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Antimicrobial Agents and Chemotherapy Sep 2022Maribavir was approved by the U.S. Food and Drug Administration in November 2021 for the treatment of adult and pediatric patients with post-transplant cytomegalovirus... (Review)
Review
Maribavir was approved by the U.S. Food and Drug Administration in November 2021 for the treatment of adult and pediatric patients with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir, or foscarnet. Maribavir is an oral benzimidazole riboside with potent and selective multimodal anti-CMV activity. It utilizes a novel mechanism of action which confers activity against CMV strains that are resistant to traditional anti-CMV agents, and also offers a more favorable safety profile relative to the dose-limiting side effects of previously available therapies. Maribavir was initially studied as an agent for CMV prophylaxis in solid organ and hematopoietic stem cell recipients, but initial phase III trials failed to meet clinical efficacy endpoints. It has been more recently studied as a therapeutic agent at higher doses for refractory-resistant (R-R) CMV infections with favorable outcomes. After an overview of maribavir's chemistry and clinical pharmacology, this review will summarize clinical efficacy, safety, tolerability, and resistance data associated with maribavir therapy.
Topics: Adult; Anti-Infective Agents; Antiviral Agents; Benzimidazoles; Child; Cidofovir; Cytomegalovirus Infections; Dichlororibofuranosylbenzimidazole; Drug Resistance, Viral; Foscarnet; Ganciclovir; Humans; Valganciclovir
PubMed: 35916518
DOI: 10.1128/aac.02405-21 -
Clinical Microbiology and Infection :... Jan 2023Bacterial prostatitis is a highly prevalent infection responsible for significant morbidity among men. The diagnosis and treatment for bacterial prostatitis remains... (Review)
Review
BACKGROUND
Bacterial prostatitis is a highly prevalent infection responsible for significant morbidity among men. The diagnosis and treatment for bacterial prostatitis remains complicated. The difficulty in diagnosis is in part owing to the paucity of high-quality evidence that guides a clinician's interpretation of patients' history, physical examination, and laboratory findings. Treatment is challenging because of the few antimicrobials capable of prostate penetration, growing antimicrobial resistance limiting effective treatment options, and the high risk of recurrence.
OBJECTIVES
We aimed to provide a useful resource for clinicians in effectively diagnosing and managing acute bacterial prostatitis (ABP) and chronic bacterial prostatitis (CBP).
SOURCES
A PubMed literature search on prostatitis was performed with no restrictions on publication date.
CONTENT
The epidemiology, pathophysiology, diagnosis, and treatment for ABP and CBP are explored using a clinical vignette as relevant context.
IMPLICATIONS
Bacterial prostatitis can be diagnosed through a focused history and microbiological investigations. The Meares-Stamey 4-glass test or modified 2-glass test can help confirm the diagnosis if uncertainty exists. Typical uropathogens are common contributors to bacterial prostatitis but there is growing interest in exploring the role atypical and traditional non-pathogenic organisms may have. Fluoroquinolones remain first-line therapy, followed by trimethoprim-sulfamethoxazole (TMP-SMX) or doxycycline if the pathogen is susceptible. Fosfomycin has emerged as a repurposed and useful agent because of the increasing incidence of multidrug-resistant pathogens. Selection of appropriate antimicrobial regimens can be challenging and is dependent on the host, chronicity of symptoms, uropathogens' susceptibilities, antimicrobials' side effect profile, and the presence of prostatic abscesses or calcifications. ABP can typically be treated similar to other complicated urinary tract infections. However, CBP requires prolonged therapy, with a minimum of 4 weeks and up to 12 weeks of therapy.
Topics: Male; Humans; Prostatitis; Anti-Bacterial Agents; Chronic Disease; Bacterial Infections; Anti-Infective Agents
PubMed: 35709903
DOI: 10.1016/j.cmi.2022.05.035 -
The Veterinary Clinics of North... Mar 2020Canine infectious respiratory disease complex (CIRDC) refers to a syndrome of diseases that can be caused by several different bacterial and viral pathogens. These... (Review)
Review
Canine infectious respiratory disease complex (CIRDC) refers to a syndrome of diseases that can be caused by several different bacterial and viral pathogens. These pathogens are often highly contagious, and coinfections are common. Clinical signs are frequently mild and self-limiting; however, some individual cases progress to severe disease. Clinical diagnosis of CIRDC is often based on history of exposure and physical examination findings; however, determining the etiologic agent requires application of specific diagnostic tests, and results can be difficult to interpret because of widespread subclinical infections.
Topics: Animals; Anti-Infective Agents; Bacterial Vaccines; Dog Diseases; Dogs; Respiratory Tract Infections; Viral Vaccines
PubMed: 31813556
DOI: 10.1016/j.cvsm.2019.10.009 -
Molecules (Basel, Switzerland) Apr 2022Quercetin, an essential plant flavonoid, possesses a variety of pharmacological activities. Extensive literature investigates its antimicrobial activity and possible... (Review)
Review
Quercetin, an essential plant flavonoid, possesses a variety of pharmacological activities. Extensive literature investigates its antimicrobial activity and possible mechanism of action. Quercetin has been shown to inhibit the growth of different Gram-positive and Gram-negative bacteria as well as fungi and viruses. The mechanism of its antimicrobial action includes cell membrane damage, change of membrane permeability, inhibition of synthesis of nucleic acids and proteins, reduction of expression of virulence factors, mitochondrial dysfunction, and preventing biofilm formation. Quercetin has also been shown to inhibit the growth of various drug-resistant microorganisms, thereby suggesting its use as a potent antimicrobial agent against drug-resistant strains. Furthermore, certain structural modifications of quercetin have sometimes been shown to enhance its antimicrobial activity compared to that of the parent molecule. In this review, we have summarized the antimicrobial activity of quercetin with a special focus on its mechanistic principle. Therefore, this review will provide further insights into the scientific understanding of quercetin's mechanism of action, and the implications for its use as a clinically relevant antimicrobial agent.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Quercetin
PubMed: 35458691
DOI: 10.3390/molecules27082494 -
Journal of Applied Microbiology Dec 2022Betalains are nitrogen-containing plant pigments that can be red-violet (betacyanins) or yellow-orange (betaxanthins), currently employed as natural colourants in the... (Review)
Review
Betalains are nitrogen-containing plant pigments that can be red-violet (betacyanins) or yellow-orange (betaxanthins), currently employed as natural colourants in the food and cosmetic sectors. Betalains exhibit antimicrobial activity against a broad spectrum of microbes including multidrug-resistant bacteria, as well as single-species and dual-species biofilm-producing bacteria, which is highly significant given the current antimicrobial resistance issue reported by The World Health Organization. Research demonstrating antiviral activity against dengue virus, in silico studies including SARS-CoV-2, and anti-fungal effects of betalains highlight the diversity of their antimicrobial properties. Though limited in vivo studies have been conducted, antimalarial and anti-infective activities of betacyanin have been observed in living infection models. Cellular mechanisms of antimicrobial activity of betalains are yet unknown; however existing research has laid the framework for a potentially novel antimicrobial agent. This review covers an overview of betalains as antimicrobial agents and discussions to fully exploit their potential as therapeutic agents to treat infectious diseases.
Topics: Humans; Betalains; SARS-CoV-2; Betacyanins; Anti-Infective Agents; COVID-19 Drug Treatment
PubMed: 36036373
DOI: 10.1111/jam.15798 -
Povidone Iodine: Properties, Mechanisms of Action, and Role in Infection Control and Decolonization.Antimicrobial Agents and Chemotherapy Aug 2020Nasal decolonization is an integral part of the strategies used to control and prevent the spread of methicillin-resistant (MRSA) infections. The two most commonly used... (Review)
Review
Nasal decolonization is an integral part of the strategies used to control and prevent the spread of methicillin-resistant (MRSA) infections. The two most commonly used agents for decolonization are intranasal mupirocin 2% ointment and chlorhexidine wash, but the increasing emergence of resistance and treatment failure has underscored the need for alternative therapies. This article discusses povidone iodine (PVP-I) as an alternative decolonization agent and is based on literature reviewed during an expert's workshop on resistance and MRSA decolonization. Compared to chlorhexidine and mupirocin, respectively, PVP-I 10 and 7.5% solutions demonstrated rapid and superior bactericidal activity against MRSA in and studies. Notably, PVP-I 10 and 5% solutions were also active against both chlorhexidine-resistant and mupirocin-resistant strains, respectively. Unlike chlorhexidine and mupirocin, available reports have not observed a link between PVP-I and the induction of bacterial resistance or cross-resistance to antiseptics and antibiotics. These preclinical findings also translate into clinical decolonization, where intranasal PVP-I significantly improved the efficacy of chlorhexidine wash and was as effective as mupirocin in reducing surgical site infection in orthopedic surgery. Overall, these qualities of PVP-I make it a useful alternative decolonizing agent for the prevention of infections, but additional experimental and clinical data are required to further evaluate the use of PVP-I in this setting.
Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Chlorhexidine; Humans; Infection Control; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Povidone-Iodine; Staphylococcal Infections; Staphylococcus aureus
PubMed: 32571829
DOI: 10.1128/AAC.00682-20 -
JAMA Nov 2022The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain. (Meta-Analysis)
Meta-Analysis
Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.
IMPORTANCE
The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain.
OBJECTIVE
To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care.
DATA SOURCES
The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022.
STUDY SELECTION
Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo.
DATA EXTRACTION AND SYNTHESIS
Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework.
MAIN OUTCOMES AND MEASURES
The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms.
RESULTS
There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty.
CONCLUSIONS AND RELEVANCE
Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.
Topics: Humans; Anti-Infective Agents; Bacteremia; Bayes Theorem; Gastrointestinal Tract; Hospital Mortality; Intensive Care Units; Pneumonia, Ventilator-Associated; Respiration, Artificial; Critical Illness; Drug Resistance, Microbial; Infection Control
PubMed: 36286098
DOI: 10.1001/jama.2022.19709 -
Biomedicine & Pharmacotherapy =... Aug 2023Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several of the medications currently available... (Review)
Review
Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several of the medications currently available on the market have various unfavourable side effects, necessitating the development of alternative therapeutic choices. Researchers are increasingly interested in alternative medications or active components derived from natural sources. Naringenin is a commonly consumed flavonoid found in many plants, and since it was discovered to have nutritional benefits, it has been utilized to treat inflammation and infections caused by particular bacteria or viruses. However, the absence of adequate clinical data and naringenin's poor solubility and stability severely restrict its usage as a medicinal agent. In this article, we discuss naringenin's effects and mechanisms of action on autoimmune-induced inflammation, bacterial infections, and viral infections based on recent research. We also present a few suggestions for enhancing naringenin's solubility, stability, and bioavailability. This paper emphasizes the potential use of naringenin as an anti-inflammatory and anti-infective agent and the next prophylactic substance for the treatment of various inflammatory and infectious diseases, even though some mechanisms of action are still unclear, and offers some theoretical support for its clinical application.
Topics: Humans; Flavanones; Anti-Inflammatory Agents; Inflammation; Anti-Infective Agents
PubMed: 37315435
DOI: 10.1016/j.biopha.2023.114990 -
Journal of Global Antimicrobial... Sep 2020Multidrug-resistant (MDR) bacteria are a major public-health concern. Bacteriophage endolysins (lysins) can be used as novel antimicrobial agents against bacterial...
OBJECTIVES
Multidrug-resistant (MDR) bacteria are a major public-health concern. Bacteriophage endolysins (lysins) can be used as novel antimicrobial agents against bacterial infections. In this study, a novel endolysin (LysSS) containing a lysozyme-like domain was evaluated for its antibacterial activity against various species of bacteria.
METHODS
The LysSS-encoding gene was analyzed and cloned and the LysSS recombinant protein was expressed and purified. Purified LysSS was used to determine its antimicrobial activity against various bacterial species in vitro and to measure its protection rate against Acinetobacter baumannii systemic infection in an in vivo murine model.
RESULTS
Recombinant LysSS showed activity against MDR A. baumannii, MDR Escherichia coli, MDR Klebsiella pneumoniae, MDR Pseudomonas aeruginosa and Salmonella sp. without pre-treatment with an outer membrane permeabiliser. Moreover, LysSS inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of LysSS against 16 MDR A. baumannii strains ranged from 0.063-0.25mg/mL. LysSS had no cytotoxic effect on A549 human lung cells below 250μg/mL. In an animal model, mice infected with A. baumannii were protected (40% survival rate with 125μg LysSS) by intraperitoneal injection of LysSS.
CONCLUSION
The current results demonstrate that LysSS may be a novel and promising antimicrobial agent against MRSA and MDR Gram-negative bacteria, including A. baumannii and P. aeruginosa.
Topics: Acinetobacter baumannii; Animals; Anti-Infective Agents; Bacteriophages; Endopeptidases; Methicillin-Resistant Staphylococcus aureus; Mice; Pseudomonas aeruginosa
PubMed: 32006750
DOI: 10.1016/j.jgar.2020.01.005 -
Journal of Enzyme Inhibition and... Dec 2023Natural products and analogues are a source of antibacterial drug discovery. Considering drug resistance levels emerging for antibiotics, identification of bacterial... (Review)
Review
Natural products and analogues are a source of antibacterial drug discovery. Considering drug resistance levels emerging for antibiotics, identification of bacterial metalloenzymes and the synthesis of selective inhibitors are interesting for antibacterial agent development. Peptide nucleic acids are attractive antisense and antigene agents representing a novel strategy to target pathogens due to their unique mechanism of action. Antisense inhibition and development of antisense peptide nucleic acids is a new approach to antibacterial agents. Due to the increased resistance of biofilms to antibiotics, alternative therapeutic options are necessary. To develop antimicrobial strategies, optimised and models are needed. In vivo models to study biofilm-related respiratory infections, device-related infections: ventilator-associated pneumonia, tissue-related infections: chronic infection models based on alginate or agar beads, methods to battle biofilm-related infections are discussed. Drug delivery in case of antibacterials often is a serious issue therefore this review includes overview of drug delivery nanosystems.
Topics: Peptide Nucleic Acids; Bacteria; Anti-Infective Agents; Anti-Bacterial Agents; Biofilms
PubMed: 36629427
DOI: 10.1080/14756366.2022.2155816