Antibiotic resistance, and, in a broader perspective, antimicrobial resistance (AMR), continues to evolve and spread beyond all boundaries. As a result, infectious diseases have become more challenging or even impossible to treat, leading to an increase in morbidity and mortality. Despite the failure of conventional, traditional antimicrobial therapy, in the past two decades, no novel class of antibiotics has been introduced. Consequently, several novel alternative strategies to combat these (multi-) drug-resistant infectious microorganisms have been identified. The purpose of this review is to gather and consider the strategies that are being applied or proposed as potential alternatives to traditional antibiotics. These strategies include combination therapy, techniques that target the enzymes or proteins responsible for antimicrobial resistance, resistant bacteria, drug delivery systems, physicochemical methods, and unconventional techniques, including the CRISPR-Cas system. These alternative strategies may have the potential to change the treatment of multi-drug-resistant pathogens in human clinical settings.

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.

Healthcare-associated infections (HCAIs) are a major source of morbidity and mortality and are the second most prevalent cause of death. Furthermore, it has been reported that for every one-hundred patients admitted to hospital, seven patients in high-income economies and ten in emerging and low-income economies acquire at least one type of HCAI. Currently, almost all pathogenic microorganisms have developed antimicrobial resistance, and few new antimicrobials are being developed and brought to market. The literature search for this narrative review was performed by searching bibliographic databases (including Google Scholar and PubMed) using the search terms: “Strategies,” “Prevention,” and “Healthcare-Associated Infections,” followed by snowballing references cited by critical articles. We found that although hand hygiene is a centuries-old concept, it is still the primary strategy used around the world to prevent HCAIs. It forms one of a bundle of approaches used to clean and maintain a safe hospital environment and to stop the transmission of contagious and infectious microorganisms, including multidrug-resistant microbes. Finally, antibiotic stewardship also has a crucial role in reducing the impact of HCAIs through conserving currently available antimicrobials.

The history of antimicrobial resistance (AMR) evolution and the diversity of the environmental resistome indicate that AMR is an ancient natural phenomenon. Acquired resistance is a public health concern influenced by the anthropogenic use of antibiotics, leading to the selection of resistant genes. Data show that AMR is spreading globally at different rates, outpacing all efforts to mitigate this crisis. The search for new antibiotic classes is one of the key strategies in the fight against AMR. Since the 1980s, newly marketed antibiotics were either modifications or improvements of known molecules. The World Health Organization (WHO) describes the current pipeline as bleak, and warns about the scarcity of new leads. A quantitative and qualitative analysis of the pre-clinical and clinical pipeline indicates that few antibiotics may reach the market in a few years, predominantly not those that fit the innovative requirements to tackle the challenging spread of AMR. Diversity and innovation are the mainstays to cope with the rapid evolution of AMR. The discovery and development of antibiotics must address resistance to old and novel antibiotics. Here, we review the history and challenges of antibiotics discovery and describe different innovative new leads mechanisms expected to replenish the pipeline, while maintaining a promising possibility to shift the chase and the race between the spread of AMR, preserving antibiotic effectiveness, and meeting innovative leads requirements.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.

OBJECTIVE—Adipose tissue serves as an integrator of various physiological pathways, energy balance, and glucose homeostasis. Forkhead box–containing protein O subfamily (FoxO) 1 mediates insulin action at the transcriptional level. However, physiological roles of FoxO1 in adipose tissue remain unclear. RESEARCH DESIGN AND METHODS—In the present study, we generated adipose tissue–specific FoxO1 transgenic mice (adipocyte protein 2 [aP₂]-FLAG-Δ256) using an aP₂ promoter/enhancer and a mutant FoxO1 (FLAGΔ256) in which the carboxyl terminal transactivation domain was deleted. Using these mice, we analyzed the effects of the overexpression of FLAGΔ256 on glucose metabolism and energy homeostasis. RESULTS—The aP₂-FLAG-Δ256 mice showed improved glucose tolerance and insulin sensitivity accompanied with smaller-sized adipocytes and increased adiponectin (adipoq) and Glut 4 (Slc2a4) and decreased tumor necrosis factor α (Tnf) and chemokine (C-C motif) receptor 2 (Ccr2) gene expression levels in white adipose tissue (WAT) under a high-fat diet. Furthermore, the aP₂-FLAG-Δ256 mice had increased oxygen consumption accompanied with increased expression of peroxisome proliferator–activated receptor γ coactivator (PGC)-1α protein and uncoupling protein (UCP)-1 (Ucp1), UCP-2 (Ucp2), and β3-AR (Adrb3) in brown adipose tissue (BAT). Overexpression of FLAGΔ256 in T37i cells, which are derived from the hibernoma of SV40 large T antigen transgenic mice, increased expression of PGC-1α protein and Ucp1. Furthermore, knockdown of endogenous FoxO1 in T37i cells increased Pgc1α (Ppargc1a), Pgc1β (Ppargc1b), Ucp1, and Adrb3 gene expression. CONCLUSIONS—These data suggest that FoxO1 modulates energy homeostasis in WAT and BAT through regulation of adipocyte size and adipose tissue–specific gene expression in response to excessive calorie intake.