SMX were notably few. (+info)
Suppression of macrophage activation with CNI-1493 increases survival in infant rats with systemic Haemophilus influenzae infection.
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CNI-1493, a potent macrophage deactivator, was used to treat infant rats systemically infected with Haemophilus influenzae type b (Hib). CNI-1493 was injected 1 h prior to bacterial inoculation and 24 h later and resulted in a 75 percent increased rate of survival compared to that for untreated controls. The effect of CNI-1493 on the inflammatory response was studied by immunohistochemical detection of individual tumor necrosis factor alpha (TNF-alpha)-, interleukin 1 beta (IL-1beta)-, and gamma interferon (IFN-gamma)-producing cells in the spleen. A significant reduction of the incidence of TNF-alpha- and IL-1beta-expressing cells was found for CNI-1493-treated animals. IFN-gamma expression was not suppressed by CNI-1493, indicating that cytokine inhibition was specific in macrophages. CNI-1493 significantly reduced the number of infiltrating granulocytes in the brain from that for controls. This study provides evidence that CNI-1493 protects against lethal Hib infection by deactivating the inflammatory cascade in infant rats. (+info)
Invasive Haemophilus influenzae disease in adults.
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We reviewed retrospectively all invasive Haemophilus influenzae (Hi) infections in adults ascertained from reference laboratory records and notifications from five NHS regions over the 5 years from 1 October 1990, a period encompassing the introduction of routine Hib childhood immunization (October 1992). A total of 446 cases were identified, a rate of 0.73 infections per 10(5) adults per annum. Though numbers of Hib infections in adults fell after the introduction of Hib vaccines for children (P = 0.035), and there was no increase in infections caused by other capsulated Hi serotypes, total numbers of invasive Hi infections increased due to a large rise in infections caused by non-capsulated Hi (ncHi) strains (P = 0.0067). There was an unexpectedly low rate of infections in those aged 75 years or more (P < 0.0001). The commonest clinical presentations were pneumonia with bacteraemia (227/350, 65%) and bacteraemia alone (62/350, 18%) and the highest rates of disease were in the 65-74 years age group (P < 0.0001). Clinical presentation was not influenced by the capsulation status of the invading Hi strain. 103/350 cases (29%) died within 1 month, and 207/350 (59%) within 6 months of their Hi infection. Case fatality rates were high in all age groups. Pre-existing diseases were noted in 220/350 cases and were associated with a higher case fatality rate (82% vs. 21%, P < 0.0001). After the introduction of Hib immunization in children, invasive Hib infections in unimmunized adults also declined, but the overall rate of invasive Hi disease in adults increased, with most infections now caused by non-capsulated strains. Physicians and microbiologists should be aware of the changing epidemiology, the high associated mortality and high risk of underlying disease. Invasive haemophilus infections in adults should be investigated and treated aggressively. (+info)
Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections.
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We conducted a multicenter prospective study to document changes in nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis during antibiotic therapy. A cohort of 629 children with respiratory tract infections underwent nasopharyngeal sampling before and after antibiotic treatment. Susceptibility testing, serotyping, arbitrarily primed polymerase chain reaction, and pulsed-field gel electrophoresis were used to compare pretreatment and posttreatment strains of S. pneumoniae. A significant decrease in carriage of all 3 species (especially S. pneumoniae and B. catarrhalis) was recorded. The increase in the proportion of penicillin-resistant pneumococci (PRP; 66% vs. 44%) was due to the decreased carriage of penicillin-susceptible pneumococci (71 of 629 vs. 176 of 629). The risk of PRP carriage in a given child did not increase. None of the children was found to harbor genetically related strains with increased minimum inhibitory concentrations. Given the multiple resistance of PRP, beta-lactam antibiotic therapy also increased the incidence of macrolide-resistant strains, whereas macrolides selected both macrolide- and penicillin-resistant strains. (+info)
Pharmacodynamics to combat resistance.
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The ability to identify agents with the optimal combination of potency, pharmacokinetics and pharmacodynamics should help to maximize bacteriological cure and thus minimize the potential for selection and spread of resistance. Gemifloxacin demonstrated excellent correlation between efficacy and the AUC0-24h/MIC ratio whereas there was little correlation with time above MIC. Thus, gemifloxacin is similar to other quinolones in that it is the amount of drug present, not the frequency of administration, that determines antibacterial effect. In a neutropenic murine thigh model of infection, caused by Gram-negative bacilli, a AUC0-24h/MIC ratio of approximately 100 was necessary to protect >90% of the animals, which is similar to data reported previously for other quinolones. However, in order to achieve the same protection in an immunocompetent murine infection caused by Streptococcus pneumoniae, the AUC-24h/MIC ratio was approximately 25. The magnitude of this AUC0-24h/MIC ratio did not alter for strains exhibiting penicillin or macrolide resistance. Importantly, when gemifloxacin was examined against strains of S. pneumoniae with well-characterized ciprofloxacin resistance (including mutations in gyrase, parC and parE as well as efflux strains) there was little impact on the in vivo efficacy. Overall, the data showed a trend towards a decrease in the AUC0-24h/MIC ratio for these more resistant strains. The lower AUC0-24h/MIC ratio was especially noticeable for the efflux mutants suggesting that the quinolone efflux mechanism may be down-regulated in vivo and may be of minimal relevance to the clinical activity of gemifloxacin against S. pneumoniae. The efficacy of gemifloxacin, in comparison with other oral agents used to treat respiratory infections, has also been evaluated in a rat model using doses, and therefore AUC0-24h/MIC ratios, that approximate those in man. These data confirm the excellent activity of gemifloxacin against strains of Haemophilus influenzae and S. pneumoniae, including those demonstrating penicillin, macrolide and quinolone resistance. (+info)
Haemophilus influenzae infection and Guillain-Barre syndrome.
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It has been reported recently that Haemophilus influenzae can elicit an axonal form of Guillain-Barre syndrome. To investigate the incidence and features of H. influenzae-related Guillain-Barre syndrome, anti-H. influenzae antibody titres were measured by enzyme-linked immunosorbent assay (ELISA) in 46 consecutive Japanese patients with Guillain-Barre syndrome, 49 normal controls, 24 patients with multiple sclerosis and 27 patients with amyotrophic lateral sclerosis (ALS). Whole bacteria of non-encapsulated (non-typable) H. influenzae isolated from one of the Guillain-Barre syndrome patients was the antigen used. Elevated anti-H. influenzae antibodies for two or three classes of IgG, IgM and IgA were found in six (13%) Guillain-Barre syndrome patients, but not in the normal controls and patients with multiple sclerosis or ALS. The incidence was significantly higher in patients with Guillain-Barre syndrome than in the normal controls (P = 0.01) and patients with multiple sclerosis or ALS (P = 0.009). Western blot analysis confirmed that the H. influenzae-positive patients' IgG recognized the lipopolysaccharides of H. influenzae. Guillain-Barre syndrome patients with anti-H. influenzae antibodies showed relatively uniform clinical and laboratory features: prodromal respiratory infection, less frequent cranial and sensory nerve involvement, pure motor axonal degeneration on electrophysiology, and positivity for IgG anti-GM1 antibodies. Although the features were similar to those in Guillain-Barre syndrome patients infected by Campylobacter jejuni, the recoveries seemed to be better in patients with H. influenzae-related Guillain-Barre syndrome. It is concluded that a form of Guillain-Barre syndrome occurs after respiratory infection by H. influenzae in the Japanese population. A particular strain of non-typable H. influenzae has a ganglioside GM1-like structure and elicits axonal Guillain-Barre syndrome similar to C. jejuni-related Guillain-Barre syndrome. (+info)
Prevention of Haemophilus influenzae type b colonization by vaccination: correlation with serum anti-capsular IgG concentration.
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Concentrations of serum anti-Haemophilus influenzae type b (anti-Hib) capsular polysaccharide (CPS) >/=0.15 and >/=1.0 microgram/mL are widely used as surrogates for protection against invasive Hib disease. However, the relationship between serum anti-Hib CPS following immunization and protection against colonization is not known, making it difficult to evaluate new Hib vaccines or combination vaccines. In the Dominican Republic, nasopharyngeal swabs were collected from 546 9-month-old infants who had received Hib conjugate vaccine at ages 2, 4, and 6 months and from 600 unvaccinated infants of the same age. The prevalence of Hib colonization was lower among vaccinated infants than among unvaccinated infants (0.9% vs. 2.3%). Among vaccinated infants, protection against colonization was significantly correlated with anti-Hib CPS concentrations >/=5 microgram/mL 1 month following the third dose of vaccine. These results suggest that the concentration of serum anti-Hib CPS needed for protection against colonization is greater than that needed for protection for invasive disease. (+info)
Toward elimination of Haemophilus influenzae type B carriage and disease among high-risk American Indian children.
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OBJECTIVES: This report describes the epidemiology of Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal colonization among Navajo and White Mountain Apache children younger than 7 years in an era of widespread immunization. METHODS: We conducted active surveillance for invasive H influenzae disease from 1992 to 1999 and an oropharyngeal carriage study from 1997 to 1999. The predominant vaccine used was PedvaxHib. RESULTS: The average annual incidence of invasive Hib disease among children younger than 24 months was 22 cases per 100,000. Of 381 children younger than 7 years, only 1 (0.3%; 95% confidence interval = 0.0%, 1.3%) was colonized with Hib; 370 (97%) had received 2 or more doses of Hib conjugate vaccine. CONCLUSIONS: Among Navajo and White Mountain Apache children, Hib conjugate vaccines have led to a sustained reduction in invasive Hib disease and a reduction in oropharyngeal Hib carriage. The disease incidence among children younger than 24 months remains 20 times higher than in the general US population. Hib elimination will require additional characterization of colonization and disease in these high-risk populations. (+info)