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Current Opinion in Microbiology Oct 2019The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human... (Review)
Review
The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human lifespan by 23 years. The discovery of penicillin in 1928 started the golden age of natural product antibiotic discovery that peaked in the mid-1950s. Since then, a gradual decline in antibiotic discovery and development and the evolution of drug resistance in many human pathogens has led to the current antimicrobial resistance crisis. Here we give an overview of the history of antibiotic discovery, the major classes of antibiotics and where they come from. We argue that the future of antibiotic discovery looks bright as new technologies such as genome mining and editing are deployed to discover new natural products with diverse bioactivities. We also report on the current state of antibiotic development, with 45 drugs currently going through the clinical trials pipeline, including several new classes with novel modes of action that are in phase 3 clinical trials. Overall, there are promising signs for antibiotic discovery, but changes in financial models are required to translate scientific advances into clinically approved antibiotics.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Discovery; History, 20th Century; History, 21st Century; Humans
PubMed: 31733401
DOI: 10.1016/j.mib.2019.10.008 -
Trends in Microbiology Oct 2021Bacterial coinfections increase the severity of respiratory viral infections and were frequent causes of mortality in influenza pandemics but have not been well... (Review)
Review
Bacterial coinfections increase the severity of respiratory viral infections and were frequent causes of mortality in influenza pandemics but have not been well characterized in patients with coronavirus disease 2019 (COVID-19). The aim of this review was to identify the frequency and microbial etiologies of bacterial coinfections that are present upon admission to the hospital and that occur during hospitalization for COVID-19. We found that bacterial coinfections were present in <4% of patients upon admission and the yield of routine diagnostic tests for pneumonia was low. When bacterial coinfections did occur, Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae were the most common pathogens and atypical bacteria were rare. Although uncommon upon admission, bacterial infections frequently occurred in patients with prolonged hospitalization, and Pseudomonas aeruginosa, Klebsiella spp., and S. aureus were common pathogens. Antibacterial therapy and diagnostic testing for bacterial infections are unnecessary upon admission in most patients hospitalized with COVID-19, but clinicians should be vigilant for nosocomial bacterial infections.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; COVID-19; Coinfection; Humans; SARS-CoV-2
PubMed: 33934980
DOI: 10.1016/j.tim.2021.03.018 -
Clinical Microbiology Reviews Dec 2022All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues... (Review)
Review
All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, , Pseudomonas, and normal respiratory flora. Urine antigen detection is useful in identifying and pneumococcus. The low yield of bacteria in recent studies is due to the failure to obtain valid sputum samples before antibiotics are administered. The use of high-quality sputum specimens enables identification of recognized ("typical") bacterial pathogens as well as a role for commensal bacteria ("normal respiratory flora"). Nucleic acid amplification technology for viruses has revolutionized diagnosis, showing the importance of viral pneumonia leading to hospitalization with or without coinfecting bacterial organisms. Quantitative PCR study of sputum is in its early stages of application, but regular detection of high counts of bacterial DNA from organisms that are not seen on Gram stain or grown in quantitative culture presents a therapeutic dilemma. This finding may reflect the host microbiome of the respiratory tract, in which case treatment may not need to be given for them. Finally, host transcriptional signatures might enable clinicians to distinguish between viral and bacterial pneumonia, an important practical consideration.
Topics: Adult; Humans; Bacteriology; Pneumonia, Bacterial; Streptococcus pneumoniae; Pneumonia, Viral; Bacteria; Community-Acquired Infections
PubMed: 36165783
DOI: 10.1128/cmr.00015-22 -
Journal of Molecular Biology Jul 2019The human oral cavity harbors diverse communities of microbes that live as biofilms: highly ordered, surface-associated assemblages of microbes embedded in an... (Review)
Review
The human oral cavity harbors diverse communities of microbes that live as biofilms: highly ordered, surface-associated assemblages of microbes embedded in an extracellular matrix. Oral microbial communities contribute to human health by fine-tuning immune responses and reducing dietary nitrate. Dental caries and periodontal disease are together the most prevalent microbially mediated human diseases worldwide. Both of these oral diseases are known to be caused not by the introduction of exogenous pathogens to the oral environment, but rather by a homeostasis breakdown that leads to changes in the structure of the microbial communities present in states of health. Both dental caries and periodontal disease are mediated by synergistic interactions within communities, and both diseases are further driven by specific host inputs: diet and behavior in the case of dental caries and immune system interactions in the case of periodontal disease. Changes in community structure (taxonomic identity and abundance) are well documented during the transition from health to disease. In this review, changes in biofilm physical structure during the transition from oral health to disease and the concomitant relationship between structure and community function will be emphasized.
Topics: Bacteria; Biofilms; Dental Caries; Dental Plaque; Diet; Homeostasis; Humans; Periodontal Diseases
PubMed: 31103772
DOI: 10.1016/j.jmb.2019.05.016 -
Journal of Nanobiotechnology Dec 2021Antibiotic resistance is spreading rapidly around the world and seriously impeding efforts to control microbial infections. Although nucleic acid testing is widely... (Review)
Review
Antibiotic resistance is spreading rapidly around the world and seriously impeding efforts to control microbial infections. Although nucleic acid testing is widely deployed for the detection of antibiotic resistant bacteria, the current techniques-mainly based on polymerase chain reaction (PCR)-are time-consuming and laborious. There is an urgent need to develop new strategies to control bacterial infections and the spread of antimicrobial resistance (AMR). The CRISPR-Cas system is an adaptive immune system found in many prokaryotes that presents attractive opportunities to target and edit nucleic acids with high precision and reliability. Engineered CRISPR-Cas systems are reported to effectively kill bacteria or even revert bacterial resistance to antibiotics (resensitizing bacterial cells to antibiotics). Strategies for combating antimicrobial resistance using CRISPR (i.e., Cas9, Cas12, Cas13, and Cas14) can be of great significance in detecting bacteria and their resistance to antibiotics. This review discusses the structures, mechanisms, and detection methods of CRISPR-Cas systems and how these systems can be engineered for the rapid and reliable detection of bacteria using various approaches, with a particular focus on nanoparticles. In addition, we summarize the most recent advances in applying the CRISPR-Cas system for virulence modulation of bacterial infections and combating antimicrobial resistance.
Topics: Animals; Bacteria; Bacterial Infections; CRISPR-Cas Systems; Drug Delivery Systems; Drug Resistance, Bacterial; Humans; Mice
PubMed: 34863214
DOI: 10.1186/s12951-021-01132-8 -
Clinical Microbiology and Infection :... Dec 2020Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood.
AIMS
To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19.
SOURCES
We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection.
CONTENT
Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4-6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6-18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3-9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3-13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%).
IMPLICATIONS
Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.
Topics: Asia; Bacteria; Bacterial Infections; COVID-19; Coinfection; Critical Illness; Data Management; Female; Humans; Male; Pandemics; Prevalence; Respiratory Tract Infections; United States
PubMed: 32711058
DOI: 10.1016/j.cmi.2020.07.016 -
Gut Microbes 2021The gut bacterium has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and...
The gut bacterium has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model. Mice treated with efficiently reversed MAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in the antibiotics-treated obese mice. treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress-induced cell apoptosis in gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate or in mice displayed the similar beneficial metabolic effects mentioned above and efficiently ameliorated MAFLD. Together, these data indicate that the anti-MAFLD activity of correlated with lipid oxidation and improved gut-liver interactions through regulating the metabolism of L-aspartate. could be a potential agent for clinical intervention in MAFLD.
Topics: Akkermansia; Animals; Aspartic Acid; Bacteria; Diet, High-Fat; Fatty Liver; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Liver; Male; Mice; Mice, Inbred C57BL
PubMed: 34030573
DOI: 10.1080/19490976.2021.1927633 -
Aging Aug 2021
Topics: Animals; Bacteria; Bone and Bones; DNA Damage; Gastrointestinal Microbiome; Humans; Intestines; Radiation, Ionizing; Radiotherapy
PubMed: 34406126
DOI: 10.18632/aging.203446 -
Frontiers in Cellular and Infection... 2019Alterations to the gut microbiota have been previously suggested to be tightly linked to chronic systemic inflammation, which is a major contributing factor to...
Alterations to the gut microbiota have been previously suggested to be tightly linked to chronic systemic inflammation, which is a major contributing factor to complications and disease progression in chronic kidney disease (CKD). Nevertheless, the effect of gut dysbiosis on the pathogenesis and/or production of inflammatory factors in CKD has not been extensively studied to date. In the present study, we conducted 16S ribosomal DNA pyrosequencing using fecal microbiota samples and analyzed the production of serum inflammatory factors in 50 patients with CKD and 22 healthy control (HC) subjects. The results revealed that compared to the HC subjects, patients with CKD exhibited a significant reduction in the richness and structure of their fecal microbiota. At the phylum level, compared to the HC group, patients with CKD also presented reduced abundance of Actinobacteria but increased abundance of Verrucomicrobia. Moreover, the genera , and were enriched in the fecal samples of patients with CKD, while and were enriched in those of the HC subjects. The abundance of in the CKD group was significantly lower than that in the HC group (3.08 vs. 0.67%); this decrease in the abundance of , an important probiotic, in patients with CKD is a striking discovery as it has not been previously reported. Finally, we analyzed whether these changes to the fecal microbiota correlated with CKD clinical characteristics and/or the production of known inflammatory factors. Altered levels of the microbiota genera , and were shown to be correlated with CKD disease-severity indicators, including the estimated glomerular filtration rate. Most notably, was significantly negatively correlated with the production of interleukin-10. The results of the present study suggest that microbiota dysbiosis may promote chronic systemic inflammation in CKD. Furthermore, they support that modifying the gut microbiota, especially , may be a promising potential therapeutic strategy to attenuate the progression of, and/or systemic inflammation in, CKD.
Topics: Adult; Aged; Bacteria; Biomarkers; China; Cytokines; DNA, Bacterial; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Inflammation; Male; Middle Aged; Probiotics; RNA, Ribosomal, 16S; Renal Insufficiency, Chronic; Verrucomicrobia
PubMed: 31245306
DOI: 10.3389/fcimb.2019.00206 -
Microbiology Spectrum Dec 2021The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial...
The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children's hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs' potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteria; COVID-19; Child; China; Communicable Diseases; Drug Resistance, Bacterial; Escherichia coli; Humans; Klebsiella pneumoniae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Moraxella catarrhalis; Pseudomonas aeruginosa; SARS-CoV-2; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus pneumoniae; Streptococcus pyogenes
PubMed: 34730410
DOI: 10.1128/Spectrum.00283-21