Antimicrobial activity of octenidine against multidrug-resistant Gram-negative pathogens

Multidrug-resistant (MR) Gram-negative (GN) pathogens pose a major and growing threat for healthcare systems, as therapy of infections is often limited due to the lack of available systemic antibiotics. Well-tolerated antiseptics, such as octenidine dihydrochloride (OCT), may be a very useful tool in infection control to reduce the dissemination of MRGN. This study aimed to investigate the bactericidal activity of OCT against international epidemic clones of MRGN. A set of five different species (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii, and Pseudomonas aeruginosa) was studied to prove OCT efficacy without organic load, under “clean conditions” (0.3 g/L albumin) and under “dirty conditions” (3 g/L albumin + 3 mL/L defibrinated sheep blood), according to an official test norm (EN13727). We used five clonally unrelated isolates per species, including a susceptible wild-type strain, and four MRGN isolates, corresponding to either the 3MRGN or 4MRGN definition of multidrug resistance. A contact time of 1 min was fully effective for all isolates by using different OCT concentrations (0.01% and 0.05%), with a bacterial reduction factor of >5 log₁₀ systematically observed. Growth kinetics were determined with two different wild-type strains (A. baumannii and K. pneumoniae), proving a time-dependent efficacy of OCT. These results highlight that OCT may be extremely useful to eradicate emerging highly resistant Gram-negative pathogens associated with nosocomial infections.     

First European conference on aspartame: putting safety and benefits into perspective. Synopsis of presentations and conclusions.

A Conference was held in Paris in 2006 to review the safety and benefits arising from the replacement of sucrose with the intense sweetener aspartame. The intakes of aspartame are only about 10% of the acceptable daily intake, even by high consumers, so that the safety margin is about 3 orders of magnitude. The safety of aspartame was confirmed in the EFSA Opinion of a recent controversial rodent cancer bioassay. There is increasing evidence that even modest reductions in the intake of calories can reduce the risk factors associated with a number of diseases, such as diabetes and cardiovascular disease. A key issue addressed at the conference was whether the replacement of sucrose with aspartame could result in a prolonged decrease in calorie intake that was of similar magnitude to that necessary to produce a health benefit. A recent meta-analysis of published data showed that an adequate, prolonged weight reduction could be achieved with aspartame. It was recognised that risk assessment alone gave an unbalanced impression to regulators and consumers, and that in the future quantitative risk-benefit analyses should be able to provide more comprehensive advice.     

Measurement of health‐related quality of life with glaucoma: validation of the Glau‐QoL© 36‐item questionnaire

Purpose: To validate a glaucoma‐specific health‐related quality of life (HRQoL) questionnaire: the Glau‐QoL^©. Methods: Patients with ocular hypertension (OHT) or glaucoma took part in a cross‐sectional psychometric validation study (n = 573) and a separate reproducibility study (n = 244). Patients answered the 36‐item Glau‐QoL^©, designed from in‐depth patient interviews. Results: The clinical validity of the Glau‐QoL^© was excellent and clearly demonstrated that as disease severity and visual field impairment increased, HRQoL scores for the Psychological Wellbeing, Self‐image, Daily Life, Driving, Anxiety and Burden of Treatment domains were negatively affected. Increased age and lower visual acuity were also associated with lower HRQoL scores, although to a lesser extent than the previously mentioned criteria. Worsening of HRQoL domains correlated with the clinical stage of glaucoma: Anxiety and Burden of Treatment scores dropped noticeably when patients were first diagnosed and started treatment, followed by a decrease in scores for Driving, Daily Life, Psychological Wellbeing, and Self‐image as clinical conditions worsened. Psychometric validation showed acceptable convergent and discriminant validity of the Glau‐QoL^©, and good reproducibility, with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC) ≥ 0.69. Internal consistency reliability was high (Cronbach's α coefficients > 0.70) for the Daily Life, Psychological Wellbeing, Burden of Treatment and Driving domains; acceptable (coefficients of 0.65 and 0.68, respectively) for the Self‐image and Anxiety domains; and weak (coefficient = 0.58) for the Confidence in Health Care domain. Conclusions: The Glau‐QoL^© questionnaire is a valid and specific HRQoL instrument that demonstrates excellent correlations with disease progression in patients with glaucoma and/or OHT.     

Recurrent chest pain as the presenting manifestation of spinal meningioma

We report the case of a 9-year-old boy with a spinal cord meningioma whose only manifestations were recurrent episodes of chest pain lasting for 2 years. This case shows that spinal cord meningioma should be considered among the possible causative factors of chronic chest pain in childhood. Chest pain, meningioma, spinal tumors     

Acquired carbapenem-hydrolyzing beta-lactamases and their genetic support

Carbapenem-hydrolyzing beta-lactamases of several Ambler molecular classes have been reported as the source of acquired beta-lactam antibiotic resistance in Gram negative bacteria. The metallo-enzymes of Ambler class B are the most prevalent enzymes in this case. These clavulanic-acid resistant enzymes have a large spectrum of hydrolysis including penicillins, cephalosporins (third and fourth generations), carbapenems but not monobactams. They are responsible for acquired resistance in several Gram negative species of clinical relevance in human medicine. IMP-1 was the first reported as acquired in Japan, mostly from Serratia marcescens and Pseudomonas aeruginosa isolates, and has been detected in Europe recently. Several variants of IMP-1 (IMP-2 to -9) have been characterized, possessing 85 to 99% amino acid identity, mostly from P. aeruginosa isolates. In addition, VIM-1 to -3 beta-lactamases have also been described, first in Europe (Italy, France, and Greece) and now in Korea. The VIM series shares 30% amino acid identity with the IMP-series. Most of these class B enzymes have genes that are integron- and plasmid-located. Finally, a few Ambler class A (SME-1, NMC-A, IMI-1, KPC-1) and class D (OXA-23 to -27) beta-lactamases involved in carbapenem hydrolysis have been reported also from rare isolates of Gram-negative rods. This review underlines the worldwide spread of carbapenem-hydrolyzing beta-lactamases as representing an important threat for efficacy of antibiotics in the near future.     

Gram staining of protected pulmonary specimens in the early diagnosis of ventilator-associated pneumonia

We evaluated prospectively the use of Gram staining of protected pulmonary specimens to allow the early diagnosis of ventilator-associated pneumonia (VAP), compared with the use of 60 bronchoscopic protected specimen brushes (PSB) and 126 blinded plugged telescopic catheters (PTC) obtained from 134 patients. Gram stains were from Cytospin slides; they were studied for the presence of microorganisms in 10 and 50 fields by two independent observers and classified according to their Gram stain morphology. Quantitative cultures were performed after serial dilution and plating on appropriate culture medium. A final diagnosis of VAP, based on a culture of > or = 10(3) c.f.u. ml-1, was established after 81 (44%) samplings. When 10 fields were analysed, a strong relationship was found between the presence of bacteria on Gram staining and the final diagnosis of VAP (for PSB and PTC respectively: sensitivity 74 and 81%, specificity 94 and 100%, positive predictive value 91 and 100%, negative predictive value 82 and 88%). The correlation was less when we compared the morphology of microorganisms observed on Gram staining with those of bacteria obtained from quantitative cultures (for PSB and PTC respectively: sensitivity 54 and 69%, specificity 86 and 89%, positive predictive value 72 and 78%, negative predictive value 74 and 84%). Increasing the number of fields read to 50 was associated with a slight decrease in specificity and positive predictive value of Gram staining, but with a small increase in its sensitivity and negative predictive value. The results obtained by the two observers were similar to each other for both numbers of fields analysed. Gram staining of protected pulmonary specimens performed on 10 fields predicted the presence of VAP and partially identified (using Gram stain morphology) the microorganisms growing at significant concentrations, and could help in the early choice of the treatment of VAP. Increasing the number of fields read or having the Gram stain analysed by two independent individuals did not improve the results.     

Effects of sulfhydryl inhibition on the regulation of basal lipolysis and glucose uptake in human adipose tissue.

Stimulation of basal lipolysis and inhibition of glucose uptake by N-ethylmaleimide (NEM) was demonstrated in vitro in human omental adipose tissue. NEM, at concentrations ranging from 4 to 5 × 10^?4 M, produced a maximal stimulation of basal lipolysis as well as a 50 per cent inhibition of the rate of glucose uptake, whereas concentrations above 1 × 10^-3M reduced the basal rate of glycerol release. In contrast, under the conditions in which it stimulated basal lipolysis, NEM strongly inhibited theophylline induced lipolysis. NEM-stimulated lipolysis was not directly related to decreased glucose uptake to α- or β-adrenergic mechanisms or to inhibition of phosphodiesterase. The lipolytic response of human adipose tissue to NEM was, however, markedly reduced by insulin and nicotinate, suggesting that adenylcyclase activation could be responsible for the lipolytic effect of NEM. The inhibitory effect exerted by NEM on glucose uptake was similarly reversed by the addition of insulin. The rate of basal lipolysis and glucose uptake by fat pads removed from diabetic patients was unaffected by NEM. A possible involvement of insulin in the effects induced by NEM on both basal lipolysis and glucose uptake in normal human adipose tissue is discussed.