[Resistant enterobacteria: explosion of extended-spectrum beta-lactamases]. / Entérobactéries résistantes: explosion des beta-lactamases à spectre élargi.

During the past recent years, Enterobacteriaceae have supplanted Gram-positives in terms of frequent resistant bacteria seen in the outpatent setting. This change involves common opportunistic pathogens such as E. coli and K. pneumoniae. It is mainly due to the appearance and dissemination of extended-spectrum beta-lactamases (ESBL), that hydrolyse penicillins and cephalosporins. Bacteria producing these enzymes are often also resistant to quinolones and trimethoprime-sulfamethoxazole. This article, illustrated by a clinical case, presents the current epidemiology of ESBL-producing Enterobacteriaceae and the possible prevention measures and treatment options to fight the growing number of infections that they are causing.

Depressed mood in a cohort of elderly medical inpatients: prevalence, clinical correlates and recognition rate.

The objectives of this prospective cohort study were to 1) determine the prevalence of depressed mood, 2) identify the characteristics associated with it, and 3) evaluate the recognition rate of depressed mood by clinicians. The study population was a cohort of 401 elderly patients, aged 75 years and older, admitted to the internal medicine service of a tertiary care academic medical center in Western Switzerland over six months. We excluded patients with severe cognitive impairment, terminal disease or those living in a nursing home. Data on demographics, medical, physical, social and mental status were collected upon admission. Presence of depressed mood was defined as a score > or = 6 on the Geriatric Depression Scale (GDS), short form (15-item). An independent reviewer performed a discharge summary abstraction to assess recognition rate. Subjects' mean age was 82.4 years, 60.9% were women. Overall, 90 patients (22.40%) had an abnormal GDS score (> or =6). Compared to those without a depressed mood, these subjects were (all p<0.05) older (83.5 vs 82.0 years), more frequently living alone (66.7 vs 55.0%), dependent in both basic activities of daily living (BADL) and instrumental ADL (48.9 vs 36.0%, and 91.1 vs 84.9%, respectively), and cognitively impaired (47.8 vs 27.7% with MMSE score<24). In addition, they had more comorbidities (Charlson index 1.6 vs 1.2). In multivariate analysis, an independent association remains for subjects living alone (OR 1.8, 95%CI 1.1-3.0), with cognitive impairment (OR 1.9, 95%CI 1.1-3.2), and comorbidities (OR 1.3 per point, 95%CI 1.1-1.5). Detection rate during the index hospitalization was only 16.7% (15/90). In conclusion, depressed mood was frequent but rarely detected in this population. These findings emphasize the need to improve screening efforts, and to develop additional strategies such as using a pre-screening question to enhance clinical recognition.

Pilot investigation of thyrotropin-releasing hormone-induced thyrotropin and prolactin release in anxious patients treated with diazepam.

Benzodiazepines have been reported to inhibit thyrotropin (TSH) and prolactin (PRL) secretion in response to stressful and pharmacologic stimuli in experimental animals. The current study investigates basal and thyrotropin-releasing hormone (TRH)-stimulated TSH and PRL release in anxious patients treated with diazepam. Six hospitalized patients having generalized anxiety or adjustment disorder with anxious mood (DSM III-R criteria) were treated during 1 week with diazepam (mean daily dose 33.3 mg). TRH testing was performed comparatively before and after 7 days of diazepam administration (with 250 micrograms protirelin and blood sampling at 15-min intervals over 60 min). Steady-state plasma levels of diazepam and its metabolite nordazepam (desmethyldiazepam) were determined by high-performance liquid chromatography. After 7 days of diazepam treatment, basal plasma levels of TSH and PRL were not affected compared with pretreatment values. Similarly, the time-course of TRH-induced TSH release was not modified by the treatment. By contrast, there was a trend to decrease in the TRH-induced PRL release, and the decrease in the PRL response to TRH on day 7 was significantly correlated with plasma nordazepam concentrations (rs = 0.943, p = 0.02). These preliminary results suggest that benzodiazepines, at therapeutic doses for the treatment of anxiety, may alter TRH-induced PRL release in humans.

Clonazepam in acute mania: time-blind evaluation of clinical response and concentrations in plasma.

This study was performed to evaluate the optimal doses and clinical efficacy of clonazepam as a first-line drug in acute mania, as well as to determine its effective plasma concentrations. Clonazepam was administered orally to 11 newly admitted inpatients. On day 0, the loading dose was titrated upward according to the clinical global impression; the maintenance dose was calculated with intent to maintain the plasma level that had been achieved after initial dose escalation. Clinically based dose adjustments were allowed on days 4 and 7. Manic symptoms were scored on days 0, 4 and 14 according to a time-blind procedure; clonazepam plasma levels were measured by HPLC. On day 14, there was a significant decrease in manic symptoms and 66.7% of the patients who completed the trial were markedly improved. Steady-state plasma levels of clonazepam were significantly correlated with daily doses (rs = 0.795, P < 0.005) and therapeutic concentrations ranged between 6.5-83.9 micrograms/l. At the onset of therapy, the clinically titrated loading dose resulted in plasma concentrations within the narrow range of 18.9-34.0 micrograms/l. These results support the potential value of clonazepam in the short-term management of acute mania; the initial control of agitation was achieved with plasma drug levels in a remarkably narrow range as compared with the further control of mania.

An imidazopyridine anxiolytic alters glucose tolerance in patients: a pilot investigation.

We have recently shown that compounds with high affinity for peripheral-type benzodiazepine receptors inhibited glucose-induced insulin secretion in vitro. We therefore performed an oral glucose tolerance test in anxious inpatients treated with the imidazopyridine derivative alpidem, which has been shown to display high affinity for these binding sites. The test was performed before and after 1 week of daily administration of the drug. As compared with pretreatment values, a significant alteration of the insulin response to glucose was observed. It is suggested that daily administration of alpidem, at therapeutically effective doses for the treatment of anxiety, may alter glucose tolerance.

A double-blind comparison of clonazepam and placebo in the treatment of neuroleptic-induced akathisia.

The present study was designed to investigate the efficacy of clonazepam in neuroleptic-induced akathisia. Twelve patients were treated during 2 weeks with clonazepam or placebo in a double-blind randomized design. Akathisia was scored by an independent rater before and after treatment, as well as 1 week after medication withdrawal. Clonazepam (0.5-2.5 mg/day) induced a significantly higher reduction in the akathisia scores than placebo (p < 0.05). One week after stopping the drug, there was a partial but significant relapse in the treated group as compared with controls, in whom the symptoms remained stable. In addition, the clinical improvement was significantly correlated with the daily dose of clonazepam (rs = 0.827; p < 0.002). These results support the potential usefulness of clonazepam in the treatment of neuroleptic-induced akathisia and suggest an optimal daily dose in the range of 10-40 micrograms/kg.

Carbamazepine and its 10,11-epoxide metabolite in acute mania: clinical and pharmacokinetic correlates.

The study was designed to investigate the antimanic profile of carbamazepine as a first-line drug in affective or schizoaffective disorders, to correlate the clinical efficacy with the plasma level of carbamazepine and its 10,11-epoxide metabolite, and to test the potential value of monitoring the salivary level. It was administered alone for 3 weeks to 21 acute manic inpatients. During the first week, the dosage was rapidly increased to 800 mg/day in order to produce steady-state plasma levels of carbamazepine on Day 7. The individual dose was then adjusted to maintain the therapeutic range of 8-12 mg/l. Plasma and saliva levels of the drug and its metabolite, as well as clinical status were assessed weekly. Overall, there was 62% globally improved patients and 77% in affective disorders. The improvement of manic symptoms was significantly lower in schizoaffective than in affective disorders, whereas the dropout rate and the need for antipsychotic medication was higher in the former group. The antimanic response was significantly correlated with the plasma levels both of carbamazepine and its epoxide metabolite, with a time-lag consistent with a delayed drug effect. Drug and metabolite concentrations in saliva were close to their plasma free fraction and were strongly correlated with their plasma levels, suggesting the potential value of salivary drug monitoring.

[Use of very high doses of haloperidol in the treatment of acute psychotic episodes. Clinical and pharmacokinetic analysis apropos of 15 cases]. / Utilisation de très fortes posologies d'halopéridol dans le traitement des épisodes psychotiques aigus. Analyse clinique et pharmacocinétique à propos de quinze cas.

High-dosage haloperidol treatment was administered during three weeks in a rapid neuroleptization technique to fifteen patients suffering from acute psychotic episodes. Haloperidol plasma levels were determined by radioimmunoassay. The efficacy of such a therapeutic design seemed fairly good, particularly the rapid improvement during the first week. Yet, tolerance appeared to be low, with a high incidence of adverse effects, some of them unexpected. A very good correlation was observed between haloperidol plasma levels and haloperidol oral doses. By contrast, there was no correlation between plasma levels and clinical improvement. In the same way, the occurrence of adverse effects did not seem to be related to haloperidol plasma levels.

[Corneal and lens deposits due to treatment by phenothiazine type neuroleptics]. / Dépôts cornéens et cristalliniens dus aux traitements par neuroleptiques de type phénothiazine

The authors have studied the corneal and lens lesions which appeared following a prolonged treatment by phenothiazines. They examined 186 patients: 147 took phenothiazines of which 35 of them presented anterior segment alterations. It seems that all phenothiazines can be held responsible for the apparition of these lesions. At this point the authors evaluated the global dose of the various phenothiazines which were administered. The threshold at which the association of these lesions seem to appear, seems to be situated around 300 gr. The total quantity of phenothiazines which are absorbed seems to be a good measure of the risk of ocular toxicity. In the case of one patient they observed that his visual keenness was lowered due to the importance of his corneal and lens lesions.