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Revista Espanola de Quimioterapia :... Feb 2018Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly... (Review)
Review
Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice.
Topics: Animals; Anti-Bacterial Agents; Blood-Brain Barrier; Central Nervous System; Central Nervous System Infections; Diffusion; Humans
PubMed: 29390599
DOI: No ID Found -
Emerging Microbes & Infections Dec 2024The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens -... (Review)
Review
The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative β-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People's Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People's Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What's more, as a vast nation, People's Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.
Topics: Humans; Anti-Bacterial Agents; Bacterial Infections; Klebsiella pneumoniae; Drug Resistance, Multiple, Bacterial; Enterococcus faecium
PubMed: 38356197
DOI: 10.1080/22221751.2024.2317915 -
The Yale Journal of Biology and Medicine Dec 2022Antimicrobial resistance is an increasing public health problem worldwide. The interest of a focus on antimicrobial resistance in acne lies on the facts that acne... (Review)
Review
Antimicrobial resistance is an increasing public health problem worldwide. The interest of a focus on antimicrobial resistance in acne lies on the facts that acne vulgaris (acne) is the most common skin disease worldwide, that the bacterium (, formerly ) plays a key role in the pathogenesis of acne, while at the same time being part of the skin flora, and that antibiotics are commonly recommended for acne treatment. The overuse of topical and/or systemic antibiotics, the long treatment courses used for acne, and the availability of over-the-counter antibiotic preparations, have led to the worldwide emergence of resistant strains in acne patients. In this review, we discuss the epidemiological trends of antimicrobial resistance in acne, the need to avoid the perturbation of the skin microbiome caused by anti-acne antibiotics, and the clinical practice considerations related to the emergence of resistant strains in acne patients. In light of the increasing risk of antimicrobial resistance, raising concerns over the misuse of antibiotics, prescribing patterns can be a critical target for antibiotic stewardship efforts. Also, the selection of non-antibiotic therapies for acne, whenever possible, may offer significant advantages.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Acne Vulgaris; Skin; Propionibacterium acnes
PubMed: 36568833
DOI: No ID Found -
Annual Review of Virology Sep 2023The global rise of antibiotic resistance in bacterial pathogens and the waning efficacy of antibiotics urge consideration of alternative antimicrobial strategies. Phage... (Review)
Review
The global rise of antibiotic resistance in bacterial pathogens and the waning efficacy of antibiotics urge consideration of alternative antimicrobial strategies. Phage therapy is a classic approach where bacteriophages (bacteria-specific viruses) are used against bacterial infections, with many recent successes in personalized medicine treatment of intractable infections. However, a perpetual challenge for developing generalized phage therapy is the expectation that viruses will exert selection for target bacteria to deploy defenses against virus attack, causing evolution of phage resistance during patient treatment. Here we review the two main complementary strategies for mitigating bacterial resistance in phage therapy: minimizing the ability for bacterial populations to evolve phage resistance and driving (steering) evolution of phage-resistant bacteria toward clinically favorable outcomes. We discuss future research directions that might further address the phage-resistance problem, to foster widespread development and deployment of therapeutic phage strategies that outsmart evolved bacterial resistance in clinical settings.
Topics: Humans; Phage Therapy; Bacterial Infections; Bacteriophages; Bacteria; Anti-Bacterial Agents
PubMed: 37268007
DOI: 10.1146/annurev-virology-012423-110530 -
MBio Aug 2020The continued rise in antibiotic resistance is precipitating a medical crisis. Bacteriophage (phage) has been hailed as one possible therapeutic option to augment the...
The continued rise in antibiotic resistance is precipitating a medical crisis. Bacteriophage (phage) has been hailed as one possible therapeutic option to augment the efficacy of antibiotics. However, only a few studies have addressed the synergistic relationship between phage and antibiotics. Here, we report a comprehensive analysis of phage-antibiotic interaction that evaluates synergism, additivism, and antagonism for all classes of antibiotics across clinically achievable stoichiometries. We combined an optically based real-time microtiter plate readout with a matrix-like heat map of treatment potencies to measure phage and antibiotic synergy (PAS), a process we term synography. Phage-antibiotic synography was performed against a pandemic drug-resistant clonal group of extraintestinal pathogenic (ExPEC) with antibiotic levels blanketing the MIC across seven orders of viral titers. Our results suggest that, under certain conditions, phages provide an adjuvating effect by lowering the MIC for drug-resistant strains. Furthermore, synergistic and antagonistic interactions are highly dependent on the mechanism of bacterial inhibition by the class of antibiotic paired to the phage, and when synergism is observed, it suppresses the emergence of resistant cells. Host conditions that simulate the infection environment, including serum and urine, suppress PAS in a bacterial growth-dependent manner. Lastly, two different related phages that differed in their burst sizes produced drastically different synograms. Collectively, these data suggest lytic phages can resuscitate an ineffective antibiotic for previously resistant bacteria while also synergizing with antibiotics in a class-dependent manner, processes that may be dampened by lower bacterial growth rates found in host environments. Bacteriophage (phage) therapy is a promising approach to combat the rise of multidrug-resistant bacteria. Currently, the preferred clinical modality is to pair phage with an antibiotic, a practice thought to improve efficacy. However, antagonism between phage and antibiotics has been reported, the choice of phage and antibiotic is not often empirically determined, and the effect of the host factors on the effectiveness is unknown. Here, we interrogate phage-antibiotic interactions across antibiotics with different mechanisms of action. Our results suggest that phage can lower the working MIC for bacterial strains already resistant to the antibiotic, is dependent on the antibiotic class and stoichiometry of the pairing, and is dramatically influenced by the host microenvironment.
Topics: Anti-Bacterial Agents; Bacteriophages; Drug Antagonism; Drug Resistance, Multiple, Bacterial; Drug Synergism; Escherichia coli; Humans; Microbial Sensitivity Tests; Phage Therapy
PubMed: 32753497
DOI: 10.1128/mBio.01462-20 -
Molecules (Basel, Switzerland) Jun 2020The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed... (Review)
Review
The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant , vancomycin-resistant , and drug-resistant are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacteria; Microbial Sensitivity Tests; Phage Therapy; Probiotics
PubMed: 32586045
DOI: 10.3390/molecules25122888 -
ELife Mar 2023The global spread of antibiotic resistance could be due to a number of factors, and not just the overuse of antibiotics in agriculture and medicine as previously thought.
The global spread of antibiotic resistance could be due to a number of factors, and not just the overuse of antibiotics in agriculture and medicine as previously thought.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Agriculture
PubMed: 36884273
DOI: 10.7554/eLife.86697 -
JAMA Internal Medicine May 2020The requirement of prolonged intravenous antibiotic courses to treat infective endocarditis (IE) is a time-honored dogma of medicine. However, numerous antibiotics are... (Review)
Review
IMPORTANCE
The requirement of prolonged intravenous antibiotic courses to treat infective endocarditis (IE) is a time-honored dogma of medicine. However, numerous antibiotics are now available that achieve adequate levels in the blood after oral administration to kill bacteria. Moreover, prolonged intravenous antibiotic regimens are associated with high rates of adverse events. Accordingly, recent studies of oral step-down antibiotic treatment have stimulated a reevaluation of the need for intravenous-only therapy for IE.
OBSERVATIONS
PubMed was reviewed in October 2019, with an update in February 2020, to determine whether evidence supports the notion that oral step-down antibiotic therapy for IE is associated with inferior outcomes compared with intravenous-only therapy. The search identified 21 observational studies evaluating the effectiveness of oral antibiotics for treating IE, typically after an initial course of intravenous therapy; none found such oral step-down therapy to be inferior to intravenous-only therapy. Multiple studies described an improved clinical cure rate and an improved mortality rate among patients treated with oral step-down vs intravenous-only antibiotic therapy. Three randomized clinical trials also demonstrated that oral step-down antibiotic therapy is at least as effective as intravenous-only therapy in right-sided, left-sided, or prosthetic valve IE. In the largest trial, at 3.5 years of follow-up, patients randomized to receive oral step-down antibiotic therapy had a significantly improved cure rate and mortality rate compared with those who received intravenous-only therapy.
CONCLUSIONS AND RELEVANCE
This review found ample data demonstrating the therapeutic effectiveness of oral step-down vs intravenous-only antibiotic therapy for IE, and no contrary data were identified. The use of highly orally bioavailable antibiotics as step-down therapy for IE, after clearing bacteremia and achieving clinical stability with intravenous regimens, should be incorporated into clinical practice.
Topics: Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Drug Administration Schedule; Endocarditis; Humans; Practice Patterns, Physicians'
PubMed: 32227127
DOI: 10.1001/jamainternmed.2020.0555 -
International Journal of Molecular... Aug 2020Although the introduction of antibiotics in medicine has resulted in one of the most successful events and in a major breakthrough to reduce morbidity and mortality... (Review)
Review
Although the introduction of antibiotics in medicine has resulted in one of the most successful events and in a major breakthrough to reduce morbidity and mortality caused by infectious disease, response to these agents is not always predictable, leading to differences in their efficacy, and sometimes to the occurrence of adverse effects. Genetic variability, resulting in differences in the pharmacokinetics and pharmacodynamics of antibiotics, is often involved in the variable response, of particular importance are polymorphisms in genes encoding for drug metabolizing enzymes and membrane transporters. In addition, variations in the human leukocyte antigen (HLA) class I and class II genes have been associated with different immune mediated reactions induced by antibiotics. In recent years, the importance of pharmacogenetics in the personalization of therapies has been recognized in various clinical fields, although not clearly in the context of antibiotic therapy. In this review, we make an overview of antibiotic pharmacogenomics and of its potential role in optimizing drug therapy and reducing adverse reactions.
Topics: Anti-Bacterial Agents; Bacterial Infections; Genome-Wide Association Study; HLA Antigens; Humans; Pharmacogenomic Variants; Precision Medicine
PubMed: 32825180
DOI: 10.3390/ijms21175975 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Aug 2022(Ashby) Downson is a quarantine pest for importing plants to China that causes leaf scald bacterial disease on sugarcane. . produces a potent phytotoxin/antibiotic... (Review)
Review
(Ashby) Downson is a quarantine pest for importing plants to China that causes leaf scald bacterial disease on sugarcane. . produces a potent phytotoxin/antibiotic called albicidin. As a pathogenic factor, albicidin causes typical white leaf stripes by inhibiting plastid DNA gyrase and disturbing chloroplast differentiation. Meanwhile, the antibacterial activity of albicidin gives . a competitive advantage against rival bacteria during their colonization. Furthermore, albicidin has a rapid bactericidal activity against a variety of Gram-positive and Gram-negative pathogenic bacteria of human species at nanomolar concentrations, making it a potential antimicrobial drug for clinical application. This article reviews the advances of albicidin from the aspects of its molecular structure, traditional extraction methods, mechanism of action, biosynthetic genes and processes, chemical synthesis method and improvement, in order to provide insights into the prevention and treatment of the sugarcane leaf scald disease, and the development of new antibiotics.
Topics: Anti-Bacterial Agents; China; Humans; Organic Chemicals; Xanthomonas
PubMed: 36002407
DOI: 10.13345/j.cjb.210832