Pharmacodynamics of Aerosolized Fosfomycin and Amikacin against Resistant Clinical Isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae in a Hollow-Fiber Infection Model: Experimental Basis for Combination Therapy

There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs of 16 mg/liter and 64 mg/liter) and Klebsiella pneumoniae (MICs of 2 mg/liter and 64 mg/liter) using a dynamic hollow-fiber infection model over 7 days. Targeted peak concentrations of 300 mg/liter amikacin and/or 1,200 mg/liter fosfomycin as a 12-hourly dosing regimens were used. Quantitative cultures were performed to describe changes in concentrations of the total and resistant bacterial populations. The targeted starting inoculum was 108 CFU/ml for both strains. We observed that neither amikacin nor fosfomycin monotherapy was bactericidal against P. aeruginosa while both were associated with rapid amplification of resistant P. aeruginosa strains (about 108 to 109 CFU/ml within 24 to 48 h). For K. pneumoniae, amikacin but not fosfomycin was bactericidal. When both drugs were combined, a rapid killing was observed for P. aeruginosa and K. pneumoniae (6-log kill within 24 h). Furthermore, the combination of amikacin and fosfomycin effectively suppressed growth of resistant strains of P. aeruginosa and K. pneumoniae. In conclusion, the combination of amikacin and fosfomycin was effective at maximizing bacterial killing and suppressing emergence of resistance against these clinical isolates

Quantum state-dependent diffusion and multiplicative noise: a microscopic approach

The state-dependent diffusion, which concerns the Brownian motion of a particle in inhomogeneous media has been described phenomenologically in a number of ways. Based on a system-reservoir nonlinear coupling model we present a microscopic approach to quantum state-dependent diffusion and multiplicative noise in terms of a quantum Markovian Langevin description and an associated Fokker-Planck equation in position space in the overdamped limit. We examine the thermodynamic consistency and explore the possibility of observing a quantum current, a generic quantum effect, as a consequence of this state-dependent diffusion similar to one proposed by B\"{u}ttiker [Z. Phys. B {\bf 68}, 161 (1987)] in a classical context several years ago.Comment: To be published in Journal of Statistical Physics 28 pages, 3 figure

Capacity Building in Female Pelvic Medicine and Reconstructive Surgery: Global Health Partnership Beyond Fistula Care in Ethiopia

Objective: Obstetric fistula is a devastating childbirth injury that leaves women incontinent, stigmatized and often isolated from their families and communities. In Ethiopia, although much attention has focused on treating and preventing obstetric fistula, other more prevalent childbirth-related pelvic floor disorders, such as pelvic organ prolapse, non-fistula-related incontinence and post-fistula residual incontinence, remain largely unattended. The lack of international and local attention to addressing devastating pelvic floor disorders is concerning for women in low- and middle-income countries. The objective of this article is to highlight the need for a more comprehsive approach to pelvic floor care and to share our experience in addressing it. Methods: Here, we share our experience launching one of the first formal training programs in Female Pelvic Medicine and Reconstructive Surgery (FPMRS) in Ethiopia. Results: This fellowship program provides quality care while strengthening the health system in its local context. This program has positioned Ethiopia to be a regional leader by providing comprehensive training of surgeons and allied health professionals, building appropriate health system and research infrastructure, and developing a formal FPMRS training curriculum. Conclusion: We hope that sharing this experience will serve as a template for others championing comprehensive pelvic floor care for women in low- and middle-income countries

Challenges of Informal Urbanization

Informal urbanization refers to a form of urbanization that is independent from formal framework and that do not comply with formal rules and regulations. It is a quasi-urbanization driven by local economic development and market forces. It refers to informal housing, informal settlements, and informal economy. Informal settlements are areas that are not formally planned but nevertheless occupied illegally by the dwellers. Slums are the most deprived and excluded form of informal settlements characterized by poverty and dilapidated housing often located in the most hazardous urban land (UN-Habitat III 2016)