Combating multidrug-resistant bacteria: current strategies for the discovery of novel antibacterials.
O'Connell Kieron M G,Hodgkinson James T,Sore Hannah F,Welch Martin,Salmond George P C,Spring David R
Angewandte Chemie (International ed. in English)
The introduction of effective antibacterial therapies for infectious diseases in the mid-20th century completely revolutionized clinical practices and helped to facilitate the development of modern medicine. Many potentially life-threatening conditions became easily curable, greatly reducing the incidence of death or disability resulting from bacterial infections. This overwhelming historical success makes it very difficult to imagine life without effective antibacterials; however, the inexorable rise of antibiotic resistance has made this a very real and disturbing possibility for some infections. The ruthless selection for resistant bacteria, coupled with insufficient investment in antibacterial research, has led to a steady decline in the efficacy of existing therapies and a paucity of novel structural classes with which to replace them, or complement their use. This situation has resulted in a very pressing need for the discovery of novel antibiotics and treatment strategies, the development of which is likely to be a key challenge to 21st century medicinal chemistry.
10.1002/anie.201209979
[Management strategy of intra-abdominal infection caused by multidrug-resistant bacteria].
Liu Haiyan,Zhou Zheng
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
Most of the intra-abdominal infections are benign and critical diseases caused by trauma, surgery and gastrointestinal diseases, which require the attention of surgeons. The increase of drug resistance of pathogens is a common clinical problem. The intra-abdominal infection caused by multidrug-resistant bacteria is a huge challenge faced by clinicians, and is mainly found in hospital-acquired abdominal infections, of which gram-negative bacteria are the most common. This paper firstly summarizes the common types, early diagnosis and risk factors of multidrug-resistant bacteria according to the literature, and then describes the treatment strategy of intra-abdominal infection caused by multidrug-resistant bacteria from four aspects: anti-infective medication, infection source control, resuscitation and organ support, and nutritional support treatment. In addition, we should promote gastrointestinal function recovery through nutritional support treatment and prevent intestinal source infection, on the basis of understanding the risk factors of multidrug-resistant infection, rational use of anti-infective medication and infection source control measures. At the same time, proper organ function support can help to improve the success rate in the treatment of multidrug-resistant intra-abdominal infection.
Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens.
Santajit Sirijan,Indrawattana Nitaya
BioMed research international
The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.
10.1155/2016/2475067
New antibiotics for the treatment of infections by multidrug-resistant microorganisms.
Escolà-Vergé Laura,Los-Arcos Ibai,Almirante Benito
Medicina clinica
One of the current priorities of the World Health Organization is multidrug-resistant bacteria, because they are a global problem due to their rapid spread and the difficulty of their treatment. In addition, they are associated with high morbidity, mortality and high economic costs. There are multidrug-resistant bacteria, both Gram-positive and Gram-negative, including Pseudomonas aeruginosa and Acinetobacter baumannii resistant to carbapenems, enterobacteria producing carbapenemases, Staphylococcus aureus resistant to methicillin and/or with intermediate sensitivity to vancomycin, and Enterococcus faecium (and less frequently Enterococcus faecalis) resistant to vancomycin. This review will comment on the new antibiotics that have been incorporated into the therapeutic arsenal in recent years, as well as other promising antibiotics that are in their final stages of development.
10.1016/j.medcli.2019.11.002
Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the diagnosis and antimicrobial treatment of infections due to carbapenem-resistant Gram-negative bacteria.
Enfermedades infecciosas y microbiologia clinica (English ed.)
Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although 'old' antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the 'new' beta-lactams such as ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria.
10.1016/j.eimce.2022.06.014
Multidrug-resistant bacteria in hematology patients: emerging threats.
Tatarelli Paola,Mikulska Malgorzata
Future microbiology
Multidrug-resistant (MDR) bacteria, particularly Gram negatives, such as Enterobacteriaceae resistant to third-generation cephalosporins or carbapenems and MDR Pseudomonas aeruginosa, are increasingly frequent in hematology patients. The prevalence of different resistant species varies significantly between centers. Thus, the knowledge of local epidemiology is mandatory for deciding the most appr-opriate management protocols. In the era of increasing antibiotic resistance, empirical therapy of febrile neutropenia should be individualized. A de-escalation approach is recommended in case of severe clinical presentation in patients who are at high risk for infection with a resistant strain. Targeted therapy of an MDR Gram negative usually calls for a combination treatment, although no large randomized trials exist in this setting. Infection control measures are the cornerstone of limiting the spread of MDR pathogens in hematology units.
10.2217/fmb-2015-0014
Multidrug-Resistant Bacteria in the Community: An Update.
van Duin David,Paterson David L
Infectious disease clinics of North America
Multidrug-resistant bacteria are among the most important current threats to public health. Typically, they are associated with nosocomial infections. However, some have become prevalent causes of community-acquired infections, such as Neisseria gonorrhoeae, Shigella, Salmonella, and Streptococcus pneumoniae. The community spread of multidrug-resistant bacteria is also a crucial development. An important global threat on the horizon is represented by production of carbapenemases by community-acquired hypervirulent Klebsiella pneumoniae. Such strains have already been found in Asia, Europe, and North America. Prevention of further community spread of multidrug-resistant bacteria is of the utmost importance, and will require a multidisciplinary approach involving all stakeholders.
10.1016/j.idc.2020.08.002
Renaissance of vancomycin: approaches for breaking antibiotic resistance in multidrug-resistant bacteria.
Mühlberg Eric,Umstätter Florian,Kleist Christian,Domhan Cornelius,Mier Walter,Uhl Philipp
Canadian journal of microbiology
The emergence of multidrug-resistant bacteria demands innovations in the development of new antibiotics. For decades, the glycopeptide antibiotic vancomycin has been considered as the "last resort" treatment of severe infections caused by Gram-positive bacteria. Since the discovery of the first vancomycin-resistant enterococci strains in the late 1980s, the number of resistances has been steadily rising, with often life-threatening consequences. As an alternative to the generation of completely new substances, novel approaches focus on structural modifications of established antibiotics such as vancomycin to overcome these resistances. Here, we provide an overview of several promising modifications of vancomycin to restore its efficacy against vancomycin-resistant enterococci.
10.1139/cjm-2019-0309
Tackling Threats and Future Problems of Multidrug-Resistant Bacteria.
Medina Eva,Pieper Dietmar Helmut
Current topics in microbiology and immunology
With the advent of the antibiotic era, the overuse and inappropriate consumption and application of antibiotics have driven the rapid emergence of multidrug-resistant pathogens. Antimicrobial resistance increases the morbidity, mortality, length of hospitalization and healthcare costs. Among Gram-positive bacteria, Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) Mycobacterium tuberculosis, and among the Gram-negative bacteria, extended-spectrum beta-lactamase (ESBLs)-producing bacteria have become a major global healthcare problem in the 21st century. The pressure to use antibiotics guarantees that the spread and prevalence of these as well as of future emerging multidrug-resistant pathogens will be a persistent phenomenon. The unfeasibility of reversing antimicrobial resistance back towards susceptibility and the critical need to treat bacterial infection in modern medicine have burdened researchers and pharmaceutical companies to develop new antimicrobials effective against these difficult-to-treat multidrug-resistant pathogens. However, it can be anticipated that antibiotic resistance will continue to develop more rapidly than new agents to treat these infections become available and a better understanding of the molecular, evolutionary and ecological mechanisms governing the spread of antibiotic resistance is needed. The only way to curb the current crisis of antimicrobial resistance will be to develop entirely novel strategies to fight these pathogens such as combining antimicrobial drugs with other agents that counteract and obstruct the antibiotic resistant mechanisms expressed by the pathogen. Furthermore, as many antibiotics are often inappropriately prescribed, a more personalized approach based on precise diagnosis tools will ensure that proper treatments can be promptly applied leading to more targeted and effective therapies. However, in more general terms, also the overall use and release of antibiotics in the environment needs to be better controlled.
10.1007/82_2016_492
Multidrug-resistant bacteria and travel.
De Vallière Serge
Revue medicale suisse
Antimicrobial resistance is a global problem which affects also tropical countries. Travelers to these regions expose themselves to the risk of being colonised and infected with multidrug-resistant bacteria. The region visited, the occurrence of diarrhoea and the use of antibiotics are the principal risk factors leading to colonisation with multidrug-resistant Enterobacteriaceae, which can affect up to 80% of travellers. Colonisation with meticillin resistant Staphylococcus aureus and vancomycin resistant enterococci are often due to contacts with the health care system of the visited country. For the practitioner evaluating a patient returning from abroad it is important to consider the risk of infection with multidrug-resistant bacteriae. Screening for these bacteriae in the stool or by mucocutaneous swabs can be discussed in certain situations.