Extended-spectrum ß-lactamase (ESBL) polymerase chain reaction assay on rectal swabs and enrichment broth for detection of ESBL carriage.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL) screening and contact precautions on patients at high risk for ESBL carriage are considered important infection control measures. Since contact precautions are costly and may negatively impact patient care, rapid exclusion of ESBL carriage and therefore earlier discontinuation of contact precautions are desired. AIM: In the present study, the performance of an ESBL polymerase chain reaction (PCR) targeting blaCTX-M genes was evaluated as a screening assay for ESBL carriage. METHODS: Two methods were assessed: PCR performed directly on rectal swabs and PCR on enrichment broth after incubation overnight. The reference standard was culture of ESBL-producing Enterobacteriaceae on selective agar after overnight enrichment and confirmation by the combination disc diffusion method. Microarray was used for discrepancy analysis. A secondary analysis was performed to evaluate the added value of including a blaSHV target in the PCR. FINDINGS: A total of 551 rectal swabs from 385 patients were included, of which 28 (5%) were ESBL positive in culture. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 86%, 98%, 67%, and 99%, respectively, for PCR directly on swabs, and 96%, 98%, 75%, and 100%, respectively, for PCR on enrichment broth. Adding a blaSHV target to the assay resulted in a lower PPV without increasing the sensitivity and NPV. CONCLUSION: Screening for ESBL by PCR directly on rectal swabs has a high negative predictive value, is up to 48h faster than traditional culture and therefore facilitates earlier discontinuation of contact precautions, thereby improving patient care and saving valuable resources in the hospital.

Urinary tract infections with Aerococcus urinae in the south of The Netherlands.

Aerococcus urinae is an uncommon urinary tract pathogen that causes infections predominantly in elderly persons with local or general predisposing conditions. During a one-year study, the clinical features of Aerococcus urinae urinary tract infections (> or = 10(5) cfu/ml) were investigated in two large medical microbiology laboratories in the Netherlands. The incidence of Aerococcus urinae urinary tract infections ranged between 0.31 and 0.44% for the two laboratories. The median age (range 35-95 years) of patients with this infection was 82.5 years for women and 77.5 for men. Men had significantly (p < 0.01) more local predisposing conditions than did women. Underlying systemic diseases such as diabetes mellitus, malignancy, and dementia were found in 67.5% of patients. Most patients (97.5%) had the classic signs of a urinary tract infection, but none of them developed serious symptoms. All isolates tested were susceptible to penicillin, amoxicillin, and nitrofurantoin, 78.3% were susceptible to norfloxacin, and all were resistant to sulfonamides. The majority of patients were treated with amoxicillin, amoxicillin with clavulanic acid, or norfloxacin.

Astemizole-D causes less sleep impairment than loratadine-D.

This randomized, double-blind, double-dummy, parallel-group trial was initiated to evaluate and compare the tolerability of once-daily astemizole-D capsules (10 mg astemizole/240 mg pseudoephedrine) and twice-daily loratadine-D tablets (5 mg loratadine/120 mg pseudoephedrine), with particular reference to the impact of treatment on quality of sleep. A total of 240 healthy volunteers participated in this study with a treatment duration of 3 days. Astemizole-D consistently produced less sleep impairment than loratadine-D with statistically significant differences in favour of astemizole-D reported for night-time waking on days 4 and 5 (P = 0.004 and P = 0.006, respectively), as well as for night-time restlessness on day 4 and the total score for all sleep parameters on day 4 (P < 0.05). Global evaluations of overall sleep quality at the end of the trial also revealed some statistically significant differences in favour of astemizole-D. Both drugs were well tolerated and there were no differences in the incidence and type of adverse events reported in the two treatment groups. Slight changes in heart rate and blood-pressure were observed in both treatment groups, but these were small and were not considered to be of clinical significance. In conclusion, once-daily astemizole-D is well tolerated and appears to cause less sleep impairment than twice-daily loratadine-D.

Levocabastine: a new topical approach for the treatment of paediatric allergic rhinoconjunctivitis.

Levocabastine is a novel H1-receptor antagonist for topical use, which is being investigated in allergic rhinitis (nasal spray) and conjunctivitis (eye drops). Its anti-allergic effects have been demonstrated in nasal and ocular provocation tests. Clinical studies have been performed in 1,363 patients with allergic rhinitis and 1,218 patients with allergic conjunctivitis, comparing levocabastine mainly to placebo and cromoglycate. Levocabastine was effective when used at a dose of 2 sprays per nostril or 1 drop per eye twice daily, which if necessary can be increased up to four times daily. Levocabastine was superior to placebo in alleviating symptoms such as sneezing, itchy nose, runny nose, itchy eyes, red eyes and lacrimation. In global evaluations some 60% of patients had good to excellent results with the nasal spray and some 75% with the eye drops. Levocabastine was shown to be as good or even slightly better than cromoglycate. Onset of action was fast, with 73% of patients reporting symptom relief within 30 min after administration of levocabastine nasal spray. Adverse experiences were similar in type and incidence with levocabastine, cromoglycate and placebo, for nasal spray as well as eye drops. The most frequent complaints were nasal and ocular irritation, respectively, with a similar incidence for the three drugs. Limited data are available in children so far, but they indicate response rate and adverse-experience profile to be similar to what was observed in adults. Levocabastine, thus, is an interesting new antihistamine available for topical use in allergic rhinoconjunctivitis. It has been extensively evaluated in adults, and preliminary data indicate that it can also be useful in allergic children.

Levocabastine: an effective topical treatment of allergic rhinoconjunctivitis.

The new H1-receptor antagonist levocabastine is the most potent antihistamine available, as shown in classical animal tests for antihistamine activity. Its effects also are very specific, with doses as high as 40,000 times the effective antihistamine dose not displaying other pharmacological effects. In nasal and ocular provocation tests, levocabastine nasal spray and eye drops protected against allergen-induced nasal and ocular symptoms. Twenty-three clinical trials have been performed with levocabastine nasal spray in 1363 patients with allergic rhinitis. At a dose of two sprays per nostril twice daily (if necessary to be increased up to four times daily), levocabastine was significantly better than placebo and as good as or slightly better than cromoglycate in alleviating nasal symptoms. Good to excellent results were reported in about 60% of patients on levocabastine, compared with 37% with placebo and 47% with cromoglycate. Levocabastine eye drops were studied in 21 clinical trials including 1218 patients with allergic conjunctivitis. One drop per eye twice daily (up to four times daily) provided significantly better symptom control than placebo and similar effects as those observed with cromoglycate. Response rates were 71-80% with levocabastine, 55% with placebo and 76% with cromoglycate. Levocabastine has a fast onset of action, with 94% of patients experiencing symptom relief within 15 min after the first instillation of levocabastine eye drops. Three long-term studies (10-16 weeks' duration) showed absence of tachyphylaxis during prolonged treatment with levocabastine. The incidence of adverse experiences was similar for levocabastine, cromoglycate and placebo, for nasal spray as well as eye drops.(ABSTRACT TRUNCATED AT 250 WORDS)

Onset of action of astemizole.

Astemizole has been described to have a slow onset of action and this has to a large extent been attributed to its unusual pharmacokinetic profile. Yet, pharmacokinetically, there are no reasons why astemizole should not act within the first hours after intake, since plasma levels of unchanged astemizole are maximal within 40 min and there is fast tissue distribution. Animal pharmacology data show effective antihistamine activity with astemizole within 1 h after intake. Clinical data referring to the onset of action of astemizole with regard to symptom relief were available from 27 studies on over 7000 patients. These studies showed astemizole to provide symptom relief within 4 to 6 h of intake in 16-85% of patients, and within 24 h in 42-90% of patients; these figures are comparable to those reported for other new antihistamines. Comparative studies between astemizole and other new antihistamines (terfenadine, loratadine and cetirizine) indicated no or only minor differences in onset of clinical effect. Two recent studies compared astemizole to both terfenadine and loratadine under well-controlled circumstances. One was a pollen challenge study showing all three drugs to be able to reverse the challenge-induced effects within 1-3 h after intake. In the other, the mean time to relief of at least one rhinitis symptom was assessed as 18 min for astemizole, 24 min for terfenadine and 36 min for loratadine. Compared with the systemic decongestant pseudoephedrine, time to first relief of symptoms was similar for astemizole (4 h) and pseudoephedrine (3.5 h). Controlled clinical trials thus show astemizole to provide fast symptom relief. This was confirmed in patient surveys in Canada and Switzerland: over 80% of patients were very satisfied with astemizole and experienced onset of action within hours. In conclusion, astemizole results in symptom relief within hours after its administration. Its onset of action is not different from that of other nonsedating antihistamines and is also similar to that of pseudoephedrine.

International study of ketanserin in Raynaud's phenomenon.

PURPOSE: The effects of ketanserin on primary or secondary Raynaud's phenomenon due to connective tissue disease were studied in a large, international group of patients. PATIENTS AND METHODS: The study population consisted of 222 patients from 10 countries. After a run-in period of one month of placebo therapy, patients were randomly assigned in a double-blind manner to receive ketanserin 40 mg three times daily (n = 113) or placebo (n = 109) for three months. Total finger blood flow was measured in 41 patients in a warm and cool room before and during treatment. Vasospastic episodes were assessed by diaries and global evaluations. RESULTS: A significant reduction of 34% in frequency of episodes occurred with ketanserin, compared to 18% with placebo (p = 0.011). There was a 1% reduction in duration of episodes with ketanserin therapy, compared to a 2% increase with placebo therapy, but this finding was not statistically significant (p = 0.29). No difference was observed in severity of attacks. Global evaluations by investigators (p = 0.03) and patients (p less than 0.01) showed an overall benefit with ketanserin compared to that seen with placebo. Patients with primary or secondary Raynaud's phenomenon responded similarly to treatment. No changes in total finger blood flow were found. CONCLUSION: Ketanserin significantly improves the subjective symptoms of patients with primary or secondary Raynaud's phenomenon and is an appropriate agent to use in this disease when conservative measures fail.