Effect of 1-(1-naphthylmethyl)-piperazine on antimicrobial agent susceptibility in multidrug-resistant isogenic and veterinary Escherichia coli field strains.

The objective of this study was to evaluate the interaction of the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) when combined with different families of antimicrobial agents against isogenic strains and multidrug-resistant (MDR) Escherichia coli field strains isolated from animals. Laboratory isogenic strains of E. coli with different levels of expression of efflux pumps were used as quality controls. Ten MDR E. coli strains were collected from healthy animals in a cross-sectional study in four commercial dairy farms. The MICs of florfenicol, ciprofloxacin, tetracycline and ampicillin were determined by a serial microdilution method in Luria-Bertani broth in the presence or absence of NMP. NMP used with ampicillin exerted no effect on the isogenic or field strains. In most of the field MDRE. coli strains and in an acrAB-overexpressing (AG112) isogenic strain, the MICs of florfenicol, ciprofloxacin and tetracycline decreased at least fourfold when the antimicrobial was combined with the highest NMP concentrations. In the wild-type strain (AG100), there were no decreases of more than twice the MIC, whilst in strain AG100A, an efflux pump-deficient strain, the MIC did not change, regardless of the concentration of NMP used with these three antimicrobials. Thus, ampicillin was not affected by the efflux pump mechanism, whereas ciprofloxacin, tetracycline and florfenicol were shown to be substrates of efflux pumps, with a consequent significant reduction in MICs. Resistance could not be completely reversed in the E. coli field strains by NMP, probably because other resistance mechanisms were also present. However, in strain AG112, the MIC results demonstrated that NMP expressed an important synergistic activity with florfenicol. The reduction in florfenicol MIC value was sufficient to reverse antimicrobial resistance completely for AG112.

Concentrations of danofloxacin 18% solution in plasma, milk and tissues after subcutaneous injection in dairy cows.

Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mgkg(-1)). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 microghmL(-1) and its elimination half life (T(beta)(1/2)) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T(beta)(1/2) from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal.

The backpack load in schoolchildren: clinical and social importance, and efficacy of a community-based educational intervention. A prospective controlled cohort study.

AIM: The aims of this paper were: to establish the efficacy of an educational intervention in reducing school backpack weight and, possibly, back pain; to verify the content of backpacks and the social importance of the problem; to confirm existing data in the literature. DESIGN: controlled prospective educational intervention. SETTING: community. PARTICIPANTS: the entire Year 6 population (402 pupils) of 2 randomly chosen rural school districts of the province of Mantua (Italy); of these, we took 108 (selected according to position in the class register): 82.4% completed the study; 402 parents and 124 teachers entered the study, 77.1% and 37.1% respectively completed it. INTERVENTION: instructive meeting and written material for teachers, and a leaflet for parents on backpack management. MAIN OUTCOME MEASURES: backpack weight and content; back pain; subjective perceptions of backpack load; packing and carrying methods; backpack load: importance, management and education; backpack characteristics. RESULTS: We obtained a statistically significant reduction in the backpack weight in each of the groups (study 11.2%; control 7.9% - not a statistically significant difference); 90.1% of the material carried is necessary. Backpacks are considered a problem by 95.1% of parents, 73% of teachers, and 60.3% of pupils. Backpack weight: 8.75+/-1.26 kg (19.9+/-5.3% of body weight); fatigue during backpack carrying: 72.7%; back pain life prevalence: 58.4%; fatigue during backpack carrying and considering backpacks a problem were associated with back pain (odds ratios 4.4 and 5). CONCLUSIONS: Educational intervention is not the answer to the problem and solutions, like the clear legal limits established for adults, need to be found.