A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics

Despite the growing threat of antimicrobial resistance, pharmaceutical and biotechnology firms are reluctant to develop novel antibiotics because of a host of market failures. This problem is complicated by public health goals that demand antibiotic conservation and equitable patient access. Thus, an innovative incentive strategy is needed to encourage sustainable investment in antibiotics. This systematic review consolidates, classifies and critically assesses a total of 47 proposed incentives. Given the large number of possible strategies, a decision framework is presented to assist with the selection of incentives. This framework focuses on addressing market failures that result in limited investment, public health priorities regarding antibiotic stewardship and patient access, and implementation constraints and operational realities. The flexible nature of this framework allows policy makers to tailor an antibiotic incentive package that suits a country’s health system structure and needs

Antibiotic Resistance in Animal and Environmental Samples Associated with Small-Scale Poultry Farming in Northwestern Ecuador

The effects of animal agriculture on the spread of antibiotic resistance (AR) are cross-cutting and thus require a multidisciplinary perspective. Here we use ecological, epidemiological, and ethnographic methods to examine populations of Escherichia coli circulating in the production poultry farming environment versus the domestic environment in rural Ecuador, where small-scale poultry production employing nontherapeutic antibiotics is increasingly common. We sampled 262 “production birds” (commercially raised broiler chickens and laying hens) and 455 “household birds” (raised for domestic use) and household and coop environmental samples from 17 villages between 2010 and 2013. We analyzed data on zones of inhibition from Kirby-Bauer tests, rather than established clinical breakpoints for AR, to distinguish between populations of organisms. We saw significantly higher levels of AR in bacteria from production versus household birds; resistance to either amoxicillin-clavulanate, cephalothin, cefotaxime, and gentamicin was found in 52.8% of production bird isolates and 16% of household ones. A strain jointly resistant to the 4 drugs was exclusive to a subset of isolates from production birds (7.6%) and coop surfaces (6.5%) and was associated with a particular purchase site. The prevalence of AR in production birds declined with bird age (P _ 0.01 for all antibiotics tested except tetracycline, sulfisoxazole, and trimethoprim-sulfamethoxazole). Farming status did not impact AR in domestic environments at the household or village

Attitudes and Behaviours to Antimicrobial Prescribing following introduction of a Smartphone App

Our hospital replaced the format for delivering portable antimicrobial prescribing guidance from a paper-based pocket guide to a smartphone application (app). We used this opportunity to assess the relationship between its use and the attitudes and behaviours of antimicrobial prescribers. We used 2 structured cross-sectional questionnaires issued just prior to and 3 months following the launch of the smartphone app. Ordinal Likert scale responses to both frequencies of use and agreement statements permitted quantitative assessment of the relationship between variables. The smartphone app was used more frequently than the pocket guide it replaced (p < 0.01), and its increased use was associated with sentiments that the app was useful, easy to navigate and its content relevant. Users who used the app more frequently were more likely to agree that the app encouraged them to challenge inappropriate prescribing by their colleagues (p = 0.001) and were more aware of the importance of antimicrobial stewardship (p = 0.005). Reduced use of the app was associated with agreement that senior physicians' preferences for antimicrobial prescribing would irrespectively overrule guideline recommendations (p = 0.0002). Smartphone apps are an effective and acceptable format to deliver guidance on antimicrobial prescribing. Our findings suggest that they may empower users to challenge incorrect prescribing, breaking well-established behaviours, and thus supporting vital stewardship efforts in an era of increased antimicrobial resistance. Future work will need to focus on the direct impact on drug prescriptions as well as identifying barriers to implementing smartphone apps in other clinical settings

Predictors of mortality in multidrug-resistant Klebsiella pneumoniae bloodstream infections

The dramatic increase of antibiotic resistance in Klebsiella pneumoniae has been associated with fatal outcomes. First, bloodstream infections (BSIs) caused by extended-spectrum \u3b2-lactamases (ESBL) Enterobacteriaceae have been associated with treatment failure, more recently BSIs caused by carbapenem-resistant K. pneumoniae (CR-KP) have been reported to be fatal in approximately 50% of cases. Severity of underlying disease, intensive care unit stay at infection onset, infection with ESBL or CR-KP strain and delay in administration of appropriate therapy are among the most common risk factors for mortality in patients with K. pneumoniae BSI, while infection source control and early appropriate antimicrobial treatment have been associated with survival. Thus, risk assessment for ESBL and/or CR-KP is mandatory in patients with suspicion of K. pneumoniae BSI. Here, we examine current evidence regarding risk factors for mortality in patients with K. pneumoniae BSI and address the issue of a risk prediction model for CR-KP BSI

A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies

The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature's genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2',5'-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes