Evaluation of a mobile team dedicated to behavioural disorders as recommended by the Alzheimer Cooperative Valuation in Europe joint action: observational cohort study.

BACKGROUND AND PURPOSE: Preventing behavioural crises appears to be crucial to promote quality of life of the patient-caregiver dyad, to reduce inappropriate hospitalizations and to delay institutionalization. The Alzheimer Cooperative Valuation in Europe promotes mobile care to prevent patients from severe behavioural and psychological symptoms in dementia. This study assessed the potential efficacy of a mobile team for Alzheimer's disease on hospitalization sparing and behavioural disorder reduction. METHODS: A cohort study was set up from 1 January 2012 to 31 December 2013 by the Clinical and Research Memory Centre of Lyon (France). It included patients with behavioural and psychological symptoms living at home or in a nursing home. An interview explored the alternative patient pathways used by general practitioners (GPs) if the mobile team had not existed (hospitalization sparing). The Neuropsychiatry Inventory score was assessed at inclusion and 30 days later. The sample included 424 consecutive patients with Alzheimer's disease or related disorders and behavioural disorders at any cognitive and functional stage of the disease, taken in charge by the mobile team. RESULTS: Amongst the 424 patients (84.0 ± 7.2 years), 220 (51.9%) hospitalizations were considered by their GPs and 181 (82.3%) were avoided. The Neuropsychiatric Inventory score declined after mobile team intervention (45.8-29.9, P < 0.001). Sleep and appetite disorders, endangered situation and caregiver burnout were associated with higher risk of hospitalization at 30 days. CONCLUSIONS: The mobile team for Alzheimer's disease allows a high proportion of hospitalizations related to behavioural disorders to be avoided and may help to reduce behavioural disorders.

Evidence for a true post-beta-lactamase-inhibitor effect of clavulanic acid against Klebsiella pneumoniae and Haemophilus influenzae.

OBJECTIVE: The purpose of this study was to investigate and characterize in vitro the post-beta-lactamase inhibitor effect (PLIE) of clavulanic acid against two beta-lactamase-producing species of bacteria. METHODS: The PLIE was investigated against one strain of Klebsiella pneumoniae and one strain of Haemophilus influenzae. A stationary-phase inoculum of about 107 colony-forming units per mL of each bacterium was pre-exposed for 2 h to clavulanic acid, either alone or in combination with amoxicillin at various concentrations. After pre-exposure, the dilution required to remove the beta-lactamase inhibitor was 1:100 or 1:1000 according to the bacterial species and their susceptibilities to clavulanic acid. Bacteria were counted hourly after drug removal, on solid agar medium. RESULTS: Control cultures exposed to amoxicillin alone after dilution, showed a delay in growth, which may be inherent to the time required to synthesize sufficient beta-lactamase after the dilution steps. Control experiments clearly distinguished the post-antibiotic effect and the growth delay from the PLIE. CONCLUSION: The PLIE could be one of several factors explaining why beta-lactam/beta-lactamase inhibitor combinations remain effective throughout the dosing interval, even if a few hours after in vivo administration, serum concentrations of beta-lactamase inhibitor fall below levels that are active in vitro.

Activity of CI-960 alone and in combination with amoxycillin against Listeria monocytogenes, and comparison with other quinolones.

In-vitro activity of CI-960 against seven strains of Listeria monocytogenes was compared to that of other fluoroquinolones. MICs/MBCs were: ciprofloxacin and sparfloxacin: 0.5-2/1-4 mg/L;PD 131628: 0.125-0.5/0.25-2 mg/L; CI-960: 0.06-0.25/0.25-0.5 mg/L. At 4 h, CI-960 (4 x MIC) reduced the inoculum (log10 cfu) by 2.88 +/- 0.61 compared with 1.78 +/- 0.48 for ciprofloxacin, 1.5 +/- 0.46 for sparfloxacin, and 1.35 +/- 0.47 for PD 131628 (P < 0.05). At 24 h, the bactericidal effects were similar (-4 log10 cfu). The amoxycillin/CI-960 (8 x MIC) combination was bactericidal, without emergence of resistant mutants.

Ex vivo 12 h bactericidal activity of oral co-amoxiclav (1.125 g) against beta-lactamase-producing Haemophilus influenzae.

The aim of the study was to evaluate the in vitro/ex vivo bactericidal activity of a new coamoxiclav single-dose sachet formulation (1 g amoxicillin + 0.125 g clavulanic acid) against a beta-lactamase-producing strain of Haemophilus influenzae. The evaluation covered the 12 h period after antibiotic administration. Serum specimens from the 12 healthy volunteers included in the pharmacokinetic study were pooled by time point and in equal volumes. Eight of 12 pharmacokinetic sampling time points were included in the study. At time points 0.5, 0.75, 1, 1.5, 2.5, 5, 8 and 12 h post-dosing, the kinetics of bactericidal activity were determined for each of the serial dilutions. Each specimen was serially diluted from 1:2 to 1:256. The index of surviving bacteria (ISB) was subsequently determined for each pharmacokinetic time point. For all the serum samples, bactericidal activity was fast (3-6 h), marked (3-6 log(10) reduction in the initial inoculum) and sustained over the 12 h between-dosing interval. The results obtained also confirmed that the potency of the amoxicillin plus clavulanic acid combination was time dependent against the species under study and that the time interval over which the concentrations were greater than the MIC (t > MIC) was 100% for the strain under study. The data thus generated constitute an interesting prerequisite with a view to using co-amoxiclav 1.125 g in a bd oral regimen.

[In vitro demonstration of a true post-beta-lactamases inhibitor effect (PLIE) of clavulanic acid on Klebsiella pneumoniae and Haemophilus influenzae]. / Mise en évidence in vitro d'un véritable effet post-inhibiteur de bêta-lactamases (EPIBLA) de l'acide clavulanique sur Klebsiella pneumoniae et Haemophilus influenzae.

In vivo, serum concentrations of beta-lactamase inhibitors measured during the last part of the dosing interval are below the levels associated with in vitro activity. Nevertheless, beta-lactam plus beta-lactamase inhibitor combinations remain active in vivo throughout the dosing interval. One of the many reasons for this contradiction may be the PLIE. The PLIE can be evaluated only in the light of the postantibiotic effect (PAE). Also, accurate determination of the PLIE requires a careful investigation of all bacterial regrowth delays (BRDs) inherent to the technical procedures used. The purpose of the study reported herein was to determine the true in vitro PLIE of clavulanic acid (CA) against two beta-lactamase-producing strains, a Klebsiella pneumoniae strain (amoxicillin [AMX] MIC > 256 mg/L; CA MIC = 64 mg/L; and AMX + CA MIX = 4 mg/L) and a Haemophilus influenzae strain (AMX MIC = 32 mg/L; CA > 32 mg/L; AMX-CA = 1 mg/L). For each strain, a stationary phase inoculum of 10(7) was preexposed for 2 h to either CA alone or CA + AMX in various concentrations. Dilution to 10(-2) or 10(-3) was performed to eliminate the CA and/or AMX after the preexposition phase. Hourly bacterial counts were done between 0 and 8 h and after 24 h. Control cultures exposed to AMX after dilution showed a growth delay possibly ascribable to the time needed for bacteria to produce a large enough amount of beta-lactamases. Control experiments were done to unequivocally differentiate PLIE from PAE and BRD. The true PLIE values thus obtained ranged from 0 to 4.5 h for K. pneumoniae and from 0 to 15 h for H. influenzae. For both strains, a PLIE was demonstrated after exposure to CA alone.

[Bacterial growth delay in E. coli: demonstration and evaluation of the beta-lactamase post-inhibitor effect on 6 strains with different resistance phenotypes]. / Retard de recroissance bactérienne chez E. coli: mise en évidence et évaluation d'un effet postinhibiteur de beta-lactamases sur six souches de phénotypes de résistance différents.

Six E. coli, whose phenotypes of resistance were different, were tested in vitro in order to evaluate a regrowth delay, the post beta-lactamases inhibitor effect (PLIE). This PLIE was investigated after a brief incubation in contact with clavulanic acid (CA) alone or associated with amoxicillin (AMX). After removal of the drugs used during the pre-exposure phase, the bacteria were incubated with AMX at different concentrations. The PLIE was shown not to be in association with any other regrowth delay (post-antibiotic effect or effect inherent to the technical procedures used). A PLIE was evaluated on the five intermediary or high-level beta-lactamases-producing strains. Generally, the duration of the PLIE was prolonged after the CA alone pre-exposure phase and could reach values up to 22 hours. The concentrations of AMX added in cultures previously exposed to sufficient CA concentrations were related to an extended PLIE.

[Chronic experimental bacteremia in Yucatan micropigs]. / Bactériémie chronique expérimentale du microporc Yucatan.

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.