Past,Present, and Future of Antibacterial Economics: Increasing Bacterial Resistance,Limited Antibiotic Pipeline,and Societal Implications

Growing antimicrobial resistance and a dwindling antibiotic pipeline have resulted in an emerging postantibiotic era, as patients are now dying from bacterial infections that were once treatable. The fast‐paced “Golden Age” of antibiotic development that started in the 1940s has lost momentum; from the 1980s to the early 2000s, there was a 90% decline in the approval of new antibiotics as well as the discovery of few new novel classes. Many companies have shifted away from development due to scientific, regulatory, and economic hurdles that proved antibiotic development to be less attractive compared with more lucrative therapeutic areas. National and global efforts are focusing attention toward potential solutions for reinvigorating the antibiotic pipeline and include “push” incentives such as public–private partnerships and “pull” incentives such as reimbursement reform and market exclusivity. Hybrid models of incentives, global coordination among stakeholders, and the appropriate balance of antibiotic pricing, volume of drug used, and proper antimicrobial stewardship are key to maximizing efforts toward drug development to ensure access to patients in need of these therapies.     

Immunization with viable Brucella organisms: Results of a safety test in humans

In many parts of the world contact with infected livestock may involve a serious risk of the spread of human brucellosis. Partial control of bovine brucellosis has been achieved by slaughter of infected herds and immunization of cattle with Brucella abortus strain 19 living vaccine. However, in areas where such measures are unpractical there remains a need for protection of humans. This study compares the safety of two living Brucella vaccine preparations in human volunteers.     

Unusual Enterobacteriaceae: a Salmonella cubana that is Urease Positive

This is the first report of a naturally occurring Salmonella that is urea positive. The strain was identified as Salmonella cubana and it was typical in all biochemical, serological, and bacteriophage reactions, except that is produced urease strongly.     

Antiarthritic profile of BF-389 — A novel anti-inflammatory agent with low ulcerogenic liability

BF-389, dihydro-4-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2methyl-2H-1,2-oxazin-3(4H)-one, is a potent, orally active, antiarthritic and analesis agent with low ulcerogenic potential. A comparison of the activity profiles of BF-389 and naproxen showed similarities in: (1) suppression of developing and chronic adjuvant arthritis (AA); (2) maximal inhibitory response, as shown by theE(max0 values in the developing and established AA models; (3) inhibition of bone degenerative changes associated with chronic adjuvant arthritis; and (4) analgesic activity in the acetic acid and phenylquinone writhing assays. Though BF-389 has been shown to be a potent inhibitor of cyclooxygenase, IC₅₀=0.84±0.25 M against the production of PGE₂ in vitro, there is a great difference from most cyclooxygenase inhibitors; it also inhibits the 5-lipoxygenase enzyme. For BF-389, the IC₅₀ for invitro LTB₄ formation was found to be 3.65±1.19 M. The ulcerogenic potential of BF-389 was compared to that of naproxen using a five-dayin vivo ulcerogenic rat assay. The UD₅₀ for naproxen was found to be approximately 30 mg/kg/day, p.o. Based upon efficacy in the DEV AA and EST AA models, UD₅₀/ED₅₀ values for naproxen were estimated to be 0.7 and 1.9, respectively. For BF-389 the UD₅₀ was shown to be 520 (389–695) mg/kg/day, p.o., and the corresponding UD₅₀/ED₅₀ values were calculated to be 84 and 28, respectively, thus demonstrating the wide margin of safety between efficacy and ulcerogenicity in rats.     

Effects of convergent strabismus on spatio-temporal response properties of neurons in cat area 18

Summary Single-cell recording experiments were carried out to determine whether rearing kittens with surgically induced convergent strabismus (esotropia) alters the development of receptive field (RF) properties of neurons in area 18. In agreement with previous work on kittens with divergent strabismus (exotropia), there was a marked loss of binocularly driven cells in area 18 of esotropic cats. In contrast to the striate cortex of strabismic cats, the spatial properties of area 18 neurons, including receptive-field size and spatial frequency tuning, did not differ from those in normal controls. On the other hand, we found that contrast thresholds, measured at an optimal spatial frequency, were significantly elevated, and that the contrast gain in many cells was reduced in strabismic cats. These deficits were observed in both eyes, though the cells dominated by the deviating eye had a lower response amplitude at all contrasts. Furthermore, temporal frequency tuning curves were abnormal in strabismic cats in that the optimal frequencies and temporal resolutions were shifted to lower values. These effects were also bilateral. Velocity tuning, measured with a high-contrast bar stimulus, revealed that area 18 neurons in strabismic cats were unable to respond to very high velocities compared to normals. This reduced response was more severe when measured with the deviating eye in spite of the bilateral nature of the deficit. Finally, latencies to electrical stimulation of the optic chiasm or the optic radiation were significantly longer in strabismic cats. The magnitude of these effects was virtually the same for both eyes. From these observations, we conclude that the temporal properties of area 18 neurons, particularly the cells abilities to follow fast temporal modulations, are affected by raising kittens with surgically induced convergent strabismus.     

Empirical Note: Self-Report Versus Recorded Sleep in Healthy Seniors

Although insomnia is a major public health problem in the elderly, little information concerning the relation between subjective reports of sleep and laboratory measures in the elderly has been published. Also, while laboratory studies of the healthy elderly typically show that women steep better than men, epidemiologic studies suggest that women complain more often than men about disturbed sleep. We report here a study of 20 healthy elderly subjects without sleep complaints (10M. 10F), in which relations between subjective and objective measures of sleep were explored. Both men and women showed significant correlations between objective measures of Sleep Latency (SL) and subjective estimates of fall asleep time; similarly, in both groups, subjective estimates of sleep duration were significantly and positively correlated with Time Spent Asleep (TSA). However, in the women, but not in the men, “restlessness” of sleep was significantly correlated with WASO (wake time after sleep onset), while “soundness” of sleep was positively related to amount of slow wave sleep. In general, women showed a higher proportion of significant and more stable correlations between subjective and objective measures than did men. These findings suggest that elderly women may report sleep loss more accurately than elderly men.