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Biomedical subjects

K Roos

Publications and source records attributed to K Roos.

At least 19 recordsLinked to original sources

Bacteriological efficacy of 5-day therapy with telithromycin in acute maxillary sinusitis.

Increasing resistance among the key pathogens responsible for community-acquired respiratory tract infections, namely Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, has the potential to limit the effectiveness of the antibacterial agents available to treat these infections. Moreover, there are regional differences in the susceptibility patterns observed and, as treatment is usually empirical, choosing an effective treatment can be challenging. Telithromycin, the first ketolide to be approved for clinical use, offers an activity profile that covers the key respiratory pathogens including penicillin- and macrolide-resistant S. pneumoniae as well as beta-lactamase-producing H. influenzae and M. catarrhalis. In a pooled analysis of three large controlled clinical trials involving patients with acute maxillary sinusitis, the bacteriological efficacy of 5- or 10-day treatment with telithromycin and 10-day treatment with comparators was evaluated. Telithromycin administered as a once-daily 800 mg dose for 5 days achieved eradication rates of 91.8, 87.5 and 92.9% for S. pneumoniae, H. influenzae and M. catarrhalis, respectively. Bacteriological eradication of 8/10 and 12/14 isolates of S. pneumoniae resistant to penicillin and erythromycin, respectively, was also reported following 5-day treatment with telithromycin. The clinical efficacy of this regimen was equivalent to that of a 10-day regimen of telithromycin or standard 10-day courses of amoxicillin-clavulanic acid or cefuroxime axetil. Telithromycin 800mg given for 5 days was well tolerated, with the majority of adverse events being of mild or moderate intensity. These data suggest that telithromycin provides effective first-line therapy for use in patients with acute maxillary sinusitis in a short and convenient once-daily dosage regimen.

Adolescent↗

Clinical and bacteriological efficacy of 5-day telithromycin in acute maxillary sinusitis: a pooled analysis.

OBJECTIVES: To compare the efficacy and tolerability of a 5-day course of telithromycin (800 mg once daily) with a 10-day course of telithromycin or standard comparators (amoxicillin-clavulanate 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily) in patients with acute maxillary sinusitis (AMS). METHODS: Data from three randomised double blind studies were pooled. The studies included patients with clinical symptoms of AMS and sinus X-ray findings of total opacity, air-fluid levels or mucosal thickening. RESULTS: Pooled analysis of results for 5-day telithromycin revealed overall clinical cure rates of 83.6% (383/458 patients) at post-therapy (days 17-24) and 78.9% (330/418 patients) at late post-therapy (days 31-45) in the per-protocol population. Clinical cure rates at post-therapy were equivalent to those observed with 10-day telithromycin (82.5% vs 81.7%) or comparator treatment (80.9% vs 77.4%). Moreover, clinical cure rates exceeded 80% in subgroups of patients of interest, including those with severe infection and those fulfilling more stringent criteria for bacterial AMS. A satisfactory bacteriological outcome was achieved in 87.6% of patients. The 5-day telithromycin regimen was well tolerated. CONCLUSIONS: Telithromycin once daily for 5 days offers effective treatment for AMS and is comparable to 10-day courses of standard treatments.

Acute Disease↗

CD4+CD25+ T lymphocytes in human tonsils suppress the proliferation of CD4+CD25- tonsil cells.

Animal studies define CD4+CD25+ T cells as a subset that protect against autoimmune inflammation. We wanted to investigate whether CD4+CD25+ T cells from patients with recurrent tonsillitis could suppress the proliferation of other tonsil cells, in vitro, as this immunological tissue also may serve as a model for chronic inflammation. Tonsil CD4+CD25+ cells markedly suppressed the proliferation of CD4+CD25- T cells in Concanavalin A-stimulated cocultures compared with cultures containing CD4+CD25- T cells only. The suppression exerted by the CD4+CD25+ cells was abrogated if these cells were irradiated before coculture or if interleukin (IL)-2 was added to the culture medium. CD4+CD25+ T cells proliferated poorly in response to mitogen, when cultured alone. Substitution with CD4+CD25+ T cells isolated from peripheral blood, enriched by similar methods, did not downregulate the proliferation of CD4+CD25- responder cells from tonsils. The augmented suppressive ability of tonsil CD4+CD25+ T cells compared with cells of this phenotype from blood, on CD4+CD25- responder cells from tonsils, suggests that there may be a functional difference between CD25+ cells from the two locations. In conclusion, CD4+CD25+ T cells from inflamed tonsils distinctly suppressed T-cell responses to mitogen in vitro, pointing to a regulatory role for CD4+CD25+ cells retrieved from inflammatory reactions in humans.

Adolescent↗

Efficacy and tolerability of once-daily therapy with telithromycin for 5 or 10 days for the treatment of acute maxillary sinusitis.

BACKGROUND: The efficacy and tolerability of oral telithromycin 800 mg once daily for 5 vs. 10 days were assessed in patients with acute maxillary sinusitis (AMS). METHODS: Adults (n = 341) with confirmed AMS diagnosed on clinical signs and symptoms and sinus X-ray showing total opacity or air-fluid level were randomized to receive oral telithromycin for 5 days (followed by placebo for 5 days; n = 170) or 10 days (n = 171). Causative pathogens were isolated by pretreatment sinus puncture (day 1). Clinical and bacteriologic outcomes, and safety and tolerability endpoints were assessed. RESULTS: Clinical cure rates post-therapy (per-protocol; days 17-21) were comparable (91.1% in the 5-day group, n = 123; 91.0% in the 10-day group, n = 133). Bacteriologic eradication rates (per-protocol) were also similar (90.7 vs. 91.3%). Both regimens were well tolerated. CONCLUSIONS: A 5-day course of telithromycin 800 mg once daily is an effective, well-tolerated treatment for adults with AMS, comparable to a 10-day regimen.

Acute Disease↗

Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial.

OBJECTIVE: To study the effect of recolonisation with alpha streptococci with the ability to inhibit the growth of otopathogens ("interfering" activity) on the recurrence of acute otitis media in susceptible children and the effect on the frequency of secretory otitis media. DESIGN: Double blind, randomised, placebo controlled study. SETTING: Ear, nose, and throat clinic with three doctors. PARTICIPANTS: 130 children prone to otitis media aged between 6 months and 6 years, 108 of whom were eligible and followed for 3 months. MAIN OUTCOME MEASURES: Recurrence of otitis media during follow up and a normal tympanic membrane at the last valid visit. INTERVENTIONS: Children with no recurrences during the last month received phenoxymethylpenicillin (n=22), and those with a recurrence within 1 month received amoxicillin clavulanic acid (n=86), both twice daily for 10 days. These were followed by a streptococcal or placebo solution sprayed into the nose for a further 10 days. At day 60 the same spray was started for another 10 days. RESULTS: At 3 months 22 children (42%) given the streptococcal spray were healthy and had a normal tympanic membrane compared with 12 (22%) of those given placebo. This difference was shown separately for recurrences of both acute otitis media and secretory otitis media. CONCLUSIONS: Selected bacteria with the ability to inhibit the growth of common otopathogens can be used to protect against recurrent acute otitis media and secretory otitis media in children.

Aerosols↗

Efficacy of ceftibuten in 5 versus 10 days treatment of recurrent acute otitis media in children.

OBJECTIVE: in recurrent acute otitis media (AOM) several alternative treatments are suggested, e.g. cephalosporins. Information about the optimal duration of treatment in recurrent AOM is sparse. The aim of the present study was to compare the efficacy of ceftibuten in 5 versus 10 days treatment in recurrent AOM in children. METHODS: this was a single-blind (doctor blinded), randomized, multicentre study with two parallel groups. Eleven investigators at six centres in the west of Sweden enrolled a total of 180 patients. Outpatients with a new clinical AOM within 1 month were randomized to 5 or 10 days treatment with ceftibuten, 9 mg/kg/day, as a single dose. RESULTS: the mean age of the patients was 1.2 years (range 6 months-8 years). The patients had on average had three antibiotic treatments during the preceding 12 months. The recurrence rates in the 5- and 10-day groups were 21.4 and 4.5%, respectively, at first follow-up visit day 12 (P=0.001). The total recurrence rates between the two groups during the whole follow-up period of 40 days, 35 and 30%, respectively, did not differ significantly. The rate of recurrence did not correlate to nasopharyngeal findings of Streptococcus pneumoniae or Haemophilus influenzae. Pneumococci with decreased susceptibility to penicillin were found in 5% of all pneumococci, and beta-lactamase producing H. influenzae in 8%. Adverse events were reported less frequently in the 5- compared with the 10-day treatment group. CONCLUSION: this study on young children with recurrent otitis media has shown no statistical difference between ceftibuten given once daily for 5 and 10 days as determined on day 40. The 10-day treatment was significantly better at early follow-up.

Acute Disease↗

Tolerance and efficacy of interfering alpha-streptococci in recurrence of streptococcal pharyngotonsillitis: a placebo-controlled study.

A total of 342 patients with clinical signs of tonsillitis and suspected group A beta-haemolytic streptococci (GAS) aetiology, verified with rapid test and GAS culture, were enrolled in a randomized, placebo-controlled, double-blind, multicentre study. They received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococcal or placebo spray treatment in the ratio of 2 : 1. Pharyngeal status, throat culture and adverse events were investigated up to 75 days after treatment. The frequency of bacteriologically verified clinical recurrence was 13% in the alpha-streptococcal group and 15% in the placebo group at the follow-up on day 22. The corresponding figures at the last valid visit after 45-75 days were 19% and 30%, respectively, a statistically significant difference (p = 0.037). Furthermore, at the last valid visit 5% of subjects in the alpha-streptococcal and 12% in the placebo group were healthy carriers, bacteriological treatment failures, of GAS (p = 0.029). Treatment with alpha-streptococci and placebo spray were equally well tolerated. Thus, re-colonization with alpha-streptococci seem to hinder late recurrences of GAS pharyngotonsillitis.

Adolescent↗

Perianal streptococcal dermatitis. The possible protective role of alpha-streptococci against spread and recurrence of group A streptococcal throat infection.

OBJECTIVE: To follow the spread of beta-haemolytic streptococci group A (GAS) within a family and examine the protective activity of normally occurring alpha-streptococci against GAS tonsillitis. DESIGN: Follow up of recurrent GAS throat infection within a family. SETTING: Intra familial spread of GAS. PATIENTS: A family of four, the mother suffering from recurrent streptococcal tonsillitis and a son with perianal streptococcal dermatitis. RESULTS: The strain of the GAS found in the perianal region of the boy was identical with that found in the throat of his mother. She had recurrent streptococcal tonsillitis, while the boy remained healthy in the throat. She lacked interfering alpha-streptococci in the throat, while the boy had a massive growth of alpha-streptococci in his throat with capacity to inhibit the growth of the streptococcal isolate. MAIN OUTCOME MEASURES: Infection with GAS within a family correlated with the growth-inhibiting activity of the alpha-streptococci in vitro. CONCLUSIONS: The study demonstrated the spread of GAS from a patient with streptococcal dermatitis to the throat of another person within the family, and the hindrance of induction of infection in patients carrying interfering alpha-streptococci.

Anus Diseases↗

Investigation of prandial effects on hydrophilic matrix tablets.

The prolonged release of drug from hydrophilic matrix tablets can be greatly affected by administration in connection with the intake of food. Changes of the tablet erosion are one of the main components of this effect. The aim of the present study was to identify the postprandial factors responsible for changes in tablet erosion and to develop predictive in vitro tests. Two formulations, one sensitive and the other robust to prandial effects in vivo, were investigated in vitro (a) in a complex physiological media simulating fasting and fed conditions; (b) according to a factorial experimental design that included agitation and pH concentrations of salt, surface-active agent, and nonionic solute as factors; and (c) at varying agitation intensities in three different sets of dissolution apparatus. Of the studied factors, only increased agitation enhanced the erosion of tablets in accordance with the in vivo effects of a meal. The other factors retarded erosion or had only minor effects. The hydrodynamic mechanical stress was thus considered to be the main factor responsible for postprandial effects on tablet erosion. The influence of changes in agitation and the opportunity to discriminate between sensitive and robust formulations differed among the three sets of dissolution apparatus. The modified USP II apparatus, operated at speeds of 50 and 100 rpm, is proposed as a discriminatory test.

Chemistry, Pharmaceutical↗

Loracarbef versus phenoxymethylpenicillin in the treatment of recurrent streptococcal pharyngotonsillitis.

Knowledge of the treatment of recurrent group A streptococcal pharyngotonsillitis has, so far, been based on studies of non-recurrent rather than recurrent episodes of the disease. This multicentre, double-blind, randomized trial was designed to compare the efficacy of loracarbef (200 mg twice daily) vs phenoxymethylpenicillin (penicillin V) (800/1000 mg twice daily) each for 10 days in the treatment of recurrent group A streptococcal pharyngotonsillitis. Among the 331 patients enrolled in the study, 265 were evaluable for efficacy. The combined clinical and bacteriological failure rate was 8.2% in the loracarbef group and 21.5% in the penicillin V group (p = 0.008). Bacterial eradication was noted in 90% of loracarbef-treated patients compared to 66% of penicillin V-treated patients (p < 0.0005). The higher bacteriological eradication and clinical efficacy rate among loracarbef patients might be related to higher stability of loracarbef in the presence of beta-lactamases produced by the oral microflora. These results suggest loracarbef to be a strong candidate for treatment of patients with recurrent group A streptococcal pharyngotonsillitis.

Cephalosporins↗

Comparison of ELISA and HI for detection of antibodies against Wesselsbron disease virus.

A two-graph Receiver Operating Characteristic analysis was done to determine the optimal cut-off value of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Wesselsbron disease (WSL) virus. When ELISA and haemagglutination-inhibition (HI) results of WSL-positive and WSL-negative control sheep sera were compared, the sensitivity of ELISA was 97.9% and that of HI, 87.5%, while the specificity of ELISA and HI were 95.7% and 100%, respectively. The ELISA's superior sensitivity was confirmed by the results of the two assays performed on a simulated range of low-positive sera, which showed that the ELISA was able to detect WSL-antibody levels at least ten times lower than those the HI could. The ELISA was also less cross-reactive than the HI to guinea-pig antisera against nine flaviviruses relevant to southern Africa. The combination of the ELISA's ability to test untreated sera in single dilution and its superior sensitivity and lower cross-reactivity as compared to that of the traditional HI, makes it the assay of choice for automation and large-scale screening of animals for antibodies to WSL virus.

Animals↗

Recolonization with selected alpha-streptococci for prophylaxis of recurrent streptococcal pharyngotonsillitis--a randomized placebo-controlled multicentre study.

In a randomized, placebo-controlled, double-blind, multicentre study, 130 patients with recurrence of group A beta-hemolytic streptococci (GAS) and clinical signs of pharyngotonsillitis were enrolled. The patients received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococci-inhibitory to GAS-or placebo spray treatment. Patients taking antibiotic treatment for at least 9 days and using the spray for at least 5 days were included in the efficacy analysis. In addition, recurrence within the first 5 days of spray treatment was classified as 'early treatment failure'. The clinical recurrences (bacteriologically verified) in the alpha- (n = 51) and placebo-treated (n = 61) patient groups were 2% (n = 1) and 23% (n = 14) respectively, in patients given spray for at least 5 days (p = 0.004). The inclusion of 'early treatment failures' reduces this difference (p = 0.064). Both treatments were equally well tolerated. Thus, alpha-streptococci given as a spray and used for at least 5 days significantly prevented recurrence of GAS pharyngotonsillitis.

Adolescent↗

The economic cost of a streptococcal tonsillitis episode.

OBJECTIVE: To estimate the cost of a streptococcal tonsillitis episode from the data of a questionnaire. SETTING: Five primary health centres in the west of Sweden. PARTICIPANTS: 101 consecutive patients treated for streptococcal tonsillitis. MAIN OUTCOME MEASURE: The cost estimation included costs for physician visit and drug, travel costs to and from the primary health centre, cost of lost production resulting from the patient's or the guardian's absence from work for physician visit or sick-leave, and cost of telephone consultation with a physician or nurse. RESULTS: The period of illness was on average seven days, time to recovery after treatment five days, and the mean period of sick-leave 2.5 days. The total cost of a tonsillitis episode was about SEK 3,300 (385 USD). Of this sum, the cost for the antibiotic accounted for only 3% and loss of production for 75%. CONCLUSION: Differences in the cost of drugs only have a minor influence on the total cost, while factors causing loss of production, such as efficacy and side effects of the drug, have a greater influence. Economic evaluation of pharmaceuticals will be more relevant in the future, and in the search for the most effective treatment, cost effective studies will be integrated with clinical trials.

Adolescent↗