Antibiotic resistance has progressively diminished the effectiveness of conventional antibiotics, necessitating the cessation of clinical treatment. Consequently, novel antibacterial agents are urgently needed. We review studies on antimicrobial agents published during 2002-2023. Most of these studies were published within the last 10 years. By analyzing recent articles on antibiotic resistance and the development of new antibacterial drugs, we showed that although drug resistance is inevitable, the issue is being addressed gradually via the discovery and clinical application of antimicrobial peptides, nanomaterial drugs, and bacteriophage therapy. In light of the emergence of antimicrobial resistance, the development of new antimicrobial agents will require innovation in a field that has relied on traditional methods of discovery and development.

New Delhi Metallo-β-lactamase is an enzyme produced by gram-negative bacteria which has become one of the global concerns for physicians to treating the infection. These Metallo- β-lactamase are capable of catalyzing the hydrolysis of almost all β-lactam antibiotics, endangering infection treatment. Substitution of single or multiple amino acids results in new NDM variants. Forty NDM variants have been identified in different bacterial strains across the globe. In this review, we focused on the structural insight of all NDM variants including the type of amino acid residues and their position of substitution, country of origin, and type of bacteria carrying these resistant markers. We also discussed the carbapenemase activity and stability of enzymes that helps to design potent inhibitors to combat drug-resistant infections.

BACKGROUND: Routine microbiology results are a valuable source of antimicrobial resistance (AMR) surveillance data in low- and middle-income countries (LMICs) as well as in high-income countries. Different approaches and strategies are used to generate AMR surveillance data.
OBJECTIVE: We aimed to review strategies for AMR surveillance using routine microbiology results in LMICs and to highlight areas that need support to generate high-quality AMR data.
METHODS: We searched PubMed for papers that used routine microbiology to describe the epidemiology of AMR and drug-resistant infections in LMICs. We also included papers that, from our perspective, were critical in highlighting the biases and challenges or employed specific strategies to overcome these in reporting AMR surveillance in LMICs.
BACKGROUND: Topics covered included strategies of identifying AMR cases (including case-finding based on isolates from routine diagnostic specimens and case-based surveillance of clinical syndromes), of collecting data (including cohort, point-prevalence survey, and case-control), of sampling AMR cases (including lot quality assurance surveys), and of processing and analysing data for AMR surveillance in LMICs.
CONCLUSIONS: The various AMR surveillance strategies warrant a thorough understanding of their limitations and potential biases to ensure maximum utilization and interpretation of local routine microbiology data across time and space. For instance, surveillance using case-finding based on results from clinical diagnostic specimens is relatively easy to implement and sustain in LMIC settings, but the estimates of incidence and proportion of AMR is at risk of biases due to underuse of microbiology. Case-based surveillance of clinical syndromes generates informative statistics that can be translated to clinical practices but needs financial and technical support as well as locally tailored trainings to sustain. Innovative AMR surveillance strategies that can easily be implemented and sustained with minimal costs will be useful for improving AMR data availability and quality in LMICs.

Gram-negative bacteria cause the majority of highly drug-resistant bacterial infections. To cross the outer membrane of the complex Gram-negative cell envelope, antibiotics permeate through porins, trimeric channel proteins that enable the exchange of small polar molecules. Mutations in porins contribute to the development of drug-resistant phenotypes. In this work, we show that a single point mutation in the porin PorB from Neisseria meningitidis, the causative agent of bacterial meningitis, can strongly affect the binding and permeation of beta-lactam antibiotics. Using X-ray crystallography, high-resolution electrophysiology, atomistic biomolecular simulation, and liposome swelling experiments, we demonstrate differences in drug binding affinity, ion selectivity and drug permeability of PorB. Our work further reveals distinct interactions between the transversal electric field in the porin eyelet and the zwitterionic drugs, which manifest themselves under applied electric fields in electrophysiology and are altered by the mutation. These observations may apply more broadly to drug-porin interactions in other channels. Our results improve the molecular understanding of porin-based drug-resistance in Gram-negative bacteria.

Background  The global burden of infections due to multidrug-resistant organism (MDRO) has a significant impact on patients\' morbidity and mortality along with increased healthcare expenditure. Aim  This article estimates the prevalence of MDRO and the spectrum of clinical infectious syndromes caused by these organisms in medical wards of a tertiary care hospital in India. Design and Methods  A cross-sectional observational study was performed among patients admitted in medicine wards diagnosed with the various infectious syndromes and one or more clinically significant positive culture at a tertiary care hospital in North India over a period of 18 months. Results  Out of 323 clinically significant microbiological culture isolates from 229 patients included in the study, 86 (27%) isolates showed multidrug resistance (MDR) pattern, 197 (61%) isolates showed possible extremely drug-resistance pattern, and only 40 (12%) isolates showed nonmultidrug-resistance pattern of antibiogram. Conclusion  The prevalence of MRDOs is high in clinically significant culture isolates from medicine wards in India. This emphasizes the importance of appropriate antibiotic usage and implementation of antibiotic stewardship programs in this part of the world.

METHODS: A priority-setting process (PSP) was launched to define priorities for patient-centered antimicrobial resistance (AMR) surveillance and research in low- and middle-income countries (LMICs). A list of uncertainties related to AMR surveillance in human health was generated using an online survey of stakeholders in LMICs, which asked for unanswered questions about diagnosis, treatment, or prevention of antibiotic resistance.
RESULTS: A total of 445 respondents generated 1076 questions that were mapped to a final shortlist of 107 questions. The most common theme was the treatment of drug-resistant infections, followed by diagnosis, then prevention, and requests for local AMR data. The most asked question was a request for local AMR data, revealing the lack of basic information in many LMICs to guide actions to tackle AMR. The steering group recommended three research areas to be prioritized for funding in the next five years: infection prevention and control in LMICs, improved electronic patient records, starting with laboratory information management systems, and sustainable behavior change among doctors and other health care professionals with a focus on diagnostic stewardship.

Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention.
We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance.
We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified.
Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice.
PROSPERO CRD42018029432.

暂无摘要。

Escalating antibiotic resistance is now a serious menace to global public health. It may be led to the emergence of \"postantibiotic age\" in which most of infections are untreatable. At present, there is an essential need to explore novel therapeutic strategies as a strong and sustainable pipeline to combat antibiotic-resistant infections. This review focuses on recent advances in this area including therapeutic antibodies, antimicrobial peptides, vaccines, gene therapy, genome editing, and phage therapy for tackling drug-resistant infections.

The recent declaration by the United Nations to establish an interagency coordination group (IACG) on antimicrobial resistance (AMR) emphasises the global nature of the AMR threat. Rapid dissemination and spread of AMR is exacerbated by the movements of humans, animals, foods and materials. International monitoring and surveillance of AMR indicates to policy makers, regulators and auditors the magnitude of the problem and also informs appropriate and mindful interventions that will impact public health policy and mitigate AMR. Identifying the drivers of AMR requires a \'one-health\' approach to capture cross-sectoral utilization, phenotypic and genetic data. Capacity building in diagnostic and reference laboratories is required for traditional phenotypic testing as well as newer technologies (e.g. whole genome sequencing, WGS), in order to enhance the detection, characterisation, tracking and surveillance of AMR. The Gulf Health Council (GHC) for the cooperation council states have developed national AMR plans and will standardise pathogen identification and susceptibility testing to gain useful, reliable and comparable data. Additional plans are to establish, for the region, a state-of-the-art \'one-health\' WGS service to identify and examine emerging AMR issues as well as the associated healthcare and financial burden(s). Currently, there is a paucity of WGS based research for tackling AMR challenges in the GHC countries. In this article, we have considered the current surveillance landscape and the potential role of whole genome sequencing (WGS) for monitoring antimicrobial resistance in the Arabian Peninsula. We highlighted the importance of using WGS for monitoring AMR in these countries as there remains a dearth of microbial genomic data and studies from the GHC countries. Development of WGS-based AMR surveillance is required to identify the burden and prevalence of AMR in the GHC countries.